Apply for a Travel Award! We Are Accepting Applications Jan 1 - March 1, 2023

Travel Awards

One of the most rewarding and unique features of the symposium is that we provide travel awards to domestic and international students to come to UW and learn with us. These scholarships go to students at all levels of their education including: undergraduates, grad students, PhD students, post-doctoral fellows, MD students and residents training in psychiatry.

This year the HealthEmotions Research Institute will support the expenses of 10-15 trainees from the US and around the world to come to Madison and participate in the symposium. This is a wonderful opportunity for students at all levels to interact with world class scientists, meet UW-Madison faculty, and forge connections with others conducting research in the broad field of affective neuroscience.

The HealthEmotions Research Institute will provide $300 for travel and 2 nights gratis hotel accommodations for 10-15 students to attend the Wisconsin Symposium on Emotion (April 19-20, 2023) and present a poster during the poster session and reception.

The 2023 travel award competition will accept applications Jan 1st through midnight on March 1, 2023. Winners will be announced March 15, 2023 and notified by email.

Eligibility

Undergraduates, graduates, doctorates, post-doctorates, fellows, medical students, and residents are eligible to apply for a travel award.

Application

Please submit your application to healthemotions@wisc.edu in the form of one PDF file that contains the following documents in this exact order:

  1. 2023 Wisconsin Symposium on Emotion Travel Award Application Form
  2. Current CV
  3. Abstract for the poster you will be presenting (not to exceed 250 words)
  4. Personal Statement of Research Interest (one page limit)
  5.  Letter of Student Merit
    Please request that your mentor email a support letter that includes a statement of student merit directly to healthemotions@wisc.edu (due on March 1, 2023)

This is a competitive award. All application materials are due by midnight on March 1, 2023. Only complete applications will be considered. The entries will be judged by a selection committee of HealthEmotions Research Institute faculty members and the winners will be notified by email on March 15, 2023.

2022 travel award recipients:

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Ben Yang, PhD | Northwestern University

University: Northwestern University
Department: Neuroscience
Program or lab: Jones Parker & Anis Contractor’s labs
Mentor or PI: Jones Parker & Anis Contractor

Poster Title: Modulating D1 rather than D2 receptor-expressing spiny-projection neurons corresponds to optimal antipsychotic effect

Abstract: 
Excess dopamine transmission in psychosis is predicted to unbalance striatal output via D1- and D2-dopamine receptor-expressing spiny-projection neurons (SPNs). Antipsychotic drugs are thought to re-balance this output by attenuating striatal D2-receptor signaling. Here we imaged D1- and D2-SPN Ca2+ dynamics in vivo to determine whether they can predict antipsychotic effect. Initially we compared effective (clozapine and haloperidol) to ineffective (MP-10) antipsychotic treatments. Clozapine and haloperidol normalized hyperdopaminergic D1-SPN ensemble dynamics, while MP-10 only normalized D2-SPN activity. Clozapine, haloperidol or chemogenetic manipulations of D1-SPNs also normalized sensorimotor gating. Given this link between D1-SPN modulation and antipsychotic effect, next we evaluated compounds selectively targeted to D1-SPNs. D1R partial agonism, antagonism, or positive modulation of M4 cholinergic receptors all normalized the levels of D1-SPN activity, locomotion, and sensorimotor gating. Our results suggest that D1-SPNs are a more relevant therapeutic target than D2-SPNs in psychotic disorders and adjudicate basic strategies for doing so.


Personal Statement: 

My initial interest in science was driven by a child’s question of “Who am I?” After I read the books of Erwin Schrödinger on the beauty of life and mind that I decided to turn to biology for answers and started a new journey into biomedical research. Over the past 15 years, I have explored different fields with different approaches, including my undergraduate research on fish development and evolution for which I used genetic strategies and computational analysis, my job as a research assistant that allowed me to study cancer “evolution” using molecular and cellular methods, and my PhD training with electrophysiological, optical, and behavioral approaches to study the brain – the most complicated organ that makes who we are as humans. The primary focus of my PhD work was on the mechanism of dopaminergic cell loss in Parkinson’s disease (PD) that causes the cardinal motor symptoms. However, other than movement disorders, Parkinson’s patients develop multiple psychiatric symptoms, which are less studied. Towards the end of my PhD, I became interested in mental disorders and developed a research project that differed from my lab’s main focus. Specifically, I explored how stress can regulate feeding behavior and found a surprising role of locus coeruleus (LC) neurotransmitter co-release in mediating fear-induced suppression of feeding. This novel finding of neurotransmitter co-release from LC not only challenged the Dale’s law in neuroscience (one type of neuron release one type of transmitter), but also revealed, for the first time, a physiological and biological function of neurotransmitter co-release. My study provided new targets for treating anxiety and trauma-related feeding disorders and stress-induced anorexia. Given that LC neurons are also lost in PD, my study also provides new insights into the psychiatric dysfunctions in PD. For the postdoctoral work, I want to better understand the neural mechanisms of Schizophrenia and the function of dopamine. In collaboration with another postdoctoral fellow, we found that antipsychotic drugs, despite being selective type 2-dopaminergic receptor (D2R) antagonists, modulate both D1 and D2 striatal neuron (SPN) activities. Importantly, the modulation of D1-SPN activity, but not D2-SPN activity correlates with their clinical antipsychotic efficacies, suggesting targeting D1Rs may provide better treatment for Schizophrenia. Currently, I am using cutting-edge genetic and imaging techniques to understand the functional organization of the striatum and the roles of dopamine in different psychiatric disorders, including Schizophrenia. Psychiatric disorders have become the leading causes of disability worldwide. A better understanding of psychiatric disorders and their biological basis – emotions – is in urgent need. Some great ethologists, including Charles Darwin, Konrad Lorenz and Niko Tinbergen, were limited by the techniques of their times for studying emotional behavior without a deeper understanding of the underlying neural mechanisms. Sydney Brenner once said, “Progress in science depends on new techniques, new discoveries, and new ideas, probably in that order.” We now have the tools to study the underpinnings of emotional behavior at multiple levels, from molecular genetics to cellular electrophysiology, to mesoscopic and brain-wide recordings and computational decoding. We are beginning to be able to continue their lines of behavioral observation and provide profound understanding of the neural mechanisms. For my long-term career goal, I would look upward to understand and appreciate the beauty of brain functions, particularly emotions, and at the same time look downward into the details of psychiatric disorders and to develop better treatments.

Ellie P. Xu, BA | University of Southern California

Name: Ellie P. Xu, BA
University:
University of Southern California
Department: Psychology
Program or Lab: Clinical Science
Mentor or PI: Dr. Jonathan Stange

Poster:  A meta-analysis on the uncinate fasciculus in depression

Abstract:
Ellie Xu, BA, Lynn Nguyen, BA, Jonathan P. Stange, PhD, & Julia O. Linke, PhD

Background: Major depressive disorder (MDD) has been linked to the habitual use of dysfunctional emotion regulation strategies such as rumination. One white matter tract that has been repeatedly associated with emotion regulation is the uncinate fasciculus (UNC). Thus, it has been suggested that the UNC plays a role in the pathophysiology of MDD. Yet, the existing literature has been largely inconclusive in determining whether such alterations in this white matter tract are indeed present in individuals with MDD. To close this gap, we meta-analytically integrate existing empirical evidence.

Methods: We identified diffusion tensor imaging studies on PubMed that examined the UNC using a region-of-interest approach. We conducted meta-analyses to compare UNC fractional anisotropy (FA) and radial diffusivity (RD) between individuals with MDD and healthy controls
(HC).

Results: We included 42 studies (NMDD=4853, NHC=18272). Individuals with MDD showed reduced FA in the left (β=-0.24, p<0.04) and right UNC (β=-0.29, p<0.002) compared to HC. We found no significant differences in RD in the UNC between the two groups.

Conclusions: Our results support a link between atypical UNC microstructure and MDD; however, our data does not support aberrant myelination as the cellular mechanism. Future work in individuals with MDD should investigate whether and how aberrancies in UNC microstructure contribute to emotion regulation deficits.


Personal Statement:

As an undergraduate economics major, I learned to normalize the assumption that individuals make rational decisions to optimize their well-being; however, this assumption was challenged when I first learned about the marshmallow test on delayed gratification in an introductory psychology course. Economists might predict that children, as rational agents, would wait to eat two marshmallows. In reality, experimenters found that some children immediately ate the first marshmallow. This initial exposure to psychology research sparked my curiosity to understand mechanisms of self-regulation. Did children who waited for the second marshmallow exhibit higher levels of inhibitory control than those who did not? Were individuals with higher levels of inhibitory control better equipped to regulate emotions accompanying stress and frustration? What biological processes might be associated with emotion regulation and dysregulation across development? Through my research experiences, I have begun to investigate deficits in emotion regulation, as well as their neurobiological underpinnings, and how they contribute to risk for affective disorders. Now, as a first-year Ph.D. student, I plan to continue to investigate these types of questions, with the ultimate goal of identifying treatment targets for affective disorders. After college, I was awarded a National Institutes of Health Postbaccalaureate Intramural Research Training Award to conduct research with Dr. Ellen Leibenluft and Dr. Julia Linke in the National Institute of Mental Health (NIMH) Section on Mood Dysregulation and Neuroscience on pediatric irritability. Pediatric irritability refers to a temperament characterized by extreme anger that confers risk for suicidality and depression. To date, it is unclear how irritability relates to deficits in regulating negative affect. At the NIMH, I focused on parsing irritability from general emotion regulation deficits. My poster abstract of this work has been peer-reviewed and selected for publication in the supplement of Affective Science. A second line of my work at the NIMH focused on the role of the uncinate fasciculus, a white matter tract largely implicated in emotion regulation processes, in the risk-architecture of bipolar disorder. I conducted a meta-analysis and found that alterations in the uncinate fasciculus could be identified in individuals with bipolar disorder, but not their first-degree relatives (Xu et al., 2022). Altogether, my work at the NIMH furthered my interest in continuing to investigate the role of emotion dysregulation in affective disorders. I was awarded a National Science Foundation Graduate Research Fellowship to support my graduate school studies. As a first-year graduate student in Dr. Jonathan Stange’s lab, I aim to investigate how emotion regulation deficits contribute to the development, maintenance, and recurrence of depression. To achieve this aim, I investigated how the flexible or rigid employment of emotion regulation strategies impacts risk for depressive symptomatology. I will be presenting a poster on this work at the 2022 Society of Affective Science Annual Conference next month. In a second line of work, I examined the role of the uncinate fasciculus in depression. Using a meta-analytic approach, I found that individuals with depression exhibit alterations in the uncinate fasciculus (Xu et al., in prep). In the future, I aim to pursue an academic career focused on elucidating neural mechanisms underlying risk and resilience for depression, with a focus on emotion dysregulation. Ultimately, this research will inform the development of personalized interventions for depression. As a first-year graduate student, I am eager to communicate my current work to a broad audience and learn from and network with leading experts studying emotion in the fields of psychiatry and affective neuroscience. As I formulate my master’s thesis project, it is critical for me learn more about novel statistical techniques and neuroimaging methods. This travel award would provide me with the necessary funding to attend and present a poster at the 27th Annual Wisconsin Symposium on Emotion, and discuss my work and research plans with experts in the field. This opportunity is crucial to building my skills in scientific communication and expanding my professional network at this pivotal stage in my career. I look forward to opportunities to learn about the latest developments in emotion science, and to network with scientific leaders and trainees across varying levels. Thank you for your time and consideration.

Aditii Wakhlu | Marquette University

University: Marquette University
Department: Biomedical Sciences
Program or Lab: Hearing Lab
Mentor or PI: Dr. Matthew Hearing

Poster Title: Role of D1- and D2-receptor prefrontal-accumbens circuits in mediating cognitive flexibility

Abstract:
Deficits in cognitive flexibility (the ability to adapt behavior in response to changing environmental contingencies) is one of the most consistently documented cognitive problems in neuropsychiatric disorders and contributes to increased susceptibility to negative life events (e.g., stress), reduced emotional control and development of maladaptive behaviors (i.e., substance abuse). This behavior requires coordinated activity of pyramidal neurons in the prelimbic region of the medial prefrontal cortex (PrL-PFC) projecting to brain regions such as the mediodorsal thalamus (MDT) and nucleus accumbens core (NAc). Within these circuits lie subcircuits that selectively express dopamine type 1 and type 2 receptors – thought to differentially contribute to information processing related to decision-making, however their exact contributions remain unknown. To gain insight into this question, we combine a model of attentional set-shifting akin to the Wisconsin Card Sorting Task with chemogenetic approaches in transgenic mice to express inhibitory receptors (DREADDs) in D1 and D2-expressing PrL-Core pyramidal cells – permitting us to “turn off’ neural activity and examine how performance during our test of flexible decision-making is impacted. Preliminary findings indicate that inactivation of the D2 but not D1-expressing PrLC-NAc subcircuit results in deficits in cognitive flexibility in males. Alternatively, inhibition of either circuit fails to impair performance in females. Ongoing studies are examining the impact of PrL-NAc inhibition agnostic of subcircuits. These data highlight a potential fundamental sex differences in neural circuits utilized by males and females to engage in flexible decision-making, suggesting that treating impaired flexibility may need to be tailored based on sex.


Personal Statement: 

A keen and personal interest in biology, psychology, and learning more about the underlying mechanisms of mental illnesses — combined with the lack of neuroscience research opportunities available in my home country (India) — encouraged me to seek exposure to neuroscience research and ultimately pursue an undergraduate education in the United States. In Summer 2019, I had the opportunity to shadow Dr. Gagan Joshi, an autism specialist and researcher at The Alan & Lorraine Bressler Program for Autism Spectrum Disorder at Massachusetts General Hospital. As part of this brief but formative experience, I got the chance to shadow a physician scientist, assist his team in literature searches and data compilation from clinical trials studying the use of methylphenidate in adult ADHD populations and was introduced to functional neuroimaging in autism research. This experience further solidified my preliminary interest in neuroscience research, as well as provided me with exposure to career paths at the intersection of medicine and research. To explore this interest and potential career path, I decided to move to the United States and pursue a degree in Biomedical Sciences and Neuroscience at Marquette University. Taking advantage of the vast array of opportunities available through Marquette’s faculty at the Integrative Neuroscience Research Center, I have had the opportunity of gaining experience in both rodent and translational neuroscience research. I opted to enroll as a Research Assistant in Dr. Jacklyn Fitzgerald’s lab to fulfil elective requirements for my minor in neuroscience. The Translational Affective Neuroscience lab studies emotional dysregulation and psychopathology resulting from stress and trauma. Since Fall 2021, I have been assisting on a study investigating patterns of physiological arousal using measures of skin conductance responses to fearful, safe, and rewarding stimuli. This experience has allowed me to gain valuable skills in measuring and conducting data analysis of skin conductance responses, as well as recruitment of study participants and outreach. Learning about the cellular and circuit-specific mechanisms that underlie complex brain processes like memory consolidation, habit formation, decision making in my neuroscience and physiology courses, encouraged me to seek research experiences that would allow me to critically engage with the same. Dr. Hearing’s lab in the Department of Biomedical Sciences, utilizes in vivo cell-type and circuit specific manipulations of neural activity in awake behaving animals. During my sophomore year, I began assisting on a study investigating the effect of adolescent morphine exposure on cognitive flexibility. Cognitive flexibility is defined as the ability change behaviour in response to the changing needs of the environment. Deficits in flexible decision making is one of the most consistently documented cognitive problems in psychiatric and neurodevelopmental disorders including OCD, addiction, and autism. In Summer 2021, I began my Honors Thesis study in Dr. Hearing’s lab investigating the role of cortical-striatal circuits in flexible decision-making with a focus on prelimibic cortex-nucleus accumbens subcircuits in mediating cognitive flexibility. This project utilizes cutting edge chemogenetic approaches to inhibit the activity of distinct neurons in the prelimbic-accumbens circuits and measures the effect of those manipulations on flexible decision making. Through my training in the lab, I have acquired skills in rodent stereotaxic surgery, histological assessment, and data analysis – as well as a greater appreciation for the complex mechanisms that underlie behaviour and brain processes. Combined, these experiences have culminated in my aspiration to apply to MD-PhD programs after my undergraduate education.

Sydney Timmer-Murillo, PhD | Medical College of Wisconsin

University: Medical College of Wisconsin
Department: Surgery, Division of Trauma and Acute Care
Program or Lab: Milwaukee Trauma Outcomes Project
Mentor or PI: Terri deRoon-Cassini, PhD

Poster Title: Facets of Emotion Dysregulation differentially Predict Psychopathology Following Traumatic Injury

Abstract: 

Intro: Emotion dysregulation is a hallmark characteristic of psychopathology following trauma. While the association between dysregulation (as a whole) and psychopathology is well-established, greater understanding of what aspects of emotion dysregulation predict psychopathology following traumatic injury is needed to better inform intervention. The aim of the current longitudinal study was to evaluate how factors of dysregulation (assessed using the Difficulties in Emotion Regulation Scale subscales; DERS) differentially predicted PTSD symptoms clusters and depressive symptoms six months post-injury. Methods: Traumatically injured adults (N = 99) presenting to a Level 1 trauma center completed the DERS within 2 weeks of injury and the Clinician Administered PTSD Scale (CAPS-5) and the Center for Epidemiologic Studies Depression Scale (CES-D) at 6 months post-injury. Results: Using linear regressions controlling for age, gender, race, and injury severity, results showed that the subscales of the DERS significantly predicted the four symptom clusters of PTSD. Notably, difficulty with impulse and lack of clarity of emotions were significant predictors of both avoidance and negative alterations of mood and cognition. Hyperarousal symptoms and re-experiencing symptoms were predicted by lack of clarity and impulse, respectively. On the other hand, depressive symptoms were significantly predicted by difficulty accessing regulation strategies. Discussion: Results highlight that specific facets of emotion dysregulation predict different symptoms of psychopathology after injury. Indeed, greater impulse and lack of emotional clarity appear to predict PTSD symptomatology, whereas lack of regulation strategies predicted subsequent depressive symptoms. This demonstrates the need to tailor early intervention of emotion dysregulation based on psychopathology.


