Travel Awards

Name: Alaa Abouelela Abdou Abdalla, MD, MSc
University: University of Minnesota
Department: Psychiatry and Behavioral Sciences
Program or Lab: RADLab
Mentor or PI: Dr. Kathryn R. Cullen

Poster Title: “Alexithymia and Self-Injurious Thoughts and Behaviors Among Adolescents: A Three-year Longitudinal Study”

Background: Adolescent non-suicidal self-injury (NSSI) and suicidal thoughts/behaviors (STBs) are growing mental health issues, which have been found relevant to problems with feeling emotions (i.e. alexithymia). Utilizing longitudinal data from The Brain Imaging Development of Girls’ Emotion and Self, this study explores dynamic changes in the relationship between alexithymia and Self-Injurious Thoughts and Behaviors (SITBs) and the potential mediating role of impulsivity, particularly considering negative urgency.

Methods: 164 adolescents, assigned female at birth, aged 12 to 16 (Mean = 14.97∓1.20), with a history of self-injurious behaviors, underwent assessments at three time points (T1, T2, and T3): the Toronto Alexithymia Scale (TAS), Urgency-Premeditation-Perseverance-Sensation Seeking-Positive Urgency (UPPS-P), Self-Injurious Thoughts and Behaviors Interview (SITBI), and Beck Scale for Suicidal Ideation (BSSI). Correlations were applied to explore the relationship between the changes in time in total TAS scores and NSSI and BSSI scores. Structural Equation Modeling (SEM) assessed negative urgency’s mediating role in T2 between alexithymia in T1 and NSSI and BSSI in T3.

Results: Adolescents showed declining TAS scores over time, positively correlated with NSSI last-year episodes, as well as BSSI from T1 to T2. These correlations were non-significant from T2 to T3. SEM revealed that negative urgency at T2 significantly mediated the relationship between alexithymia at T1 and BSSI at T3 (β= 0.152, p = 0.001 and β = 0.057, p = 0.001).

Conclusion: This study underscores dynamic changes in the alexithymia-SITBs relationship, emphasizing the mediating role of negative urgency. Interventions targeting adaptive emotion-
regulating strategies could help adolescents with recovery from self-harm.

Name: Chase Antonacci, MPhil
University: Stanford University
Department: Department of Psychology
Lab: Stanford Neurodevelopment, Affect, and Psychopathology Laboratory
Mentor or PI: Ian Gotlib, PhD

Poster Title: “Frontolimibic Resting-State Connectivity Mediates the Association Between Early Life Stress and Adolescent Psychopathology”

Early environments exert a profound and lasting effect on children’s development and well-being. Youth growing up in adverse conditions are often subject to diverse forms stress including poverty, neglect, air pollution, and maltreatment. This multicollinearity in early exposure has made it challenging to disentangle relations between specific stressors and outcomes. In the current study, 186 youth (Mage=11.33, 59%F) completed assessments of stress exposure, parenting, neighborhood pollution, and resting state fMRI at baseline. Two years later, families completed self-report measures indexing psychopathology and behavioral difficulties. We conducted separate exploratory factor analyses on measures of stress exposure in childhood and psychopathology in adolescence. We then examined associations among obtained latent factors and conducted an exploratory mediation analysis of frontolimbic functional connectivity. Factor analyses yielded three distinct domains of stress exposure: ‘Parenting,’ ‘Neighborhood Deprivation,’ and ‘Household Threat/Unpredictability,’ along with a single latent factor of ‘Psychopathology’ at follow-up. Regression analyses indicated that Parenting (b=.20, p=.003) and Household Threat/Unpredictability (b=.18, p=.007), but not Neighborhood Deprivation (b=-.003, p=.647), predicted Psychopathology in adolescence. Mediation analyses yielded a significant indirect effect for the association between Household Threat/Unpredictability and Psychopathology through functional connectivity between the right hippocampus and left dorsolateral prefrontal cortex (b=.03, p=.036). Sensitivity analyses indicated this effect was unique to Household Threat/Unpredictability, underscoring the potentially domain-specific nature of early stressors in shaping brain development and behavioral outcomes. Our results suggest broad dimensionality in the relation between stress exposure and
psychopathology, warranting further investigation of such dimensions, es ecially with respect to individual differences and implications for intervention targets.

