Grey Matters Journal VC Issue 3 Fall 2021 by greymattersjournalvc

FEATURING Have No Fear, Your Hidden Fear Response Regulators Are Here: How Our Caregivers Shaped Our Fear Regulation System

THE 50TH ANNIVERSARY OF THE NEUROSCIENCE & BEHAVIOR PROGRAM AT VASSAR COLLEGE: ALUMNAE/I FEATURES A World of Pure Imagination: The Neuroscience of Lucid Dreaming

FALL 2021 SPECIAL

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Table of Contents

TABLE OF CONTENTS COVER ARTICLE

A WORLD OF PURE IMAGINATION: THE NEUROSCIENCE OF LUCID DREAMING by Clem Doucette and Gerasimos Copoulos / art by Sophie Sieckmann

THE 50TH ANNIVERSARY OF THE NEUROSCIENCE & BEHAVIOR PROGRAM AT VASSAR COLLEGE: ALUMNAE/I FEATURES

APHANTASIA AND THE BLIND IMAGINATION by Lucy Posner / art by Ayane Garrison

SPECIAL K: THE UNEXPECTED ANTIDEPRESSANT by Kaiya Bhatia / art by Ella Kolk FEATURED ARTICLE

HAVE NO FEAR, YOUR HIDDEN FEAR RESPONSE REGULATORS ARE HERE: HOW OUR CAREGIVERS SHAPED OUR FEAR REGULATION SYSTEM by Lotus Lichty / art by Sneha Das

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Table of Contents

404 ACCESSIBILITY NOT FOUND: DISABILITY AND TECHNOLOGY

by Nick Weiner / art by Yuchen Wang

GROWING BRAINS IN A DISH: ORGANOIDS PRESENT GREAT PROMISE IN MODELING NEURAL TISSUE

by Salome Ambokadze and Melissa Roybal / art by Tori Kim

by Benjamin Kheyfets / art by Max Freedman

DO YOU SEE WHAT I SEE?: BODY DYSMORPHIC DISORDER AND SELFPERCEPTION

NEUROLAW: TAKING THE STAND ON MENTAL ILLNESS

BETRAYED BY MY BODY: THE SCIENCE BEHIND ALIEN HAND SYNDROME by Lucas Angles / art by Cherrie Chang

REFERENCES

by Sudiksha Miglani / art by Natalie Bielat

ISSUE NOTES ON THE COVER

LEARN MORE

Art by Sophie Sieckmann

Check out our website to read our blog, find out how to get involved, and more at greymattersjournalvc.org.

LET US KNOW If you have any questions or comments regarding this Issue 3, please write a letter to the editor at brainstorm.vassar@gmail.com.

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 3

Production Staff

PRODUCTION STAFF

DANIELLA LORMAN

LUCAS ANGLES

Editor-in-Chief

Senior Managing Editor

TALIA MAYERSON

MARA RUSSELL

Senior Editor, General Editing

LIA RUSSO

Accessibility Director

CLEM DOUCETTE

Senior Managing Editor

KAYEN TANG

ELEANOR CARTER Senior Editor, Lay Review

MYA KAHLE

Art Executive

Production Manager

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FILIPP KAZATSKER

CARINA D’SOUZA

HAROUN HAQUE

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CHRISTOPHER CHO Senior Editor, Scientific Review

JULIÁN AGUILAR

Layout Executive and Graphic Designer

HANNAH DALEY

Graduate Student Executive

Production Staff

ARTISTS

AUTHORS

Melanie Carolan Sneha Das Max Freedman Anna Bishop Ella Kolk Sophie Sieckmann Yuchen Wang Natalie Bielat Ayane Garrison Cherrie Chang Tori Kim

Lotus Lichty Kaiya Bhatia Ben Kheyfets Nick Weiner Sudiksha Miglani Salome Ambokadze Melissa Roybal Clem Doucette Gerasimos Copoulos Lucas Angles Lucy Posner

SCIENTIFIC REVIEW

LAY REVIEW

GENERAL EDITING

Annie Xu Elisa Sung Zach Johnson Alexander Roth Hao Dong Tian Ninamma Rai Anshuman Das Victoria Armitage Talia Roman Dhriti Seth Claire Tracey Amber Huang Madison Wilson Avery Bauman Marina Alfano Keara Ginell

Emma San Filippo Rebecca Zhao Rileigh Chinn Lilah Lichtman Caris Lee Nicole Stern Anjali Krishna Claire Tracey Lyla Menaker

Tessa Charles Nanako Kurosu Olivia Gotsch Jason Jin Katherine Nelson Naomi Tomlin Rebecca Zhao Lillian Lowenthal Sam Dorf Cherrie Chang Lucy Volino Ty Langford Haylee Backs Ninamma Rai Claire Tracey Elsa Wiesinger Lilah Lichtman Izzy Kaufman-Sites Kalina Rashkov

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Editor's Note

EDITOR’S NOTE This year marks the 50th anniversary of the Neuroscience and Behavior program at Vassar College. To commemorate this milestone, we share with you a special edition by both Vassar College students and alumni. This third issue of Grey Matters Journal VC is an emergent property of the collaborative efforts of generations of Vassar students, each contributing a unique perspective. Our cover article, “A World of Pure Imagination: The Neuroscience of Lucid Dreaming” dives into the emerging science of lucid dreaming — the ability to consciously reshape your dreams. The intersection of neuroscience and law are examined in “Neurolaw: Taking the Stand on Mental Illness,” while the the great potential of organoids in metamorphosing research is explored in “Growing Brains in a Dish: Organoids Present Great Promise in Modeling Neural Tissue.” Alumni provide invaluable commentary on how studying the brain sciences at Vassar College has impacted their life, work, and overall trajectory post-Vassar. Milestones are meant to be celebrated. As we shine a light on the milestone this issue commemorates, I invite you to reflect on the experiences, people, and moments that have created the emergent property that is you. What you do. Why you do it. What you value. How you harness those values through your craft. For me, this ends with expressing my gratitude to everyone who played a part in creating this special edition. Thank you to the Neuroscience and Behavior program for your endless support. Thank you to Dr. Zupan, Chair of our program, for this fantastic opportunity to collaborate, and for extending your time so generously throughout this publication cycle. Thank you to my Neuroscience and Behavior mentors, Dr. Newman and Dr. Bergstrom, who have cultivated my passion for scientific communication and taught me how to harness that passion via invaluable lessons in collaboration, leadership, and flexibility. Thank you to the impassioned team members that comprise our Grey Matters community for your dedication towards our shared goal of promoting accessibility in science. And to you, our readers, our deepest thanks for tuning in. We are delighted to reconnect with you, and we hope you learn something wonderful. Cheers,

Daniella Lorman Editor in Chief

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Aphantasia and the Blind Imagination

APHANTASIA AND THE BLIND IMAGINATION by Lucy Posner/ art by Ayane Garrison

hat does it mean to imagine? In 350 BC, Aristotle insisted that “whenever one contemplates, one necessarily at the same time contemplates in images” [1]. This ability to visualize people, places and events, to form mental pictures of that which may or may not exist in real life, was coined phantasia by the Greek philosopher. We’ve all been there: about to give a presentation in class, our stomach in knots, when someone tells us not to worry. “It’s no big deal,” we’re reassured, “just imagine everyone in their underwear!” For many of us, picturing a classroom full of our naked peers is neither difficult nor daunting. But for 3% of the global population, visualizing something as mundane and uniform as an uppercase ‘A,’ nevermind a sea of students in their underpants, is inconceivable [1]. In ancient Greece, phantasia, or imagination, was thought to be a strictly visual faculty. It wasn’t until the late 19th century, with a series of studies conducted by Francis Galton — the problematic yet unavoidable architect of the eugenics movement — that the previously held conception of the universal power to form mental images was disputed. Galton systematically investigated variations in the vividness of visual imagery. In 1880, Galton asked one hundred ‘men of science’ to rate “the illumination, definition and coloring of your breakfast table as you sat down to it this morning” [2]. When asked to call to mind a picture of what they had for breakfast, Galton found that for six of his participants, “the power of visualization was zero, ,” meaning they saw nothing when attempting to imagine their meals [2]. In 2015, the phenomena of the ‘blind imagination’ was finally given a name: aphantasia. We are only now beginning to understand these invisible differences in imaginative experience. The ways in which we do or do not visualize information affects everything from how we remember events to how we plan for our future, from the jobs we take to the things we’re afraid of. In becoming aware of our own imaginative processes and the imaginative processes of others, we can become better communicators and grow more in-tune with our own specific breed of thinking.

A BLIND IMAGINATION?: APHANTASIA AND BLIND INJURIES In 2009, a sixty-five year-old former surveyor, now referred to as ‘Patient MX,’ underwent a heart surgery [3]. Up until his procedure, MX, like many of us, had the habit of re-playing recent events in his mind before drifting off to sleep. As a surveyor, MX was accustomed to visualizing buildings and landscapes. An alarm sounded off in the medical field when, four days post-op, MX found he had lost the ability to visualize. The man’s imagination had become blind. He had no difficulty recognizing familiar or famous faces from photographs. He retained the ability to navigate his immediate environment. He could give descriptions of scenes and landmarks around his hometown of Edinburgh. But, when asked how he could do this he revealed, “I can remember visual details, but I can’t see them.” MX remained unable to summon visual imagery at will, or bring to mind the faces of relatives or close friends. He had become aphantasic. Patient MX was subjected to a wide range of neuropsychological assessments. Despite insisting he was no longer capable of generating visual images, MX performed normally on standard tests of perception, visual imagery and visual memory. For example, when it came to recognizing famous faces, MX had no issue. When asked to imagine the face of a celebrity whose name was shown on screen, however, fMRIs suggested that MX utilized the front of his brain, namely the prefrontal cortex, when attempting visualization. The prefrontal cortex, much like a central computer, is responsible for our decision making and, in the case of MX, memory retrieval. During this experiment, MX lacked the ability to picture the face in his mind, so he resorted to recalling from memory who the person was instead of an image of that person’s face. When faced with the task of mental visualization, individuals with-

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Aphantasia and the Blind Imagination

out aphantasia frequently use regions of the brain that activate when receiving visual stimuli. Researchers have observed that when subjects are asked to picture faces, they display increased activation of the occipital lobe, the region of the brain directly attached to our eyes that is responsible for interpreting what we see. When imagining the likeness of something, non-aphantasic people quite literally “see” the object in their brains [3]. Therefore, MX can interpret visual stimuli while paradoxically remaining incapable of re-visualizing them.

MX’s aphantasia was brought on by a brain injury — a side effect of his heart surgery [3]. People born with aphantasia, however, go their whole lives without experiencing visual imagery. They typically become aware of their condition in their teens when, through reading or conversation, they realize that expressions like ‘where do you see yourself in ten years?’ or ‘picture yourself in your happy place,’ refer to a real, quasi-visual experience they themselves do not possess. This, of course, does not mean that aphantasics cannot participate in these kinds of mental exercises. Someone with aphantasia may very well ‘see’ themselves as a practicing doctor in ten years. They won’t, however, be able to summon an image of themselves wearing a white coat with a stethoscope around their neck in their mind’s eye. MX was able to recall visual details but could not ‘see’ such details, because while he might have a memory of a specific building, he cannot access that memory in the form of an image. MX knows that the Statue of Liberty is green, that it depicts a woman with a crown lifting a torch, but he does not first picture the landmark in his own brain before describing it to someone else. Aphantasics may not be able to prime themselves with imagery of their own making, but they are nonetheless capable of solving visual tasks [4].

REMEMBERING WITHOUT VISUALIZING: NON-VISUAL PROBLEM SOLVING A visualization exercise made rounds on Twitter last year. The tweet asked users to close their eyes, imagine an apple and select one of five images, each a

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Aphantasia and the Blind Imagination different degree of vividness, that corresponded to what they saw in their mind’s eye. Image number one looked, more or less, like a photograph. Image five was completely black — the absence of any mental picture. The tweet was shared forty-three thousand times. People were shocked when they realized that a select few twitter users were unable to conjure images with their imaginations. Mary, the woman who created the tweet, is an illustrator and an artist. She’s also aphantasic. Mary revealed that when she shuts her eyes and tries to imagine an apple, all she sees is black. Still, she is able to conceptualize the fruit in terms of its shape, size and color, despite not being able to effectively ‘see’ it. Mary cannot picture an apple, yet she can draw one with impressive detail. How is it that a person without the ability to visualize can represent objects artistically? No one, aphantasic or not, would be able to draw an apple without having encountered one in life — whether that be in the form of a photograph or the three-dimensional object at a grocery store. For Mary, all the memories, connections, and experiences she associates with apples exist in her brain, just not in a way that is visually accessible. Whereas a non-aphantasic might represent the fruit by first retrieving an image of the apple from memory, displaying it in their mind’s eye, someone like Mary relies on non-visual methods to

illustrate and describe the fruit. Those without visual imagery show deficits in object-specific memory [5]. Although the memory of said object exists, aphantasics cannot recall an image of that object voluntarily. To compensate, they rely on verbal and spatial techniques when confronted with problems that the majority of people would use their visualization skills to solve [5]. Let’s say a friend asks Mary to draw an apple. Instead of an image of the fruit popping up in her

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Aphantasia and the Blind Imagination head, the word ‘apple’ presents itself to her. While she does not ‘see’ the word ‘apple’ or the apple itself, the sound of biting into it might occur to her, or maybe an association with the name ‘Issac Newton’ or ‘New York City.’ Mary has a non-visual concept of how the object appears on paper. She knows the apple is ‘red’ and ‘round.’ She knows it has a ‘stem;’ perhaps a ‘sticker’ on the outside. In order to draw an ‘apple,’ Mary might search for reference images. She might google something along the lines of ‘red apple with a stem and sticker,’ after making a few sketches to determine where in space the apple should be depicted within her composition. Mary uses a primarily verbal strategy to approach the problem of representing an object from memory.

side-table, people with aphantasia weren’t as privy to such false memories.

APHANTASIA AND SENSE OF SELF

Who are we if not our memories? Before his life-changing procedure, Patient MX would visualize friends and family, recalling his past life experiences at bedtime. How many of us have been kept awake, haunted by that one, embarrassing moment on loop in our mind’s eye? What about the face of that one person we can’t stop thinking about from the moment we wake up? Aphantasia exists on a spectrum [2]. While many with the condition can dream in images, voluntary retrieval of visual memories is impossible [2]. Some aphantasics, though they do While the object-specifnot have the capacity ic memory of aphantasics to visualize, can recall IN APHANTASICS, REGIONS OF THE BRAIN KNOWN might be impaired, their sounds, scents and TO BE ASSOCIATED WITH THE RETRIEVAL OF PAST spatial memory — the tastes [6]. Others canPERSONAL EXPERIENCES WERE LESS ACTIVATED brain’s capacity to retrieve not recreate sensory WHEN EXAMINED WITH AN FMRI. THESE AREAS information needed to loexperiences whatsocate objects — is not [5]. INCLUDED THE MEDIAL PORTION OF THE ever. At the opposite In 2020, self-reporting end of this spectrum PREFRONTAL CORTEX, AS WELL AS WITHIN THE aphantasics were asked are the hyperphanTEMPORAL LOBE, BOTH OF WHICH FUNCTION IN to study a photograph of a tasics — people who THE FORTIFICATION OF MEMORY. room full of furniture and can have extremely later draw that room from vivid mental imagery. memory. While non-aphantasics approached this task Hyperphantasics tend to be highly visual lereners. by visualizing the room in their mind and using that When they close their eyes and think of an apple, hymental picture as a basis for their drawing, those with perphantasics ‘see’ something similar to a photograph aphantasia met the problem differently. Instead of — image number one on Mary’s scale. The way we remembering the appearances of the various objects think of ourselves as individuals is deeply connectin the room, aphantasics recalled the names of the ed to the ways we revisit our pasts and project our objects as well as where those objects were placed futures. Aphantasia is associated with self-reported in relation to one another. For example, if the photo- impairment of autobiographical memory [7]. While graph depicted a bedroom, the participant might map aphantasics and non-aphantasics perform equally on out the room on paper using words before drawing standard memory tests and are able to retain new the objects themselves. They might write ‘bed’ in the information, those with aphantasia often have diffiupper left corner of the paper, ‘side-table’ on the up- culties recalling their personal history in detail [7]. In per right corner and ‘vase’ above ‘side-table.’ Then, aphantasics, regions of the brain known to be assobased on associations they have with the word ‘bed,’ ciated with the retrieval of past personal experiencbegin to draw a frame, mattress and pillows using es were less activated when examined with an fMRI. a strategy similar to Mary’s in an effort to give the These areas included the medial portion of the pretext visual form. Aphantasic participants remembered frontal cortex, as well as within the temporal lobe, fewer objects than non-aphantasics. Their drawings both of which function in the fortification of memory. were made largely with the help of labels and their in- Aphantasia has also been linked to reduced activity in terpretations of such words from their memory. Their the precuneus, a portion of the occipital lobe relevant spatial accuracy, however, was equivalent to that of to mental imagery [6]. non-aphantasics. Furthermore, those with aphantasia made significantly fewer memory errors than Nicholas W. Watkins, a renowned physicist at the Lonnon-aphantasic counterparts [5]. Where non-aphan- don School of Economics, is aphantasic. Not all people tasics saw extra chairs, carpets that were never actu- with aphantasia report deficits in their autobiographially there, and vases on every table instead of just the

“

”

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Aphantasia and the Blind Imagination

cal memory — as the condition exists on a spectrum — but Watkins does. “My [memory deficit] doesn’t seem to disconnect me from my past and future as much as one might expect,” he writes. “I am still very much a product of my own past, it’s just that I can’t subjectively go back there. A good example of what I do have is my experience of seeing Holst’s St Paul’s suite performed in London on a school outing in the early 1970s. I have no emotion-laden episodic memory of being there, but nonetheless somehow know that I found it joyous, and feel that it helped me towards a lifelong love of classical music [6].” Watkins experiences a lack of visceral emotion when revisiting the past or imagining the future.

If you can, picture this: you’re grocery shopping when a song plays through the PA system. Recalling the opening bars, you’re instantly transported back to that time you tripped on your dress and embarrassed yourself in front of everyone at that tenth grade dance. If you’re a non-aphantasic, this memory will likely be accompanied by a physical — or, to use Watkins’ words, an ‘emotion-laden’ — experience. You might feel your face flush; maybe your stomach drops. Perhaps you inadvertently palm your face in the produce aisle, reliving the experience as though it were yesterday. A proposed function of mental imagery, or the capacity for visualization, is to make our thoughts more emotionally evocative through sensory stimulation [8]. This can be helpful, of course, in planning for future events and in remembering the past; but, it can also be a hindrance. Our thoughts so often grow overwhelming and maladaptive, as is evident in certain anxiety disorders.

Aphantasia has been associated with a flat-line physiological response to both reading and imagining frightening stories. While aphantasics had a visceral response when perpetually viewing scary images, they did not have the same response when asked to imagine these images on their own or with the help of a book [8]. Where non-aphantasics may fall victim to their own fearful, imagined-scenarios, those with aphantasia may find it easier to move through the world without the same kind of visceral dread that accompanies intrusive thoughts. Someone with aphantasia probably wouldn’t be distracted at the grocery store after hearing a song associated with an unpleasant memory. This is because they wouldn’t be prompted to visualize, and essentially re-live, the experience associated with that song. The behavior signatures of aphantasia, or the lack thereof, may have some effect on the jobs we take, our relationship to the world, and the people we become. Aphantasia has been associated with more analytical occupations, whereas hyperphantasia has been linked to creative professions. That said, plenty of aphantasics, like Mary, become artists. Glen Keane, the animator who created The Little Mermaid, has aphantasia. So does co-founder of Pixar Ed Cattrall and world-famous magician Penn Jilette of Penn and Teller. While some evidence suggests aphantasia is linked to behavioral disorders like autism, hyperphantasia is thought to be related to afflictions like PTSD and schizophrenia [1]. Though aphantasics are limited when it comes to visualizing their pasts and may have difficulties imagining, those without the condition might be bogged down by upsetting memories or an intense fear of the future [8]. The bottom line is, there is no ‘correct’ way to have an inner life. Imagination exists on a spectrum. Creativity takes many forms. Many aphantasics assert that aphantasia is not a condition, it’s just a different way of thinking and perceiving. We are all programmed with unique minds that allow us to interpret the world in infinite ways. In learning about differences in imaginative experience as well as how our own imaginations work, we can lead more fulfilling lives and become more understanding people. References on page 82.

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Special K

SPECIAL K: THE UNEXPECTED ANTIDEPRESSANT by Kaiya Bhatia art by Ella Kolk

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Special K

id you know that Special K could be the key to effectively treating depression? No, we’re not talking about cereal, we’re talking about ketamine. Similar to other psychedelic drugs, like LSD and hallucinogenic mushrooms, high doses of ketamine can cause altered consciousness and changes in self-perception [1]. However, while you may think of ketamine as merely an illicit club drug or hallucinogen, it actually serves a variety of medical purposes. Ketamine was first introduced to the world of medicine as an anesthetic, preventing patients from processing sensory information [4]. More recently, however, ketamine has demonstrated great promise as a novel treatment for major depressive disorder (MDD) [2]. This common mental health condition causes patients to experience persistent feelings of sadness, often coupled with the loss of interest in daily activities; frustratingly, the treatments widely used for MDD have major drawbacks [2, 3]. Ketamine, however, offers a new way of addressing debilitating depressive symptoms, potentially without the concerns of safety and efficacy that are typical of traditional antidepressants.

tonin to work as a mood regulator, it is first released by one neuron into the small space that sits between the original neuron and another one nearby. This space is called the synapse. The nearby neuron then receives some of the serotonin, thereby getting the message of satisfaction. However, once the message is appropriately received, some serotonin remains in the synapse. To bring back this remaining serotonin so that it can be re-used for later signaling, the original neuron undergoes a process called “reuptake,” pulling the leftover serotonin back into the cell. This is where SSRIs come in: they block reuptake and prevent the disappearance of serotonin from the synapse. Think of SSRIs like a plug in a

You may be wondering how ketamine could travel from the floors of operating rooms and chic dance clubs to a psychiatric clinic near you. About 20 years ago, it was found that lower doses of ketamine could also be used to treat symptoms of MDD [5]. Drugs that activate the same brain receptors as ketamine have antidepressant effects, suggesting that ketamine does the same [6, 5]. Based on these findings, psychiatrists began to use ketamine as an emergency treatment for suicidal ideation due to its fast-acting properties and lack of harmful side effects characteristic of traditional depression treatments such as higher rates of suicidal ideation [7, 8]. Because of these properties, ketamine may potentially constitute our best treatment for MDD yet [2]. But what neural mechanisms underlie these crucial differences that cause ketamine to work better than traditional treatments for MDD? Let’s delve into the neuroscience behind the miraculous antidepressant qualities of “Special K.”

PUTTING THE “SPECIAL” IN SPECIAL K The most common treatments for depression today are selective serotonin reuptake inhibitors (SSRIs), or drugs that increase the concentration of serotonin in the brain. Serotonin is a neurotransmitter, or chemical messenger, that helps regulate our mood by sending messages of satiation throughout the brain via neuronal, or brain cell, communication. In order for sero-

bathtub. When you plug a drain, all the water remains in the tub rather than disappearing down the pipes. Similarly, SSRIs “plug” the reuptake mechanism so that serotonin remains in the synapse rather than disappearing back into the cell. Ketamine treatment, however, combats depression differently. Understanding the complex biochemistry of ketamine can seem a bit overwhelming; but, generally, we know that ketamine works via the glutamate

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Special K system to produce its effects [9]. Glutamate is an excitatory neurotransmitter, meaning it increases the firing rate of neurons after binding to receptors on the outside of another neuron. Glutamate interacts specifically with AMPA and NMDA receptors, as these two receptors have channels that allow positive charges to enter the cell and cause the neuron to fire when necessary. When glutamate binds to an AMPA receptor, it passes through a channel and then binds to an NMDA receptor. In this way, AMPA and NMDA receptors are linked: when AMPA receptors are activated, NMDA receptors become activated as well. However, this constant glutamate signaling mechanism is disrupted when ketamine is ingested;

on the other hand, facilitates the direct binding of glutamate to receptors. And, because direct binding occurs more immediately than the indirect binding caused by SSRIs, the antidepressant effects of ketamine set in much quicker [9].

after ingestion, the drug binds to NMDA and blocks the receptor’s ability to be activated by glutamate. The remaining glutamate that can no longer bind to the NMDA receptor preferentially binds to the AMPA receptors, causing the neuron to fire or send an excitatory signal to other cells. This process, known as “direct binding,” is what sets ketamine treatment apart from traditional antidepressants like SSRIs. SSRIs merely increase the chance that a neurotransmitter will bind to a receptor. Ketamine administration,

WHAT MAKES “SPECIAL K” SO SPECIAL?: THE THERAPEUTIC PROPERTIES OF KETAMINE IN ACTION

In addition to the speedy effects of direct binding, ketamine may also act more quickly than other drugs by facilitating neural plasticity, a construct typically associated with the way the brain changes to accommodate learning and memory. MDD has been associated with a breakdown in neuroplasticity, and recent findings have consequently linked the promotion of neuroplasticity with antidepressant effects [11]. In other words, since the disruption of neuroplasticity is thought to be the basic pathological mechanism underlying the disorder, the restoration of plasticity should ameliorate depression [13]. When ketamine binds to NMDA receptors, and AMPA receptors are activated in parallel, this AMPA activation increases the production of brain-derived neurotrophic factor (BDNF) [10]. BDNF is a protein that promotes the formation and strengthening of neuronal connections [12]. As these connections get stronger, neurons can send signals and relay information more quickly and effectively. These stronger neuronal connections react to ketamine much more quickly, leading to a more powerful antidepressant effect [12]. Further, ketamine may support neural plasticity by changing the structure of neurons themselves [4]. The neuron’s dendrites, which resemble the branches of a tree, have small protrusions called spines, which receive signals from other neurons. Spines increase the number of connections that the dendrite can make to other neurons; this measure is considered a direct indication of increased brain plasticity. Thus, ketamine differs from traditional antidepressants by restoring neuroplasticity lost through MDD and promoting the direct binding of glutamate for quick and effective enhancement of mood regulation. But what do these fascinating neural mechanisms of ketamine actually look like in practice? What behavioral or emotional changes can we observe in depression patients who try ketamine in medical trials?

First, contrary to what you might imagine recreational ketamine use to look like, employing ketamine as an antidepressant doesn’t mean that patients will be snorting lines in order to receive their treatment. In fact, initial studies administered ketamine to patients using an IV [5]. However, this method present-

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Special K ed an accessibility issue: patients would be required to take hospital trips in order to receive treatment. Consequently, intranasal sprays have become the leading form of treatment administration. As of 2019, the FDA has approved an intranasal ketamine spray specifically for patients with treatment-resistant depression, as it was found to significantly reduce MDD symptoms such as fatigue and feelings of hopelessness [14]. However, this means that intranasal ketamine is currently only legal for depression patients after traditional treatments fail to provide any meaningful improvement [15]. Ketamine use has not yet been approved for all MDD patients; but, this may be subject to change in the coming years. With more and more findings pointing toward intranasal ketamine’s efficacy in reducing depressive symptoms, we may see a broadening of legal treatment criteria. This seems especially possible considering ketamine’s success as an antidepressant when compared with other treatments on the market. As discussed earlier, ketamine works differently than other antidepressants, but it also may work better. Ketamine appears to represent a drastically safer and more effective option than our two currently well-established depression treatments: SSRIs and electroconvulsive therapy (ECT). ECT, which is most frequently administered in cases of treatment-resistant depression, uses electric currents to stimulate the brain. However, this treatment is controversial because it sometimes results in memory loss and other harmful symptoms [16]. Notably, ketamine treatment reduces symptoms of depression significantly more than both ECT and SSRIs, without these treatments’ dangerous side effects [14]. However, its unique success as an antidepressant is also rooted in its timeline of effectiveness. One of the biggest drawbacks of SSRIs is that they take a long time to start showing behavioral effects,

and these effects wear off very quickly. This makes the treatment process difficult as individuals have to wait upwards of two months to figure out if their medication works — not to mention that forgetting a single dose can lead to a relapse of symptoms [19]. In contrast, ketamine takes effect roughly two hours after administration, which is very exciting given that most current treatments do not show such a rapid onset of beneficial effects [18, 17]. Because ketamine acts so rapidly, we believe that it directly interacts with the biochemical pathway underlying depression. Ketamine is paradoxically known to have a relatively short half-life, meaning that it doesn’t take long for its active components to leave the body, despite it having incredibly long-lasting effects [17]. This phenomenon suggests that when ketamine binds to receptors, it alters some aspect of the brain, which causes effects to continue long after the drug has left the body [17]. Most traditional antidepressants require daily intake because they cause temporary alterations to neurotransmitter concentrations, rather than causing permanent alterations to the brain itself. But, this long-lasting property of ketamine would mean less frequent doses are needed. Therefore, in comparison to current treatment options, ketamine appears to be remarkably more effective because of its fast action and longevity.

IS SPECIAL K COMING TO A CLINIC NEAR YOU?: ADDRESSING KETAMINE TREATMENT UNCERTAINTIES So, it’s clear that ketamine shows great promise as a treatment for MDD, but how long will it take for this new antidepressant to gain widespread acceptance? Scientists are quite confident that ketamine will be a successful treatment option; but, only if it manag-

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Special K amine are interested in implementing additional monitoring if they choose this treatment route. Knowing that someone is following their progress reduces the anxiety that many MDD patients feel about the safety of their at-home ketamine treatment [20, 21]. Therefore, while some apprehension surrounding ketamine treatment exists, there are also creative ways of addressing patient concerns.

es to overcome all the hurdles that stand in its way. One of the biggest obstacles to ketamine treatment implementation is the social stigma surrounding the drug. How can a popular club drug become a useful treatment for something as serious as MDD? There is already a stigma surrounding antidepressants as a whole, and adding ketamine into the mix is a turn-off for many patients [20]. Many believe that the widespread legalization of the drug as a depression treatment could help reduce the stigma surrounding it [20]. However, even with legalization, many patients may still be hesitant to try ketamine treatment due to its uncertain long-term effects. While short-term use of ketamine as an antidepressant has proven to be safe, there is currently not much research on the effects of long-term use, including the potential for addiction. Ketamine can be an addictive drug, which may pose problems if ketamine therapy becomes a long-term treatment option [21]. Consequently, many MDD patients who are considering the use of ket-

Similarly, despite these hurdles, many of the thousands of people who struggle to find respite from their depression symptoms remain hopeful for ketamine’s legalization [21, 20]. In 2020, a chemical cousin of ketamine, esketamine, was approved by the FDA for MDD patients experiencing acute suicidal ideations or behaviors; this decision was essential as it broadened the drug’s previous legal usage criteria from only individuals with treatment-resistant depression [22]. Still, these treatments are currently only approved for use in clinical settings, so they are not yet ready to be implemented as a common practice [22]. More research on the long-term effects and development of protocols to maintain patient safety will be needed before we see this drug become the new and improved, common antidepressant. Hopefully, people who suffer from depression will soon be able to experience the miraculous benefits of this “special” and unexpected treatment. References on page 82.

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Have No Fear, Your Hidden Fear Response Regulators Are Here

HAVE NO FEAR, YOUR HIDDEN FEAR RESPONSE REGULATORS ARE HERE: HOW OUR CAREGIVERS SHAPED OUR FEAR REGULATION SYSTEM by Lotus Lichty

art by Sneha Das

magine you are two years old and going to a relative’s house for the holidays. As you enter through the door, the aroma of freshly baked sugar cookies fills the air, and the crackling fire gently warms your face. Everything is tranquil. Suddenly, a colossal creature with floppy ears comes bounding over to you out of the blue. Your pupils dilate and your heart starts to race a mile a minute. You quickly rush to your parents, nestling yourself in their arms so they can protect you from the terrifying beast. If you were not raised with a pet, this may have been your first encounter with a dog. It may seem obvious that your parents played an important role in calming you down when you became distressed during new and frightening situations. What may not be as obvious is that when your parents comforted you, they actually shaped how your fear regulation system, the system that helps you respond to scary situations, developed. By creating a nurturing and safe environment for you to initially experience fear, your parents critically influenced the formation of the neurological processes and structures that underlie your ability to regulate stress in your mind and body later in life.

