Grey Matters Journal VC Issue 2 Spring 2021 by greymattersjournalvc

FEATURING RNA: A New Face in the Fight Against Neurodegeneration Just Another Face in the Crowd: The Evolution and Mechanisms of Primate Facial Processing Encounters With the Third Kind: The Twilight Zone of Aliens and False Memory Formation Beware the Post-Vaccine Blues

ISSUE 2

greymattersjournalvc.org

TABLE OF CONTENTS COVER ARTICLE

SEX DIFFERENCES AND DEPRESSION: THE MALECENTRIC RESEARCH MODEL’S HARMFUL EFFECTS ON FEMALES

by Hannah Daley / art by Natalie Bielat

FAKING IT ‘TILL YOU MAKE IT: WHY WE SHOULD ALL SMILE MORE by Natalie Pettirossi / art by Allie Verdesca and Mara Russell

REWIRING THE BRAIN: HOW THE NERVOUS SYSTEM HEALS ITSELF

A HOT ISSUE: TEMPERATURE-DEPENDENT TOXICITY IN HERBIVOROUS MAMMALS by Daniella Lorman and Clem Doucette / art by Alex Tansey, Mara Russell, and Hannah Weisman

by Lucas Angles / art by Yuchen Wang

DEFYING THE “WAR ON DRUGS”: THE REBIRTH OF PSYCHEDELIC MEDICINE & RESEARCH by Nick Beebe / art by Cherrie Chang

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Table of Contents

DEPRESSION AND ANXIETY: THE FRENEMIES NO COLLEGE STUDENT WANTS TO MEET by Kaiya Bhatia / art by Ayane Garrison

BRAIN BUSTERS by Ally Thayer / art by Sophie Sieckmann

FEATURED ARTICLES

ISSUE NOTES

JUST ANOTHER FACE IN THE CROWD: THE EVOLUTION AND MECHANISMS OF PRIMATE FACIAL PROCESSING by Clem Doucette and Daniella Lorman / art by Adlai Brandt-Ogman

ENCOUNTERS WITH THE THIRD KIND: THE MEMORY TWILIGHT ZONE

ON THE COVER Art by Natalie Bielat

by Zoe Curran / art by Naomi Tomlin

BEWARE THE POST-VACCINE BLUES

LET US KNOW If you have any questions or comments regarding this Issue 2, please write a letter to the editor at brainstorm.vassar@gmail.com.

by Brenna McMannon / art by Darling Garcia

RNA: A NEW FACE IN THE FIGHT AGAINST NEURODEGENERATION

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

by Benjamin Kheyfets, Daniella Lorman, and Clem Doucette / art by Phoebe Kinder

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

PRODUCTION STAFF

DANIELLA LORMAN Editor-in-Chief

Senior Managing Editor

LUCAS ANGLES

ELEANOR CARTER

HANNAH WEISMAN

TALIA MAYERSON

MARA RUSSELL

ZOE CURRAN

JULIÁN AGUILAR

Senior Editor, General Editing

Layout Executive and Outreach Coordinator

Senior Editor, General Editing

Graphic Designer

Senior Editor, Lay Review

CHRISTOPHER CHO Senior Editor, Scientific Review

KAYEN TANG

Art Executive

Production Manager

FILIPP KAZATSKER

BEN KHEYFETS

Social Media Manager

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Treasurer

Production Staff

ARTISTS

AUTHORS

Natalie Bielat Adlai Brandt-Ogman Cherrie Chang Ayane Garrison Darling Garcia Phoebe Kinder Mara Russell Sophie Sieckmann Alex Tansey Naomi Tomlin Allie Verdesca Yuchen Wang Hannah Weisman

Lucas Angles Nick Beebe Kaiya Bhatia Zoe Curran Hannah Daley Clem Doucette Benjamin Kheyfets Daniella Lorman Brenna McMannon Natalie Pettirossi Ally Thayer

SCIENTIFIC REVIEW

LAY REVIEW

GENERAL EDITING

Marina Alfano Tori Armitage Avery Bauman Samata Bhattarai Keara Ginell Haroun Haque Amber Huang Kathleen Nevius Natalie Pettirossi Ninamma Rai Griffin Scott-Rifer Dhriti Seth Claire Tracey Emma Trasatti Madison Wilson

Claire Tracey Benjamin Fikhman Nicole Stern Naima Nader Adalyn Schommer Caitlin Wong Clement Doucette Rebecca Zhao Anjali Krishna Lia Russo Lyla Menaker Yi Hua Sung Huda Rahman Elsa Wiesinger

Cherrie Chang Alex Tansey Claire Tracey Khadeejah Abdul-Basser Nanako Kurosu Grace Willoughby Tessa Charles Jason Jin Mina Turunc Naomi Tomlin Olivia Gotsch Ty Langford Haylee Backs Caitlin Patterson Sam Dorf Nick Beebe Ninamma Rai Rebecca Zhao Katherine Nelson Catherine Hansa Lucy Leonard Elsa Wiesinger Lillian Lowenthal

Annie Xu

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Editor's Note

EDITOR’S NOTE A few short months ago, Grey Matters Journal VC was just a courageous idea discussed on a stoop in Brooklyn. Now, Grey Matters is a cooperative, nationwide effort at six college campuses and counting. To date, more than 150 Vassar College students have contributed thousands of hours writing, illustrating, editing, and composing two journal issues. The remarkable reach of Grey Matters’ mission can be attributed to the grounded confidence of its contributors. More specifically, the confidence to learn and un-learn, be present and curious, and commit to the shared goals of increasing public understanding, trust, and participation in science dialogue. Vassar College’s second issue of Grey Matters Journal provides countless possibilities for connection and conversation. If you’re enthusiastic about common misconceptions in neuroscience, check out “Brain Busters.” Begin reaping the psychological and physiological benefits of smiling detailed in “Faking It ‘Till You Make It.” For those passionate about the climate crisis, explore how rising ambient temperatures impact animal behavior in “A Hot Issue.” We hope to share neuroscience with you in the most relevant, accessible, and impactful way possible. Cheers,

Daniella Lorman Editor in Chief

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Rewiring the Brain

REWIRING THE BRAIN: HOW THE NERVOUS SYSTEM HEALS ITSELF by Lucas Angles / art by Yuchen Wang

ou wake up one morning and immediately feel that something is off. As you grab a shirt and a pair of pants off the floor, you realize you can somehow put your shirt on with your right hand and your pants on with your left. You decide to further test your newfound ability; after making a pot of coffee, you discover that you’re fully capable of pouring the coffee with one hand while simultaneously reading a book with the other. This skill may sound like a superpower to most of us, but for those with “splitbrain,” or callosal syndrome, these experiences are common. In neurotypical individuals, the brain is separated into the left and right hemispheres. The two halves communicate through the corpus callosum, which can be thought of as a drawbridge, allowing each

hemisphere of the brain to coordinate neural activity. This neural bridge consists of a network of connections spanning the midsection of the brain. Neural “checkpoints” carefully guard against unlawful travelers by monitoring for abnormal signals. However, in epileptic brains, these checkpoints are absent, allowing any neural signal to cross this bridge. Those with epilepsy experience seizures as a result of random signals traveling through the corpus callosum uninhibited. Logically, in one form of epilepsy treatment, surgeons sever the corpus callosum, effectively “raising the drawbridge” to stop any signals from getting across. This disconnection results in the “split-brain” phenomenon that gives the syndrome its name. As the two hemispheres can no longer communicate, the movement of a body part is not registered by the rest of the brain, causing half of the body to operate unconsciously. However, seizures may still persist after the corpus callosum has been severed. In this case, surgeons remove the regions where uncontrolled signaling originates. These procedures involve full or partial removal of the damaged brain region, the size of which can range from a fraction of a centimeter to an entire hemisphere [1].

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Rewiring the Brain

SURGERY: THE LAST RESORT FOR EPILEPSY TREATMENT However, the removal of an entire hemisphere of the human brain is a significant clinical decision and typically only reserved for epileptic patients who have already tried every other possible treatment. In fact, only about 3% of eligible Americans elect to undergo any sort of epileptic surgery each year due to its invasive nature. More than 2.2 million Americans are currently diagnosed with epilepsy, making it the fourth most common neurological disease in the United States [1]. “Epilepsy,” however, is often used as an umbrella term. Because there are hundreds of similar neurodegenerative conditions that may result in epileptic seizures, neurologists typically group them all together for ease of treatment. As these conditions all manifest in the same symptoms, they can generally be treated in the same manner. Doctors commonly prescribe a combination of strict diet and medication, which works to stop indiscriminate neural signaling, regardless of the underlying condition. [2]. Hospitals in the U.S. perform around 100 hemispherectomies per year, primarily to treat severe childhood brain damage [3]. The culprit in most surgical cases is Perinatal Arterial Ischemic Stroke (PAIS), a severe form of fetal stroke [4]. Much like how barges move cargo up and down a river, red blood cells act as couriers and deliver oxygen to other cells they pass by. A stroke is actually much like the recent blockage of the Suez Canal. Blood flow to the brain is obstructed, depriving neurons of oxygen and thereby killing them. Neurological damage from PAIS manifests as rapid convulsions of a specific body part. These seizures result from the haphazard firing of neurons controlling voluntary movement. Antiseizure medicine is often used as a primary form of treatment for PAIS damage. These drugs act as a bouncer, blocking signals before they begin in order to stop neurons from firing repeatedly [2]. However, if neurologists observe no noticeable improvement with medication, surgery may be performed as a last resort [4].

HOW TO DETACH A HEMISPHERE, IN PART OR IN WHOLE A hemispherectomy can take anywhere from five to twelve hours to complete, and it consists of three phases: incision, removal, and reattachment. [5]. After the brain is exposed, surgeons begin by severing the corpus callosum [6]. This procedure ensures that the damage stays localized to the extracted hemisphere

and cannot cause seizures after the operation. The impaired hemisphere is then disconnected from the brainstem and inner lining of the skull before being removed. The extracted skull fragment is then replaced, and the scalp is sutured shut [5, 6]. The first procedure of this kind, performed in the 1920s, was termed an “anatomical hemispherectomy” and has since been used to treat a variety of seizure disorders [3]. In an anatomical hemispherectomy, surgeons remove the patient’s entire hemisphere. The frontal, parietal, temporal, and occipital lobes are all separated from the healthy brain, leaving only essential deep-brain systems like the thalamus and basal ganglia behind. These structures can remain intact, as they may actually work to prevent seizures [7]. Since the outer structures control vision and movement, patients often experience partial peripheral vision loss and weakness in half of their body after surgery. Prolonged operation times and extensive blood loss are relatively common risks of the procedure because so much of the brain tissue is removed. A buildup of excess fluid in the space of the removed hemisphere, called hydrocephalus, also occurs in about 20% of patients. Because of these risks, surgeons today tend to remove an entire hemisphere only when the whole region is damaged [5]. Similarly, the inherent risks associated with anatomical hemispherectomies have led surgeons to seek a more targeted approach when treating neurological damage. Over the last two decades, functional hemispherectomies have risen in popularity as a safer, less invasive alternative to anatomical resection [8]. In this procedure, rather than removing one full hemisphere, only the regions responsible for communication between hemispheric connections to deep-brain structures are severed to prevent seizures. However, both halves of the brain still remain inside the skull. This technique drastically lowers the risk of complications compared to an anatomical hemispherectomy. Leaving both halves of the brain intact is like plugging a leak with a cork. This approach makes fluid buildup in the brain rare, and surgeons can perform the surgery with minimal blood loss. After all of its connections are severed, the targeted hemisphere cannot respond to messages from its complement and acts as a static placeholder. With a success rate comparable to that of an anatomic hemispherectomy at over 85% and 90% reduction in hydrocephalus, functional resections have become a much more standard procedure in the United States [8, 9].

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Rewiring the Brain The sheer scale of this eight-hour surgery can seem frightening. However, recent research has shown rapid neural restructuring in the brains of children who underwent hemispherectomies can compensate for this loss of tissue. Many young patients exhibit striking improvements in motor and cognitive functioning in the years following surgery [10]. This adaptive response demonstrates the brain’s versatility and allows scientists to study neural changes following a hemispherectomy to potentially rewire neural pathways and bypass areas of neural damage.

STRUCTURAL CHANGES IN THE BRAIN For much of the 20th century, the world regarded the brain as one of the most structurally static organs in the human body. During development, cognitive and intellectual advances were thought to be purely psychological, with no relation to the brain’s anatomical structure. Scientists did not observe neurons multiplying after birth, nor were patients observed regrowing lost portions of grey matter [11]. However, studies in the mid-1900s conducted on people who suffered strokes suggested that the brain could adapt its structure to accommodate substantial alterations. Researchers noticed that subjects with large regions of cell death repurposed their remaining neurons to make up for functional loss, coining the term “neuroplasticity” to describe the phenomenon [11]. While scientists 100 years ago were primarily concerned with the brain’s general structure, today we can begin to understand neuroplasticity mechanisms at a cellular level. A process called long-term potentiation (LTP) helps explain neuroplasticity at the neuronal level. When a neuron in the brain regularly fires due to a repeated thought or action, the cell is modified to enhance that connection, creating branched structures that attach to the receiving cell body. This growth, combined with the increased production of chemical signals, leads to a significant increase in signaling strength [12]. The neuron then fires more readily and requires a less powerful stimulus to activate, resulting in a domino effect that can stimulate thousands of connected neurons. Put simply, neurons that fire together wire together. Researchers have observed this transformation in children, adults, and the elderly. They have concluded that LTP is the mechanism behind processes such as learning and memory since it results in the rapid creation of novel connections that encode new thoughts and experiences. Although LTP occurs on a molecular level at any age, the drastic structural

reorganization of brain cells after a hemispherectomy is primarily seen in very young children. These impressive changes have been attributed to three significant neural shifts: developmental, adaptive, and reactive plasticity.

DEVELOPMENTAL PLASTICITY Developmental plasticity refers primarily to the flexibility of neuronal connections in an infant’s brain after birth. Synapses, or the cellular bridges between individual neurons, are primarily formed through LTP, which means connections are only developed and strengthened through continued use and experience. In the first two years of a newborn’s life, the rate of synapse formation skyrockets as they experience the world around them [13]. For example, when a baby learns a new sound or color, neurons responsible for hearing or vision begin making connections with other neurons that code for memories. This phenomenon is why certain childhood memories come to mind after listening to a song or taking in a smell! After the period of synaptic development, neurons undergo ‘synaptic pruning,’ a process similar to housekeeping, in which the connections to infrequently used neurons are destroyed to free up space for synapse formation later in life. This process explains why young children can pick up foreign languages much more readily than adults – the synaptic connections used for the language are used early and therefore safe from destruction [14, 15]. Researchers have observed brain volume to decrease over time, suggesting that this synaptic cleanup actually changes the brain’s physical structure [16].

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Rewiring the Brain though these alterations can continue well into adulthood [18]. The time dependency of adaptive plasticity is reflected in the top athletes and musicians today. Most have started honing their craft exceptionally early in their lives, quickly developing the neural connections they need with each practice.

REACTIVE PLASTICITY

ADAPTIVE PLASTICITY While developmental plasticity is principally concerned with the nervous system’s maturation over time, adaptive plasticity involves practice and repetition. This process is prevalent in athletes, musicians, and others who go through repeated motions or tasks. As you rehearse a given action, the required neurons develop their connections, leading to easier recall and repetition, allowing you to perform the activity faster and more accurately [17]. Researchers examining musicians’ brains have revealed a significant increase in grey matter in the regions associated with music production and speech, indicating actual structural changes in the brain in response to practice [17]. Similar to findings related to developmental plasticity, studies have shown that children and adolescents are most prone to developing structural modification,

The final type of neural change –– reactive plasticity –– is concerned with the deprivation of neural signals from a part of the brain. This process follows the loss of sensory input over long periods of time and is most commonly associated with people who are blind or deaf [19]. Pop culture often portrays blind and deaf individuals as having heightened senses. Characters like Matt Murdock in Marvel’s Daredevil are portrayed to gain superhuman levels of perception, allowing them to experience the world in a novel way. Although this phenomenon has been exaggerated for dramatic effect, researchers have observed alteration in brain structure and added sensory strength in blind and deaf people as a compensatory mechanism. A study of infants born deaf found that neurons typically utilized in hearing can instead participate in the visual pathway to enhance optical acuity [19]. As is the case with other types of plasticity, reactive plasticity is most active during early childhood and decreases in intensity with age. The same study found that adults who were born deaf had difficulty recognizing speech even after receiving a cochlear implant, a device that partially restores hearing. Neurons responsible for processes of hearing had already shifted to the visual system in early childhood and were now fixed in that position [10]. As all types of plasticity have a high dependence on age, many surgeons will only perform hemispherectomies on children younger than five years old to avoid debilitating loss of brain function. The change in brain structure following surgery is truly astounding.

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Rewiring the Brain

IMPLICATIONS OF NEUROPLASTICITY ON HEMISPHERECTOMY OUTCOME We can witness many of these changes occurring in real-time in the sensorimotor system, a neuronal pathway that encompasses both the sensory system (responsible for touch) and the motor system (responsible for muscle contraction). Many think that each hemisphere of the brain gives and receives signals from the same side of the body, such as your right hemisphere controlling your right hand. Instead, your nerve cords “twist” and change sides at the junction where the brain meets the spine. Fibers originating in the right hemisphere cross over, connecting to muscles on your left side and vice versa [19]. This crossover explains why numbness and weakness in the side of the body opposite of the removed brain tissue are common after a hemispherectomy. Patients

who have had their left hemisphere detached may have trouble raising their right arm or may walk with a limp in their right leg, as neurons that were once present to control such actions have been completely removed during surgery. But how do patients move their arms and legs at all after a hemispherectomy if these pathways are severed? The answer lies in the remarkable plasticity of the brain. Scientists have recently observed that hemispherectomy patients show activation of the brain after a brief sensory stimulus on their skin [20]. Activation of the motor cortex through magnetic stimulation also resulted in movement on the same side of the body [21]. This phenomenon is most likely due to the combined effort of developmental, adaptive, and reactive plasticity, which work in tandem to strengthen signals through nerve pathways that do not “cross over.” The very act of trying to move a finger

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Rewiring the Brain begins the process of LTP in these motor neurons, making the action progressively easier through the creation of more efficient synapses. By shifting the pathways typically used for movement and touch, half of the brain can take on the entire body’s sensorimotor processing. Sensorimotor systems have existed in our evolutionary history for millions of years. From the first fish to humans, the direct pathway that such signals take through the brain has remained extremely simple and unchanged. However, the neurons that govern speech utilize a much more complex network of connections to help manage the intricacies of language. As a result, it is exponentially more challenging to recover functionality in a language than simply moving your arm. Although each hemisphere of the brain may appear identical, one half is dominant over the other in conducting specific tasks. In fact, in 90% of people, the left hemisphere plays a primary role in speech and language comprehension [22]. Therefore, if the left hemisphere is the half that requires surgery, it may not be easy for the individual to retain language and speech. This fact is reflected in the lower language test scores of those who have had their speechdominant left hemisphere removed. Conversely, researchers have found minimal decreases in the language capacity in those who have had their nondominant hemisphere removed [23].

of human neuroplasticity. As you read this sentence, your brain’s neurons are constantly modifying themselves so that you can remember, interpret, and communicate information more effectively. Scientists hope to model these processes to aid with neural rehabilitation from strokes, traumatic brain injury, or neurodegeneration. This damage can result in debilitating loss of function in multiple aspects of cognition, preventing the individual from participating in many day-to-day activities. Much of the current research on treating such disorders focuses on regrowing missing neurons [25]. However, by researching how and when plastic responses occur, scientists may one day be able to induce malleability in the brain long past the so-called “critical period” of adolescence. With this reconstruction, adults with lost function in areas like the motor cortex or the language pathway could rewire their neuronal circuitry to bypass damaged areas. Much like a detour around a blocked road, plastic neurons would form new connections that avoid these injured regions, instead utilizing alternative pathways to transmit messages. By studying the response of those who have lost vital brain tissue, we can turn our attention from regrowth to reuse.

However, those who undergo surgery — even in their dominant hemisphere — show significant improvement in speech over time [23]. Because of reactive neuroplasticity, patients who are minimally vocal in the weeks following surgery can reroute their speech pathways to the opposite hemisphere. Areas that once served as secondary functional regions to their dominant counterparts are “switched on” and used similarly to the original pathway. As the brain is structurally symmetrical, similar areas on the non-dominant hemisphere send and receive the same signals as the original, essentially acting as a replacement. In the same way that you can wear the same sock on different feet as they are physically similar, your brain can utilize these rarely used regions to regain function. The remaining hemisphere can gain further support by recruiting surrounding neurons to help deal with this new processing burden. These nearby cells aid in the signaling involved with language interpretation, association, and production, allowing the patient to speak more easily [24]. Researchers often examine patients with hemispherectomies to analyze the universal patterns

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

SEX DIFFERENCES AND DEPRESSION: THE MALECENTRIC RESEARCH MODEL’S HARMFUL EFFECTS ON FEMALES Sex Differences and Depression

by Hannah Daley art by Natalie Bielat

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Sex Differences and Depression

id you know that the prevalence of depression diagnoses varies depending on sex? It might surprise you that females are twice as likely to be diagnosed with depression as males, even though treatments are largely standardized across all sexes [1]. Although depression isn’t always apparent on the surface level, chances are you know someone who has been diagnosed or affected by the disease. In fact, depression is the most common mood disorder in the US, with approximately 7.1% of adult Americans being diagnosed with a depressive episode in 2017 [1]. Despite depression’s prevalence, much remains unknown about the disease, especially in terms of its disproportionate impact on females. Uncovering the differences in depression between the sexes might be the key to developing more effective treatments, enhancing outcomes, and improving experiences for many.

SEX VS. GENDER Before discussing sex differences in depression and treatment, it is important to first distinguish between the terms “sex” and “gender.” Sex usually refers to one’s biological genotype and the accompanying physiological processes. Gender, on the other hand, refers to an individual’s identity and does not necessarily depend on their anatomy or genetics. In medicine, the term “sex” refers to a binary system of male or female. As such, from this point on, the terms “male” and “female” will be used to refer to the sex of an individual, not their gender.

WHAT IS DEPRESSION AND HOW IS IT DIAGNOSED? Depression, or major depressive disorder (MDD), arises from a combination of genetic, environmental, social, and neurological factors [2]. The Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V) outlines nine criteria for the diagnosis of MDD. In order to be diagnosed with depression, one must experience five or more of the following symptoms in the same two week span. At least one of the symptoms must be depressed mood, loss of interest, or loss of pleasure, while others include appetite and/or weight changes, sleep difficulties, reduction of physical movement, fatigue or loss of energy, diminished ability to think or concentrate, feelings of worthlessness, and thoughts of suicide [3]. Generally, people with depression experience feelings of prolonged sadness, which affects their ability to perform daily tasks and contributes to an overall feeling of hopelessness. Since there are a wide

variety of qualifiers for MDD, 227 total combinations of symptoms could result in a depression diagnosis [4]. Thus, individuals with depression can have very different symptoms and should not be classified as one and the same.

WHY DOES SEX MATTER IN DIAGNOSES? It is especially important to avoid grouping all individuals with depression together when diagnosing between sexes, as symptoms are often very different. However, clinicians largely prescribe the same medication and treatments across the sexes. Current treatments for depression are not always effective, and one potential explanation for this phenomenon may be that, up until recently, studies of antidepressants have been primarily based on male subjects. In other words, because women have infrequently been studied with regard to depression treatment, there is very little research describing the effect of sex differences on treatment efficacy, or the ability of treatment to improve symptoms. Biological differences between the sexes arise from differences in chromosomes and hormone production between males and females. Typically, males produce more of the sex hormone testosterone, while females produce more of the sex hormone estrogen, though both sex hormones are present at varying levels in all sexes. Additionally, females experience a menstrual cycle due to the fluctuation of these hormones, and its onset puts them at a higher risk for developing mood disorders [5]. One example of the impact of sex hormones on depression is demonstrated by the increased incidence of the disorder among girls who are beginning puberty and the typical decrease in depression serverity with the onset of menopause [4]. It is thought that the surge of estrogen and progesterone (another sex hormone) that occurs with the onset of menstruation is responsible for increased depression rates among girls going through puberty, and the decrease of these hormones during menopause decreases the severity of depression [6]. These findings suggest that research regarding the role of sex hormones in depression severity should be expanded. Uncovering the reasons behind these observations can lead to a better understanding of the disease and help develop more effective treatments.

SEX DIFFERENCES IN BIOLOGICAL SYSTEMS MAY LEAD TO DIFFERENTIAL DEPRESSION PRESENTATIONS Females are approximately twice as likely to be

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Sex Differences and Depression

diagnosed with depression, and two thirds of all suicides are attempted by females. Furthermore, females are more likely than males to report the depressive symptoms of chronic negative strain, low confidence in their skills, and rumination (i.e. the process of continuously thinking negative thoughts). Beyond this, females are more likely to have comorbid, or co-existing, mental health conditions along with their depression, such as anxiety-related disorders or eating disorders [4]. Moreover, the effects of depression manifest differently in males and females. Understanding the similarities and differences between males and females in the presentation and prevalence of depression can help inform diagnostic techniques and tailor treatments to increase efficacy. Not only do males and females differ in their presentation of depression, but they also differ in the ways that their bodies process medications. The monoaminergic system, a biological system thought to be implicated in the development of depression, is known to function differently between the sexes [6]. This is a system that is often targeted by drug therapy treatments for depression. Some studies have shown that TCA (tricyclic antidepressant imipramine), one of the main drugs used as a therapeutic treatment, is more effective in males than females, though this disparity tends to disappear after menopause. However, female subjects are often given the same medication dosages as males, despite this plethora of evidence suggesting that drugs are broken down at different speeds between the sexes [7]. The fact that drug efficacy changes with the hormonal shifts of menopause further suggests an interaction of sex hormones and depression systems such as the monoaminergic system. Multiple studies also suggest that women respond preferentially to SSRIs (selective serotonin reuptake inhibitors) compared to TCAs and other antidepressants. Serotonin, the neurotransmitter involved in the use of SSRIs, is known to significantly interact with estrogen, which can cause changes in serotonin release, receptor binding, and breakdown [6]. The differential responses that females have to these common pharmaceutical treatments imply that depression may operate differently in females than in males, potentially due to

interactions between estrogen and the monoaminergic system.