Name: Kendall Coden, MS
University: University of Michigan
Department: Neuroscience Graduate Program
Mentor or PI: Drs. Karen Parker and Joseph Garner

Poster Title: “Proteomic Insights into the Developmental Pathophysiology of Stereotypy”

Stereotypies (abnormal, repetitive, and seemingly goal-less behaviors) are a key feature of several neurodevelopmental disorders. We previously established that spontaneous stereotypy in animals resembles human stereotypy, including evidence of both homologous cortico-striatal dysfunction and presence of knowledge-action dissociation—a deeply distressing affective state. Despite well documented risk factors contributing to stereotypies in individual species, a common developmental pathophysiology remains elusive. There is compelling evidence that REDOX imbalance is a causal developmental pathophysiology of compulsive behaviors. Compulsive behaviors are related to, yet distinct, from stereotypies—compulsive behaviors are repetitive, goal- directed behaviors. However, to our knowledge, the relationship between REDOX balance and stereotypy has not been examined. We first tested whether glutathione (GSH), the gold-standard biomarker of oxidative stress, predicted severity of stereotypy in N=19 mice (all on a C57BL/6 background), as it does in our other mouse models of compulsive behaviors (e.g. Trichotillomania; Ulcerative Dermatitis). We next used a novel proteomics approach to identify a more specific and sensitive biomarker profile. We found expression of 9 proteins to correlate with plasma GSH, and expression of 15 proteins to correlate with severity of stereotypy. Supporting a role for REDOX imbalance in the developmental pathophysiology of stereotypy, the identified proteins were tightly associated with REDOX physiology, dopamine physiology, and stereotypy-presenting neurodevelopmental disorders. A subset of proteins were also associated with disorders characterized by compulsive behaviors. These data suggest REDOX imbalance may be a shared
developmental pathophysiology across abnorma nd highlight promising novel targets for early detection and intervention.

Name: Maya Evans, BA
University: University of Iowa
Department: Psychiatry
Program or Lab: Interdisciplinary Graduate Program in Neuroscience Mentor or PI: Hanna Stevens, MD, PhD

Poster Title: “The effects of prenatal stress on distinct dorsal striatal cell types and autism spectrum disorder-relevant behaviors in mice”

Many people with autism spectrum disorder (ASD) show abnormalities of the dorsal striatum on the levels of morphometry, connectivity, and molecular biology. Several of these changes have been associated with symptoms in ASD, especially in the domain of restrictive, repetitive behavior. These striatal changes arise early and are dynamic over development. One early developmental risk factor for ASD is prenatal stress (PS), or maternal stress during pregnancy. In this project, we studied the effects of PS on striatal neurobiology and striatal-dependent behaviors using a mouse model. We performed single-cell RNA sequencing on dorsal striatum from adult male PS offspring, revealing transcriptomic changes in multiple cell types compared to controls. Pathway enrichment analysis of differentially expressed genes showed themes including upregulation of glutamatergic synaptic transmission and downregulation of ribosomal biogenesis. Additionally, differentially expressed genes had significant overlap with ASD- associated genes. Behavioral testing was performed on male and female adult mice. PS had no effect on overall activity or anxiety-like behavior in an open field test. However, PS mice showed increased motor learning on Rotarod (p=0.019) and faster timing in an interval timing task (p=0.029). Neural recordings from the dorsomedial striatum during the interval timing task revealed a greater percentage of neurons displaying timing-related ramping activity, as well as a greater increase in neuronal firing rate over the interval in PS mice. Overall, PS led to ASD- relevant changes in striatal transcription and striatal-dependent behaviors. Our results implicate glutamatergic synapses and ribosomes as potential mechanistic targets in the development of novel interventions.

