Hannah Alton (Neuroscience), Developing Human Stem Cell Models to Probe Mechanisms of Therapeutic Psychedelics (advisor Stephen Haggarty, HMS) – Video Presentation 
Psychedelic compounds are predominantly known for their effects on cognition and sensory experiences, but a growing body of research suggests that they have therapeutic potential to combat psychiatric disorders such as depression and post-traumatic stress disorder. The therapeutic effect of psychedelics is hypothesized to occur via serotonin 2A receptor (5-HT2AR)- mediated neuroplasticity. However, a deeper understanding of mechanisms of action of these compounds is necessary for future development of psychedelics as novel therapeutics. In this study, I established the first human neuronal model to evaluate psychedelic-induced neuroplasticity. I differentiated neural progenitor cells derived from human induced pluripotent stem cells (iPSCs) for up to 6 weeks; imaging via immunocytochemistry showed expression of mature neuronal markers at the appropriate timepoints. Western blots of the 5-HT2A receptor confirmed its presence and increase in expression throughout differentiation, and immunocytochemistry showed that the receptor was correctly localized. After I treated 6-week differentiated neurons with 1 μM 2,5-Dimethoxy-4-iodoamphetamine (DOI), Western blots revealed a significant increase in p-PAK and p-ERK over the course of 1 hour, validating the functionality of the 5-HT2AR and suggesting a new time course of 5-HT2A activation in human neurons. The 5-HT2A antagonist ketanserin did not block DOI’s effect on PAK and ERK phosphorylation, meriting further studies on ketanserin dosage and non-5-HT2A-specific effects. Finally, Western blots detecting p-PAK and p-ERK levels in neural progenitor cells suggested a developmental difference in 5-HT2AR functionality. These results encourage further experiments using human iPSC-derived neuronal models to evaluate the pharmacology of psychedelic compounds and mechanisms of 5-HT2AR.

Thet (Michelle) Aye (Neuroscience), Characterization of Drug Penetration through the Rhesus Monkey Blood-Brain-Barrier using MALDI Mass Spectrometry Imaging and Immunohistochemistry (advisors Nathalie Agar, HMS & Sylwia Stopka, HMS & Elisa York, HMS) – Video Presentation 
The blood-brain barrier (BBB) is a highly selective barrier that regulates the molecular and cellular traffic between blood and brain, effectively maintaining cerebral homeostasis. The BBB’s importance in proper brain function is undeniable but a complication that arises from its relative impermeability is in the treatment of central nervous system (CNS) disorders, including brain cancers. Most cancer drugs cannot reliably bypass the BBB through traditional oral or intravascular administration, making the treatment of brain tumors remarkably challenging. Therefore, there is a need for better understanding the BBB and its mechanisms, which will support the development of more efficient drug therapies and/or delivery systems. This thesis explored drug penetrance through the BBB using the novel approach of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI). To have a system most relevant to and predictive of the CNS in humans, we studied the dynamics of drug uptake and metabolism in the Rhesus macaque monkey using MALDI MSI and immunohistochemistry (IHC). Using MALDI MSI, we identified regional heterogeneity in drug distribution. Notably, we found the highest concentrations of drug in the choroid plexus as well as tissue surrounding the cerebral ventricles, highlighting a potential role of the blood-cerebrospinal fluid barrier in drug delivery. In conjunction, we profiled regional differences in expression of BBB regulators such as astrocyte end-feet and tight junction proteins with IHC to characterize the molecular makeup of the BBB relative to drug penetration.