Personal Statement: 

Emotion regulation, or how we manage and express our emotion, is integral to basic human functioning. I profoundly believe this. And, empirically, it is connected to mental health and well-being. I first explored the subject as an undergraduate research assistant and evaluated the influence of emotion regulation on improving experiential and physiological responses to interpersonal transgressions. Even in my initial foray into research, I saw the vast influence of emotion regulation across domains such as trauma and interpersonal functioning. My appreciation of emotion regulation grew throughout my graduate training as I explored the nuances of regulation across a host of contexts, including stress, physiology, and trauma. For instance, I examined automatic and unconscious emotion regulation processes, which are incredibly difficult to quantify and often not assessed in the literature. I published this work examining how cognitive bias modification methods could implicitly prime emotion regulation strategies in response to acute distress. Similarly, to better account for the flexibility of emotion regulation, I worked with colleagues to publish methods on how to assess individual profiles of regulation. This work also demonstrated how the array of strategies an individual uses is connected to psychopathology. Collectively, these projects grew my appreciation for the diverse techniques needed to answer our most meaningful questions about emotion and regulation. As I considered my early research program, I desired to engage in more translational research that highlights the significance of emotion regulation across social issues, with an emphasis in trauma. With a manuscript currently in development, my dissertation used an innovative virtual reality approach to promote empathy and reappraisal between police and community members, demonstrating reappraisal could reduce police officer’s implicit racial bias and increase empathy for community members. This project exemplifies my drive to evaluate the role of emotion regulation within key societal issues. This has continued in my post-doctoral fellowship in Trauma and Health Psychology at the Medical College of Wisconsin in the Trauma and Acute Care Surgery division. Posttraumatic reactions, such as posttraumatic stress disorder, are invariably tied to emotion dysregulation and fear generalization after trauma. I strive to use my foundation in emotion research to shape the questions I ask about how individuals experience trauma and what leads to chronic psychopathology. For instance, in a recent publication, we demonstrated how skin conductance can successfully predict subsequent emotion dysregulation in trauma survivors. Similarly, another aspect of this work (presented at two conferences and in two publications) demonstrated that negative emotionality acutely during trauma and avoidance during recovery are critical factors to assess after trauma. In my next steps, I plan to continue highlighting how dysregulation of emotion contributes to risk post-trauma and propose mechanisms for symptom-specific intervention. In another line of my fellowship research, I emphasize that trauma is not equally experienced, and often, disadvantaged communities disparately experience violence and its negative outcomes, including dysregulation. We know that following trauma, negative emotionality and chronic psychopathology can have deleterious physical and mental health outcomes. As such, we are testing comprehensive care strategies to promote greater access to support and intervention for this population. Through teamwork across psychological research, public service organizations, and comprehensive medical teams, the research process has been enhanced and has a deeper purpose shaping how I aim to support the unique needs of trauma survivors.

Tara Srirangarajan, BSc | Stanford University

University: Stanford University
Department: Psychology
Program or Lab: Symbiotic Project on Affective Neuroscience (spanlab)
Mentor or PI: Prof. Brian Knutson

Poster Title: Reward-related neural activity predicts alcohol consumption and weight gain in first-year college students

Abstract:

Brain activity has been used to predict outcomes relevant to mental and physical health
(including weight gain and sexual activity) in young adults. We sought to replicate and extend this work by examining whether neural responses to food and alcohol cues in mesolimbic regions would be associated with baseline alcohol consumption and body fat, and would predict future levels of alcohol consumption and body fat in healthy young adults. At baseline, we found that ventral tegmental area (VTA) response to alcohol cues was associated with past-month alcohol consumption, and caudate nucleus response to food cues was associated with past-month body fat percentage. Moreover, VTA responses to alcohol cues predicted the change in alcohol consumption four months later, while caudate responses to food cues similarly predicted future body fat percentage. These findings partially replicate and extend previous work, and suggest that individual reward-related brain responses to alcohol and food cues can predict changes in consumption. Thus, the findings have implications for predicting motivated behavior and potentially forestalling risk factors relevant to disorders of impulse control.


Personal Statement: 

Our internal states color every aspect of our daily lives and govern the decisions we make, ranging from the minor to the most meaningful. Despite great advances in our understanding of sensory and motor neural processes, it remains a mystery how the nervous system gives rise to our subjective experiences. As a PhD student in Psychology at Stanford University, I am interested in the neural underpinnings of affective states and am combining insights from behavioral experiments and neuroimaging to understand the dynamic neural substrates of emotion and motivated behavior. I am applying to the travel award for the Wisconsin Symposium on Emotion because the theme, “Psychopathology and Well-Being: Perspectives from Transdiagnostic Translational Neuroscience” aligns perfectly with my research interests. I believe the diverse presentations will provide further insights into the types of emotion-related questions I have in mind for my own work. Participating in this year’s program will allow me to deepen my knowledge of the neural substrates of emotion, forge collaborations with colleagues from diverse research domains, and ultimately use the newfound knowledge to bolster my doctoral research. One of the main reasons why I was initially intrigued by the Wisconsin Symposium on Emotion was this year’s focus on examining emotion from a translational viewpoint: across domains with a strong emphasis on transdiagnostic work. I believe that my interest in thinking about the brain and subjective experience across different domains was sparked when I joined a systems neuroscience laboratory at Janelia Research Campus to work with Dr. Karel Svoboda. While implementing a tactile decision-making task to probe neocortical function in mice, I was amazed by the spatial and temporal resolution with which individual dendritic spine activity could be visualized in vivo using a combination of optogenetic techniques and two-photon microscopy. This experience left me hungry to learn how neural activity on such a tiny scale gets compounded, ultimately supporting complex behavior in humans. Inspired to study the brain on a larger scale, I worked with Dr. Tali Sharot in the Affective Brain Lab at MIT and University College London. There, I contributed to fMRI data acquisition and analysis to investigate the role of mesolimbic reward circuitry in affective decision-making processes. As a result of my exposure to fMRI, I realized that I loved being able to visualize the brain on a macro scale, and became even more eager to learn how complex cognitive states and behaviors arise from the activity of neural circuits. This curiosity led me to work with Professor Lisa Feldman Barrett in the Interdisciplinary Affective Science Lab. After learning how to examine correlated activity in the brain across distributed systems, my goal was to transition to working with event-related fMRI designs, which would allow temporally precise localization of critical components in affective experience. In line with this, I am conducting my graduate research with Dr. Brian Knutson to deepen my understanding of how affective states guide decision-making processes that are relevant to real-world outcomes. I am particularly interested in examining how neural activity can be used as a predictor of future outcomes related to physical and mental health. The work I hope to present at this year’s symposium builds upon these questions to examine whether reward-related neural activity can be used to predict alcohol consumption as well as weight gain in college students, with important implications for understanding physical and mental well-being during the transition between adolescence and early adulthood. Participating in this year’s Wisconsin Symposium on Emotion will equip me with critical knowledge to explore the neural bases of emotion from a rigorous interdisciplinary and multi-level perspective. I am especially eager to join in this year’s program as the theme directly aligns with the questions guiding my graduate research, and I look forward to acquiring new knowledge from a diverse array of perspectives and modes of thinking.

Micah Shelton, MS | University of Pittsburgh

University: University of Pittsburgh
Department: Psychiatry
Program or Lab: Translational Neuroscience Program, Seney Lab Mentor or PI: Marianne Seney

Poster Title: Genetic sex mediates stress susceptibility in adult mice

Abstract: 

Women are twice as likely to have depression compared to men, but the underlying mechanisms of female susceptibility remain elusive. To investigate, our lab has used the subchronic variable stress model, to which females are vulnerable, but males are resilient. Using the Four Core Genotypes mouse line, in which we can differentiate between gonadal sex (ovaries vs. testes) and sex chromosome effects (XX vs. XY), we found that female stress susceptibility was driven by genetic sex. Regardless of gonads, XX mice were stress susceptible, while XY mice were stress resilient, which suggests sex differences in stress susceptibility are hormone independent. To examine the potential molecular drivers, we performed RNA-seq on tissue isolated from the prefrontal cortex (PFC) and nucleus accumbens (NAc). In both regions, SCVS exposure resulted in differentially expressed (DE) transcripts with very little overlap in DE transcripts between sexes, which is consistent with our findings in humans with MDD. Representative pathways were also divergent. Inflammatory response and acetylcholine metabolic process were enriched in females exposed to stress, while central nervous system myelination was enriched in males exposed to stress. Males do not exhibit a behavioral difference after SCVS, suggesting these transcriptional alterations promote resilience. Many of these male-specific DE transcripts in the NAc represent pathways which are not found in females exposed to stress, including cytokine activity, extracellular matrix, and adrenergic receptor signaling. Ongoing studies are determining the underlying cellular alterations in the PFC and NAc, with a focus on whether any alterations are sex specific.


Personal Statement:

The sphere of my research interests surrounds understanding how alterations at the molecular level contribute to the development and symptomology of psychiatric disease. Disorders such as schizophrenia (Sz), addiction, and major depressive disorder (MDD) are characterized by massive shifts in an individual’s behavior, emotional regulation, cognition, and subjective quality-of-life. However, despite the profundity of the change to affect and behavior characteristic of all these disorders, identifying consistent markers of disease at the gene and protein levels has remained elusive. Even with the advances that the field has made in developing techniques to scan the entirety of an organ’s molecular makeup, the search for a central driver of pathology continues in full. What drives my research pursuits is the idea that it is the collection of dozens or even hundreds of small molecular contributions, as opposed to the loss of function of a single gene or protein that produces psychiatric disease. Further, I am passionate about understanding how an individual’s environmental milieu produces those many molecular changes to produce psychiatric disease in the context of biologic vulnerability.