Name: Princess Felix, BS
University: University of Michigan
Department: Rackham Graduate School; Neuroscience Graduate Program Program or Lab: Flagel Lab
Mentor or PI: Dr. Shelly Flagel

Poster Title: “The Effect of Glucocorticoid Receptor Knockdown in a Corticostriatal Pathway on Cue-Motivated Behaviors”

Abstract:

Glucocorticoid receptors in a “top-down” cortico-striatal pathway play a role in the inhibitory control of cue-motivated behaviors

Princess Felix, Alexandra Turfe, Stephen E. Chang, Jaydin Adams, Elena Cooper, James P. Herman, Shelly B. Flagel

The glucocorticoid receptor (GR) is best known for its role in stress responsivity and emotionality but is also known to play a role in reward processing. GRs been implicated in the pathophysiology of multiple psychiatric disorders, including impulse control and substance use disorders, and associated with an increased risk of suicidality. As deficits in inhibitory control is a common characteristic shared across psychiatric disorders, we postulate that GR within a “top- down” cortico-striatal pathway play a critical role in this regard. Here we used GR-CRISPR transgenic rats to selectively knock-down GR in glutamatergic afferents projecting from the prelimbic cortex (PrL) to the nucleus accumbens core (NAcC). We assessed the effect of this manipulation on the propensity to attribute incentive salience to a reward-associated cue using a Pavlovian conditioned approach paradigm. Prior studies have revealed that rats with a greater propensity to attribute incentive salience to reward-cues (i.e., sign-trackers) show increased impulsive action, have attentional deficits, and are more likely to exhibit cue-induced reinstatement of drug-seeking behavior relative to rats that primarily attribute predictive value to reward-cues (i.e., goal-trackers). We found that GR knockdown within the PrL-NAcC pathway results in an increased propensity to sign-track regardless of sex. These findings suggest that GR function in a top-down corticostriatal circuit plays a role in incentive motivation and the
ability of cues to attain control over and elicit maladaptive behavior.

Name: Shannon Grogans, M.S.
University: University of Maryland, College Park
Department: Department of Psychology
Program: Clinical Psychology Doctoral Program
Lab: Affective and Translational Neuroscience Laboratory
Mentor or PI: Alexander J. Shackman, Ph.D.

Poster Title: “The neural systems and real-world mood dynamics underlying dispositional risk for internalizing illness”

Background: Internalizing disorders impose a staggering burden on public health. Existing interventions are inconsistently effective, underscoring the need to understand the mechanisms that confer risk. Neuroticism/negative emotionality (N/NE) is a well-established risk factor for future anxiety and depression diagnoses. Yet, the neural systems and real-world psychological processes underlying these prospective-longitudinal trajectories remain unclear.

Method: We addressed these questions using a novel combination of data—including threat-anticipation and emotional-face fMRI paradigms and repeated waves of smartphone experience-sampling and internalizing symptom assessments—acquired from an ethnoracially diverse, risk-enriched sample of emerging adults followed for 2.5 years (n=217-220; ps<.05).

Results: Robust GLM analyses demonstrated that elevated baseline N/NE was associated with longitudinal increases in internalizing symptoms. Variation in the N/NE phenotype was uniquely associated with heightened bed nucleus of the stria terminalis (BST) reactivity to uncertain-threat anticipation, and unrelated to BST/amygdala reactivity to certain-threat anticipation or negative faces. HLM analyses demonstrated that N/NE was associated with elevated levels of tonic (stressor-independent) and reactive (stressor-dependent) negative affect, whereas BST reactivity to uncertain-threat was selectively associated with heightened stressor reactivity.

Discussion: These observations provide a first glimpse at the processes that link a prominent dispositional risk factor to the emergence of internalizing illness. They suggest that elevated levels of the risk-conferring N/NE phenotype reflect exaggerated BST threat-reactivity, which manifests as potentiated reactivity to everyday stressors and challenges. These observations provide a neurobiologically grounded framework for conceptualizing internalizing illness and prioritizing mechanistic work focused on the BST. A relatively large, well-characterized sample enhances confidence in the robustness of these findings.