Jacob Blair (Neuroscience-Philosophy), We Can’t All Be Right: The Neural Correlates of Distinguishing between Fact and Opinion Statements in a Political Context (advisor Mina Cikara, FAS/Psychology) – Video Presentation 
Political beliefs present a particularly salient example where making a distinction between facts and opinions can be difficult, but failing to do so can be costly. Through the advent of technology, the public has unprecedented access to information in the forms of both opinions and data. Despite this, people struggle to differentiate between factual and opinion statements they encounter in the vast informational landscape. Through a series of behavioral studies and a functional magnetic resonance imaging study, I investigated neural representations of statements about the world that were political and nonpolitical in nature. Participants viewed political and nonpolitical propositions phrased as either opinions or facts, and made explicit judgments about the class of each statement (opinion statement or factual statement). Multivariate representational analyses of neural pattern responses to each statement revealed clearer neural pattern separation among non-political fact vs. opinion statements than among political fact vs. opinion statements. This conclusion suggests that the distinction between “fact” and “opinion” contains both objective and social components. Through this thesis, I also develop language to describe this phenomenon – parsing the epistemic status of a statement as fact or opinion from the psychological feeling that a statement falls into one of these categories. Further, I explore and demonstrate the utility of this language in helping us understand and discuss this common phenomenon.


Alexandre Chaumette (Neuroscience), Psychosocial Adversity and Language Learning Outcomes of 2- and 5-year-old Bangladeshi Children: An fNIRS Analysis (advisor Charles Nelson, HMS) – Video Presentation 
While early life adversity is understood to confer long-lasting influences on behavior, physical, and mental health outcomes, the neurobiological basis of these influences remains to be well understood. The present work investigated associations between early life psychosocial adversity and neuroimaging and cognitive outcomes in children at two (N=72) and five years (N=93) of age in the urban slums of Dhaka, Bangladesh. The analysis aimed: (1) to evaluate neural responses to auditory cues of varying predictabilities; (2) to assess whether variation in neural responses was explained by indicators of early life adversity; and (3) to further explore the relationships between neural responses, psychosocial adversity, and cognitive outcomes. Functional near-infrared spectroscopy (fNIRS), a neuroimaging technique increasingly employed in developmental neuroscience research, was used to record hemodynamic responses during an auditory statistical learning task. Cumulative and domain-specific exposures to adversity from the Childhood Psychosocial Adversity Scale (CPAS) were incorporated to determine the relationship between adverse exposures and neuroimaging and behavioral outcomes. While higher levels of oxygenated hemoglobin in response to the predictable condition were found for the children at 2 years of age, children at 5 years of age exhibited consistently higher levels of oxygenated hemoglobin in response to the novel condition. Higher levels of adversity explained decreased discrimination between auditory cues, although the relationship between adversity and cognitive outcomes was not mediated by these neural responses. These results suggest that sensitivity to auditory structure emerges as early as 2 years of age, calling for interventions that address the early life psychosocial environment.


Jenny Gan (Neuroscience), Investigating Alterations in Neural Responses During Evoked Pain Following Mindfulness Intervention in Patients with Anxiety and Depression (advisors Zev Schuman-Olivier, HMS & Mike Datko, HMS) – Video Presentation
Background: Mindfulness Training for Primary Care (MTPC) is a mindfulness-based intervention designed for primary care patients with depression and anxiety. We studied how mindfulness influenced mechanistic self-regulation targets (i.e., emotion regulation, interoceptive awareness), as assessed by fMRI. Learning about brain mechanisms can support clinical behavioral effects and has implications for the effective treatment of this population. Methods: To investigate the effects of MTPC on brain mechanisms of evoked pain, adults (n=41) with depression and/or anxiety completed baseline and post-treatment fMRI visits. Results: Following MTPC, participants showed significantly increased levels of interoceptive awareness, decreased levels of anxiety, and significant decreases in subjective ratings of pain intensity and unpleasantness. At post-treatment, decreased fMRI response during pain was observed in right ventrolateral prefrontal cortex (RVLPFC) as compared to baseline. Additionally, decreased fMRI response during pain anticipation was observed in RVLPFC, left ventrolateral prefrontal cortex (LVLPFC), and right supplementary motor area (RSMA). Furthermore, there was a significant correlation between increased MAIA score and decreased posterior cingulate cortex fMRI activity during the pain response. Discussion: The decreased activation at post-treatment of key emotion regulation areas during pain and pain anticipation, decreased recruitment of a key node in the default mode network, and participant’s improved anxiety and interoceptive awareness point to MTPC’s effectiveness. This study suggests that MTPC can decrease the need for emotional regulation during the experience and anticipation of negative stimuli and/or decrease the salience of the painful stimulus itself.