Past and Current Research:

I obtained my Masters in Neuroscience in 2015 at the University of Pittsburgh, with a dissertation focused on alterations to the dendritic structural protein MAP2 and, further, correlating these changes to spine loss in schizophrenia. This work was performed under the supervision of UPMC Endowed Professor in Psychiatric Neuroscience and Professor of Neurology and Clinical and Translational Science, Robert Sweet, MD. In Sz, a number of studies have revealed that MAP2’s typically robust immunoreactivity (IR) was significantly reduced across several cortical regions. Using quantitative spinning disk confocal microscopy in two cohorts of Sz subjects and matched control subjects, I measured MAP2-IR as well as dendritic spine density and spine number in primary auditory cortex, a site of conserved pathology in Sz. I found a significant reduction in MAP2-IR in a subset of Sz subjects independent of neuron loss or loss of MAP2 protein. Spine density was significantly reduced only in that set of Sz subjects with low MAP2-IR. This suggests that in some patients there is a dramatic reorganization of pyramidal cytoarchitecture with potential implications for auditory processing. My current research efforts are aimed at elucidating the intersection of biologic sex and MDD pathophysiology in postmortem human tissue as well as in transgenic mouse models. Women are twice as likely to experience depression within their lifetime, and the symptomology, severity, and comorbidities are distinct from men who experience depression. This is one of the most replicated epidemiological findings in MDD, but the causal factors remain unclear. Our transgenic mouse model allows us to distinguish between the effects of genetic and gonadal sex in contributing to anxiety and depression-like behaviors. This approach is a powerful tool for modeling the effect of life stressors to understand how MDD develops in the context of biologic sex. In parallel, my research efforts in human tissue have focused on transcriptional alterations specifically in the subgenual anterior cingulate cortex (sgACC), a region which plays an important role in emotional regulation, and which several lines of evidence point to as central in the pathology of MDD. The transcriptional profile of this region is markedly distinct between males and females with MDD, mirroring at the RNA level what is evident at the level of the individual. This work points out the necessity for developing targeted therapeutics for treating the disorder and further adds even greater evidence for the necessity of having balanced groups with regards to sex in all research.

Nikki A. Puccetti, M.S. | University of Miami

University: University of Miami
Department: Psychology
Program or Lab: Clinical Psychology
Mentor or PI: Aaron S. Heller, PhD

Poster Title: Behavioral tasks indexing individual differences in negative interpretation bias relate to real-world, daily affect

Abstract: 
Humans face a barrage of ambiguous events and information in daily life. Negative interpretation bias, appraising ambiguous stimuli as negatively valenced, is a stable trait that is proposed to shape our everyday emotional experiences. Negative interpretation bias is often measured through a variety of laboratory tasks, which have unique attributes that could yield differential affective correlates. Yet, how various behavioral tasks measuring negative interpretation bias map onto individual differences in real-world emotion is unknown. The current research investigated how 2 different laboratory-based interpretation bias tasks are linked with two months of daily negative (NA) and positive affect (PA) reports via experience sampling using multilevel regression models. Study 1 (N = 69) demonstrates that a verbal task measuring interpretation bias is related to heightened NA, but not PA in daily life. Study 2 (N = 110), shows that interpretation bias when rating images of ambiguous facial expressions and scenes is also related to daily NA. Only negative interpretation bias for face stimuli was related to lower PA. Together, these results highlight both converging and unique relationships between distinct interpretation bias tasks and everyday emotional experiences. Crucially, individual differences captured in the laboratory indeed relate to real-world emotional profiles which has implications for affective and clinical science.


Personal Statement: 

As a clinical affective neuroscientist, I aim to build integrative and ecologically-valid models of the neurobiological, cognitive, and emotional risk factors for mood and anxiety disorders. These prevalent and impairing disorders demand more precise vulnerability models for early identification and intervention with at-risk individuals. I believe the themes and speakers of year’s Wisconsin Symposium on Emotion: Psychopathology and Well-Being: Perspectives from Transdiagnostic Translational Neuroscience are extremely valuable and well-aligned with my own research program. Specifically, I have investigated three interconnected research areas using experimental methods, psychophysiological measures, ecological momentary assessment (EMA), functional MRI (fMRI) and advanced statistical techniques. Identifying shared and unique real-world affective dynamics among comorbid psychiatric conditions: The ubiquity of psychiatric comorbidity suggests that disorders possess both shared and unique etiological factors. In line with theoretical and empirical work, I believe that dynamic patterns of emotion may be key to understanding comorbidity. To investigate this, I have applied multilevel vector autoregression models to intensive longitudinal EMA data. I found that depression symptom severity, compared with anxiety severity, was uniquely predicted by weaker connections between positive emotions across time. Additionally, my colleagues and I used structural equation modelling (according to recent psychopathology taxonomies) to differentiate psychiatric spectra, subfactors, and syndromes by unique profiles of day-to-day emotion (Heller et al., 2021). Providing ecological support for theories of psychopathology vulnerability: Cognitive models of psychopathology assert that maladaptive cognitive patterns shape one’s emotional landscape and ultimately lead to psychopathology. Yet, traditional measures of negative cognitive styles have rarely been linked to real-world affect. To explore this gap, I have completed projects linking cognitive vulnerabilities, such as repetitive negative thinking, anxiety sensitivity (Baez, Puccetti et al., under review), and negative interpretation bias (Puccetti et al., under review) to longitudinal patterns of EMA-derived affect. Moving forward, I aim to design more naturalistic behavioral and EMA-based studies to precisely index individual differences in cognitive and affective processes. It is paramount that, as a field, our behavioral and biological risk factors provide powerful prediction of and explanation for real-world patterns of behavior. Exploring neurobiological mechanisms governing both psychological well-being and, conversely, risk for psychopathology: I also aim to identify neural underpinnings of real-world patterns of emotion and behavior. For example, I used multivariate pattern analysis (MVPA) to link greater persistence of amygdala representations of negative images to higher negative and lower positive emotion in day-to-day life (Puccetti et al., 2021). These results suggest that persistent neural encoding of negative daily events color how subsequent events are appraised. To contextualize the neural basis of affective persistence, I have also led a cross-species review paper synthesizing the circuit-level mechanisms that contribute to affective dynamics (Puccetti, Villano & Heller, 2021 Puccetti, Villano, Fadok & Heller, 2022). I look forward to extending this work into clinical samples. My dissertation project will identify the overlapping neural substrates of worry and rumination to capture the higher-order, transdiagnostic risk factor of repetitive negative thinking. I expect that individual differences in connectivity within and between the default mode and salience networks will predict symptoms of depression and generalized anxiety. I am currently analyzing data, writing up results, and plan to defend my dissertation before beginning my predoctoral clinical internship at the Ohio State University Wexner Medical Center this summer.

Nickole Moon, MD/PhD candidate | University of Maryland, Baltimore

University: University of Maryland, Baltimore
Department: Pharmacology
Program or Lab: Medical Scientist Training Program, Program in Neuroscience
Mentor or PI: Tracy, L Bale, PhD.

Poster: The soul of allostasis is housed in the mitochondria

Abstract:
Parental stress experiences initiate cellular reprogramming of reproductive tissues influencing offspring neurodevelopment. In males, mechanistic studies identified lasting changes following chronic stress at epididymal epithelial cells (EECs), which provide sperm with essential maturation signals. As stress-responsive modulators of cellular energy, mitochondria are attractive potential mediators of allostasis. However, the role of the mitochondria in regulating the cellular set point following stress and the molecular mechanisms initiating this process are unclear. The glucocorticoid receptor (GR) is a key regulator of the stress response and a known target orchestrating allostasis. To examine the hypothesis that stress initiates GR-dependent EEC programming to influence offspring neurodevelopment, we reduced EEC GR expression. Remarkably, paternal EEC GR reduction normalizes offspring stress responsivity. At the EEC active translatome, we detect two large clusters of differentially expressed, co-regulated genes related to mitochondrial and chromatin-modifying processes. Using CUT&RUN sequencing, we revealed increased binding by the ubiquitous transcriptional repressor, H3K27me3, at 7283 regions of the genome determined to be associated with mitochondrial processes by GSEA. Given these data, we predict that stress drives GR to alter mitochondrial respiration. Using cell-based respirometry, we demonstrate that prior stress decreases basal EEC mitochondrial respiration, and that GR knockdown protects against this change. Together, these studies demonstrate a novel role of GR in programming the chromatin landscape to impact energy requirements and mitochondrial respiration to regulate cellular allostasis in response to prior stress. Such mechanistic results demonstrate the lasting effects of parental experiences on reproductive tissues that influence germ cell maturation and fetal neurodevelopment.