THE MALE-CENTRIC MODEL The lack of attention to sex differences in the treatment of not only depression, but also other diseases, highlights a much larger problem present in scientific research: the male-centric research model. According to one study, clinical trials for new drugs in the U.S. predominantly consisted of males up until 1988, despite females consuming 80% of all pharmaceuticals [7]. This male-centric model of research has been the standard for many years, as using females in both clinical and animal research is considered “expensive and risky.” This is likely due to research institutions’ fear of infertility as an adverse reaction that may result in lawsuits and subsequent economic turmoil. Additionally, hormonal fluctuations related to the menstrual cycle are often treated by researchers as an unavoidable confounding variable in research with female subjects. It is thought that this confounding variable will potentially prevent studies from finding any significant results, making them unable to get FDA approval to get the drug on the market. It is important to note that while female sex hormones are considered a confounding variable in drug studies, male hormones are not, even though hormonal fluctuations in males may offer similar confounding effects. Currently, less than half of the drugs approved by the FDA were tested on female subjects during clinical trials. Oftentimes, individuals assume that therapeutic responses will be the same between the sexes [7]. However, the male-centric model isn’t just ineffective for identifying inclusive treatment methods — it has also proven itself to be quite dangerous, often leaving females vulnerable to adverse drug reactions. For example, females are statistically more likely to use multiple medications simultaneously, putting them at risk for harmful drug interactions that were not otherwise investigated [8]. Additionally, the intervals between female heart beats are slightly longer due to relatively reduced levels of testosterone, which can be exacerbated by taking multiple medications at once. This phenomenon, called long QT syndrome, puts some females at higher risk for cardiac events and death. Since sex is often not accounted for when physicians write prescriptions, long QT syndrome can be overlooked. As a result, some females may experience cardiac events from routine treatments for UTIs or back pain.

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Sex Differences and Depression

The popular sleep aid, Ambien, provides another example of the massive oversight of sex in medicine efficacy. Researchers recently found that females metabolize Ambien slower than males, leaving some of the drug active in their system upon awakening. As a result, they experience extreme drowsiness the next day, putting them at increased risk for motor vehicle accidents and other dangers [8]. This oversight is just one of the many resulting from the malecentric research model, all of which could be avoided if researchers took sex into account when determining drug efficacy during clinical trials. It is clear that sex must be considered in medical practice if treatments are to be safe and effective for everyone. In order for this to happen, major systemic changes are required in the way research is conducted. Since the Office of Research on Women’s Health at the NIH was created in 1990, inequities in clinical drug research have begun to be addressed [7]. However, there are thousands of drugs on the market, so this task is no easy undertaking. Moving forward, females need to be routinely included in clinical drug trials so that additional remedial studies do not need to take place after a drug is already approved. It would also be useful to perform clinical trials on both preand post-menopausal females, as it is clear that

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Sex Differences and Depression

the menstrual cycle affects many body systems. In addition, medical school curriculums must be updated so that doctors are more aware of the potential of sex as a confounding factor in treatment. Surveys suggest that medical schools currently do not discuss sex in relation to treatments for most health problems, meaning that doctors are not aware of factors such as QT syndrome, or other sex related differences in their diagnoses [8]. As a whole, females have been largely ignored in clinical research and in the doctor’s office. Taking these few steps to acknowledge them is a step in right direction towards equity.

LOOKING AHEAD In general, our current treatment options for depression are ineffective; despite the prescription of antidepressants and other therapeutic techniques, many people continue to be affected by the disorder. However, females are affected at a disproportionate rate, as the male-centric research model has neglected to consider sex as a confounding factor for disease pathology and treatment. Research must continue to discover the specific interactions that sex-related differences have on the development of depression if more effective drug therapies are to be created. While there are many areas in modern society that require more progress towards gender equality, this pursuit is especially important in the context of scientific research, as it can have a real impact on individuals’ survival and quality of life. Sex bias in drug development should not be an additional risk factor for increased mortality for certain diseases; however, this is a problem that our society has created, and steps need to be taken to lessen this burden.

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Just Another Face In The Crowd

JUST ANOTHER FACE IN THE CROWD: THE EVOLUTION AND MECHANISMS OF PRIMATE FACIAL PROCESSING by Clem Doucette and Daniella Lorman / art by Adlai Brandt-Ogman

at least ten miles away from the nearest town; your only option is to flag down a passing motorist for help. Fortunately, a driver pulls over and offers to help you. Can you trust them?

ou are driving down a winding country road when you notice that your car’s “check engine” light turns on. Moments later, you feel the gears in the car’s engine begin to grind before failing completely. As you gently bring your vehicle to a stop along the side of the road, the gravity of your predicament begins to set in. There is no cell service and you are

You notice signs that may lead you to trust the driver. Perhaps there is a child in the back seat of the car. Or, the driver may be roughly the same age or gender as you. But, there are other factors that contribute to forming a perception of trustworthiness that you may not be aware of. These cues can be as conspicuous as the individual’s age and gender, or

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Just Another Face In The Crowd as subtle as the shape and contours of their face. What if we were to tell you that before you can even consciously think through this information, you have already subconsciously decided from the driver’s face alone whether they are trustworthy or not? In fact, it takes just 33 milliseconds for your brain to form a first impression [1]. While trust and first impressions seem to us like innately human experiences, evidence suggests that non-human primates interpret faces very similarly to how we do. In the past few decades, scientists have researched and debated the existence of brain regions specific to facial processing, and have investigated the mechanisms behind how human and non-human primates recognize and judge faces. This research posits that there is an evolutionary benefit to these mechanisms; they may help primates identify threats and effectively navigate complex social environments.

FIRST IMPRESSIONS COUNT: ARE SOME FACES INHERENTLY TRUSTWORTHY? Imagine that your town is in the midst of a local election. Campaign signs dot lawns throughout your neighborhood bearing the names and faces of various different candidates. You don’t know anything about the candidates themselves or their political affiliations. What you may not realize is that you have already formed an opinion of the candidates based on their facial features alone. This is an example of a phenomenon termed the “first impression effect,” or the rapid judgement of one’s character based solely on one’s facial characteristics and structure. In a 2008 study, undergraduate student volunteers were asked to assess a series of computer generated faces on qualities of trustworthiness, dominance, and threat [2]. Researchers found that the faces perceived as being most trustworthy were ones that featured more feminine and youthful structural characteristics. Conversely, faces with more masculine characteristics were perceived as being untrustworthy, dominant, and aggressive. Why? Researchers posited that expressions of dominance and anger subconsciously signal the capability and intent to cause harm, resulting in these faces being labeled as untrustworthy [2]. In many situations we can identify a person’s mood or intentions based on their facial expressions and characteristics alone. We can usually infer that someone who is smiling and laughing is in a good mood, while the person scowling and glaring angrily from the corner of the room, is not. But what happens to our facial perception skills when we are tasked with analyzing the expressions of non-human primates?

Can we distinguish a threatening ape from a friendly one? Unless you are familiar with non-human primate behavior, the answer is probably no. Imagine that you have finally stumbled upon the opportunity of a lifetime: the chance to visit a nature park and see apes in their natural habitat. As you hop into the driver’s seat of your rented camo Jeep, you can barely contain your excitement. Suddenly, a large macaque monkey bounds towards your car, baring its teeth and hooting. He is happy to see you! Or, at least that is what your first impression effect is telling you. On the contrary, if you see a macaque or another non-human primate “smile” at you, you should probably back off. For macaques, the bared-teeth facial expression is one closely associated with a few different emotional states [3]. A wide, open-mouthed grin is typically a threat; the monkey shows off its sharp teeth in an attempt to intimidate [3]. Other expressions that resemble a human smile or grin may signify fear and submission [4]. On the surface, many of these nonprimate facial expressions bear close resemblance to our own familiar expressions, such as smiles, frowns, and grimaces. Your first impression of the macaque you encounter is likely based on your anthropomorphic (or human-based) concept of what a friendly and welcoming face should look like. This may make you wonder: does a similar effect occur when a macaque glances at a human face? A 2018 study conducted on macaque monkeys hypothesized that the first impression effect is also exhibited by non-human primates [5]. Researchers theorized that faces deemed trustworthy by macaques would feature a low facial width to height ratio (fWHR). Faces with a low fWHR are long and narrow, while those with a high fWHR are short and round. They concluded that the macaques, just like humans, displayed a preference for faces with a low fWHR and a more feminine, youthful appearance [5]. Furthermore, faces with high fWHR are not merely perceived as being more masculine and aggressive, but may indicate hostile personality traits. A 2015 survey of male hockey players demonstrated that sportsmen with a high fWHR often had higher baseline levels of testosterone, and consequently behaved more violently on the ice [6]. Resultantly, macaques and other primates are more inclined to approach individuals with low fWHR faces; we implicitly associate these faces with fearful and weak tendencies, regardless of what feeling they outwardly display [7]. Over time, primates have adapted to their lives in

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Just Another Face In The Crowd close-knit social groups by developing this common facial perception mechanism [5]. Consider a round of the game “Among Us”; to succeed and ensure your group’s survival, you must quickly identify the dangerous impostor. When scanning the map for clues, you notice that Red is behaving erratically, failing to complete tasks, and is even following and covertly killing your teammates. Immediately, you know that this player is a dangerous outsider. Similarly, in the setting of a primate social group, effectively identifying which individuals are a threat benefits the survival of its members and the integrity of the group. At this point, you may be wondering how all of these mechanisms actually work. How does your brain even recognize what a face is? Let’s delve into the neuroscience behind facial recognition, and how our brain perceives faces.

suggesting that facial perception gets its own real estate within the brain. In other words, we think the FFA is face specific [8]. The FFA’s activity is often studied using fMRI machinery. As research subjects are exposed to images of faces or different facial stimuli, the fMRI machine captures images illustrating the activity levels of different regions within their brains [8]. fMRI machines use magnetic fields and radio waves to non-invasively image bodily tissues, such as the brain [8]. This technique works because brain activity requires blood flow. As blood flow increases, the ratio of oxygenated blood to deoxygenated blood in the part of the brain that is working extra hard also increases. The MRI machine then detects this image. In several studies, fMRI scans showed increased blood flow, or activity,

HOW DO OUR BRAINS PERCEIVE FACES? All faces are pretty similar. Of course, your dad looks different from Theo James, who looks different from your best friend. But most faces have two eyes, a nose and mouth. And, we know how facial features are usually arranged in relation to one another. It turns out that our brains are actually set up to prioritize processing information about faces. The fusiform face area (FFA) is responsible for helping us determine what kind of objects we are looking at [8]. This tiny brain region, located within the brain’s temporal lobe, may partially account for our ability to distinguish between the face of our celebrity crush or best friend. Though scientists are still debating if the FFA is actually specific to faces — or just really good at identifying complex objects that we see a lot — there is a plethora of evidence

in the FFA when looking at faces compared to other objects [9]. In fact, this result is observed across a wide range of faces, such as front views, side views, cartoons, and even dog faces [9]!

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Just Another Face In The Crowd Ninety-seven percent of neurons in the FFA have been recorded to selectively respond to faces [10]. In a 1997 study, participants were shown various images of random inanimate objects, hands, the “faces” of houses, and, of course, human faces [9]. Scans showed that the FFA responded much more to the pictures of faces than the other objects. This study established the FFA as the most important area of the brain for processing facial stimuli and prompted a slew of further research on the topic [9]. Almost ten years after this groundbreaking study, scientists questioned whether the FFA functions similarly in non-human primates [10]. Researchers tested how macaque monkeys responded to different images, and found that neurons in the FFA responded specifically to images that displayed facial stimuli [10]. Furthermore, a recent study found that face-specific areas of the brain will respond to faces even if you have never seen one before [11]. Researchers asked volunteers who were blind from birth, as well as several sighted people, to explore a series of 3D printed objects — such as a chair, a maze, a face, and a hand — by touch. When sighted people looked at the 3D-printed faces, an MRI scan showed activation in the FFA. More strikingly, however, as sighted participants explored objects by touch only, the FFA lit up again, but not as brightly. When blind volunteers explored facial objects, the FFA lit up again. Researchers ran the experience three times to make sure they were really seeing this effect [11]. These results were significant because they helped researchers discredit previous theories of facial recognition. One such theory was that face-specific regions developed in response to visual information that comes from the center of your visual field, or your fovea, as opposed to from the periphery of your visual field [12]. Since we normally shift our gaze to center other human faces, it was thought that this brain area might be triggered simply because we

happen to put faces in the middle of our visual field [12]. The aforementioned study contradicts this theory because no visual cues were necessary to make the FFA regions of blind participants light up [11]. Another earlier theory was that the FFA may just be sensitive to curved objects rather than rectangular ones, rather than being face-specific [13]. In one study, researchers asked blind participants to handle 3D shapes-- like cubes, spheres, and eggs-- and the FFA did not respond any more to curved objects than rectangular ones [11]. To test for additional variables, researchers played different sounds for blind participants. Some were related to behaviors involving facial features, like laughing and chewing, while others depicted natural scenes such as waves crashing. The FFA was found to respond specifically to face related sounds [11]. In a case study, researchers placed electrodes on the brain of a volunteer, Ron Blackwell [14]. As electrodes move over the brain, their contact acts like a microphone, listening in on brain activity. The researchers stimulated different brain neurons and watched in amazement as Ron lost the ability to recognize faces as neurons within the FFA were stimulated! He said that the “face metamorphosed” [14]. In summary, significant research suggests that the FFA plays a crucial role in our ability to recognize and perceive faces. But how can we explain times when our brains perceive faces in instances where there are none?

MONKEY SEE, MONKEY… DON’T: THE PHENOMENON OF PAREIDOLIA Have you ever wondered why the electrical outlets in your house look perpetually surprised? Or, why, right as you are about to fall asleep, the pile of laundry in the corner of your room seemingly morphs into a menacing face? These visual phenomena, known as pareidolia, have fascinated (and frightened) us for centuries. Pareidolia occurs when we incorrectly perceive an abstract set of visual stimuli as something that we are familiar with [15]. A classic example of this is the infamous Rorschach inkblot test. You’ve probably seen this depicted numerous times in vintage spy dramas and cop shows; the hardboiled detective shows the cold-hearted killer a series of abstract splotchy images, while the killer reports what they think the pictures look like. While pareidolic images can resemble animals, inanimate objects, and a myriad of other easily recognizable forms, facial pareidolias occur most frequently [15]. The theory of gestalt psychology suggests that organisms perceive whole patterns and configurations, and not just their individual components [16]. We are intrinsically

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Just Another Face In The Crowd aware that a face consists of several pieces, such as two eyes, a mouth, ears, and a nose. For example, when someone texts you a :-) icon, you likely see a simplistic representation of a smiling face and not just a random assemblage of punctuation marks. Why, then, do our minds seemingly trick us into seeing faces when they aren’t there? Actually, our ability to see silly faces in power outlets and emoticons likely serves an important evolutionary function. In a 2017 study conducted on rhesus monkeys, scientists showed subjects a series of both pareidolic and non-pareidolic images [17]. On average, the monkeys fixated on the pareidolic images for over twice as long as the non-pareidolic ones. Furthermore, after tracking and mapping the gaze patterns of the monkeys, researchers determined that subjects focused on the regions where the eyes and mouth are usually found [17]. So, how does this hypersensitive facial recognition mechanism help us survive? Imagine you are a wild primate, swinging through the trees of a dense jungle. In the dark shadows on the forest floor, you see what appears to be a glowing pair of eyes and a menacing mouth. As you leap to safety, a large leopard jumps out of the bushes and devours your (much less perceptive) peer. In short, primates that quickly spot face-like patterns in nature are more likely to survive and protect themselves from threats than those primates that could not. Our hypersensitive facial detection mechanisms may be heritable, passed down from our well-adapted primate ancestors [18].

HAVE I SEEN YOU BEFORE? The ability to perceive faces as a whole also enables us to recognize individual faces, like those of our friends, acquaintances, and particularly famous celebrities. However, this mechanism can sometimes malfunction. Prosopagnosia, commonly known as face blindness, is a cognitive disorder marked by an inability to recognize familiar faces [19]. This is vastly different from the occasional slip-ups many of us have when encountering an old acquaintance or a distant work colleague. Face blindness can manifest in different forms and severities; some people are capable of recognizing close family members, but experience great difficulty telling coworkers apart. In some severe cases, prosopagnosics can even struggle to recognize their own face [19]. Most cases of prosopagnosia result from damage to brain regions responsible for facial processing and the

amygdala in instances of trauma or stroke [20]. As the amygdala functions in emotional memory, these two structures work together to form a databank of faces a given person has seen during their life and the emotions they associate with each face. When the structures are injured, this databank is essentially wiped. Not only can a patient no longer remember the faces of people they have seen, the brain no longer files new faces away for later retrieval [21]. Prosopagnosia and pareidolia have provided important insight into how facial recognition works and may indicate the existence of a specific facial perception mechanism in the brain. For instance, if you see a slender, metallic object with wings and propellers, you know that it is an airplane. However, if someone were to ask you what the exact model of the airplane is, or how it is different from other airplanes, it’s likely that you would have no idea unless you are an aviation enthusiast. Similarly, many people with prosopagnosia can recognize an object as a face based on its fundamental layout but are unable to interpret unique facial structures as a whole face. These phenomena demonstrate that facial perception is potentially a holistic, or gestalt, process; we recognize a face as the sum of its different parts, or facial features.

A FACE IS WORTH A THOUSAND WORDS From spotting dangerous predators on the savanna to determining whether or not a stranger can be trusted, our facial perception mechanisms have helped ensure

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Just Another Face In The Crowd

our survival for millennia. For primates, faces are some of the most essential visual stimuli; our acute ability to monitor and interpret them is fundamental to how we interact, socialize, and identify with one another. Research on the development and evolution of facial processing has boomed in the past few decades, and certain findings — such as the existence of a specific facial processing mechanism in the brain — provide critical and groundbreaking insight into how we perceive faces. Still, facial perception is an incredibly complex and multifaceted subject that intersects with a wide array of disciplines, ranging from neuroscience to anthropology and psychology. Conducting further comprehensive, interdisciplinary research on primate facial processing and its evolution may help scientists better understand and elucidate the many aspects of this intriguing topic.

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Faking It ‘Till You Make It

FAKING IT ‘TILL YOU MAKE IT: WHY WE SHOULD ALL SMILE MORE by Natalie Pettirossi / art by Allie Verdesca and Mara Russell

e’ve all heard the expression “fake it till you make it.” Whether it’s a friend telling you to be nice to someone who drives you crazy, a teammate encouraging you to play through the pain of an injury, or a parent reminding you to act more confident at school, this phrase might make you roll your eyes. But for all the eye-rolling and annoyance this phrase can bring, there’s actually some truth behind it. “Fake it till you make it” holds notable merit in the case of faking a smile. Smiles are officially classified into two main categories: the standard smile and the Duchenne, or genuine smile. The standard smile is that small, usually forced expression we offer to someone to be polite or to show that we are paying attention. This smile is representative of the common phrase, “the smile did not reach their eyes,” which is often used to critique ingenuine reactions. While standard smiles merely activate the muscle surrounding the mouth (the zygomaticus muscle), Duchenne smiles activate both the zygomaticus muscle and the muscles surrounding the eyes (orbicularis oculi muscles) [1]. Thus, when you are “smiling with your eyes,” you are actually performing the Duchenne smile. Unlike the standard smile, a Duchenne smile is an unbridled form

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Faking It ‘Till You Make It of expression that transforms the entire face as both the mouth and the eyes react and change position [2]. Even though both smiles are different, they each trigger the release of beneficial chemicals, improving psychological and physiological body responses.

SMILING ACTIVATES IMPORTANT SUBCORTICAL STRUCTURES The changing position of facial muscles in both the standard and the Duchenne smile activates the amygdala -- a structure found in the temporal lobes of the brain. The amygdala is responsible for decisionmaking and emotional responses [3]. For example, if you were in the middle of a forest and encountered a bear, your amygdala would trigger the fight or flight response, preparing you to either run away in the opposite direction or stand up to the bear and scream. Your amygdala regulates emotions and behaviors, serving as an alarm to the hypothalamus, another structure in the brain that regulates the release of a variety of chemicals such as neurotransmitters and endorphins [4]. When you smile and your zygomaticus muscle changes position, your amygdala is activated, alerting the hypothalamus to secrete four important moodboosting chemicals: neuropeptides, proteins that combat body stress responses; dopamine, a hormone involved in motivation pathways; endorphins, the body’s natural pain killer; and serotonin, a hormone connected to happiness and mood regulation[5]. These chemicals have many functions in the body, contributing to both physiological and psychological processes. Notably, the release of neuropeptides and endorphins improves the body’s physiological responses. Neuropeptides have a calming effect on the nervous system while endorphins function similarly to opioids, mitigating pain in the body. When neuropeptides and endorphins are released together, the body becomes more relaxed. The release of dopamine and serotonin, on the other hand, play an even larger role in improving the body’s psychological processes. Increasing dopamine levels in the body also increase motivation by heightening reward and pleasure pathways, and raised levels of serotonin increase overall feelings of happiness [5]. Therefore, these “Big Four” components are exactly why we should smile more; the more neuropeptides, dopamine, endorphins, and serotonin our body releases, the better we feel both physically and emotionally. However, a smile does not need to be Duchenne

to feel this pleasurable rush. Your amygdala cannot differentiate between a fake or a genuine smile and therefore triggers the same release of neurotransmitters and endorphins regardless if it is “real.” Even when you have to force a smile at someone’s cheesy joke, the zygomaticus muscle changes position, alerting the amygdala to activate the hypothalamus and release the same endorphins and neurotransmitters, regardless of the type of smile [1]. In other words, we no longer need to entertain ourselves with John Mulaney or Trevor Noah to find an excuse to smile; we really can “fake it till we make it,” reaping the same psychological and physiological benefits with an ingenuine smile.

SMILING CAN CHANGE YOUR MOOD A recent study examined how changing participants’ facial expressions could impact their mood and interpretation of ambiguous stimuli, or stimuli that do not have an explicitly positive or negative connotation [6]. In this experiment, psychology students were shown a slideshow of images and asked to rank each slide as very negative, neutral (ambiguous), or very positive [6]. Electrodes attached to the subject’s facial muscles allowed researchers to control and manipulate these muscles into either a standard smile or a frown as the participants watched the slideshow [6]. The team found that significantly more positive ratings were given to ambiguous stimuli when participants were smiling compared to when they were frowning. This suggests that the activation of the zygomaticus muscle can positively influence how people perceive neutral stimuli [6]. All in all, this study corroborates the point that smiles, even forced ones, can improve your mood, allowing you to view your surroundings and environment in a more positive light [7]. On the other hand, additional studies have shown that the inhibition of facial expressions can actually weaken some emotional experiences [8]. This finding, as well as the one detailed above, prompted researchers to consider the negative consequences of facial muscle activation by looking at the effects of BOTOX injections on decreased amygdala activation and emotional capacity [9]. Botulinum toxin, commonly referred to as BOTOX, is a neurotoxin protein that is used for a variety of medical reasons, though, most notably, by dermatologists to treat wrinkles. BOTOX causes muscle paralysis by blocking the neurotransmitter acetylcholine, which is responsible for smooth muscle contraction [10]. With limited facial muscle movement, fine lines and wrinkles are smoothed out, along with

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Faking It ‘Till You Make It depression, and addiction [13]. Some techniques used to counter these responses promote relaxation through visualization and mindfulness practices, deep breathing exercises, and physical activity such as yoga or tai chi [13]. Beyond these, newer research is starting to consider the effects of social support in alleviating bodily stress reactions. So, why not consider the potential benefits of smiling as well? facial expressions and the corresponding visual cues of mood and emotion. In fact, a study conducted in 2020 found that BOTOX patients experienced a significant decrease in the strength of their emotional experiences, again suggesting that facial expressions may impact emotional experience [11]. Through the inhibition or exhibition of facial expressions, one is able to change one’s own mood.

SMILING MAY IMPROVE STRESS RESPONSES Not only do facial expressions, such as smiling, make up an integral component of mood and emotional state, but they also impact our physiological health. For example, one of the most important jobs of the smile is to decrease our bodies’ stress response. Stress can be understood as a real or perceived threat to our wellbeing that disrupts homeostasis — our body’s ability to maintain internal stability—and causes our body to react [12]. The stress response is the fight or flight reaction mentioned earlier, like when you encounter a bear in the forest and your body is prompted to decide what to do next. This is an important survival mechanism as the response activates the necessary neuroendocrine systems for a suitable reaction to the threat. However, the activation of our stress response is not always beneficial. While the acute stress response is evolutionarily necessary, chronic stress is a major physiological problem that affects more and more people at an increasing rate [13]. Chronic stress is characterized by a variety of symptoms, but notable characteristics include high blood pressure, obesity, and brain changes that can contribute to anxiety,

As such, a recent study looked at how manipulated smiles affected stress recovery and heart rate. Participants were divided into three groups and were trained to hold different facial expressions through the placement of chopsticks in their mouths. The chopstick placement replicated and activated facial muscles responsible for neutral expressions, standard smiles, or Duchenne smiles. After being put through a stressful activity, the participants in both the standard and the Duchenne smile group had lower heart rates than the neutral expression group. While the Duchenne smile group had a trend of lower heart rates than the standard smile group, the difference was not statistically significant, meaning that both types of smiles are considered effective [1]. This goes to show that, just as smiles can increase the secretion of mood-boosting chemicals in the brain and improve positive experiences, they can also alleviate stress responses, therefore improving physiological health.

