Poster Session

Name: Nakul Aggarwal, PhD
University: University of Wisconsin-Madison
Department: Psychiatry
Program or Lab: Kalin Lab
Mentor or PI: Dr. Ned Kalin

Poster Title: “A preliminary multimodal investigation of white matter microarchitecture in preadolescent females using DTI, NODDI, and quantitative relaxometry”

Background: Diffusion tensor imaging (DTI) has been widely used to delineate white matter (WM) alterations in individuals with psychiatric disorders. Other WM neuroimaging methods have the potential to further elucidate specific characteristics of WM alterations. Neurite orientation dispersion and density imaging (NODDI), which employs a more sophisticated model of water diffusion, can provide information related to axonal or neurite density (NDI) and orientation dispersion (ODI). Quantitative relaxometry (qR1), relying on a different mechanism, captures magnetic relaxation of protons and is highly sensitive to myelin sheaths. Here, we report results from youth comparing DTI, NODDI, and qR1 metrics.

Methods: Multi-shell diffusion-weighted and T1-weighted MPnRAGE images were collected in 22 females (M=10.2y). Inter-modality Pearson correlations (p<0.01) were examined among diffusion weighted metrics (fractional anisotropy-FA, NDI, ODI) and longitudinal relaxationrates (qR1) for five ROIs from the JHU WM atlas (UF, CC, CING, SLF, IC).

Results: qR1 was largely uncorrelated with any DTI or NODDI metric. FA, a global measure of WM integrity, was positively (mean-r=0.72) and negatively (mean-r=-0.78) associated with NDI and ODI, respectively, in 4/5 ROIs. NDI and ODI were uncorrelated. Age and qR1showed a trend towards positive correlation (mean-r=0.39, p<0.1).

Conclusion: DTI and NODDI measures were moderately correlated, suggesting that they likely capture distinct but related biophysical properties of WM dynamics. qR1 was unrelated to any DWI metric, is thought to be specific to myelination, and does not rely on water diffusion. Future studies will leverage these modalities to investigate how different components of WM microarchitecture may be altered in childhood psychopathologies.

Name: Hazal Arpaci, MS – Travel Award Winner
University: University of Iowa
Department: Psychological and Brain Sciences
Program or Lab: Behavioral and Cognitive Neuroscience-NAP Lab
Mentor or PI: Dr. Bengi Baran

Poster Title: “Anxiety Alters NREM Sleep Oscillations in Young Adults”

Sleep is essential for emotional regulation, and even one night of sleep deprivation can heighten anxiety and impair affective processing. However, the role of Non-REM sleep (NREM) oscillations in sleep-dependent emotion regulation remains unclear. In this study, we examined whether NREM oscillations are altered in individuals with heightened trait anxiety and how they relate to emotional memory, anxiety symptoms, and negative affect. Forty-two non-help-seeking young adults (M = 19.3, SD = 1.8 years; 77% female) with high (n = 26) vs. moderate-to-low (n = 16) trait anxiety were monitored with sleep EEG during a 2-hour midday nap. Slow oscillations (SOs), and sleep spindles during NREM 2 and NREM 3 stages of sleep were quantified, and participants completed a sleep-dependent emotional memory task, and reported anxiety (STAI) and affect (PANAS) levels upon awakening. Across the sample, greater SO activity was associated with lower state anxiety (pcorrected=.046, 7 electrodes), and negative affect (pcorrected=.045, 7 electrodes), while higher spindle activity correlated with increased anxiety and negative affect. The high-anxiety group exhibited reduced SO activity (pcorrected =.04, 6 electrodes) and delta power (pcorrected=.04, 21 electrodes), but no differences in sleep-dependent emotional memory consolidation or sleep architecture was observed. These findings suggest that SOs may play an anxiolytic role, with greater activity linked to reduced anxiety and negative affect. Additionally, reduced SO activity in highly anxious individuals may reflect a potential biomarker or intervention target for anxiety symptoms. Understanding the mechanisms underlying this relationship could inform future treatments leveraging NREM sleep to enhance mental health.