Personal Statement:

Human and animal studies demonstrate that parental risk for offspring disease is comprised of genetic and environmental factors that impact offspring neurodevelopmental and adult health outcomes. As an undergraduate, I focused on genetic contributions to neuropsychiatric disease through collaborative work with Drs. Stewart Anderson and Jorge Alvarez at the University of Pennsylvania. Transitioning to the Medical Scientist Training Program at the University of Maryland, I joined Dr. Tracy Bale’s lab to study the cellular mechanisms underpinning the intergenerational transmission of paternal stress. By engaging in the Wisconsin Symposium on Emotion, I will broaden this training to better understand how socioeconomic and experiential influences integrate with biological risk factors to impact patient health. The polygenic nature of neuropsychiatric disorders such as schizophrenia have complicated the search for genetic risk factors and our understanding of their contribution to disease. 22q11.2 deletion syndrome (22q11DS) is characterized by the deletion of 46 protein coding genes on chromosome 22, including genes important for blood brain barrier (BBB) immunoquiesence. 22q11DS conveys a 25-fold increased risk for schizophrenia and poses a unique genetic framework to investigate risk. Importantly, schizophrenia is associated with altered BBB function and immune privilege. As an undergraduate in the Anderson and Alvarez labs, I studied barrier function and immune activation in BBB-like cultures differentiated from human induced pluripotent stem cells from patients with 22q11DS and schizophrenia. This work discovered reduced BBB integrity and increased immune activation in patients with 22q11DS and schizophrenia and was published in Brain in 2021. Though clearly biologically important, genetic variation accounts for only a proportion of neuropsychiatric disease risk. Furthermore, in utero and preconception parental stress exposures are linked to negative offspring mental health outcomes, however, the signals associated with prior parental stress exposure and the mechanism of their transmission is unclear. Disruption of sleep homeostasis activates canonical stress signaling pathways, inflammation, and subsequently increases kynurenic acid (KYNA), a neuroactive metabolite of tryptophan. Sleep deprivation during pregnancy has a lasting impact on offspring behavioral and physiological outcomes, though the mechanism mediating these changes and the role of KYNA has yet to be studied. As a rotation student in Dr. Ana Pocivavsek’s lab, I hypothesized that sleep deprivation during pregnancy activates the maternal stress axis to elevate maternal KYNA as a signal of parental stress to the fetus. While sleep deprivation during pregnancy did not impact maternal KYNA, it increased maternal corticosterone, placental proinflammatory cytokines, and KYNA formation in the fetal brain. My contributions were published in Neurobiology of Stress and implicated fetal KYNA as a potential mediator of offspring outcomes following maternal stress during pregnancy. To further investigate cellular mechanisms underlying the intergenerational transmission of parental stress, I began studying with Dr. Tracy Bale. During my graduate rotation I discovered that stress imparts dramatic differences in the protein composition of extracellular vesicles (EVs), key intercellular signaling particles that play a role in intercellular communication between male reproductive organs, like the epididymis, and sperm. This analysis was published in Nature Communications and these studies established that lasting differences in EV cargoes following stress causally influence offspring neurodevelopment. Furthermore, differences in EV protein composition from epididymal epithelial cells (EECs) after stress suggest that a novel mechanism regulates the EEC baseline, or allostatic set point, in response to stress. However, the cellular mechanisms underlying changes in the EEC allostatic set point to maintain these signals are unclear. Current work in the lab has established the paternal EEC glucocorticoid receptor (GR) as a mediator of offspring phenotypes following paternal preconception stress. Interestingly, EEC GR regulates expression of genes related to mitochondria and chromatin-modifying processes following stress. Given these data, I employed CUT&RUN sequencing to demonstrate impressive differences in the binding of histone modification, H3K27me3, a ubiquitous transcriptional repressor and demonstrated that these differentially bound regions of the genome are associated with mitochondrial processes. To further test the hypothesis that GR drives changes in mitochondrial function to regulate the allostatic set point, I compared basal mitochondrial respiration in wildtype and GR knockdown EECs using whole cell respirometry. These studies demonstrate that prior stress impairs basal mitochondrial function, and that GR knockdown protects against this change, implicating GR as a mediator of mitochondrial regulation of allostasis. By understanding these fundamental cellular and mitochondrial mechanisms, I will uncover key targets for future work probing environmental contributions to disease risk in the context of stress. As a future psychiatrist-scientist, my combined training enables me to lead translational studies linking genetic and environmental risk factors with patients’ lived experiences to inform future care. Upon completing my doctorate, I will complete the required clinical clerkships and the Combined Accelerated Program in Psychiatry before graduating from medical school. I will then enter a research residency program in psychiatry to continue to hone my skills in both disciplines. My participation in the Wisconsin Symposium on Emotion will inform these goals and future studies by providing me with new perspectives on emotion in the context of the complex interactions between genetic and environmental risk factors.

Bethany McCurdy, M.S. | Iowa State University

University: Iowa State University
Department: Human Development and Family Studies
Program or Lab: Weems Lab
Mentor or PI: Carl Weems, Ph.D.

Poster: Using Cortical Activation Patterns to Predict Treatment Response among Youth with Trauma and PTSD Symptoms

Abstract:

Background: Identifying neural activation patterns that predict youths’ treatment response may aid in the development of imaging-based assessment of emotion dysregulation following trauma and foster tailored intervention. Changes in cortical hemodynamic activity measured with functional near-infrared spectroscopy (fNIRS) may provide a time and cost-effective option for such work. We examined youths’ PTSD symptom change following treatment and tested if previously identified activation patterns would predict treatment response.

Methods: Youth (n=73, Mage=12.97, SD=3.09) were randomly assigned to trauma-focused cognitive behavioral therapy (TF-CBT), cue-centered therapy (CCT), or treatment as usual (TAU). Parents and youth reported on youth’s PTSD symptoms at pre-intervention, post-intervention, and follow-up.

Neuroimaging data (n=40) assessed at pre-intervention were obtained while youth were engaged in an emotion expression task. Treatment response slopes were calculated for each youth’s PTSD symptoms.

Results: Overall, youth showed decreases from pre-intervention to post-intervention to follow-up across conditions with evidence of relative benefit of TF-CBT and CCT over TAU but significant individual variation in treatment response. Cortical activation patterns were strongly correlated with PTSD symptom improvement slopes (r=0.53). In particular, there was increased cortical activation to fearful facial stimuli in the left dlPFC and increased cortical activation to neutral facial stimuli in the left dlPFCC and the right dlPFC.

Conclusions: The use of fNIRS provides a method of monitoring and assessing cortical activation patterns in a relatively inexpensive and portable manner. Associations between functional activation and youths’ PTSS treatment response is a promising avenue for understanding emotion regulation dysregulation in clinical applications.


Personal Statement: 

Difficulties in mental health deeply affect youth and their trajectories of growth and development. To improve lives, there is a need to further understand the complex relationships surrounding youth’s mental health outcomes, as all youth deserve to transition into a healthy, happy, and successful adulthood.

My research interests are grounded in developmental psychopathology, focusing on how chronic stress and biobehavioral regulation affect youth development. My research foci are transdisciplinary, utilizing strategies from psychology, endocrinology, and neuroscience, and are centered around mental health and stress physiology in children, adolescents, and young adults. These foci include biomarkers of stress (including hormones, autonomic nervous system functioning, and brain development) in the context of emotional and behavioral difficulties that follow stress-related disorders.

My overarching goal is to conduct research concerning the effects of chronic and acute stress on mental health and behavior and ultimately benefit populations vulnerable to the effects of stress. Specifically, I seek to understand youth development in the context of exposure to stress and expand the field of knowledge of treatment, intervention, and ultimately prevention of stress-related disorders. Statistical analyses also take precedent in my research interests. As a student of developmental psychobiology, I explore different methodological designs to observe changes in psychological health and biomarkers on a longitudinal scale. The application of sophisticated statistical techniques to analyze longitudinal data (such as through Repeated Measures ANOVAs, Regression Coefficient Analyses, and Hierarchical Linear Modeling) holds high importance in my research process.

Additionally, my research interests include bridging the gap between experimental science and improved health outcomes through translational research. I find value and importance in how science can advance practice and policy in favor of improved health outcomes through translational research. I work with colleges in various disciplines (e.g., Human Sciences, Education, Kinesiology) to implement programs and practices that promote broader impacts, community engagement, and public health.

Currently, I lead research by facilitating university-wide use of a data tracking system and interactive tool that allows communication and collaboration between the university and local communities. Data captured reflects the breadth of impact an individual or organization has and how individuals, organizations, and the university provide services and improve lives as a network.

With the guidance of my mentors, peers, the surrounding community, and fellow scientists, integrating longitudinal biological and psychological phenomena to explore youth development guide my current research and support my future research efforts.

Michael W. Lewis, Ph.D., M.P.H. | Harvard Medical School

 University: McLean Hospital/ Harvard Medical School
Department: Center for Depression, Anxiety and Stress Research / Psychiatry
Program or Lab: Anxiety and Traumatic Stress Disorders Laboratory
Mentor or PI: Isabelle M. Rosso, Ph.D.

Poster:

Toward Consistent Findings in Fear Learning Research: A Multiverse Analysis of Fear Acquisition and Extinction Retention in Posttraumatic Stress Disorder 

Abstract:
Deficient fear extinction retention is a candidate mechanism of posttraumatic stress disorder (PTSD), but methodologies and findings differ across studies. We performed a literature review to identify methodological parameters that vary across extant studies of fear extinction retention in PTSD. We then performed Multiverse Analysis, in a new sample, to quantify the impact of those methodological parameters on statistical findings. In 25 PTSD patients (15 female) and 36 trauma-exposed non-PTSD controls (TENC; 20 female), we recorded skin conductance response (SCR) during fear acquisition and extinction learning (day 1) and extinction recall (day 2). Our Multiverse Analysis included all possible combinations of methods to compare SCR-based fear extinction retention in PTSD versus TENC. In a comparison Multiverse Analysis, we examined the effects of methodological parameters identified by our review on the well-established finding of elevated SCR to a learned danger cue (CS+) versus a learned safety cue (CS-). Both the reviewed literature and the Multiverse Analysis yielded inconsistent findings for fear extinction retention in PTSD versus TENC, and most analyses found no statistically significant group difference. Methodological parameters involving sample sex, fear extinction retention quantification, and outlier removal most impacted results. By contrast, elevated SCR to CS+ versus CS- was consistently found across all analyses in the reviewed literature and Multiverse Analysis of new data. Evidence from the reviewed studies and Multiverse Analysis did not support robust PTSD versus TENC group differences for fear extinction retention. We provide specific recommendations to standardize methodological decision-making and reporting.