COMPOUNDING EFFECTS: SMILES AND LAUGHTER But it doesn’t just stop there: the findings that a smile can improve stress responses bring forth new questions. One research team decided to build off of previous studies of the smile’s impact on stress levels by investigating how both smiling and laughter may affect stress responses. This study was conducted to better understand positive affect, or the state of experiencing pleasure, which typically decreases mental and physiological stress responses [14]. To quantify positive affect, the researchers cited laughter as the highest level or display of pleasure, followed by a Duchenne smile and then no smile at all. The major goal of this study was to determine if laughter

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Faking It ‘Till You Make It has a stress-buffering effect on participants. Both the frequency and intensity of laughter were studied and it was found that higher frequencies of laughter reduced self-reported stress response symptoms [14]. Interestingly, this study was actually a test of the stress-buffering model of the positive affect hypothesis, which states that positive affect reduces the health-harming effects of physiological stress [15]. A previous study had determined that greater positive affect was found to be associated with lower mortality risk, inspiring the researchers who studied laughter’s effects to build off of this work and determine significant associations between greater positive affect and lower perceived stress. Stress contributes to mortality risk and therefore when positive affect mitigates stress responses, it also mitigates mortality risk too. These studies can be looked at together to understand how smiling and the release of moodboosting chemicals can play a crucial role in mitigating the stress responses that often take a toll on the body.

THE POWER OF FAKING IT In the age of COVID and the heightened stress, worry, and isolation that accompanies this pandemic, it often feels like there is a lot less to smile about. The loss of routine, education, jobs, time with loved ones, and opportunities can be an incredibly challenging weight to bear. However, it’s clear that, now more than ever, it is important to coax those facial muscles to turn on and smile. Doing so will help our brains and bodies stay healthy and prepared to face whatever challenge comes next. Moreover, smiling will set us up for success in other ways, improving our mood and our brain’s chemical balance, therefore decreasing our perception of stress. So now really is the time to fake it till you make it: keep smiling through these challenging times and know that doing so will benefit you both psychologically and physiologically.

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Encounters With the Third Kind

ENCOUNTERS WITH THE THIRD KIND: THE MEMORY TWILIGHT ZONE by Zoe Curran / art by Naomi Tomlin SOMETHING IN THE SKY

our car careens around sharp turns as you make your way home on a dark, forested highway. You drive through unfamiliar territory tonight, far from streetlights and neighbors. Even the trees look different out here. You’re passing a road sign when you first hear it: a high-pitched whine infiltrating the car through the cracked windows. The whine ascends to a scream. You notice a spotlight piercing through the darkness, cutting across the treetops, shining through your windshield. In a moment of panic, you crash into the highway barrier. Suddenly, the spotlight is on you. You finally see the source of the sound and light: a wide, chrome saucer hovering 50 feet above you, beaming you up! A door begins to open, tall grey figures illuminated within. You wake up the next morning in your own bed. Outside your window, your car is intact. And yet, your body is covered in scratches and you can’t shake the image of the saucer and the tall grey figures. Who took you that night, and where did you go?

THE ORIGIN OF THE EXTRATERRESTRIAL When reading the story above, could you see the bright saucer lights and hear the crunching car metal as you collided with the highway barrier? What features can render a false memory easy to believe? To begin untangling the neural complexity of false memory formation, we must first understand how memory salience can change how, and what, we remember. Salience is defined as being particularly noticeable or prominent; therefore, a salient memory is one that readily comes to mind out of a sea of surrounding memories. Cultural relevance plays a key role in the salience of a memory. For example, iterations of the alien abduction narrative have invaded popular culture since the early 1960s. The true origin of this narrative actually belongs to the Puritan fisherman James Everell [1, 2]. As documented by John Winthrop, governor of the mid1600s Massachusetts Bay Colony, Everell claimed he saw a mysterious light that “ran as swift as an arrow” darting across the marshland of “Muddy River.” Future fishermen described seeing the same unexplained

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Encounters With the Third Kind light appearing on the marsh. Some heard voices or commands. Everell even claimed that the light had carried his boat a mile upstream [2]. Flashing lights, strange beings, and lost time – sound familiar? The details of the Puritans’ experiences echo elements of another Encounter with the Third kind: Betty and Barney Hill’s 1961 tale of an extraterrestrial encounter deep in New Hampshire’s White Mountains. Their story begins with Betty and Barney in the final stretch of their late- night drive home; a sleepy Barney was behind the wheel when he first saw the lights of a strange object flying overhead, following the movement of their car and growing brighter with each passing mile [1]. The extraterrestrial powers of their abductors rendered the couple paralyzed and unconscious. When they awoke two hours later, they realized that they had traveled 35 miles down the road.

extraterrestrial encounters were painted as friendly, albeit strange. The fact that the Hills were attacked challenged this notion, explaining why their narrative made for such great storytelling. Second, the Hills provided an incredible amount of detail when presenting their encounter. The couple could remember how many miles away from a rest stop they had traveled, the structure of the tailing UFO, and the color of the lights on the spacecraft. Lastly, the recollections only emerged after the couple had been placed in a hypnotic trance and asked a series of leading questions by their psychiatrist. In this hypnosis-induced state of heightened susceptibility,

Before the story’s publication, the Hills lived a quiet suburban life, untouched by extraterrestrials or media frenzy. However, their story forever changed how alien abduction accounts were both told and understood. In the years after their alleged encounter, the couple developed severe psychosomatic symptoms: crippling anxiety, disturbing dreams, and even stomach ulcers. Plagued by their physical and mental ailments, the couple sought out a hypnotherapist to determine if there was a relationship between that fateful encounter and the onset of their suffering. It took weeks of hypnosis for the ulcers to heal and the anxiety to diminish, and as their mental health began to recover, the Hills felt compelled to tell their curious tale [1]. Three key characteristics of this encounter are worth examining. First, prior to the Hills’ experience,

the Hills could have been led to believe that anything had happened to them. In a sense, their own memories

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Encounters With the Third Kind were up for grabs, ripe for manipulation. In addition to sparking an American fascination with saucers in the night sky, Betty and Barney revealed a crucial paradox of memory: humans often believe irrational things for rational reasons. For example, encoding a salient memory after being attacked by a terrifying figure is rational, but improperly encoding the figure as an alien is irrational. Moreover, being “rational” does not exempt someone from forming false memories. False memory formation can occur in all of us.

HOW A FALSITY BECOMES A TRUTH: THE FORMATION OF FALSE MEMORIES The human brain can form memories fairly easily, even ones involving aliens. But how, exactly, do these memories form? Think of an equation you are trying to memorize for a class. You begin by looking at your notes, taking in the details, the length, the meaning of each variable, and its application. Your notes and the elements of the equation serve as sensory input: the initial stage of memory formation. This information is then stored in a temporary memory bank. While the equation waits patiently in this bank, you repeat the information by rewriting the equation over and over. This process is called rehearsal. As you rehearse the equation, it leaves the sensory memory bank and travels to a new storage location: your short-term memory. From here, the information will be encoded and remembered for the long haul and is said to be a component of your long-term memory, divided into two subsets: explicit and implicit memory. Learning a math equation is a form of explicit memory, requiring conscious effort to recall. Remembering your mother’s name is an example of implicit memory, or something that is recalled effortlessly. Many tend to incorrectly assume that these memory processes all occur in one location: the famed hippocampus. Although peripherally involved in a number of memory processes, the hippocampus is primarily involved in the storage of episodic memory, or autobiographical accounts of specific life events [3]. The formation of long-term memories, however, requires the simultaneous engagement of multiple neural pathways outside of the hippocampus [3]. Auditory sensory input undergoes initial processing in a different location of the brain than visual sensory input. To encode and store this sensory information, additional structures are needed. This neural process of memory formation seems nearly as intricate as Betty and Barney’s tale!

However, it doesn’t just stop there; several other brain structures are also involved in memory formation, such as the neocortex and amygdala. The neocortex is the largest part of the cerebral cortex, characterized by the wrinkly layer of tissue that covers the surface of the brain. It is responsible for sensory perception, motor commands, spatial reasoning, and elements of language. Sensory perception is defined as the processing of an element in the environment, while spatial reasoning refers to an individual’s capacity to picture objects in 3-dimensional space and draw conclusions about them based on limited information. Interestingly, the neocortex also acts as a storage unit; memories that were temporarily stored in the hippocampus can also be stored in the neocortex as everyday knowledge. The amygdala, on the other hand, is responsible for attaching emotional significance to memories. Memories with strong emotional ties are the hardest to forget, regardless if the memory formation was accurate or falsely conceived. For example, because fear is a particularly powerful emotion, overpowering other strong emotions like joy or shame, memories associated with fear are more likely to be ingrained in our long-term memory. Thus, the stability, or propensity for the long-term duration, of a memory is largely determined by interactions between the hippocampus, neocortex, and amygdala. However, while the brain has developed these complex processes for memory formation and storage, it still lacks a foolproof mechanism for differentiating between real and false encoded information. This means that false memories can be remembered as real ones, though these are typically only constructed in a susceptible state of mind when information is suggested as real, or when a prior experience is confused with a new one [4]. The incorporation of this information resembles the slow addition of small strokes to a painting of a village; a dash of green on a villager’s arm, a splotch of purple on a cloud, a tinge of red on a building. Each revisit to that same memory will lead to more and more strokes of paint added onto the original painting, until the villagers’ skin is green and the sky is purple: a completely changed scene. Memories characterized by something fearful, such as being experimented on by unfamiliar beings, are particularly memorable. The sensory system, hit with flashy, fresh stimuli, desires to learn every detail it can about this incoming information. Simultaneously, parallel neurological processes work to determine the importance of retaining these details. While visual features of the stimuli are processed in the visual

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Encounters With the Third Kind brain region, the auditory and tactile features are synchronously processed elsewhere. But how does the brain decide whether or not this potential memory should take precedence over other incoming stimuli? New stimuli, referred to as novel stimuli, have high salience (prominence of a stimuli and the likelihood it will be remembered) when compared to repeating stimuli [3]. Earlier, we also examined the importance of cultural relevance in salience. The UFO and the extraterrestrial figures offer a double punch of both cultural relevance and novelty, making them fantastic candidates for encoding. Further, emotion inhabits another key role in memory, with memories generated on the basis of the valence, or the attractiveness or aversiveness, of the emotion [4]. An attractive emotion, such as excitement, has “positive valence,” whereas an aversive emotion, such as fear, has “negative valence.” Emotions that lie on either end of this scale, such as highly positive or negative ones, are more likely to be remembered. In the Hills’ case, fear of the alien lifeforms provided negative valence, while the overall traumatic experience created high arousal, as the situation contained many novel stimuli. These, combined with the physical and psychosomatic trauma the Hills allegedly endured while aboard the saucer, created the perfect memoryencoding storm. So, their brains went to work on the long-term neocortex storage of their Encounter with the Third Kind. It’s important to note, though, that many experiences may be encoded even without the salient features present in the Hills’ alleged abduction. The brain subconsciously notices countless stimuli in our environment, leading to some passive integration of stimuli into memory. Aside from this small bit of subconscious encoding, most of the information we recall best, or is stored in long-term memory the longest, is the result of conscious processing. Conscious processing occurs when an individual is aware and in control. In this way, we do have some autonomous control over what we remember vividly. Of course, there are exceptions to this, such as the impact of emotions and stimulus novelty on the stickiness of a memory. There are also many situations that can disrupt the typical memory processing chain, generating mild to severe encoding failures. One example is being in an altered state of consciousness, such as sleep or hallucination, both of which are capable of reducing one’s ability to consciously evaluate the accuracy of the “memory.” Thus, memory processing is highly dependent on the situation at hand and the state of the individual’s brain.

SLEEP DEPRIVATION AND HYPNOSIS: WHEN ARE YOU SUSCEPTIBLE TO SUGGESTION? The Hills’ journey home was fueled by black coffee purchased from a diner and chugged quickly before hitting the road around 10:30 pm. Given the long days of travel before and the hours of driving ahead, one can assume that Barney was partially sleep deprived at the wheel. Sleep is heavily involved in the process of translating memories from the short-term bank into a long-term savings facility [6]. In addition to memory translation, sleep is also responsible for replenishing your ability to encode details more accurately. Sleep deprivation, then, runs the risk of increasing inconsistencies when encoding memories and recalling personal events. But can sleep deprivation also lead to false memory formation? In 2016, researchers investigated this proposed link using two memory tasks: learning a list of semantically related words, and “misleading” the subject before asking them to recall a memory. The tasks were both designed to determine if, and how much of, the false information was encoded while playing with the same key memory salience characteristics mentioned earlier: stimulus novelty and emotional valence. Researchers found that partial sleep deprivation significantly elevated faulty encoding while having a smaller impact memory recall [6]. The prevalence of memory encoding failures may help to provide a potential explanation for why the Hills encoded the wrong story but remembered it in fantastic detail. The ability to provide such detail is oddly striking; wouldn’t more details make the abduction harder to recall? Interestingly, perhaps not. Another study found that certain types of details can be stored in large amounts, actually enhancing these memories [7]. Any detail an individual sees as relevant to themselves is associated with stronger memories. Cultural context is critical, as you’re more likely to falsely remember an event that somehow makes sense; are there contextual details that would further suggest this particular detail is likely? Have you seen these details or images around you [7]? From the Hills onward, alien abductions were marked by the deeply personal trauma abductees endured. The attacks harmed the body, and were therefore inherently personal. And although most people would probably not jump to “alien abduction” to explain the development of their bumps and bruises, the prevalence of these narratives provides a tantalizing explanation for otherwise unexplained trauma. The

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Encounters With the Third Kind usage of an abduction narrative is typically presented under a semi-specific set of factors, but nonetheless, they remain omnipresent in the cultural fabric of American mythos.

truly produced those ideas entirely on their own. Still, knowing that the Hills were entering his office with severe trauma produced under strange circumstances would motivate anyone to uncover the root cause.

When the Hills began attending hypnosis sessions with Simon, they were initially seen separately for confidentiality reasons. Simon claims that the abduction claims appeared fast and furious; Barney’s retelling was riddled with frequent emotional outbursts, and Betty had been dreaming of the events for months so her final account mimicked the dreams closely. According to Barney, Betty would often cry out in the night and experience periods of intense sleep paralysis and hallucinations. Despite being separated for the majority of sessions, Betty and Barney produced similar narratives while in hypnotic regression. Simon chose to dig deeper into these claims, interfering very little during the sessions and instead opting to listen and provide occasional guidance. Hypnosis is defined as a “waking state of consciousness,” in which an individual is detached from the outer world and fully absorbed in internal experiences. It is particularly useful for increasing susceptibility to suggestion and heightening the mind-body link [8]. In hypnosis, words are used to evoke specific imagery, calling events lodged deep in the subconscious mind to the forefront. For Barney and Betty, Simon may have asked them to return to the darkness of that New Hampshire night and tell him everything they knew. Being in a hypnotic state of detachment can allow an individual to perceive a memory using their right hemisphere of the brain more than their left hemisphere. The right hemisphere is involved in symbol and image production (among many, many other tasks – it is a whole hemisphere after all!) and shows an increase in activity when we are relaxed or deeply involved in an activity. Thus, when the right hemisphere is highly active in this detached state, images can be more easily accessed from the unconscious mind and brought into the conscious mind [8]. It’s impossible to know if Simon asked leading questions directly related to extraterrestrial encounters, or if the Hills

It’s particularly interesting to consider how Betty’s narrative developed, as well as how this may have significantly impacted Barney’s account. As mentioned earlier, Betty had experienced a series of extraterrestrial-infused night terrors accompanied by sleep-talking, shouting, and occasional bouts of sleep paralysis. Disrupted sleep is a common somatic symptom of trauma, particularly repressed trauma, even if the memories are different from the events themselves. Disrupted sleep as a result of trauma can be infused with sleep paralysis and hallucinations. Paralysis occurs when an individual awakens from Rapid-Eye-Movement, or REM sleep, and is often accompanied by tactile and visual hallucinations [9]. These hallucinations can be mistakenly viewed as a “reliving” of past experiences or encoded as entirely new memories [9]. Of course, hallucinations and memories differ, but sleep, and REM sleep in particular, is an altered state of consciousness where

one’s ability to accurately differentiate between reality and falsity is diminished. Did Betty and Barney have an alien-themed film playing before they went to sleep? Was the theme of abduction prevalent in the Hills’ childhoods or adulthoods? Were they perhaps

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Encounters With the Third Kind attacked by a group of people, and in an effort to contend with the pain of being attacked, framed it as something non-human entirely? Speculation alone is worth little, but it is worth considering the impact and influence of these different elements on the final stored memories. Just like with hypnosis, a sleeping individual is in a vulnerable state, and any of these variables could have affected the contents of the night terror.

THE IMPORTANCE OF RECOGNIZING AND TREATING TRAUMA, REGARDLESS OF ORIGIN Simon ultimately argued that Barney borrowed his narrative from snippets overheard from Betty, and Betty had misremembered her night terrors for reality [1]. It was a logician’s attempt to explain the impossible. Although Simon’s analysis provided a rationale for both the matching narratives and the extremity of the experience, it fails to negate that the Hills did, in fact, encounter something in the woods that night. That particular something was also deeply distorted and responsible for the development of severe psychological perturbations. Repressed memories, now also referred to as dissociative amnesia, are frequently mischaracterized as “materializing out of nowhere” or “appearing purely because of suggestions.” These memories remain a hotly contested topic in psychological research for neuroscientists and psychologists, with their reputation being born out of early therapeutic techniques used to examine childhood sexual trauma. More extensive cross-examination of these techniques revealed frequent instances of reinterpretation and misassigned meaning, often crossing the line into the formation of entirely false memories. These techniques were phased out as our understanding of human memory and memory formation improved. Psychologists learned that often certain aspects of trauma are relatively well-remembered, flashbacks and intrusive memories are relatively common, and complete memory loss is rare [10]. In addition, it was discovered that traumatic memories can be painted as entirely different events, with the original details being temporarily replaced by more salient details [10]. The core components of the traumatic event typically remain the same, however. The Hills did not display severe repression per say; there was a lapse in time between the beginning and end of their abduction, but their reaction and investigation of the events began relatively quickly.

As we have uncovered through an admittedly brief exploration into false memories, memories are remembered for a reason. Sometimes, the details that provide a memory’s backbone and flesh are falsified, e v e n t u a l l y appearing twisted, d e f o r m e d , even alien-like. Sometimes it isn’t this dramatic. But even an illogical narrative sticks as a memory because it is somehow salient. Repressed memories are referenced most frequently within the realm of trauma [10]. A traumatic event occurs and is characterized by extremely aversive emotions, which are difficult for an individual to bear; the memory is almost too sticky, like molasses. Its presence gums up the neurological workings of the brain, oozing out in unexpected ways. With the Hills, this dark ooze was anxiety, panic attacks, night terrors. It looks different for everyone, but it is nearly always disrupting the system, and takes time and care to be treated effectively and empathetically. Recognizing the validity of the Hills’ trauma is critical; though their experience may be labeled as “false,” “whacky,” or “unsettling,” the couple still experienced life-altering consequences, both in

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Encounters With the Third Kind painstakingly detailed accounts, the night terrors, and the public frenzy would certainly suggest a high degree of believability. Yet, only the Hills will ever truly know. That’s the core reality to keep in mind; their memory of that night is inevitably subjective, ever-shifting, and fallible. Our interpretation of their experience is just as fallible because sometimes, memories just aren’t correct, no matter how much we believe (or want to believe) them. With difficult or traumatic memories, whether they are false or true can have significant implications. With the story of the Hills, their impact was both individual and collective. That fateful night drive through the White Mountains blew their understanding of life to pieces, literally. Earth was no longer the only place home to life, and not all other life forms were friendly. It rendered them psychologically disturbed, desperate for an explanation for their suffering. In the 1960s, their trauma, their healing, and their story resonated with millions. This tale of the extraterrestrial continues to have a profound impact on us all. Seeking answers to impossible questions is part of being human. Is there a God? Where do I go after I die? If I drove 76 miles unconsciously and woke up bruised and scratched, who took me and where did I go? Perhaps we don’t all turn to aliens and saucers to quell our thirst for explaining life’s uncertainties, but we all surely turn to something.

the context of their personal battles and in the larger lens of their cultural impact. However, within this recognition a key question still remains: did the abduction really occur? The

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

BEWARE THE POST-VACCINE BLUES

Beware the Post-Vaccine Blues

by Brenna McMannon art by Darling Garcia

ave you ever had the post-vaccine blues? It’s hard to imagine that such a minor experience could manage to impact your mental health. However, in recent years, evidence has emerged supporting a possible link between bodily inflammation and depression. This idea — that inflammation, the body’s natural response to injury, can have a psychological impact — has expanded our perception of mental health, adding to the enigma of the human brain. The mystery of the brain has made mental health, and depression specifically, incredibly hard to study and even harder to treat. This is mainly due to the fact that no one brain region or molecule has been identified as the sole cause of major depressive disorder (MDD), despite the fact that about 21% of women and 12% of men in the United States alone will experience depressive symptoms at some point in their lives [5]. This gap in understanding poses a real threat to people suffering from MDD across the world. However, recent research suggests a link between bodily inflammation and depression, expanding our

understanding of the many causes of depression and aiding in the development of treatments. Before we get into that, let’s explore our existing knowledge of depression.

DEPRESSION: WHAT WE KNOW Many of the key players in depression are concentrated in the limbic system: the set of brain structures involved in emotion and memory. Despite this knowledge of where depression occurs in the brain, the treatment of depression doesn’t focus on these brain regions; rather, it targets the tiny chemicals that send messages between them. Yes, I’m talking about neurotransmitters, the famous chemical messengers of the brain. Brain cells called neurons send signals to one another via neurotransmitters. Therefore, the amount of neurotransmitters being produced are important to their functionality, because having too little or too many can cause problems.

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Beware the Post-Vaccine Blues

Over the past half century, psychiatrists have prescribed depressed patients with drugs that aim to correct a chemical imbalance in the brain, usually involving a reduction in the neurotransmitter serotonin. Enter: Prozac. Also known as fluoxetine, this drug is currently the most commonly prescribed antidepressant and is classified as a selective serotonin reuptake inhibitor (SSRI). The drug functions to correct serotonin imbalances in the brain by allowing more serotonin to accumulate in the spaces between neurons, called synapses, through which neurotransmitters travel from one neuron to another. Then, neurotransmitters bind to the receiving cell and convey their signal. SSRIs work to keep serotonin from being recycled back into the neuron that released it, leading to an accumulation of serotonin in the synapse. When the concentration of serotonin in the synapse increases, the neuron receiving the signal can be activated more frequently. SSRIs work for many people with depression, boosting their mood and stripping them of their depressive symptoms. However, the causal link between serotonin and depression is still widely unknown. While a serotonin imbalance may play an important role in some patients’ depression, this is not the case for every person with MDD. Unfortunately, SSRIs and other antidepressants don’t work for everyone suffering from depressive symptoms. In fact, about 30% of people with depression do not respond to any antidepressant treatments [1]. These patients suffer from treatment resistant depression (TRD) and end up trying every kind of treatment you can imagine (meditation, talk therapy, medication, and medical procedures), often to no avail. Depression research is ongoing and consistently funded, so why don’t we know more about its cause, especially in people with treatment resistant depression? Because most people suffering from MDD display such a wide array of responses to different treatments, its root cause remains elusive. Many people with TRD resort to electroconvulsive therapy (ECT) — one of the most effective TRD treatments, with a response rate of 50%-70% [3]. ECT uses electrodes to send an electric current through the brain, inducing a brief seizure. But here’s the kicker: nobody really knows how or why ECT is an effective treatment for TRD. This common theme in the study of MDD makes it difficult to formulate consistently effective solutions. Treatments like SSRIs and ECT reveal the high degree of variation among MDD patients, signaling how important it is to examine each case individually and

treat the patient based on the suspected cause rather than employing a universal approach. This is where the immune hypothesis comes in as another potential cause of depression.