Andrew Siyoon Ham (Neuroscience), Nociceptor Control over Resolution of Inflammation and Tissue Repair in the Skin (advisor Clifford Woolf, HMS) – Video Presentation 
Tissue injury and repair processes are always associated with inflammatory pain, but the role of pain-triggering neurons in the resolution of inflammation has been largely unexplored, particularly in skin tissue. Nociceptors, sensory neurons that initiate the sensation of pain, modulate inflammation through bi-directional interactions with the innate immune system. We created two in vivo injury models (plantar incision and Zymosan fungal infection) to investigate the role of TRPV1+ nociceptors and their major neurotransmitter CGRP in the resolution of skin inflammation. TRPV1+ nociceptors were ablated in mice using the expression of diphtheria toxin and its receptor while CGRP was inhibited by its antagonist BIBN, and downstream effects on immune cell populations were quantified using flow cytometry. We found that neutrophil levels were significantly elevated after TRPV1+ nociceptor ablation compared to controls 96 hours after paw incision, a timepoint where WT mice have largely achieved homeostasis, and visible impediments to wound healing were observed. Neutrophil levels were also moderately elevated in mice with CGRP’s action blocked in vivo by BIBN. In vitro studies of macrophages suggested that CGRP reduces levels of the pro-inflammatory cytokine TNFα directly and reduces pro- inflammatory IL-6 through IL-10 as an intermediary cytokine, providing a potential mechanistic explanation for the delayed resolution of inflammation in mice lacking nociceptor and CGRP activity. Our results suggest that nociceptors appear to promote inflammation resolution through CGRP release, which activates anti-inflammatory secretions from macrophages to control neutrophil levels at sites of injury. Understanding, in more detail, the neuronal mechanisms that govern resolution will be immensely helpful for the modulation of inflammatory pain.


Katrina Hon (Neuroscience), Sexual Dimorphism of the Hippocampus Structure and Function in Psychosis (advisor Marek Kubicki, HMS) – Video Presentation 


Pechthida Kim (Psychology), The Evaluative Nature of Summaries (advisors Tomer Ullman, FAS/Psychology and Julian De Freitas, HBS) – Video Presentation
Life is filled with experiences over time. How do people summarize them? Previous work on the summary of continuous trajectories (such as the unfolding of a life) has focused on singular features, such as duration (Varey & Kahneman, 1992), peak value (Fredrickson & Kahneman, 1993), and end value (Carmon & Kahneman, 1996). Here, we consider the broader hypothesis that people evaluate a trajectory based on its overall pattern over time. While previous work has considered simple patterns that test the role of a single feature at a time, we examine 27 patterns and quantitatively assess the role of 20 predictors—spanning literal features of the line to words that people used to describe them—in predicting participant ratings. We put these features to the test in three domains, asking people to summarize 1) lifelines, representing a person’s happiness over their entire life; 2) interview performance lines, representing how impressed an interviewer was with a job candidate throughout their interview; and 3) customer journeys, representing a customer’s happiness over time with a solar panel firm. In a fourth study, we tested whether people are naturally evaluative when it comes to summarizing experiences by asking them to simply describe trajectories without making accompanying judgments. We found that, across all three domains, a trajectory’s pattern significantly affected participant judgments of how meaningful, satisfying, or desirable it was. In addition, participants naturally utilized a combination of features to evaluate whether the experience was positive or negative, which then informed their judgments.