Name: Brandon King, PhD
University: University of California, Davis
Department: Center for Mind and Brain
Program or Lab: Saron Lab
Mentor or PI: Clifford Saron

Poster Title: “Validating a Diversity-informed Database of Emotional Images for Affective and Clinical Science”

Compassion and personal distress are distinct emotional experiences that arise from observing suffering in others or from witnessing vicarious harm. However, few standardized research tools exist to elicit and differentiate these important domains of affective experience. In addition, the relative lack of diverse representations of people, cultures, and situational contexts in established stimulus sets can limit their generalizability across populations and groups. To address this gap, we have curated and normed a novel stimulus set of 1,440 emotionally evocative images of suffering, threat, and interpersonal conflict. The Thematic Affective Picture Set (TAPS) depicts a thematically and socially diverse set of content, including themes of human, animal, and environmental suffering, direct danger, interpersonal violence, perpetrators of harm, as well as pleasant and neutral scenes. Example themes of suffering include people experiencing homelessness, poverty, grief, displacement, illness, conflict or war, starvation, and loneliness. I will present normative data showing that themes of suffering, threat, and harm can be discriminated in affective space based on individual differences in empathy and approach–withdrawal tendencies. Among 237 university participants, higher trait empathy predicted greater feelings of avoidance and negativity towards threat, but more approach motivation and negativity towards suffering. I will also describe attributes of the image set that make it advantageous for
experime oimaging, to behavioral measures of emotional memory.

Name: Jiani Li, B.S.
University: University of Southern California Department: Psychology
Program or Lab: Cognition and Affect Regulation Lab, Ph.D. in Clinical Science Mentor or PI: Dr. Jonathan Stange

Poster Title: “Ambulatory Physiological State Dynamics Predict Proximal Behavioral Markers of Depression in Everyday Life”

Human physiology reflects the body’s capacity for self-regulation that is crucial for flexible adaptation to changing environmental demands. Leveraging wearable sensors and machine learning, we aimed to uncover latent physiological states in ambulatory recordings of cardiac, respiratory and activity signals that predict momentary affective outcomes relevant to depression, with implications for informing just-in-time adaptive interventions. 51 participants with remitted major depressive disorder (rMDD) and 42 healthy volunteers (HVs) completed seven-day ecological momentary assessments of affect, affect regulation and impulsivity while their heart rate variability, respiration, and movement were passively monitored. Using Hidden Markov Models for state decoding, we found that transitions into stressed physiological states identified proximal increases in behavioral markers of psychopathology, including negative affect, maladaptive emotion regulation (ER), and momentary impulsivity. Furthermore, compared to HVs, individuals with rMDD showed lower positive affect when dwelling in relaxed states, and more maladaptive ER after transitioning into and out of stressed states.
Relative to HVs, individuals with rMDD reported higher negative affect and less adaptive ER after dwelling in active and average states while more adaptive ER after visiting relaxed states. Findings underscore the utility of passive physiological phenotyping for tracking momentary affective processes that could be hard to actively sample but may be crucial to informing optimal moments for intervention. Moreover, group differences in the relationships between physiological state dynamics and psychological outcomes suggest potential alterations in physiology-affect coupling related to depression history, which could reveal novel physiological mechanisms of and treatment targets for depression.

Name: Sara Beth Mitchell, BA
University: University of Iowa
Department: Molecular Physiology and Biophysics, Psychiatry
Program or Lab: Interdisciplinary Graduate Program in Neuroscience
Mentor or PI: Dr. Rainbo Hultman, PhD, and Dr. Hanna Stevens, MD, PhD

Poster Title: “Stress, vulnerability, and the maternal experience: Electrical network and behavioral assessments of the maternal mouse brain”

Abstract: 
Coordinated brain changes accompany the transition to motherhood. These neural adaptations benefit the young through enriched parental care abilities. However, they may not be entirely adaptive, leaving the maternal brain open to the potential development of psychiatric disorders. Maternal early life experiences, such as exposure to early life stress (ELS), are known to increase the risk of negative phenotypes in adulthood through lasting developmental brain changes heightening vulnerability. The aim of this investigation is to elucidate changes of electrical dynamics in the maternal brain relating to previously identified stress and vulnerability- associated electrical brain networks. This study also examines correlations of network activity with observed maternal care behavior and assesses alterations according to ELS history. A combination model of ELS was used to increase vulnerability in CD1 mice, a highly maternal strain. Female mice were surgically implanted with multi-site in vivo recording electrodes prior to breeding for the continued observation of brain-wide electrical dynamics. Recordings of network activity were captured in the home-cage at multiple time points from pre-gestation through weaning to capture the full course of maternal brain change. In line with previous studies of stress vulnerability networks and in consideration of parental network literature, electrodes targeted the following regions: prelimbic and infralimbic cortices, nucleus accumbens, basolateral, medial, and central amygdala, ventral hippocampus, ventral tegmental area.
Maternal behaviors were recorded at parturition and during assessment time points for evaluation alongside electrical dynamics. Initial findings suggest intriguing overlaps between
neural circuit correlates of maternal brain adaptations and changes with early adversity.