THE IMMUNE HYPOTHESIS The immune hypothesis proposes a possible link between inflammation in the body and depression in the brain. However, the existence of an important brain structure, called the blood brain barrier (BBB), has made it hard for scientists to causally link bodily inflammation with depression. The BBB is a filtration mechanism built into the endothelial cells that surround the brain. These cells form an important layer within blood vessels that regulate the exchange of materials. The primary function of the BBB is to prevent toxins and other potentially harmful substances from entering the central nervous system (i.e. the brain and spinal cord). The filter also blocks out large molecules, cells, and other structures, meaning that many substances — like immune cells — circulating in the periphery of our bodies are not able to enter and affect the brain. For example, when you stub your toe, it usually becomes inflamed. However, scientists never thought that this simple inflammatory response could reach the brain because the immune cells are too big to cross the BBB. Now, we know that this is far from the whole story. In order to fully understand the connection between inflammation and depression, we must first familiarize ourselves with some important members of the immune system. Inflammation is the body’s natural reaction to injuries or viruses. When you sprain your ankle or get a root canal, your body generates a cytokine storm. Cytokines, the messenger cells of the immune system, are released from immune cells and sent out to promote inflammation and protect affected areas. In other words, your body starts vigorously pumping out cytokines to spread the word that there is an injury or foreign invader. This maelstrom of angry cytokines arrives on the scene and removes damaged tissue so that the healing process can begin. The main player in inflammation is a proinflammatory cytokine called tumor necrosis factor (TNF). While TNF is too big to cross the BBB, in the past few decades, scientists have discovered a correlation between increased blood levels of proinflammatory cytokines, like TNF, and depressive symptoms [4]. But, how is this possible if cytokines can’t cross the BBB? This is where we find out that stubbing your toe can

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Beware the Post-Vaccine Blues actually affect your mental health, bringing a mindbody connection into play. Pathogens, like influenza or Salmonella virus, have previously been associated with depressive symptoms, such as feelings of sadness or apathy [14]. Interestingly, these pathogens have the ability to cause the release of cytokines and the consequent activation of microglial cells in the brain [12]. Microglia are the first line of immune defense for the central nervous system, as the immune cells of the brain. Inflammatory cytokines are able to get their message across the BBB and to the microglia without actually entering the brain, by binding to receptors within the endothelial cells. When microglia pick up the signal that there is inflammation in the body, they start pumping out their own cytokine storm into the brain. The involvement and function of cytokines in the brain is still poorly understood, but we do know that it is the brain’s response to receiving an inflammatory message. Although this is a natural biological response, microglial activation can be harmful, especially in the context of depression. When these angry microglia activate cytokines in the brain, they often impact serotonin production. Normally, cells in the brain produce serotonin from an amino acid called tryptophan. But when cytokines are released into the brain and start causing trouble, they can potentially instruct cells to use tryptophan to create other products in place of serotonin. Not only are these new products toxic to other cells in the brain, but they also decrease levels of serotonin. In this sense, it is no surprise that depressive symptoms tend to correlate with an increase in nonserotonin, tryptophan-derived molecules, resulting in a decrease of serotonin in the brain [9]. Decreased serotonin levels may also render some SSRIs ineffective, which may help explain why some people don’t respond to them. SSRIs work to inhibit the reuptake of serotonin, so if there is not enough serotonin being produced to begin with, they would have no effect. In fact, one study found that MDD patients who don’t respond well to SSRIs and other antidepressants are more likely to already have some sort of inflammation present in their body [8].

INFLAMMATION: WHERE DO WE GO FROM HERE? There are so many ways for the body to become inflamed— it’s downright unavoidable. For instance, simply being female puts you at higher risk of inflammation due to factors such as childhood adversity, obesity, and interpersonal stressors, all of which disproportionately affect women [2]. Coincidentally, women also experience depression at a higher rate than men [5]. However, one of the most common causes of inflammation is psychological stress, as sustained feelings of stress can result in the chronic release of pro-inflammatory cytokines in the brain [6]. What’s more, chronic stress can lead to severe conditions like coronary heart disease (CHD) [13]. Even episodes of short-term stress can induce CHD in a more vulnerable subset of people [13]. This subset of patients has one thing in common: all are inflamed. Furthermore, the events of your childhood can affect levels of inflammation during adulthood [7]. Recent studies have found that experiencing some kind of childhood adversity (e.g. parental separation,

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Beware the Post-Vaccine Blues low socioeconomic status, or familial mental illness/ disorders) is often coupled with both inflammation and depression later on in life [7].

evolving, and this new link between inflammation and depression is simply the beginning of another chapter in understanding the complexities of the brain.

There’s a good chance that you will experience some level of inflammation-linked depression at some point in your life. So, how can you get ahead of it? There is compelling evidence that exercise can have a protective effect against the danger of stress, specifically chronic stress [11]. Of course, exercise is not going to be the perfect solution for everyone. What about people with chronic inflammation that isn’t caused by psychological stress, like rheumatoid arthritis? Conditions like these are considered to be autoimmune, meaning the immune system is overactive and producing inflammation where it isn’t needed. Scientists have started to develop experiments to invent drugs targeting this inflammatory response, though very few studies in the past decade have rendered promising results. One study conducted in 2013 included 60 people with MDD, half of which were taking antidepressants and half of which were resistant to treatments (moderate TRD). They were given either a placebo drug or a drug that contained a TNF antagonist, which worked to block the binding of TNF and prevent an inflammatory response. Over a 12 week period of drug administration, they found no overall differences in depressive symptoms between the placebo group and the antagonist group. However, when they reexamined the data, researchers found that when they took into account baseline inflammation, the drug had a significant effect. In other words, the participants that had a higher baseline level of inflammation at the start of the study experienced significantly more antidepressant effects than those who had less inflammation, suggesting that inflammation may have greatly contributed to their symptoms of depression [10].

Only when future developments enable us to look past the diagnosis of MDD and determine the specific causes for each person, will relief be an option for everyone. For now, this developing link between inflammation and depression may clear the way for the development of new and effective treatments. And it may explain why you feel a little down in the dumps after getting your COVID-19 vaccine.

This brings us back to the importance of individual differences and creating treatments based on the individual rather than the condition they suffer from. It’s clear that various risk factors, including childhood adversity, biological sex, and disease, produce different experiences of depression. In the same way that SSRIs may not work for those who are struggling with a serotonin imbalance, TNF antagonist drugs may be ineffective in treating those without inflammation. Eventually, there needs to be a comprehensive diagnostic test to determine the cause of a patient’s symptoms. Then, an individualized treatment plan could be developed to target that cause. But don’t hold your breath — these kinds of things take time. Depression research is constantly

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

RNA

by Benjamin Kheyfets, Daniella Lorman, and Clem Doucette / art by Phoebe Kinder

RNA: A NEW FACE IN THE FIGHT AGAINST NEURODEGENERATION

n the time it takes for you to read this sentence, over seven million cells in your body have died. And by this same time tomorrow, an unfathomable 1011 more of your cells will have died and been replaced by new cells [1]. As alarming as this fact may sound, cell death, known as apoptosis, is an essential process to biological life. Apoptosis is critical in regulating a number of different bodily functions, ranging from the shapes of our organs to the amount of neurons in our nervous system [1]. However, certain conditions, like neurodegenerative diseases (NDDs), can cause apoptosis to go haywire, and when unplanned apoptosis occurs in the brain, it can result in catastrophic effects [2]. Right now, nearly 6.5 million Americans are suffering from some form of neurodegenerative disease, and estimates show that by 2030, as many as 12 million Americans may suffer from a NDD [3]. NDDs occur when the cells of the nervous system — including those of the brain, spinal cord, and nerves — function abnormally. Symptoms may be mild at first; short-term memory loss or coordination issues are common early indications of NDDs. However, as cells continue to deteriorate, symptoms such as loss of communication, seizures, and skin infections gradually increase in severity until they become fatal [4]. Unfortunately, no NDD is currently curable [5]. While some treatments do exist, such as medications and therapies, these interventions can only slow disease progression and manage symptoms. Given the ever-increasing urgency to find cures and treatments for NDDs, biotech and pharmaceutical companies have been heavily investing into research endeavors. A growing body of new research shows that genetic regulation, specifically via RNA, may play a huge role in the development of these diseases [6]. With

this new and extensive research, RNA and its role in NDD development and progression has garnered a considerable spike in interest. This review will explore the role of RNA in neurodegenerative disease, with the goal of illuminating potential options for future treatments or cures.

RNA: MORE THAN A MESSENGER In order to explore how RNA is involved in NDDs, it is essential to first understand RNA’s relationship to DNA. Imagine that you are in charge of developing a standardized cookbook for a nationwide fast food chain. Each restaurant receives the same cookbook, which has specific information about the ingredients needed to make each meal and exactly how to prepare it. Our DNA, found in the nuclei of most of our cells, is just like this cookbook. A DNA molecule consists of alternating sugars and phosphate groups; these components create DNA’s famous double helix structure. The “steps” of DNA’s ladder-like structure are made up of four different molecules called nucleotides: adenine, thymine, guanine, and cytosine, abbreviated with the letters A, T, G, and C [7]. A group of three letters (i.e. CCG, ATG, and ACT) is called a codon, which codes for an amino acid — the building blocks of proteins, and the ingredients in our recipes. Like recipes in a cookbook, these unique orderings of nucleotides provide the blueprints for creating different amino acids, and subsequently proteins. Just like cooking, where the ingredients you use determine the dish you end up with, the order of the amino acids in a protein determines the identity and function of that protein, and the order of the letters of DNA determine the genetic code of the individual.

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

RNA recipe copy is brought to the ribosome (i.e. the chef). The ribosome then uses the mRNA recipe to create proteins; this process is known as translation. Because both transcription and translation are essential to cell functioning, they are regulated very closely to minimize the potential for missteps or errors.

But how are these DNA recipes then turned into proteins? Enter: RNA. If DNA is a cookbook with recipes, then RNA is a copy of one recipe, containing the same information. However, RNA doesn’t write this recipe in the exact same code. Unlike DNA, RNA is a single stranded molecule with a slightly different chemical composition; in place of the DNA’s T, RNA uses a different nucleotide, uracil, abbreviated U [8]. Like in DNA, the order of nucleotides in RNA is critical. While the order of nucleotides in DNA determines an individual’s genetic code, the order of nucleotides of RNA determines the RNA’s function or the corresponding protein that will be made. RNA’s most well-known role is that of the messenger RNA (mRNA) molecule. Messenger RNA serves as the genetic intermediary between DNA and ribosomes, or the organelles that manufacture proteins in our cells. Ribosomes are the chefs of our restaurant analogy. This process of creating mRNA from DNA is known as transcription, where, after being created, the mRNA

While bringing a copy of a recipe to the cook is the most common job of RNA, recent research has found that RNA does far more than just carry messages. Researchers have identified different classes of RNAs based on their length and function [9]. One such class is microRNA (miRNA); these mainly bind to mRNA molecules in order to block the ribosome from producing the mRNA’s encoded protein. If you are the ribosomal chef, this is like trying to read a smudged or water-stained copy of the recipe. While some portions of it may be legible, using it to prepare a meal would be virtually impossible. Another class of RNA is small interfering RNA (siRNA); these are short RNA molecules that bind to certain other RNA molecules, triggering their destruction. Cells can use siRNAs as a defense mechanism, protecting themselves from viruses and other foreign entities by destroying foreign nucleic acids [10]. In our restaurant analogy, siRNA would be a health inspector stopping by a restaurant where a number of customers have suffered severe food poisoning. To prevent further illnesses, the health inspector throws out the restaurant’s recipes causing sickness. Additionally, long noncoding RNAs (lncRNAs) are lengthy RNA molecules that, like siRNAs and miRNAs, do not actually code for proteins. Because of their length, they can take on many different shapes, and, depending on the specific characteristics of the RNA, can aid in the regulation of many different genes [9].

A KEY PLAYER IN NDD ONSET Abnormalities in certain processes involving RNAs have been increasingly implicated in neurodegenerative diseases [11]. For example, a recent study suggested that flaws within proteins that bind to RNA, termed toxic aggregates, are a potential cause of certain NDDs [12]. Additionally, recent research has shown that NDDs can also be caused in part by the presence of too many RNA protein aggregates, which influence how mRNA is processed after it is formed. The role of RNA in NDDs is thought to be due to its self-assembling

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

RNA nature: certain RNAs can spontaneously assemble without the need for any energy or assistance from the cell [13]. One mechanism related to RNA that may contribute to the cell degradation characteristic of NDDs can be found in the functioning of lncRNAs [14]. LncRNAs are highly expressed in our central nervous system, and their expression is regulated so that they are only present in certain regions of the cell at certain times. This selective expression allows the cell to respond efficiently to environmental changes. In patients suffering from several NDDs, lncRNAs have been demonstrated to dysregulate proteins throughout the

proteins bind to other classes of proteins. For example, lncRNAs in Parkinson’s disease patients increase the rate at which ribosomes create certain proteins from RNA. Several types of lncRNAs have also been found to be dysregulated in patients with Huntington’s disease, becoming either over- or under-produced [15]. More specifically, researchers have found that certain lncRNAs play a role in the development and onset of Alzheimer’s. One known connection between RNA and Alzheimer’s disease includes the lncRNA BACE1-AS, which protects certain mRNAs from being degraded by certain miRNAs. This process can lead to the buildup of the plaques that contribute to Alzheimer’s. Another lncRNA named 51A leads to the formation of compounds that are involved in the onset of Alzheimer’s [16]. These molecules play an intricate role in NDDs and regulating neurons, and researching their dysregulation may be the key to improved treatments, and perhaps even cures [14].

RNA DRUGS IN NDD TREATMENTS In light of our new understanding of RNA’s role in NDDs, researchers have explored the efficacy of RNAtargeted drugs to address problems created by the dysregulation of proteins. In 2018, two new drugs, inotersen and patisiran, were approved in the United States and Europe to treat hereditary transthyretin (hATTR) amyloidosis [17]. This disease is caused by a mutated form of the gene that codes for transthyretin, a blood protein made in the liver. This mutation makes transthyretin dissolve less easily, so instead of freely traveling throughout the blood as it should, the protein clumps up around nerves and destroys neuronal tissue function. To treat this, inotersen and patisiran bind to the mRNA that encodes for the mutated form of transthyretin, blocking the ribosome from using this mRNA, preventing the clumps of mutant protein from forming. The drug inotersen, a modified form of DNA, accomplishes this by binding to the transthyretin mRNA and blocking it from producing mutated transthyretin proteins. Meanwhile, when patisiran (an siRNA drug) binds to the mutated transthyretin mRNA molecule, the cell destroys the mRNA strand [17]. Thinking back to our cookbook, the functioning of patisiran is like having your recipe copy come out either smudged and unclear, making it unreadable, or having the copy torn up, making it unusable. In either case, the meal doesn’t get made.

central nervous system, interfering with how certain

Even though these drugs show enormous potential for NDD treatments, there is still a long way to go

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

RNA until such medicines can become commonplace. First, RNA tends to degrade in a cell relatively quickly [17, 18]. A drug made of RNA must be able to survive in the body long enough to enter the cells or organs of interest and interact with other molecules. To combat this degradation, the RNA is often packaged in lipid nanoparticles, which are spheres made of lipids (a type of fat molecule). Second, these treatments are somewhat invasive. RNA-based medicine cannot be taken orally; the technology still hasn’t developed to that point of convenience. For treatment to be effective, it needs to be injected either subcutaneously (under the skin) or intravenously (into the bloodstream). Third, there are potential side effects of RNA medicines, many of which we may not know of yet. For example, intotersen can lower one’s blood platelet count, potentially leading to difficulty in clot formation and, therefore, severe bleeding. Additionally, patients who receive patisiran also need to receive steroids to suppress other unwanted infusion-related reactions [17]. As such, researchers are still trying to uncover the consequences of, or risks associated with, RNAbased medicines.

RNA: THE FUTURE OF MEDICINE? RNA may be useful in the treatment of NDDs and other physiological diseases. In fact, the COVID-19 pandemic may be accelerating RNA-based research, as both the Pfizer and Moderna vaccines are mRNA vaccines [19]. When you get either vaccine, you are injected with mRNA that codes for all or part of the spike protein found on the surface of SARSCoV-2 (i.e. the virus that causes COVID-19) [20]. Your immune cells then manufacture that very protein, and its presence triggers an immune response. Then, if you are infected with SARS-CoV-2 following your vaccination, the immune system will already be equipped with the ability to handle the virus quickly before it can cause any serious damage [20]. Arming the immune system with preemptive knowledge of a disease is the basic premise of vaccines. However, some vaccines accomplish this using a different strategy. The Sinopharm vaccine created by the Beijing Institute of Biological Products, for example, uses a handicapped version of the actual SARS-CoV-2 virus to reach immunity [21]. NDDs are very different from viral infections, but the success of these RNA vaccines coupled with increased research behind RNA’s roles in NDDs still may lead researchers to develop RNAbased medicines for NDDs [22].

Despite expectations of RNA acting solely as a messenger (or a copier of recipes), recent research has proven it to be a molecule of many trades. With its diverse classes and forms, RNA is a multifaceted player in many essential neural processes. Considering the increasing prevalence of NDDs, discoveries of neurodegenerative implications associated with RNAmediated protein production are more imperative than ever. While we still have a lot to learn about RNA’s role in the process of neurodegeneration, RNA-based medications offer a promising new treatment option to the millions of people suffering from NDDs and may be the first step taken toward finding a cure.

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

A Hot Issue

A HOT ISSUE: TEMPERATUREDEPENDENT TOXICITY IN HERBIVOROUS MAMMALS by Daniella Lorman and Clem Doucette art by Alex Tansey, Mara Russell, and Hannah Weisman 42

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

A Hot Issue

A HOT MEAL

ife on our planet is facing a serious environmental threat. If we allow greenhouse gas emissions to continue increasing, it is estimated that the Earth’s average surface temperature will rise by roughly 11.5 degrees Fahrenheit by the end of this century [1]. At a glance, 11.5 degrees may not seem like a big change. However, daily air temperatures, or the numbers we see when we check the weather apps on our phone, are vastly different measurements than the average temperature of our Earth’s surface. Seemingly small global temperature increases of two to five degrees Fahrenheit may cause superstorms like Hurricane Sandy and Katrina to occur more frequently [1]. Even greater increases will cause flooding in coastal cities due to rising sea levels. On top of these highly visible impacts, increasing temperatures are causing more obscure — but still immensely dangerous — problems. Imagine subsisting on a diet consisting solely of white rice and Coca-Cola. After a few days, you would likely begin to feel weak and ill without the nutrients necessary for maintaining your body. The wellbeing of all mammals, including humans, is dependent on their ability to acquire sufficient amounts of food and nutrients. For herbivorous mammals, these intrinsic properties of food are especially important, since many consume plants that contain plant secondary compounds (PSCs) [2]. PSCs are toxic compounds that plants produce in order to deter pests and consumers, such as insects and herbivorous mammals. Under no heat or cold stress (or no temperature extremes), herbivorous mammals can, to an extent, metabolize and detoxify plant compounds. However, with rising global temperatures, plant secondary compounds may become much more toxic and difficult for herbivores to metabolize. In the years to come, this phenomenon, known as temperature-dependent toxicity, may devastate herbivorous mammals across the globe.

DANCING WITH DEATH: THE DETRIMENTAL EFFECTS OF ERGOT ALKALOID POISONING In 1518, a strange plague struck the city of Strasbourg, France. It all started when townspeople observed a woman convulsively dancing through the streets. Soon after, somewhere between 50 and 400 more citizens joined the woman in her frenzied dance, and after continuing for several days, many of those infected died [3]. While contemporary physicians and clergy attributed the plague to demonic possession or witchcraft, today, many suspect that the “dancing fever”

was in fact caused by an extreme case of mass ergot fungi poisoning [3]. Ergot are a group of fungi that commonly infect grasses and cereals such as rye, barley, and many varieties of wheat [4]. The re l at i o n s h i p between the fungi and the grass is mutualistic, meaning that both species benefit from the fungal infection; the fungus obtains nutrients from the plant, while certain chemicals produced by the fungus shield the plant from predators. These chemicals, created by ergot and other fungi such as Epichloë, are known as ergot alkaloids [4]. While ergot substances proved fatal for the people of medieval Strasbourg, they are often used today for therapeutic purposes and vary considerably in toxicity. Ergot alkaloids are often found in drugs used to treat Parkinson’s disease, migraines, and hemorrhaging [5]. In fact, ergot alkaloids are even found in LSD, a common psychedelic [5]. Although the ecological roles of ergot alkaloids are still poorly understood, evidence suggests they protect fungi and host plants from insects and other predators [5]. In essence, the ergot acts like a guard dog for the grass; in exchange for the protection offered by the dog’s fearsome jaws (i.e. the ergot alkaloids), the owner provides the dog with food and shelter. What, then, gives some ergot alkaloids their bite?

AGROCLAVIN: AN INSIDIOUS TOXIN Many ergot alkaloids are powerful toxins that can

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

A Hot Issue

damage mammalian nervous and cardiovascular systems. Agroclavin, a common ergot alkaloid that is both cytotoxic and neurotropic, is one such toxin [5]. Cytotoxic compounds kill cells, and neurotropic ones infect and damage specifically nerve cells, resulting in lasting damage to the nervous system. Agroclavin works by latching onto and activating dopamine receptors, while simultaneously blocking serotonin receptors [6]. This results in an excess of dopamine. Studies conducted on mice and livestock have shown that excess dopamine can impact a wide range of bodily functions, ranging from memory creation to reproduction [6, 7]. Excess dopamine suppresses the reproductive hormone, prolactin, which plays a critical role in the final stages of pregnancy and birth. In horses, prolactin is essential in letting a mare’s body know when it is time to give birth [5]. While agroclavin and other ergot alkaloids inflict devastating effects on mammals at standard temperatures, studies show that extreme temperature changes can render these substances even more toxic for horses and cattle [5,7]. Notably, when extreme heat or cold stress causes ergot alkaloids to become toxic to livestock, they may induce a neurological and biochemical process termed fescue toxicosis [5, 7]. Fescue toxicosis is a dangerous condition characterized by changes in blood flow and necrosis, or death, of fat cells in livestock [4]. Studies show that horses are more resistant to fescue toxicosis and the detrimental effects of ergot alkaloids than other herbivores, such as cattle, sheep, and rodents [4].

violently vomiting. You have come down with food poisoning. When a certain food makes us sick, we often feel a strong aversion to it for months or even years after consuming it. This phenomenon, known as conditioned taste aversion, is a survival mechanism

As temperatures continue to rise, some animals will suffer the adverse effects of volatile alkaloids more than others. While scientists are attempting to develop non-toxic fungi for grasses eaten by livestock as a potential solution, ergot alkaloids form only a small portion of the toxic PSCs that are harming herbivores at alarming rates [5]. Since livestock are commercially important, it is vital to prevent PSC poisoning. Without the costly funding of innovative treatments, other herbivores will need to adapt and fend for themselves.

FOUL TASTES: MARSUPIALS AND THE DETECTION OF TOXIC JENSENONE Imagine that you are dining on your favorite dish at your favorite restaurant. It’s a meal you have eaten dozens of times; as you pick up your fork, your mouth waters in anticipation. However, when you arrive home, you proceed to spend the next four hours

that trains our bodies to avoid damaging substances before they can cause us harm [8]. Taste aversions occur in many different mammal species, and studies have shown that some herbivorous marsupials use

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

A Hot Issue

them to minimize the ingestion of toxins.

amounts of food and obtain more nutrients.

Common brushtail possums, ringtail possums, and koalas are marsupials that consume large quantities of Eucalyptus leaves. Eucalyptus contains jensenone, an organic compound that can cause damage to the marsupials that consume it. When marsupials eat jensenone, it binds to molecules in their gastrointestinal (GI) tract, disrupting metabolism and leading to symptoms such as nausea, anorexia, and malaise [9]. This is because, before it can be metabolized or sequestered to other tissues, jensenone conjugates (or combines with) various compounds that stimulate serotonin 5HT receptors [9, 10]. Serotonin is a neurotransmitter commonly found in GI tract cells and is responsible for modulating a variety of bodily functions, including mood and appetite. However, excess concentrations of serotonin in the GI tract can induce nausea and vomiting by stimulating the vagus nerve and causing the abdominal muscles and diaphragm to contract [9, 10]. The vagus nerve runs directly from the brain to the digestive system and regulates many essential bodily functions, including heart rate, digestive movements, and the gag reflex. Similarly to how we become averse to certain foods after they make us vomit, marsupials develop a transient aversion to jensenone compounds after they stimulate nausea [8]. These taste aversions may play a role in how common brushtail possums — and other animals — determine and mediate toxin levels in their diets.

Scientists have sought to expand upon research concerning diet selection by studying marsupial feeding habits in more realistic environments. Specifically, more recent studies account for other environmental variables, such as predation risk and varying toxin concentrations in plants [12]. In a 2011 study, researchers performed an experiment in which possums chose between a non-toxic food in a risky predation region, or foods with one of five varying toxin concentrations at a safe predation region [12]. The study showed that if toxin amounts increased in food found in the safe areas, possums would start migrating to riskier areas to feed [12]. In another study, the interplay between predation risk and plant toxin effects on food intake was similarly tested, and results confirmed that both factors influence possum foraging behavior [13]. These findings suggest that some herbivores are capable of analyzing and comparing two different costs when feeding, similar to the cost/ benefit analyses we might perform before making an important decision. The animals then adjust their feeding behavior to respond to the apparent risks.

A PICKY EATER: THE SELECTIVE DIET OF THE COMMON BRUSHTAIL POSSUM In the past few years, researchers have investigated how exactly toxin concentration interacts with the foraging choices of various herbivorous mammals. One study asked whether the common brushtail possum alters its feeding behavior in order to increase its capacity to detoxify benzoic acid, a common PSC [11]. Possums are known to conjugate jensenone with amino acids in order to metabolize them more rapidly [11]. By extension, scientists theorized that possums may select diets that help detoxify other PSCs faster [11]. Furthermore, researchers questioned whether possums are capable of recognizing excess toxin amounts in their diets, triggering nausea and vomiting in response [11]. This same study also found that the amount of food possums could eat varied, depending on how quickly they could detoxify PSCs in their diet [11]. By altering their diets to break down toxic compounds faster, possums can potentially eat larger

As increasing temperatures begin to alter the nutrient composition of plants, the brushtail possum’s ability to select its diet may prove useful in its ability to adapt to changing nutrient availability. However, warmer temperatures may have devastating effects on all herbivores and their abilities to metabolize PSCs, regardless of their feeding behavior.