Name: Ashton Barber
University: University of Wisconsin-Madison
Department: Psychiatry
Program or Lab: Neuroscience Training Program
Mentor or PI: Dr. Ned Kalin

Poster Title: “Ketamine interacts with opioid receptors in the nonhuman primate amygdala and nucleus accumbens”

Ketamine is an NMDAR antagonist that has rapid-acting antidepressant effects. Despite ketamine’s known action at the NMDAR, it also acts as an agonist at 𝜇 and 𝜅 opioid receptors with slightly lower binding affinity. Previous studies in humans have demonstrated that activation of opioid receptors is necessary for ketamine’s antidepressant effects, and work in rodents supports these findings. No studies have been performed in nonhuman primates (NHPs) investigating ketamine’s interactions with opioid receptors. NHPs are well-suited for preclinical studies to investigate treatments for psychiatric illnesses because they have similar stress-related behaviors, social structures, and prefrontal cortical brain development to those of humans. Using brain tissue slices from the amygdala and the nucleus accumbens from one rhesus macaque, we conducted receptor and [35S]GTP𝛾S autoradiography to investigate ketamine’s ability to bind to 𝜇 and 𝜅 opioid receptors as well as elicit G-protein signaling. 10 𝜇M but not 1 𝜇M of ketamine significantly reduced 𝜇 and 𝜅 opioid receptor binding in both regions, suggesting that ketamine competes with high affinity ligands at 𝜇 and 𝜅 opioid receptors in a concentration-dependent manner. However, 10 𝜇M of ketamine did not significantly increase G-protein signaling. These initial findings suggest that ketamine binds directly to opioid receptors in the NHP amygdala and nucleus accumbens, but it is not efficient at producing intrinsic G-protein signaling. Future work will expand the number of animals in this study as well as examine the role of the opioid receptor system in ketamine’s effect on anxiety-like NHP behavior.

Name: Kush V. Bhatt, MD – Travel Award Winner
University: University of California, San Diego
Department: Psychiatry
Program or Lab: VA San Diego Neuromodulation Program
Mentor or PI: Dhakshin Ramanathan MD, PhD

Poster Title: “Ketamine-Occasioned Mystical Experience In Veterans With Treatment-Resistant Depression”

Mystical experiences are powerful psychological experiences that may have therapeutic value. However, limited research has explored these phenomena in the context of ketamine treatment. We examined the occurrence of mystical experiences in Veterans with treatment-resistant depression (TRD) receiving ketamine treatment. Clinical data from 60 Veterans who underwent a total of 189 ketamine treatments were analyzed. Veterans received either intranasal esketamine or racemic ketamine (intravenous or intramuscular). The Revised Mystical Experience Questionnaire (MEQ-30) was administered following treatment to assess the presence and intensity of mystical experiences. A linear mixed model was used to evaluate the relationship between MEQ-30 scores and treatment-related factors, including treatment number, dose, co-morbid PTSD, pre-treatment PHQ-9 scores, age, and gender. Complete mystical experiences were reported in 17.0% of esketamine treatments and 18.2% of racemic ketamine treatments. In the esketamine group, a greater number of treatment sessions was associated with higher MEQ-30 scores (p = 0.05). In the racemic ketamine group, higher doses were significantly correlated with greater MEQ-30 scores (p = 0.002). These findings suggest that ketamine can induce mystical experiences in Veterans with TRD, and that treatment-related variables such as dose and session number may influence this effect. Further research is needed to clarify the role of mystical experiences in ketamine’s therapeutic efficacy and their potential contribution to treatment outcomes.

Name: Morgan Brody
University: Loyola University Chicago
Department: Psychology
Program or Lab: Memory & Neuromodulatory Mechanisms Lab
Mentor or PI: Stephanie Grella, PhD

Poster Title: “Artificial Reactivation of a Cocaine-Associated Engram in the Dorsal Dentate Gyrus Attenuates Cocaine Prime-Induced Reinstatement of Drug-Seeking”

Substance abuse is characterized by a continual propensity to relapse. Relapse-prevention strategies aimed at reducing the likelihood and severity of relapse following abstinence, focus on reducing cravings that lead to drug-seeking. Factors precipitating drug-seeking include exposure to drug-related cues, to the drug itself, and to stress. We are interested in the contribution of drug-related memories in drug-seeking behaviors. Recent technological advances have given us the ability to genetically tag and manipulate memories in mice, such that we can reactivate them with light post-encoding. To investigate the role of these memories in promoting or protecting against relapse, we tagged hippocampal dorsal dentate gyrus cells involved in encoding a cocaine-related memory using a Tet-tag system to express ChR2 driven by the c-Fos promoter, in male and female c57BL/6 mice. Using the conditioned place preference (CPP) paradigm, we assessed whether artificial reactivation of a cocaine-tagged memory could be used in place of the drug to reinstate CPP. We found that optical reactivation of the cocaine engram did not induce locomotor effects, nor did it reinstate CPP. However, when paired with a cocaine prime injection, it blocked reinstatement. These data suggest that such reactivation of a first exposure to cocaine may confer protective effects, potentially reducing relapse risk, and therefore has therapeutic significance. Building on our previous research with fear memories, we hypothesize that this manipulation resulting in attenuation of CPP may be due to extinction-like effects where the significance of the drug-paired context is changed in the presence of the drug.