Personal Statement:
As an affective neuroscientist, I seek to translate methodological advances into a greater understanding of the impact of traumatic stress on emotional learning. Inspired by my desire to contribute to the effort to understand and alleviate trauma-induced psychiatric illness, I am developing into an independent translational neuroscientist who investigates transdiagnostic endophenotypes of posttraumatic stress. My multimodal line of research has primarily focused on fear learning physiology and genetic underpinnings of emotion dysregulation. Attending the 2022 Wisconsin Emotion Symposium will allow me to discuss my research with leading field experts which is critical to accelerate my development into an independent translational neuroscientist and to maximize my long-term potential as a scientist. In a literature review published in Translational Psychiatry, I identified differences in trauma type as a critical determinant of alterations in the genetic expression of the serotonin 1A receptor (5-HT1A) and consequent behavioral dysregulation (Lewis et al., 2020). Specifically, I compared results across rodent trauma model studies that were identical across all methodological parameters other than the type of trauma model used. Synthesizing the literature in this way, I demonstrated that the effect of trauma on 5-HT1A covaries with the type and chronicity of trauma model. Further, I identified translational studies to demonstrate that this observation likely applies to posttraumatic stress in humans and may be a critical transdiagnostic determinant of the impact of trauma on emotion. Building on these insights, I completed a dissertation using gene-set analysis that harnessed recent statistical breakthroughs to investigate the association of posttraumatic stress disorder
(PTSD) with groups of single nucleotide polymorphisms that converge onto neural circuits that are known to be involved in emotion regulation (Lewis, 2020). To translate breakthroughs in the basic science of fear learning into improved understanding and treatment of trauma-induced psychiatric illness, an understanding of the impact of methodology on results is essential. In a study recently published in Psychology & Neuroscience, I harnessed recent advances in machine learning to identify distinct subpopulations based on fear conditioning data (Lewis et al., 2021). Specifically, I applied latent class growth analysis to fear potentiated startle (FPS) data collected during conditioning and identified a majority group (83.1%) for which FPS decreased (based on a significant negative slope) and a minority group (16.9%) for which FPS increased (based on a significant positive slope). Thus, when faced with a repeated mild stressor, a minority of individuals may be more susceptible to elevations in conditioned fear. For comparison, I also demonstrated that a mean-centered analysis of the same sample suggested that fear conditioning had occurred but had not changed over time (based on a positive intercept and non-significant negative slope). This pattern of findings highlights the importance of accounting for latent subpopulations in physiological fear learning data; what is true of the group on average may not apply to individuals within the group (Lewis et al., 2021). More recently, I have focused on the impact of methodological inconsistency on findings from group comparisons of fear extinction retention in PTSD versus trauma-exposed controls (TENC). Previous research has identified deficient fear extinction retention as a promising treatment target for PTSD, but clinical translation depends, in part, on consistent and reliable findings. By combining a systematic literature review with complementary Multiverse Analyses, my colleagues and I are finding that methodological differences in group comparisons of fear extinction retention in PTSD versus TENC can directly cause inconsistent results (Lewis et al., in prep). Our findings identify specific methodological barriers to investigating such purported group differences and provide empirical support for actionable recommendations to increase across-study consistency in reporting, methodological decision-making, and, ultimately, results. I hope to present these findings and their implications for translational neuroscience at the 2022 Wisconsin Symposium on Emotion. When I learned of this year’s Wisconsin Symposium on Emotion theme, I recognized an unmatched opportunity to gain exposure to cutting-edge translational science and to connect with leaders in the field of affective neuroscience whose interests and goals align with my own. I am excited about the prospect of being able to learn from and establish relationships with future mentors, colleagues, and collaborators. The 27th Wisconsin Symposium on Emotion is an ideal opportunity for me to further my growth as a translational neuroscientist.

Karina Kruth, PhD | University of Iowa

University: University of Iowa
Department: Psychiatry
Program or Lab: Aislinn Williams
Mentor or PI: Aislinn Williams
Poster Title: Lithium treatment alters cellular metabolism, glutamate, and GABA.

Abstract: 

In recent years, metabolomic and protein expression studies have identified significant differences in cellular energy metabolism in patients with bipolar disorder compared to healthy control subjects. In bipolar subjects, metabolite and gene expression patterns suggest cells are increasingly reliant on glycolysis rather than oxidative phosphorylation for ATP production. Such a glycolytic shift would likely reduce the efficiency of ATP production and could alter rates of neuronal firing due to energy depletion. In addition, synthesis and consumption of glutamate and GABA are tied into energy metabolism through interconversion with α-ketoglutarate, a component of the TCA cycle. We thus questioned whether modulating cellular metabolism could prove therapeutic in bipolar disorder. As a first step toward testing this hypothesis, we performed metabolomic analyses on 293T cells treated with lithium to assess whether the most effective known treatment for bipolar disorder affects metabolism. 293T cells were selected as a preliminary model due to their clean, robust performance in metabolomics assays, as well as their overall metabolic similarity to neurons. Here, we show that lithium treatment of 293T cells significantly raises glutamate and GABA levels and significantly reduces fructose 2,6-bisphosphate, a key activator of glycolysis. These results suggest that at least some of lithium’s therapeutic activity may arise from its ability to modulate metabolism in a way that shifts it to more closely resemble that of healthy controls. If bipolar disorder is at least in part a metabolic disorder, it is possible that metabolism-modulating drugs, such as metformin, may have therapeutic potential in bipolar disorder. 


Personal Statement of Research Interest 

My undergraduate and PhD degrees are both in biochemistry, and biochem has always been the perfect fit for me. I love proteins in all their complexities, and the spiderwebbing of metabolic networks is my favorite logic puzzle ever. I didn’t plan to be a neuro-biochemist, but life had other ideas, and I wouldn’t change a thing. 

As a graduate student, I studied the structure and function of deafness-causing actin mutations, purifying proteins and doing in vitro assays to understand how modifications to different parts of actin change its behavior. Actin is the most fascinating protein I’ve ever encountered. It is the cell’s Swiss army knife. Depending on the environment and what you need, it adapts to generate force, regulate transcription, or even affect metabolism. And, as I began to suspect as a graduate student, I think it may have an important interaction with the cellular redox system. To my grad-studently dismay, purified actin only retained maximum polymerization capacity for three days after purification unless stored under nitrogen or in the presence of extremely high concentrations of DTT. Most proteins are stable for weeks to months. Three days in air and actin starts dying. Nature doesn’t do anything by accident, and I’ve wanted to know ever since then why on earth actin is so sensitive to oxygen and how the cell can use oxidized actin. 

The oxygen + actin question is where my brain lay when I got my PhD. But rather than pursue a postdoc wherever I wanted, I was unable to move from the University of Iowa because my husband became dangerously ill and was too unstable for us to move. About eight months after we married, my husband had a mental breakdown while writing his PhD thesis. The normally kind, sweet man I married turned erratic and nasty and began saying and doing things that were irrational and bizarre. He retreated into himself, severing all ties with friends and family. He became bitter and angry, and even on one occasion, physically violent. This was a man who once refused to kill a tick he had found crawling on him because “all creatures have a right to live.” He was diagnosed with Major Depressive Disorder, though he displays enough symptoms of schizophrenia that the doctors seriously considered schizoaffective disorder. Through psychiatrists and therapists, I learned words like “psychosis,” “cognitive dysfunction,” and “negative symptoms.” But the medications didn’t help, and my husband took to carrying razor blades in his wallet for when the time “felt right” to finish things. I spent so many nights on suicide watch, checking under doors, panicking every time he spent just a little too long in the bathroom. 

The first real change I saw in my husband’s condition came unexpectedly from a treatment he was given not for his depression, but for high homocysteine: methylfolate. Just a couple days after taking an over-the-counter supplement, his mood began lightening. I didn’t trust the change at first, but it lasted. That inexpensive vitamin pulled him one step back from the edge of suicide. A vitamin did that. I was stunned. I wanted to know why and how this happened, and more than anything, I wanted to know if we could further tap this system for more improvements. I spent hours and hours on PubMed and began to learn about the interactions between metabolic pathways and brain function. I was already training to be a metabolism scientist in my postdoc. Now, it was time to take that knowledge into the brain. 

I joined the Williams Lab in 2019, and Aislinn has been a constant support in my effort to learn neuroscience. And the more I learn, the more excited I get. There really is something to this metabolism thing, and it looks like actin might be a key player. In fact, I was awarded a 2021 NARSAD Young Investigator Award to study the role of the MICAL family of proteins in bipolar disorder. MICALs are regulated by metabolism (NADPH levels, specifically) to reversibly oxidize actin, which causes it to rapidly depolymerize, leading to actin network collapse. All three MICALs localize to synapses, and MICAL2 expression has been correlated with lithium treatment sensitivity in bipolar disorder. There is also evidence that NADPH production is increased in people with bipolar disorder. I hypothesize that metabolic imbalances are leading to increased MICAL activity, destabilizing synapses or interfering with synaptic transmission. 

I hope to open my own lab in a year or two focusing largely on understanding the role of MICALs in synaptic dynamics in both healthy and disease conditions. Currently, MICALs have been only minimally studied in brain, and their function remains largely unknown. I also plan to investigate how energy metabolism affects neurotransmitter levels and neuronal firing. For all projects, I generate neurons from pluripotent stem cells derived from bipolar and control study subjects. I will investigate the relationship between metabolism, morphology, and function. I will also test supplements and drugs in vitro. Metabolism is by its nature flexible, designed to sustain cellular functions with diverse food sources and energy demands. This flexibility makes metabolism inherently malleable through diet, exercise, and pharmacotherapies. It is possible that dietary supplements or metabolism-modifying drugs like metformin can correct metabolic imbalances in bipolar disorder, which may improve symptoms. I’m still looking for the next methylfolate, and I plan to find it. 