THE HEAT DISSIPATION LIMIT HYPOTHESIS: TROUBLE FOR HERBIVORES If you pass by a lake or a stream on a sweltering summer day, you might see a lizard cooling itself on a shady rock or a snake slithering underneath a dark bush. Reptiles like lizards and snakes are known as ectotherms, meaning they use external sources, such as a warm rock or a patch of cool grass, to regulate their body temperatures. In contrast, all mammals are endothermic, meaning that they generate and regulate their body temperature internally when they expend and generate energy. A significant portion of energy expenditure in mammals occurs through routine bodily functions, such as liver metabolism. In fact, liver metabolism is responsible for nearly 25% of heat production in mammals [14]. Scientists posit that any kind of energy expenditure generates heat, which poses a risk of hyperthermia, a potentially deadly condition in which an animal’s body absorbs more

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

A Hot Issue

change is rendering PSCs more toxic.

IMPLICATIONS FOR OTHER HERBIVORES In the past decade, a theory has emerged regarding how herbivore livers detoxify PSCs. Think of the liver as a large wastewater treatment plant. As polluted water enters the facility, various different filters sort out and break down the largest and most visible pollutants. The polluted water then continues through the facility as the pollutants are gradually purged from the system. Scientists theorize that when a brushtail possum consumes a variety of PSCs, different compounds are metabolized in distinct detoxification pathways at the same time [15].

heat than it is capable of dissipating [14]. Therefore, animals are constrained in their ability to expend energy [14]. This theory is referred to as the heat dissipation limit hypothesis [14]. Studies show that for herbivores, metabolizing toxic PSCs in the liver results in increased heat production [14]. If PSC detoxification increases body heat to the point where the animal can no longer dissipate it, hyperthermia may occur. To account for these dangerous increases in body heat, liver metabolism slows which causes the animal’s ability to break down toxic PSCs to decrease. [14]. Further research suggests that PSC toxicity may be related to the interplay between the animal’s body temperature and that of the environment. In one study, scientists investigated woodrats that consumed juniper, a tree containing high levels of toxic PSCs [2]. Researchers found that body temperatures of woodrats that consumed a juniper-containing diet at a higher temperature were higher than body temperatures of woodrats that consumed a junipercontaining diet at lower temperatures [2]. These findings may suggest that as temperatures increase, other PSCs, in a similar fashion to juniper, may be more harmful to herbivorous mammals at warmer temperatures. Researchers have determined that PSCs take a significant amount of energy to detoxify and can cause neurotoxicity or disrupt nutrient intake. Therefore, studying the mechanisms that herbivores have evolved to detoxify and cope with plant toxins is imperative to understanding how exactly climate

Dose-dependency — the relationship between the amount of a substance consumed and its effects — may also play a role in herbivore diet selection [8, 16]. For instance, if the effects of a drug increase with gradually higher doses, that drug would be considered dosedependent. When herbivores experience harsh postingestive consequences, such as nausea or vomiting, they will be more inclined to avoid eating the food that resulted in the negative result. This passing avoidance behavior is termed a transient aversion. Animals that eat less of diets with high jensenone concentrations are conditioned to develop more detrimental postingestive effects, due to the ingestion being an irregular occurrence [8]. This finding suggests that aversions to toxic compounds in herbivores are a conditioned response rather than a physiological inability to detoxify PSCs. Therefore, there is likely a degree of plasticity involved in a herbivore’s ability to cope with changing concentrations of toxins in their environment, via acquired behavioral responses such as taste aversions. In all, knowledge of these underlying biochemical and neurological mechanisms is critical to understanding how foraging herbivores navigate diet choices. Furthermore, evidence suggests that specialist and generalist herbivores may differ in their ability to process toxic PSCs. Studies show that specialist herbivores, which consume a very narrow range of food sources, may detect PSCs more quickly than generalists that eat a wide variety of different foods [17]. On the other hand, generalists, such as the brushtail possum, proved to be far more capable

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

A Hot Issue

than specialists at regulating and adjusting their meal sizes to respond to PSC levels in food. Since specialist herbivores struggled to modulate their PSC consumption, they experienced more cell and nerve damage [17]. In other words, global warming could impact generalist and specialist herbivores at different rates, based on the species’ ability to recognize and process the changing amounts of toxins in their food.

FOOD FOR THOUGHT

tackling this crisis will require a better understanding of how animals regulate their food intake and detoxify PSCs. Conducting comprehensive research on these topics is urgent. Although the crisis of global warming will eventually impact all life on Earth, herbivores appear to be particularly susceptible to its ravages. As temperatures rise, herbivorous mammals including livestock, mice, voles, possums, and many other animals will continue to experience the effects of temperature-dependent toxicity.

Currently, research regarding how elevated temperatures affect PSC toxicity is still in its infancy. While evidence shows that some herbivores can adapt to cope with toxins, others may struggle to alter their feeding behaviors. The effects of rising temperatures on PSC toxicity are quite complex, and

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

A Hot Issue

DEFYING THE “WAR ON DRUGS”: THE REBIRTH OF PSYCHEDELIC MEDICINE & RESEARCH by Nick Beebe / art by Cherrie Chang

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Defying The "War On Drugs"

idely recognized by U.S. historians as igniting the “Summer of Love” (1967), San Francisco’s “Human Be-In” gathering made for anything but a typical day; more than 30,000 hippies flooded the Golden Gate Park in what ultimately became a defining moment for America’s counterculture movement. United by support of nonviolence and primary disdain for the U.S.’ role in the Vietnam War, hippies resulted during the 1960s as predominantly young Whites (ages 15–25) fully ‘dropping out’ of their everyday lives. One participant of the demonstration himself, Dr. Timothy Leary, psychologist and prominent LSD advocate, first vocalized the phrase “tune in, turn on, drop out.” In his signature soft-yet-monotone voice, this simple saying would soon blossom into an iconic saying amongst psychedelics users and the collective counterculture movement [1]. To the delight of its everyday supporters alongside hopeful scientists, including the late Dr. Leary, psychedelics are experiencing an enthusiastic rebirth across various healthcare systems. In the past, psychedelics (also known as hallucinogens) had stood as a promising “North Star’’ within U.S. medicine; however, the eclectic array of wavy chemicals saw its luster vanish just as the Nixon administration (1969– 1974) anchored itself to a fervent anti-drug attitude. With the government’s “War on Drugs” surging ahead, the Nixon administration illegalized drugs to thwart the anti-establishment mentality sweeping the country [2,3]. As evidenced, the inexplicable allure of psychedelics is enough to instigate its use amongst humanity— from recreational use to scientific investigation. Most notably, their current return results from an entirely new psychedelic-based practice: microdosing. Even in just partial dosage (a microdose), their ‘rebirth’seeking clientele spreads far—from the innovative architects of Silicon Valley to the ceremonial yogis leading spiritual retreats [4–6]. Until recently, few researchers were permitted to revisit the past studies that had halted following psychedelic criminalization. Of the few psychedelic trials allowed to occur from the early 1970s until the late 2000s, most centered on rodent test subjects in preclinical contexts [3,7,8]. In stark contrast, studies of psychedelics — including psilocybin (the key compound of magic mushrooms, or “shrooms”), MDMA, and LSD — have finally entered into the clinical stages. Emerging evidence continues to highlight the drug class as game-changing for the treatment of various conditions, many of which are neuropsychological [9,10]. Despite the legal

suppression psychedelics have faced, they continue to mesmerize and modify users’ minds. Recent studies of psychedelics have even helped researchers pinpoint some cognitive processes to specific brain regions [11]. Ultimately, current psychedelics research aims to alter and expand the scope of emerging medicine [12]. But is the world really ready for psychedelic-infused healthcare?

Psychedelics: Beyond Woodstock & Tame Impala As is the case with most drugs, psychedelics have a complex history shaped by numerous sociocultural pressures. In regards to their origin(s), lies persisting across mainstream society still allow some to deem the emergence of psychedelics as a spontaneous “flower child” of the counterculture age. In reality, however, the first humans to interact with psychedelics were Indigenous populations, who have incorporated entheogens (plant-based psychedelics) into religious and ceremonial practices for centuries (and counting) [4,5]. Additionally, in the medical sector, psychedelics were incorrectly classified as “psychotomimetic,” implying that their use would invoke psychosis, or the alteration of the brain’s connection to reality. Naturally, this was able to overwhelmingly instill fear, panic, and consequent objection throughout the American public. However, as recent research refutes, any continuing association between psychedelics and psychosis stems from baseless assumptions [13,14]. In other words, psychedelics pose nearly none of their once-expected threat — provided that they are used under appropriate professional supervision. Continued research has demonstrated that the toxicity of psychedelics is relatively low, meaning that these drugs may not be associated with oncefeared adverse health conditions (e.g., organ damage, overdose fatality, and cancer instigation) [15]. The success behind psychedelic administration also lies in the compiled testimonials that confirm these drugs promote unmatched changes in brain function and personality. In particular, improvements have best been demonstrated amongst individuals with major depressive disorder and post-traumatic stress disorder (PTSD) [2]. Regardless of the success of short-term clinical studies, much still remains uncertain about the long-term effects of psychedelics. As such, the gap spanning between possible and known information has been deeply perpetuated by widespread restrictions on access to psychedelics for the purpose of performing knowledge-expanding research.

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Defying The "War On Drugs"

“Biohacking” by Microdosing In recent years, there has been a significant uptick in “biohacking,” or the process of developing one’s optimal self through the use of particular drugs, vitamins, and exercises [6]. One of the various “biohacking” practices gaining traction is the act of microdosing. Microdosers take psychedelic drugs, often several times a week, in small amounts to prevent a “trip.” Typically, this dosage level falls between 10–20% of any particular drug’s “normal” dose [16]. Similarities between user reports collectively suggest that microdosing can elevate cognitive performance, creativity, and productivity [16]. However, more clinical research is needed to explore these claims empirically. One recent survey-based study with over 2,400 microdosing participants determined that those identifying as male were nearly twice as likely to microdose than females—and that tech industry workers and retired people were most likely to partake [17]. With the bounds of technology rapidly expanding, employment within this sector might overwhelm one’s creative abilities and cause them to microdose—though it is not entirely certain why retirees also prominently microdose. Furthermore, of 393 microdosers, nearly half reported using LSD, followed by psilocybin (~25%) and MDMA (~12%). Many in this pool also reported improvements to depression (~72%), sociability (~67%), increased focus (~59%), and decreased anxiety (~57%) following microdosing [17]. However, these rates are self-reported, meaning they only represent participants’ perceptions of their own experiences. Aside from these initial reports, very little is known about microdosing — particularly its effects, both during and after the duration of dosage [18,4]. One recent source shares that a participant’s optimism regarding microdosing treatment may impact its outcome, demonstrating one of the many variables relevant to developing effective psychedelic treatments [18]. Nevertheless, it has proven exceedingly difficult to decode the neurobiological mechanisms responsible for psychedelics’ beneficial impact on cognition with certainty. Due to the abundant ambiguity, some argue that these drugs are veering towards gaining the status of a panacea — a hypothetical remedy for all diseases and difficulties — despite the lack of scientific support for this position [19]. However, due to legal constraints, research into psychedelic drugs remains far from comprehensive. Researchers can rarely investigate beyond the most common drugs and

have visibly failed to study the newest psychedelics of all: new psychoactive substances (NPS) [20,21]. Regardless of one’s stance, further research must be conducted on the use of psychedelics and NPS, particularly through microdosing, in order to assess their medicinal properties. To develop a consistent understanding of the potential benefit held within these drugs, additional supporting research is needed to decode them — most urgently being the substances most commonly used by microdosers: LSD, psilocybin, and MDMA (sometimes incorrectly referred to as “ecstasy”).

LSD In an attempt to mirror the positive effects of plant-based ergotamine—once widely used to treat migraines—practicing drug manufacturers of the early 1900s began searching for synthetic molecules to act as superior medicines [22]. Swiss chemist Albert Hofmann was able to extract one portion of ergotamine’s dense structure: lysergic acid [1,8]. Years later, Hofmann sought to mix the lysergic acid he had produced with other organic molecules to create new drugs. During his twenty-fifth trial, Hofmann was able to fuse lysergic acid with nikethamide—known commercially as Coramine, a circulatory stimulant. However, this produced an array of unexpected behaviors in test rats and was subsequently ignored [8,1]. Years later, still captivated by his creation, Hofmann unknowingly consumed an indefinite amount of LSD while handling it in the lab [9,1]. When he first realized something was abnormal, Hofmann reported “a remarkable restlessness combined with a slight dizziness” in his notebook. Shortly after, he found himself exposed to “fantastic pictures, extraordinary shapes, with intense kaleidoscopic plays of color” [1]. Much later, Hofmann was unable to even handle pen and paper to record his experienced sensations. We now know that LSD has the potential to decrease brain connectivity in ways that can last for years, potentially even impacting one’s personality (“sense of self” network, formally named the default mode network) [23,24]. This network is responsible for one’s capacity for mental time travel (the ability to think in past or future tense), self-reflection, and autobiographical memory. When these functions are disturbed, it becomes difficult for an individual to maintain their personal identity and connection with the physical world. So, should LSD temporarily skew the framework of the default mode network, a user may struggle to process the world around them, leading to

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Defying The "War On Drugs" the experience of ego dissolution (disintegration from one’s self-identity) [24,25]. This comes as no surprise, given that immediately after consumption, LSD is known to distort one’s perception of time, identity, depth, size, and shape [26]. Following its accidental creation by Hofmann, LSD would soon be used to combat addiction, anxiety, and depression in over 40,000 patients up until the mid-1960s [1]. LSD has also demonstrated success in the treatment of alcoholism and other substance addictions [15,25]. The performed studies of LSD (on participants) have ultimately permitted researchers to further understand brain systems previously regarded as entirely unrelated to each other—one example being the brain’s visual processing component; LSD increases activity in brain regions tagged responsible for creating intense and dreamlike visions [24]. Ultimately, since LSD research was restricted during the War on Drugs, we have much more to learn about the fascinating compound. The resurrection of LSD, like other psychedelics undergoing clinical trials, has been astonishing — though it is clear that future trials and literature must weigh its potential negative effects with efficacy in changing the mind for the better [24,25].

PSILOCYBIN In 1958, psilocybin was initially identified by Albert Hofmann, following its extraction from mushrooms [27]; in comparison to Hofmann’s other psychedelic ‘child’ (LSD), psilocybin is roughly 100x less potent [28]. However, the first clinical study involving psilocybin only concluded six years ago, resulting in 10 participants’ complete recovery from alcohol use disorder [9]. Today, the FDA has remarkably referred to psilocybin as a “breakthrough therapy” for the treatment of major depressive disorder, including treatment-resistant depression [29]. Most of the 30 registered trials currently studying psychedelic drugs center around psilocybin, examining its uses for treating anorexia, obsessive-compulsive disorder (OCD), addiction and substance use disorders, and depression [30,10,31]. As of 2018, similar trials also conducted with psilocybin were seeking to demonstrate its efficacy in alleviating alcoholism, tobacco addiction, and cocaine addiction [7]. In terms of tobacco addiction, two-thirds of 15 participants in a 2014–2016 study

reported sustained abstinence from tobacco use in the year following initial treatment of psilocybin-aided psychotherapy [32,33]. While the U.S. has prioritized substance abuse and depression treatment in regards to psilocybin, there are several other conditions that psilocybin may treat—including Alzheimer’s and OCD [34–36]. For example, a recent case study found that a 38-year-old male subject with OCD reported a significant decrease in intrusive thoughts following psilocybin administration, despite initially finding the drug’s immediate effects unpleasant [36]. Though this source represents just one individual’s experience, it highlights one of the many circumstances where psilocybin can assist in healing [37]. Nevertheless, many newer studies have begun to further explore the role of psilocybin for individuals facing OCD [38]. Furthermore, psilocybin has been praised for its ability to improve the quality of life of patients facing advanced or terminal cancer [39,9]. A recent study exploring this type of psilocybin use confirmed that even years following initial treatments, over 80% of participants maintained improved spirituality, positive behavior, and satisfaction. However, since most of these participants were White cancer patients, these findings cannot be generalized to individuals outside of these categories. While psilocybin shows

Defying The "War On Drugs" promise in treating numerous conditions such as addiction and depression, additional studies are needed to determine how the drug could affect larger populations [39].

MDMA MDMA, alongside LSD and psilocybin, is another example of a psychedelic with gleaming value for medicine [40]. Initially designed by pharmaceutical company Merck to control bleeding, MDMA improves one’s overall mood by decreasing anxiety, while enhancing relaxation and sociality [41,42]. However, MDMA’s legacy is tainted by its association with ecstasy. While many people believe these drugs to be synonymous, ecstasy can actually contain several other substances apart from MDMA — though this fact remains widely unknown due to the prevailing public uncertainty surrounding most things psychedelicrelated [42]. Early research in MDMA’s effect of PTSD found that over half of participants experienced relief so significant that they no longer matched the criteria for a definitive PTSD diagnosis [4]. However, the study’s participant pool contained very little diversity, especially biogeographic ancestry — a common issue within clinical research. As briefly noted above, while some forms of psychedelic therapy might work for a White person, the same methods might not work for someone of differing biogeographic ancestry [4]. MDMA actively stimulates the release of neurotransmitters and hormones known to enhance prosocial behaviors, such as serotonin, oxytocin, and vasopressin. Psychiatrists have found numerous positive effects linked to MDMA-aided psychotherapy for patients with PTSD, including sensory intensification, increased emotional awareness, slight ego dissolution, and changes in interpersonal relationships [43]. Traumatic events are often followed by a critical period, a brief time span where the brain is more plastic (or subject to potential change[s]). Irreversible neuronal changes can occur during this period, however, meaning MDMA’s therapeutic success (for PTSD) may decrease with the passage of time. However, study participants receiving MDMA during the critical period reported elevated feelings of closeness and trust [41]. This means that MDMA, even when administered during one’s critical period, can still assist PTSD treatment. Closeness and trust, particularly, can prove vital to treatment success as they enhance patient-therapist bonding [41]. As such, MDMA-aided PTSD psychotherapy may help

patients overcome the complex mental barriers that commonly already challenge PTSD treatment. Individuals with PTSD construct internal boundaries to protect themselves from experiencing the intense negative e m o t i o n s that typically accompany the memory of traumatic events—and MDMA works to help unravel them. Undoubtedly, dissolving these boundaries with MDMA treatment offers an incredibly novel clinical approach to PTSD therapy [41]. Of a study devoted to MDMA-aided psychotherapy with participants of color, one participant memorably remarked that MDMA might be the best catalyst for those with PTSD to “push things along [and] enjoy their lives again” [4]. Given these positive clinical trials, approval of MDMA for medical use is likely to occur around in the next year or so, depending on the pandemic’s impact on research execution [42].

HOW WILL WE NAVIGATE PSYCHEDELIC MEDICINE? Supported by the results of pertinent past work, the future of psychedelic medicine appears promising, though its trajectory remains vastly uncertain. Given the resistance that cannabis legalization has faced in the past decade, pushback is almost expected [17]. Along those lines, a collaborative recentering of mainstream attitudes towards potentially drugs with potentially restorative benefits is desperately needed. As psychologist Dr. Jamilah George, of the Multidisciplinary Association for Psychedelic Studies (MAPS), admits: “I’ve always seen drugs as dangerous, leading to violence and incarcerations[—n]ever something… as a means [of] healing” [43]. The intensive and holistic studies of psychedelics available infer that the body’s psyche wants to recover from traumatic experiences, much like how one’s immune system

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Defying The "War On Drugs" tends to a physical wound. However, the complex nature of the human psyche does not succinctly signal where one most needs a neurobiological bandage; this is the basis for psychotherapy which, in the presence of psychedelics, displays deeper and swifter strives. As with any drug, it is imperative to examine potential risks before choosing to experiment. Nearly one in twenty individuals (~5%) reported self-directed psychedelic use as a means of treatment reported v i s i t s to the emergency department [44]. Though not a significant portion of the population, this statistic still exhibits that a “trip” (from any psychedelic) can force a user to hail medical attention. Since the outcome of a “trip” relies on a multitude of variables (e.g. biochemical, neurocognitive), it might be impossible to weave common threads through this small subgroup of users. In this regard, researchers may opt to rely on mechanisms, like scales, to derive numeric values from qualitative, intangible elements (e.g. personality, upbringing). However, one variable to certainly account for in this context is a user’s dependency on their psychedelic(s) of choice.

tripping [28]. With clinical steps being made towards FDA approval, addiction rates may vary [20,7]. Though relatively rare, a hallucinogen use disorder (HUD) arises with one’s extensive use and experienced addiction to any psychedelic(s); even if addiction does not occur, prolonged psychedelic use may pose other severe neural impacts. For example, hallucinogen persisting perception disorder (HPPD) results when someone who has used psychedelics prior experiences extended visual hallucinations, similar to the distorted visual effects brought about by one’s use of psychedelics. The condition is most exaggerated for users of LSD and can be bolstered by stress, anxiety, exercise, or the use of other drugs [12,7]. With all of this in mind, it is imperative to continue clinical research to grow the understanding of psychedelics to create guidelines for all use to be safe. An important thing to remember is that the clinical use of psychedelics is more often than not done alongside psychotherapy. That said, findings surrounding unassisted, self-administration of psychedelics have not yet reflected positive psychological benefits [45]. Leaving the administration of psychedelics to users could easily prompt abuse. Instead, the drugs have been successfully used to enhance physiological exploration within controlled therapy settings. With the country’s first legal psychedelic product coming in the form of fruity seltzers (and on sale now), it is clear that this drug class will likely remain prominent in the coming years, in various forms. Thus, the question still remains: are we ready for a psychedelic future? While we have much to learn about these distinctive drugs, the literature to-date significantly speculates an encompassed role of psychedelics within future medicine—though there is certainly no telling what that may look like.

The Substance Abuse and Mental Health Services Administration recently concluded that although some psychedelic addiction exists in younger users (particularly those just entering adulthood), addiction in people over 25 is very rare. Considering the near-doubled rate of psychedelic use in America’s young(est) adults (ages 18–25), it is essential to understand what factors are motivating any use of psychedelics—from sporadic microdosing to intense

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Depression and Anxiety

DEPRESSION AND ANXIETY: THE FRENEMIES NO COLLEGE STUDENT WANTS TO MEET by Kaiya Bhatia / art by Ayane Garrison

renemies. We all know Jim and Dwight from The Office, or Perry the Platypus and Dr. Doofenshmirtz from Phineas and Ferb. Each side of these pairs has opposing agendas, but like all good frenemies, they occasionally work together to help one another out. College students, however, deal with a different kind of frenemy relationship: one that lives inside their heads. The most common and insidious pair of frenemies present in the lives of college students is anxiety and depression, a difficult and sometimes deadly duo. The energetic volatility of anxiety versus the dull monotony of depression ignites a fierce rivalry within the host’s mind. And yet, each condition makes us more vulnerable for the other’s attack on our neural systems. For example, imagine you get anxious about failing your upcoming test, making you question if you’re prepared enough or how you might fare. In turn, you may begin to fear that you have no chance of passing the exam at all, leading you to feel hopeless and lost. These swells of depression may then render you unmotivated to study, compounding your initial anxiety of failure [1]. This cycle repeats itself over and over, enabling anxiety and depression to feed off of each other, ultimately

leaving you paralyzed. It is a selfdefeating, self-fulfilling prophecy — one that can lead to fatal consequences if misunderstood.

THE DIAGNOSES

While depression and anxiety exist in many different forms, college students are most commonly diagnosed with Generalized Anxiety Disorder (GAD) and/or Major Depressive Disorder (MDD). GAD is characterized by persistent and excessive worrying that is difficult to control, usually without apparent or rational cause for concern [2]. Experiencing these symptoms over a period of six months warrants an official diagnosis of GAD. MDD, on the other hand, is characterized by a period of at least two weeks of depressed mood or loss of interest. Related symptoms of MDD include issues with sleep, eating, energy, or concentration [3]. The “frenemy” relationship between GAD and MDD is clinically referred to as a comorbid relationship, which

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Depression and Anxiety this relationship actually plays a significant role in the college mental health crisis, as a recent study found an astronomical 29.8% of college females and 13.9% of college males are diagnosed with both GAD and MDD [6]. As comorbid GAD and MDD diagnoses are associated with much greater impairment compared to that of just one of the conditions alone, identifying and exploring this comorbidity is essential to providing better treatment to those affected. A recent study has sought to address this lack of research attention on comorbidity, delving into the impact of comorbid GAD and MDD on college students’ wellbeing [6]. Researchers found that those who screened positive for both of the two psychiatric disorders showed a significant decrease in quality of life as compared to those diagnosed with either one [6]. One of the main explanations for this phenomenon lies in the cognitive impairment associated with comorbid MDD and GAD. The combination of MDD and GAD makes individuals generally more inclined to express negativity towards day-to-day problems. The overthinking and self-doubt characteristic of GAD are compounded, causing the individual to overassess a problem, leading to increased anxiety [7]. All the while, MDD stirs up feelings of hopelessness towards the issue at hand [7]. And, even beyond these affective symptoms, researchers also found that college students with comorbid MDD and GAD show cognitive impairments, despite their constant need to harness cognitive skills. These impairments often cause students to struggle with school work and other daily tasks, likely leading to an increase in stress. This build-up of stress significantly worsens the patient’s primary condition and quality of life. describes one or more additional conditions that exist with a primary condition; in this case, the primary condition can be either MDD or GAD.