CRITICAL PERIODS: A CRITICAL CONCEPT IN CAREGIVING A child’s brain is like play-doh, pliable and easily molded by external factors. Though it is difficult to remember your early childhood experiences, the close emo-

tional connections you shared with your caregivers during this time shaped who you are today. At birth, your brain contains billions of neurons, or cells that can transmit information. However, despite being born with these billions of neurons, you were not born with the neuronal connections needed to perform essential life skills, like coping with novel stressful situations. In order to build these connections, there are specific periods of time — dubbed “critical periods” or “sensitive periods” — in which the brain is especially sensitive to rapid restructuring and rewiring [1]. These periods are essential for your development, as they lead to the acquisition of critical skills such as language, movement, and emotion regulation. Since technical and ethical limitations make it difficult to study these discrete windows of time, we don’t know when exactly critical periods occur. Nevertheless, it appears the brain has a critical period sometime between birth and age three [1, 2]. Because children are dependent on their caregivers for survival during the first three years of their life, their brain primarily receives inputs from interactions with their caregiver. Therefore, caregiver interactions can significantly influence how the brain develops, given that environmental input received during critical periods can drastically and enduringly change the brain [1,3]. A pivotal way that parents mold your brain early in life

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Have No Fear, Your Hidden Fear Response Regulators Are Here is by shaping the neural circuitry of your fear regulation system during critical periods. To better understand how your interactions with your parents influence the development of your brain, let’s take a look at how the fear regulation system works.

SHOULD I STAY OR SHOULD I GO: THE FEAR REGULATION SYSTEM When you encountered a dog for the first time — whether it was at your relative’s house for the holidays or during a walk around the neighborhood — you probably didn’t see a friendly, fluffy creature. Instead, you saw an outlandish beast twice your size. The dog most likely caused you to feel fear, which made you want to flee. But what causes this sensation of fear? When there is a threatening stimulus in the environment, the amygdala, a region of the brain that processes fear, responds [4, 5]. The amygdala has evolved to detect and immediately respond to threats or dangers in the environment. During childhood, when everything is new and the need to learn what is safe is great, the amygdala is very active [6]. Therefore, the first time you met a dog, your amygdala detected that this stimulus was unfamiliar and responded. In response to amygdala activation, another brain region called the hypothalamus acts like a mailman, receiving the message of a nearby threat from the amygdala and sending it to the rest of the body. Through a series of chain reactions, the hypothalamus prepares the body for the perceived threat by making you more alert. The hypothalamus triggers the release of stress hormones adrenaline and cortisol; these hormones make your pupils dilate and your heart race a mile a minute when you first meet a dog [5]. Collective-

ly, these physiological and physical changes make up our fear response. Taken together, when you encounter something stressful in the environment, your amygdala initiates the fear response to help your body prepare for the perceived threat. However, while the amygdala can protect you from real dangers in the environment, it does a poor job discriminating between a real threat and a false alarm [7, 8]. In order to distinguish between real threats and false

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Have No Fear, Your Hidden Fear Response Regulators Are Here alarms, the amygdala needs to form a connection with our brain’s “emotional control center,” the medial prefrontal cortex. While the amygdala sounds the alarm for fear-inducing stimuli, the medial prefrontal cortex helps us determine if the alarm is justified [7,8]. However, connectivity between these two brain regions does not mature until around adolescence [8]. Therefore, as a child, you did not have the cognitive ability to accurately judge whether or not an environment was safe. The ability to discriminate between a real imminent threat, such as a venomous snake, from a perceived or imagined threat, such as a big gentle dog, is critical for survival. The brain must be able to determine whether something is actually dangerous; otherwise, your fear response would be constantly activated. When caregiving is insufficient, this circuit between the amygdala and the medial prefrontal cortex does not always develop properly, and neither does your ability to distinguish between real and imagined threats.

THE FEAR REGULATION SYSTEM ON OVERDRIVE

erally feel more apprehension or dread because they see the world as a dangerous or stressful place [11]. If you had insufficient caregiving and met a dog for the first time, even when you were no longer in the presence of the giant, fluffy “beast,” your feelings of stress and danger may have lingered. Since the brain is an intricate and complex organ, its development must not be rushed. Researchers have proposed that premature development of the amygdala may initiate premature connectivity to the medial prefrontal cortex, disrupting proper connectivity between the two brain regions [8]. This lack of connections ultimately reduces the brain’s ability to regulate the fear response [7]. In turn, this phenomenon can hinder the order of regular connectivity development between the amygdala and medial prefrontal cortex [12]. For example, it may be that the medial prefrontal cortex develops sooner in an attempt to keep the amygdala in check. However, if this

Children who are used to living in a stressful environment (i.e. one that lacked consistent, responsive caregiving) may not be able to acclimate to a safer environment with dependable caregivers. The consequences of this shift can be seen most clearly among children after they have been adopted. When compared to non-adopted children, adopted children have larger amygdalas [6, 9, 10]. It is possible that this is because their amygdalas have begun to develop sooner due an early absence of comfort during stressful situations [6, 9, 10]. Oftentimes, children raised in orphanages do not have stable caregivers since care is limited and often fluctuates. Therefore, children who experience prolonged negative caregiving experiences may have to “grow up” faster; their brains begin to develop sooner to form the connections needed to cope with stressful situations independently [7]. In the absence of a stable caregiver, faster maturation of the amygdala may be adaptive because it can facilitate adult-like fear learning and avoidance, such as learning not to eat spoiled or toxic food. This “fear learning” and avoidance can help children navigate stressful environments, thereby increasing their chance of survival [7]. However, while accelerated development of the amygdala may be adaptive in adverse environments, it may be maladaptive in safe environments. Children that have larger amygdalas may be more sensitive to cues for danger than their peers, making them more anxious. These children may gen-

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cir-

Have No Fear, Your Hidden Fear Response Regulators Are Here cuit develops at an accelerated rate, it will not be as effective at reducing fear responses after the stressor has passed; this prevents an individual from orienting towards more goal-directed behavior, such as deep breathing, to help them calm down [12]. Notably, parents can help children navigate stressful environments by reducing fear responses, effectively preventing this disruption of normal maturation. Early parental deprivation is linked to premature development of this circuitry, impacting a child’s ability to deal with difficult situations later in life. Responsive caregivers equip children with the cognitive ability to cope with stressful situations on their own [7].

WHAT’S LOVE GOT TO DO WITH IT?: HOW PARENTS REGULATE FEAR RESPONSE Although you may have been terrified of the unfamiliar dog at first, you most likely calmed down after your parents held and comforted you. Your parents may have pet the dog to show you that it was friendly rather than dangerous. After some time, you may have even felt brave enough to pet the dog yourself, as long as your parents were nearby. This situation is an example of parents providing sensitive caregiving — that is, they were attentive to your needs [13,14]. Sensitive caregivers can make children feel safe and secure by calming them down in the presence of environmental stressors [15]. When a child and a caregiver interact, a hormone important in strengthening the parent-child bond, called oxytocin, is secreted [16,17,18, 21]. A common example of child-caregiver bonding is when a mother makes baby-talk noises while her infant babbles. This phenomenon is called parental synchrony: a caregiver mimics or coordinates their behavior with the child’s non-distress cues, such as touch, gaze, and vocal or facial expressions [19]. Parental synchrony may even look like a nuanced dance where the caregiver subtly responds to the child’s cues [20]. As the two interact, the levels of oxytocin — the “love hormone” — increase in both the child and the caregiver [21]. Oxytocin then attaches to its receptors found

throughout the amygdala, causing the child to feel calmer when faced with a fear-inducing stimuli [22, 23, 24, 25]. Thus, parents may be able to calm their children’s stress response with their presence, which stimulates the secretion of oxytocin and effectively reduces amygdala activity. Furthermore, when parents are able to facilitate the release of oxytocin and reduce their child’s stress response to threatening situations, the child is more likely to develop the proper circuitry important for emotion regulation. The calming effects of their presence promote proper connectivity between the child’s amygdala and medial prefrontal cortex. Sensitive caregiving enhances this connectivity by activating both brain regions simultaneously; if this activation occurs repeatedly, the circuitry between the amygdala and the medial prefrontal cortex is more likely to develop properly [6,7,8]. This reciprocal connection is necessary because it supports effective fear regulation: the medial prefrontal cortex works to reduce the duration of the amygdala’s responses to false alarms. Medial prefrontal cortex-amygdala connectivity prevents feeling excessive or unwarranted fear, reducing the chance that a child may experience anxiety later in life. In sum, caregivers’ sensitivity shapes the strength and nature of amygdala-medial prefrontal cortex connectivity development, in turn, influencing their child’s stress management skills.

HELP, I NEED SOMEBODY! NOT JUST ANYBODY Think back to when you first encountered that scary dog. Having your parents guide you through this fear-inducing experience created long-lasting influences on how you perceive and respond to threats in your environment. We have all developed coping mechanisms to help us ease our nerves before, during, and after stressful situations, whether it

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Have No Fear, Your Hidden Fear Response Regulators Are Here

be listening to music to distract ourselves or pacing around the room and taking deep breaths. Whatever coping mechanisms you use today may be effective because your early caregivers equipped you with the mental capacity to calm yourself down. So, the next time you find yourself taking a deep breath to calm down before giving an oral presentation or going to a job interview, you may have your parents to thank. References on page 83.

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404 Accessibility Not Found

404 ACCESSIBILITY NOT FOUND: DISABILITY AND TECHNOLOGY by Nicholas M. Weiner art by Yuchen Wang

magine living in a world that isn’t built for you. Perhaps the stairs on the way to class are too high, or every door you go through is just a bit too narrow. Unfortunately, this is just a snippet of reality for many people with disabilities: they live in a world that was built specifically for their non-disabled peers. A disability is a condition of the mind or body that makes it difficult to perform essential everyday tasks and interact with the world as it is currently structured [2]. To lessen these difficulties for disabled folks, those who design public-facing facilities need to make sure peo-

ple with disabilities can use the facilities as easily as those without. The practice of ensuring that people with disabilities have equal access to resources is called accessibility [3]. The disabled community often faces difficulty accessing public facilities designed without their needs in mind. People with disabilities make up 15% of the world’s population and 26% of the United States’ populace, meaning that large swaths of the population are unable to access resources that are intended for everyone [5, 6]. For example, if voting takes place in a building without ramps, those who use wheelchairs will have a significantly harder time participating in elections. One of the most promising implementations for accessibility is the development of usability-increasing technologies, which addresses the varied needs of those with disabilities. However, even technologies that increase usability often have barriers. Designers may not acknowledge the diversity of needs when expanding accessibility in the digital sphere. Our society needs to place more emphasis on creating and researching new accessible technologies and making current technologies more accessible to all, regardless of disability status.

AN INTRODUCTION TO NEURODIVERSITY Think back to when you were in first grade. Your teacher drones on and on about grammar rules and multiplication tables, and you find it difficult to concentrate. The sound of the teacher calling your name interrupts the seemingly endless lesson. When you struggle to respond, they scold you for not paying attention, unaware that you weren’t able to think through the question yet, or that a condition, such as dyslexia, may have interfered with your ability to process the class reading. This frustrating situation demonstrates the reality faced by many neurodi-

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404 Accessibility Not Found verse individuals. In the fields of neuroscience and cognitive science, patterns of thinking and learning have been sorted into two categories: neurodivergent and neurotypical. The word “neurodivergent” describes people who have neurological conditions, such as autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and dyslexia [7]. Conversely, the term “neurotypical” refers to individuals without any sort of neurodevelopmental condition [8]. Therefore, neurodiversity is the spectrum of variations in human brain function, which includes both neurodivergent and neurotypical individuals [7]. The concept of neurodiversity posits that both neurotypical and neurodivergent thinkers fall into this expected variation [7]. Unfortunately, much of society’s physical and social infrastructure is not constructed to accommodate neurodiversity [9].

nologies that may serve the large community of individuals experiencing difficulty accessing essential public resources.

FICTIONAL PEOPLE SOLVING REAL-WORLD PROBLEMS: PERSONAS, HCI, AND UX Mia is a university student who loves an eclectic mix of podcasts about true crime, history, and comedy. She also happens to be deaf. What can the developers of a podcast app do to support users like Mia? In this case, the developers need to address the inherent difficulty of using an audio-based podcast app as a deaf person. Consequently, they construct a fictional character, Mia, to gain perspective on their product from her imagined point of view. By using Mia’s experience as a guide, the developers are encouraged to implement transcription functionality for their app.

There are many tasks that neurotypical and non-disFictional characters like abled people trivialize: Mia, who represent uswalking, speaking, absorb- THE US GOVERNMENT DEFINITION OF ACCESSIBILITY ALLOWS ers with disabilities, are FOR SEGREGATED PRODUCTS AND ENVIRONMENTS, AS ing information in a classknown as personas. Perroom setting, or using their OPPOSED TO UNIVERSAL DESIGN, WHERE ALL PRODUCTS sonas help developers senses to interact with the AND ENVIRONMENTS ARE BUILT FOR EQUAL ACCESS BY plan for variability in the world, to name a few. Some DISABLED AND NON-DISABLED PEOPLE [3, 4]. IN PRACTICE, user base by creating people struggle with these EFFECTIVE ACCESSIBLE DESIGN IS ALMOST ALWAYS diverse, imagined chareveryday processes due acters [11]. Without perSYNONYMOUS WITH UNIVERSAL DESIGN [4]. to disabilities. Disabilities sonas, it is easy for decan manifest in a variety of signers to generalize their forms: impairments in audiuser base. In doing so, designers fail to acknowledge tory, cognitive, neurological, physical, speech, or visual the wide variety of individuals using their product, systems; they can arise at birth or develop later in life some of whom may be neurodiverse or living with as a result of illness, accident, injury, or old age [2, 10]. a disability. Creating personas based on disabled or There are more than 61 million Americans with disa- neurodivergent consumers, such as Mia, allows debilities, and over a billion disabled people worldwide; velopers to better conceptualize this variability [12, yet, as noted earlier, many public resources do not take 11]. When tech designers construct personas to repthis significant demographic into account [5, 6, 9]. To resent users with disabilities, like blind users, deaf address these common barriers to accessibility, scien- and hard-of-hearing users, colorblind users, or ustists have designed devices called accessible technolo- ers with Parkinson’s disease, their new designs are gies. These technological tools make the lives of people more likely to be accessible to people from a greater with disabilities substantially easier. For example, peo- variety of backgrounds [10]. Further, the creation of ple with auditory impairments can use hearing aids to personas increases developer awareness of disabilhelp them interpret sound and speech, while amputees ity-related issues, while prompting developers to can use prostheses to stand in for limbs. Those with consider how their technologies can be effectively mobility issues can use wheelchairs instead of walking, used by the widest audience [11, 13]. Thus, to design and non-verbal people have the option to use text-to- products for users with disabilities, it is essential to speech apps to participate in verbal communication. In first understand how disabled users prefer to interfact, you may even use a form of accessible technolo- act with their devices. gy yourself; eyeglasses allow many people with minor visual impairments to more easily navigate the world. Human-Computer Interaction (HCI) is the study of With this in mind, let’s take a look at some of the new how humans interact with computers [14]. The goal and increasingly advanced forms of accessible tech-

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404 Accessibility Not Found human-computer system gives them the ability to perform tasks they might not be able to do otherwise. For example, people living with Amyotrophic Lateral Sclerosis (ALS) are often affected by dysarthria, a condition that causes the muscles used to produce speech to atrophy or weaken, preventing them from speaking [18]. Thankfully, devices exist that help people with ALS produce speech [18]. Stephen Hawking used this kind of speaking device during the progression of his ALS, allowing him to continue contributing to the scientific community until the end of his life [19]. Still, more research is needed to understand how computer design can provide disabled users the same opportunities as non-disabled ones.

of HCI is to create a continuous relationship between human users and computers, allowing computers to become a useful tool and an extension of their user [15]. HCI integrates several fields, such as computer science, cognitive science, linguistics, cultural anthropology, sociology, ergonomics, and visual design [14]. Many neuroscientists view HCI as one of the best approaches to restore independence among people living with extreme paralysis, or “locked-in syndrome,” a rare neurological disability that causes individuals to retain consciousness but lose all motor control, except in their eyes [16, 17]. HCI principles can be used to create technology that allows individuals living with locked-in syndrome to communicate via a computer by using input sensors which track eye movements. Even in instances in which people have disabilities less severe than extreme paralysis, creating a continuous

Along with an understanding of HCI and personas, User Experience (UX) research is another essential piece of the design process for accessible technologies. UX is the study of users, how they interact with technology, and what limitations exist that create distance between the user and technology [20]. In short, UX puts the theories of HCI into practice. In order to collect information about how users interact with products, UX researchers conduct experiments to collect and observe physiological and neurological data surrounding participants’ experience with the new technology; the results of such studies signal the effectiveness of the human-computer systems at work [21]. If the physiological responses indicate that a system is causing users stress, for example, UX researchers can brainstorm ways to eliminate this stress while preserving the human-computer system’s benefits. By using this quantitative data in combination with qualitative data from user stories, UX researchers piece together the best ways to improve the users’ encounters with their product [21]. It’s important that UX experts make a conscientious effort to include disabled research participants in their studies. By doing so, these researchers can design and prototype the next generation of accessibility technologies.

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404 Accessibility Not Found

VIRTUAL REALITY: A WHOLE WORLD OF ACCESSIBLE POSSIBILITIES What if you were able to experience the whole world while remaining in one place? You could hike through the Amazon Rainforest, score touchdowns as a star Super Bowl quarterback, or even travel to the moon. Through the development of virtual reality (VR) technology, such fantasies are quickly becoming a reality. Unlike a traditional computer interface, VR typically uses headsets and motion sensors to place the user inside a completely immersive, simulated environment [22]. However, VR technologies have more uses than mere recreational fun. With broad applications for treatment and rehabilitation of many forms, VR technologies have the potential to radically deconstruct barriers to access for people with disabilities. VR technologies are especially promising tools to provide occupational therapy and education to children with ASD. Individuals with ASD often struggle to develop executive functions — a combination of working memory, mental flexibility, and self control — that are essential for daily life [23]. There are two leading methodologies for supporting ASD children through the process of developing executive functions: behavioral therapy and Theory of Mind (ToM) [24]. Behavioral therapy involves a complex process of reinforcement and repetition in different types of environments. One example of behavioral therapy would be a special education program that combines the efforts of several teachers, aides, and the child’s parents. This type of program might have the child alternate between mathematics and writing tasks for many consecutive days to practice the executive functions required for these tasks. Conversely, ToM involves the repetition of simple tasks under more static conditions. For instance, a child might attend occupational and speech therapy for an hour a day, where a single therapist instructs them through multiple short reading and speaking tasks. VR-based therapy for ASD children combines the best of both methods; it creates variable and safe environments for autistic children to

experiment, while requiring fewer financial and labor resources than traditional behavioral therapy. ASD children might use educational VR modules that teach the same concepts as the behavioral therapy modules in a preprogrammed environment, allowing children to experiment and learn with minimal supervision [24]. Further, VR-based treatments are especially promising because they are easily customizable. Among individuals with ASD and other cognitive disabilities, there is great variability in cognitive skills, motor skills, and therapeutic and education needs [25]. Since VR design applications such as Unity and Microsoft Hololens are customizable, specialized treatment can be made for users with different types of cognitive disabilities. For instance, treatments that

incorporate storytelling are thought to be most effective for young children with ASD [25]. It might be easier to explain money management to young children with ASD by having them think through how to run a lemonade stand, rather than simply giving them mathematical equations to solve. Due to its customizability, it is easy to create VR story-based educational programs for children with ASD. Therefore, given that the American public education system is not always set up to support students with autism, VR technologies are a great potential solution to help support their educational experience. VR technologies also have great applicability for rehabilitation, as they can help patients recovering from a stroke or a traumatic brain injury (TBI) regain the ability to perform daily functions in a digital environment [26, 27]. VR allows patients with TBI to

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404 Accessibility Not Found simulate activities such as moving throughout a virtual kitchen space or village [26]. These types of technologies are empowering and effective rehabilitation tools, since they help people regain lost executive function, such as attention and balance, more quickly than via physical rehabilitation. VR-based treatment has been shown to improve executive functions in patients with TBI; the inability to control the difficulty of tasks and high distractibility of patients can make rehabilitation onerous [26]. VR technologies allow control over task difficulty and distractions, enabling an earlier start in the recovery process [26, 28]. From its applications in deconstructing barriers faced by both neurodivergent and disabled people, to its ability to speed up recovery from neurological conditions, VR is incredibly promising as a new tool for accessibili-

ty. However, additional research is needed to determine the best method to mass-produce VR technology and seamlessly integrate it into society. Currently, the main limitations of VR systems are their price and lack of fully developed rehabilitative software. Many disabled people who could benefit from VR-based treatments and rehabilitation are prevented from using it due to its high cost. And, since the size of the user base is limited by the cost of entry, VR apps are not as polished as apps on other platforms. These financial and practical barriers currently inhibit VR from being truly accessible. In the meantime, designers can focus on making an extremely pervasive technology more accessible to users with disabilities: the internet.

CAN THE “WORLD WIDE WEB” LIVE UP TO ITS NAME?

Imagine applying for a job, researching for a term pa-

per, or video calling friends without using the internet. What if every time you visited a certain website, key elements of it were broken and unusable? In our modern age, it is almost impossible to opt out of smartphone, computer, and internet use. However, 15% of Americans with disabilities report that they never go online, compared to the 5% of Americans without disabilities [29]. Since more than 25% of the population of the United States identifies as having some form of disability, this amounts to an estimated 12.9 million Americans with disabilities who never go online [6, 29]. The large discrepancy between disabled and non-disabled Americans’ use of the internet suggests a lack of web infrastructure to support internet-users with disabilities. Unsurprisingly, only 2.6% of websites are fully accessible [30]. This alarmingly low percentage indicates that there is not enough awareness or consideration of accessibility needs during the design process. This section will review the attributes that render a website accessible or inaccessible in order to convey the obstacles disabled internet-users experience, as well as the methodologies used to remedy these obstacles. To accommodate disabled users, software engineers have created programs that offer a variety of ways to engage with the internet. These programs, known as accessibility aids, are tools designed for disabled people to interact with modern devices. For example, blind users can use screen reader applications to narrate the contents of a website as they scroll. Deaf and hard of hearing users can add closed captioning extensions to their internet browsers to compensate for video and audio services that do not come with captions by default. Users with low vision can add extra magnification functionality to their browsers, allowing them to read text they can’t see with default browser configurations. Each of these pieces of technology can be useful to allow users with disabilities to access web pages. However, the most effective way to ensure web page accessibility is for web developers to design their websites with accessibility in mind from the start.

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404 Accessibility Not Found To promote website usability, The World Wide Web Consortium (W3C) sets standards for accessible web pages. The W3C’s Web Content Accessibility Guidelines (WCAG) is a series of design guidelines developed to provide uniform standards for web content accessibility [31]. The WCAG recommend including screen reader support for users who are blind and have low vision, subtitles on video content and transcripts of audio content for users who are deaf or hard of hearing, and the ability to navigate websites exclusively with the keyboard for users with limited mobility. The WCAG also provide layout suggestions that make websites more predictable for neurodivergent users. For example, those with ASD often feel more comfortable with predictable website layouts, because a lack of a cohesive design can cause unnecessary stress [10]. Consistent headings across a website’s pages promote easy navigation, allowing neurodivergent and disabled users to participate while simultaneously creating a better interactive experience for neurotypical users.

ten experience, we can create a more equitable world. Many techniques for implementing accessible technologies already exist. Researchers use concepts from the field of Human-Computer Interaction to design computer systems which compensate for barriers between users and their environment. Through this process, they create personas, fictional characters which serve as a reminder of the diverse user base for whom they are designing. These experts perform market research by reaching out to disabled people to ask their advice on how to improve their product’s accessibility. Non-disabled users also interact with the technical and physical worlds in a variety of ways, so providing equal support to each of these methods is beneficial for all. For example, ramps for wheelchair users also make it easier to move strollers, suitcases, and package deliveries inside a building. Normalizing design that considers a variety of users destigmatizes accommodations for disabilities.

When web developers ignore the WCAG and build online spaces without disabiled people in mind, there are often glaring design issues that make technology use impossible. One common mistake that creates barriers for blind internet-users is forgetting to label images with alt text [32]. Alt text is an attribute within image tags in HTML website code that was originally designed to describe images if they were unable to load. Nowadays, alt text is used to allow blind people to interact with images through screen readers. Similarly, another mistake that results in web inaccessibility is using unhelpful alt text that fails to convey an image’s contents or meaning (ex. “Home_page_image_2.jpg”). Web designers may also lock their pages’ font size, which prohibits resizing text for users with low vision. Likewise, users with mobility issues such as those caused by Parkinson’s disease often use the tab key to interact with websites if they are unable to exert enough fine motor control to operate a mouse. If website designers do not take tab functionality into account, users with Parkinson’s disease might be unable to fully traverse the site [32]. Not only do these poor design choices adversely affect accessibility for disabled persons, they also limit navigation and reading options for non-disabled users. Therefore, maintaining accessible practices on websites benefits all users, and should be commonplace in web design.

Despite the fact that these accessible techniques exist, the main obstacle to a truly equitable physical and digital world is the lack of awareness about the issues impacting people with disabilities [13]. Even if you, the reader, do not end up programming the next Facebook or designing the user interface for the next Google, you can take some lessons away from this article. When you create any product, whether that be a website for your small business, a menu for a restaurant, or a stairway for a local library, the users of your product will be people with a diverse set of needs. By raising awareness of these issues, and prioritizing access for all people, we can mitigate the difficulties that people with disabilities face and show compassion and inclusion to an otherwise underserved community.

THE FUTURE IS NOW: IMPLEMENTING ACCESSIBLE TECHNOLOGY

DUE TO THE SCARCITY OF PEER REVIEWED SOURCES DISCUSSING THE TOPIC OF ACCESSIBILITY, SOME NONPEER REVIEWED SOURCES WERE USED IN THIS ARTICLE. HOWEVER, ALL SOURCES USED IN THIS ARTICLE ARE REPUTABLE, INCLUDING THOSE PRODUCED BY STANDARDS ORGANIZATIONS, RESEARCH INSTITUTIONS, AND GOVERNMENT BUREAUS THAT ARE EXPERTS IN THEIR FIELDS. Special thanks to the Vassar Disability Coalition (VDC) References on page 84.

By emphasizing the development of accessible technologies to address barriers that disabled people of-

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Growing Brains In A Dish

GROWING BRAINS IN A DISH: ORGANOIDS PRESENT GREAT PROMISE IN MODELING NEURAL TISSUE by Benjamin Kheyfets / art by Max Freedman

If you saw miniature brains, livers, and pancreases suspended in jars of viscous broth, would you think you were in a mad scientist’s lair? While this sounds like an image lifted directly from a low budget sci-fi film, this scene is actually more plausible than you might expect. Artificially grown tissues resembling human organs are becoming increasingly popular in neuroscience research [1]. These fascinating structures, known as organoids, are incredibly similar in both structure and function to their corresponding organs, even down to the microscopic level. This striking degree of similarity makes organoids great candidates for novel research in medicine. Organoids of neural tissue, in particular, allow the use of innovative neuro-therapeutic techniques to study the human nervous system [2]. But how exactly do these seemingly magical structures work?

WHAT ARE ORGANOIDS? The term organoid refers to tissues that have been derived and grown from stem cells [1]. Stem cells can specialize into any cell subtype; theoretically, a stem cell can turn into a blood cell, immune cell, or neuron depending on the environment in which it’s grown. Remarkably, it takes just a few stem cells to grow any type of organ tissue. And, while this tissue may be small in size, it appears nearly identical to its corresponding organ when magnified [2]. For instance, tissue can form into specific regions of a developing brain and give rise to certain types of neurons, allowing us to study the brain in great detail [3, 4]. In this way, organoids are powerful tools that broaden the scope of what neuroscientists can study.

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Growing Brains In A Dish Because the human brain is shielded by the skull, neuroscience has historically been stymied by our inability to microscopically study a living brain. Currently, we can either study brains post-mortem, or use large-scale imaging technology like the MRI to analyze the brains of living humans. While scans like the MRI provide information about brain tissue, they fail to provide information at the cellular level. The invention of neural organoids, however, offers a unique and up-close look at living brain cells; neural organoids can act as a proxy for the brain by accurately mimicking its structure and development. Depending on the environment in which the organoid is grown, the tissues that form can capture the vast array of neural cell types, including those from specialized brain regions [5, 6]. Neural organoids can even grow into complex structures like our cerebral cortex, the outermost region of our brain associated with language, memory, and reasoning [7]. Amazingly, organoids can accurately model the development of brain tissue. Similar to sowing a seed and watching it grow, when we place stem cells into a dish to develop, organoids will form and organize themselves into the brain tissue they are modeled after. This pattern of growth, similar to that of naturally grown brain tissue, offers us a means to study and analyze human neurodevelopment like never before [8].

STEP ASIDE, RODENTS: ORGANOIDS ARE HERE TO STAY

Generally, when scientists want to test something in humans, they first use animal models to get some sense of what results may occur. Organoids are particularly useful as a complement to animal models and other popular testing techniques in neuroscience. Typically, researchers use rodents — like rats, mice, or guinea pigs — as animal models in research due to their low cost of care, quick breeding time, and high degree of similarity to humans on an anatomical and physiological level [9]. However, using these animals still comes with disadvantages. Testing anything on an animal, whether it be a genetic change or a newly developed drug, introduces new variables that often complicate the study’s results. One such complication arises from the constant cross-talk that occurs between the brain and other physiological systems. For example, the immune system can influence the nervous system’s development by regulating whether synaptic connections are kept or eliminated; this, in turn, influences how our brain develops into adulthood [10]. Certain genes associated with immunity have even been identified as risk factors for Alzheimer’s — a surprising example of this

physiological cross-talk [11]. Unfortunately, interactions between body systems are inherent to any animal model and cannot be controlled for or eliminated, making it difficult to interpret results in isolation. Further complications arise from the potentially limited transferability of animal model research to humans. For instance, rodents can not model human diseases perfectly, nor can they always replicate symptoms of a disease [13]. Thus, even though animals like rodents generally make for useful models, they can’t be used to study everything [13]. In some cases, uncommon, non-model species are used in specific fields of research; for example, the mouse lemur and African turquoise fish are ideal species to study aging in vertebrates [13]. However, while all of these animal models are greatly useful for specific research, the results of these studies still may not apply directly to humans. In fact, most drugs tested in these studies don’t make it to human trials; of those that do, most fail the clinical trials necessary to gain medical approval [14]. Since organoids are highly controllable and customizable, their use can help address many of the issues posed by animal testing. In an organoid model, a change is made to brain tissue alone, allowing us to visualize how cells respond to stimuli without interference from or modulation via other bodily processes [15]. In this way, using human brain organoids to model real human brains makes scientific results more translatable to real world applications. It’s important to note, however, that organoids can never entirely replace animal testing. Some fields of neuroscience, such as neuropsychology and behavioral studies, require animal subjects with working brains. Animal models are necessary to study how the brain will respond in the context of existing in a living body, as we are not brains with bodies in tow. Further, myriad similarities between mice, rats, and humans make animals valid candidates for research subjects. Still, organoid research is incredibly useful for filling the knowledge gaps left by animal testing.

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Growing Brains In A Dish Replicating the progression of microcephaly using organoids revealed the disorder’s cause: defective neuron development [18]. Identifying the genetic mutations of debilitating conditions such as microcephaly is essential to understanding and developing treatments.