Elizabeth Kinard (Neuroscience), Opioid Dependence and Withdrawal-Driven Modulations of Feeding Behavior in Male and Female Rats (Elena Chartoff, HMS) – Video Presentation 
Opioids are a class of endogenous and exogenous compounds that bind to endogenous opioid receptors in the brain (mu, kappa, and delta). Opioid abuse interferes with the role of endogenous opioids, disrupting normal feeding behaviors. Chronic opioid abuse results in dependence, characterized by withdrawal syndrome upon drug cessation. Opioid dependence is associated with weight gain and opioid withdrawal is associated with weight loss, which could be due in part to alterations in food intake and motivation to eat. Multiple and overlapping brain circuits are necessary for homeostatic and hedonic feeding, and although opioids are implicated in both, the neurobiological mechanisms are not fully understood. A key neural circuit modulating feeding involves interactions between orexin (ORX) and melanin concentrating hormone (MCH) in the lateral hypothalamus (LH) and their projections to brain regions such as the nucleus accumbens (NAc) and paraventricular nucleus of the thalamus (PVT). This study aims to investigate the way in which opioid dependence and withdrawal modulates homeostatic and hedonic feeding, and the role of ORX and MCH. Since opioid withdrawal is associated with an increase in orexin (ORX) expression but decreased feeding, we hypothesize that this could be explained by a simultaneous decrease in melanin-concentration hormone (MCH) activity, resulting in an overall decrease in motivation to eat. Using male and female rats, we measured food and water intake, body weight, and motivation to eat via progressive ratio sucrose administration tasks to get a baseline, then took the same measurements during morphine dependence and naloxone-precipitated withdrawal. Lastly, we quantified cFos-induced LH activation and MCH/ORX co-expression with cFos using immunohistochemistry to determine if MCH/ORX neuronal activity changes as a result of naloxone treatment. Naloxone-induced withdrawal suppressed body weight gain and decreased chow intake in placebo and morphine male rats. The reinforcing effects of sucrose and the motivation to work for sucrose are highly variable during development of morphine dependence. Naloxone decreases the reinforcing and motivational properties of sucrose in both placebo and morphine treated male and female rats. Finally, naloxone increased cFos expression in the LH of morphine dependent male rates but did not affect co-expression of cFos with MCH or ORX neurons.


Caroline Kremer (Neuroscience), Perceptual Hypersensitivity to Sound Following Acoustic Trauma (advisor Daniel Polley, HMS) – Video Presentation 
Across sensory systems, perceptual disorders that involve hypersensitivity to normal stimuli are enigmatic, but often appear following damage to the sensory periphery that reduces or eliminates input to higher brain regions. Recent studies suggest that sensory cortices respond to peripheral sensory deprivation with a drastic increase in neuronal activity, which may drive subjective reports of perceptual hypersensitivity. Hyperacusis, a disorder in which normal auditory stimuli are perceived as being excessively loud, is thought to follow this model. However, the causal link between a loss of peripheral input, cortical hyperactivity, and perceptual hypersensitivity is ill-defined. We studied these phenomena in mice, using a two-alternative forced choice (2AFC) task that required mice to categorize tones as either loud or soft, thereby quantifying their perception of loudness. Following a training period, we noise-exposed mice to damage the auditory periphery, using two well-established hearing loss protocols, in order to visualize their changes in loudness perception as compared to sham-exposed mice. Additionally, through optogenetic inhibition experiments, we transiently inactivated the auditory cortex (ACtx) by selectively activating PV+ inhibitory interneurons on trials of the 2AFC task. We found that acoustic trauma reliably induced an increase in loudness perception, which causally linked peripheral sensory deprivation to perceptual hypersensitivity. Furthermore, this expression of loudness perception depended on cortical activity, in that optogenetic silencing of ACtx led to a decrease in loudness perception. Taken together, these results indicate that, following damage to the auditory periphery, compensatory cortical hyperactivity may drive the perceptual hypersensitivity that defines hyperacusis.


Darius Lam (Computer Science), Video Representation Learning via Actons (advisor Hanspeter Pfister, FAS/SEAS) – Video Presentation 
In this paper, we propose a novel method for dense video representation learning. Through our method, we are able to learn compressed frame representations known as “actons”. By extracting actons, we strike a middle ground between expressive but computationally de- manding frame-wise features and low information whole-video features. Our model consists of two-branch processing using a VQ-Codebook and a Transformer encoder trained on the Masked-Language Modeling protocol. In order to fit within the scope of this work, we extract small-scale datasets from TinyVIRAT and UCF101, both action recognition datasets, which we use to evaluate our methods. We find that our acton representations are far smaller than original video lengths, reaching compression ratios up to 18x, that are also more expressive than framewise features. We also find that fine-tuning using our representations achieves better test-set accuracy on action classification when compared to a C3D baseline.