THE COLLEGIATE MENTAL HEALTH CRISIS GAD and MDD are the two most common mental health issues reported in college students, affecting 41.6% and 36.4% of students, respectively [5]. In fact, their presence is much more prevalent on college campuses than anywhere else in the country — a mere 2.7% of adults in the United States are estimated to have GAD, and only 7.1% are diagnosed with MDD [2, 3]. Interestingly, even with the overwhelming prevalence of both disorders in college students, this comorbidity is often overlooked in the investigation of mental health on college campuses [6]. However,

While this combination of symptoms would make it difficult for anyone to deal with arising problems, college students can become especially frustrated and burnt out, as their academic and social environments push them to confront urgent and intellectually complex issues every day. As such, to deal with this emotional distress, college students with GAD and MDD often also develop a tendency for cognitive avoidance — the process of avoiding or eliminating negative thoughts — leading to high levels of overall thought suppression [7]. This is cause for concern, as college students are expected to reflect on highly conceptual material both in and out of the classroom. The college experience of comorbid GAD and MDD is presenting major barriers to academic success and emotional well-being.

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Depression and Anxiety

GAD & MDD BRAIN CHEMISTRY Before we consider how to treat these comorbid disorders, we first need to understand the key players involved. Brain chemistry refers to the activity of neurotransmitters and their effects on behavior or brain functioning. Neurons are a type of brain cell that communicate using neurotransmitters — chemical messengers that each serve a distinct purpose. These molecules are released by one neuron, the presynaptic neuron, and attach to the receptor of another, the postsynaptic neuron, resulting in either an inhibitory or excitatory response. This process is like receiving a letter in the mail, containing information regarding your future plans. The news could be disappointing, making you less likely to go through with your plans, or it could be exciting, preparing you to move forward. In this analogy, the letter is a neurotransmitter; inhibitory neurotransmitters render the postsynaptic neuron less likely to send a signal after the neurotransmitter binds to its receptor, while excitatory neurotransmitters make the neuron more likely to do so. Gammaaminobutyric acid (GABA) and serotonin are the two major players in the brain chemistry of anxiety and depression. A new focus of research regarding GAD and MDD treatment centers around GABA. Recent studies have found that increased presence of GABA can have both antidepressant and anti-anxiety effects [8]. To achieve an anxiolytic effect, GABA binds to receptors on neurons in the amygdala, a brain region responsible for our fear and stress responses, inhibiting signals of fear and stress [9]. However, patients with anxiety have a decreased abundance of GABA receptors, meaning that they are less likely to get this antianxiety effect in their system [10]. Benzodiazepines are one of the most common treatments for anxiety, working to correct this imbalance by helping GABA neurotransmitters inhibit the postsynaptic neuron. By doing this, the benzodiazepines work to reduce anxiety

effects within an individual. This medication has been used for 50 years to treat anxiety, and, while effective, it also raises concerns for long-term dependence and sedative effects [9]. In contrast, our understanding of GABA’s role in MDD

has been much more recent. Unlike in anxiety disorders, we do not see a change in GABA receptor abundance in patients suffering from MDD. However, this does not mean GABA has no role in MDD. On the contrary,

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Depression and Anxiety there is significant evidence showing patients with MDD to have overall reduced levels of GABA in brain regions such as the amygdala [10]. Furthermore, there is evidence that those with MDD may have an altered gene expression for GABA receptors as well [10]. Our current treatments for depression do not target the GABA system, but still increase inhibitory signals [11]. Researchers have proposed that targeting GABA receptors will help reduce depression, as the inhibitory nature of GABA may help slow down the cognitive processes involved with depressive thoughts [11]. While the specific mechanisms involved with GABA in MDD are not completely understood, related research still conveys the need for future antidepressants to correct neurological chemical imbalances rather than the symptoms themselves [10]. Serotonin’s role in MDD, on the other hand, is much clearer. Serotonin is important for regulating the mood, well-being and cognition of an individual. This inhibitory neurotransmitter has been consistently implicated as a cause for MDD but has not yet been strongly linked to GAD. Despite these differences in links, selective serotonin reuptake inhibitors (SSRIs) are still the starting point for the treatment of comorbid GAD and MDD. SSRIs work to influence the concentration of serotonin in the brain [12]. When neurotransmitters are released, SSRIs enter into the space between the presynaptic and postsynaptic neuron, known as the synaptic cleft. After some time, the neurotransmitters are absorbed back into the presynaptic neuron to be recycled. SSRIs work to prevent this reuptake so that more serotonin is present in the synaptic cleft, increasing the neurotransmitter’s effectiveness in the postsynaptic neuron. However, as mentioned earlier, despite the success SSRIs have had with treating GAD, serotonin’s role in the disorder is not very well understood. Our best inferences on the role of serotonin in GAD come from looking at how SSRIs work to treat GAD. For example, a recent study found that the use of SSRIs in anxiety and depression treatment normalizes amygdala activity in the brain, as well as a decrease in activity in the limbic system (i.e., the region responsible for emotion) [13]. These changes were seen to cause a reduction in anxiety symptoms experienced by individuals. This suggests that reduction in activity is a potential mechanism of anxiety reduction. However, that the observed effective treatment of GAD with SSRIs is more of an accidental action than an intentional action of the drugs, further understanding of the mechanisms and serotonin’s role is still needed.

Serotonin is arguably the most famous of the neurotransmitters implicated in MDD. The serotonin hypothesis was first proposed half a century ago, stating that decreased activity of serotonin pathways has a causal role in the pathophysiology of depression [14]. Like many hypotheses developed in psychiatry, the study claimed that the condition is caused by serotonin because we see that a drug involving serotonin is an effective treatment. While we cannot outright refute this hypothesis, as it does hold some truth, we need to acknowledge that MDD is not likely an issue due to the activity of a single neurotransmitter. The reason this can be said is because SSRIs do not work for everyone, suggesting that there are other neurotransmitters at play here (e.g. GABA).

COMORBID MDD & GAD TREATMENT One of the biggest issues we face in the treatment of depression and anxiety is the lack of knowledge surrounding the nature of their comorbidity. Generally, researchers believe that the high prevalence of both GAD and MDD suggests there are commonalities in their causes. However, our current pharmaceutical tactic for treating GAD and MDD is to throw different drugs at the symptoms and hope that one sticks (without making any symptoms worse). The intention of this treatment is to reduce symptoms to allow the individual to improve functionality. However, the presence of one disorder often reduces the efficacy of treatment for the other, creating a tricky situation [15]. Thus, the first step towards effective treatment is being able to recognize the presence of a comorbidity, which increases chronicity and recurrence, and typically requires long-term pharmaceutical treatments [16]. Incomplete diagnoses, likely due to the symptom overlap associated with the disorders, may result in incomplete treatment. As such, the recognition of these conditions is essential in guiding treatment plans. When considering medication to treat comorbid anxiety and depression, experts flock to SSRIs as their primary treatment option [16]. However, as we have discussed, SSRIs do not work for everyone. Furthermore, we see antidepressants improving symptoms for each disorder alone, but are such results enough to ensure that antidepressants will effectively treat both illnesses at the same time? It’s a difficult question to answer conclusively, yet it certainly highlights the need for more research concerning MDD and GAD treatment. As of now, treatment research for comorbidity is lacking, and there is no existing medication that

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Depression and Anxiety

works to treat comorbid anxiety and depression [16]. Our current void in research suggests that our attempt at treatment is a patchwork of guesses with hints of understanding. Therefore, furthering our understanding of the similarities between GAD and MDD, as well as their differences, may help us improve treatment availability for the future.

LOOKING AHEAD With so much uncertainty in our current understanding of comorbid depression and anxiety, it’s no wonder we are struggling to treat patients. Our tunnel-vision, symptom-based approach to treatment has blinded us to the significance of comorbidity, especially in the case of comorbid MDD and GAD. Yet, it’s also true that there is no easy fix. The collegiate mental health crisis won’t magically resolve itself with a few days

off for student wellness or an email encouraging selfcare. A solution relies on recognizing the importance of comorbid conditions and redefining our focus, not just pharmaceutically. There is a crisis that is leaving a significant portion of college students emotionally and cognitively impaired, and we can only alleviate the stress of their conditions by addressing the issue headon. It may be unrealistic to implore every institution to divert resources towards funding treatment for comorbid GAD and MDD. However, it is necessary to ask schools to reconsider how they help students manage their symptoms, so that they may improve their emotional and academic well-being, and steer clear of these frenemies for good.

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Brain Busters

BRAIN BUSTERS by Ally Thayer / art by Sophie Sieckmann

n 2013, the Obama Administration launched the BRAIN Initiative: a research effort aimed towards understanding how the human brain functions. When he spoke at its unveiling, President Obama pointed out the largest paradox of neuroscience: “As humans, we can identify galaxies light-years away and we can study particles smaller than an atom, but we still haven’t unlocked the mystery of the 3 pounds of matter that sits between our ears.” This “mystery,” otherwise known as the brain, has intrigued humanity for millenia, as human beings have always possessed an innate curiosity and desire to understand ourselves. Many fields, such as philosophy, sociology, psychology and anthropology, have stemmed from this fascination, attempting to answer the fundamental questions of what makes us human. Neuroscience addresses these questions head on, investigating the human mind by exploring neural connections in the brain. Generally, neuroscience strives to answer: What is consciousness? How do we experience dreams and emotions? What neural factors are involved in cognition? None of these questions have a simple answer; hence, our everpresent interest in the workings of the mind. This innate human curiosity has also led to the everincreasing prominence of neuroscience in pop culture and movies. However, filmmakers often inaccurately represent the science behind different neural phenomena. For example, the movie 50 First Dates (2004) tells the story of a woman who suffers from “Goldfield’s syndrome” after an accident. Each day her memory completely resets. Goldfield’s Syndrome is a fictional condition, but it is loosely based on a combination of several real types of memory loss. The critically acclaimed film Inception (2010) is also,

neurologically speaking, inaccurate. The central premise of the movie is that while one sleeps, the dreamer can access several parallel realities and travel to other people’s dreams. Although fascinating, the events are not based on factual science. Film portrayals of complex neuroscience topics, such as dreams and memory have changed, disregarded, and even fabricated science. Because most viewers of these hit films do not have neuroscience backgrounds, they may be more inclined to believe this scientific misinformation. As a result, oversimplifications of complex neurological phenomena evolve into commonly believed myths that are eventually regarded as facts. In order to distinguish fact from fiction, I surveyed the neuroscience faculty at Vassar College, asking which popular neuroscience myths frustrate them the most. Here are the most common answers:

MYTH ONE: “WE ONLY USE 10% OF OUR BRAIN.” The idea that we don’t utilize our full brains is one of the most commonly believed neuroscience myths. Several surveys have demonstrated that 65% of

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Brain Busters Americans, 1 in 3 people with a bachelor’s degree in psychology, and more than 1 in 20 neuroscientists agree with this claim [12, 10, 9]. The idea still lingers in modern-day pop culture, as movies like Lucy (2014), Defending Your Life (1991), and Limitless (2011) use plotlines emphasizing the “untapped superpower” residing in the supposed remaining 90% of the brain. However, despite how common this belief is, it is entirely false. Many trace this myth back to Albert Einstein and William James, often referred to as the father of American psychology. Einstein has been misquoted as arguing that his above-average intelligence resulted from the ability to use more of his brain. In reality, though, Einstein never said this; but, it is very common to see quotes misattributed to him. Einstein’s brain was extensively studied after his death and it was actually found to be smaller than average;, however, he was reported to have higher-than-average numbers of a specific type of brain cell called glia [8]. William James did propose a theory that most of our brain and cognitive potential goes untapped; however, he never specified a percentage of brain use [11]. So, how did this myth get linked to James? Dale Carnegie’s best-selling book, How to Win Friends and Influence People, includes a misinterpretation of James’ work and implies we do not use all of our brain power [6]. This book was one of the first self-help books written and is considered by TIME magazine to be the 19th most influential nonfiction book written in English since 1923, meaning that many readers of Carnegie’s work likely took his misrepresentation of James’ theory as fact [18]. This myth may have also come from a misinterpretation of neurological research in the early twentieth century regarding glial cells. Glial cells are one of the two main cell types within the brain, lesser known to the general public than the other main cell type: neurons. While neurons fire to transmit neural information, glial cells act as the brain’s structural support, protecting and nourishing neurons. Several studies from the 1960s to the 2000s report a 10:1 glia-to-neuron ratio in the brain [19]. Because glial cells were thought to have no neural utility, researchers inferred that only 10% of the cells in the brain had a function. Thus, the idea that we only use 10% of our brain was born. Neuroscientist Dr. Barry Beyerstein has provided several pieces of evidence to dispute this myth. First, Beyerstein reasons that if it were true that only 10% of the brain was in use, most neural damage would have no impact on normal functioning [5]. If 90% of

the brain is inactive, most brain injuries would miss essential brain tissue and there would be no adverse effects. However, damage to virtually any part of the brain may cause personality changes, paralysis, sensory dysfunction, or the loss of language abilities. Brain imaging such as PET and fMRI (functional MRI) scans also show neural activity in all brain regions, no matter what the individual is doing [5]. This means that whether you are meditating, sleeping, or taking an exam, your brain is fully engaged. Finally, Beyerstein also makes an efficiency argument, explaining that the human brain spends 20% of the body’s total energy despite making up only 2% of the human body weight. If only a tenth of the brain is in use, devoting this much energy to the body part would be wasteful, and natural selection would have eliminated this inefficiency over the course of human evolution [5].

MYTH TWO: “DOPAMINE MAKES US HAPPY” The media often refers to dopamine as the “feel-good chemical.” However, happiness is a complex emotion and neurological topic, and there is no single chemical or brain region responsible for one’s happiness. Dopamine is a neurotransmitter, or a specialized chemical that allows two neurons to communicate. Two communicating neurons do not physically touch one another; rather, a small space, called the synaptic cleft, separates them. When one neuron is activated, it releases a neurotransmitter into the synaptic cleft. This neurotransmitter makes its way to the second neuron to activate it, and the message is passed along. The “feel-good chemical” myth arose from a 1950s study in rats by Dr. James Olds. Olds studied neurons that communicated via dopamine in rat brains; when these dopamine-releasing neurons were stimulated, Olds found that the rats were prompted to repeat the same activity over and over again, and he concluded that this repetition was due to the rats enjoying the activity [15]. It is also well known in the psychiatric community that individuals with depression have lower levels of dopamine and therefore, it is logical to connect dopamine to lower mood [3]. These theories have been disproven because animals still experience pleasure even if their dopamine neurons are killed [4]. In the late 1980s, Dr. Kent Berridge eliminated the dopamine neurons in rat brains and tested their responses to a sugar solution. He discovered that these rats, despite not having dopamine neurons, still showed signs of enjoyment and pleasure similar to the rats who had intact dopamine neurons [4].

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Brain Busters If dopamine is not responsible for happiness, then what exactly is its role in the brain? Today, dopamine is thought to be involved in motivational behaviors [1, 7]. Because motivation can appear similar to pleasure and happiness, it can be easy to confuse them. But neurons that use dopamine aren’t actually telling us that we like performing an activity or task; rather, they are

communicating that we should do or pursue that activity again. This is essentially the difference between wanting something and liking something, and it is especially clear in individuals with depression. Depressed people are often less likely to pursue social interactions, but this is not because they do not enjoy the company of others. In fact, they might still appreciate time with friends, but the effort needed to engage in social situations might prevent them from joining in. Similarly, people and animals with low levels of dopamine are less likely to work for a reward. Therefore, this behavior is more of an internal debate on how to spend one’s time and energy than a reflection of personal enjoyment. Interestingly, dopamine also plays a large role in drug addiction, as many addictive drugs cause dopamine levels in the brain to increase by promoting more dopamine release from neurons [20]. You may have heard the term “dopamine rush” and associated it with a rush of happiness. However, a dopamine rush is actually a rapid increase in dopamine that instructs your brain to seek out whatever caused the surge more frequently, motivating the brain to overcome boundaries to access the source of the rush. In the case of drugs, the powerful motivational force of an extreme dopamine rush can compel a person to pursue a substance no matter how serious the obstacles and consequences are . For some, this can mean life or death — especially those most vulnerable to developing substance use disorders or addictive behavior patterns. So, no: dopamine may motivate us,

but it certainly does not always make us happy.

MYTH THREE: “RIGHT VS. LEFT-BRAINED PEOPLE”

Another common neuroscience myth exists in the classification of people as either left-brained and right-brained. This idea is based on the brain’s two hemispheres and posits that people who think more logically, linearly, and sequentially (often excelling in science and math) have a dominant left hemisphere, while people who think more visually, imaginatively, and holistically (often excelling in the arts) have a dominant right hemisphere. This myth originated from the work of neurologist Dr. Roger Sperry, winner of the 1982 Nobel Prize in Physiology or Medicine for research on the brain’s two hemispheres [17]. Sperry aimed to investigate the role of the corpus callosum, the bundle of neurons that connects the two hemispheres of the brain. Because surgery cutting the corpus callosum was one of the earliest treatments for epilepsy, Sperry studied the abilities of patients who had undergone this procedure and pioneered studying the functional differences between brain hemispheres. In his experiments, Sperry would present a word to either the participant’s left or right eye for only a moment and then would ask them what they saw [17]. At the time, Sperry knew that the right hemisphere of the brain exclusively responded to the image seen in the left eye, and vice versa. When he placed the word in front of individuals’ right eye, they were able to tell him what word they saw. However, when the word was presented to their left eye, participants could not tell Sperry what they

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Brain Busters saw. From this, Sperry concluded that the left brain is necessary for language articulation and understanding. Next, he asked the same participants to draw the word that was presented only to their left eye with their left hand, knowing that, similar to visual control, muscular control is also governed by the opposite brain hemisphere. These individuals were able to draw the word and recognize their drawing as a word

but could not say it aloud. Sperry concluded that the right hemisphere can identify words as shapes, but can not articulate them. This contributed to the false notion that the combination of the two hemispheres

is necessary for normal language functioning. This study provides evidence for differences in hemispheres, and, therefore, evidence for the rightbrained left-brained myth, right? There is no dispute that there is functional lateralization within the brain; the two hemispheres are not identical, and there are functions that one primarily holds over the other. For example, the majority of language processing is governed by the left hemisphere, as Sperry suggested [13]. The left hemisphere is home to the brain regions Broca’s area and Wernicke’s area, which are responsible for language production and comprehension, respectively. This myth, however, incorrectly conflates the idea of functional differences with personality. Human beings love to classify each other into personality groups, as shown by the Myers-Briggs personality test, astrological signs, and Hogwarts houses. While yes, everyone’s brain has functional differences that vary by hemisphere, these differences are not necessarily related to personality. A 2013 study investigated whether or not brain activity in each hemisphere differs from person to person, looking at just over 1,000 individuals and analyzing over 7,200 cortical regions via fMRI. The results showed some variability in brain activity by region, but those differences were consistent across all individuals [14]. The researchers found no separation of the cohort into “left-brained” and “right-brained” individuals, thus disproving the common myth. So what could explain individual differences in creative and logical thinking capabilities? In 2018, a group of researchers sought out to answer this question by using fMRI data to observe connectivity between brain regions of study participants after they had completed creative thinking tasks [2]. The study found that connectivity patterns and creativity scores were

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Brain Busters

so strongly correlated that they could predict the creativity of a participant’s response by looking at their brain scan. They concluded that a person’s creative ability is based on the connectivity of three prominent brain networks: the default, salience, and executive networks. The default network includes regions in the cortex, the cerebellum, and striatum, which are best known for roles in thinking, balance, and movement respectively. These regions are activated when people are brainstorming or imagining. The executive network resides primarily in the frontal cortex and is responsible for evaluating if the brainstormed idea will actually work. Finally, the salience network is composed of the cingulate cortex and insula, which are brain regions necessary for emotion regulation, maintaining homeostasis, and switching between the two other networks.

to mislead society. When we are confronted with a neurological phenomenon in our daily lives, it is important that we question its scientific accuracy before blindly accepting it as true.

In other words, the default network puts the mind into dreamer mode, the executive network puts the mind into realist mode, and the salience network mediates when each mode is necessary. Interestingly, while these three networks are rarely all activated at the same time, this study suggests the more creative a person is, the better able they are to co-activate the networks [2]. These results are also consistent with another fMRI study of jazz musicians as they improvise melodies [16]. If you are trying to understand why, neurologically speaking, one person is more creative than another, resist the urge to categorize people into left and right brained individuals. As with every topic in neuroscience, the true explanations are very complex.

Billions of brain cells work together to govern the human body and construct the human mind. One can devote their entire life to studying the brain and only scratch the surface of its inner workings. Every brain region has subregions. Every subregion has several different types of cells. Each of these cells have multiple, unique functions, which can also vary based on the types of cells that surround them. It’s easy to see why neuroscience can be so complicated to understand. Even neuroscientists find themselves subspecializing within the field because it is impossible to study it all. When neuroscientific findings are published, they can be difficult to interpret, even by someone with a science background; therefore, misinterpretations are inevitable. These misinterpretations manifest in popular culture as facts even if there is no intent

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

References

REFERENCES REWIRING THE BRAIN: HOW THE NERVOUS SYSTEM HEALS ITSELF 1. Schiltz, N. K., & Fernandez-Baca Vaca, G. (2018). Epidemiologist’s view: Addressing the epilepsy surgery treatment gap with minimally-invasive techniques. Epilepsy Research, 142, 179–181. doi: 10.1016/j.eplepsyres.2018.01.013 2. Rogawski, M. A., Löscher, W., & Rho, J. M. (2016). Mechanisms of action of antiseizure drugs and the ketogenic diet. Cold Spring Harbor Perspectives in Medicine, 6(5). doi:10.1101/cshperspect.a022780 3. Lin, Y., Harris, D. A., Curry, D. J., & Lam, S. (2015). Trends in outcomes, complications, and hospitalization costs for hemispherectomy in the United States for the years 2000-2009. Epilepsia, 56(1), 139–146. doi: 10.1111/epi.12869 4. Armstrong-Wells, J., & Ferriero, D. M. (2014). Diagnosis and acute management of perinatal arterial ischemic stroke. Neurol Clin Pract, 4(5), 378–385. doi: 10.1212/CPJ.0000000000000077 5. Fountas, K. N., Smith, J. R., Robinson, J. S., Tamburrini, G., Pietrini, D., & Di Rocco, C. (2006). Anatomical hemispherectomy. Child’s Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery, 22(8), 982–991. doi:10.1007/s00381-006-0135-2 6. Miller, J. W., & Hakimian, S. (2013). Surgical treatment of epilepsy. Continuum (Minneapolis, Minn.), 19(3 Epilepsy), 730–742. doi:10.1212/01. CON.0000431398.69594.97 7. Deransart, C., Vercueil, L., Marescaux, C., & Depaulis, A. (1998). The role of basal ganglia in the control of generalized absence seizures. Epilepsy Research, 32(1–2), 213–223. doi:10.1016/s09201211(98)00053-9

8. Villemure, J.-G., & Daniel, R. T. (2006). Periinsular hemispherotomy in paediatric epilepsy. Child’s Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery, 22(8), 967–981. doi:10.1007/s00381-006-0135-2 9. Kim, J.-S., Park, E.-K., Shim, K.-W., & Kim, D. S. (2018). Hemispherotomy and functional hemispherectomy: Indications and outcomes. Journal of Epilepsy Research, 8(1), 1–5. 10. Campbell, J., & Sharma, A. (2016). Visual crossmodal re-organization in children with cochlear implants. PLOS ONE, 11(1), e0147793. doi:10.14581/ jer.18001 11. Shaffer, J. (2016). Neuroplasticity and clinical practice: Building brain power for health. Frontiers in Psychology, 7, 1118. doi:10.1371/journal.pone.0147793 12. Morris, R. G. M. (2003). Long-term potentiation and memory. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 358(1432), 643–647. doi:10.3389/fpsyg.2016.01118 13. Huttenlocher, P. R., & Dabholkar, A. S. (1997). Regional differences in synaptogenesis in human cerebral cortex. The Journal of Comparative Neurology, 387(2), 167–178. doi:10.1098/rstb.2002.1230 14. Klein, D., Mok, K., Chen, J.-K., & Watkins, K. E. (2014). Age of language learning shapes brain structure: a cortical thickness study of bilingual and monolingual individuals. Brain and Language, 131, 20–24. DOI:10.1002/(sici)10969861(19971020)387:2<167::aid-cne1>3.0.co;2-z 15. Ismail, F. Y., Fatemi, A., & Johnston, M. V. (2017). Cerebral plasticity: Windows of opportunity in the developing brain. European Journal of Paediatric Neurology: EJPN: Official Journal of the European Paediatric Neurology Society, 21(1), 23–48. doi:10.1016/j.bandl.2013.05.014

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

References 16. Sussman, D., Leung, R. C., Chakravarty, M. M., Lerch, J. P., & Taylor, M. J. (2016). The developing human brain: age-related changes in cortical, subcortical, and cerebellar anatomy. Brain and Behavior, 6(4), e00457. doi:10.1016/j.ejpn.2016.07.007 17. Abdul-Kareem, I. A., Stancak, A., Parkes, L. M., & Sluming, V. (2011). Increased gray matter volume of left pars opercularis in male orchestral musicians correlate positively with years of musical performance. Journal of Magnetic Resonance Imaging, 33(1), 24–32. doi:10.1002/brb3.457 doi:10.1002/jmri.22391 18. Schnack, H. G., van Haren, N. E. M., Brouwer, R. M., Evans, A., Durston, S., Boomsma D. I., , Khan, R. S., & Hulshoff Pol, H. E. (2015). Changes in thickness and surface area of the human cortex and their relationship with intelligence. Cerebral Cortex (New York, N.Y.: 1991), 25(6), 1608–1617. doi: 10.1093/cercor/ bht357 19. Kinsbourne, M. (2013). Somatic twist: a model for the evolution of decussation. Neuropsychology, 27(5), 511–515. doi:10.1093/cercor/bht357 20. Graveline, C. J., Mikulis, D. J., Crawley, A. P., & Hwang, P. A. (1998). Regionalized sensorimotor plasticity after hemispherectomy fMRI evaluation. Pediatric Neurology, 19(5), 337–342. doi:10.1037/ a0033662 21. Benecke, R., Meyer, B. U., & Freund, H. J. (1991). Reorganisation of descending motor pathways in patients after hemispherectomy and severe hemispheric lesions demonstrated by magnetic brain stimulation. Experimental Brain Research, 83(2), 419–426. doi:10.1016/S0887-8994(98)00082-4 22. Corballis, M. C. (2014). Left brain, right brain: facts and fantasies. PLOS Biology, 12(1), e1001767. doi:10.1007/BF00231167 23. Liégeois, F., Connelly, A., Baldeweg, T., & VarghaKhadem, F. (2008). Speaking with a single cerebral hemisphere: fMRI language organization after hemispherectomy in childhood. Brain and Language, 106(3), 195–203. doi:10.1371/journal.pbio.1001767 24. Ivanova, A., Zaidel, E., Salamon, N., Bookheimer, S., Uddin, L. Q., & de Bode, S. (2017). Intrinsic functional organization of putative language networks in the brain following left cerebral hemispherectomy. Brain Structure & Function, 222(8),

3795–3805. doi:10.1016/j.bandl.2008.01.010 25. Björklund, A., & Lindvall, O. (2000). Self-repair in the brain: Neurobiology. Nature, 405(6789), 892–893, 895. doi:10.1007/s00429-017-1434-y

SEX DIFFERENCES AND DEPRESSION: THE MALE-CENTRIC RESEARCH MODEL’S HARMFUL EFFECTS ON FEMALES 1. National Institute of Mental Health. (2019). Major depression. Retrieved April 05, 2021, from https://www.nimh.nih.gov/health/statistics/majordepression.shtml 2. Cassano, P., & Fava, M. (2002). Depression and public health: an overview. Journal of psychosomatic research, 53(4), 849–857. doi:10.1016/s00223999(02)00304-5 3. Tolentino, J. C., & Schmidt, S. L. (2018). DSM-5 Criteria and Depression Severity: Implications for Clinical Practice. Frontiers in psychiatry, 9, 450. doi:10.3389/fpsyt.2018.00450 4. LeGates, T. A., Kvarta, M. D., & Thompson, S. M. (2019). Sex differences in antidepressant efficacy. Neuropsychopharmacology, 44(1), 140–154. doi:10.1038/s41386-018-0156-z 5. Altemus, M., Sarvaiya, N., & Neill Epperson, C. (2014). Sex differences in anxiety and depression clinical perspectives. Frontiers in Neuroendocrinology, 35(3), 320–330. doi:10.1016/j. yfrne.2014.05.004 6. Sramek, J. J., Murphy, M. F., & Cutler, N. R. (2016). Sex differences in the psychopharmacological treatment of depression. Dialogues in clinical neuroscience, 18(4), 447–457. doi:10.31887/ DCNS.2016.18.4/ncutler 7. Schiebinger, L. (2003). Women’s health and clinical trials. Journal of Clinical Investigation, 112(7), 973977. doi:10.1172/jci200319993 8. McGregor, A. J. (2020). Sex Matters: how malecentric medicine endangers women’s health and what we can do about it. QUERCUS PUBLISHING.