ORGANOIDS IN ACTION Beyond being a potential alternative to animal models, the applications of organoid research extend into several fields of neuroscience and other scientific disciplines. Multidisciplinary fields such as neuroendocrinology — which connects the nervous system and our hormonal system — and neuropsychiatry — which combines neuroscience, behavior, and social psychology — can be effectively studied using organoids. Neural organoids can even be used to determine the genetic mutations associated with neurodevelopmental disorders like microcephaly, a condition which causes a child to be born with an abnormally small head [15, 16, 17]. For example, since neural organoids develop similarly to human brains via the development of distinct lobes and structures, they can also successfully model the progression of microcephaly.

Organoids can advance our understanding of neuropsychiatric disorders, such as Alzheimer’s and schizophrenia. Many neuropsychiatric disorders are difficult to study because individuals affected tend to have a variety of genetic profiles, lifestyles, and symptoms [20]. However, organoids allow each of these factors to be isolated with ease. In one instance, collagen-producing cells from schizophrenic patients were collected and manipulated to become brain organoids [21]. These organoids were then used to identify twenty five potential genes involved in the onset of schizophrenia, deepening our understanding of the role genetics might play in the disorder’s onset [21]. Important findings like these typically result from the manipulation of gene activity in neural organoids. Genes can be altered to be more or less active, and then observed to determine what changes follow; for example, this method has allowed us to determine the precise proteins that are involved in the neurodegeneration associated with Alzheimer’s disease [22]. Identifying these proteins is critical for pharmaceutical manufacturers to develop drugs that slow neurodegeneration and disease progression. While there are currently animal models that allow us to study the onset of Alzheimer’s before it becomes clinically diagnosable, there are still major differences in brain development and structure that limit the translatability of these models [23, 24]. Because Alzheimer’s is unique to humans, and experimenting on living human brains is not an ethical option, organoids can help us to develop treatments by providing us with functioning brain tissue to test [22]. However, the benefits of organoid research are not just limited to neurodegenerative disorders; recently, organoids have helped us understand the mechanisms underlying some infectious diseases. One example of organoids’ potential in this regard concerns an infectious disease known as the Zika virus, which causes microcephaly in developing fetuses. You may have heard of the Zika virus, since it garnered public attention after an outbreak in 2016. Using organoids, different genes related to the virus’s onset were isolated by accurately recreating a fetus’s developing brain tissue [25]. As a result, an existing drug was

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Growing Brains In A Dish discovered to block the spread of the Zika infection, helping us understand the virus while simultaneously improving patient care [26]. Recently, neural organoids were used to study SARS-CoV-2, the virus behind the COVID-19 pandemic. When exposed to SARS-CoV-2, neural organoid models demonstrated that the virus could enter brain organoids and alter the distribution of certain proteins within neurons, culminating in neuronal death [27]. Using an organoid model, COVID-19, which is mainly regarded as a respiratory disease, was shown to adversely affect the central nervous system, too [27]. These are just a couple examples of neural organoids’ broad potential in revolutionizing infectious disease research. However, in spite of the immense progress in this research field, organoid technology is still in its infancy [28]. A significant hurdle encountered in organoid research is that live animal brains do not operate in a vacuum; rather, they respond to inputs from the rest of the body. As isolated pieces of tissue, organoids currently cannot model this interaction between body systems. Fortunately, this problem can be addressed by combining multiple organoids into a singular larger structure, called an “assembloid” [15]. Assembloids are particularly useful for studying the brain’s development because they can model interactions between different regions of the brain and parts of the central nervous system, such as the spine. Assembloid research can also explore how neurons organize themselves on a larger scale during development, and the formation of long range connections between them. In fact, this technique has already been used to study the interactions between different types of cells during early brain development or in response to an injury [15, 29]. It’s important to note though that, like organoids, assembloids are still a very new development in scientific history. Current assembloid research mainly seeks to develop more accurate models of the interplay between our brain and the rest of our body [10, 30]. Furthermore, since assembloids are simplified models of physiological systems, they cannot account for the influences of environmental and psychological factors like childhood nurturing, emotion, and memory [15]. Therefore, while organoid and assembloid models allow researchers to explore otherwise unobservable brain processes, their novelty in the world of science and lack of connection to other bodily systems still leaves us with doubts surrounding their potential for real-world applications.

GROWING PAINS: ADDRESSING ETHICAL CONCERNS IN ORGANOID RESEARCH Organoids are revolutionary new tools in neuroscience and biomedicine; their development has even led to a new field of research known as personalized medicine. Personalized medicine uses organoids developed from a patient’s cells to create custom medicines best suited to their needs. A cancer sample, for example, can be collected from the patient, grown into an organoid, and then tested to determine which treatment is most effective against the malignant cells characteristic of cancer [31, 32]. While this may seem like a miraculous development, this branch of organoid research also raises some complicated questions. One major ethical concern brought about by organoid research is the issue of ownership and consent. Since these novel treatments could generate millions in profit, there is a clear incentive for research institutions, companies, and patients to claim ownership of organoids and the products developed from them. Because organoids carry the genetic information of the patient from whom the cells were first taken, patients may seek the right to own organoids developed using their cells. At the same time, an organoid’s successful growth and development requires the knowledge and resources of research institutions and large corporations. A high profile case of a similar dispute is that of Henrietta Lacks, whose cervical cancer cells were removed without her consent [33]. These cells, called HeLa cells, were found to have an incredible ability to survive and reproduce as they were essentially immortal. HeLa cells were widely shared in biomedical research communities and corporations made immense profits through their contributions to cancer research, immunology, and even COVID-19 vaccine development [33]. However, Lacks’s family never received any financial compensation for such use, and fair ownership of the cells is still being fought over in courts. To avoid disputes like the one Lacks’s family is facing, there is a clear need for regulations that ensure fair ownership is taken into consideration when researching, developing, and marketing treatments derived from organoids. In sum, while organoids may originate from patient tissue, outside institutions and corporations are an integral component of successful organoid research. This nuanced relationship must be discussed when discussing ownership and consent. When it comes to brain organoids in particular, mo-

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Growing Brains In A Dish tioning human neurons into the brains of living mice — should not be performed at all. Advanced organoid development calls our understanding of consciousness into question; do these structures deserve status as conscious beings, and the inherent protections that entails [34]? As organoid development continues to advance, scientists and lawmakers alike are forced to contend with these complexities. With this in mind, the US National Academies of Sciences, Engineering, and Medicine recently launched a study to determine the potential legal and ethical issues associated with brain organoids. Even so, there are currently no regulations in the United States that ban the creation of a conscious organoid. This is complicated by the fact that neuroscientists don’t yet have any established way to measure consciousness. Until a standard to measure consciousness is developed, it is unclear how to tell if an experiment crosses a line [34].

rality is a greatly controversial issue [34]. While brain organoids are undoubtedly simpler than real brains, researchers continue to make them more complex, so that a wider range of conditions can be studied. In fact, a recent study demonstrated that brain organoids exhibit patterns of electrical activity similar to the brains of premature infants [35]. This form of brain activity is a hallmark of our conscious brains, raising the question of whether brain organoid development should be allowed to reach stages of advanced development. Some neuroethicists even feel that some experiments — such as adding live, func-

Research involving brain organoids is a double edged sword. Studying human brain organoids may be critical to understanding and developing treatments for conditions that uniquely affect humans. At the same time, brain organoid research poses moral uncertainties that warrant proper regulation [34]. However, halting all research due to these uncertainties would undoubtedly close doors in research targeting potential cures or treatments for a wide range of disorders and diseases. When used properly, responsibly, and ethically, brain organoids have the potential to improve lives and develop remarkable medical treatments and products. References on page 86.

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THE 50TH ANNIVERSARY OF THE NEUROSCIENCE & BEHAVIOR PROGRAM AT VASSAR COLLEGE: ALUMNAE/I FEATURES

Alumnae/i Features

A. HARRISON BRODY CLASS OF 2012

Harrison recently completed his PhD in neuroscience from Yale University. His dissertation work involved validating targets and developing novel therapeutics for the treatment of Alzheimer’s disease. I graduated from Vassar with a degree in Neuroscience and Behavior in 2012, which was unquestionably a very exciting time for science. Jennifer Doudna and Emmanuelle Charpentier had, in conjunction with Feng Zhang and George Church, just discovered a revolutionary method of introducing targeted mutations into mammalian genomes with unprecedented levels of ease and fidelity through a process known as CRISPR Cas9. Shortly before, Shinya Yamanaka and colleagues had recently published a protocol to reprogram mature human cells into induced pluripotent stem cells (iPSCs). Once reverted to a pluripotent state, these cells could then be further differentiated into a multitude of different cell types, forever transforming basic, translational and clinical science, and effectively establishing an entirely new field of personalized medicine. Around the same time, Karl Deisseroth had developed a technique of manipulating neural activity using light. The application of optogenetics, in which lasers are used to either excite or inhibit neurons made to express light-sensitive proteins, suddenly gave researchers an unparalleled degree of both spatial and temporal control over neuronal firing. Such precision continues to yield remarkable insights into the roles specific neuronal populations play in mediating motor function, motivation, memory and cognition. This immense wave of progress and excitement in the scientific community was exhilarating, and, after a post-baccalaureate stint as a research assistant at Rockefeller University, I began my PhD in neuroscience in 2016. While I was and still am fascinated by broad questions of how neurons function together to mediate complex behaviors, memory and consciousness, after rotating in a laboratory focused on neurodegeneration, I became expressly interested in understanding how these neural systems that are so vital to our humanity break down during the course of disease. How, for example, can Alzheimer’s disease (AD), the most common cause of dementia, completely rob a person of their agency, memory and personality, and what, if anything, can be done to stop it? In the United States, Alzheimer’s disease is the 6th leading cause of death overall and the 5th lead-

ing cause of death in individuals 65 years and older. Since age is by far the largest risk factor for AD, as deaths due to heart disease, stroke, and cancer continue to decline, the number of individuals who live long enough to become susceptible to AD is growing at a rapid pace. The Alzheimer’s Association, which publishes an epidemiological snapshot of AD annually, predicts that the number of Americans suffering from AD will increase from 6.2 million in 2021 to 13.8 million by 2060. While no dollar amount can be assigned to the suffering of those with AD and their loved ones, the financial burden associated with AD care has grown to shockingly inequitable and unsustainable levels; according to the Alzheimer’s Association, the lifetime cost of care for an individual with AD in the US is now more than $373,000. In aggregate, the direct cost of care for Americans with AD was an estimated $355BN in 2021. This, combined with opportunity costs of an estimated $256BN in lost wages (from a staggering 15.3 billion hours of unpaid care), creates a total annual cost that represents almost 3% of US GDP. In addition to age, risk factors for AD can be environmental and lifestyle-related, though there has been considerable excitement surrounding a growing list of genetic factors associated with AD risk, all of which have been identified through a massive, global effort to better understand the genetic contributions to a disease that is overwhelmingly sporadic in nature. Already, this list of thirty or so genes has yielded critical insights into the pathophysiology of AD and, most optimistically, has the potential to reveal novel targets for the safe and effective treatment of the most common form of dementia. Yet simply knowing which genes are associated with variable AD risk is insufficient to drive progress towards the discovery of new therapeutics. Understanding how these genetic risk factors contribute to AD and identifying which, if any, might make suitable pharmacological targets is crucial. Alzheimer’s, an unquestionably complex disease, is further complicated by the fact that, unlike many other forms of dementia that involve the aberrant pro-

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Alumnae/i Features cessing, misfolding and aggregation of a single protein, AD is defined instead by the dysregulation of two separate proteins, amyloid beta (Aβ) and Tau. As AD progresses, Aβ accumulates outside of neurons, building up to form dense structures called senile plaques. Tau, on the other hand, aggregates within neurons forming tangled webs of protein fibrils aptly called neurofibrillary tangles. While the most widely accepted view of AD pathophysiology, often referred to as the “amyloid cascade hypothesis,” suggests that Aβ aggregation precedes and leads to the aggregation of Tau, there is little consensus over which protein might make the better pharmacological target. Both proteins, when misfolded, are toxic to neurons, and both are known to cause loss of synapses. Preserving synapses, the junctions between neurons that allow them to communicate with one-another, is of utmost importance in the fight against dementia. Given how necessary these structures are for memory, cognition and behavior, it is not surprising that synapse loss is the strongest pathological correlate of cognitive decline in AD. Yet regardless of where one stands in prioritizing either Aβ or Tau for the treatment of Alzheimer’s, a complete understanding of the disease is not possible without considering the contribution of both. Likewise, knowing how a specific genetic risk factor for AD might increase one’s susceptibility to dementia also depends on learning how that risk factor interacts with both Aβ and Tau. My PhD dissertation began where another graduate student, Santiago Salazar’s, left off. Santiago’s work found that one AD risk factor in particular, a protein called Pyk2, contributed to and was necessary for Aβ toxicity. Removing Pyk2 from mice that express high levels of (or “over-express”) Aβ halted synapse loss, preserved synaptic function and improved the animals’ memories. These results, combined with work from a post-doctoral researcher in our group, Suho Lee, who found that Pyk2 was also necessary for Aβ toxicity in cultured neurons, were extraordinarily exciting. Immediately, questions were raised about the suitability of Pyk2 as a potential therapeutic target. Since Pyk2 contributed to Aβ’s ability to damage synapses in these model systems, drugs that inhibit Pyk2’s activity might also prevent Aβ toxicity in people. However, one pivotal question remained: would removing Pyk2 from mice that over-express Tau also improve their memory? At that point, there was promising evidence for the affirmative. Pyk2, whose activity increases in presence of Aβ, was known to interact with and activate other proteins that compromised the stability of Tau, modifying it in such a way (through a process called hyperphosphorylation) that leads to

its misfolding and aggregation. Initially perplexing results were impossible to dismiss as they were replicated, time and time again, across multiple model systems. Although, as Santi and Suho’s work demonstrated, the deletion of Pyk2 improved the conditions of mice that over-express Aβ, the deletion of Pyk2 in mice that overexpress Tau consistently produced the opposite effect. Removing Pyk2 from these animals further reduced their survivorship, impaired their memory and led to even greater degrees of Tau hyperphosphorylation. Even more, inhibiting Pyk2 pharmacologically in cultured human cortical neurons derived from iPSCs demonstrated similar effects. The conclusions were clear: Pyk2 was playing divergent roles with respect to Aβ and Tau. On the one hand, a convincing body of evidence strongly suggested that Pyk2 contributes to Aβ toxicity, and on the other, an equally compelling body of evidence suggested that Pyk2 protects against the pathological processing and toxicity of Tau. The implications of these results quickly extinguished any hope of a simple pharmaceutical intervention designed to target Pyk2. Inhibiting Pyk2 might protect neurons from Aβ-induced damage only to make them more susceptible to harm from Tau. Conversely, while activating Pyk2 might suppress tau aggregation, it might simultaneously expose neurons to even greater levels of Aβ toxicity. Though these were not the results for which we had initially hoped, they call to mind an axiom familiar to scientists from every field, often spoken with equal parts exasperation and humility- “the data are the data.” Pyk2 may not make a suitable target with today’s technology, but the endeavor was in no way unproductive. Every incremental scientific discovery helps construct a more complete understanding of the universe, and in the case of AD, knowing which risk factors to target is just as important as knowing which to avoid. It might appear now that the more we learn about AD, the more complicated it seems, and I’ve certainly wrestled with that frustration throughout the course of my training. As the global population ages, and as the number of individuals suffering from this devastating disease grows, the need for effective treatments becomes increasingly urgent. But there is also reason for cautious optimism. The funds Congress appropriates to the NIH for AD-related research have been growing every year, and in June of 2021, the FDA approved the first new AD therapeutic in nearly two decades – a monoclonal antibody called Aduhelm (aka aducanumab) from Biogen.

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Alumnae/i Features

My hope is that the approval of Aduhelm will galvanize a wave of new interest and investment in experimental AD therapeutics. Biogen has, for all intents and purposes, established a proof-of-concept that next-generation AD drugs can be approved and brought to market in the 21st century. Until now, AD has been somewhat of a perilous crusade for the biotech and pharma industry. The incredible impact (and massive returns) associated with successfully bringing a new AD therapeutic to market have been tempered by an abundance of failures. For decades companies have spent billions on drugs that have all, until recently, failed in clinical trials. Whether Biogen’s success portends a new era for AD research is still unknown, but Aduhelm’s approval offers a fitting rejoinder to a lesson I’ve learned during my PhD. Though the toughest and most meaningful questions we face are still unanswered, every small step, every incremental discovery, still guides us forward.

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Alumnae/i Features

ALEXA MOUSLEY CLASS OF 2020

Mousley aims to understand human structural brain organization in early life using machine learning mechanisms to simulate developmental patterns. When I arrived at Vassar, I was excited and nervous just like everyone else. Despite my enthusiasm to be on campus, I wasn’t all that eager to start classes. Twelve years of listening to uninspired teachers had turned this science-obsessed five year old into an unmotivated and uninterested 18 year old. I had fallen out of love with learning. Going to college was the expected next step, and I could continue playing basketball, which I loved, but I was unclear about what I wanted to learn. I picked classes somewhat aimlessly. I showed up to my classes (often a few minutes late) and listened with mild interest. I went through the motions with no clear goal. In my second year, I signed up for principles of physiology with little understanding of what physiology would entail. As the semester progressed, I started telling my friends about what I was learning. I also began to show up to class, not just on time, but early. Without realizing it, I was slowly reengaging with learning through the wonders of action potentials and neuroanatomy. It finally hit me when my friend asked if I could stop talking about the role of GABAergic interneurons in neural activation — I was enjoying studying for my upcoming test. What a shocking turn of events! My science-obsession, beaten down over the years by standardized testing, had been reignited, and I was ready to capitalize on the many opportunities Vassar provides for its students. By my senior year (2020), I had slowly checked off many experiences that are common for Vassar neuroscience students. I’d spent many late hours in the basement of Olmsted, pretended I was not terrified while presenting my first poster, and experienced the excitement of discussing my first ever scientific results. The cliché is true: there were many lows (RIP to Hansel the rat that I unwisely named), but there were many, many more highs. The culmination of my research experiences at Vassar both helped me to find my passion and prepared me to take on new challenges. After I graduated, I spent the first year of the pandemic applying for PhD programs and funding. Through this process, I began to truly appreciate how, during my

time at Vassar, I had learned skills in project development, data collection and analysis, writing up scientific results, and presenting research at academic conferences. After an intense interview with a panel of researchers, I realized that graduate programs weren’t assessing my content knowledge. They were exploring my research skills. They wanted to see that I could flexibly answer challenging “what if” questions in a way that demonstrated I understood how to design a good research study. I didn’t need to know it all— I had to show I could figure it out. In October 2021, I accepted a Gates Cambridge scholarship to study for a PhD in medical sciences at the University of Cambridge’s MRC Cognition and Brain Sciences Unit in the United Kingdom. Now, I’m using artificial intelligence to explore the mechanisms of structural brain development in infants (supervised by Dr. Duncan Astle). Eventually, I’m hoping to use simulations of brain development to explore the relationship between emerging brain structures and cognitive development in early childhood. This differs dramatically from my days of immunohistochemistry research and performing surgeries on mice in Olmsted. Transitioning from an undergraduate student to a PhD student has also meant overcoming the steep learning curve of moving from animal neuroscience to cognitive neuroscience. I’ve said, “I don’t know,” about a million times, and Google is my best friend. I may not have walked into this PhD program knowing about preterm brain development or how to pronounce words like ‘Euclidean,’ but I do know how to ask the right questions. My best advice for future graduates of Vassar neuroscience is to strike a balance between being open-minded and critical and to be honest when you don’t know something. I was lucky to learn these things from incredible professors, advisors, and lab-mates at Vassar. If your post-graduate experience is anything like mine, you won’t know everything you need to know, but Vassar neuroscience will have taught you how to learn it.

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Alumnae/i Features

AMY ROTHMAN SCHONFELD CLASS OF 1973

Thank you to Grey Matters for giving me the opportunity to stop and reflect on my career as the fiftieth year since my graduation from Vassar (1973) looms ahead. I majored in biopsychology, which was a new major at that time, because the requirements included both the psychology courses I enjoyed and the basic sciences such as biology, physiology and chemistry which I needed. I was also able to do an independent research project exploring the effect of estradiol on cognition. My career goal was medical school and, frankly, when that did not work out, my future seemed murky indeed. But, as they say, when one door closes, another opens. That is my message to you as college students today. The summer after graduation, I saw a job posting in The New York Times for a lab assistant in the laboratory of Michael Gazzaniga, a biopsychologist noted for his “split-brain” research. I am sure I got the job because of my biopsychology major at Vassar. My responsibilities were to conduct research experiments in rats and monkeys on brain laterality (how the two sides of the brain specialize in brain functions and how they interact). This job was a game changer, for it introduced me to the world of academic research as well as the importance of medical communications (research papers, grants, oral presentations). With a new career goal to be an academic researcher, I applied to the doctoral program at the City University of New York/Mount Sinai School of Medicine in the department of pharmacology to work for a prominent neuropharmacologist, Stanley Glick. I was fortunate enough to be given a stipend to cover my basic living expenses living in New York City. My first two years in the program focused on coursework, including neuroanatomy and neuropharmacology. My doctoral thesis explored the relationship between brain laterality and seizures, using gerbils who were bred to have natural seizures as a model for epilepsy. I learned the importance of being able to write research papers, give oral presentations, and get critically-needed funding to continue one’s research. I loved academia for its intellectual challenges, opportunity to interact with brilliant and exciting people,

and the inner self-satisfaction of contributing to the pool of medical knowledge. To sharpen my skills, I accepted a post-doctoral fellowship in neuropathology at the Albert Einstein College of Medicine and subsequently became a research associate and then assistant professor in the department of neurology at the same institution, working with a wonderful researcher/clinician Dr. Robert Katzman. His specialty was Alzheimer’s disease. My research focused on evaluating a possible growth factor for cholinergic neurons, which are dysfunctional in those with this debilitating neurological condition. A bulk of my time was spent writing research papers and submitting grant applications to governmental and non-governmental agencies. This part of research can be disheartening because, at least at that time, funding was very limited and very competitive to secure. Then my life took a different turn. I had two young children at that time, and I could no longer devote so much of my evenings and weekends to my career responsibilities. My husband, a neuroradiologist (note I even married someone involved with “neuro”) finished all his training and accepted a job in New Jersey. Again, I was at a career crossroads. Fortunately, I discovered medical writing as a career, thanks to a great degree to the American Medical Writers Association (AMWA), which is a wonderful resource to develop skills and find opportunities in medical communication. Professionally, I now describe myself as a medical writer who specializes in neurology and pharmacology. Over the years, I have had lots of clients. Most of my work comes from medical communication agencies, which act as middlemen between writers/editors and pharmaceutical and device companies. I have written peer-reviewed manuscripts that have been published in medical journals on Alzheimer’s disease management and imaging, dementia, epilepsy and anticonvulsants, depression, cerebral palsy, sleep disorders, restless legs syndrome, brain tumors, pain, stroke, and neuroimaging. Although I am not usually listed as an author, I am listed under “Acknowledgements.” In addition to manuscript writing, projects often include preparation of scientific literature analyses, research summaries, posters, newsletters, continuing medical

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Alumnae/i Features education materials, lecture slides, curriculum kits, and web content. This work involves constant interaction with investigators and support staff and requires extensive literature research and data analysis. Some of my most fun assignments can be categorized as medical journalism. Pre-COVID, I traveled to medical meetings, attended lectures, and was able to interview amazing leaders in their fields. My writings have appeared in such publications as Neurology Today, Psychiatry Today, Rheumatology News, and Radiology News and many of these stories are re-circulated by other medical sources (you can check these out by googling Amy Rothman Schonfeld). The goal of these stories is to translate hard science into readable material for physicians, and to inform non-experts about important advances in their fields. I also wrote many entries for the psychiatry division of WebMD. I was proud to have received an award in medical journalism from the American Academy of Neurology. If you want to know more about medical journalism, a good resource is the Association of Health Care Journalists (AHCJ). So, yes, my degree in biopsychology from Vassar has served me well. I am grateful that I am always learning new things and interacting with very smart people. As a freelancer, I have had more flexibility in my personal life than most. My message for you is get as much training as possible and enjoy the journey wherever it takes you.

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Alumnae/i Features

MADHAVI JERE CLASS OF 2020

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Alumnae/i Features

DARYL ANTONIO DURAN CLASS OF 2012

Daryl is currently working on an addiction medicine research project, with a MD/PHD Family Medicine Physician, aimed at collecting data on the effects of marijuana use on men and women over the age of 25 years old. His research works toward the goal of estimating the impact of early vs. late initiation of regular marijuana use on measures of cognitive function, impulsivity, and biomarkers of stress and inflammation in adults, as well as estimating sex differences on each of these markers.

DEFYING EXPECTED OUTCOMES AND OVERCOMING ABLEISM: AN ALL-ENCOMPASSING APPROACH OF “MEETING THE PATIENT WHERE THEY ARE AT” As a pre-med college graduate looking to build experience through meaningful job opportunities before applying to medical school, little did I know that one Craigslist ad I came across would change my life forever. A mother was looking for more volunteers to add to a team that was carrying out a social behavioral therapy intervention, called the “Son-Rise Program,” for her daughter Maria.* The Son-Rise program tells the incredible story of a severely autistic boy and how his parents help him to grow out of his autism. I read the book and viewed several videos provided by the mother in order to better prepare myself for working with Maria. I was in awe at how simple, but impactful and effective, some of the ideologies seemed to be. One of the most powerful messages that stuck with me involved the judgment that society often places on neurodiverse children; autism is often viewed as a tragedy. While it instead can be seen as an opportunity to learn from your child, and try to be a part of their world so that you are then able to share the world as you experience it with them. Another central tenet includes the idea of parents knowing what is best for their child. The attitudes of parents can determine how effective individuals can be in enabling a child’s growth and remaining motivated over time: “embracing without judgment where your child is today and believing that your child can go anywhere tomorrow.” The Son-Rise model distinguishes autism as a social relational disorder, not a behavioral disorder; thus, behaviors are symptoms of autism and extinguishing behaviors will not get rid of autism. The behavior of a neurodiverse child plays a key part in the technique lauded in this program: joining. The book describes joining as copying a child when doing a repetitive behavior that excludes other people; this behavior is referred to as an “ism.” The best way to join a child’s “ism” is to use genuine energy, excitement, and engagement to find the fascination in your child’s behavior. Joining is found to promote social engagement

and eye contact; once you have the opportunity, invite the child to participate in an activity or game based on something the child likes and keep it going for as long as possible. The four main fundamentals of the Son-Rise developmental model include: eye contact/ nonverbal communication, verbal communication, interactive attention span/looped conversations, and general flexibility. And, most importantly, incessantly celebrating the little successes when we see the desired behaviors with the child along the way. Learning about the story, ideals, and techniques of this intervention, I was excited to join a team of volunteers working towards improving the quality of life of this young girl. I will never forget the day that I met Maria, a thirteenyear-old girl. As the mother introduces me to her child in her playroom, I see that Maria is sitting at a table drawing. She quickly looks up at me barely making eye contact and in a unique cadence says, “Hello Daryl.” As an uncle who always enjoys playing with my five nieces, I excitedly say back “Hi Maria, it’s really nice to meet you!” Maria continues to work on her art and begins to sing to herself. I quickly notice that Maria does not seem to have control over how she expresses herself through language. She often speaks in a stream of consciousness, narrating things as they happen, or bringing up a random fact related to her interest in Disney movies. When called by her name, she does not respond, nor does she demonstrate any acknowledgment of someone calling her name. At times, Maria is on a loop, repeating the same phrase several times in different voices or making nonsensical sounds. As I get to learn more about Maria’s behavioral deficits, I see that she often has episodes where she is overstimulated by her environment, not able to handle her visual, auditory, and tactile inputs, followed by a shutdown process. This shutdown can include laughing loudly, making squealing noises, or

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Alumnae/i Features jumping up and down on a trampoline. I also start to see green lights, my opportunities to engage in conversation or in a simple game or activity. Maria loves to listen to music and sing, so in order to capitalize on my opportunities for social interaction, as a professional classically trained musician, I used music as a bargaining tool. At first, when I began to play my flute, Maria started yelling for me to stop. I continued to play and she eventually realized I was playing a Disney song she liked. Our play sessions grew increasingly successful with my new tool of music bargaining, as I got Maria to play games with me and engage in conversations about the plots of all the Disney movies I had watched on repeat in my childhood. I spent the next two years developing a working relationship with Maria and her family, learning and mastering the SonRise techniques, and I felt a sense of accomplishment regarding Maria’s progress. As Maria started to get older, the mother began to feel as if she had achieved maximum gains with the SonRise program; additionally, the mother wanted more for Maria and thought she was starting to outgrow the Son-Rise program. After one of my sessions with Maria, her mother approached me about taking my work with Maria in a new direction: “I would like you to begin teaching her music and to play the flute.” Immediately, I thought this would be impossible. Based on the time I had spent working with Maria thus far, I did not think that her global cognitive deficits would allow her to learn something as complex as playing music. My other concerns included the expense of the instrument, the possibility that Maria could break the instrument, and most of all, I did not want the mom to get her hopes up. After sharing my concerns with Maria’s mother, she reassured me: “I know that Maria can do this and I know that you can do this with her.” After further discussion, I decided that the least I could do was try, regardless of what the outcome would be. After a few more months of Son-Rise work, I came to work one day with an instrument for Maria to use, and so my journey began. I began teaching Maria how to put together and take apart the instrument, how to hold the instrument, as well as make a sound. Maria picked up these first few goals in a few weeks, much quicker than I anticipated. I worked through trial and error in order to figure out how to make this happen; luckily, all successful efforts produced by Maria acted as positive reinforcement which helped us move forward quickly. Maria was very engaged and excited about learning to play the instrument, so I used her intrinsic motivation to propel forward to success. After she could consis-

tently make a sound, I began with teaching her simple children’s songs, starting with “Mary Had a Little Lamb.” I had Maria copy my finger movements repetitively in short sections of the song until she was able to produce it from memory. As her mind began to understand that she was learning the song, she was able to synthesize the short sections and coherently play the song. I was astounded! I did not believe I would be able to get this far. This first song led to a short library of children’s songs, ranging from nursery rhymes to holiday songs. Eventually, Maria had copied enough of my finger patterns learning different songs that she was able to start to learn to play songs by ear, without any demonstration from me. During the holiday season, Maria puts on a performance for her family and friends of all the songs we had spent the year learning. Her parents and I reflected on her progress and could not believe what Maria had been able to accomplish. As I am discussing things with her family, her mother approaches me with a new goal for Maria: learning to play written sheet music. Immediately, my mind was experiencing déjà vu. Again, I was certain that this was something that I did not think Maria would be capable of learning. While I had been successful with teaching her to play music without written sheet music, the added complexity of reading music composition seemed indubitably impossible. The mother insisted not only that Maria would be able to learn to play written music, but there was something special about the work I was doing with her. The mother told me she knew that I was able to do it. With this new goal of teaching Maria to play written music, I started to try to teach Maria to play out of an introductory flute book from the Suzuki method. After a few attempts, I was unable to get Maria to learn to read or play the music. If I was going to make this happen, I had to get creative. I began to develop an individualized music therapy program for her. I had to figure out how to break down the components of harmony, music notation, and rhythm in a way for Maria to not only understand, but then to effectively remember and produce behaviors that require her to integrate many different sensory and cognitive experiences. I created short written, verbal, and drawing exercises for Maria to complete during each session. These exercises alternated with breaks to play and listen to music, as well as play a physical game to get our bodies moving. We completed the same exercises every session, for ninety minutes, two to three times per week. I would modify activities to introduce new material and build on prior concepts, when I saw she was ready. Each week, for about two years, we would do the same thing, slowly working through our activ-

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Alumnae/i Features ity list and ingraining them in Maria until they were second nature. As the months went by, I noticed that there were connections being solidified and Maria continuously demonstrated an increased understanding of the material we were learning. Her parents and I start to notice overall improvements in her memory, ability to regulate her sensory input, language and communication, as well as an increased sense of self-actualization. Maria started to take pride in her work as a flute player with an increased sense of accomplishment along with measurable growth that had not really been demonstrated since she learned to read, speak, and write, as a younger child. After being accepted to medical school in a different state and knowing that I would only be able to work with Maria when I come home during school breaks, it was time to see if my individualized program was enough to teach Maria how to play written music. We returned to the Suzuki book that Maria had attempted to play out of nearly two years prior. Before I moved away for medical school, Maria demonstrated her ability to play music by reading musical notation and we worked through the first ten pages of the book. At my last session with Maria before moving away, I could not believe what I had accomplished; the most absurd part of it all was that I automatically assumed that Maria would not be capable of learning any of it. When I came home for various breaks over the next two years, Maria’s mother insisted on me returning to work at my leisure and was adamant that I see Maria’s progress with her new flute teacher. It was amazing to see that Maria not only retained the majority of what I taught her, but her technique improved significantly. When she performed what she was working on with her new teacher, she sounded like a completely different student. During my time developing Maria’s musicianship, I did not focus my time on getting her to “sound” good: long term learning was my focus. In the months that I was away, another teacher was able to build on Maria’s foundation and focus more on the quality of her sound. While Maria lost some of the concepts that her and I had worked through, it amazed me to see that I had equipped her with what she needed in order to continue to learn from someone else who may not have had the special combination of personality, patience, and skill set, in order to accomplish something so miraculous.

sion led me to accomplishing the goal of teaching Maria to read and play music, all while battling my societally ingrained ableism telling me that it would be impossible for Maria to do so. The outcome in this child far exceeded my own expectations as well as the expectations of her parents. As a society, we have been wrong to create the narrative that neurodiverse individuals are unable to amount to the capabilities of a neurotypical person. Implications for this approach in education, development, and healthcare for neuro-diverse children could dramatically change the course of these individuals’ lives, adding to their ability to contribute more meaningfully to society and realize their true potential. Name has been changed for patient confidentiality.