Cecilia A. Hinojosa, PhD | Emory University

University: Emory University
Department: Department of Psychiatry and Behavioral Sciences
Program or Lab: The Grady Trauma Program
Mentor or PI: Jennifer Stevens, PhD

Poster Title: Understanding the co-emergence of PTSD and alcohol use: exploring time since trauma and the role of the vmPFC.

Abstract: 

Author List: Cecilia A. Hinojosa, Ph.D, Sanne van Rooij, Ph.D., Nathaniel G. Harnett, Ph.D., Lauren A. M. Lebois, Ph.D., Vishnu P. Murty, Ph.D., Tanja Jovanovic, Ph.D., Stacey House M.D., Ph.D., Negar Fani, Ph.D., Samuel A. McLean, M.D., M.P.H., Kerry Ressler, M.D., Ph.D., & Jennifer Stevens, Ph.D.

Posttraumatic stress disorder (PTSD) and excessive alcohol use often co-occur. Two hypotheses proposed to explain the potential underlying mechanisms are the susceptibility and self-medication hypotheses. Using a multisite longitudinal study design, we explored the relative fit of each of the theoretical models.

Participants were recruited from emergency departments across the U.S. as part of the AURORA study (n = 436; 278 female). Alcohol consumption (drinks per week; PhenX Toolkit) and PTSD symptoms (PCL-5) were assessed first at pre-trauma, then 2 weeks, 8 weeks, and 6 months following emergency department trauma. A cross-lagged panel model for alcohol consumption and PCL-5 scores over the four time points was conducted using Lavaan (v0.6-9) in R Studio (v1.4.1717). Reward-related neural activation was assessed at 2 weeks using fMRI during a monetary reward task and analyzed in fMRIprep and SPM12.

Eight-week PCL-5 scores significantly predicted 6-month alcohol consumption, B=.23, SE=.12, p = .048, but there was no such effect of 8-week alcohol consumption on later PCL-5 scores. During the fMRI task at 2 weeks, whole-brain analysis (Gain>Loss) showed that a cluster in the ventromedial prefrontal cortex (vmPFC) was associated negatively with 8-week PCL-5 scores (kE=8; p=.005), but positively with 6-month alcohol consumption (kE=7; p=.005).

Clarifying the causal relationship between these co-occurring disorders will improve risk screening tools and interventions for these comorbid disorders. The findings presented were more consistent with the self-medication hypothesis and suggest that vmPFC activation may contribute to rewardseeking behavior in individuals experiencing posttraumatic stress symptoms.

Lana Ruvolo Grasser, PhD | Wayne State University School of Medicine

University: Wayne State University School of Medicine
Department: Psychiatry and Behavioral Neurosciences
Program or Lab: Jovanovic Lab; Stress, Trauma, and Anxiety Research Clinic (STARC Lab)
Mentor or PI: Tanja Jovanovic, PhD; Arash Javanbakht, MD

Poster Title: The Fear that Remains: Deficits in Fear Extinction in Youth Resettled as Refugees with Posttraumatic Stress Disorder

Abstract: 

Authors: Lana Ruvolo Grasser, Bassem Saad, Celine Bazzi, Hiba Abu Suhaiban, Dalia Mammo, Ragda Izar, Noor Abou Rass, Raya Nashef, Ayat Abed Ali, Arash Javanbakht, and Tanja Jovanovic

Background: Fear-potentiated startle (FPS) combines Pavlovian fear conditioning and the acoustic startle response to measure fear and safety learning—behaviors affected by trauma that may provide indications of related psychopathology. In adults, a failure to extinguish learned fear is a hallmark feature of posttraumatic stress disorder (PTSD). The goal of the present study was to test whether this same pattern would be observed in youth with and without PTSD.

Methods: Syrian youth (n=71, 35F, Mage=12.7 years) exposed to civilian war trauma were enrolled in a longitudinal study of refugee health. Eyeblink electromyogram (EMG) data from a differential conditioning FPS paradigm were obtained 2.5 years after resettlement. Probable diagnosis of PTSD was based UCLA PTSD Reaction Index scores of 35 or greater.

Results: A repeated measures ANOVA indicated a significant effect of stimulus type (threat v. safety) by probable PTSD in the last block of extinction, F=4.02, p=.049, p2=.06. FPS to threat cue was significantly greater in the PTSD+ group compared to the PTSD- group at the end of extinction, t=-2.50, p=.015, but FPS to safety cue did not differ, t=-.31, p=.67.

Conclusions: In accordance with the literature from adults, we observed a deficit in extinction learning for the first time in youth with PTSD. These results support the use of trauma-informed cognitive behavioral therapy based on the learning principles of extinction, in youth with PTSD.


Personal Statement: 
I am a recent graduate of Wayne State University Translational Neuroscience PhD program and an incoming post-doctoral fellow in the Neuroscience and Novel Therapeutics Unit (PI: Melissa Brotman) at the National Institute of Mental Health. My research focuses on identifying biomarkers of child and adolescent psychopathology and, informed by neurobiological correlates of psychopathology, developing, implementing, and assessing scalable intervention programs for youth with psychopathology—bridging the gap between bench and bedside. Throughout my research training, I have strived to be a neuroscience trainee with a deep appreciation and passion for both rigorous and reproducible neuroscience, as well as the clinical treatment space. Supported by my mentors Drs. Tanja Jovanovic and Arash Javanbakht, my PhD work with youth who have resettled as refugees of Syria has filled gaps not only in the study of children and adolescents, but also in that of underrepresented populations. My F31 funded dissertation work has aimed to identify biological indicators of trauma-related psychopathology. I used scalable, cost-effective, and mobile measures including a) skin conductance responses (SCR) to trauma interviews using a smartphone app, b) threat and safety learning using the fear-potentiated startle (FPS) paradigm, and c) immune-related responses through salivary markers of inflammation. This work has indicated that increased trauma exposure was associated with elevated autonomic reactivity as evidenced by heightened SCR to trauma interview and increased FPS to both threat and safety cues following fear conditioning. Perhaps most notably, this work is the first to show that, similar to adults, while youth with and without PTSD did not show differences in fear conditioning, youth with PTSD show deficits in extinction of learned fear responses compared to youth without PTSD. These findings fill a gap in the extant literature of fear and safety learning in youth, as my advisor and I identified in our 2021 Behavioural Brain Research review on safety learning. In line with that review, these findings further support safety learning as both a biomarker of psychopathology and a treatment target in youth. My findings to date also highlight an opportunity for interventions that promote emotion regulation, enhance vagal tone, and modulate autonomic reactivity may be beneficial. Informed by these findings, our team has piloted creative arts and movement-based intervention programs for over 400 individuals school children, caregivers, and families resettled as refugees in the metro Detroit area. For refugees in particular, these non-verbal, community-based methods importantly overcome cultural and language barriers, are cost effective, and improve accessibility. Moving into my future research and training goals, I look forward to gaining expertise in clinical trials design, implementation, and analysis as well as neuroimaging. My ultimate goal is to provide a robust evidence base to support the addition of creative arts and movement therapies to providers’ treatment toolkits, and to advocate for the implementation of such programs within schools and communities where they could have preventative benefits for mental health at a larger scale. In this light, I am especially excited for Dr. Melissa Rosenkranz’s talk on mind-body health mechanisms and interventions at the symposium this year.

Last year, I enjoyed attending the virtual symposium for the first time. My mentor and past awardees have spoken enthusiastically of the symposium as an especially beneficial experience for postdocs, and with the line-up of experts with a variety of interests that align with mine, I am highly motivated and looking forward to attending the meeting again this year. Receipt of this award would provide me with a platform to share science—through the poster session and conversations at the meeting—that is tightly aligned with the goals of the HealthEmotions Research Institutes and within the framework of this year’s programming. My work also focused on an underrepresented and marginalized community—youth resettled as refugees and underserved youth in urban environments. In this context I would be especially enthusiastic to learn from Dr. Sidney Hankerson on their approach to formulating community partnerships motivated towards promoting mental health equity. This and other connections fostered at the symposium may even evolve into a mentorship team to enhance my postdoctoral training. I look forward to honing skills in neuroimaging and hope to connect with Dr. Deanna Barch at the symposium to learn more about her work with the ABCD cohort studying brain development. Further, I hope to connect with NNT’s collaborator Dr. Ned Kalin. These experiences at and evolving from the symposium, in tandem with my next-stage mentorship within the Emotion & Development Branch (branch chief: Daniel Pine) will prepare me for career using the neurobiological methods of mechanistic inquiry to assess mind-body treatment modalities (particularly creative arts & movement-based interventions) through randomized controlled trials. The opportunity to establish an extended network of mentors and collaborators through this award, and to bring new perspectives to my growing body of work through the research presentations and discussions, will be transformative for my career.