Name: Jairo Chavez, BS – Travel Award Winner
University: University of California Davis
Department: Psychology
Program or Lab: Foxlab
Mentor or PI: Andrew S. Fox

Poster Title: “Quantifying Behaviors in Non-Human Primates Using Deep Learning”

Background: Anxiety disorders are prevalent and debilitating, affecting one in four individuals and increasing the risk of depressive disorders and substance abuse. Behavioral inhibition, characterized by wariness or avoidance of unfamiliar situations, is a risk factor for anxiety disorders. To better understand anxiety, we study non-human primates (Macaca mulatta), whose behavioral complexity, social structures, and physiological similarities to humans make them invaluable models. Advances in machine learning and computer vision provide unprecedented insights into behavior, reducing the need for manual annotations. Deep learning can track individuals and identify significant behaviors indicative of anxiogenic phenotypes.

Methods: We present novel approaches to applying machine learning for behavior quantification in non-human primates using deep learning, timeseries analysis, and UMAP clustering during the no-eye-contact condition of the human-intruder paradigm (n = 141).

Results: We successfully coded freezing behavior and analyzed posture to identify behavioral motifs. Using dynamic thresholding, median cluster sizes were retained, yielding 2,673 clusters and preserving 48.01% of all clusters. Each motif appeared in an average of 11.67 subjects. Several motifs correlated with freezing (p<.05), providing additional insight into behavioral responses to potential threats.

Conclusions: These advancements offer scalable methods for analyzing complex behaviors in unrestrained, naturalistic settings. Real-world conditions, where anxiety develops, are critical for broad-based insights into non-human primate behavior. Ultimately, these approaches may transform how we study anxiety and related behaviors in naturalistic environments.

Name: Kerstin C. Creutzberg, PhD – Travel Award Winner
University: University of Colorado
Department: Department of Psychiatry
Program or Lab: Laboratory of Translational Psychiatry
Mentor or PI: Tracy L. Bale

Poster Title: “Cellular mechanisms linking paternal stress with reproductive function and embryo development”

Stress is an important determinant of human behavior and physiology and can lead to long-term health issues. In males, studies have identified prolonged effects of stress on reproductive somatic cells that can influence offspring development. Within the epididymis, sperm undergo a critical maturation process facilitated by factors secreted into the caput lumen by epididymal epithelial cells (EECs). Our previous work demonstrated that paternal stress exposure disrupted offspring neurodevelopment and altered adult stress responsivity. However, the mechanistic link between stress-induced epididymal changes and sperm function remains poorly understood. To mechanistically examine this, we utilized a transgenic chemogenetic mouse model to mimic the cellular effects of stress by chronically increasing EEC intracellular calcium signaling thereby increasing sperm mitochondrial activation and extracellular vesicle secretion. We employed chronic activation of caput EECs (LCN5-expressing cells) that express the Gq-coupled Designer Receptor Exclusively Activated by Designer Drugs (DREADD) receptor hM3Dq. Remarkably, we found that chronic treatment with the DREADD ligand clozapine-N-oxide (CNO) induced changes in sperm mitochondrial signal intensity. Additionally, DREADD males exhibited enhanced reproductive function, as evidenced by larger litters. These findings suggest that EECs respond to environmental cues and regulate sperm function, potentially mediating the effects of paternal stress on offspring. Understanding this pathway provides key insights into how paternal experiences may shape reproductive outcomes and ultimately offspring neurodevelopment, linking epididymal signaling to intergenerational stress transmission.

Name: Mark Flores, BS
University: University of Iowa
Department: Health and Human Physiology
Program or Lab: Integrative Laboratory of Applied Physiology & Lifestyle Medicine
Mentor or PI: Dr. Nathaniel Jenkins

Poster Title: “Depression and anxiety symptoms are positively related to mitochondrial reactive oxygen species in CD8+ T-cells among young adults with Adverse Childhood Experiences”

Introduction: Adverse childhood experiences (ACEs) are severe psychosocial stressors in childhood that are associated with increased anxiety and depression symptomology. We hypothesized that immune-mediated oxidative stress would be associated with mood symptoms in individuals with ACE exposure.

Purpose: To explore associations between ACE exposure, anxiety and depression symptoms, and T-cell mitochondrial reactive oxygen species (mtROS) in young adults.