The Son-Rise principles coupled with her mother’s persistent guidance into “meeting her daughter where she is” attitude, reminiscent of the philosophy that I have learned in medical school about “meeting patients where they are at,” allowed me to work through trial and error; problem solving from session to ses-

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Alumnae/i Features

DOMINIC DEMETERFI CLASS OF 2020

ACADEMIC HIERARCHIES AND IMPOSTER SYNDROME: A LOVE STORY Hierarchies exist across all industries and social groups that humans are involved in. Whether you are a business person climbing up the corporate ladder trying to get into the E-Suite, or a graduate student dreaming of running your own lab, you will be subject to the natural pecking order in your field of choice. When you do finally scale the heights of your ambitions, you may come to a strange place, one where you feel like you are a fraud and have tricked others into believing that you are competent even though deep down inside you know that you are not. This feeling is so common in those who become successful that psychologists have a name for it: imposter syndrome. Those afflicted experience thought patterns that tell them that the success they have achieved is a result of dumb luck or being given a favorable circumstance. Furthermore, these individuals rarely acknowledge their own hard work and talent in relation to their successes, even when there is ample evidence that shows that luck played little part in their success. This culminates in the individual developing a pervasive fear of being “unmasked” and revealed for what they truly are: a fraud. It turns out, I am one of those individuals. I know that I am not alone, and I think that the reason many of my colleagues in science share this fraudulent feeling is due to the nature of academic hierarchies. My story with imposter syndrome starts after I presented my project at an National Institutes of Health (NIH) conference. I was one of three people, the other two being postdoctoral scientists, from my lab presenting. By contrast, I am a research technician. For those unfamiliar with the lab hierarchy, technicians are the lowest on the totem pole, followed by graduate students, then postdoctoral fellows, and then finally principal investigators (PIs) who run their own labs. As soon as I saw that I was the only tech presenting, my mind began hurling accusations at itself. It must be impossible that the data I collected was real. If it was even real, then I just got lucky and it probably was not replicable. I am going to go on that stage and

lie to people to trick them into believing that what I was showing them was actual science. I bet they will not even believe me, and they will ask me questions that I won’t be able to answer and out there, on that stage, I will finally be exposed for what I really am— a giant fraud. My brain was not thinking about the three straight Saturdays leading up to the conference that I spent running my experiment to collect the last pieces of data necessary. It did not give me credit for practicing my presentation until I practically could not make a mistake. None of those factors surfaced on my psychic radar. All I had was that unshakable feeling that I was just a fraudulent tech who somehow had enough luck to fool everyone into thinking that I was doing science, but whose luck was bound to run out. After my talk, one of the senior scientists in my lab came up to me and said “that was a really good talk, for a tech.” Incidentally, another scientist was standing nearby and quipped back, “No, that was just a good presentation.” The senior scientist was quite embarrassed and apologized multiple times for being demeaning. With the first comment I was left feeling my quality of work had a firm boundary, that my work could only be good work for a tech. In the greater scope of things, of course I must be a fraud because I am just a lab tech. I had no business presenting my work at this conference, and I do not know how I was even allowed to do it. The second comment made me feel I had done good work, irrespective of my status in the academic hierarchy. It did not absolve all my feelings of fraudulence, but it temporarily made me feel that what I had accomplished did not need an asterisk. Clearly then, the academic hierarchy can foster both feelings of belongingness, as well as feelings of fraud. We cannot completely remove hierarchies from academia, and we cannot change the many reasons outside of academic hierarchy that lead people like my-

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Alumnae/i Features self to experience imposter syndrome. However, we can all do better within the hierarchy to make others feel included and worthy of contributing to science, instead of like they are less than and unworthy. With the length of training needed to become an independent scientist, all aspiring scientists spend a lot of time on the lower tiers of the scientific hierarchy. If the messages they hear during this time are more like the first comment that I received, it is hard to believe that a simple change in job title will be enough for them to actually believe in their worth as scientists. However, if the feedback they receive is more like the second comment I got, then when it finally comes time for them to sit atop the hierarchy, I believe they will not feel quite as fraudulent. It is up to all of us in the scientific community to remain aware of the ways our feedback and our treatment of others impacts how they feel. It is often comforting to absolve our own shortcomings by “kicking down” and further cementing a false feeling of superiority through job title or role. Instead, it is harder to acknowledge the good work of others regardless of where they are on their scientific journey. I am not so naïve that I believe that this will completely change the nature of imposter syndrome in academia; but, I do believe that softening the boundaries of the hierarchical organization of labs will remove unwarranted feedback based on position within the pecking order, and make the lives of many scientists like myself struggling with feelings of fraud just a little bit better. I am a person before being a scientist, and a scientist before being a research technician. I hope we can shape academic hierarchies in the future to reflect that universal truth.

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Alumnae/i Features

EVE DE ROSA CLASS OF 1991

ADAM ANDERSON CLASS OF 1991

Eve De Rosa ‘91 and Adam Anderson ‘91 co-direct the Affect & Cognition Laboratory in the Department of Psychology at Cornell University. We examine influences on cognition, like emotions and neurochemistry, across the lifespan, and across species. We also co-direct a family; we have a daughter named Noa and a son named Seth. We have Vassar to thank for a life well lived in so many respects. We met each other sitting in a circle on the grass in front of Noyes on our first day at Vassar. We were both born in Brooklyn but were raised as “Island people;” Eve was raised in Bermuda and Adam was raised in Staten Island. Clearly you can see the connections! In true Vassar fashion, our initial connection and even our first collaborations were through art, not through science. Eve was the Biopsychology major who danced, and Adam was the Cognitive Science major who played classical guitar. We were both attracted to Vassar because of its strength in the arts and sciences. When we reflect on our path from Vassar to where we are today, it started with having an interdisciplinary education throughout our undergraduate career and also having exposure to research and research techniques in our later years. Jay Bean and Carol Christensen were very influential in our choice to pursue graduate school in Cognitive Neuroscience because of their natural and early inclinations to bring cognition into neuroscience in both human and nonhuman animals. Some of you might want to know that Abigail Baird was also influential back in 1991; she helped us perform our first neurosurgery as our student teaching assistant (TA) for Bean’s Psychological Psychology Laboratory in our final year at Vassar. Without exposure to the Vassar interdisciplinary, “synthetic,” way of thinking about science, we might not have really seen ourselves in the discipline of neuroscience. But how did we get from Vassar to Cornell? Even though we maintained our personal connection throughout this journey, we took distinct paths during our graduate and postdoctoral training until our first jobs as principal investigators in the Department of Psychology at the University of Toronto. It was then that we decided to share resources and co-direct the Affect and Cognition Laboratory for the first decade as faculty. As new faculty members, we were welcomed, supported, and our voices had value. It was a thrilling place to start our careers and we will always have the utmost affection for everyone we worked with there. We made the difficult decision to leave everything

that Toronto had to offer for an opportunity at Cornell University. At this point, our Vassar education that valued interdisciplinary science called us back home to “upstate” New York.

EVE’S PATH

At Vassar, I spent maybe more of my time in the dance studios at Kenyon Hall and the piano studios at Skinner Hall than the basic science labs. The Arts sustained me and allowed me to bring my whole self to my courses. But once I started to work in research labs and run an independent research project, that’s when I realized that there is art in science and I never looked back. At Vassar, I prepared for a career in modern dance and medicine. However, after graduation, I had the good fortune of working as a research assistant in a surgical metabolism research lab at Harvard University School of Medicine, with Danny O. Jacobs, where I fell in love with research. I couldn’t believe I was getting paid for the work. Even though I had important mentors along the way, Danny was my most inspiring mentor. As an African-American man who did cross-species work, in humans and rats, in his clinical and basic research labs, respectively, he made everything possible. Now might be a good place to state that I am a first-generation, African-American, female neuroscientist who uses a cross-species approach, in rats and humans, to examine how brains, neurochemistry, and cognitive faculties change across the lifespan. I left Danny’s lab to attend Harvard University to pursue my Ph.D. There, I trained in animal neuroscience in the Department of Psychology, with Michael Hasselmo and Mark Baxter, to examine to influence of the neurochemical acetylcholine on attention, learning, and memory mechanisms in rats. And then I trained in human neuroscience as a postdoctoral fellow, funded by the NIH, in the Department of Psychiatry at Stanford University School of Medicine, with Edie (the formidable) Sullivan and Adolf Pfefferbaum, to translate findings from my dissertation in rats to humans with neuropsychological and functional neuroimaging techniques. Adam and I selected University of Toronto – Saint George to start our careers as principal investigators. It’s here that I made the

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Alumnae/i Features fateful decision to bring basic neuroscience research in rats back into my daily research life and combine it with human neuroscience techniques to examine how neurochemistry and its neural sources affect how we attend, learn, and think about the world.

ADAM’S PATH

Vassar was one of the few undergraduate schools, at that time, that had a formal program in cognitive science. And, as I see it, Cognitive Science — with required courses in psychology, philosophy, neuroscience, computer science, and linguistics — was the major for those of us who had trouble picking a major.. My most influential mentors were Janet Andrews, who met weekly with me to supervise my honors thesis, and Terry Champlin, my classical guitar instructor. Terry had left studying science and mathematics at the Massachusetts Institute of Technology to pursue a life in music; I left music and fine arts for a life in science. Much of what I learned about myself emerged from conversations with Terry while holding a classical guitar in Skinner Hall. During my senior year, I developed an interest in visual cognition and wrote an honors thesis on the topic. Vassar was a wonderful place for studying, but I acquired little in the way of practical experimental skills so I accepted a research assistant position at a visual cognition laboratory at Harvard University. This work was exciting, challenging, and dispiriting because I realized I was a terrible research assistant and really wished to be a graduate student pursuing my own research ideas. Unfortunately, this challenging time did not end so readily. All of my graduate applications were rejected except for one. I moved back to Staten Island and applied for a research fellowship at the Center for Developmental Neuroscience at the Institute for Basic Research in Developmental Disabilities, an institute I had not known existed a few miles from my childhood home. After a year of taking graduate classes at City College of New York, I reapplied to graduate schools. I accepted an offer at Yale University’s Department of Psychology where I started to change focus to examine the emotions, which was cemented after a class with the now President of Yale University, who was one of the originators of Emotional Intelligence. Eve always told me I was an emotional creature and now I was going to make a career out of it. Much of my graduate education was spent driving around a not-so-portable lab to examine epilepsy patients in the comfort of their own homes to understand how their emotions changed (or not) following removal of the medial temporal lobes in one hemisphere. Following graduation, I was awarded a NIH postdoctoral fellowship to extend

my methodological base to include functional neuroimaging at the Stanford University Department of Psychology. I learned a lot during that time, but more than methods, was the art of telling the narrative of a scientific story. When it came time to become a principal investigator, I was attracted to Canada by the offer of a Canada Research Chair in cognitive and affective neuroscience, where I intended to stay for my career. It’s here that my research extended in new directions, from examining evolutionary theories of emotions to the present-day utility of emotions in regulating complex cognitive and bodily states. I’m back in “upstate” NY hoping to contribute to its revival through understanding how to support aging brains and bodies to live good long healthy lives and contributing to the greater good.

EVE AND ADAM TODAY

At Cornell not only are our children growing up surrounded by family, but we also are in a place that values interdisciplinary science. We are in the Department of Psychology in The College of Human Ecology, which embodies interdisciplinary science and the land grant mission of Cornell to take our science out of the lab and into communities throughout the State of New York. We re-established our laboratory almost a decade ago, and, as a part of our Community Neuroscience Initiative, have developed a program to teach neuroscience to elementary school children in under-resourced school districts. Our Get to Know Your Brain program uses STEAM (science, technology, engineering, arts, and mathematics) to get young people to become experts in themselves (and others) by providing them with a manual on how their brains learn, think, and feel at an early age. Art is central to its success. This program supports our passion for how neuroscience needs diversity in both ideas and the people who wish to pursue them. Our Vassar roots continue to sustain us and new extensions of our science and ourselves. In reflection, we are sharing our Vassar experience, whether in the urban elementary classroom or an aging residential home, inviting all brains to join us in a lifetime of learning about ourselves and others.

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LAURIE HOUSE KRAMER CLASS OF 1986

Laurie Kramer founded LHK Insight to work with individuals, teams and/or companies to maximize their potential through evidence-based executive coaching tools and techniques. As a certified Executive and Leadership Development Coach, she specializes in developing organizational leadership, performance enhancement, career and business growth, effective feedback, collaboration, embracing change, and stress management.

FULL CIRCLE… WITH A TWIST: STRAIGHT LINES ARE OVERRATED In the Fall of 1982, I arrived at Vassar College like many of my 18-year old peers… young, a little cocky, idealistic, ready to take on the world, yearning for independence, and completely, utterly clueless. I just didn’t know the clueless part for quite a while. Let me set the stage here. I grew up in a small, rural town in the deep South, and from the time I was a young child, I knew I wanted out. I had never been on an airplane prior to enrolling at VC. I was the first to go to college in my family, and was only able to go to Vassar because I had a full scholarship. In other words, my young parents had literally no money to spare. Notwithstanding, I felt pretty confident as I strode into my first calculus class in Rockefeller wearing my ruffly, puffy-sleeved southern gal shirt. I mean I had graduated at the top of my public high school class after all. And all my teachers had called me a “smart cookie,” even as they puzzled my decision to go way up North to a school of which no one I knew had ever heard. And hey, I was great in math in high school, so obviously I would major in computer science, which was, at that time, an obscure rather nerdy major that would surely lead me on a straight line to a good job after college. What could go wrong? The very first day of calculus class, I was lost. I mean “wandering in deep dark woods without so much as a mark on a tree” kind of lost. I had progressed as far as trigonometry by my senior year in high school and this first level college calculus class might as well have been in Greek. As I stumbled out of class feeling thoroughly dejected, someone from my dorm said “Now, how adorable is your little shirt. Do you have cowboy boots to go with it? Can you say something with your cute little southern accent, like maybe ‘yall?’” Seriously. Two littles in one conversation. And said with the full disdain of a pretentious 18-year-old dressed in all black who had grown up in NYC, gone to the best private school and seemingly oozed with confidence. I

was starting to feel what I now know is “imposter syndrome” — that I really didn’t belong at VC after all. At that moment, in my mind, I was a stereotypical dumb southerner in a land of shiny, uber-educated, ridiculously sophisticated, stylishly beautiful city people. Wrong accent, horrendous shirt, and not that smart after all. It wasn’t a great day for the home girl. Well, I thought, surely computer science is still for me. I knew that even with a scholarship, associated expenses for me to go to Vassar were a hardship for my family and I thought it was very important that I land a high-paying job when I graduated. You know, to prove it was all worth it and frankly that I was worth it. Confidence dinged but not yet erased, I headed into my first computer science programming class. This was no longer Greek, it was all-out language warfare. I had no idea what was going on, and I was embarrassed to ask for help. The smartest girl in the room never asks for help. At least that’s what I thought. (Have I mentioned that I was clueless?) So, shortly after a disastrous midterm, I stopped going to the computer class completely. Just stopped and pretended it simply didn’t exist — and this was way past the “drop” deadline. For the first time in my life, I failed in spectacular fashion. I squeaked out a C- in the dreaded calculus class but outright flunked the computer class. As a result, I assumed my days at Vassar were numbered, and the digits were not high. Over winter break that year, I waited nervously to be told that I was no longer welcome at the mighty VC, or that my scholarship had been rescinded. When neither happened, I picked myself up, got on that plane, and headed back to Poughkeepsie. Very quickly I uncovered my inner resilience and learned some coping skills. I let go of my fixed mindset that math and computers were my destiny. And, although I’m a little sad to say it now, I shed my southern accent and my ruffly-puffy shirts like yesterday’s news. I did this on

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Alumnae/i Features purpose and with full intention of fitting in rather than standing out. The imposter syndrome loomed large, but I told myself that instead of being an imposter, I was a master chameleon… remarkably adaptable and fit for survival. And all of that was true at the same time. During my second semester, I took my first biopsychology class with the brilliant Janet Gray who later became my advisor. I became enamored with the brain/body/behavior continuum and fascinated by neurotransmitters. The brain science relating to behavior was new to me and captivating. Pure psychology, as I thought of it, was too “talky” for me — I wanted to understand the biology underlying why we act the way we do. At that time, the field was mostly focused on abnormal behavior and I was all in. Combining the studies of biology and psychology into a Biopsychology major was very appealing to me. I didn’t know it then, but the “why” of human behavior began to drive me to a certain extent. During that time, I developed what I now know is a growth mindset that permeated my decisions. I stopped thinking about the high-powered job I would seek upon graduation and threw myself fully into just being a college kid. Through biopsychology classes, and the VC experience in general, I literally felt my mind expanding. As that happened, a free-spirited nature either blossomed in me, or returned to me, unclear which. Unshackled from the need for the big career immediately after college, I saved enough money to travel through Europe and Israel for a year, working odd jobs to keep the adventure going. It was amazing and eye-opening to say the least. When I returned to the States, I had no idea what I wanted to do with my Biopsych degree. To support myself, I took a temp job in Washington DC with a commercial real estate firm. That “temp” job lasted almost 30 years as I climbed the ranks from receptionist for a small, local real estate development firm to Executive Vice President of a publicly traded real estate company— the largest commercial landlord in both New York City and Washington, DC. That 30-year period is a story for another day, but suffice to say, it was quite the ride. In a nutshell, during the early days of that career, I rediscovered my love for “math,” became an analytical whiz, went back to business school and later became one of the very few women leaders in a male dominated industry. I guess we might say this was my first “full circle” moment. Back to math, only this time in a language I fully understood and could translate in my sleep. The chameleon (for-

merly, and sometimes still, known as the imposter) occasionally reared her head, but mostly I mastered my domain and took very few prisoners. It was an incredibly interesting, massively empowering time, and a period of my life for which I will always be grateful. I discovered my strengths, my secret sauce, what made me indispensable, and a whole lot more. And, I finally had the high-powered job with the big paycheck to validate that fancy education. Throughout most of that time, the southern accent stayed in the closet. As did the ruffly-puffy shirts. After almost 25 years of my hard-charging career, as our youngest child was heading off to college, I finally paused long enough to consider the future. Some of the excitement and glamour of the corporate world had dwindled for me. I no longer felt the rush of adrenaline when working on a deal and found myself pondering the proverbial “what’s next.” Once again, I felt the familiar pull of the “why” of human behavior. Why were some leaders amazing and others only passable? What motivated people at work? While I continued with my day job, I hired an executive coach to help me sort it all out. She pointed me to a year-long course in positive psychology that completely changed my life. Suddenly I was back to an evidence-based approach to human behavior. Only this time, with a focus on what’s right versus what’s wrong. Tapping into human potential has never been more exciting or revolutionary. Back to Biopsychology. Can someone say Full Circle? For another five years, I informally studied positive psychology and leadership coaching while putting what I had learned and experienced into practice in my corporate job. I developed and ran workshops about topics including Loving Stress, Growth Mindset, the Science of Resiliency, and Work/Life Balance. I loved it. Yet, I was still afraid to make the leap, to actually leave my very safe, very well-paying corporate job. So, back to my coach I went. I knew my passions lay elsewhere, yet my survival brain kept me in protection mode. Still, I began thinking about every possible career path I might take next. Through lots of twists and turns, a common denominator revealed itself among all of the things I was considering. I was done climbing the ladder, and ready to dedicate myself to helping other professionals reach their potential. I knew that was my purpose and my mission going forward. In 2017, I launched my own consulting and coaching business called LHK Insight that both represents my initials and my core concept of “Leadership = Heart plus Knowledge.” Today, I work with companies and individuals to develop and hone leadership abilities

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Alumnae/i Features using my evidence-based positive psychology background. And I couldn’t be happier or more excited. For all of it. For the journey. For what came before and for what is coming next. For the ever-evolving next chapters in my twisted circle. There was something else I did about 20 years ago that created another “full circle” moment. Although my entire working world would continue to be based in Washington and New York, when our kids were 3 and 6 years old, my VC husband and I moved to North Carolina. Not to that same small rural town… but still, I came “home” after many years away. Maybe I had proven all I needed to prove. Maybe I missed my parents and brothers. Maybe I wanted a quieter place to raise children. Or maybe this chameleon just got tired of running. In any case, here we remain, all these years later. I used to think that somehow I got really lucky. Lucky to get the scholarship to Vassar. Lucky to travel for a year before buckling down. Lucky to land that “temp” job. Lucky to have a boss who both challenged me and treated me like a valuable co-pilot. Lucky to work with wonderful, talented people for a company at the top of its game. Lucky to take plenty of time off when both of my amazing children were born and to be able to work from home when I needed to – before it became fashionable to do so. Lucky to find my second calling as an Executive Leadership Coach. Lucky to bring home the bacon AND fry it up in the pan. Now, I know that luck may have brought me to the door, but this chameleon kicked the door down with sheer will, a brilliant mind, a lot of style and ferocious power. And I have been known to rock my cowboy boots often, and even an occasional ruffly shirt, in the many years since. And that, yall, is called Full Circle…with a Twist.

FUN FACT

Married to Jonathan Kramer, VC Class of 1985

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ART BY MARA RUSSELL

Alumnae/i Features

MATTHEW MENDOZA, MD CLASS OF 2015

KONRAD BEN CLASS OF 2015

Dr. Mendoza is an intern in Internal Medicine at The Christ Hospital in Cincinnati, OH, currently researching neuroprognostication after cardiac arrest. Konrad is a 4th year medical student at Stony Brook University applying into anesthesiology with an interest in critical care.

IMPERFECT PREDICTIONS & DIFFICULT DECISIONS You have just been admitted to the emergency room for chest pain. The heart monitor in the corner of your room begins alarming — signaling that your heart rate is falling. Suddenly, you become pulseless, cold, and pale. A “code blue” is called, alerting hospital staff that you have experienced cardiac arrest. A rapid response team hastily gathers around you to begin performing cardiopulmonary resuscitation (CPR). One nurse takes initiative, positions his hands just left-of-center, and begins rhythmically compressing your chest to manually simulate the work of the heart. Meanwhile, at the head of the bed, a respiratory therapist and physician pair place a breathing tube in your airway to administer breaths from a compressible bag of oxygen. Every few minutes, medications are delivered into your veins to maintain circulation to vital organs and, algorithmically, a pulse check is performed. Then, 18 minutes later, almost as quickly as it disappeared, the pulse reappears. Weak, but palpable — enough for the heart monitor to sense a heartbeat. ••• In the wake of almost any significant life-threatening condition, which leaves a patient unresponsive and unable to make their own decisions, the patient’s loved ones are often consulted by the medical team to determine plans of care. Loved ones suddenly find themselves in unimaginable circumstances under immense emotional stress while suddenly tasked with complicated healthcare decisions. To aid in this difficult process, doctors are often asked to provide a prognosis — Will the patient survive? Will they awaken? And, if they awaken, would they still be the same person they once were? Often through a series of discussions, doctors help families determine which life-saving measures will be pursued and, in some cases, whether life support would continue to be provided at all. In the specific case of cardiac arrest, the heart’s failure to pump leaves the brain without enough blood flow, sometimes for extended

periods of time, even when perfect CPR technique is employed. This lack of blood flow to the brain can have lasting effects on a person’s consciousness, memory, function, personality, and quality of life. Currently, predicting the extent to which a patient will recover or remain disabled after cardiac arrest remains an imperfect science and, in some cases, appears to be more of an art crafted from a clinician’s own professional experience. Nonetheless, well-studied techniques do exist to aid in making predictions, and the field of neuroprognostication is still rapidly evolving. Despite the imperfect nature of the prediction, providing a neurological prognosis is incredibly important for families and surrogate decision-makers (i.e. someone who advocates for a patient unable to make decisions for themselves) in order to develop realistic expectations and decide on further treatment. For example, if cardiac arrest were to recur, should the patient undergo more CPR and aggressive treatments? An analysis of over 200,000 cases indicates that only about one-in-four patients who experience in-hospital cardiac arrest will survive to hospital discharge [1]. Considering this, sometimes loved ones decide that the treatment team should continue with their current plan, but refrain from heroic measures in the event of a loss of pulse. A patient’s code status is how the healthcare team determines whether to attempt resuscitation in the event that the patient’s heart stops or they stop breathing. Code status is often determined on admission to the hospital, but any one person may specify their decisions about end-of-life care at any time. For instance, some people decide to document their code status as do-not-resuscitate (DNR) in their living will. When a patient’s code status is DNR, the treating team will not perform CPR in the event of cardiac arrest. Instead, the focus of care is on comfort and symptom relief. In stark contrast, when a patient or their surrogate wants “everything done,” code status is designated as FULL; all aggressive measures are taken to resuscitate the patient, includ-

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Alumnae/i Features ing chest compressions, intubation, electric shocks, and other life-saving interventions. Patients also have the option of a PARTIAL code status in which specified interventions are acceptable while others are not (i.e. chest compressions are OK, but shocks are not). Although 18 minutes is quite a long time for someone to be pulseless (considering irreversible brain damage can occur after just a few minutes), high-quality CPR should presumably have helped support circulation to the brain [2]. However, even with high-quality CPR, blood flow (and thus oxygen supply) to the brain is compromised. In general, the further away a particular organ tissue is from the heart, the more susceptible it is to injury due to inadequate blood flow, or ischemia. One of the most critical molecules delivered by blood to organs is oxygen. Thus, ischemia in the brain leads to anoxic brain injury. Different areas of the brain are selectively vulnerable to ischemia. For instance, the surface of the brain, known as the cerebral cortex, is the most vulnerable to ischemic injury. Deeper brain structures are less vulnerable, but still majorly susceptible given their high demand for oxygen. Permanent injury to the cerebral cortex and/or deeper brain structures may result in memory loss, personality changes, or significant impairments in speech, motor skills, and sensation. The brainstem is generally considered to be least susceptible, but carries the responsibility of regulating critical life functions such as breathing, heart rate, and wakefulness. Taken together, brain damage sustained post-cardiac arrest can result in a spectrum of possible neurological outcomes for patients who survive — from no noticeable impairment to permanent loss of consciousness and inability to perform normal activities of daily living. Although a spectrum of neurological outcomes exists for the few patients who survive cardiac arrest, consideration of quality-of-life in the setting of various disabilities is irrelevant if the patient stands little chance of regaining consciousness at all. Consciousness — its origins and manifestations — remain incompletely understood and definitions differ depending on intellectual or spiritual context. From a medical perspective, however, consciousness is essentially defined by the presence of awareness, which arises as a result of a concerted effort between the cerebral cortex, deeper structures, and brainstem systems [3]. If a single component is damaged, then the manifestation of consciousness is compromised. Studies suggest that the vast majority of patients destined for a good neurological outcome will recover consciousness within a week [4,5,6]. Hence, the most common cause of death in those who survive car-

diac arrest is withdrawal of life-sustaining treatment (WLST), which is largely influenced by the neurological prognosis conveyed by the medical team to the surrogate decision-maker [7]. One can imagine that premature WLST based on a poor prognosis could conceivably result in the death of a patient who may have the potential to recover. In contrast, WLST based on an accurate prognosis not only allows for the reallocation of precious hospital resources, but also prevents further suffering from futile treatments and can provide some closure for loved ones. Given the significant consequences of making the “wrong” decision, an accurate determination of neurological outcome is of utmost importance. ••• On transfer to the intensive care unit, you lay still and glassy-eyed. Your loved ones are at the bedside, distraught at the sight of you reliant on a breathing machine, shock pads still attached to your chest, with dozens of tubes that can be traced from your extremities to a series of monitors and medication pumps. Several hours pass and your eyes abruptly shift to the left, your right leg stiffens, and the whole of your body begins shaking. Your medical team rushes to the bedside to assess and intervene. ••• So how then, from a neurological standpoint, does your medical team determine whether you will regain consciousness? The most commonly used and longstanding tool for neuroprognostication is the neurological exam. The neurological exam is a set of techniques taught in medical school that allows the examiner to assess the nervous system functions by eliciting responses to stimuli such as light, sound, vibration, temperature, and sharp or dull touch. A common example of a focused portion of the neurological exam is when a doctor takes a reflex hammer and gently taps the knee to elicit a knee jerk reflex. The presence of such a response conveys to the examiner that the neurological circuitry responsible for producing the reflex is intact. There are several reflexes associated with brainstem integrity including the cough and gag reflexes, pupil reactivity to light, and blinking when the eye is touched. Because the brainstem is the least susceptible to ischemic injury, the absence of any of these reflexes may be indicative of more severe underlying injury. Sometimes, anoxic brain injury increases the risk of seizures. Seizures, often depicted in media as a sud-

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Alumnae/i Features den loss of muscle tone accompanied by generalized body shaking followed by persistent confusion that resolves with time, are caused by electrical dysfunction in the cerebral cortex. Although seizures have traditionally been thought to portend a poor prognosis after cardiac arrest, they can sometimes be terminated with medications when detected by means of electroencephalography (EEG; a technique used to measure electrical activity in the cortex) [8]. Yet, EEG is not routinely employed by many healthcare institutions given limited resources and a lack of standardization in post-cardiac arrest care and monitoring.

in the field can be expected to further enhance its reliability and, ultimately, its impact on consequential decisions central to the lives of patients and their families. References on page 87.