Huong Le (Neuroscience), Molecular RNA and protein machinery within subtype-specific corticospinal neurons and their synapses as potential underpinnings of selective vulnerability in amyotrophic lateral sclerosis (advisor Jeffrey Macklis, FAS/HMS, Stem Cell and Regenerative Biology) – Video Presentation 


Uriel Martinez (Neuroscience), An Exploration of the Relationship between REM Theta Power Spectral Density and Extinction Retention (advisor Edward Pace-Schott, HMS) – Video Presentation 
Emotional learning by association and its regulation by extinction is paramount for understanding anxiety disorders like PTSD, where individuals may have impaired emotional learning and memory. Rapid eye movement (REM) sleep is thought to play a role in emotional memory. REM electroencephalogram (EEG) theta rhythm, a defining feature of REM in human rodents, has also been associated with contextual memory consolidation. This thesis examines the relationship between REM theta spectral power density (PSD) during the consolidation night and extinction retention in trauma-exposed controls (TECs) as well as participants with posttraumatic stress disorder (PTSD). 139 TECs or participants with PTSD underwent Milad’s Fear Conditioning, Extinction, and Extinction Recall protocol. This protocol provided the information necessary to calculate physiological and expectancy measures of fear retained. Theta spectral power density (PSD) was measured with EEG during all three nights including the consolidation night on the second day. After identifying the non-normal distribution of the predictor variables with the Shapiro-Wilk test, a non-parametric Whitney-Man U test confirmed that none of the spectral or fear retention measures differed between the PTSD and TEC groups. While Spearman's rank correlation coefficient pointed to a nonsignificant positive trend for the second expectancy measure of unextinguished fear across two measures of theta spectral power, extinction retention was not found to be associated with physiological and expectancy measures of REM theta spectral power.