Methods: Seventeen apparently healthy young adults (l 1F/6M; 22±3 y) who reported no ACE (ACE-; n=8) or high (2′.:3) ACE (ACE+; n=9) exposure provided a blood sample and completed the Center for Epidemiological Studies Depression and Zung Self Rating Anxiety scales to quantify depression and anxiety symptoms. Using flow cytometry, CD8+ T­ cells were identified and stained (MitoSOX) to measure mtROS. ACEs-related differences in depression, anxiety, and mtROS were examined using two-sample t-tests. Relations between depression and anxiety with mtROS were examined using Spearman’s correlation coefficients (p) stratified by ACE exposure.

Results: Depression (+20±12 arbitrary units (au),p=0.014) and anxiety (+34±6 au,p=0.006) symptoms were greater in ACE+ than ACE-. There was a large (Hedges’ g=-0.92), but non-significant group difference for mtROS (-726±384 au;p=0.078). Both depression (p=0.69,p=0.041) and anxiety (p=0.67,p=0.049) symptoms correlated positively with mtROS in ACE+, but not ACE- (ps2′.:0.64).

Conclusion: Unexpectedly, mtROS was practically lower in ACE+ than ACE-. However, both depression and anxiety symptoms were positively related to mtROS in ACE+ only. These preliminary findings serve as a foundation on which to further interrogate the role of mitochondrial metabolism in ACEs-related depression and anxiety.

Name: Paloma Frautschi, MSc
University: University of Wisconsin-Madison
Department: Radiology
Program or Lab: Clinical Investigation
Mentor or PI: Dr. Jon-Paul Yu

Poster Title: “Psilocybin and Ketamine Alter Neurites in a Stressed Rat”

Recently, psilocybin, a 5-HT2A agonist, and ketamine, a NMDA antagonist, have shown promise in clinical trials for alleviating symptoms associated with treatment-resistant major depressive disorder (MDD), however the mechanism of action remains unclear. Diffusion-weighted MR techniques like neurite orientation dispersion and density imaging (NODDI) offer insight into structural changes taking place in the brain. This study uses a preliminary diffusion MR analysis to look at changes that occur after a single injection of psilocybin or ketamine following a chronic restraint paradigm to model stress-induced depression. P35-37 Sprague-Dawley female rats were divided into a chronic restraint (CRS+) or non- chronic restraint (CRS-) group. The CRS+ groups were immobilized for 3h daily, for two weeks. On day 14, rats were injected with 2mg/kg psilocybin, 5ml of saline (psilocybin group), 10mg/kg ketamine or 5ml saline (ketamine group). One week after the injection, the brains were perfused, extracted, and ex-vivo imaged (n=6 per treatment x behavior group). The four treatment groups were compared with 2-way ANOVA (Tukey) for diffusion metric means of NODDI (NDI, ODI) in the hippocampus, neocortex, amygdala, thalamus, and basal ganglia. Significant differences were found between stressed and non-stressed groups for both treatment and drug, namely a “reversal” in stress-induced ODI increases in the neocortex. This preliminary study points to a distinct effect of psilocybin and ketamine on neurites in a stress-induced animal model of depression.

Name: Sydney Gifford
University: University of Wisconsin-Madison
Department: Psychiatry
Program or Lab: Kalin Lab
Mentor or PI: Dr. Ned Kalin

Poster Title: “Acute Behavioral Effects of Psilocybin in Nonhuman Primates”

Psilocybin, a drug well-known for its psychedelic effects in humans, is a 5HT_2A receptor agonist that has sparked interest within the field of psychiatric research for its potential therapeutic effects across several mental health conditions. Further investigation of these effects in preclinical animal models has primarily been done in rodents, with little work done in nonhuman primates (NHPs). Studying the effects of psilocybin on anxiety-related behaviors in NHPs will further our understanding of the therapeutic effects of psilocybin in humans.

This study aims to observe the effects of acute psilocybin treatment on behavior in rhesus macaques with the goal of establishing a human equivalent dose. This study utilized a within-subjects, crossover design where five primates (2M, 3F), were administered vehicle, 0.3 mg/kg psilocybin, or 1 mg/kg psilocybin intramuscularly with 2 weeks between treatments. Immediately after treatment, animals were observed for 3 hours. The animals were alone for the observation period except for 15, 30, 60, 90, 120, and 180 minutes post-injection during which a human intruder entered the room and stared at the animal for 3 minutes. Alone and Stare conditions function to contrast behaviors observed in non-threatening and aversive contexts. Across both contexts, we observe a psilocybin-induced increase in drowsiness, a behavior not typically observed in either context, and a decrease in locomotion. During the Stare condition specifically, we see a decrease in typical aggressive behaviors (teeth grinding) and an increase in maladaptive, anxiety-related freezing. These findings suggest an acute increase in anxiety with psilocybin treatment.