Moreover, the increasing implementation of targeted temperature management (TTM; previously known as therapeutic hypothermia) is further augmenting prognosis because there is evidence that anywhere between 10-30% of those treated with TTM are so-called “late awakeners” [9]. Still, neuroimaging remains one of our most reliable methods of establishing neurological prognosis. An ideal neuroprognostication tool would have a false positive rate (FPR) of zero — meaning, the tool correctly predicts poor neurological outcomes 100% of the time. One study reports that certain neuroimaging findings detectable by a specific type of magnetic resonance imaging (MRI) has an FPR of 4% [10]. Few neuroprognostication tools exist with this magnitude of specificity [10]. And yet, 4% still seems unacceptable. When there is even a small chance that a good outcome is possible, that may be enough for surrogate decision-makers to choose to keep the patient’s code status FULL. Neuroprognostication is a process that relies on advanced techniques in neuroscience. However, these techniques are not infallible. The process is also not devoid of emotion. In fact, the driving forces behind the decision to withdraw life-sustaining treatment is rooted in emotion. In the absence of clear answers provided by reliable neuroprognostication techniques, what is the appropriate amount of time to wait for signs of neurological improvement? Meanwhile, is the brutality of intensive care worth enduring? With the breathing and feeding tubes, needles, pumps, life-support machines, anxiety, and poor sleep, intensive care can itself cause immense pain and suffering. The medical community provides it, and loved ones agree to it, with hopes that the patient will recover and live some kind of meaningful life — that it’s all “worth it.” The neuroprognostication techniques available today can help determine the likelihood of a meaningful recovery, but they are, in their current form, far from conclusive. While neuroprognostication is likely to remain an art form, ongoing advancements

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NIKKI ELLER, MPH CLASS OF 2010

Eller is currently an epidemiologist for the Washington State Department of Health in the Office of Nutrition Services. Eller works on research, analysis, and evaluation of the WIC (Special Supplemental Nutrition Program for women, Infants, and Children) and SNAP-Ed (Supplemental Nutrition Assistance Program Education) programs.

HOW PUBLIC HEALTH IS REALLY NEUROSCIENCE When people ask what I studied in college I usually say “neuroscience,” but I should probably say “behavior,” as that’s the aspect of our program that has had the biggest impact on my career. I found lab work too messy and memorizing all the neurotrophic cascades at the cellular level not particularly exciting — but trying to figure out why people do things? What could be more interesting! After trying out a few jobs — building cookstoves in the Peace Corps, volunteering in neuroscience and bioengineering labs at the University of Washington, and working on a training program for Peruvian neurologists — I eventually found public health was my passion. And a large part of public health work is trying to get people to adopt health-promoting behaviors, like frequent hand-washing, exercise, and wearing seat belts. I think it’s so fascinating the way small cues influence our behavior. Asking customers if they want a plastic bag rather than automatically handing them one cuts down on their use. Putting fresh fruits and vegetables at eye level in a food pantry or in an attractive display in a cafeteria makes people more likely to choose them. Many of the programs I work on for the Washington State Department of Health are aimed at making policy, systems, and environmental adjustments to make the healthy choice the easy choice. After taking one of Professor Cleaveland’s classes, I was actually convinced for a while that choices and free will were just an illusion. We were all just enacting stimulus-responses based on our upbringings, and given the same set of circumstances and environmental cues, we would make the same “choice” every time. I’ve actually changed my mind on that after getting into mindfulness and meditation. If we can learn to resist the urge to scratch an itch, or move a cramped leg, we do have choices — but whether we actually put thought into them is a separate matter. There are many theories of behavior change that in-

fluence public health practice, but one that I’ve found useful is the technology adoption curve, invented by Dr. Everett Rogers in 1962. I’m not sure how well the percentage of the population estimates hold out, and I wouldn’t label anyone a “laggard,” as there can be really good reasons for being slow to adopt new technologies, but I have seen this rough idea play out a number of times. My primary project in the Peace Corps was promoting the construction and use of cocinas mejoradas (improved cookstoves), with key features being an insulated combustion chamber and a chimney to improve fuel efficiency and reduce indoor smoke exposure. I gave the same presentation and opportunity to construct one to everyone in my town in rural Peru, but, without ever having seen a working model, only a handful of families were willing to invest in the materials and trust me to help them build one. With a few constructed, a few more families who had seen them at their neighbors’ wanted them too, and by the time two years had passed, the mason I had trained to build them was in high demand.

From “Design Strategies for Technology Adoption,” by A. Canada, P. Mortensen, and D. Patnaik, Jump (https://www.jumpassociates. com/learning-posts/design-strategies-technology-adoption/).

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Although vaccine hesitancy has a lot of complicated factors, and politics have obviously influenced acceptance of the COVID-19 vaccine, I think to some extent we see the same pattern of the technology adoption curve. A lot of the reasons people cite for still not being vaccinated are about the vaccine’s novelty, and I would bet a lot of the people who are receiving their first vaccinations now (who weren’t coerced by mandates), had some personal experience that made them feel it was worth it — perhaps simply seeing that their friends who’ve been vaccinated aren’t getting sick. Or perhaps a source they trust urged them to get it, as I know from working on hesitancy towards childhood vaccinations that trust is an important factor in who people listen to [2]. The past two years of the COVID-19 pandemic have been a really challenging time to be an epidemiologist, and I, like everyone, have had to make personal sacrifices. One of the few positives has been bringing public health to the spotlight, which has meant receiving (nearly) adequate funding for the first time in decades, and having people think my job is cool again. Public health is broad, and a degree in engineering or environmental science might be more appropriate for working on drinking water or toxic algae blooms, but I can’t think of any preparation better than neuroscience and behavior for the sort of applied behavioral science work I do. So if you’re graduating soon and thinking about where to go next—public health needs you. One final memory I wanted to share from Vassar — that time Professor Holloway saved a rat’s life with CPR! We were adjusting its stitches following a hysterectomy when I noticed the glow had gone out of its eyes. Professor Holloway immediately began chest compressions, and that glow came back! I’ve kept my CPR certification current ever since. References on page 88.

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A World of Pure Imagination

A WORLD OF PURE IMAGINATION: THE NEUROSCIENCE OF LUCID DREAMING

by Gerasimos Copoulos and Clem Doucette art by Sophie Sieckmann

Side. As I gazed up at the beautiful Victorian buildings lining the narrow streets, I felt as During a visit to New York City several years if I were being drawn back into some forago, I took a walk through the Lower East gotten era. Across the street, I spied a tiny, old-fashioned Italian market and decided to IS THIS THE REAL LIFE… IS THIS JUST FANTASY?

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go inside. I passed by the store clerk, headed to the back wall of the shop, and passed through a small door. As I walked through, the modern cars and taxis of Delancey Street were replaced with horses and buggies; men wearing flat caps and women donning long dresses and bonnets rushed down the street shouting things in various languages, while a group of children played baseball in a back alley. At this point, you might be thinking that I had experienced some kind of wild delusion or hallucination. In reality, what I am describing are the events of a particularly vivid lucid dream. Have you ever been fully aware that you were dreaming? If so, then you have experienced a lucid dream. When a dreamer enters a lucid state, they can often control, or “rewrite,” the environments, events, characters, and even physics of their dream. Anything is possible in a lucid dream; you can fly between tall buildings, fight off hordes of zombies, or live out your wildest fantasies. In many cases, the experiences of your lucid dreams are limited only by your own imagination. Once described by Freud as the “royal road to the unconscious,” dreams have both fascinated and baffled philosophers and scientists for millennia. While lucid dreaming may seem like a miraculous or otherworldly occurrence, the neurological and psychological underpinnings of these dreams are the focus of a growing body of research. Though the precise neural correlates underlying lucid dreaming remain uncertain, lucid dreaming holds immense therapeutic potential.

are the non-rapid eye movement (nREM) stages, and the fourth stage of sleep is rapid eye movement (REM) sleep [2]. The first of the three nREM stages, N1, is the lightest stage of sleep and occurs shortly after your head hits the pillow, typically lasting for only 1-5 minutes. The second, N2, is a somewhat deeper stage of sleep, lasting for roughly 25 minutes. During N2, your heart rate and body temperature begin to drop. N3, the last of the three nREM stages, is the deepest; if you wake up during this period, you may experience a period of mental fogginess. After remaining in nREM sleep for roughly 90 minutes, you pass into the fourth stage, referred to as rapid eye movement (REM) sleep. The vast majority of our dreams occur during REM sleep [2]. For a while, scientists could not come to a consensus on why dreaming occurs during the REM stage, or the function of REM in general. However, in the last decade, several hypotheses have emerged that shed light on the functions of REM sleep.

One hypothesis suggests that REM plays a role in the development of motor learning and memory, since newborn mammals spend a lot of time in active sleep, an early form of REM that is crucial to that development [3]. During active sleep, young mammals are often observed producing a flurry of muscle twitches and vocalizations as evidence of ongoing motor learning. Mammal species born with less developed motor and learning memory, like humans and most primates, spend relatively more time in active sleep than mammal species born with more developed motor skills and memory, like horsTHE STUFF OF DREAMS: THE SCIENCE BEHIND DREAMING es [3]. The excess time that some mammals AND REM SLEEP spend in REM or active sleep may suggest REM fosters the development of the systems In order to understand the mechanisms be- underlying motor learning and memory [4, 3]. hind lucid dreaming, let’s first discuss how A better understanding of REM can improve sleeping and dreaming generally work. Sleep our understanding of lucid dreaming. When occurs in four distinct stages. The first three we lucid dream during REM, we enter a hyGREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 3

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brid state of sleep and wakefulness [1]. Even though the exact purpose of REM sleep isn’t well understood, REM and even lucid dreams are easily identifiable via imaging techniques [6]. IMAGING A DREAM: THE ELECTROPHYSIOLOGY OF LUCID DREAMING Various technologies can be used to differentiate between standard REM sleep and a lucid dreaming state; but, some of the most useful are imaging technologies. Imaging the brain during a lucid dream allows for further study of the mechanisms behind lucid dreaming [1]. One common imaging technique uses a machine that reads different electrical signals produced in the brain: an electroencephalogram (EEG) [7]. When a sleeping person’s brain is examined with this technology, the EEG reading displays different kinds of waves depending on the sleep stage [6]. REM sleep waves, for example, are short and frequent [6]. As lucid dreaming involves a different mental state than a normal REM dream, lucid dreaming produces a different EEG reading than standard REM sleep [8]. There are visible differences in the EEG readings observed between lucid dreaming and either REM or wakefulness. However, EEGs can detect interference from eye movements during REM, casting doubt on if these EEG readings actually show lucid dreaming. Verifying the EEG readings with fMRI, another method of brain imaging, provides further evidence that lucid dreaming is distinct from standard REM. Functional MRI imaging records activity in various brain regions over a period of time and then displays it visually on a model of the brain [10]. Traditionally, dreams are closely associated with REM; 58

but, one can also lucid dream during nonREM sleep [13]. When using fMRI alongside the EEG to examine people lucid dreaming in both REM and nREM, REM lucid dreams appear distinct from nREM lucid dreams [14]. Some wave patterns apply only to REM or nREM lucid dreams. More specifically, lucid dreaming appears differently on the EEG and fMRI depending on what sleep stage one enters the lucid dream from, indicating more differences in wave patterns among lucid dreams than previously thought [14]. If different varieties of lucid dreams exist between REM and nREM, there may not be a single wave pattern that shows lucidity in

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any sleep stage [14]. The question remains as to why lucid dreams look so different in the EEG depending on if they occur during REM or nREM. After all, aren’t they all lucid dreams [14]? Fortunately, there is one explanation readily available, though it raises as many questions as it does answers: different methods of becoming lucid lead to different wave patterns [15]. nREM and standard REM lucid dreams involve becoming lucid at different times and through different means, explaining the discrepancy between these two kinds of lucid dreams in the EEG [13]. THE LASTING EFFECTS OF LUCID DREAMING The EEG can give us fascinating insight into a lucid dreamer’s brain as they dream; but, it is impossible to deduce the long-term effects of lucid dreaming from an EEG reading [7]. One possible way to examine these effects is to look at the brain structure of lucid dreamers. It turns out that lucid dreaming correlates with a number of differences in the brain, such as in grey matter volume and connectivity [16, 17]. Grey matter is brain tissue that contains the most neural connections, linking it to overall cognitive performance, memory, and decision-making [18]. Grey matter volume is significantly higher in frequent lucid dreamers; this volume difference may provide insight as to how some people are better able to frequently lucid dream than others. [17]. Lucid dreamers also exhibit increased connectivity between brain regions that modulate attention and sensory processing [16]. The increased grey matter volume and connectivity in frequent lucid dreamers suggest that lucid dreaming has a measurable long-term effect on the brain’s structure [16, 17]. However, whether lucid dreaming is innate or learned may affect EEG recordings or observed brain anatomy [1]. More reliable lucid dreaming induction techniques must be developed before research-

ers can isolate the neurological differences between innate and learned lucid dreamers. ENTERING THE LUCID STATE: HOW YOU CAN INDUCE A LUCID DREAM The act of induction, or causing a lucid dream to happen, is often hit-or-miss. Today, no consistent way to induce lucid dreaming exists, which has made conducting research on the subject matter difficult [13]. The mnemonic induction of lucid dreams, or MILD, was pioneered by lucid dreaming research specialist Stephen LaBerge and is currently considered the most reliable means of lucid dream induction [19]. Prospective lucid dreamers perform the MILD technique during a brief period that occurs roughly five hours after falling asleep; while awake, individuals can repeat phrases such as, “next time I’m dreaming, I’ll remember that I’m dreaming” or, “I will have a lucid dream” before returning to sleep. People who practice the MILD technique consistently for two weeks experience lucid dreaming approximately one out of every six nights [19]. Therefore, while MILD is currently the most reliable induction method available, it is by no means a highly consistent way of inducing lucid dreaming [19]. However, other methods to induce lucid dreaming outside of the MILD technique exist [13]. These methods, such as the use of pharmaceuticals and electrical stimulation, seek to induce lucidity through more direct interventions and may provide greater insight into how lucid dreaming works. In the sci-fi film Inception, Yusuf, a chemist, concocts a mysterious sedative that is powerful enough to induce three levels of lucid dreaming: a dream within a dream within a dream. For now, the development of such a substance is far outside the realm of current possibilities, since we currently know only of substances which increase the odds of a lu-

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cid dream occurring [1]. Pharmacological, or drug-based, induction of lucid dreaming may be necessary if lucid dreaming is to be used in clinical or research settings [1]. One drug that has shown great promise in the induction of lucid dreams is galantamine, especially when used alongside the MILD technique

and other traditional induction techniques [16, 20]. Galantamine works by inhibiting acetylcholinesterase (AChE), an enzyme responsible for breaking down acetylcholine (ACh). ACh is a neurotransmitter in the brain that impacts REM sleep [21, 22, 23]. Galantamine administration increases excitation

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in brain regions typically inactive during REM sleep, enhancing cognitive performance and making it easier to lucid dream [16, 1]. The success of galantamine has spurred similar investigations into other substances that increase acetylcholine levels [1]. One of these is an acetylcholine precursor, called α-GPC, which is available as a prescription-free drug [24]. A precursor refers to a molecule that the body uses in a chemical reaction to produce another molecule; in this case, the product is acetylcholine. However, α-GPC has had no success in the induction of lucid dreaming. No other drugs that reliably induce lucid dreaming have been found [1]. Isolating additional drugs that can induce lucid dreaming is warranted to advance lucid dreaming research and therapy.

when using lucid dreaming for therapeutic or research purposes, making electrical stimulation of the lower gamma band a promising avenue for future lucid dreaming research.

Trans-cranial direct electrical stimulation (tDCS) is another method of electrically stimulating the brain, allowing researchers to target specific brain regions [27]. When used to stimulate frontal regions of the cortex, tDCS increases the chances that a lucid dream will occur in a given sleep session [28]. However, lucidity is not immediately induced, and the positive effect of tDCS only applied to already-experienced lucid dreamers, possibly because lucid dreamers already have a more active prefrontal cortex [28]. Uncovering an effective and consistent means of inducing lucid dreaming will provide invaluable Current induction methods merely increase benefits to lucid dreaming research, and can the odds of a lucid dream occurring and rely even benefit people who suffer from chronic largely on self-induction [19, 24]. What if there nightmares. were a direct, consistent way for researchers to cause a dreaming person to become lucid? TAKING CONTROL OF YOUR WORST NIGHTMARES: THE One exciting possibility involves electrically CLINICAL APPLICATIONS OF LUCID DREAMING stimulating the brain [1]. Unlike other methods of induction, electrical stimulation could Imagine that you are in the midst of an exnot only provide the most reliable route to tremely vivid and terrifying nightmare. Perhaving a lucid dream, but it could also shed haps you are being chased down a narrow light on the cause of the EEG readings taken hallway by a grotesque monster, or re-exduring lucid dreams [25]. Electrically stimu- periencing a traumatic event. Often during lating the fastest electrical waves produced these petrifying dreams, we feel as though inside the brain, or the lower gamma band- we have no choice but to sit through them width, is thought to provoke a greater sense until we wake up shaking and drenched in of self-awareness while dreaming. Electri- a cold sweat. However, in the last decade, a cal stimulation can even induce a sudden growing body of research has emerged to inchange in state of consciousness, indicating vestigate lucid dreaming as a potential therthat a person becomes lucid as soon as the apy for those with chronic, intense nightstimulation begins [25]. Increased activity mares stemming from traumatic experiences in the lower gamma band has been linked [29, 30]. Chronic nightmares can significantly to mindfulness and self-awareness, possi- impact the quality of life of those who suffer bly explaining why suddenly stimulating this from them; many patients experience these band causes around three out of four people nightmares for decades and, in severe cases, to become lucid [26]. Being able to induce existing therapy has failed to provide meanlucidity on-command is certainly appealing ingful improvement [29]. GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 3

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Since lucid dreamers can often take control of the events and situations occurring in their dreams, lucid dreaming holds therapeutic potential in interrupting the nightmares of individuals with PTSD [30]. Lucid dreaming may work in tandem with Gestalt therapy and image reversal therapy (IRT), two traditional therapeutic approaches used to treat PTSD [30, 31]. During dream-specific Gestalt sessions, a therapist helps the participant safely re-experience the nightmare by discussing and interpreting it [30]. IRT works similarly to Gestalt therapy; however, IRT patients are often asked to rewrite or envision an alternate ending to their nightmares at the end of the session [31]. Individuals who participate in Gestalt and IRT exhibit a profound reduction in nightmare frequency [31, 30]. However, people who undergo these therapies in combination with lucid dreaming therapy experience only a slight reduction in nightmare frequency and intensity over those

who completed IRT and therapy alone [32, 33, 30]. Furthermore, no studies investigate LDT in isolation, but rather explore it as a supplement to either Gestalt or IRT therapy. The existing body of clinical studies on lucid dreaming is small and methodologically flawed, and more research is needed to determine whether lucid dreaming has therapeutic potential. DREAMING BIG: CURRENT SHORTCOMINGS AND FUTURE DIRECTIONS FOR LUCID DREAMING RESEARCH Thanks to recent popular media such as Inception and internet message boards, interest in lucid dreaming has increased rapidly in the last thirty years. While the body of research investigating the neuroscience and psychology behind lucid dreaming has been expanding, delving into these studies’ findings can sometimes present an unclear picture. A common limitation of the research discussed so far is that many findings are strictly correlational [16, 17]. Correlational research can be helpful in studying certain aspects of lucid dreaming; but, it fails to tell us about the mecha n i s m s that underlie lucid dreaming. Therefore, additional research should in-

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corporate EEG and fMRI technology, both of which allow for more direct research into the neural components of lucid dreaming. Current research also lacks widespread replication, or the recreation of existing research to ensure that findings were not made in error or due to a statistical anomaly [1].

they experienced a lucid dream [34]. Since we know that lucid dreamers can “scan” the scene of their dream by moving their eyes back and forth, pre-agreed eye movements (PAEM) could be used to determine when someone is entering a lucid dream. [35]. While the use of PAEM in tracking lucid dreams is still largely hypothetical, scanning is one way Replicating studies can become difficult, to ensure that problems with self-reporting however, when existing research contains do not interfere with the conclusions of lucid vague and inconsistently defined terms. In dreaming research. lucid dreaming research, there is little consistency in defining what constitutes a “fre- SWEET DREAMS quent lucid dreamer.” This is because different studies use inconsistent operational defini- Lucid dreaming research has undoubtedly tions to quantify lucid dreaming. Operational come a long way in the last three decades; definitions are simply what researchers use but, there is still a lot of ground to cover in to quantify nebulous concepts. The use of understanding this exciting phenomenon. operational definitions is helpful in making Fortunately, lucid dreaming is both safe and a study easy to read and in letting research- accessible for most people to try with just ers measure things that do not have a strict a little practice. While we still don’t know definition. That said, operational definitions everything about lucid dreams, there is one can be problematic when comparing results thing we do know: they’re really fun! Conacross studies in which the same term is tinuing research ensures that this once unoperationally defined in a different way. For known aspect of dreaming is becoming more example, some researchers dub individuals popular and better understood with time. who experience lucid dreams naturally as Not to mention, work on clinical applications “frequent lucid dreamers,” while other re- means that lucid dreaming may one day be searchers use the phrase to refer to people used to relieve nightmares. Now that you unwho have trained themselves to regularly lu- derstand how lucid dreaming works, consider cid dream [19]. The existence of different op- trying it out yourself — after all, there are no erational definitions means that two studies downsides! Lucid dreaming for the first time can draw conclusions about “frequent lucid can feel immensely liberating, beautiful, and dreamers,” while actually referring to two stimulating. See for yourself what it feels like completely different groups. to live in a world of pure imagination. Lastly, one of the largest obstacles in lucid dreaming research is consistently inducing References on page 88. and reporting lucid dreams. Even with the most tried-and-true induction methods, like MILD, some participants may have never actually learned how to lucid dream, or may infrequently induce them [30]. Studies that rely on self-reporting measures are not reliable because participants can falsely report that GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 3

DO YOU SEE WHAT I SEE?: BODY DYSMORPHIC DISORDER AND SELF-PERCEPTION Do You See What I See?

By Sudiksha Miglani art by Natalie Bielat

magine that you are visiting a local carnival with your family. You step into the House of Mirrors and marvel at the different reflections of varying heights, shapes, and sizes. As you stand in front of a large mirror and look at your reflection, you can barely recognize yourself. The curved, irregular surface of the mirror alters the angle at which reflected light hits your eyes, making your body appear very different from what you actually look like. Your body seems longer, wider, and strange. Fortunately, because you know the mirror is distorted and the reflection does not display your true appearance, it’s initially easy to dismiss what you see. But if you were to stare into the mirror for a long time, with no other reference for your appearance, you might begin to believe that the reflection is accurate. This overwhelming, dissociative experience can be faced by individuals with body dysmorphic disorder (BDD) on a daily basis. For people with BDD, every mirror becomes like the one from the carnival, as the way they see their body is distorted. BDD is a mental health disorder characterized by an individual’s constant fixation on perceived physical flaws. People with BDD are extremely uncomfortable with flaws in their appearance, and they typically try to conceal them by isolating themselves socially, covering themselves with clothes or accessories, or grooming themselves obsessively [1]. Sadly, these actions typically provide little respite. Individuals diagnosed with BDD may also suffer from other mental health issues such as depression, self-harm, or suicidal thoughts [2]. While BDD affects roughly 2% of the general population, the neurophysiological, genetic, and cognitive causes underlying this disorder are not well understood [3]. However, we know that biological factors — such as irregularities in specific brain regions and low neurotransmitter levels — as well as sociocultural standards, may increase the risk of developing BDD. Shedding light on the causes and symptoms of BDD is critical to increase awareness of this serious and under-recognized condition, so that it

is better understood by the general public [4].

BDD: A PERSONAL HOUSE OF MIRRORS Chances are, your morning routine goes something like this: you roll out of bed, brush your teeth, fix your hair, and spend some time choosing an outfit for the day ahead. As you briefly gaze at your reflection in the mirror, your brain subconsciously interprets and processes all the distinct elements of the visual scene in front of you. However, for individuals with BDD, something occurs differently in the brain that distorts this reflection. Why do individuals with BDD see a different reflection in the mirror? One answer may lie in abnormal higher-order visual processing. Higher-order visual processing refers to cognitive processes involving the visual system that are more complex than simply perceiving an object, and can include identifying the perceived object or locating it in space [5]. When individuals with BDD fixate on one part of their body, they may be stuck on local visual processing [6]. In contrast to global visual processing — or the holistic interpretation of a visual scene — local visual processing involves focusing on a scene’s smaller details [7]. Imagine you are looking at a picture of the beach. Recognizing that what you are looking at is a beach is an example of global visual processing. Upon further inspection, you may notice a child making a sandcastle or someone tossing around a beach ball in the water, which is due to local processing. Individuals with BDD have slower rates of local processing, which can delay the rate of global processing [8]. One explanation for slower local processing might be that those with BDD fixate on small flaws for a longer period of time. Focusing on the smaller details may cause them to struggle with global processing, or seeing their body holistically. For instance, a person without BDD may not notice that their nose is slightly larger than average; but, for someone with BDD, this same detail would be quite

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noticeable and distressing. Another component of higher-order perception is visuospatial processing. Visuospatial processing is the ability to identify an object’s location in space in relation to other objects, such as when someone throws a ball to you and your eyes follow its movement [9]. People with BDD struggle with visuospatial organization, especially when they are looking at complex figures, such as shapes which contain two or more other shapes. They have a hard time organizing different visual components of an object and placing them in relation to each other, which could lead to an inaccurate understanding of bodily dimensions [10]. For example, a person with BDD may struggle with determining the distance between their facial features in relation to one another; perhaps they think their eyes are too close together or too far apart. Thus, it seems

that poor visuospatial skills prevent individuals with BDD from perceiving their features accurately, potentially making their perceived flaws more prominent.

ALWAYS IN THE SPOTLIGHT Not only does an individual with BDD see their warped reflection from the House of Mirrors as their own body, but they also believe everyone else sees them in that way, too. Unlike individuals with other mental disorders related to obsessive tendencies, people with BDD tend to fear that others negatively judge them for their perceived flaws [11]. It’s as though your perceived distortions in the mirror follow you out of the funhouse and cause everyone at the carnival to stare at you in disgust. Recognizing negative reactions from others is a necessary social cue that individuals utilize in order to thrive in social settings. In order to “fit-in”

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Do You See What I See? ingly, individuals with social phobia demonstrate the same heightened amygdala activity in social situations [14]. Social phobia is an anxiety disorder that causes individuals to feel uncomfortable in social situations because they are afraid of being judged and rejected by those around them [15]. This heightened amygdala activity supports the idea that people with BDD feel levels of discomfort in social situations that parallel those caused by their perceived flaws when no one is watching. Since individuals with both social phobia and BDD exhibit heightened amygdala activity, this phenomenon may be related to the common symptoms of the two disorders, namely, feeling self-conscious around others and fearing judgment [13]. The aforementioned finding may also explain why individuals with BDD often avoid social interactions, contributing to a reclusive lifestyle.

socially, we must be able to interpret the unspoken cues given to us by others through facial and body expressions. The amygdala, a brain region involved with emotional processing, helps us navigate these social interactions by allowing us to perceive, recognize, and interpret these facial expressions [12].

The amygdala also helps people recognize others’ emotions by interpreting facial expressions, and it is particularly sensitive to expressions that signal fear and anger [16]. During social situations, individuals with BDD are more likely to interpret emotionally neutral faces as expressing negative emotions such as anger and contempt [17]. Negatively misinterpreting facial expressions might reinforce patients’ concerns about their perceived ugliness and social undesirability. Individuals with BDD feel as though they are constantly put under a spotlight, judged by everyone simply because of their appearance. On top of this, they are also incredibly harsh critics of themselves.

People with BDD exhibit increased activity in the amygdala when viewing visual stimuli [13]. Interest-

A deficiency in the binding of serotonin, a neurotransmitter responsible for stabilizing one’s mood, may

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Do You See What I See? further contribute to the dissatisfaction felt by those with BDD. While the role of serotonin is unclear when it comes to BDD, low serotonin levels have been linked to body image disturbances and dissatisfaction in other disorders, such as anorexia nervosa [18]. Neurotransmitters like serotonin work by passing chemical signals from one neuron (i.e. brain cell) to another to communicate a particular message. In order for the message to make it from one neuron to another, the neurotransmitters must bind to specific receptor sites. Unfortunately, in patients with BDD, there are less serotonin binding sites. This causes less serotonin to effectively bind and pass on chemical signals [19]. Consequently, low serotonin binding levels may cause BDD symptoms to worsen, causing individuals to possess more negative feelings about their bodies, like discontent or disgust [20]. Furthermore, BDD doesn’t always act alone: low serotonin is associated with other disorders such as depression and anxiety, which can occur in tandem, or be “comorbid” [21]. This overlap in serotonin deficiency means the same drugs used to combat depression can sometimes help with BDD treatment [22]. For example, selective serotonin reuptake inhibitors (SSRIs), antidepressants which increase the effects of serotonin in the body, also aid in reducing symptoms of BDD [23]. While a variety of biological factors can influence BDD, social and cultural factors may also play a critical role in the development of the disorder.

TRYING TO MEET SOCIETY’S STANDARDS When scrolling through Instagram or TikTok, pictures of models and influencers with idealized and unachievable bodies often flash by. When we are repeatedly exposed to only certain types of bodies, we mentally ingrain them as societal beauty s t a n d a rd s , leading us to scrutinize our own bodies and appearances if they do not align. Spending long periods of time on social media platforms such as Instagram and Snapchat has been associated with the development of BDD symptoms

[24]. People with BDD were also found to compare their appearances to celebrities on social media more often than those without the disorder, worsening a person’s self-perception and body dissatisfaction [24]. By comparing themselves to airbrushed and altered images of attractive celebrities, individuals with BDD become more critical of their appearance, a phenomenon known as “priming” [25]. For example, watching a five-minute Sports Illustrated video of swimsuit models primes individuals to be more critical of their own bodies and physical flaws. The effect was reversed when the same subjects watched a “body-positive” video [26]. These “priming” experiences draw attention to physical imperfections and are associated with a pressure to attain the “perfect body” [20]. While merely scrolling through social media can be harmful for those with BDD, posting your own photos poses other risks. Choosing the best photo to post on a social media platform may entail fixating on the visual representation of one’s own body and amplifying small flaws, which are behaviors associated with BDD [1]. To adhere to society’s beauty standards, some individuals with BDD may even seek out surgical options to address their perceived imperfections. Specific societal beauty standards surrounding body size, weight, height and the desirability of certain features may determine which body parts individuals tend to fixate upon [27] . For example, rhinoplasties, or nose jobs, are one of the most commonly performed surgeries on women in the Middle East [28]. Due to the dress codes that many Islamic women practice, only part of their face is exposed to the public, making the nose very prominent. This causes women to feel pressured to ensure that their nose is “perfect” [28]. On the other hand, one of the most popular surgeries in East Asia and for Asians in the United States is blepharoplasty, or double-eyelid surgery [29]. Interviews with in-

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dividuals who identify as East Asian or of Asian descent reveal that this fixation over double-eyelids has several motivations: namely, experiencing discrimination for their “small” eyes, or ethnocentric beauty standards being centered around western ideals [30]. Even after such surgeries, there is often no change to BDD symptoms, and individuals may actually seek out these procedures more often [31]. The need to obtain social approval regarding whether one’s body is “attractive” or not is important, especially with young women [32]. Therefore, the promotion of unrealistic sociocultural ideals of female beauty makes women feel dissatisfied with their bodies. Plastic surgeons should be trained to recognize patients who seek out surgical operations as a result of BDD, and the media must make efforts to acknowledge different body types as attractive, instead of promoting one standard of beauty.

SHATTERING THE FUNHOUSE MIRROR: FUTURE DIRECTIONS IN BDD RESEARCH AND AWARENESS BDD has been described as a “secret” obsession [33]. Individuals with BDD tend to end up dealing with their symptoms privately after realizing that others cannot see the flaws that they find so obvious. When peo-

ple with BDD are told by others that they “look fine” despite what they feel about their appearance, they may begin losing trust in those around them, including mental health professionals. Because of poor understanding of the condition and distrust towards medical professionals, some patients may never know that they have BDD, and if they do, they may refuse to seek help [33]. Therefore, it is crucial to promote greater awareness and understanding of BDD amongst both the general public and medical practitioners. Raising awareness of this disorder will help to ensure that those experiencing symptoms reach out for assistance. Further, if more people are made aware of BDD, those diagnosed with the disorder may be more likely to offer themselves compassion during treatment, as they know they are not alone in their struggle with body image self-perception. Countering the stigmas surrounding BDD with increased research and awareness is essential; with access to proper treatment, those suffering can look beyond the broken mirror and work to accept their perceived flaws. References on page 90.