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

References

JUST ANOTHER FACE IN THE CROWD: THE EVOLUTION AND MECHANISMS OF PRIMATE FACIAL PROCESSING 1. South Palomares, J. K., & Young, A. W. (2018). Facial first impressions of partner preference traits: Trustworthiness, status, and attractiveness. Social Psychological and Personality Science, 9(8), 990– 1000. doi: 10.1177/1948550617732388 2. Oosterhof, N., & Todorov, A. (2008). The functional basis of face evaluation. Proceedings of the National Academy of Sciences, 105(32), 11087–11092. doi:10.1073/pnas.0805664105 3. Burrows, A. M. (2008). The facial expression musculature in primates and its evolutionary significance. BioEssays, 30(3), 212–225. doi: 10.1002/ bies.20719 4. Waller, B. M., Julle-Daniere, E., & Micheletta, J. (2020). Measuring the evolution of facial ‘expression’ using multi-species FACS. Neuroscience & Biobehavioral Reviews, 113, 1–11. doi: 10.1016/j. neubiorev.2020.02.031 5. Costa, M., Gomez, A., Barat, E., Lio, G., Duhamel, J.R., & Sirigu, A. (2018). Implicit preference for human trustworthy faces in macaque monkeys. Nature Communications, 9(1), 4529. doi:10.1038/s41467-01806987-4 6. Haselhuhn, M. P., Ormiston, M. E., & Wong, E. M. (2015). Men’s facial width-to-height ratio predicts aggression: a meta-analysis. PloS one, 10(4), e0122637. https://doi.org/10.1371/journal.pone.0122637 7. Deska, J. C., Lloyd, E. P., & Hugenberg, K. (2018). The face of fear and anger: Facial width-to-height ratio biases recognition of angry and fearful expressions. Emotion, 18(3), 453–464. doi: 10.1037/ emo0000328 8. Gore J. C. (2003). Principles and practice of functional MRI of the human brain. The Journal of Clinical Investigation, 112(1), 4–9. doi: 10.1172/JCI19010 9. Kanwisher, N., McDermott, J., & Chun, M. M. (1997). The fusiform face area: A module in human extrastriate cortex specialized for face perception. doi:10.1523/JNEUROSCI.17-11-04302.1997

10. Tsao, D. Y. (2006). A cortical region consisting entirely of face-selective cells. Science, 311(5761), 670–674. doi: 10.1126/science.1119983 11. Ratan Murty, N. A., Teng, S., Beeler, D., Mynick, A., Oliva, A., & Kanwisher, N. (2020). Visual experience is not necessary for the development of face-selectivity in the lateral fusiform gyrus. Proceedings of the National Academy of Sciences, 117(37), 23011–23020. doi:10.1073/pnas.2004607117 12. Mäkelä, P., Näsänen, R., Rovamo, J., & Melmoth, D. (2001). Identification of facial images in peripheral vision. Vision Research, 41(5), 599–610. doi:10.1016/ s0042-6989(00)00259-5 13. Kosslyn, S. M., Hamilton, S. E., & Bernstein, J. H. (1995). The perception of curvature can be selectively disrupted in prosopagnosia. Brain and Cognition, 27(1), 36–58. doi:10.1006/brcg.1995.1003 14. Parvizi, J., Jacques, C., Foster, B. L., Withoft, N., Rangarajan, V., Weiner, K. S., & Grill-Spector, K. (2012). Electrical stimulation of human fusiform faceselective regions distorts face perception. Journal of Neuroscience, 32(43), 14915-14920. doi:10.1523/ JNEUROSCI.2609-12.2012 15. Voss, J. L., Federmeier, K. D., & Paller, K. A. (2012). The potato chip really does look like Elvis! Neural hallmarks of conceptual processing associated with finding novel shapes subjectively meaningful. Cerebral Cortex, 22(10), 2354–2364. doi:10.1093/ cercor/bhr315 16. Sternberg, R. J., Sternberg, K., & Mio, J. S. (2012). Cognitive Psychology. Wadsworth/Cengage Learning. 17. Taubert, J., Weldon, K.B. & Parr, L.A. (2017). Robust representations of individual faces in chimpanzees (Pan troglodytes) but not monkeys (Macaca mulatta). Anim Cogn 20, 321–329. doi: 10.1007/s10071-016-10546 18. Wilmer, J. B., Germine, L., Chabris, C. F., Chatterjee, G., Williams, M., Loken, E., Nakayama, K., & Duchaine, B. (2010). Human face recognition ability is specific and highly heritable. Proceedings of the National Academy of Sciences, 107(11), 5238–5241. doi: 10.1073/pnas.0913053107 19. Biotti, F., & Cook, R. (2016). Impaired perception of facial emotion in developmental prosopagnosia. Cortex, 81, 126–136. doi: 10.1016/j.cortex.2016.04.008

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

References 20. Gainotti, G., & Marra, C. (2011). Differential contribution of right and left temporo-occipital and anterior temporal lesions to face recognition disorders. Frontiers in Human Neuroscience, 5, 55. doi: 10.3389/fnhum.2011.00055 21. Corrow, S. L., Dalrymple, K. A., & Barton, J. J. (2016). Prosopagnosia: Current perspectives. Eye and Brain, 8, 165–175. doi: 10.2147/EB.S92838

FAKING IT ‘TILL YOU MAKE IT: WHY WE SHOULD ALL SMILE MORE 1. Kraft, T. L., & Pressman, S. D. (2012). Grin and bear it: The influence of manipulated facial expression on the stress response. Psychological Science, 23(11), 1372-1378. doi:10.1177/0956797612445312 2. Ekman, P., Davidson, R. J., & Friesen, W. V. (1990). The Duchenne smile: Emotional expression and brain physiology: II. Journal of Personality and Social Psychology, 58(2), 342–353. doi: 10.1037/00223514.58.2.342 3. Gothard, K. M. (2014). The amygdalo-motor pathways and the control of facial expressions. Frontiers in Neuroscience, 8(43). doi: 10.3389/ fnins.2014.00043 4. 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), 21,180-21,181. doi: 10.1073/ pnas.1219167110 5. Farhud, D. D., Malmir, M., & Khanahmadi, M. (2014). Happiness and health: The biological factorsSystematic review article. Iranian Journal of Public Health, 43(11), 1468-1477. PMID: 26060713 6. Meeten, F., Ivak, P., Dash, S. R., Knowles, S., Duka, T., Scott, R., Kaiser, J., & Davey, G. C. L. (2015). The effect of facial expressions on the evaluation of ambiguous statements. Experimental Psychology, 6(3), 253-263. doi:10.5127/jep.039613 7. Marmolejo-Ramos, F., Murata, A., Sasaki, K., Yamada, Y., Ikeda, A., Hinojosa, J. A., Watanabe, K., Parzuchowski, M., Tirado, C., & Ospina, R. (2020). Your face and moves seem happier when I smile. Facial action influences the perception of emotional faces and biological motion stimuli. Experimental Psychology, 67 (1), 14-22. doi:10.31234/osf.io/4uvdq

8. Davis, J. I., Senghas, A., & Ochsner, K. N., (2009). How does facial feedback modulate emotional experience. Journal of Research in Personality, 43(5), 822-829. doi:10.1016/j.jrp.2009.06.005 9. Ehrenfeld, T. (2013, February 23). Does botox blunt emotions? Psychology Today. Retrieved from https://www.psychologytoday.com/us/blog/opengently/201302/does-botox-blunt-emotions 10. Dutta, S. R., Passi, D., Singh, M., Singh, P., Sharma, S., & Sharma, A. (2016). Botulinum toxin the poison that heals: A brief review. National Journal of Maxillofacial Surgery, 7(1), 10-16. doi:10.4103/09755950.196133 11. Davis, J. I., Senghas, A., Brandt, F., & Ochsner, K. N. (2010). The effects of BOTOX® injections on emotional experience. Emotion, 10(3), 433-440. doi:10.1037/a0018690 12. Ulrich-Lai, Y. M., & Herman, J. P. (2014). Neural regulation of endocrine and autonomic stress responses. Nature Reviews Neuroscience, 10(6), 397409. doi: 10.1038/nrn2647 13. Harvard Health Publishing (2020, July 6). Understanding the stress response. Harvard Medical School. Retrieved from https://www.health.harvard. edu/staying-healthy/understanding-the-stressresponse 14. Zander-Schellenberg, T., Collins, I. M., Miché, M., Guttmann, C., Lieb, R., & Wahl, K. (2020) Does laughing have a stress-buffering effect in daily life? An intensive longitudinal study. PLOS ONE, 15(7),1-11. doi:10.1371/journal.pone.0235851 15. Okley, J. A., Weiss, A., & Gale C. R. (2017). The interaction between stress and positive affect in predicting mortality. Journal of Psychosomatic Research, 100, 53-60. doi:10.1016/j. jpsychores.2017.07.005

ENCOUNTERS WITH THE THIRD KIND: THE MEMORY TWILIGHT ZONE 1. Friedman & Marden. (2007). Captured! The Betty and Barney Hill UFO Experience. Weiser.

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

References 2. Winthrop, J. (1996). The Journal of John Winthrop, 1630-1649 (R. S. Dunn, J. Savage, L. Yeandle, Eds.). Harvard University Press. (Original work published 1630-1649). 3. Queensland Brain Institute. (2018). Where are memories stored in the brain?. Queensland Brain Institute. Retrieved from https://qbi.uq.edu.au/brainbasics/memory/where-are-memories-stored 4. Hellenthal, M. V., Knott, L. M., Howe, M. L., Wilkinson, S., & Shah, D. (2019). The effects of arousal and attention on emotional false memory formation. Journal of Memory and Language, 107, 54-68. doi:10.1016/j.jml.2019.03.010. 5. Williamson, A. (2019). What is hypnosis and how might it work? Palliative Care: Research and Treatment, 12. doi:10.1177/1178224219826581. 6. June, C. (2016). Sleep deprivation increases formation of false memories. Journal of Sleep Research, 25, 673-682. doi: 10.1111/jsr.12436. 7. Hessen-Kayfitz, K. & Scoboria, A. (2012). False memory is in the details: Photographic details differentially predict false memory formation. Applied Cognitive Psychology, 26, 333-341. doi: 10.1002/ acp.1839 8. Williamson, A. (2019). What is hypnosis and how might it work? Palliative Care: Research and Treatment, 12. 9. McNally, R. & Clancy, S. (2005). Sleep paralysis in adults reporting repressed, recovered, or continuous memories of childhood sexual abuse. Journal of Anxiety Disorders, 19, 595-602. doi: 10.1016/j. janxdis.2004.05.003. 10. Otgaar, H., Howe, M., Patihis, L., Merckelbach, H., Lynn, S., Lilienfeld, S., Loftus, E. (2019). The return of the repressed: The long persistent and problematic claims of long-forgotten trauma. Perspectives on Psychological Science, 14, 1072-1095. doi: 10.1177/174569161862306.

2. Derry, H. M., Padin, A. C., Kuo, J. L., Hughes, S., & Kiecolt-Glaser, J. K. (2015). Sex differences in depression: Does inflammation play a role? Current Psychiatry Reports, 17(10). doi:10.1007/s11920-0150618-5 3. Fournier, J. C., DeRubeis, R. J., Hollon, S. D., Dimidjian, S., Amsterdam, J. D., Shelton, R. C., & Fawcett, J. (2010). Antidepressant drug effects and depression severity: A patient-level meta-analysis. JAMA - Journal of the American Medical Association, 303(1), 47–53. doi:10.1001/jama.2009.1943 4. Haapakoski, R., Mathieu, J., Ebmeier, K. P., Alenius, H., & Kivimäki, M. (2015). Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder. Brain, Behavior, and Immunity, 49, 206–215. doi:10.1016/j.bbi.2015.06.001 5. Kessler, R. C., Berglund, P., Demler, O., Jin, R., Koretz, D., Merikangas, K. R., Rush, A. J., Walters, E. E., Wang, A., Rovner, B., & Casten, R. (2003). The epidemiology of major depressive disorder. EvidenceBased Eye Care, 4(4), 186–187. doi:10.1097/00132578200310000-00002 6. Kim, Y. K., Na, K. S., Myint, A. M., & Leonard, B. E. (2016). The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 64, 277–284. https://doi.org/10.1016/j. pnpbp.2015.06.008 7. Miller, G. E., & Cole, S. W. (2012). Clustering of depression and inflammation in adolescents previously exposed to childhood adversity. Biological Psychiatry, 72(1), 34–40. doi:10.1016/j. biopsych.2012.02.034 8. Maes, M. (1995). Evidence for an immune response in major depression: A review and hypothesis. Progress in Neuropsychopharmacology and Biological Psychiatry, 19(1), 11–38.doi:10.1016/02785846(94)00101-M

BEWARE THE POST-VACCINE BLUES 1. Al-Harbi, K. S. (2012). Treatment-resistant depression: Therapeutic trends, challenges, and future directions. Patient Preference and Adherence, 6, 369–388. doi:10.2147/PPA.S29716

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

References 9. Raison, C. L., Dantzer, R., Ph, D., Kelley, K. W., Marcus, A., Woolwine, B. J., Vogt, G., Spivey, J. R., Saito, K., & Miller, A. H. (2010). CSF concentrations of brain tryptophan and kynurenines during immune stimulation with IFN-alpha: relationship to CNS immune responses and depression. Molecular Psychiatry, 15(4), 393–403. doi:10.1038/mp.2009.116. CSF

2. Ghavami, S., Shojaei, S., Yeganeh, B., Ande, S. R., Jangamreddy, J. R., Mehrpour, M., Christofferson, J., Chaabane, W., Moghadam, A., R., Kashani, H., H., Hashemi, M., Owji, A., A., & Łos, M. J. (2014). Autophagy and apoptosis dysfunction in neurodegenerative disorders. Progress in Neurobiology, 112, 24–49. doi:10.1016/j. pneurobio.2013.10.004.

10. Raison, C. L., Rutherford, R. E., Woolwine, B. J., Shuo, C., Schettler, P., Drake, D. F., Haroon, E., & Miller, A. H. (2013). A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: The role of baseline inflammatory biomarkers. Archives of General Psychiatry, 70(1), 31–41. doi:10.1001/2013. jamapsychiatry.4

3. Harvard Medical School. (n.d.). The challenge of neurodegenerative diseases. Harvard NeuroDiscovery Center. Retrieved from https://neurodiscovery. harvard.edu/challenge

11. Tsatsoulis, A., & Fountoulakis, S. (2006). The protective role of exercise on stress system dysregulation and comorbidities. Annals of the New York Academy of Sciences, 1083: 196-213. doi:10.1196/ annals.1367.020 12. Vollmer-Conna, U., Fazou, C., Cameron, B., Li, H., Brennan, C., Luck, L., Davenport, T., Wakefield, D., Hickie, I., & Lloyd, A. (2004). Production of pro-inflammatory cytokines correlates with the symptoms of acute sickness behaviour in humans. Psychological Medicine, 34(7), 1289–1297. doi:10.1017/ S0033291704001953 13. Wirtz, P. H., & von Känel, R. (2017). Psychological stress, inflammation, and coronary heart disease. Current Cardiology Reports, 19(11). doi:10.1007/s11886017-0919-x 14. Yirmiya, R., Rimmerman, N., & Reshef, R. (2015). Depression as a microglial disease. Trends in Neurosciences, 38(10), 637–658. doi:10.1016/j. tins.2015.08.001

4. U.S. Department of Health and Human Services. (n.d.). What are the signs of Alzheimer’s Disease? National Institute on Aging. Retrieved from https:// www.nia.nih.gov/health/what-are-signs-alzheimersdisease. 5. Durães, F., Pinto, M., & Sousa, E. (2018). Old drugs as new treatments for neurodegenerative diseases. Pharmaceuticals, 11(2), 44. doi:10.3390/ph11020044 6. Liu, E. Y., Cali, C. P. &, Lee. E. B. RNA metabolism in neurodegenerative disease. Dis Model Mech. 2017 May 1;10(5):509-518. doi:10.1242/dmm.028613. 7. Ferry, G. (2019). The structure of DNA. Science, 575, 35-36. doi:10.1038/d41586-019-02554-z 8. Clancy, S. (2008) Chemical RNA structure. Nature Education, 7(1):60. Retrieved from https://www. nature.com/scitable/topicpage/chemical-structureof-rna-348/ 9. Chan, J. J., & Tay, Y. (2018). Noncoding RNA: RNA regulatory networks in cancer. International Journal of Molecular Sciences, 19(5), 1310. doi:10.3390/ ijms19051310

RNA: A NEW FACE IN THE FIGHT AGAINST NEURODEGENERATION

10. Qureshi, A., Tantray, V. G., Kirmani, A. R., & Ahangar, A. G. (2018). A review on current status of antiviral siRNA. Reviews in Medical Virology, 28(4), e1976. doi:10.1002/rmv.1976

1. Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. The Cell Death Pathways. Available from: https://www.ncbi. nlm.nih.gov/books/NBK10103/

11. Belzil, V. V., Gendron, T. F., & Petrucelli, L. (2013). RNA-mediated toxicity in neurodegenerative disease. Molecular and Cellular Neurosciences, 56, 406–419. doi:10.1016/j.mcn.2012.12.006

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

References 12. Nussbacher, J. K., Tabet, R., Yeo, G. W., & LagierTourenne, C. (2019). Disruption of RNA metabolism in neurological diseases and emerging therapeutic interventions. Neuron, 102(2), 294–320. doi:10.1016/j. neuron.2019.03.01 13. Ramaswami, M., Taylor, J. P., & Parker, R. (2013). Altered ribostasis: RNA-protein granules in degenerative disorders. Cell, 154(4), 727-736. doi:10.1016/j.cell.2013.07.038. 14. Riva, P., Ratti, A., & Venturin, M. (2016). The Long Non-Coding RNAs in Neurodegenerative Diseases: Novel Mechanisms of Pathogenesis. Current Alzheimer Research, 13(11), 1219–1231. doi:10.2174/1567 205013666160622112234 15. Johnson R. (2012). Long non-coding RNAs in Huntington’s disease neurodegeneration. Neurobiology of disease, 46(2), 245–254. https://doi. org/10.1016/j.nbd.2011.12.006 16. Idda, M. L., Munk, R., Abdelmohsen, K., & Gorospe, M. (2018). Noncoding RNAs in Alzheimer’s disease. Wiley interdisciplinary reviews. RNA, 9(2), 10.1002/ wrna.1463. https://doi.org/10.1002/wrna.1463 17. Drew, L. (2019). Why rare genetic diseases are a logical focus for RNA therapies. Nature Outlook, 574, S16-S18. doi 10.1038/d41586-019-03075-5 18. Arraiano, M.C., Andrade, J.M., Domingues, S., Guinote, I.B., Malecki, M., Matos, R.G., Moreira, R.N., Pobre, V., Reis, F.P., Saramago, M., Silva, I.J., & Viegas, S.C. (2010). The critical role of RNA processing and degradation in the control of gene expression. FEMS Microbiology Reviews, 34(5), 883–923. doi:10.1111/ j.1574-6976.2010.00242.x 19. Katella, K. (2021, April 13). Comparing the COVID-19 vaccines: How are they different? Retrieved from https://www.yalemedicine.org/news/covid-19vaccine-comparison. 20. Centers for Disease Control and Prevention. (2021, March 4). Understanding mRNA COVID-19 Vaccines. Centers for Disease Control and Prevention. Retrieved from https://www.cdc.gov/coronavirus/2019-ncov/ vaccines/different-vaccines/mrna.html.