Name: Tea Graham, BA
University: Marquette University
Department: Department of Psychology
Program or Lab: Translational Affective Neuroscience Lab
Mentor or PI: Dr. Jacklynn Fitzgerald

Poster Title: “Sociodemographic Correlates of Learned Fear: Preliminary Results from a Conditional Fear, Reward, and Neutral Discrimination Task”

Background: Contingency awareness — recognizing that a conditioned stimulus (CS) predicts threat — is critical for shaping conditioned fear responses. However, only limited research has examined sociodemographic differences in awareness. Such information may be critical to understanding factors associated with successful fear learning.

Methods: Participants (N = 93) completed a Fear, Reward, and Neutral Discrimination task; geometric shapes (CS) were associated with fear (aversive noise unconditioned stimulus [US]), reward (monetary US), or neutral (no outcome). Skin conductance responses (SCR) provided a measure of physiological response to the CS; self-reported likeability provided a measure of contingency awareness such that fear learners were those who rated the fear cue aversively. Chisquare and t-tests were used to test sociodemographic differences fear learning status. Moderated linear regressions tested whether fear learning status moderated the relationship between sociodemographic predictors and SCR to conditioned fear cues.

Results: Fear learner status was related to ethnoracial minoritized identity (p = 0.037). Ethnoracial minoritized individuals comprised 29% of the sample but were disproportionately represented as non-fear learners (50% of non-fear learners). Fear learning status was unrelated to gender (p = 0.451) and age (p = 0.945). Being a non-fear learner was associated with less SCR to the conditioned fear cue (p = 0.023), but fear learning status did not moderate the relationship between race and SCR to conditioned fear cues (p = .16).

Conclusions: Results support limited prior work that also found ethnoracial minoritized individuals do not form a learned fear response as readily as their white non-Hispanic peers.

Name: Alicia Henson, BS
University: University of Wisconsin-Madison
Department: Psychiatry
Program or Lab: Kalin Lab
Mentor or PI: Drs. Lisa Williams and Ned Kalin

Poster Title: “Pediatric Anxiety: Fear Learning and Extinction Recall”

Background: Anxiety disorders (ADs) commonly begin in childhood and increase risk for future psychopathology. AD individuals exhibit differential physiological, subjective, and neural responses during fear conditioning, extinction, and recall of extinction learning, but few studies have examined in children. Here we present initial results examining anxiety-related differences in fear Conditioning, Extinction, and Extinction Recall (ER) in preadolescent girls with a range of anxiety symptoms.

Methods: Participants included girls aged 8-11 in 3 groups: 1)AD –diagnosis of generalized, separation, and/or social ADs 2)SubAD -subthreshold AD symptoms 3)controls. 25 girls (AD=5/SubAD=9/Control=11) completed the Screaming Lady paradigm, which presents 2 neutral faces, one paired with a scream sound (CS+) and one presented alone (CS-). Two weeks later, 19 girls (AD=5/SubAD=7/Control=7) completed ER, viewing 5 facial morphs from CS+ to CS- and rating their fear (Afraid) and whether the face screamed during Conditioning (Scream). Skin conductance response (SCR) and subjective fear measures were collected, and task- and anxiety-related effects were examined using linear mixed-effects models.

Results: After Conditioning and Extinction, all participants demonstrated increased SCR and fear responses to the CS+ vs CS- (p<0.01). After Extinction, fear ratings were higher for AD vs. SubAD (p<.05). During ER, SCR and subjective (Afraid/Scream) responses increased across morphs from CS- to CS+ (p<.05); no anxiety-related differences were observed.

Conclusion: Initial results demonstrate the Screaming Lady paradigm effectively conditions differential physiological and subjective responses to the CS+ vs. CS- that are maintained into Extinction and ER two weeks later. Minimal anxiety-related effects were observed with the current sample.

Name: Olivia Imberger, BS – Travel Award Winner
University: University of Wisconsin-Madison
Department: Psychiatry
Program or Lab: Women’s Mental Health Program
Mentor or PI: Dr. Zachary Stowe

Poster Title: “Women’s Perinatal Experiences with Media-Based Information”