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NEUROLAW: TAKING THE STAND ON MENTAL ILLNESS By Melissa Roybal and Salome Ambokadze / art by Tori Kim

“A

ll jurors this way!” As you walk down the courthouse hallway, your palms begin to sweat. You, Juror #4, sit down and get ready to hear opening arguments. The sound of the judge’s gavel smashing against the podium grabs your attention. After running through a list of the defendant’s charges, the judge asks the defense attorney how the defendant pleads. “Not guilty by reason of insanity.” The defense attorney’s words echo dully throughout the courtroom. “What does ‘guilty by insanity’ even mean? Am I cut out for this?” you wonder, as you begin to grasp what your civic duty truly entails. Let’s take a second to pause and explain what’s going on. There are a couple of terms that you must understand before we proceed. In most jurisdictions in the United States, defendants have the right to plead not guilty by reason of insanity; this plea indicates that the defendant should not be considered culpable for their actions. The court must determine that the defendant did not fully understand the implications of their actions at the time the crime was committed [1, 2]. The defendant also must be declared “competent” to stand trial and receive the death penalty; in this case, being declared competent means that the defendent is capable of fully understanding the consequences of their actions at the time of the trial [1]. While these terms may seem foreign, putting them into context helps a potential juror understand how to proceed in the following scenarios. In the United States, it is all too common that people who are incompetent to stand trial are declared competent because of misunderstandings surrounding mental illness. Incorporating neuroscience research into the legal system will help people with mental disorders get the treatment that they require, rather than keeping them locked away in prison. Considering that one day you might be called to be a juror in a case involving mental illness, we ask that you consider the cases of Scott Panetti, Judge Patrick Couwenberg, and Andrea Yates as if you were tasked

with deciding their verdicts yourself. As we explain the case at hand, we ask you to make a judgement as a juror. After we explore the neurobiology at play, we ask that you reconsider your original verdict, deciding for yourself what role underlying neuroscience and abnormal psychology might play in the legal assessment of heinous crime.

SCOTT PANETTI: THE MAN WHO SUBPOENAED JESUS When remembering her son Scott Panetti’s childhood, his mother described him as “having something dreadfully wrong.” No one understood what Panetti was really experiencing until he was formally diagnosed with schizophrenia at the age of 20 [1]. Schizophrenia is a psychological disorder characterized by delusions that can interfere with daily life. Along with delusions, someone with schizophrenia may also experience hallucinations, an inability to focus, poor mood, and disorganized thinking. While there were attempts to treat Panetti’s illness, they proved ineffective and his condition worsened [1]. He was hospitalized on multiple occasions due to recurrent threats against his wife and her family [1]. On September 8, 1992, these threats unfortunately became reality. After dressing in camouflage, shaving his head, and gathering a variety of weapons, Panetti went to his in-laws’ house [1]. There, he killed his wife’s parents in front of his immediate family, and later confessed to the police [1]. After being declared competent to stand trial, Panetti fired his lawyers and decided to defend himself [1]. He tried to subpoena over 200 people, including John F. Kennedy and Jesus Christ [1]. During the trial, Panetti referred to himself in the third person and acted erratically [1]. Though his behavior was characteristic of someone who was presently detached from reality, the jury was highly offended and did not interpret Panetti’s actions as a clear sign of mental illness. Even though Panetti was unwell, the judge allowed the trial to proceed normally [1]. This decision reflects a great failure of the judicial system; though it was clear that

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Neurolaw Panetti was incapable of defending himself, the judge went forward with the prosecution. Juror, provided with this account of the event, what verdict would you deliver Panetti? Take a second to think. Now, we will explain the neurobiological mechanisms of the illness at hand. The exact neural correlates of schizophrenia remain a mystery. Different schizophrenic symptoms are defined into subcategories, and many of the symptoms Panetti exhibited would be considered “positive.” Positive symptoms refer to behaviors that “add” experiences or elements to a person’s typical functioning [3]. In schizophrenia, these behaviors typically include delusions, hallucinations, disordered and incoherent thinking, and an inability to correctly assess reality [3]. In Panetti’s case, his inability to assess reality (which resulted in his violent behavior), delusional belief that he could subpoena Jesus or J.F.K., and auditory and visual hallucinations are all examples of positive schizophrenia symptoms. But where do these symptoms come from? Schizophrenia is thought to primarily affect the relationship between two parts of the brain: the prefrontal cortex and the mesolimbic area [4]. The prefrontal cortex controls decision making, planning, and personality, while the mesolimbic system regulates goal-directed behavior and our reward system [5]. The prefrontal cortex responds to cues, which in turn limits activity in the mesolimbic areas [4]. This process is termed feedback inhibition, and it works like a thermostat: when a room reaches the desired temperature, the thermostat turns off, and when a room drops below the set temperature, the thermostat turns on. Similarly, the brain uses feedback inhibition mechanisms to maintain “desired” functioning. Some researchers believe that this feedback regulation is impaired in schizophrenics, which would explain the relationship between the positive and negative symptoms in the disease’s progression. If scientists had been able to

analyze Panetti’s brain, we believe that this dysfunctional feedback mechanism would be found, connecting his atypical behavior to a biological explanation, which may have altered the jury’s verdict. Symptoms of schizophrenia are also thought to be affected by an excess of dopamine, the “reward neurotransmitter,” in the frontal lobe of the brain [4]. This neural region is responsible for advanced cognitive skills such as planning, abstract thinking, and decision making. But too much dopamine in the frontal lobe can cause hallucinations and delusions characteristic

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Neurolaw of schizophrenia [3, 4]. This effect can be mimicked by drugs that increase dopamine levels in the brain, such as L-DOPA, cocaine or amphetamine [4]. Scientists do not know why dopamine causes hallucinations and psychotic episodes. However, if we conducted an analysis of the dopamine in Panetti’s brain, we would expect to see greatly increased levels as compared to those of a neurotypical person’s brain. Unfortunately, at the time of Panetti’s case, no neurobiological evidence was collected. Panetti’s jury found him guilty of capital murder in less than two hours, and he was sentenced to death shortly thereafter [1]. In judicial law, the defendant must also be declared competent for execution, just as they must be declared competent to stand trial [1]. While Panetti was originally declared competent for execution, the Supreme Court reversed the decision after years of debate [1]. Despite this reversal, Panetti remains on death row to this day [1]. Panetti’s case provides us with a drastic, but very important, example of how mental illness and its effects can be seriously misunderstood by judges and jurors in the legal system. Panetti is not at all representative of the entire schizophrenic population, and murder is clearly not a side effect of schizophrenia [5]. However, people with schizophrenia are disproportionately represented in the prison population. Schizophrenia affects less than 1% of the general population; but, the rate of similar serious disorders among prison populations is thought to be as high as 25% [7]. This statistic is alarming, especially considering the fact that most prison facilities cannot offer proper treatment to schizophrenic people. Medical facilities, on the other hand, do have the resources to provide pharmacotherapeutic and behavioral options to reduce violent behavior and recidivism, or the tendency for a convicted criminal to reoffend. The frequent interactions of schizophrenic people with the criminal justice system, as well as Panetti’s complicated trial, point to an urgent need to reform how the system understands and responds to mental illness. Reevaluating the criteria for institutionalization and educating jurors on the seriousness of mental illness could make our legal system far more just. As suggested by the alarming rate of individuals with schizophrenia and similar affective disorders in prisons, it is extremely important to make these neural mechanisms understood by the public. Doing so may completely change a jury’s ver-

dict and help more people with schizophrenia get the treatment that they need.

JUDGE PATRICK COUWENBERG: UNRAVELING A COMPLEX WEB OF LIES Patrick Couwenberg lived a life of great prestige and adventure. Before attending law school at the University of La Verne, he earned a Purple Heart for being struck by a debilitating barrage of shrapnel in Vietnam [8]. Not one to be tied down, the wounded Couwenberg soon began working as an undercover CIA agent, embarking on dangerous covert missions to Africa and Laos. Couwenberg’s credentials were clearly enough to impress California governor Pete Wilson, who granted him a judicial appointment in 1997. However, investigators quickly realized that Couwenberg’s life story was completely fabricated [8]. In 2001, he was removed from office on the basis of generating self misrep-

resentations in order to become a judge, continuing to make false claims while in office, and deliberately lying to the commission during the course of its investigation [8]. A psychiatrist expert witness concluded that Couwenberg was suffering from pseudologia fantastica. Commonly known as “pathological lying,” this disorder is characterized by storytelling that extensively combines facts with fantasy [8].

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Juror, what do you think? Should Couwenberg be jailed for lying, or is there enough evidence to declare him not guilty by reason of insanity? Whether we care to admit it or not, we all lie. The average person lies as much as once or twice per day [9]. For many individuals, these lies are often minor and relatively inconsequential. However, for people with pseudologia fantastica, lying can become a debilitating mental condition. In fact, we can even trace the roots of pathological lying to specific brain regions and processes [10]. In order to understand Couwenberg’s case, let’s walk through what happens in the brain of a person with pseudologia fantastica. Pathological liars have more white matter and less grey matter than the average person [11]. White matter acts as the information highway of the brain, bringing activating and inhibitory signals through criss-crossing neuronal “cables” called axons. These extend from the body of one neuron to another, and are the primary method by which neurons communicate. Grey matter makes up the functional lobes of the brain and consists of neuron cell bodies. These structures receive and transmit commands through axons to relevant parts of the body. For example, if you pick up a particularly hot coffee cup, cell bodies in your grey matter will send signals to the hand through white matter so you don’t burn yourself. There are two possible explanations for the excess white matter in the brains of pathological liars: white matter either facilitates verbal processing, or slows down decision-making. Both of these processes could result in the propensity towards deception. In the case of the first hypothesis, excess white matter helps facilitate information processing during deception, which makes sense in the context of increased white matter being associated with superior verbal abilities [11]. In other words, increased white matter allows for these individuals to craft a logical narrative and then believably convey it. Alternatively, an increased volume of prefrontal white matter might prevent the inhibition of neural transmission, halting rational and sensible decision making [11]. Without proper and efficient systems of rational decision making, people may find it easier to lie [11]. However, other processes may

also contribute to pseudologia fantastica. Even minute changes in neural activity can alter deceptive responses, and may help explain the mechanisms at play in pseudologia fantastica [11]. By intentional-

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Neurolaw ly inhibiting the prefrontal cortex, scientists have observed a breakdown in reflective thought and guilt [11]. Think back to a time when you were caught lying. Maybe you stole a cookie from the cookie jar and had time to enjoy it in peace. When your parents eventually asked where the cookie went, you thought about how delicious it was, felt no remorse, and promptly created a lie to avoid punishment. This process, which dulls an individual’s sense of morality, is similar to what occurs when prefrontal cortex activity is inhibited. This alteration of neuronal activity facilitates deceptive behavior by bypassing the guilt response, which helps create a lie [11]. Importantly, the act of pathological lying may not be intentional. Impeding morality prevents individuals from recognizing when their actions are harmful to others or themselves. With all that being said, Juror #4, what’s your decision? Even though Judge Couwenberg repeatedly gave false testimony under oath, the jurors did not believe that he had any mental condition that excused or mitigated his actions [8]. A three-judge panel reported that the presentation of a symptom such as lying, without any underlying mental disorder diagnosis, is of little legal consequence [8]. While it might be possible to argue that Couwenberg’s lying was uncontrollable, it is unrealistic to expect pathological lying to meet

the criteria of insanity in most jurisdictions. Since uncontrollable pathological lying often coexists with ordinary lies for self-benefit, it becomes difficult to differentiate between the two [8]. However, Couwenberg’s case sheds light on the underlying neurobiological dysfunctions associated with pathological lying, which may be more common than you would expect.

ANDREA YATES: A TRAGIC STORY OF POSTPARTUM ILLNESS Andrea Yates and her husband were very successful; she was a nurse and he worked for NASA [1]. The couple had five children [1]. However, after the birth of their fourth child, things took a turn for the worse. When Yates attempted suicide and was admitted to a mental hospital, she continued to display suicidal tendencies [1]. Doctors diagnosed Yates with postpartum depression (PPD) with psychosis [1]. In 2000, against doctors’ recommendations, Yates and her husband had their fifth child, Mary [1]. After Mary’s birth, Yates began to show postpartum symptoms again, engaging in self mutilation, child neglect, compulsive biblical study, and falling into catatonic (i.e. rigid body) states [1]. On June 20, 2001, Yates drowned all five of her children while her husband was at work [1]. Yates immediately called the police to confess, explaining that she had done it because she believed that she needed to be punished for being a bad mother [1]. Juror, what would be your verdict? Yates’s story is an especially intense and heart wrenching one. For readers, it may be difficult to empathize with this mentally ill mother or come to terms with what occurred. The severity of Yates’s postpartum depression is unusual and her actions are not at all representative of all mothers who suffer from postpartum illness [13]. But, to understand what led Yates to commit these murders, let’s explain what may have brought her to this disturbing decision from a neurological lens. First, let’s consider the major role that hormones play in postpartum disorders. Hormones are chemical messengers that foster communication between the brain and the body; they can also be used to identify certain dysfunctions. Hormones are constantly released to convey all types of messages to the body, like “your stomach is full,” “pump blood faster,” or “it’s nighttime, so it’s time to get sleepy.” Oxytocin, a hormone associated with attachment and parent-child bonding, may contribute directly to the onset and severity of postpartum depression symptoms. The most affectionate and responsive parents typically have high

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Neurolaw

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Neurolaw oxytocin levels [13]. Conversely, low levels of maternal oxytocin are associated with a greater severity of PPD symptoms [14]. Since oxytocin increases maternal responsiveness to a child’s crying, low oxytocin levels caused by PPD can hurt the relationship between mother and infant. [16]. Mothers with depression are less likely to engage in face-to-face interactions with their children, such as talking to them, touching them, or smiling [16]. Therefore, the mother may fail to connect with her children, as seen in cases like Yates’s. While oxytocin levels are not responsible for Yates’s behavior, hormone observation may be useful in identifying and treating postpartum disorders. Oxytocin is not the only biological messenger implicated in the development of postpartum depression. Women with PPD also show increased levels of glutamate in their medial prefrontal cortices [17]. Glutamate is an excitatory neurotransmitter in the brain that activates other surrounding cells, while the medial prefrontal cortex is a brain region responsible for decision making [17]. Increased neural activation caused by excess glutamate may have caused Yates to suffer from severe auditory hallucinations [1]. Some pharmaceuticals have been developed to block glutamate from communicating with other neurons, which improves hallucinatory symptoms in schizophrenic patients; perhaps the same treatment could be used for those with postpartum psychosis [18]. This connection between postpartum psychosis and glutamate may help jurors understand the mechanisms behind Yates’s actions. While chemical signals are certainly implicated in postpartum depression and psychosis, the physiological anatomy of the brain contributes to this dysfunction as well. In other words, significant physical changes occur in the brains of postpartum depression patients. These changes include disrupted connectivity and reduced activity in both the anterior cingulate cortex and the amygdala [18]. To break it down, the anterior cingulate cortex is involved with empathy, impulse control, emotion, and decision making, while the amygdala is involved with processing fear and emotions. These characteristics relate to how Yates connected with her children, and how irrational fear led her to make an impulsive and dangerous decision [18]. More research is needed on the circuitry of postpartum disorders, but looking at different sections of the brain can help us see that Yates’s actions were not based on her ability to be a good mother, but on imbalances in the brain that resulted in tragic consequences.

All that being said, Juror #4, does this information sway your decision? The state of Texas charged Yates with five counts of capital murder. During her trial, Yates explained that she wanted to be found guilty and sentenced to death so that she could kill Satan [1]. Despite being in a delusional state, she was tried in a court of law. Fortunately, experts agreed that she met the legal criteria for insanity; four psychiatrists testified that Yates did not know right from wrong when she committed the crime, and the jury ultimately found her “not guilty” [1]. After the trial, Yates was committed to a psychiatric facility indefinitely [1]. Postpartum depression and psychosis are extremely complex disorders that can have drastic implications. While cases of postpartum depression as severe as Yates’s are rare, researchers have found that up to 41% of depressed mothers have had thoughts of harming their children [19]. Yates’s case still leaves us with more questions. Consider the postpartum nature of the disease; does this signify that the symptoms will eventually subside? Medical data has been unable to determine an average duration of PPD, but some women report PPD symptoms as long as five years after giving birth [20]. If there are no lasting symptoms, should patients like Yates remain in mental health institutions or prisons? While we cannot answer these questions, we encourage readers to ponder them and consider the importance of postpartum research and advocacy.

THE FINAL VERDICT By presenting readers with a variety of legal cases, we provide thought experiments that illustrate the importance of neurolaw and why it should continue to be developed as a field. We hope that you will continue to think about the cases we have presented, attempt to answer the questions we have posed, and spread awareness about the issues we have raised. While we are not experts, we would like to propose some possible improvements to the judicial system so that mental health may be adequately taken into consideration. First, educating jurors and judges is essential in trials concerning mentally ill individuals. Panetti’s story, in particular, makes it apparent that the jurors and the judges involved were uneducated about the severity to which mental illness can impact one’s control over, or understanding of, their own actions. Similarly, those who decide the futures of mentally ill defendants must also be aware of how integration into the prison system can be especially harmful for

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Neurolaw mentally ill people, in a far different way than neurotypical people [21]. Second, mental health experts and social workers should be the primary figures interacting with mentally ill individuals on trial. If police officers must be involved, they should be educated about how to properly respond to those affected by mental illness. In closing, we want to reiterate that these very rare cases are not representative of all people diagnosed with the mental illnesses being discussed. We hope readers will leave with an understanding that the only things separating Panetti, Couwenberg and Yates from us might be a few chemical imbalances and morphological changes in the brain, over which they have no control. Behind shocking and sometimes highly sensationalized cases such as these, there are real people that need help. With a little bit of explanation, the average juror can begin to understand these complex disorders. References on page 91.

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Betrayed By My Body

BETRAYED BY MY BODY: THE SCIENCE BEHIND ALIEN HAND SYNDROME By Lucas Angles / art by Cherrie Chang

ou wake up in the middle of the night to someone’s hand around your throat. You struggle and thrash as hard as you can, but the fingers tighten, and you begin to lose consciousness. You manage to turn on your nearby lamp to get a glimpse of the assailant. When the room illuminates, you open your eyes and see… no one. The space around you is empty, but as you look down, you see the hands that are gripping you so tightly. They are your own. This nightmarish experience can be common for those with alien hand syndrome (AHS), a disorder that causes a limb to act on its own accord. Those with AHS frequently find their hands performing actions that they would never do, such as hitting or forcefully gripping objects, other people, or even themselves. These complex movements are smooth and purposeful, distinct from spasms and seizures, but occur without the knowledge of the individual. One of the best-known examples of AHS in popular media is the film Dr. Strangelove, where the titular character suffers from a fictionalized variant of AHS. The German scientist is unable to stifle the Nazi salute of his right hand in front of American officials, eventually having to restrain the hand with his other. Although used for the sake of parody here, AHS affects many dealing with, or recovering from, brain damage worldwide.

FROM POSSESSION TO PHYSIOLOGY: THE DISCOVERY OF ALIEN HAND SYNDROME The curious phenomenon of involuntary movement has puzzled physicians for over a hundred years. When prominent German neurologist Kurt Goldstein first described such phenomena at the turn of the

“

THOSE WITH AHS FREQUENTLY FIND THEIR HANDS PERFORMING ACTIONS THAT THEY WOULD NEVER DO, SUCH AS HITTING OR FORCEFULLY GRIPPING OBJECTS, OTHER PEOPLE, OR EVEN THEMSELVES.

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20th century, the superstitious belief that seizures were the result of possession still held sway over many. The complex, sometimes harmful, movements associated with AHS were thought to be the work of the devil [1]. Goldstein described a woman recovering from a stroke whose left arm moved with purpose, without her knowledge or control. The hand would stroke her hair or rub her nose as if she were initiating the movements herself. At one point, the hand even attempted to strangle the woman during an examination, only stopping after being restrained by force [2]. It was not until 1972, nearly 70 years after Goldstein’s observations, that physicians coined the term “alien hand.” When shown their afflicted hand, those with the disorder cannot recognize it as their own [3]. In fact, many people with AHS name their aberrant limb, viewing it as a totally separate entity [4]. The field of neuroscience has grown exponentially in the past 50 years. In particular, the advancement of brain-imaging technology has significantly developed our understanding of alien hand syndrome. The invention of magnetic resonance imaging (MRI) allowed

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Betrayed By My Body

CELL DEATH BRINGS THE ALIEN HAND TO LIFE After patients with AHS underwent MRI, physicians were able to identify the primary cause of the disorder: widespread cell death. This destruction is the product of a wide range of diseases and trauma, and can lead to significant impairment in dayto-day cognitive function. Neurologists have tracked similar destructive patterns across those diagnosed with AHS [4].

for one brain’s overall structure to be referenced and compared to others via images. The visualization of healthy brains prompted the analysis of abnormal brains. People with neurological disorders no longer have to wait until after their deaths to be diagnosed. Using MRI, neurologists can precisely determine the “where,” “when,” “why,” and “how” of diseases like AHS.

Strokes are the most common cause of universal cell loss, affecting more than 800,000 people in the US every year [5]. But what are strokes, and how do they happen? Imagine the blood vessels in your brain as a plumbing system. Blood carries oxygen and nutrients to cells and washes waste and carbon dioxide away in order to maintain proper cellular functioning. When a stroke occurs, it either happens in the form of a burst pipe (i.e. a hemorrhage), or a blockage in the plumbing (i.e. ischemia). Oxygenated blood cannot reach a specific brain area, depriving neurons and other brain cells of oxygen and killing these cells if the stroke cannot be reversed in time. Strokes are usually localized to a particular region of the brain; individuals may exhibit slurred speech, paralysis, among other symptoms — usually limited to one side of the body — depending on where the stroke occurs [5]. Some stroke victims may even completely lose their ability to understand language [6]. Strokes can affect any area of the brain with equal likelihood; there is no one region that is always affected, which causes stroke victims to display a wide array of symptoms.

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Betrayed By My Body Other significant contributors to AHS cases include neurodegenerative disorders like Alzheimer’s Disease (AD) and Corticobasal Degeneration (CBD) [4]. Physicians characterize these conditions by the continuous death of neurons. These cells are attacked and destroyed as a byproduct of an exaggerated immune response. Patients with AD may lose 15% of their brain volume in a year due to cell death [7]. A critical component of the degeneration observed in AD and CBD is the misfolding of specific proteins. If cells are the building blocks of life, proteins are the cellular “workers” that make that life possible. With a vast array of functions, from the formation of skeletal structure to the creation of DNA to even making other proteins, the different shapes of these molecules determine their function in our bodies. A long thin protein may end up in a person’s hair, while a protein that the body can stretch may work well in an athlete’s muscles. However, in AD and CBD, proteins cannot perform their designated functions. Much like a crumpled ball of paper compared to a carefully folded paper airplane, improperly folded proteins are essentially useless and can be toxic to the body. In both CBD and AD, a protein called tau misfolds and accumulates within the cell [8]. Tau makes up much of the scaffolding that holds each cell together. When it misfolds, tau can no longer keep the neuron’s structure and the cell collapses.

communicates with itself. Think of white matter regions as the telephone lines of the brain. As they collect and transmit information, the entire system coordinates thought and action [11]. Grey matter, on the other hand, is primarily found on the outside surface of the brain and is composed of neuronal cell bodies. This is where the nucleus and most other structures within the cell are located, and is the site of signal reception [11]. In cases of AHS, destruction of the brain’s white matter irreparably shuts down the communication system between brain regions. As a result, many areas are completely cut off from others and therefore cannot coordinate activities with each other [4]. On a cellular level, each end of the brain is the equivalent of thousands of miles apart! Without the axonal information highways that connect these regions, they are working in the dark.

While extremely rare, most cases of the neurodegenerative prion disorder CreutzfeldtJakob Disease (CJD) result in AHS. Prions are similar to misfolded proteins that are “zombified.” Upon contact, a prion refolds proteins of the same type into the diseased state. These newly infected proteins then spread the disease throughout the entire body exponentially [9]. The immune system identifies clumps of prions as a foreign body and targets that area of the brain, killing all the normal surrounding cells in the process. In the 1980s and 90s, panic swept the United Kingdom after 177 people died from consuming beef tainted with “mad cow disease,” a bovine variant of CJD. Because prions can jump from one animal to another if they are sufficiently related, concern for public safety forced the U.K. to slaughter 4 million cattle [10]. The degeneration that contributes to AHS primarily affects the brain’s white matter rather than grey matter [4]. When looking at the brain, the two types of tissue are very apparent. White matter gets its name from the color of the enormous number of axons that comprise it. Axons are the parts of the neuron that carry signals and are the primary way the brain

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Betrayed By My Body

A BREAKDOWN IN COMMUNICATION It is tempting to place very distinct purposes and functions on each region, or lobe, of the brain. These concrete separations make it easier for physicians to simplify understanding of cognition. There is a lobe for vision, a lobe for hearing, a lobe for touch, and so on. However, in reality, the brain is inextricably interconnected. You would never be able to recognize a chair as a chair, have emotional responses to different smells, or unlock certain memories from the foods you eat without the communication of any given region with another. The prefrontal cortex (PFC), which encompasses the front half of your brain, is considered the “mission control” of the brain. Frequently, different lobes communicate with the PFC, where “decision making” occurs. The PFC makes choices, is responsible for much of our knowledge, and represents the largest contributor to each of our individual differences [12]. When you move, such as when you contract the muscles in your fingers to turn a page, your PFC has already decided to do so long before. The PFC then sends these signals straight behind it to the motor cortex. There, neurons pass through the basal ganglia, the site of movement

regulation, and span the brain and down the spinal cord, eventually branching off and attaching to muscle tissue [13]. When these neurons pass down a signal sent from the brain, their corresponding muscles contract. Because information flows from the PFC in the front of the brain to the motor cortex behind it, researchers have termed this process “front-to-back movement” [14]. In the neurodegeneration characteristic of AHS, frontto-back movement is disrupted. The reduction of white matter prevents the PFC from communicating with the brain region that coordinates movement, aptly named the motor cortex. This lack of coordination causes the motor cortex to activate on its own and creates movement in the absence of any conscious choice by the PFC. Functional magnetic resonance imaging (fMRI) has revealed the distinct lack of interaction between the motor cortex, the PFC, and the basal ganglia. Unlike MRI, which can only show the general structure of a subject’s brain, fMRI allows us to clearly observe areas of neural activity in real-time [15]. What usually is a synchronized orchestra of various brain regions in normal brain functioning devolves into many different instruments playing out of tune in the AHS brain. This absence of coordination and inhibition leads to the unconscious movement characteristic of AHS.

TAKING CONTROL OF THE ALIEN HAND: THERAPEUTIC OPTIONS AND FUTURE DIRECTIONS Today, there is no definitive cure for AHS. Nonetheless, treatments exist that mitigate symptoms for those with the condition so that they can recover a sense of autonomy. Treatments mainly consist of cognitivebehavioral therapy (CBT) in conjunction with medication or rehabilitation exercises [4]. CBT, a mainstay in the treatment of major depressive disorder and bipolar disorder, seeks to correct harmful behavior by creating new ways of approaching issues and problemsolving to manage stress [16]. For AHS patients who are terrified that their own body is working against them, CBT serves to stave off the anxiety associated with the disorder, allowing patients to better utilize the affected hand [4]. The more calm and focused individuals with AHS are, the more receptive they are to treatment [4]. Medicinal drugs are now the fastest growing field in the treatment of AHS. Medication treatments for AHS primarily focus on reducing movement in general, in an effort to halt non-voluntary motion. Clonazepam, an anti-seizure medication, is frequently

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Betrayed By My Body used to treat constant repetitive movement called dystonia. Clonazepam is a benzodiazepine, or a “benzo,” meaning it operates by decreasing overall neural activity, especially within the motor cortex. Benzos like clonazepam are believed to quell selfactivation of the cortex, stopping AHS-characteristic movements altogether [17]. Botulinum toxin A, or “botox,” is frequently employed to paralyze muscles for cosmetic purposes. In the case of AHS, small doses of botox can retain voluntary movement while blocking any abnormal activity, like how a strainer lets liquids through while keeping out solids [17].

limb with a job, substituting any destructive movements with constructive behavior [18]. In other cases, restricting the limb either with a free hand or inhibitive casting — like those used by patients who have broken their arms — reduces the frequency of destructive incidents [4]. A cast restricts the limb, and “muffles’’ any sort of involuntary movement. In fact, this same strategy is used in patients with cerebral palsy to overcome the seizing of specific body parts [19]. Diverting and restricting movement are the most productive forms of recovery from AHS, preventing potentially harmful side-effects that may result from the improper use of medication. Despite being categorized more than a century ago, alien hand syndrome continues to puzzle physicians and neurologists alike. Advancements in imaging technology have allowed us to gain insight into the seemingly counterintuitive way neural destruction can lead to the production of coordinated movement. However, the neural correlates of the condition are nebulous. How is activity in the motor cortex generated, if not from coordination with the PFC? Why are these movements so complex instead of seizurelike spasms? How can an individual move voluntarily at one point and lose control the next? With the constant creation of novel, efficient techniques to peer inside the brains of those with AHS, scientists may soon answer these questions. With each new finding, AHS offers advanced knowledge into how and why the body “chooses” to move. Through the analysis and treatment of such rare diseases, we can better appreciate the underlying mechanisms behind our everyday actions. References on page 92.