Name: Amar Ojha, BA
University: University of Pittsburgh Department: Neuroscience
Program or Lab: Cognitive-Affective Neuroscience and Development Lab Mentor or PI: Dr. Cecile Ladouceur

Poster Title: “Anhedonia is Associated with Altered Striatal Neurophysiology and Function in Adolescents Varying in Levels of Depression”

Abstract:
Background: Anhedonia—the reduced capacity for pleasure—is a common and debilitating feature of adolescent depression related to altered reward circuitry, but the role of striatal neurophysiology remains unclear. We examined whether regional homogeneity (ReHo), an index of regional synchronization, was associated with anhedonia beyond other depressive symptoms, and to what extent this relationship was moderated by striatal dopaminergic neurophysiology, assessed using the normalized T2* signal to index tissue iron.

Methods: 75 adolescents participated in the study, of whom 56 scored ≥ 40 on the Children’s Depression Rating Scale-Revised (CDRS-R) and 19 reported no current/past self/parent psychiatric diagnosis. Anhedonia was assessed using the Snaith-Hamilton Pleasure Scale (SHAPS) and other depressive symptoms using the Mood and Feelings Questionnaire (MFQ). We used a voxel-wise moderated mediation approach controlling for age, sex, and symptoms of depression besides anhedonia.

Results: Reduced ReHo was associated with higher levels of anhedonia in adolescents with higher striatal tissue iron in the right caudate, and with lower levels of anhedonia in adolescents with lower levels of tissue iron. Further, reduced striatal tissue iron in the left putamen was associated with higher levels of anhedonia.

Conclusions: Both lower striatal ReHo and striatal tissue iron were associated with anhedonia beyond other depressive symptoms; however, these effects were specific to the dorsal striatum and the direction of this relationship was contingent upon levels of striatal tissue iron. Future research is needed to determine the effectiveness of dopamine-targeted pharmacotherapy for adolescents with anhedonia and particularly those with altered dopaminergic functioning.

Name: Grace Schamber, senior undergraduate and first year graduate student
University: Marquette University
Department: Biomedical Sciences
Program or Lab: Gilmartin Lab
Mentor or PI: Dr. Marieke Gilmartin

Poster Title: “Prefrontal Cortical Output to the Mediodorsal Thalamus Encodes Trace Fear Conditioning”

Abstract: Anticipation of threat from available cues during trace fear conditioning processes require activity from the prelimbic cortex (PL). Neurons within this region show sustained firing to shock- predictive cues, and when these neurons are disrupted, learning is impaired. This suggests a role for the prelimbic cortex in working memory, especially in the acquisition of fear. What is unknown is how this threat signal is distributed to downstream emotional learning systems to support fear memory.
Here we investigate the role of the mediodorsal thalamus (MD) in trace fear conditioning. The MD is strongly connected to the PL and emotional systems like the amygdala and brainstem arousal systems, positioning it as a potential node important for integrating information for working emotional memory. In this study, an intersectional viral approach was used to express GCaMP6f or ArchT in PL cells projecting to the MD. Fiber photometric imaging of PL-MD revealed activation of this pathway during threat-predictive cues in trace conditioned rats and potentiated CS-evoked activity at test compared with pre-training CS-alone trials. Additional experiments were performed to test the functional significance of PL-MD activity by optogenetically silencing the pathway during training and to characterize the encoding profiles of MD neurons using in vivo electrophysiology. The outcome of this work will begin to reveal the role of this thalamic nucleus in the acquisition and expression of episodic
fear memories.