This qualitative study examined shame among women during the perinatal period in response to media-related information. Eleven women ages 18 – 45 enrolled in this study and were either pregnant or up to three months postpartum. 81.8% of participants were cohabiting and 54.5% were multigravida. Participants underwent semi-structured audio-recorded interviews that included topics related to accessing information about pregnancy and postpartum via online platforms. Interviews were transcribed and analyzed using inductive content analysis. In contrast to our original assumptions, participants described media-related information as relatable and supportive to participants’ needs. Participants stated platforms, such as Reddit (18.2%), Facebook (18.2%), Tik Tok (18.2%), and general information applications (45.5%), were useful. Furthermore, participants reported mainly positive experiences with online websites (36.4%) such as PubMed or MayoClinic. These findings pose a challenge with respect to where to provide information to patients, especially on polarizing topics related to the perinatal period. The design of this qualitative study allowed participants to respond apart from researcher biases, which a quantitative investigation may elicit. Using qualitative methods to examine patient responses regarding the perinatal period is useful in collecting nuanced experiential data. Further research is encouraged to assess which modality of online platforms would be most effective for patient intervention.

Name: Satish Jaiswal, PhD – Travel Award Winner
University: University of California San Diego
Department: Psychiatry
Program or Lab: Neural Engineering and Translation Labs (NEATLabs)
Mentor or PI: Dr. Jyoti Mishra

Poster Title: “A Multimodal Intervention (mediTMS) of Breath-focused Mindfulness and Transcranial Magnetic Stimulation in Treatment-resistant Depression (TRD) Patients”

Approximately 33% of depressed individuals do not respond to conventional pharmacological treatments and after multiple antidepressant trials become treatment-resistant. Several studies on depression characteristics have shown that breath-focused mindfulness can ameliorate ruminative symptoms of depression that stem from hyperactive default mode network (DMN) functioning. Further, it has been shown that impaired executive control functioning of the dorsolateral prefrontal cortex (DLPFC) in depression can be improved by the FDA-approved intermittent theta burst neuro-stimulation protocol (iTBS). Therefore, in this study, we sought to combine mindfulness practice, delivered digitally, with iTBS stimulation as a treatment for TRD. We compared this multimodal intervention (mediTMS, n=26) with a iTBS TMS intervention combined with a sham mindfulness control that emphasized deep breathing instead of attentive breath focus (sham mediTMS, n=26). Participants in both arms completed 30 iTBS sessions alongside their digital training. Participants completed baseline and post-intervention sessions of neuro-cognitive assessments with simultaneous EEG recordings, and additionally completed mental health surveys evaluating depression, anxiety, state mindfulness, inattentive behaviors and sleep. We observed that both groups showed improvement in depression and anxiety symptoms, but only the mediTMS group showed improvement in state mindfulness, inattention and sleep measures. Cognitively, the mediTMS group showed improved processing efficiency on a selective attention task while the sham mediTMS subjects did not show this effect. Neural analyses underlying these effects are ongoing and will be presented at the symposium.

Name: Agnieszka Kalinowski, MD, PhD – Travel Award Winner
University: Stanford University
Department: Psychiatry and Behavioral Sciences
Program or Lab: Adult Psychiatry
Mentor or PI: Alexander Urban, Phillipe Mourrain, Jong Yoon

Poster Title: “Synapses as a therapeutic target for schizophrenia”

C4A upregulation is hypothesized to exert is effect in Schizophrenia (SZ) by excessive synaptic pruning(1,2,12). However, the synaptic pruning hypothesis does not fully explain the effects of C4A upregulation(1,13–15): Evidence from large transcriptomic analysis suggests high C4A gene expression may be mediating low synaptic density through downregulation of select synaptic genes (7). Using virally-induced neurons (iNs) generated from induced pluripotent stem cells, we observed that induction of C4A expression either by plasmid overexpression or chemical stimulation (using IFN-g, a known C4 inducer(16,17)) resulted in decreased mRNA expression of GRIN2A and CACNA1 in induced neurons (iNs) cultured without microglia. Differential gene expression (DEG) analyses of RNA-seq of the untreated iNs compared to those treated with IFN-g or transfected with C4A overexpressing plasmid overlap with GWAS-loci in Syngo (annotated database of synaptic genes). More specifically, C4A protein overexpression downregulates a fraction of the DEGs compared to IFN-g, suggesting that the C4A protein (or mRNA) may be exerting an effect on synaptic gene downregulation. A functional intracellular role for C4A protein (or mRNA) has never been shown previously, though intracellular roles for complement proteins are emerging(18). This work could highlight an alternative treatment target for SZ that does not rely on blocking synaptic pruning by inhibiting microglia to interfere with the pathological effects of high C4A gene expression. Future work testing the correlation between high C4A gene expression and low synaptic density in iNs and postmortem brain tissue will be introduced.