Rehabilitative exercises are currently the most effective treatment for AHS, and are widely preferred to medication. These tasks serve to distract or restrain the limb, and are used to manage a variety of motor and sensory disorders. One of the simplest forms of treatment involves “distracting” the freely moving limb with a task to complete, such as gripping or carrying an object. This diversion occupies the problematic

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References

REFERENCES APHANTASIA AND THE BLIND IMAGINATION 1. Zeman, A., Dewar, M., & Sala S.D. (2015). Lives without imagery – congenital aphantasia. Cortex, 73, 378-380. doi:10.1016/j.cortex.2015.05.019. 2. Zeman, A., Milton, F., Sala, S.D., Dewar, M., Frayling, T., Gaddum, J., Hattersley A., Heuerman-Williamson, B., Jones, K., MacKisack, M., & Winlove, C. (2020). Phantasia – the psychological significance of lifelong visual imagery vividness extremes. Cortex, 130, 426-440. doi:10.1016/j.cortex.2020.04.003. 3. Zeman, A.Z., Sala, S.D., Torrens, L.A., Goutouna, V.E., McGonigle, D.J. & Logie, R.H. (2010). Loss of imagery phenomenology with intact visuo-spatial task performance: a case of ‘blind imagination’. Neurosychologia, 48 (1), 145-155. doi: 10.1016/j. neuropsychologia.2009.08.024. PMID: 19733188 4. Humbert-Droz, S. (2018). Aphantasia and the decay of mental images. Advances in Experimental Philosophy of Aesthetics, 1. 167-175. 5. Monzel, M., Keidel, K. & Reuter, M. (2018). Imagine, and you will find – Lack of attentional guidance through visual imagery in aphantasics. Atten Percept Psychophys, 83, 2486–2497. doi:10.3758/ s13414-021-02307-z. 6. Watkins, N. W. (2018). (A)phantasia and severely deficient autobiographical memory: scientific and personal perspectives. Cortex, 105, 41-52. doi:10.1016/j.cortex.2017.10.010. 7. Milton, F., Fulford, J., Dance, C., Gaddum, J., Heuerman-Williamson, B., Jones, K., Knight, K. F., MacKisack, M., Winlove, C. & Zeman, A. (2021). Behavioral and neural signatures of visual imagery vividness extremes: aphantasia and hyperphantasia. Cerebral Cortex Communications, 2 (2). doi:10.1093/ texcom/tgab035 8. Wicken, M., Keogh, R., & Pearson, J. (2021). The critical role of mental imagery in human emotion: insights from fear-based imagery and aphantasia. Proc. R. Soc. B, 288. doi:10.1098/rspb.2021.0267

SPECIAL K: THE UNEXPECTED ANTIDEPRESSANT 1. Hashimoto, K. (2019). Rapid-acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective. Psychiatry and Clinical Neurosciences, 73(10), 613-627.

doi:10.1111/pcn.12902 2. Shin, C., & Kim, Y-K. (2020). Ketamine in major depressive disorder: Mechanisms and future perspectives. Psychiatry Investigation, 17(3), 181-192. doi:10.30773/pi.2019.0236 3. National Institute of Mental Health. (2019). Major depression. National Institute of Mental Health. Retrieved from https://www.nimh.nih.gov/health/ statistics/major-depression.shtml 4. Li, L., & Vlisides, P. E. (2016). Ketamine: 50 years of modulating the mind. Frontiers In Human Neuroscience, 10(612), 1-15. doi:10.3389/fnhum.2016.00612 5. Berman, R. M., Cappiello, A., Anand, A., Oren, D. A., Heninger, G. R., Charney, D. S., & Krystal, J. H. (2020). Antidepressant effects of ketamine in depressed patients. Biological Psychiatry, 47(4), 351– 354. doi:10.1016/s0006-3223(99)00230-9 6. Skolnick, P., Layer, R. T., Popik, P., Nowak, G., Paul, I., & Trullas, R. (1996). Adaptation of N-methyl-D-aspartate (NMDA) receptors following antidepressant treatment: Implications for the pharmacotherapy of depression. Pharmacopsychiatry, 29(1), 23–26. doi:10.1055/s-2007-979537 7. Reinstatler, L., & Youssef, N. A. (2015). Ketamine as a potential treatment for suicidal ideation: A systematic review of the literature. Drugs in R&D, 15(1), 37–43. doi:10.1007/s40268-015-0081-0 8. Murrough J. W. (2012). Ketamine as a novel antidepressant: From synapse to behavior. Clinical Pharmacology and Therapeutics, 91(2), 303–309. doi:10.1038/clpt.2011.244 9. Maeng, S., & Zarate, C. A., Jr (2007). The role of glutamate in mood disorders: Results from the ketamine in major depression study and the presumed cellular mechanism underlying its antidepressant effects. Current Psychiatry Reports, 9(6), 467–474. doi:10.1007/s11920-007-0063-1 10. Sleigh, J., Harvey, M., Voss, L., & Denny, B. (2014). Ketamine—more mechanisms of action than just NMDA blockade. Trends in Anaesthesia and Critical Care, 4(2), 76-81. doi:10.1016/j.tacc.2014.03.002 11. Aleksandrova, L. R., & Phillips, A. G. (2021). Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics. Trends in Pharmacological Sciences, 42(11). doi:10.1016/j.tips.2021.08.003 12. Autry, A., Adachi, M., Nosyreva, E., Na, E. S., Maarten, F. L., Cheng, P., Kavalali, E. T., & Monteggia, L. M. (2011). NMDA receptor blockade at rest triggers

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References rapid behavioural antidepressant responses. Nature, 475, 91–95. doi:10.1038/nature10130 13. Liu, W., Ge, T., Leng, Y., Pan, Z., Fan, J., Yang, W., & Cui, R. (2017). The role of neural plasticity in depression: From hippocampus to prefrontal cortex. Neural Plasticity, 2017(6871089). doi:10.1155/2017/6871089 14. Ghasemi, M., Kazemi, M. H., Yoosefi, A., Ghasemi, A., Paragomi, P., Amini, H., & Afzali, M. H. (2014). Rapid antidepressant effects of repeated doses of ketamine compared with electroconvulsive therapy in hospitalized patients with major depressive disorder. Psychiatry Research, 215(2), 355-361. doi:10.1016/j.psychres.2013.12.008 15. Daly, E. J., Singh, J. B., Fedgchin, M., Cooper, K., Lim, P., Shelton, R. C., Thase, M. E., Winokur, A., Van Nueten, L., Manji, H., & Drevets, W. C. (2018). Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression: A randomized clinical trial. JAMA Psychiatry, 75(2), 139-148. doi:10.1001/jamapsychiatry.2017.3739 16. Vasavada, M. M., Leaver, A. M., Njau, S., Joshi, S. H., Ercoli, L., Hellemann, G., Narr, K. L., & Espinoza, R. (2017). Short- and long-term cognitive outcomes in patients with major depression treated with electroconvulsive therapy. The Journal of ECT, 33(4), 278–285. doi:10.1097/YCT.0000000000000426 17. Brachman, R. A., McGowan, J. C., Perusini, J. N., Lim, S. C., Pham, T. H., Faye, C., Gardier, A. M., Mendez-David, I., David, D. J., Hen, R., & Denny, C. A. (2016). Ketamine as a prophylactic against stress-induced depressive-like behavior. Biological Psychiatry, 79(9), 776-786. doi:10.1016/j.biopsych.2015.04.022 18. Hasselmann H. W. (2014). Ketamine as antidepressant? Current state and future perspectives. Current Neuropharmacology, 12(1), 57–70. doi:10.2174/ 1570159X113119990043 19. Chouinard, G., & Chouinard, V. A. (2015). New classification of selective serotonin reuptake inhibitor withdrawal. Psychotherapy and Psychosomatics, 84(2), 63-71. doi:10.1159/000371865 20. Jilka, S., Odoi, C. M., Wilson, E., Meran, S., Simblett, S., & Wykes, T. (2021). Ketamine treatment for depression: Qualitative study exploring patient views. BJPsych open, 7(1), e32. doi:10.1192/bjo.2020.165 21. Jilka, S., Murray, C., Wieczorek, A., Griffiths, H., Wykes, T., & McShane, R. (2019). Exploring patients’ and carers’ views about the clinical use of ketamine to inform policy and practical decisions: Mixed-methods study. BJPsych Open, 5(5), e62. doi:10.1192/bjo.2019.52 22. Sapkota, A., Khurshid, H., Qureshi, I. A., Jahan, N.,

Went, T. R., Sultan, W., & Alfonso, M. (2021). Efficacy and safety of intranasal esketamine in treatment-resistant depression in adults: A systematic review. Cureus, 13(8). doi:10.7759/cureus.17352

HAVE NO FEAR, YOUR HIDDEN FEAR RESPONSE REGULATORS ARE HERE: HOW OUR CAREGIVERS SHAPED OUR FEAR REGULATION SYSTEM 1. Zeanah, C. H., Gunnar, M. R., McCall, R. B., Kreppner, J. M., & Fox, N. A. (2014). Sensitive periods. Monographs of the Society for Research in Child Development, 76(4), 147-162. doi:10.1111/j.15405834.2011.00631.x. 2. McLaughlin, K. A., Sheridan, M. A., Tibu, F., Fox, N. A., Zeanah, C. H., & Nelson, C. A. (2015). Causal effects of the early caregiving environment on development of stress response systems in children. Proceedings of the National Academy of Sciences, 112(18), 5637–5642. doi:10.1073/pnas.1423363112. 3. Perry, R. E., Blair, C., & Sullivan, R. M. (2017). Neurobiology of infant attachment: Attachment despite adversity and parental programming of emotionality. Current Opinion in Psychology, 17, 1–6. doi:10.1016/j.copsyc.2017.04.022. 4. Ressler, K. J. (2010). Amygdala activity, fear, and anxiety: Modulation by stress. Biological Psychiatry, 67(12), 1117–1119. doi: 10.1016/j.biopsych.2010.04.027. 5. Smith, S. M. (2006). The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues in Clinical Neuroscience, 8(4), 383–395. doi:10.31887/dcns.2006.8.4/ ssmith. 6. Tottenham, N. & Sheridan, M. A. (2009). A review of adversity, the amygdala and the hippocampus: A consideration of developmental timing. Frontiers in Human Neuroscience. doi:10.3389/neuro.09.068.2009. 7. Gee, D. G. (2016). Sensitive periods of emotion regulation: Influences of parental care on Frontoamygdala circuitry and plasticity. New Directions for Child and Adolescent Development, 2016(153), 87–110. doi:10.1002/cad.20166. 8. Gee, D. G., Gabard-Durnam, L., Telzer, E. H., Humphreys, K. L., Goff, B., Shapiro, M., Flannery, J., Lumian, D. S., Fareri, D. S., Caldera, C., & Tottenham, N. (2014). Maternal buffering of human amygdala-prefrontal circuitry during childhood but not during adolescence. Psychological Science, 25(11), 2067–2078. doi:10.1177/0956797614550878. 9. Olsavsky, A. K., Telzer, E. H., Shapiro, M., Humphreys, K. L., Flannery, J., Goff, B., & Tottenham, N.

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 3

References (2013). Indiscriminate amygdala response to mothers and strangers after early maternal deprivation. Biological Psychiatry, 74(11), 853–860. doi:10.1016/j. biopsych.2013.05.025. 10. Mehta, M. A., Golembo, N. I., Nosarti, C., Colvert, E., Mota, A., Williams, S. C., Rutter, M., & Sonuga-Barke, E. J. (2009). Amygdala, hippocampal and corpus callosum size following severe early institutional deprivation: The English and Romanian adoptees study pilot. Journal of Child Psychology and Psychiatry, 50(8), 943–951. doi:10.1111/j.14697610.2009.02084.x. 11. Thomas, K. M., Drevets, W. C., Dahl, R. E., Ryan, N. D., Birmaher, B., Eccard, C. H., Axelson, D., Whalen, P. J., & Casey, B. J. (2001). Amygdala response to fearful faces in anxious and depressed children. Archives of General Psychiatry, 58(11),1057-63. doi:10.1001/archpsyc.58.11.1057. 12. Malter Cohen, M., Jing, D., Yang, R. R., Tottenham. N., Lee, F. S., & Casey, B. J. (2013). Early-life stress has persistent effects on amygdala function and development in mice and humans. Proceedings of the National Academy of Sciences of the United States of America, 110(45), 18274–18278. doi:10.1073/pnas.1310163110. 13. Salter Ainsworth, M. D., Blehar, M. C., Waters, E., & Wall, S. N. (2015). Patterns of attachment: A psychological study of the strange situation. Psychology Press. 14. De Wolff, M. S., & van Ijzendoorn, M. H. (1997). Sensitivity and attachment: A meta-analysis on parental antecedents of infant attachment. Child Development, 68(4), 571–591. doi:10.1111/j.1467-8624.1997. tb04218.x. 15. Hostinar, C. E., Sullivan, R. M., & Gunnar, M. R. (2014). Psychobiological mechanisms underlying the social buffering of the hypothalamic–pituitary– adrenocortical axis: A review of animal models and human studies across development. Psychological Bulletin, 140(1), 256–282. doi:10.1037/a0032671. 16. Heinrichs, M., Baumgartner, T., Kirschbaum, C., & Ehlert, U. (2003). Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress. Biological Psychiatry, 54(12), 1389–1398. doi:10.1016/s0006-3223(03)00465-7. 17. Seltzer, L. J., Ziegler, T. E., & Pollak, S. D. (2010). Social vocalizations can release oxytocin in humans. Proceedings of the Royal Society B: Biological Sciences, 277(1694), 2661–2666. doi:10.1098/ rspb.2010.0567. 18. Wismer Fries, A. B., Ziegler, T. E., Kurian, J. R., Jacoris, S., & Pollak, S. D. (2005). From the cover: Early experience in humans is associated with changes in neuropeptides critical for regulating

social behavior. Proceedings of the National Academy of Sciences, 102(47), 17237–17240. doi:10.1073/ pnas.0504767102. 19. Feldman, R. (2017). The neurobiology of human attachments. Trends in Cognitive Sciences, 21(2), 80–99. doi:10.1016/j.tics.2016.11.007. 20. Chambers, J. (2017). The neurobiology of attachment: From infancy to clinical outcomes. Psychodynamic Psychiatry, 45(4), 542–563. doi:10.1521/ pdps.2017.45.4.542. 21. Feldman, R., Gordon, I., & Zagoory-Sharon, O. (2010). The cross-generation transmission of oxytocin in humans. Hormones and Behavior, 58(4), 669–676. doi:10.1016/j.yhbeh.2010.06.005. 22. Boccia, M. L., Petrusz, P., Suzuki, K., Marson, L., & Pedersen, C. A. (2013). Immunohistochemical localization of oxytocin receptors in human brain. Neuroscience, 253, 155–164. doi:10.1016/j.neuroscience.2013.08.048. 23. Kirsch, P. (2005). Oxytocin modulates neural circuitry for social cognition and fear in humans. Journal of Neuroscience, 25(49), 11489–11493. doi:10.1523/jneurosci.3984-05.2005. 24. Petrovic, P., Kalisch, R., Singer, T., & Dolan, R. J. (2008). Oxytocin attenuates affective evaluations of conditioned faces and amygdala activity. Journal of Neuroscience, 28(26), 6607–6615. doi:10.1523/ jneurosci.4572-07.2008. 25. Domes, G., Heinrichs, M., Gläscher, J., Büchel, C., Braus, D. F., & Herpertz, S. C. (2007). Oxytocin attenuates amygdala responses to emotional faces regardless of Valence. Biological Psychiatry, 62(10), 1187–1190. doi:10.1016/j.biopsych.2007.03.025.

404 ACCESSIBILITY NOT FOUND: DISABILITY AND TECHNOLOGY 1. Rahman, L. (2019). Disability language guide. Stanford Disability Initiative Board. Retrieved from https://disability.stanford.edu/sites/g/files/sbiybj1401/f/disability-language-guide-stanford_1.pdf 2. Centers for Disease Control and Prevention. (2020). Disability and health overview. Centers for Disease Control and Prevention. Retrieved from https:// www.cdc.gov/ncbddd/disabilityandhealth/disability.html 3. Staat, D. (2020). Recently completed investigation [Investigative Reports; Monitoring Reports]. US Department of Education (ED). Retrieved from https://www2.ed.gov/about/offices/list/ocr/docs/ investigations/11116002-b.html 4. Rao, K., Ok, M. W., & Bryant, B. R. (2014). A review of research on universal design educational models.

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 3

References Remedial and Special Education, 35(3), 153–166. doi:10.1177/0741932513518980 5. World Health Organization. (2011). World report on disability 2011. World Health Organization. Retrieved from https://www.who.int/teams/noncommunicable-diseases/sensory-functions-disability-and-rehabilitation/world-report-on-disability 6. Centers for Disease Control and Prevention. (2019). Disability impacts all of us. Centers for Disease Control and Prevention. Retrieved from https:// www.cdc.gov/ncbddd/disabilityandhealth/infographic-disability-impacts-all.html 7. Stanford Neurodiversity Project. (2021). Stanford neurodiversity project. Stanford Medicine. Retrieved from https://med.stanford.edu/neurodiversity.html 8. Kong, M., & Willig, J. (2020). The 5-Es: A model for providing care for non-neurotypical patients. Pediatric Research, 88(5), 686–687. doi:10.1038/ s41390-020-0810-0 9. Brittain, I., Biscaia, R., & Gérard, S. (2020). Ableism as a regulator of social practice and disabled peoples’ self-determination to participate in sport and physical activity. Leisure Studies, 39(2), 209–224. doi:10.1080/02614367.2019.1694569 10. Web Accessibility Initiative. (2021a). Diverse abilities and barriers. Web Accessibility Initiative. Retrieved from https://www.w3.org/WAI/people-useweb/abilities-barriers/ 11. Schulz, T., & Skeide Fuglerud, K. (2012). Creating personas with disabilities. In K. Miesenberger, A. Karshmer, P. Penaz, & W. Zagler (Eds.), Computers Helping People with Special Needs, 7383, 145–152. Springer Berlin Heidelberg. doi:10.1007/978-3-64231534-3_22 12. Lazar, A., Lazar, J., & Pradhan, A. (2019). Using modules to teach accessibility in a user-centered design course. Association for Computing Machinery, 554–556. doi:10.1145/3308561.3354632 13. Loitsch, C., Weber, G., & Voegler, J. (2016). Teaching accessibility with personas. In K. Miesenberger, C. Bühler, & P. Penaz (Eds.), Computers helping people with special needs, 453–460. Springer International Publishing. doi:10.1007/978-3-319-412641_62 14. Drexel University College of Computing & Informatics. (2021). Human-computer interaction and user experience. Drexel University. Retrieved from https://drexel.edu/cci/academics/graduate-programs/human-computer-interaction-ux/ 15. Minnery, B., & Fine, M. (2009). Neuroscience and the future of human-computer interaction. Association for Computing Machinery, 6. doi:10.1145/1487632.1487649

16. Wolpaw, J. R., Birbaumer, N., McFarland, D. J., Pfurtscheller, G., & Vaughan, T. M. (2002). Brain– computer interfaces for communication and control. Clinical Neurophysiology, 113(6), 767–791. doi:10.1016/S1388-2457(02)00057-3 17. Hochberg, L. R., Serruya, M. D., Friehs, G. M., Mukand, J. A., Saleh, M., Caplan, A. H., Branner, A., Chen, D., Penn, R. D., & Donoghue, J. P. (2006). Neuronal ensemble control of prosthetic devices by a human with tetraplegia. Nature, 442(7099), 164–171. doi:10.1038/nature04970 18. Körner, S., Siniawski, M., Kollewe, K., Rath, K. J., Krampfl, K., Zapf, A., Dengler, R., & Petri, S. (2013). Speech therapy and communication device: Impact on quality of life and mood in patients with amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 14(1), 20–25. doi:10.3109/17482968.2012.692382 19. Kewley-Port, D., & M. Nearey, T. (2020). Speech synthesizer produced voices for disabled, including Stephen Hawking. The Journal of the Acoustical Society of America, 148(1), R1–R2. doi:10.1121/10.0001490 20. US General Services Administration. (2021). User experience basics. Department of Health and Human Services. Retrieved from https://www.usability.gov/what-and-why/user-experience.html 21. Mandolfo, M., Pavlovic, M., Pillan, M., & Lamberti, L. (2020). Ambient UX research: User experience investigation through multimodal quadrangulation. In N. Streitz & S. Konomi (Eds.), Distributed, Ambient and Pervasive Interactions, 305–321. Springer International Publishing. doi:10.1007/978-3-03050344-4_22 22. Ren, L. Y., Adamczyk, A., & Wong, D. (2021). What is virtual reality? University of Toronto Oise. Retrieved from https://guides.library.utoronto.ca/c. php?g=607624&p=4938314 23. Center on the Developing Child. (2012). Executive function & self-regulation. Center on the Developing Child at Harvard University. Retrieved from https://developingchild.harvard.edu/science/ key-concepts/executive-function/ 24. Teófilo, M. R. S., Lourenço, A. A. B., Postal, J., Silva, Y. M. L. R., & Lucena, V. F. (2019). The raising role of virtual reality in accessibility systems. Procedia Computer Science, 160, 671–677. doi:10.1016/j. procs.2019.11.029 25. Garzotto, F., Torelli, E., Vona, F., & Aruanno, B. (2018). HoloLearn: Learning through mixed reality for people with cognitive disability. Institute of Electrical and Electronics Engineers, 189–190. doi:10.1109/AIVR.2018.00042 26. Zanier, E. R., Zoerle, T., Di Lernia, D., & Riva, G. (2018).

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 3

References Virtual reality for traumatic brain injury. Frontiers in Neurology, 9, 345. doi:10.3389/fneur.2018.00345 27. Laver, K. E., Lange, B., George, S., Deutsch, J. E., Saposnik, G., & Crotty, M. (2017). Virtual reality for stroke rehabilitation. Cochrane Database of Systematic Reviews, 11. doi:10.1002/14651858. CD008349.pub4 28. Dvorkin, A. Y., Ramaiya, M., Larson, E. B., Zollman, F. S., Hsu, N., Pacini, S., Shah, A., & Patton, J. L. (2013). A “virtually minimal” visuo-haptic training of attention in severe traumatic brain injury. Journal of NeuroEngineering and Rehabilitation, 10(1), 92. doi:10.1186/1743-0003-10-92 29. Perrin, R., & Atske, S. (2021). Americans with disabilities less likely than those without to own some digital devices. Pew Research Center. Retrieved from https://www.pewresearch.org/ fact-tank/2021/09/10/americans-with-disabilities-less-likely-than-those-without-to-ownsome-digital-devices/ 30. WebAIM. (2021). The WebAIM million. Institute for Disability Research, Policy, and Practice. Retrieved from https://webaim.org/projects/million/ 31. Web Accessibility Initiative. (2021b). Web content accessibility guidelines (WCAG) overview. Web Accessibility Initiative. Retrieved from https://www. w3.org/WAI/standards-guidelines/wcag/ 32. Web Accessibility Initiative. (2021c). Tools and techniques. Web Accessibility Initiative. Retrieved from https://www.w3.org/WAI/people-use-web/ tools-techniques

GROWING BRAINS IN A DISH: ORGANOIDS PRESENT GREAT PROMISE IN MODELING NEURAL TISSUE 1. de Souza, N. (2018). Organoids. Nature Methods, 15(1), 23–23. doi:10.1038/nmeth.4576 2. Eisenstein, M. (2018). Organoids: The body builders. Nat Methods 15, 19–22. doi:10.1038/nmeth.4538 3. Corrò, C., Novellasdemunt, L., & Li, V. (2020). A brief history of organoids. American Journal of Physiology. Cell physiology, 319(1), C151–C165. doi:10.1152/ ajpcell.00120.2020 4. Russell, J. J., Theriot, J. A., Sood, P., Marshall, W. F., Landweber, L. F., Fritz-Laylin, L., Polka, J. K., Oliferenko, S., Gerbich, T., Gladfelter, A., Umen, J., Bezanilla, M., Lancaster, M. A., He, S., Gibson, M. C., Goldstein, B., Tanaka, E. M., Hu, C. K., & Brunet, A. (2017). Non-model model organisms. BMC biology, 15(1), 55. doi:10.1186/s12915-017-0391-5 5. Lin, V., Hu, J., Zolekar, A., Yan, L. J., & Wang, Y. C. (2020). Urine sample-derived cerebral organoids suitable for studying neurodevelopment

and pharmacological responses. Frontiers in Cell and Developmental Biology, 8, 304. doi:10.3389/ fcell.2020.00304 6. Velasco, S., Kedaigle, A. J., Simmons, S. K., Nash, A., Rocha, M., Quadrato, G., Paulsen, B., Nguyen, L., Adiconis, X., Regev, A., Levin, J. Z., & Arlotta, P. (2019). Individual brain organoids reproducibly form cell diversity of the human cerebral cortex. Nature, 570(7762), 523–527. doi:10.1038/s41586019-1289-x 7. Lancaster, M. A., Renner, M., Martin, C. A., Wenzel, D., Bicknell, L. S., Hurles, M. E., Homfray, T., Penninger, J. M., Jackson, A. P., & Knoblich, J. A. (2013). Cerebral organoids model human brain development and microcephaly. Nature, 501(7467), 373–379. doi:10.1038/nature12517 8. Benito-Kwiecinski, S., & Lancaster, M. A. (2020). Brain organoids: Human neurodevelopment in a dish. Cold Spring Harbor perspectives in biology, 12(8), a035709. doi:10.1101/cshperspect.a035709 9. Bryda E. C. (2013). The mighty mouse: The impact of rodents on advances in biomedical research. Missouri Medicine, 110(3), 207–211. 10. Dantzer R. (2018). Neuroimmune Interactions: From the brain to the immune system and vice versa. Physiological Reviews, 98(1), 477–504. doi:10.1152/ physrev.00039.2016 11. Taams L. S. (2019). Neuroimmune interactions: How the nervous and immune systems influence each other. Clinical and Experimental Immunology, 197(3), 276–277. doi:10.1111/cei.13355 12. Gabriel, E., Ramani, A., Altinisik, N., & Gopalakrishnan, J. (2020). Human brain organoids to decode mechanisms of microcephaly. Frontiers in Cellular Neuroscience, 14, 115. doi:10.3389/fncel.2020.00115 13. Pifferi, F., Epelbaum, J., & Aujard, F. (2019). Strengths and weaknesses of the gray mouse lemur (Microcebus murinus) as a model for the behavioral and psychological symptoms and neuropsychiatric symptoms of dementia. Frontiers in Pharmacology, 10, 1291. doi:10.3389/fphar.2019.01291 14. Drummond, E., Wisniewski, T. (2017). Alzheimer’s disease: Experimental models and reality. Acta Neuropathol 133, 155–175. doi:10.1007/s00401-0161662-x 15. Paşca, S. P. (2019). Assembling human brain organoids. Science, 363(6423), 126–127. doi:10.1126/ science.aau5729 16. Nawathe, A., Doherty, J., & Pandya, P. (2018). Fetal microcephaly. BMJ (Clinical research ed.), 361, k2232. doi:10.1136/bmj.k2232 17. Trujillo, C. A., & Muotri, A. R. (2018). Brain organoids and the study of neurodevelopment. Trends in Molecular Medicine, 24(12), 982–990. doi:10.1016/j.

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 3

References molmed.2018.09.005 18. Lancaster, M. A., Renner, M., Martin, C. A., Wenzel, D., Bicknell, L. S., Hurles, M. E., Homfray, T., Penninger, J. M., Jackson, A. P., & Knoblich, J. A. (2013). Cerebral organoids model human brain development and microcephaly. Nature, 501(7467), 373–379. doi:10.1038/nature12517 19. Wang, L., Li, Z., Sievert, D., Smith, D., Mendes, M. I., Chen, D. Y., Stanley, V., Ghosh, S., Wang, Y., Kara, M., Aslanger, A. D., Rosti, R. O., Houlden, H., Salomons, G. S., & Gleeson, J. G. (2020). Loss of NARS1 impairs progenitor proliferation in cortical brain organoids and leads to microcephaly. Nature Communications, 11(1), 4038. doi:10.1038/s41467-020-17454-4 20. Quadrato, G., Brown, J., & Arlotta, P. (2016). The promises and challenges of human brain organoids as models of neuropsychiatric disease. Nature Medicine, 22(11), 1220–1228. doi:10.1038/nm.4214 21. Kathuria, A., Lopez-Lengowski, K., Jagtap, S. S., McPhie, D., Perlis, R. H., Cohen, B. M., & Karmacharya, R. (2020). Transcriptomic landscape and functional characterization of induced pluripotent stem cell-derived cerebral organoids in schizophrenia. JAMA Psychiatry, 77(7), 745–754. doi:10.1001/jamapsychiatry.2020.0196 22. Zhao, J., Fu, Y., Yamazaki, Y., Ren, Y., Davis, M. D., Liu, C. C., Lu, W., Wang, X., Chen, K., Cherukuri, Y., Jia, L., Martens, Y. A., Job, L., Shue, F., Nguyen, T. T., Younkin, S. G., Graff-Radford, N. R., Wszolek, Z. K., Brafman, D. A., Asmann, Y. W., … Bu, G. (2020). APOE4 exacerbates synapse loss and neurodegeneration in Alzheimer’s disease patient iPSC-derived cerebral organoids. Nature Communications, 11(1), 5540. doi:10.1038/s41467-020-19264-0 23. Götz, J., Bodea, LG. & Goedert, M. (2018). Rodent models for Alzheimer disease. Nat Rev Neurosci 19, 583–598). doi:10.1038/s41583-018-0054-8 24. Do Carmo, S., Cuello, A.C. (2013). Modeling Alzheimer’s disease in transgenic rats. Mol Neurodegeneration 8, 37. doi:10.1186/1750-1326-8-37 25. Dang, J., Tiwari, S. K., Lichinchi, G., Qin, Y., Patil, V. S., Eroshkin, A. M., & Rana, T. M. (2016). Zika virus depletes neural progenitors in human cerebral organoids through activation of the innate immune receptor TLR3. Cell Stem Cell, 19(2), 258–265. doi:10.1016/j.stem.2016.04.014 26. Mesci, P., Macia, A., LaRock, C., N., Tejwani, L., Fernandes I., R., Suarez, N., A., Zanotto, P., M., de A., Beltrão-Braga P., C., B., Nizet, V., Muotri A., R. (2018) Modeling neuro-immune interactions during zika virus infection. Human Molecular Genetics, 27(1), 41-52. doi:10.1093/hmg/ddx382 27. Ramani, A., Müller, L., Ostermann, P. N., Gabriel, E., Abida-Islam, P., Müller-Schiffmann, A., Mariappan,

A., Goureau, O., Gruell, H., Walker, A., Andrée, M., Hauka, S., Houwaart, T., Dilthey, A., Wohlgemuth, K., Omran, H., Klein, F., Wieczorek, D., Adams, O., … Gopalakrishnan, J. (2020). Sars-cov-2 targets neurons of 3d human brain organoids. The EMBO Journal, 39(20). doi:10.15252/embj.2020106230 28. Paşca, S. P. (2019). Assembling human brain organoids. Science, 363(6423), 126–127. doi:10.1126/ science.aau5729 29. Marton, R. M., & Pașca, S. P. (2020). Organoid and assembloid technologies for investigating cellular crosstalk in human brain development and disease. Trends in Cell Biology, 30(2), 133–143. doi:10.1016/j.tcb.2019.11.004 30. Ao, Z., Cai, H., Wu, Z., Ott, J., Wang, H., Mackie, K., & Guo, F. (2021). Controllable fusion of human brain organoids using acoustofluidics. Lab on a chip, 21(4), 688–699. doi:10.1039/d0lc01141j 31. Takahashi T. (2019). Organoids for drug discovery and personalized medicine. Annual Review of Pharmacology and Toxicology, 59, 447–462. doi:10.1146/ annurev-pharmtox-010818-021108 32. Perkhofer, L., Frappart, P. O., Müller, M., & Kleger, A. (2018). Importance of organoids for personalized medicine. Personalized Medicine, 15(6), 461–465. doi:10.2217/pme-2018-0071 33. Nature. (2020). Henrietta Lacks: Science must right a historical wrong. Nature, 585(7823), 7. doi:10.1038/d41586-020-02494-z 34. Reardon, S. (2020). Can lab-grown brains become conscious? Nature, 586(7831), 658–661. doi:10.1038/d41586-020-02986-y 35. Trujillo, C. A., Gao, R., Negraes, P. D., Gu, J., Buchanan, J., Preissl, S., Wang, A., Wu, W., Haddad, G. G., Chaim, I. A., Domissy, A., Vandenberghe, M., Devor, A., Yeo, G. W., Voytek, B., & Muotri, A. R. (2019). Complex oscillatory waves emerging from cortical organoids model early human brain network development. Cell Stem Cell, 25(4), 558–569. e7. doi:10.1016/j.stem.2019.08.002

IMPERFECT PREDICTIONS & DIFFICULT DECISIONS 1. Benjamin, E. J., Muntner, P., Alonso, A., Bittencourt, M. S., Callaway, C. W., Carson, A. P., Chamberlain, A. M., Chang, A. R., Cheng, S., Das, S. R., Delling, F. N., Djousse, L., Elkind, M. S. V., Ferguson, J. F., Fornage, M., Jordan, L. C., Khan, S. S., Kissela, B. M., Knutson, K. L., … Virani, S. S. (2019). Heart disease and stroke statistics—2019 update: A report from the American Heart Association. Circulation, 139(10). doi:CIR.0000000000000659 2. Halperin, H. R., Lee, K., Zviman, M., Illindala, U.,

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 3

References Lardo, A., Kolandaivelu, A., & Paradis, N. A. (2010). Outcomes from low versus high-flow cardiopulmonary resuscitation in a swine model of cardiac arrest. The American Journal of Emergency Medicine, 28(2), 195–202. doi:10.1016/j.ajem.2009.10.006 3. Silva, S., Alacoque, X., Fourcade, O., Samii, K., Marque, P., Woods, R., Mazziotta, J., Chollet, F., & Loubinoux, I. (2010). Wakefulness and loss of awareness: Brain and brainstem interaction in the vegetative state. Neurology, 74(4), 313–320. doi:10.1212/WNL.0b013e3181cbcd96 4. Paul, M., Bougouin, W., Dumas, F., Geri, G., Champigneulle, B., Guillemet, L., ben Hadj Salem, O., Legriel, S., Chiche, J.-D., Charpentier, J., Mira, J.P., Sandroni, C., & Cariou, A. (2018). Comparison of two sedation regimens during targeted temperature management after cardiac arrest. Resuscitation, 128, 204–210. doi:10.1016/j.resuscitation.2018.03.025 5. Paul, M., Bougouin, W., Geri, G., Dumas, F., Champigneulle, B., Legriel, S., Charpentier, J., Mira, J.-P., Sandroni, C., & Cariou, A. (2016). Delayed awakening after cardiac arrest: Prevalence and risk factors in the Parisian registry. Intensive Care Medicine, 42(7), 1128–1136. doi:10.1007/s00134-016-4349-9 6. Mulder, M., Gibbs, H. G., Smith, S. W., Dhaliwal, R., Scott, N. L., Sprenkle, M. D., & Geocadin, R. G. (2014). Awakening and withdrawal of life-sustaining treatment in cardiac arrest survivors treated with therapeutic hypothermia*. Critical Care Medicine, 42(12), 2493–2499. doi:10.1097/ CCM.0000000000000540 7. Dragancea, I., Rundgren, M., Englund, E., Friberg, H., & Cronberg, T. (2013). The influence of induced hypothermia and delayed prognostication on the mode of death after cardiac arrest. Resuscitation, 84(3), 337–342. doi:10.1016/j.resuscitation.2012.09.015 8. Lybeck, A., Friberg, H., Aneman, A., Hassager, C., Horn, J., Kjærgaard, J., Kuiper, M., Nielsen, N., Ullén, S., Wise, M. P., Westhall, E., & Cronberg, T. (2017). Prognostic significance of clinical seizures after cardiac arrest and target temperature management. Resuscitation, 114, 146–151. doi:10.1016/j. resuscitation.2017.01.017 9. Golan, E., Barrett, K., Alali, A. S., Duggal, A., Jichici, D., Pinto, R., Morrison, L., & Scales, D. C. (2014). Predicting neurologic outcome after targeted temperature management for cardiac arrest. Critical Care Medicine, 42(8), 1919–1930. doi:10.1097/ CCM.0000000000000335 10. Hirsch, K. G., Fischbein, N., Mlynash, M., Kemp, S., Bammer, R., Eyngorn, I., Tong, J., Moseley, M., Venkatasubramanian, C., Caulfield, A. F., & Albers, G.