Devan Gomez, PhD candidate | Marquette University

University: Marquette University
Department: Biomedical Sciences
Program or Lab: Neuroscience
Mentor or PI: Dr. Matthew Hearing

Poster Title: Motivational shifts during protracted opioid withdrawal: a sex- and dopamine subcircuit-specific effect 

Abstract:
Opioid use disorder (OUD) is associated with enduring psychological withdrawal symptoms believed to contribute to drug abuse. Amongst these are shifts in motivational states, wherein preference for drugs overwhelms that for non-drug rewards to promote escalated opioid use and relapse vulnerability. Hence, weakening drug-reinforced behaviors while strengthening those associated with non-drug rewards remains a major treatment goal for OUD patients. A critical regulator of motivated behaviors, the mesolimbic dopamine (DA) system is thought to be both necessary and sufficient for opioid motivation. However, previous research into opioid withdrawal has been limited by generally neglecting assessments at protracted withdrawal timepoints as well as comparisons between discrete mesolimbic subcircuits. Addressing this, we find that following 14-day withdrawal, previously dependent male and female mice exhibit elevated morphine intake compared to non-dependent counterparts. Unexpectedly, escalation of intake is paralleled by a sex-unique shift in motivation away from sucrose and towards morphine. Using retrograde labeling and whole-cell slice recordings, we find that dependence-induced behavioral shifts align with reduced excitability and increased GABAAR-dependent transmission selectively in lateral ventral tegmental area (VTA) DA neurons projecting to the lateral nucleus accumbens (NAc) shell (latVTA-latShell) not observed in the more medial VTA-NAc shell subcircuit. Furthermore, chemogenetic inhibition of the lateral but not medial VTA-NAc shell subcircuit produced a significant reduction in sucrose motivation in separate mice. These data suggest that protracted opioid withdrawal is associated with a latVTA-latShell-specific hypoactive state due in part to increased GABAergic inhibition onto DA cells that may contribute to motivational shifts towards opioid intake.


Personal Statement:
My current specific interests lie in understanding how mesocorticolimbic dopamine subcircuits dynamically regulate motivated behavior and how their stress- and drug-induced plasticity dictate changes in function and behavior. As an undergraduate and research volunteer at the University of Colorado, I worked in the laboratory of Dr. Steven Maier under the direction of Dr. Michael Baratta, where I examined prefrontal cortical regulation of stress resiliency and stress-related maladaptive behaviors towards drugs of abuse. Following my tenure as an undergraduate student, I worked as a research assistant for Dr. Erik Oleson (CU-Denver), investigating changes in real-time dopamine release in the brain and their relationship to behaviors related to motivation, aversion and drug exposure. During my graduate training at Marquette University, I have continued to build on my experience in neuroscience in the lab of my primary mentor, Dr. Matthew Hearing, and my co-mentor, Dr. John Mantsch. An electrophysiologist by training, Dr. Hearing’s lab allows me to readily identify causal links between neural adaptations and behavior, and his interest in the neurobiological mechanisms underlying stress-induced pathology and addiction complement my own background. Dr. Mantsch was chosen as a co-mentor given his more extensive background in mentoring and stress and addiction research.

Currently a 6th year student of the neuroscience graduate program in Dr. Hearing’s lab, my work began with assisting in the development of a novel chronic-stress paradigm and learning patch clamp electrophysiology to examine the impact of stress on neurons in the prefrontal cortex. Using data collected in part during my initial rotation in the Hearing lab, I was able to contribute to a project that was the first to identify opposing changes in neuronal firing and strength of synaptic connections in subpopulations of neurons based on which type of dopamine receptor they expressed (Anderson et al., 2019). I was also involved in a project that included optimizing a model of opioid dependence and associated measures of somatic and affect-related withdrawal symptoms, as well as whole-cell recording techniques to assess basal synaptic transmission in the nucleus accumbens following morphine exposure (Madayag et al., 2019). In parallel with these projects, as a part of my initial training in VTA-specific electrophysiology, I also participated in a collaboration with Dr. Sergi Ferré (NIDA) examining the impact of ghrelin signaling on VTA dopamine neuron firing. To date, my primary research project in Dr. Hearing’s lab focuses on opioid dependence-induced shifts in motivation in terms of their impact on enduring susceptibility to escalated opioid use, and their underlying plasticity within subcircuits of the ventral tegmental area – nucleus accumbens (VTA-NAc) pathway. As a part of this, I have established a foundation for basic measures of synaptic transmission and intrinsic physiology and identified distinct neuroadaptations within medial vs lateral VTA-NAc dopamine neurons. I’ve also assessed causality between withdrawal-associated neuroadaptations and changes in motivated behavior using chemogenetic approaches in behaving mice. Using these data, I have been granted an NIH Blueprint and BRAIN Initiative Diversity Specialized Predoctoral to Postdoctoral Advancement in Neuroscience (D-SPAN) Award. I will continue pursuing an independent research career in addiction-related neurobiology by applying this award as a postdoctoral researcher in the lab of Dr. Erin Calipari at Vanderbilt University after obtaining my PhD this summer. My ultimate career goal is to gain expertise in behavioral, molecular and electrophysiological methods in neuroscience in order to secure a tenured professorship at an academic institution. My long-term interests lie within not only understanding contributions of mesocorticolimibic dopamine circuits to motivated behavior, but also how peripheral molecular signals originating from the microbiome and endocannabinoid signaling dynamically regulates these circuits.

Paia Amelio, BS | Northwestern University

University: Northwestern University
Department: National Institute of Mental Health
Program or Lab: Intramural Research Training Award (IRTA) recipient in Section on Development and Affective Neuroscience (SDAN)
Lab Mentor or PI: Dr. Daniel Pine

Poster Title: Evaluation of Diagnostic and Treatment Progression Validity from Development & Well-Being Assessment (DAWBA) in a Pediatric Anxiety Cohort 

Abstract:
The Development and Well-Being Assessment (DAWBA) demonstrates promise in pediatric research, utilizing parent-reported and self-reported measures to predict the probability of being diagnosed with a variety of mental health disorders. DAWBA is unique, offering increased accessibility of mental health screening. The purpose of this project was to assess the validity of the DAWBA, particularly within pediatric anxiety. Confirming DAWBA’s validity is essential because DAWBA would be beneficial to pediatric anxiety research; DAWBA can potentially serve as a supplement to clinician assessment and generate a wider population size of children screened for anxiety disorders. The method to examine DAWBA efficacy utilized 3 measures: (1) logistic regression analysis of categorical DAWBA band scores (representing probability of having a specific disorder) to binary diagnoses using the K-SADS-PL, a clinician-rated assessment (2) correlating generated DAWBA symptom scale scores with established self-reported measures (SCARED) and clinician-reported measures (PARS) (3) assessing predictive properties of DAWBA to treatment progression (shown through time-specific PARS). The results show that the DAWBA has strong predictive validity when compared to KSADS for Generalized Anxiety Disorder, Separation Anxiety Disorder, and Social Phobia Disorder. Further, the DAWBA symptom scales correlate with self-reported measures such as SCARED and clinician-reported measures such as PARS; however, does not show specific correlation with PARS treatment progression. These results suggest DAWBA’s diagnostic validity and the heterogeneity of treatment progression. The wide-scale distribution of and increased access to mental health screening is characteristic to DAWBA, and these findings support its use in pediatric anxiety research in the future.


Personal Statement: 
How do affective neurological disorders develop? What neurological mechanisms can we target to effectively treat individuals and enhance the human experience? I discovered my professional and academic interests by researching in two different neuroscience labs and majoring in neuroscience. These experiences provided me with a unique insight into psychiatric risk from cells to circuits: one lab focused closely on neural mechanisms of fear in animal models, the other focused on how neurodevelopment tracks risk for psychiatric disorders with human neuroimaging. Through research, I engaged in different scientific questions that were merely conceptualized in academic settings. Not only did I start thinking critically based on experimental data, but I also began to critically examine my academic work. My interest in research led me to apply to my current position, an Postbaccalaureate Intramural Research Training Award (IRTA) recipient at the National Institute of Mental Health. I work in the Emotion and Development Branch under Dr. Daniel Pine’s supervision in his Section on Development and Affective Neuroscience (SDAN). Here, I can engage in widely collaborative research and further my understanding of affective neuroscience. At my first lab led by Dr. Frances Lee at Weill Cornell Medicine, I conducted several independent projects observing the efficacy of safety signaling as a novel treatment for adolescent anxiety in animal models. There, I began to explore affective neuroscience and to understand the importance of developing treatment models that specifically target immature brains. After Lee Lab, my interest in developing better treatment models for youth experiencing psychiatric disorders continued. In college, I started working in Dr. Vijay Mittal’s Adolescent Development and Preventative Treatment (ADAPT) Lab. I started an independent project looking specifically at emotion regulation in individuals with depression, adjunct to a greater study regarding psychomotor slowing in current and remitted Major Depressive Disorder
(MDD). The goal of the project was to understand emotion regulation objectively (through heart rate variability measures and emotional N-back task data) to be able to supplement current clinical practices for the treatment of MDD. All of these interests have continued to grow at the SDAN lab. Here, I am researching a myriad of topics that focus on treating adolescent anxiety. Specifically, I am working on projects that examine eye gaze behavior during risk or reward trials, assess the benefit of adding music conditioning paradigms to CBT, determine mature brain circuitry with fMRI techniques, and determine the validity of the DAWBA’s diagnostic evaluation of pediatric anxiety. All of these projects reflect my research values developing better measures of anxiety in children and methods of treatment for these cohorts. My career aspirations involve going to medical school and specializing within pediatrics. These research experiences have given me my passion to work with children in a clinical setting, and to use research to supplement my understanding of adolescent mental health. It has been very eye-opening to engage with research that recognizes that most adults with certain affective disorders have grappled with these psychiatric issues since adolescence, such as we see with anxiety. It is my goal to continue the advancement of this research, by engaging with many individuals and their research within affective neuroscience and hope to strengthen treatment for years to come.