Name: Maltesh Kambali, PhD – Travel Award Winner
University: University of Illinois Urbana Champaign
Department: Comparative Biosciences
Program or Lab: Neuropsychopharmacology lab
Mentor or PI: Dr. Uwe Rudolph

Poster Title: “Modulation of Anxiety and Fear via Distinct Intrahippocampal Projections to Ventral CA1”

Anxiety and fear are distinct emotional states triggered by different factors. The ventral hippocampus is known to be involved in the modulation of anxiety- and fear-related behaviors. Previously, we showed that inhibiting dentate gyrus and CA3 principal neurons through α2-containing GABAA receptors (α2-GABAARs) is necessary for the reduction of anxiety by diazepam, whereas inhibition of CA1 pyramidal neurons via α2-GABAARs is necessary for diazepam-induced suppression of fear responses. In this study, we wanted to test the hypothesis that while the CA3 to CA1 projection would modulate anxiety-related behavior, the direct projection from EC to CA1 would modulate fear-related behavior. To test this hypothesis, we used optogenetics to modulate ventral intrahippocampal projections bidirectionally. Adult C57BL/6J mice underwent bilateral stereotaxic viral injection expressing channelrhodopsin or halorhodopsion into vCA3 or into layers II-III of entorhinal cortex, followed by bilateral implantation of fiberoptic ferrules into vCA1. After three weeks of recovery, activation of the vCA3 to vCA1 projection decreased anxiety- and increased fear-related behavior, while inhibition of this projection increased anxiety- and decreased fear-related behavior. Optogenetic activation or inhibition of the EC to vCA1 projection did not affect anxiety-related behavior. In contrast, optogenetic activation or inhibition of the EC to vCA1 projection increased or decreased fear-related behavior. The behavior of the mice was recorded under laser ‘ON’ and ‘OFF’ conditions in all experiments. These results suggest that while fear-related behavior is modulated by both inputs to vCA1, modulation of anxiety-related behavior is input-specific for the vCA3 to vCA1 projection.

Name: Galit Karpov, PhD
University: University of Wisconsin-Madison
Department: Psychiatry
Program or Lab: BRAVE Research Center
Mentor or PI: Dr. Ryan Herringa

Poster Title: “Adolescent Frontal Neurodevelopment of Emotion Regulation“

Adolescence is a period that coincides with a peak in both the onset of psychopathology and neural development. A transdiagnostic characteristic of psychopathology is dysfunctional emotion regulation (ER), a process known to preferentially engage regions of the prefrontal, insular, and limbic cortex. ER can be implicit (automatic) or explicit (conscious), although direct neural comparisons of the two are rare. The current study aims to better understand the influence of age and neural maturation on the development of the two types of ER within normative adolescents. To address these aims, the study recruited typically developing youth aged 10-17 (N = 137) to complete ER assessment during fMRI at baseline and one-year follow-up. Implicit and explicit ER were separately examined using an emotional N-Back and the cognitive reappraisal task, respectively. Linear-mixed effects modeling was used to identify regions of the frontal cortex (Schaefer atlas parcellation) and the amygdala and hippocampus (Tian IV atlas parcellation) that were significantly predicted by age-related interactions within each task, with FDR correction. Here, implicit and explicit ER exhibited overlapping activation within key nodes of the salience and ventral attention network, including the Rolandic operculum, supplementary motor area, and dorsal insula. Implicit ER showed increasing disengagement as youth age, particularly for neutral stimuli. Meanwhile activity during explicit ER converged across negative and neutral stimuli, such that the activity in older youth could not differentiate the valence. These developmental trajectories deviate from patterns of ER activity in adults, highlighting the importance of studying adolescence to better inform clinical applications.

Name: Caroline Krell
University: University of Wisconsin-Madison
Department: Department of Psychology
Program or Lab: PIVOT Lab
Mentor or PI: Dr. Kate Walsh

Poster Title: “Mapping Psychopathological Outcomes in Sexual Violence Stigma Research: A Narrative Review”

Sexual violence is associated with a range of negative psychopathological outcomes, including posttraumatic stress, depression, anxiety, suicidality, and eating disorders. While research on sexual violence stigma is growing, it remains unclear which related psychopathological outcomes are measured. Clarifying this gap could highlight inconsistencies or identify under-measured outcomes, helping researchers develop more comprehensive studies and interventions. Studies were identified through database searches in October 2024. Following the PRISMA guidelines, articles from PsycINFO, CINAHL, Embase, PubMed, Scopus, and Web of Science were collected using keywords (e.g., “sexual,” “violence,” “stigma,” “measure”). Studies were included if they were: 1) published in English, 2) published in a peer-reviewed journal, 3) quantitative studies with ten or more participants, 4) focused on sexual violence, 5) included definitions and measures, and 6) included mental health outcomes. Of 11,641 identified articles, 40 met criteria for inclusion. Post traumatic stress disorder was the most frequently measured outcome (k = 29), followed by depression (k = 28) and anxiety (k = 15). Studies were primarily cross-sectional (k = 42), community-based (k = 22), and conducted in the U.S. (k = 38). Results indicate that higher levels of sexual violence stigma experienced by survivors are associated with greater severity of mental disorders. This review highlights the gap in literature examining the association between sexual violence stigma and obsessive compulsive disorder and eating disorders, which are adverse mental health outcomes associated with sexual violence exposure. Findings demonstrate a need for longitudinal studies to better understand the mechanism of stigma among sexual violence survivors.