(2020). Prognostic value of diffusion-weighted MRI for post-cardiac arrest coma. Neurology, 94(16), e1684–e1692. doi:10.1212/WNL.0000000000009289

HOW PUBLIC HEALTH IS REALLY NEUROSCIENCE 1. Canada, A., Mortensen, P., & Patnaik, D. (2016, August 9). Design Strategies for Technology Adoption. Jump. Retrieved December 20, 2021, from https://www.jumpassociates.com/learning-posts/ design-strategies-technology-adoption/ 2. Eller, N. M., Henrikson, N. B., & Opel, D. J. (2019). Vaccine information sources and parental trust in their child’s health care provider. Health Education & Behavior, 46(3), 445–453. doi:10.1177/1090198118819716

A WORLD OF PURE IMAGINATION: THE NEUROSCIENCE OF LUCID DREAMING 1. Baird, B., Mota-Rolim, S. A., & Dresler, M. (2019). The cognitive neuroscience of lucid dreaming. Neuroscience & Biobehavioral Reviews, 100, 305– 323. doi:10.1016/j.neubiorev.2019.03.008 2. Patel, A. K., Reddy, V., & Araujo, J. F. (2021). Physiology, sleep stages. In StatPearls. StatPearls Publishing. PMID: 30252388 3. Peever, J., & Fuller, P. M. (2016). Neuroscience: A distributed neural network controls REM sleep. Current biology, 26(1), R34–R35. doi:10.1016/j. cub.2015.11.011 4. Scheiber, I., Weiß, B. M., Kingma, S. A., & Komdeur, J. (2017). The importance of the altricial - precocial spectrum for social complexity in mammals and birds - a review. Frontiers in zoology, 14, 3. doi:10.1186/s12983-016-0185-6 5. Jaseja, H. (2004). Purpose of REM sleep: Endogenous anti-epileptogenesis in man – a hypothesis. Medical Hypotheses, 62(4), 546–548. doi:10.1016/j. mehy.2003.12.010 6. Khalighi, S., Sousa, T., Pires, G., Nunes, U. (2013). Automatic sleep staging: A computer assisted approach for optimal combination of features and polysomnographic channels. Expert Systems with Applications, 40(17), 7046-7059. doi:10.1016/j. eswa.2013.06.023 7. Casson, A.J., Abdulaal, M., Dulabh, M., Kohli, S., Krachunov, S., & Trimble, E. (2017). Electroencephalogram. In Tamura T., Chen W. (Eds.) Seamless Healthcare Monitoring (pp. 45-81). Springer. doi:10.1007/978-3-319-69362-0 2 8. Voss, U., Holzmann, R., Tuin, I., & Hobson, J. A. (2009). Lucid dreaming: A state of conscious-

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 3

References ness with features of both waking and non-lucid dreaming. Sleep, 32(9), 1191–1200. doi:10.1093/ sleep/32.9.1191 9. Hipp, J. F., & Siegel, M. (2013). Dissociating neuronal gamma-band activity from cranial and ocular muscle activity in EEG. Frontiers in Human Neuroscience, 7, 338. doi:10.3389/fnhum.2013.00338 10. Heeger, D. J., & Ress, D. (2002). What does fMRI tell us about neuronal activity?. Neuroscience, 3(2), 142–151. doi:10.1038/nrn730 11. Dresler, M., Wehrle, R., Spoormaker, V. I., Koch, S. P., Holsboer, F., Steiger, A., Obrig, H., Sämann, P. G., & Czisch, M. (2012). Neural correlates of dream lucidity obtained from contrasting lucid versus non-lucid REM sleep: A combined EEG/fMRI case study. Sleep, 35(7), 1017–1020. doi:10.5665/ sleep.1974 12. Siclari, F., Baird, B., Perogamvros, L., Bernardi, G., LaRocque, J. J., Riedner, B., Boly, M., Postle, B. R., & Tononi, G. (2017). The neural correlates of dreaming. Nature Neuroscience, 20(6), 872–878. doi:10.1038/nn.4545 13. Stumbrys, T., & Erlacher, D. (2012). Lucid dreaming during NREM sleep: Two case reports. International Journal of Dream Research, 5(2), 151–155. doi:10.11588/jodr.2012.2.9483 14. Mota-Rolim S. A., Brandão D. S., Andrade K. C., de Queiroz C. M. T., Araujo J. F., de Araujo D. B., et al. (2015). Neurophysiological features of lucid dreaming during N1 and N2 sleep stages: Two case reports. Sleep Science, 8(4), 215. doi:10.11588/ijodr.2012.2.9483 15. Mota-Rolim, S.A., Erlacher, D., Tort, A.B., Araujo, J.F., & S. Ribeiro. (2010). Different kinds of subjective experience during lucid dreaming may have different neural substrates. International Journal of Dream Research, 3, 33-35. doi: 10.11588/ijodr.2010.1.596 16. LaBerge, S., LaMarca, K., & Baird, B. (2018). Presleep treatment with galantamine stimulates lucid dreaming: A double-blind, placebo-controlled, crossover study. PloS one, 13(8), e0201246. doi:10.1371/journal.pone.0201246 17. Filevich, E., Dresler, M., Brick, T. R., & Kühn, S. (2015). Metacognitive mechanisms underlying lucid dreaming. The Journal of Neuroscience, 35(3), 1082–1088. doi:10.1523/JNEUROSCI.3342-14.2015 18. Mercadante, A. A., & Tadi, P. (2021). Neuroanatomy, Gray Matter. In StatPearls. StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/ books/NBK553239/. PMID: 31990494 19. Aspy, D. J. (2020). Findings from the international lucid dream induction study. Frontiers in psychology, 11, 1746. doi:10.3389/fpsyg.2020.01746

20. Sparrow, G., Hurd, R., Carlson, R., & Molina, A. (2018). Exploring the effects of galantamine paired with meditation and dream reliving on recalled dreams: Toward an integrated protocol for lucid dream induction and nightmare resolution. Consciousness and Cognition, 63, 74–88. doi:10.1016/j. concog.2018.05.012 21. Racchi, M., Mazzucchelli, M., Porrello, E., Lanni, C., & Govoni, S. (2004). Acetylcholinesterase inhibitors: Novel activities of old molecules. Pharmacological Research, 50(4), 441–451. doi:10.1016/j. phrs.2003.12.027 22. Watson, C. J., Baghdoyan, H. A., & Lydic, R. (2010). Neuropharmacology of sleep and wakefulness. Sleep Medicine Clinics, 5(4), 513–528. doi:10.1016/j. jsmc.2010.08.003 23. Sam , C., & Bordoni, B. (2021). Physiology, acetylcholine. In StatPearls. StatPearls Publishing. PMID: 32491757 24. Kern, S., Appel, K., Schredl, M., & Pipa, G. (2017). No effect of α‑GPC on lucid dream induction or dream content. Somnologie, 21, 180-186. doi:10.1007/ s11818-017-0122-8 25. Voss, U., Holzmann, R., Hobson, A., Paulus, W., Koppehele-Gossel, J., Klimke, A., & Nitsche, M. A. (2014). Induction of self awareness in dreams through frontal low current stimulation of gamma activity. Nature Neuroscience, 17(6), 810–812. doi:10.1038/nn.3719 26. Berkovich-Ohana, A., Glicksohn, J., & Goldstein, A. (2012). Mindfulness-induced changes in gamma band activity - implications for the default mode network, self-reference and attention. Clinical Neurophysiology, 123(4), 700–710. doi:10.1016/j. clinph.2011.07.048 27. Nitsche, M. A., Cohen, L. G., Wassermann, E. M., Priori, A., Lang, N., Antal, A., Paulus, W., Hummel, F., Boggio, P. S., Fregni, F., & Pascual-Leone, A. (2008). Transcranial direct current stimulation: State of the art 2008. Brain stimulation, 1(3), 206– 223. doi:10.1016/j.brs.2008.06.004 28. Stumbrys, T., Erlacher, D., & Schredl, M. (2013). Testing the involvement of the prefrontal cortex in lucid dreaming: A tDCS study. Consciousness and Cognition, 22(4), 1214–1222. doi:10.1016/j.concog.2013.08.005 29. El-Solh, A. A. (2018). Management of nightmares in patients with posttraumatic stress disorder: Current perspectives. Nature and science of sleep, 10, 409–420. doi:10.2147/NSS.S166089 30. Holzinger, B., Klösch, G., & Saletu, B. (2015). Studies with lucid dreaming as add-on therapy to Gestalt therapy. Acta neurologica Scandinavica, 131(6), 355–363. doi:10.1111/ane.12362

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 3

References 31. Lancee, J., van den Bout, J., & Spoormaker, V. I. (2010). Expanding self-help imagery rehearsal therapy for nightmares with sleep hygiene and lucid dreaming: A waiting-list controlled trial. International Journal of Dream Research, 3(2), 111–120. doi:10.11588/ijodr.2010.2.6128 32. Spoormaker, V. I., Van Den Bout, J., & Meijer, E. J. (2003). Lucid dreaming treatment for nightmares: A series of cases. Dreaming, 13(3), 181-186. doi:10.1023/A:1025325529560 33. Spoormaker, V. I., & van den Bout, J. (2006). Lucid dreaming treatment for nightmares: A pilot study. Psychotherapy and psychosomatics, 75(6), 389– 394. doi:10.1159/000095446 34. de Macêdo, T. C., Ferreira, G. H., de Almondes, K. M., Kirov, R., & Mota-Rolim, S. A. (2019). My dream, my rules: Can lucid dreaming treat nightmares? Frontiers in Psychology, 10. doi:10.3389/ fpsyg.2019.02618 35. Mota-Rolim S. A. (2020). On moving the eyes to flag lucid dreaming. Frontiers in neuroscience, 14, 361. doi:10.3389/fnins.2020.00361

DO YOU SEE WHAT I SEE?: BODY DYSMORPHIC DISORDER AND SELF-PERCEPTION 1. Clerkin, E. M., & Teachman, B. A. (2008). Perceptual and cognitive biases in individuals with body dysmorphic disorder symptoms. Cognition & Emotion, 22(7), 1327–1339. doi:10.1080/02699930701766099 2. Angelakis, I., Gooding, P. A., & Panagioti, M. (2016). Suicidality in body dysmorphic disorder (BDD): A systematic review with meta-analysis. Clinical Psychology Review, 49, 55–66. doi:10.1016/j. cpr.2016.08.002 3. Bjornsson, A. S., Phillips, K. A., & Didie, E. R. (2010). Body dysmorphic disorder. Obsessive-Compulsive Spectrum Disorders, 12(2), 221–232. doi:10.31887/ dcns.2010.12.2/abjornsson 4. Krebs, G., Fernández de la Cruz, L., & Mataix-Cols, D. (2017). Recent advances in understanding and managing body dysmorphic disorder. Evidence Based Mental Health, 20(3), 71–75. doi: 10.1136/eb2017-102702 5. Hart, J. (2015). Higher-order visual processing. The Neurobiology of Cognition and Behavior, 107–122. doi:10.1093/med/9780190219031.003.0007 6. Li, W., Lai, T. M., Bohon, C., Loo, S. K., McCurdy, D., Strober, M., Bookheimer, S., & Feusner, J. (2015). Anorexia nervosa and body dysmorphic disorder are associated with abnormalities in processing visual information. Psychological Medicine, 45(10), 2111–2122. doi:10.1017/s0033291715000045

7. Nayar, K., Franchak, J., Adolph, K., & Kiorpes, L. (2015). From local to global processing: The development of illusory contour perception. Journal of Experimental Child Psychology, 131, 38–55. doi:10.1016/j.jecp.2014.11.001 8. Kerwin, L., Hovav, S., Hellemann, G., & Feusner, J. D. (2014). Impairment in local and global processing and set-shifting in body dysmorphic disorder. Journal of Psychiatric Research, 57, 41–50. doi:10.1016/j.jpsychires.2014.06.003 9. Kravitz, D. J., Saleem, K. S., Baker, C. I., & Mishkin, M. (2011). A new neural framework for visuospatial processing. Nature Reviews Neuroscience, 12(4), 217–230. doi:10.1038/nrn3008 10. Deckersbach, T., Savage, C. R., Phillips, K. A., Wilhelm, S., Buhlmann, U., Rauch, S. L., Baer, L., & Jenike, M. A. (2000). Characteristics of memory dysfunction in body dysmorphic disorder. Journal of the International Neuropsychological Society: JINS, 6(6), 673–681. doi:10.1017/s1355617700666055 11. Fang, A., & Hofmann, S. G. (2010). Relationship between social anxiety disorder and body dysmorphic disorder. Clinical Psychology Review, 30(8), 1040–1048. doi:10.1016/j.cpr.2010.08.001 12. Baxter, M. G., & Croxson, P. L. (2012). Facing the role of the amygdala in emotional information processing. Proceedings of the National Academy of Sciences, 109(52), 21180–21181. doi:10.1073/ pnas.1219167110 13. Feusner, J. D., Townsend, J., Bystritsky, A., McKinley, M., Moller, H., & Bookheimer, S. (2009). Regional brain volumes and symptom severity in body dysmorphic disorder. Psychiatry Research: Neuroimaging, 172(2), 161–167. doi:10.1016/j.pscychresns.2008.12.003 14. Etkin, A., & Wager, T. D. (2007). Functional neuroimaging of anxiety: A meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. The American Journal of Psychiatry, 164(10), 1476–1488. doi:10.1176/appi. ajp.2007.07030504 15. Stein, M. B., & Stein, D. J. (2008). Social anxiety disorder. The Lancet, 371(9618), 1115–1125. doi:10.1016/ s0140-6736(08)60488-2 16. Adolphs, R. (2008). Fear, faces, and the human amygdala. Current Opinion in Neurobiology, 18(2), 166–172. doi:10.1016/j.conb.2008.06.006 17. Buhlmann, U., McNally, R. J., Etcoff, N. L., Tuschen-Caffier, B., & Wilhelm, S. (2004). Emotion recognition deficits in body dysmorphic disorder. Journal of Psychiatric Research, 38(2), 201–206. doi: 10.1016/s0022-3956(03)00107-9 18. Riva, G. (2016). Neurobiology of anorexia nervosa: Serotonin dysfunctions link self-starvation with

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 3

References body image disturbances through an impaired body memory. Frontiers in Human Neuroscience, 10. doi:10.3389/fnhum.2016.00600 19. Marazziti, D., Dell’Osso, L., Presta, S., Pfanner, C., Rossi, A., Masala, I., Baroni, S., Giannaccini, G., Lucacchini, A., & Cassano, G. B. (1999). Platelet [3H] paroxetine binding in patients with OCD-related disorders. Psychiatry Research, 89(3), 223–228. doi:10.1016/s0165-1781(99)00102-x 20. Feusner, J. D., Neziroglu, F., Wilhelm, S., Mancusi, L., & Bohon, C. (2010). What causes BDD: research findings and a proposed model. Psychiatric Annals, 40(7), 349–355. doi:10.3928/00485713-2010070108 21. Phillips, K. A., Siniscalchi, J. M., & McElroy, S. L. (2004). Depression, anxiety, anger, and somatic symptoms in patients with body dysmorphic disorder. Psychiatric Quarterly, 75(4), 309–320. doi:10.1023/b:psaq.0000043507.03596.0d 22. Castle, D., Beilharz, F., Phillips, K. A., Brakoulias, V., Drummond, L. M., Hollander, E., Ioannidis, K., Pallanti, S., Chamberlain, S. R., Rossell, S. L., Veale, D., Wilhelm, S., Van Ameringen, M., Dell’Osso, B., Menchon, J. M., & Fineberg, N. A. (2021). Body dysmorphic disorder: A treatment synthesis and consensus on behalf of the International College of Obsessive-Compulsive Spectrum Disorders and the Obsessive Compulsive and Related Disorders Network of the European College of Neuropsychopharmacology. International Clinical Psychopharmacology, 36(2), 61–75. doi:10.1097/ YIC.0000000000000342 23. Ipser, J. C., Sander, C., & Stein, D. J. (2009). Pharmacotherapy and psychotherapy for body dysmorphic disorder. Cochrane Database of Systematic Reviews. doi:10.1002/14651858.cd005332.pub2 24. Alsaidan, M. S., Altayar, N. S., Alshmmari, S. H., Alshammari, M. M., Alqahtani, F. T., & Mohajer, K. A. (2020). The prevalence and determinants of body dysmorphic disorder among young social media users: A cross-sectional study. Dermatology Reports, 12(3). doi:10.4081/dr.2020.8774 25. Bermeitinger, C. (2015). Priming. Advances in Psychology, Mental Health, and Behavioral Studies, 16–60. doi:10.4018/978-1-4666-6599-6.ch002 26. Withnell, S., Sears, C. R., & von Ranson, K. M. (2019). How malleable are attentional biases in women with body dissatisfaction? Priming effects and their impact on attention to images of women’s bodies. Journal of Experimental Psychopathology, 10(2), 204380871983713. doi:10.1177/2043808719837137 27. Izydorczyk, B., & Sitnik-Warchulska, K. (2018b). Sociocultural appearance standards and risk factors for eating disorders in adolescents and wom-

en of various ages. Frontiers in Psychology, 9. doi:10.3389/fpsyg.2018.00429 28. Kalantar Motamedi, M. H., Ebrahimi, A., Shams, A., & Nejadsarvari, N. (2016). Health and social problems of rhinoplasty in Iran. World Journal of Plastic Surgery, 5(1), 75–76. PMID:27308246 29. Nguyen, M., Hsu, P., & Dinh, T. (2009). Asian blepharoplasty. Seminars in Plastic Surgery, 23(03), 185– 197. doi:10.1055/s-0029-1224798 30. Chow, K. (2014). The many stories behind double-eyelid surgery. NPR. Retrieved from https://www.npr. org/sections/codeswitch/2014/11/18/364670361/ the-many-stories-behind-the-double-eyelid-surgery 31. Clark, L., & Tiggemann, M. (2008). Sociocultural and individual psychological predictors of body image in young girls: A prospective study. Developmental Psychology, 44(4). doi:10.1037/0012-1649.44.4.1124 32. Phillips, K. A., Wilhelm, S., Koran, L. M., Didie, E. R., Fallon, B. A., Feusner, J., & Stein, D. J. (2010). Body dysmorphic disorder: Some key issues for DSM-V. Depression and Anxiety, 27(6). doi:10.1002/ da.20709 33. Vashi, N. A. (2016). Obsession with perfection: Body dysmorphia. Clinics in Dermatology, 34(6). doi:10.1016/j.clindermatol.2016.04.006

NEUROLAW: TAKING THE STAND ON MENTAL ILLNESS 1. Ewing, Charles P. (2008). Insanity: Murder, Madness, and the Law. Oxford University Press. 2. Math, S. B., Kumar, C. N., & Moirangthem, S. (2015). Insanity defense: Past, present, and future. Indian Journal of Psychological Medicine, 37(4), 381–387. doi:10.4103/0253-7176.168559 3. Brisch, R., Saniotis, A., Wolf, R., Bielau, H., Bernstein, H. G., Steiner, J., Bogerts, B., Braun, K., Jankowski, Z., Kumaratilake, J., Henneberg, M., & Gos, T. (2014). The role of dopamine in schizophrenia from a neurobiological and evolutionary perspective: Old fashioned, but still in vogue. Frontiers in Psychiatry, 5, 47. doi:10.3389/fpsyt.2014.00047 4. Arias-Carrión, O., Stamelou, M., Murillo-Rodríguez, E., Menéndez-González, M., & Pöppel, E. (2010). “Dopaminergic reward system: A short integrative review. International Archives of Medicine, 3, 24. 5. McCutcheon, R. A., Abi-Dargham, A., & Howes, O. D. (2019). Schizophrenia, dopamine and the striatum: From biology to symptoms. Trends in Neurosciences, 42(3), 205–220. doi:10.1016/j.tins.2018.12.004 6. Fazel, S., Hayes, A. J., Bartellas, K., Clerici, M., & Trestman, R. (2016). “Mental health of prisoners: Prevalence, adverse outcomes, and interventions”.

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 3

References The Lancet. Psychiatry, 3(9), 871–881. doi:10.1016/ S2215-0366(16)30142-0 7. Collier, Lorna. (2014). Incarceration Nation. American Psychological Association. Retrieved from https://www.apa.org/monitor/2014/10/incarceration 8. Dike, C.C., Baranoski, M., & Griffith, E.E. (2005). Pathological lying revisited. J Am Acad Psychiatry Law, 33(3):342-9. PMID: 16186198. 9. Verigin, B. L., Meijer, E. H., Bogaard, G., & Vrij, A. (2019). Lie prevalence, lie characteristics and strategies of self-reported good liars. PloS one, 14(12), e0225566. doi:10.1371/journal.pone.0225566 10. King, B.H., & Ford, C.V. (1988). Pseudologia fantastica. Acta Psychiatrica Scandinavica, 77: 1-6. doi:10.1111/j.1600-0447.1988.tb05068.x 11. Abe, N. (2009). The neurobiology of deception: Evidence from neuroimaging and loss-of-function studies. Current Opinion in Neurology, 22(6), 594– 600. doi:10.1097/WCO.0b013e328332c3cf 12. Pearlstein, T., Howard, M., Salisbury, A., & Zlotnick, C. (2009). Postpartum depression. American Journal of Obstetrics and Gynecology, 200(4), 357–364. doi:10.1016/j.ajog.2008.11.033 13. Scatliffe, N., Casavant, S., Vittner, D., & Cong, X. (2019). Oxytocin and early parent-infant interactions: A systematic review. International Journal of Nursing Sciences, 6(4), 445–453. doi:10.1016/j. ijnss.2019.09.009 14. Cardaillac, C., Rua, C., Simon, E. G., & El-Hage, W. (2016). L’ocytocine et la dépression du post-partum [Oxytocin and postpartum depression]. Journal de Gynecologie, Obstetrique et Biologie de la Reproduction, 45(8), 786–795. doi:10.1016/j. jgyn.2016.05.002 15. Takács, L., Kandrnal, V., Kaňková, Š., Bartoš, F., & Mudrák, J. (2020). The effects of pre- and post-partum depression on child behavior and psychological development from birth to pre-school age: A protocol for a systematic review and meta-analysis. Systematic Reviews, 9(1), 146. doi:10.1186/ s13643-019-1267-2 16. Field T. (2010). Postpartum depression effects on early interactions, parenting, and safety practices: A review. Infant Behavior & Development, 33(1), 1–6. doi:10.1016/j.infbeh.2009.10.005 17. McEwen, A. M., Burgess, D. T., Hanstock, C. C., Seres, P., Khalili, P., Newman, S. C., Baker, G. B., Mitchell, N. D., Khudabux-Der, J., Allen, P. S., & LeMelledo, J. M. (2012). Increased glutamate levels in the medial prefrontal cortex in patients with postpartum depression. Neuropsychopharmacology, 37(11), 2428–2435. doi:10.1038/npp.2012.101 18. Moreno, J. L., Sealfon, S. C., & González-Maeso, J.

(2009). Group II metabotropic glutamate receptors and schizophrenia. Cellular and Molecular Life Sciences, 66(23), 3777–3785. doi:10.1007/s00018009-0130-3 19. Hatters Friedman, S., & Sorrentino, R. (2012). Commentary: Postpartum psychosis, infanticide, and insanity—implications for forensic psychiatry. The Journal of the American Academy of Psychiatry and the Law, 40(3), 326–332. Retrieved from http://jaapl.org/content/40/3/326.abstract 20. Putnick, D.L., Sundaram, R., Bell, E.M., Ghassabian, A., Goldstein, R.B., Robinson, S.L., Vafai, Y., Gilman, S.E., & Yeung, E. (2020). Trajectories of maternal postpartum depressive symptoms. Pediatrics, 146(5):e20200857. doi:10.1542/peds.2020-0857. 21. Reingle Gonzalez, J. M., & Connell, N. M. (2014). Mental health of prisoners: Identifying barriers to mental health treatment and medication continuity. American Journal of Public Health, 104(12), 2328–2333. doi:10.2105/AJPH.2014.302043

BETRAYED BY MY BODY: THE SCIENCE BEHIND ALIEN HAND SYNDROME 1. Gross, R. A. (1992). A brief history of epilepsy and its therapy in the western hemisphere. Epilepsy Research, 12(2), 65–74. doi:10.1016/09201211(92)90028-R 2. Brainin, M., Seiser, A., & Matz, K. (2007). The mirror world of motor inhibition: The alien hand syndrome in chronic stroke. Journal of Neurology, Neurosurgery &amp; Psychiatry. doi:10.1136/ jnnp.2007.116046 3. Brion, S., & Jedynak, C. P. (1972). [Disorders of interhemispheric transfer (callosal disconnection). 3 cases of tumor of the corpus callosum. The strange hand sign]. Revue Neurologique, 126(4), 257–266. PMID: 4350533 4. Sarva, H., Deik, A., & Severt, W. L. (2014). Pathophysiology and treatment of alien hand syndrome. Tremor and Other Hyperkinetic Movements (New York, N.Y.), 4, 241. doi:10.7916/D8VX0F48 5. Ovbiagele, B., Nguyen-Huynh, M.N. Stroke epidemiology: Advancing our understanding of disease mechanism and therapy. Neurotherapeutics 8, 319 (2011). doi:10.1007/s13311-011-0053-1 6. Musuka, T. D., Wilton, S. B., Traboulsi, M., & Hill, M. D. (2015). Diagnosis and management of acute ischemic stroke: Speed is critical. Canadian Medical Association Journal, 187(12), 887. doi:10.1503/ cmaj.140355 7. Traini, E., Carotenuto, A., Fasanaro, A. M., & Amenta, F. (2020). Volume analysis of brain cognitive ar-

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 3

References eas in Alzheimer’s Disease: Interim 3-year results from the ASCOMALVA trial. Journal of Alzheimer’s Disease, 76(1), 317–329. doi:10.3233/JAD-190623 8. Chahine, L. M., Rebeiz, T., Rebeiz, J. J., Grossman, M., & Gross, R. G. (2014). Corticobasal syndrome. Neurology: Clinical Practice, 4(4), 304. doi:10.1212/ CPJ.0000000000000026 9. Geschwind, M. D. (2015). Prion diseases. CONTINUUM: Lifelong Learning in Neurology, 21(6), 1612. doi:10.1212/CON.0000000000000251 10. Manix, M., Kalakoti, P., Henry, M., Thakur, J., Menger, R., Guthikonda, B., & Nanda, A. (2015). Creutzfeldt-Jakob disease: Updated diagnostic criteria, treatment algorithm, and the utility of brain biopsy. Neurosurgical Focus FOC, 39(5), E2. doi:10.3171/2015.8.FOCUS15328 11. Wen, Q., & Chklovskii, D. B. (2005). Segregation of the brain into gray and white matter: A design minimizing conduction delays. PLOS Computational Biology, 1(7), e78. doi:10.1371/journal.pcbi.0010078 12. Siddiqui, S. V., Chatterjee, U., Kumar, D., Siddiqui, A., & Goyal, N. (2008). Neuropsychology of prefrontal cortex. Indian Journal of Psychiatry, 50(3), 202. doi:10.4103/0019-5545.43634 13. Ebbesen, C. L., & Brecht, M. (2017). Motor cortex— To act or not to act? Nature Reviews Neuroscience, 18(11), 694–705. doi:10.1038/nrn.2017.119 14. Kayser, A. S., Sun, F. T., & D’Esposito, M. (2009). A comparison of Granger causality and coherency in fMRI-based analysis of the motor system. Human Brain Mapping, 30(11), 3475–3494. doi:10.1002/ hbm.20771 15. Assal, F., Schwartz, S., & Vuilleumier, P. (2007). Moving with or without will: Functional neural correlates of alien hand syndrome. Annals of Neurology, 62(3), 301–306. doi:10.1002/ana.21173 16. Hofmann, S. G., Asnaani, A., Vonk, I. J. J., Sawyer, A. T., & Fang, A. (2012). The efficacy of cognitive behavioral therapy: A review of meta-analyses. Cognitive Therapy and Research, 36(5), 427–440. doi:10.1007/s10608-012-9476-1 17. Haq, I. U., Malaty, I. A., Okun, M. S., Jacobson, C. E., Fernandez, H. H., & Rodriguez, R. R. (2010). Clonazepam and botulinum toxin for the treatment of alien limb phenomenon. The Neurologist, 16(2), 106–108. doi:10.1097/NRL.0b013e3181a0d670 18. Kikkert, M. A., Ribbers, G. M., & Koudstaal, P. J. (2006). Alien hand syndrome in stroke: A report of 2 cases and review of the literature. Archives of Physical Medicine and Rehabilitation, 87(5), 728– 732. doi:10.1016/j.apmr.2006.02.002 19. Blackmore, A. M., Boettcher-Hunt, E., Jordan, M., & Chan, M. D. Y. (2007). A systematic review of the effects of casting on equinus in children with ce-

rebral palsy: An evidence report of the AACPDM. Developmental Medicine & Child Neurology, 49(10), 781–790. doi:10.1111/j.1469-8749.2007.00781.x

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