Te Palandjian (Philosophy), Taking People as They Could Be? Social Ethos and the Viability of Social Egalitarianism (advisor Lucas Stanczyk, FAS/Philosophy) – Video Presentation
In this thesis, I want to ask a fundamental question about the viability of liberal egalitarianism: whether a theory of justice can be committed to protecting centrally important individual liberties (freedom of occupational choice, freedom of movement and the right to live where one pleases, freedom of association including freedom of romantic partner choices), while at the same time ensuring a fair distribution of social and economic goods and eliminating intuitively objectionable inequalities. On its face, this question may strike the reader as odd. Why wouldn’t a theory of justice be able to both guarantee the basic liberties of citizens and oppose itself to intuitively objectionable inequalities? Breaking down these desiderata helps us understand where the tension lies. By a ‘theory of justice,’ I mean an account of how to arrange social and political institutions and adjudicate the competing claims of the members of a society to the products of social cooperation. A liberal egalitarian theory of justice is one that expresses a dual commitment to the value of individual freedom, on the one hand, and the importance of avoiding objectionable socioeconomic inequalities on the other hand. What counts as an ‘objectionable socioeconomic inequality’ depends on the details of a given theory, but will normally include the allocation of jobs, positions, income, and wealth¹ that favor certain people unfairly over others or provide unacceptably low quality of life for any citizens. Now, many objectionable socioeconomic inequalities constitute significant injustices and signal moral failures on the part of institutions, but such inequalities do not raise any deep questions about the viability of a liberal egalitarian theory of justice. Instead, their objectionable nature is clearly captured by all plausible liberal egalitarian theories. For example, it is unjust that many women continue to be paid less than men for the exact same work, and the workplace discrimination that is responsible for this outcome is straightforwardly condemned by all liberal egalitarian theories of justice. However, some enduring, intuitively objectionable inequalities do pose a potential problem for liberal egalitarian theories. It is these types of inequalities, that endure by virtue of a liberal egalitarian theory’s commitment to individual liberties, that I will focus my analysis on. Take for instance the differences in life prospects that can be traced to the pervasive influence of pornography, which has been labeled unethical by many feminists because its subject matter shapes people’s attitudes, preferences, aspirations, and choices in a sexist and misogynistic direction. What feminists who take issue with pornography are attacking is not simply the treatment of sex workers or their wages in our society, but that the pornographic content produced and consumed in our society gives rise to and reproduces sexist preferences and attitudes that, in turn, pervasively affect women’s life prospects. As feminist philosopher Catherine Mackinnon clarifies, pornography is not “harmless fantasy:” “through pornography, among other practices, gender inequality becomes both sexual and socially real” (Mackinnon, 1989, p. 328). Mackinnon’s point is that sexist attitudes and preferences stemming from the consumption of pornography have a “socially real” effect on gendered outcome inequalities; the clearest example may be that such preferences contribute to inequality in the division of unpaid household labor, where the choices that heterosexual couples make about who stays home have significant material consequences for girls and women.² These inequalities in earning potential seem intuitively unfair, and to be condemned as such by our theory of justice. And yet, if the consumption of pornography is a choice protected by the basic liberties of citizenship—to which liberal egalitarian theories are also committed—then liberal egalitarian theories of justice face a deep problem. Namely, can such theories really condemn as unjust, all intuitively objectionable economic and social inequalities when some of these inequalities arise and endure in part because of the choices people make when they exercise their basic liberties of citizenship? In the case of pornography, the freedom to make content, consume it, and the personal life choices that follow create objectionable inequalities of opportunity, income, and leisure between men and women. Thereby, my inquiry into the viability of liberal egalitarianism will proceed by examining a particular case of this problem. In Chapter 1, after explaining the relevant elements of John Rawls’ theory of justice as perhaps the most important exemplar of liberal egalitarianism, I will reconstruct the critique of the institutional focus of Rawls’ political theory, as developed by philosopher G. A. Cohen in a series of lectures and writing. The conclusion of Chapter 1 will be, first, that the social ethos that prevails in a society and informs individual choices is relevant to assessing the justice of a society, but second, that how the social ethos is relevant to the formulation of principles of justice depends on the empirical truth concerning what institutions are capable of doing to alter an inegalitarian or otherwise problematic social ethos using only permissible institutional means that do not violate citizen’s basic rights. To anticipate my later conclusion, I will argue that if institutions alone are, in fact, permissibly able to eliminate every problematic ethos that generates intuitively objectionable inequalities in a society, there is no need to extend the principles of justice to apply directly to personal choices and the social ethos itself. However, if institutions cannot in fact eliminate all of the causal sources of all intuitively objectionable socioeconomic inequalities using only permissible institutional means, then what I will call the “argument from institutional determinism,” under which principles apply only to institutions, will not be an adequate defense of viable Rawlsian liberal egalitarianism. Building on this analysis, Chapter 2 will go on to argue that there is at least one causal source of endring, intuitively objectionable socioeconomic inequality that liberal institutions, by themselves, are unlikely to be able to eliminate fully using only permissible means. This causal source is the tendency to form homogeneous intimate partnerships along racial lines, enabled by the liberal freedom of association,³ which is an important reason for the reproduction of racial inequality over time. In light of this inability of institutions alone to be able to do all the work that justice on any plausible liberal egalitarian theory requires, I will conclude that to be viable, liberal egalitarianism will need to give up its strictly institutional focus and admit that the social ethos and even individual choices of intimate partner are themselves directly answerable to principles of justice. Notes: ¹ In John Rawls terminology, these are called “primary social goods.” ² I will not delve further into what types of pornographic preferences lead to this trend of unequal division of labor, but a submissive and doting advertisement of women in porn is one place to start. ³ Put simply, citizens’ freedoms under liberal stheory to love and commit to whomever they please.