21. Wang, H., Zhang, Y., Huang, B., Deng, W., Quan, Y., Wang, W., Xu, W., Zhao, Y., Li, N., Zhang, J., Linag, H., Bao, L., Xu, Y., Ding, L., Zhou, W., Gao, H., Liu, J., Niu, P., Zhao, L., Zhen, W., Fu, H., Yu, S., Zhang, Z., Xu, G., Li, C., Lou, Z., Xu, M., Qin, C., Wu, G., Gao, G., F., Tan, W., & Yang, X. (2020). Development of an inactivated vaccine candidate, BBIBP-CorV, with potent protection against SARS-CoV-2. Cell, 182(3), 713–721. doi:10.1016/j.cell.2020.06.008 22. Immunisation Advisory Centre. (2020, January). A brief history of vaccination. Immunisation Advisory Centre. Retrieved from https://www.immune.org. nz/vaccines/vaccine-development/brief-historyvaccination

A HOT ISSUE: TEMPERATURE-DEPENDENT TOXICITY IN HERBIVOROUS MAMMALS 1. Parry, M. L. (2007). Climate Change 2007: Impacts, Adaptation and Vulnerability: Contribution of Working Group II to the Fourth Assessment Report of the Intergovernmental Panel on Climate Change. Cambridge: Cambridge University Press. 2. Dearing, M., Forbey, J., McLister, J., & Santos, L. (2008). Ambient temperature influences diet selection and physiology of an herbivorous mammal, Neotoma albigula. Physiological and Biochemical Zoology: Ecological and Evolutionary Approaches, 81(6), 891-897. doi:10.1086/588490 3. Waller, J. (2009). A forgotten plague: Making sense of dancing mania. The Lancet, 373(9664), 624-625. doi:10.1016/s0140-6736(09)60386-x 4. Guerre P. (2015). Ergot alkaloids produced by endophytic fungi of the genus Epichloë. Toxins, 7(3), 773–790. doi: 10.3390/toxins7030773 5. Florea, S., Panaccione, D. G., & Schardl, C. L. (2017). Ergot alkaloids of the family Clavicipitaceae. Phytopathology, 107(5), 504–518. doi:10.1094/PHYTO12-16-0435-RVW 6. Bobkova, N.V., Uteshev, V.K., Medvinskaya, N.I., Nesterova, I. V., & Arinbasarov, M. U. (2002). Mechanisms of amnestic effect of ergot alkaloid agroclavin. Bulletin of Experimental Biology and Medicine, 133, 366–368. doi: 10.1023/A:1016298005058

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

References 7. Eisemann, J. H., Huntington, G. B., Williamson, M., Hanna, M., & Poore, M. (2014, October 15). Physiological responses to known intake of ergot alkaloids by steers at environmental temperatures within or greater than their thermoneutral zone. Frontiers in Chemistry, 2. doi: 10.3389/ fchem.2014.00096 8. Lawler I. R., Stapley J., Foley W. J., & Eschler, B. M. (1999). Ecological example of conditioned flavor aversion in plant-herbivore interactions: Effect of terpenes of Eucalyptus leaves on feeding by common ringtail and brushtail possums. Journal of Chemical Ecology, 25, 401–415. doi:10.1023/A:1020863216892 9. Mclean, S., Brandon, S., Davies, N. W., Foley, W. J., & Muller, H. K. (2004). Jensenone: Biological reactivity of a marsupial antifeedant from eucalyptus. Journal of Chemical Ecology, 30(1), 19-36. doi:10.1023/ b:joec.0000013180.46747.07 10. Cubeddu, L., Hoffmann, I., Fuenmayor, N., & Malave, J. (1992). Changes in serotonin metabolism in cancer patients: Its relationship to nausea and vomiting induced by chemotherapeutic drugs. British Journal of Cancer, 66(1), 198-203. doi:10.1038/bjc. 1992.242 11. Marsh, K. J., Wallis, I. R., & Foley, W. J. (2005). Detoxification rates constrain feeding in common brushtail possums (Trichosurus vulpecula). Ecology, 86(11), 2946-2954. doi:10.1890/05-0303 12. Nersesian, C. L., Banks, P. B., & Mcarthur, C. (2011). Titrating the cost of plant toxins against predators: Determining the tipping point for foraging herbivores. Journal of Animal Ecology, 80(4), 753-760. doi:10.1111/ j.1365-2656.2011.01822.x 13. Kirmani, S. N., Banks, P. B., & McArthur, C. (2010). Integrating the costs of plant toxins and predation risk in foraging decisions of a mammalian herbivore. Oecologia, 164(2), 349–356. doi: 10.1007/s00442-0101717-y 14. Moore, B. D., Wiggins, N. L., Marsh, K. J., Dearing, M. D., & Foley, W. J. (2015). Translating physiological signals to changes in feeding behaviour in mammals and the future effects of global climate change. Animal Production Science, 55(3), 272. doi:10.1071/ AN14487

15. Marsh, K. J., Wallis, I. R., Mclean, S., Sorensen, J. S., & Foley, W. J. (2006). Conflicting demands on detoxification pathways influence how common brushtail possums choose their diets. Ecology, 87(8), 2103-2112. doi:10.1890/0012-9658(2006)87[2103:cdodp i]2.0.co;2 16. Moffett, D. B., Mumtaz, M. M., Sullivan, D. W., & Fowler, B. A. (2015). General considerations of doseeffect and dose-response relationships. In Handbook on the Toxicology of Metals (pp. 197–212). Elsevier. doi:10.1016/B978-0-444-59453-2.00010-X 17. Torregrossa, A. M., Azzara, A. V., & Dearing, M. D. (2012). Testing the diet-breadth trade-off hypothesis: Differential regulation of novel plant secondary compounds by a specialist and a generalist herbivore. Oecologia, 168(3), 711–718. doi:10.1007/ s00442-011-2121-y

DEFYING THE “WAR ON DRUGS”: THE REBIRTH OF PSYCHEDELIC MEDICINE & RESEARCH 1. History.com Editors. (2018, August 21). LSD. A&E Television Networks. Retrieved from history.com/ topics/crime/history-of-lsd. 2. Aixalà, M., dos Santos, R., Hallak, J., & Bouso, J.C. (2018). Psychedelics and personality. ACS Chemical Neuroscience, 9(10), 2304–2306. doi:10.1021/ acschemneuro. 8b00237. 3. Lewis, T. (2020, January 16). Johns Hopkins scientists give psychedelics the serious treatment. Scientific American. Retrieved from scientificamerican.com/article/johns-hopkinsscientists-give-psychedelics-the-serious-treatment. 4. Joiner, W. (2020, September 21). Who will benefit from psychedelic medicine? Washington Post. Retrieved from washingtonpost.com/ magazine/2020/09/21/psychedelic-medicine-will- itbe-accessible-to-all. 5. Walsh, Z., Hendricks, P., Smith, S., Kosson, D., Thiessen, M., Lucas, P., & Swogger, M. (2016). Hallucinogen use and intimate partner violence: Prospective evidence consistent with protective effects among men with histories of problematic substance use. Journal of Psychopharmacology, 30(7), 601–607. doi:10.1177/0269881116642538.

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

References 6. Kuchler, H. (2017, August 10). How Silicon Valley rediscovered LSD. Financial Times. Retrieved from ft.com/content/0a5a4404-7c8e-11e7-ab01a13271d1ee9c. 7. Tust, A. (2019, February 7). Would you consider trying psychedelics to take your practice to another level? Yoga Journal. Retrieved from yogajournal. com/lifestyle/yoga-trends/yoga-meditation- andpsychedelics.

15. Krebs, T., & Johansen, P-Ø. (2012). Lysergic acid diethylamide (LSD) for alcoholism: Metaanalysis of randomized controlled trials. Journal of Psychopharmacology, 26(7), 994–1002. doi:10.1177/0269881112439253.

8. Hagenbach, D., & Werthmüller, L. (2013, May 17). Turn on, tune in, drop out--and accidentally discover LSD [Excerpt]. Scientific American. Retrieved from scientificamerican.com/article/lsd-finds-itsdiscoverer.

16. Carhart-Harris, R. L., Muthukumaraswamy, S., Roseman, L., Kaelen, M., Droog, W., Murphy, K., Tagliazucchi, E., Schenberg, E. E., Nest, T., Orban, C., Leech, R., Williams, L. T., Williams, T. M., Bolstridge, M., Sessa, B., McGonigle, J., Sereno, M. I., Nichols, D., Hellyer, P. J., … Nutt, D. J. (2016). Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences, 113(17), 4853–4858. doi:10.1073/ pnas.1518377113.

9. Bogenschutz, M. P., & Ross, S. (2018). Therapeutic applications of classic hallucinogens. Current topics in behavioral neurosciences, 36, 361–391. doi:10.1007/7854_2016_464

17. Yaden, D. B., Yaden, M. E., & Griffiths, R. R. (2020). Psychedelics in psychiatry—Keeping the renaissance from going off the rails. JAMA Psychiatry. doi:10.1001/ jamapsychiatry.2020.3672.

10. Cormier, Z. (2016, April 11). Brain scans reveal how LSD affects consciousness. Springer Nature. Retrieved from www.nature.com/news/brain-scansreveal-how- lsd-affects-consciousness-1.19727.

18. New Scientist. (2021). Microdosing may be all in the mind. New Scientist, 249(3325). doi:10.1016/ s0262-4079(21)00406-1.

11. Neelkantan, N., Mikhaylova, A., Stewart, A.M., Arnold, R., Gjeloshi, V., Kondaveeti, D., Poudel, M., & Kalueff, A. (2013). Perspectives on zebrafish models of hallucinogenic drugs and related psychotropic compounds. ACS Chemical Neuroscience, 4(8), 1137– 1150. doi:10.1021/cn400090q. 12. Johns Hopkins Medicine. (2020, November 4). Psychedelic treatment with psilocybin relieves major depression, study shows. Johns Hopkins Medicine. Retrieved from https://www.hopkinsmedicine. org/news/newsroom/news-releases/psychedelictreatment-with-psilocybin-relieves-majordepression-study-shows. 13. De Gregorio, D., Enns, J., Nuñez, N., Posa, L., & Gobbi, G. (2018). d-Lysergic acid diethylamide, psilocybin, and other classic hallucinogens: Mechanism of action and potential therapeutic applications in mood disorders. Progress in Brain Research, 242, 69–96. doi:10.1016/bs.pbr.2018.07.008. 14. Cormier, Z. (2015, May 26). No link found between psychedelics and psychosis. Springer Nature. Retrieved from nature.com/news/no-link-foundbetween-psychedelics-and-psychosis-1.16968.

19. Cameron, L. P., Nazarian, A., & Olson, D. E. (2020). Psychedelic microdosing: Prevalence and subjective effects. Journal of Psychoactive Drugs. doi:10.1080/02 791072.2020.1718250. 20. Rougemont-Bücking, A., Jungaberle, H., Scheidegger, M., Merlo, M.C.G., Grazioli, V., Daeppen, J-B., Gmel, G., & Studer, J. (2019). Comparing mental health across distinct groups of users of psychedelics, MDMA, psychostimulants, and cannabis. Journal of Psychoactive Drugs. doi:10.1080/ 02791072.2019.1571258. 21. Kaertner, L., Steinborn, M., Kettner, H., Spriggs, M., Roseman, L., Buchborn, T., Balaet, M., Timmermann, C., Erritzoe, D., & Carhart-Harris, R. (2021). Positive expectations predict improved mental-health outcomes linked to psychedelic microdosing. Scientific Reports, 11(1). doi:10.1038/s41598-02181446-7. 22. Lieberman, J. A. (2021). Back to the future — The therapeutic potential of psychedelic drugs. New England Journal of Medicine, 384(15), 1460–1461. doi:10.1056/ nejme2102835.

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

References 23. Sutherland, R., Peacock, A., Whittaker, E., Roxburgh, A., Lenton, S., Matthews, A., Butler, K., Nelson, M., Burns, L., & Bruno, R. (2016). New psychoactive substance use among regular psychostimulant users in Australia, 2010–2015. Drug and Alcohol Dependence, 161, 110–118. doi:10.1016/j. drugalcdep.2016.01.024. 24. Fernández-Calderón, F., Cleland, C., & Palamar, J. (2018). Polysubstance use profiles among electronic dance music party attendees in New York City and their relation to use of new psychoactive substances. Addictive Behaviors, 78, 85–93. doi:10.1016/j.addbeh. 2017.11.004. 25. Tupper, K., Wood, E., Yensen, R., & Johnson, M. (2015). Psychedelic medicine: A re-emerging therapeutic paradigm. Canadian Medical Association Journal, 187(14), 1054–1059. doi:10.1503/cmaj.141124. 26. Davis, A., Barrett, F., May, D., Cosimano, M., Sepeda, N., Johnson, M., Finan, P., Griffiths, R. (2020). Effects of psilocybin-assisted therapy on major depressive disorder. JAMA Psychiatry. doi:10.1001/ jamapsychiatry.2020.3285.

32. American Chemical Society. (2017, October 2). Psilocybin. American Chemical Society. Retrieved from acs.org/content/acs/en/molecule-of-the-week/ archive/p/psilocybin.html. 33. Mammoser, G. (2019, February 12). Mushrooms as medicine? Psychedelics may be next breakthrough treatment. Healthline. Retrieved from healthline.com/ health-news/benefits-of-medical-mushrooms. 34. Nichols, D. (2020). Psilocybin: From ancient magic to modern medicine. The Journal of Antibiotics, 73(10), 679–686. doi:10.1038/s41429-020-0311-8. 35. Nutt, D., & Carhart-Harris, R. (2021). The current status of psychedelics in psychiatry. JAMA Psychiatry, 78(2), 121–122. doi:10.1001/jamapsychiatry.2020.2171. 36. Daniel, J., & Haberman, M. (2017). Clinical potential of psilocybin as a treatment for mental health conditions. Mental Health Clinician, 7(1), 24–28. doi:10.9740/ mhc.2017.01.024.

27. National Center for Biotechnology Information (2021). PubChem compound summary for CID 8223, Ergotamine. NCBI. Retrieved from pubchem.ncbi.nlm. nih.gov/compound/Ergotamine.

37. Agin-Liebes, G., Malone, T., Yalch, M., Mennenga, S., Ponté, K.L., Guss, J., Bossis, A., Grigsby, J., Fischer, S., & Ross, S. (2020). Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with lifethreatening cancer. Journal of Psychopharmacology, 34(2), 155–166. doi:10.1177/0269881119897615.

28. Magness, J. (2018, March 4). LSD is “harmonizing” for the brain — and can change your personality for years, studies find. Miami Herald. Retrieved from miamiherald.com/news/nation-world/ article203341684.html.

38. Johnson, M., Garcia-Romeu, A., Cosimano, M., & Griffiths, R. (2014). Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. Journal of Psychopharmacology, 28(11), 983–992. doi:10.1177/0269881114548296.

29. Fuentes, J. J., Fonseca, F., Elices, M., Farré, M., & Torrens, M. (2020). Therapeutic use of LSD in psychiatry: A systematic review of randomizedcontrolled clinical trials. Frontiers in Psychiatry, 10. doi:10.3389/fpsyt.2019.00943.

39. Johnson, M., Garcia-Romeu, A., & Griffiths, R. (2016). Long-term follow-up of psilocybin-facilitated smoking cessation. The American Journal of Drug and Alcohol Abuse, 43(1), 55–60. doi:10.3109/00952990.20 16.1170135.

30. Nichols, D., Johnson, M., & Nichols, C. (2016). Psychedelics as medicines: An emerging new paradigm. Clinical Pharmacology & Therapeutics, 101(2), 209–219. doi:10.1002/ cpt.557.

40. Vann Jones, S. A., & O’Kelly, A. (2020). Psychedelics as a treatment for Alzheimer’s disease dementia. Frontiers in Synaptic Neuroscience, 12. doi:10.3389/fnsyn.2020.00034.

31. Anderson, A. (2016, April 13). LSD may chip away at the brain’s “sense of self” network. Scientific American. Retrieved from scientificamerican.com/ article/lsd-may-chip-away-at-the-brain-s-sense-ofself-network.

41. Sessa, B., & Nutt, D. (2015). Making a medicine out of MDMA. British Journal of Psychiatry, 206(1), 4–6. doi:10.1192/bjp.bp.114.152751.

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

References 42. Wilcox, J. (2014). Psilocybin and obsessive compulsive disorder. Journal of Psychoactive Drugs, 46(5), 393–395. doi:10.1080/02791072.2014.963754. 43. Atasoy, S., Roseman, L., Kaelen, M., Kringelbach, M., Deco, G., & Carthart-Harris, R. (2017). Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire reorganization under LSD. Scientific Reports, 7(1), 17661. doi:10.1038/s41598-017-17546-0. 44. Lugo-Radillo, A., MD, PhD, & Cortes-Lopez, J. L., MD (2020). Long-term Amelioration of OCD Symptoms in a Patient with Chronic Consumption of Psilocybin-containing Mushrooms. Journal of psychoactive drugs, 1–3. doi:10.1080/02791072.2020.1 849879. 45. Weiss, S. (2018, May 24). Here’s what MDMA did for my anxiety that meds couldn’t. Vice. Retrieved from vice.com/en/article/8xeqp4/psychedelicsmdma-versus-medicine-anxiety. 46. Weiss, S. (2021, January 14). How mixing mushrooms and MDMA affects your body and brain. Vice. Retrieved from vice.com/en/article/5dpkk8/ what-happens-when-you-mix-mdma-andmushrooms. 47. Lopez, G. (2016, November 30). Ecstasy could be available for medical use by 2021. Vox. Retrieved from vox.com/science-and-health/2016/11/30/13792958/ mdma-ecstasy-molly-study-fda. 48. Alcohol and Drug Foundation (Australia). (2020). MDMA-assisted therapy for PTSD edges closer. Alcohol and Drug Foundation. Retrieved from adf.org. au/insights/mdma-ptsd. 49. Bedi, G. (2018, March 28). Is psychiatry ready for medical MDMA?. The Conversation. Retrieved from theconversation.com/is-psychiatry-ready-formedical-mdma-94105. 50. Amoroso, T. (2015). The psychopharmacology of ±3,4 methylenedioxymethamphetamine and its role in the treatment of posttraumatic stress disorder. Journal of Psychoactive Drugs, 47(5). doi:10.1080/027 91072.2015.1094156.

51. Butler, G. (2021, March 5). Study reveals more people are using psychedelics to self-treat mental health. Vice. Retrieved from vice.com/en/article/ g5b7x9/study-reveals-more-people-are-usingpsychedelics-to-self-treat-mental-health. 52. Lamkin, M. (2019, July 31). Psychedelic medicine is coming. The law isn’t ready. Scientific American. Retrieved from blogs.scientificamerican.com/ observations/psychedelic-medicine-is-coming-thelaw-isnt-ready.

DEPRESSION AND ANXIETY: THE FRENEMIES NO COLLEGE STUDENT WANTS TO MEET 1. Tjornehoj, T. (2016). The relationship between anxiety and depression. Hartgrove Behavioral Health Systems. http://www.hartgrovehospital.com/ relationship-anxiety-depression/ 2. National Institute of Mental Health (2017) Generalised Anxiety Disorder https://www.nimh.nih. gov/health/statistics/generalized-anxiety-disorder. shtml 3. National Institute of Mental Health. (2019). Major depression. https://www.nimh.nih.gov/health/ statistics/major-depression.shtml 4. Zhou, Y., Cao, Z., Yang, M., Xi, X., Guo, Y., Fang, M., Cheng, L., & Du, Y. (2017). Comorbid generalized anxiety disorder and its association with quality of life in patients with major depressive disorder. Scientific reports, 7(1), 1-8. doi:10.1038/srep40511 5. American Psychological Association. (2013). College students’ mental health is a growing concern, survey finds. APA, 44(6), 13. https://www.apa.org/ monitor/2013/06/college-students 6. Jenkins, P. E., Ducker, I., Gooding, R., James, M. & RutterEley, E. (2020) Anxiety and depression in a sample of UK college students: a study of prevalence, comorbidity, and quality of life. Journal of American College Health. 1940- 3208 doi: doi:10.10 80/07448481.2019.1709474 7. Dupuy, J. & Ladouceur, R. (2008). Cognitive processes of generalized anxiety disorder in comorbid generalized anxiety disorder and major depressive disorder. Journal of Anxiety Disorders, 22(3), 505-514. doi:10.1016/j.janxdis.2007.05.010

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

References 8. Kalueff, A. V., & Nutt, D. J. (2007). Role of GABA in anxiety and depression. Depression and Anxiety, 24(7), 495-517. doi:10.1002/da.20262 9. Nuss P. (2015). Anxiety disorders and GABA neurotransmission: a disturbance of modulation. Neuropsychiatric disease and treatment, 11, 165–175. doi:10.2147/NDT.S58841 10. Luscher, B., Shen, Q. & Sahir, N. The GABAergic deficit hypothesis of major depressive disorder. Mol Psychiatry 16, 383–406 (2011). doi:10.1038/mp.2010.120 11. Schmitz, T.W., Correia, M., Ferreira, C., Prescot, A., & Anderson, M.C. (2017). Hippocampal GABA enables inhibitory control over unwanted thoughts. Nature communications, 8(1), 1-12. doi:10.1038/s41467-01700956-z 12. Coplan, J. D., Aaronson, C. J., Panthangi, V. & Kim, Y. (2015). Treating comorbid anxiety and depression: Psychosocial and pharmacological approaches. World journal of psychiatry, 5(4), 366–378. doi:10.5498/wjp. v5.i4.366 13. Gorka, S. M., Young, C. B., Klumpp, H., Kennedy, A. E., Francis, J., Ajilore, O., Langenecker, S. A., Shankman, S. A., Craske, M. G., Stein, M. B., & Phan, K. L. (2019). Emotion-based brain mechanisms and predictors for SSRI and CBT treatment of anxiety and depression: a randomized trial. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 44(9), 1639–1648. doi:10.1038/s41386-019-0407-7 14. Cowen, P. J., & Browning, M. (2015). What has serotonin to do with depression?. World Psychiatry, 14(2), 158. doi:10.1002/wps.20229 15. Garber, J., & Weersing, V. R. (2010). Comorbidity of anxiety and depression in youth: Implications for treatment and prevention. Clinical Psychology: Science and Practice, 17(4), 293-306. doi:10.1111/ j.1468-2850.2010.01221.x 16. Hirschfeld R. M. (2001). The Comorbidity of Major Depression and Anxiety Disorders: Recognition and Management in Primary Care. Journal of clinical psychiatry, 3(6), 244–254. doi:10.4088/pcc.v03n0609

BRAIN BUSTERS 1. Baik, J. (2013). Dopamine signaling in rewardrelated behaviors. Frontiers in Neural Circuits, 7(152). doi:10.3389/fncir.2013.00152 2. Beaty, R. E., Kenett, Y. N., Christensen, A. P., Rosenberg, M. D., Benedek, M., Chen, Q., Fink, A., Qiu, J., Kwapil, T. R., Kane, M. J., & Silvia, P. J. (2018). Robust prediction of individual creative ability from brain functional connectivity. Proceedings of the National Academy of Sciences of the United States of America, 115(5), 1087–1092. https://doi.org/10.1073/ pnas.1713532115 3. Belujon, P., & Grace, A. A. (2017). Dopamine system dysregulation in major depressive disorders. The International Journal of Neuropsychopharmacology, 20(12), 1036–1046. doi:10.1093/ijnp/pyx056. 4. Berridge, K.C., Venier, I.L., & Robinson, T.E. (1989). Taste reactivity analysis of 6-hydroxydopamineinduced aphagia: implications for arousal and anhedonia hypotheses of dopamine function. Behav Neurosci, 103(1), 36-45. doi:10.1037/0735-7044.103.1.36. 5. Beyerstein, B.L. (1999). “Whence cometh the myth that we only use ten percent of our brains?” In, S. Della Sala (Ed.), Mind Myths: Exploring Popular Assumptions About the Mind and Brain (pp. 1-24). John Wiley and Sons., Ltd. 6. Carnegie, D. (1936). How to win friends and influence people. Simon & Schuster. 7. Cools R. (2008). Role of dopamine in the motivational and cognitive control of behavior. Neuroscientist, 14(4):381-95. doi: 10.1177/1073858408317009. 8. Diamond, M.C., Scheibel, A.B., Murphy Jr., G.M., & Harvey, T. (1985). On the brain of a scientist: Albert Einstein. Experimental Neurology, 88(1), 198-204. doi:10.1016/0014-4886(85)90123-2. 9. Herculano-Houzel S. (2002). Do you know your brain? A survey on public neuroscience literacy at the closing of the decade of the brain. Neuroscientist, 8(2), 98-110. doi:10.1177/107385840200800206.

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

References 10. Higbee, K.L., & Clay, S.L. (1998). College students’ beliefs in the ten-percent myth. Journal of Psychology, 132, 469-476, 471. doi:10.1080/00223989809599280

20. Wise, R.A. & Robble, M.A. (2020). Dopamine and addiction. Annual Review of Psychology, 71:79-106. doi:10.1146/annurev-psych-010418-103337.

11. James, W. (1907). The energies of men. The Philosophical Review, 16(1), 1-20. doi:10.2307/2177575. 12. Lilienfeld, S. O., Lynn, S. J., Ruscio, J., & Beyerstein, B. L. (2010). The top ten myths of popular psychology. Skeptic [Altadena, CA], 15(3), 36+. Retrieved from https:// link.gale.com/apps/doc/A220057908/ AONE?u=bron88970&sid=AONE&xid=2bc454c6. 13. Manning, L., & Thomas-Antérion, C. (2011). Marc Dax and the discovery of the lateralisation of language in the left cerebral hemisphere. Rev Neurol (Paris). 167(12), 868-72. doi:10.1016/j.neurol.2010.10.017. PMID: 21640366. 14. Nielsen, J. A., Zielinski, B. A., Ferguson, M. A., Lainhart, J. E., & Anderson, J. S. (2013). An evaluation of the left-brain vs. right-brain hypothesis with resting state functional connectivity magnetic resonance imaging. PLOS ONE, 8(8). doi:10.1371/ journal.pone.0071275. 15. Olds, J., & Milner, P. (1954). Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain. Journal of Comparative and Physiological Psychology, 47(6), 419-427. doi:10.1037/h0058775. 16. Pinho, A. L., Ullén, F., Castelo-Branco, M., Fransson, P., & De Manzano, Ö. (2015). Addressing a paradox: dual strategies for creative performance in introspective and extrospective networks. Cerebral Cortex, 26(7), 3052-3063. doi:10.1093/cercor/bhv130. 17. Sperry, R. (1982). Some effects of disconnecting the cerebral hemispheres. Science, 217(4566), 12231226. 18. Sun, F. (2011). All-TIME Nonfiction Books. TIME Magazine. 19. von Bartheld, C. S., Bahney, J., & HerculanoHouzel, S. (2016). The search for true numbers of neurons and glial cells in the human brain: A review of 150 years of cell counting. The Journal of Comparative Neurology, 524(18), 3865–3895. doi:10.1002/cne.24040.

GREY MATTERS JOURNAL AT VASSAR COLLEGE | ISSUE 2

Grey Matters Journal VC Issue 2 Spring 2021

Articles inside

BRAIN BUSTERS

DEPRESSION AND ANXIETY: THE FRENEMIES NO COLLEGE STUDENT WANTS TO MEET

RNA: A NEW FACE IN THE FIGHT AGAINST NEURODEGENERATION

BEWARE THE POST-VACCINE BLUES

ENCOUNTERS WITH THE THIRD KIND: THE MEMORY TWILIGHT ZONE

JUST ANOTHER FACE IN THE CROWD: THE EVOLUTION AND MECHANISMS OF PRIMATE FACIAL PROCESSING

SEX DIFFERENCES AND DEPRESSION: THE MALE-CENTRIC RESEARCH MODEL'S HARMFUL EFFECTS ON FEMALES

REWIRING THE BRAIN: HOW THE NERVOUS SYSTEM HEALS ITSELF

DEFYING THE “WAR ON DRUGS”: THE REBIRTH

FAKING IT ‘TILL YOU MAKE IT: WHY WE

A HOT ISSUE: TEMPERATURE-DEPENDENT