Anastasia Ryhanych (Neuroscience), Functional Magnetic Resonance Imaging-Based Individualized Mapping of the Lateral Salience System in Major Depressive Disorder (advisor Matthew Sacchet, HMS) – Video Presentation at https://vimeo.com/704208634
The objective of this thesis was to determine relations among individualized brain systems and major depressive disorder (MDD), specifically focusing on the lateral salience system. We used a computational neuroimaging approach applied to whole-brain functional magnetic resonance imaging (fMRI) data acquired from individuals diagnosed with major depression, in addition to healthy controls. Our iterative cortical parcellation approach resulted in the definition of individualized brain system "patches." Here we focused on the lateral salience system given that prior research has identified relations among its activity and major depression. We quantified the size of each brain system patch within the lateral salience system. We hypothesized that patients diagnosed with major depressive disorder would exhibit abnormal system topologies in the lateral salience system. We found that patch sizes of the parietal operculum subregion of the lateral salience system were smaller in MDD patients compared to healthy controls and that the size of these patches relates to levels of anxiety. This thesis includes a discussion of how these findings contribute to the literature and may inform future research. We also discuss the findings in the context of clinical applications.

Jason Xiliang Shen (Neuroscience), Mapping Aggression Neurocircuitry in a UBE3A Mouse Model of Autism (advisors Matthew Anderson, HMS & Clifford Saper, HMS) – Video Presentation 
Aggressive behavior is a phenotype that places a heavy burden on the lives of individuals with Autism Spectrum Disorder (ASD) and the lives of their families. Nonetheless, the etiology of ASD remains unknown at a neurocircuitry level. Recent studies have identified the ubiquitin ligase UBE3A as a prominent player in disrupting glutamatergic signaling and causing severe social impairments and aggressive behaviors when elevated in idic(15) ASD. To provide a preliminary circuit-level understanding of how excessive UBE3A drives aggression, this study investigated the relative activity levels of structures implicated in aggression. These include the ventrolateral nucleus of the ventromedial hypothalamus, the arcuate nucleus of the hypothalamus, the periaqueductal grey, the dorsal raphe, the bed nucleus of the stria terminalis, the ventral premammillary nucleus, and the medial amygdala. 2xUBE3A mice and control mice were tested in the resident-intruder paradigm, and their brains were subsequently analyzed for c-Fos levels as a measure of neuronal activation. The number of active cells in each structure was compared across test and control groups at a Bregma-matched scale using two-sample T-Tests and repeated two-way ANOVA with Bonferroni’s Multiple Correction. Test mice showed significantly less activation of the arcuate nucleus and significantly greater activation of a medioventral subregion of the VMHvl. Such evidence preliminarily suggests that the pathological aggression of idic(15) ASD may possibly arise from higher than normal VMHvl activity and lower than normal arcuate nucleus activity: a finding that may be relevant to the mechanism of the popular and effective ASD therapeutic, Risperidone.


Zoya Surani (Neuroscience), Determining the relationship between psychosocial adversity and children’s executive functioning: an fMRI study (advisor Nadine Gaab, GSE) – Video Presentation 
Exposure to psychosocial adversity (PA) early in life has been shown to impair executive functioning (EF), but the brain mechanisms explaining this relationship are unclear. Additionally, most studies on this topic have been conducted in high-resource environments, despite low-resource environments having a higher prevalence of PA risk factors. These are important considerations, not only to understand if existing trends from research done in highand middle-resource countries extend to low-resource countries, but also to examine brain function underlying impairments in EF among children exposed to PA. We collected both fMRI data acquired during a Go/No-Go (GNG) response inhibition task (which measures EF) and behavioral data of PA variables for 71 children living in Dhaka, Bangladesh, a low-resource area with a high prevalence of PA. We tested associations between PA measures (separated into categories of abuse, neglect, and household dysfunction) and brain activation during a GNG task. We observed activation in the prefrontal cortex, insula, and visual areas in the response inhibition contrast (No-Go versus Go), consistent with previous GNG studies. Significant results were found in regression analyses for abuse, household dysfunction, and total PA with brain activation in the No-Go versus Go condition, specifically in the cingulate gyrus and lentiform nucleus areas. We observed increased activation in these areas, which may be indicative of overcompensation. This research adds to existing literature by examining the brain basis of the relationship between PA and EF and offers a necessary perspective on how this relationship manifests in the brain in children in a low-resource environment with a high prevalence of PA.