Name: Julia Light, BS
University: University of Wisconsin-Madison
Department:
Program or Lab: PIVOT Lab
Mentor or PI: 

Poster Title: “Anxiety Severity Predicts Relative Slow Wave Power during NREM Sleep in Preadolescent Girls”

Background: Early-life anxiety confers risk to develop psychopathology. Most children with anxiety disorders (ADs) have disturbed sleep, but the physiological alterations related to this remain unknown. Deep, slow-wave sleep may be relevant to anxiety due to its association with emotion regulation, fear learning, and memory. We examined the relation between anxiety severity and 1) slow-wave activity (SWA) and 2) high-frequency wake-like EEG activity (alpha, beta) during sleep in a sample of preadolescent girls with a range of anxiety symptoms.

Methods: Thirty-four girls (age 8-12; 17 control, 13 subthreshold-AD, 4 AD) collected up to 10 nights of single-channel sleep EEG data at home using the Philips SmartSleep headband. Parent- and child-rated anxiety was assessed with the Screen for Child Anxiety Related Disorders (SCARED). Average absolute and relative spectral power were examined in relation to anxiety severity for alpha, beta, and delta/slow-wave frequency bands during NREM sleep using linear-mixed effects models, controlling for age.

Results: Parent and child SCARED scores were significantly correlated with relative SWA and alpha power (all p<.05 uncorrected), such that higher levels of anxiety were associated with relatively lower SWA power and relatively higher alpha power. Anxiety did not predict duration of NREM sleep or raw power values.

Conclusions: In a sample that includes girls with pathological anxiety, higher levels of anxiety are associated with parameters characteristic of less deep sleep and increased wake-like activity. Future work will explore the extent to which these alterations are relevant to understanding the pathophysiology of childhood ADs.

Name: Jennifer Meng
University: University of Michigan
Department: Michigan Neuroscience Institute
Program or Lab: Spencer-Segal Lab
Mentor or PI: Dr. Joanna Spencer-Segal

Poster Title: “Social isolation attenuates long-term behavioral and inflammatory effects of acute illness”

Sepsis, a dysregulated immune response to infection, can leave survivors with persistent inflammation and neuropsychiatric impairments. Independently, social isolation (SI), or lack of adequate social contact, is also linked to adverse mental health outcomes and dysregulated inflammation; however, its impact on the short- and long-term outcomes of acute illness is understudied. We investigated the effects of social isolation during recovery from acute illness on anxiety-like and social behaviors and systemic cytokine production, in a cecal slurry (CS) model of acute peritoneal sepsis. Adult C57BL/6J mice (n=40, half female) were assigned to treatment (CS or vehicle) and housing (SI or group housed). SI mice were single housed at time of illness induction. Acutely, CS decreased locomotion, and this sickness behavior was attenuated by SI. One-week CS survivors showed decreased total exploration of the elevated zero maze (EZM), which was also attenuated by SI. Meanwhile, SI increased anxiety-like behavior in the novelty suppressed feeding test (NSFT) and decreased social preference independently of CS. CS mice showed persistent elevation of the circulating cytokine LCN2; while this was seen in all mice, SI/CS mice had a diminished response to lipopolysaccharide (LPS) challenge compared to their GH/CS counterparts. Another cytokine, P-selectin, also remained elevated eleven days after CS induction; these levels and their response to LPS challenge were not affected by SI. Our findings suggest that in male and female mice, SI minimizes some of the acute and chronic behavioral and inflammatory sequelae of infection using the CS model.

Name: Lila Metko
University: Marquette University
Department: Biomedical Sciences
Program or Lab: Neuroscience Doctoral Program, Gilmartin Lab
Mentor or PI: Dr. Marieke Gilmartin

Poster Title: “Cellular Expression of PAC1R across the Estrous Cycle in the Prelimbic Cortex”

Women are two times more likely than men to develop PTSD, even when controlling for trauma type. This unequal prevalence may be linked to sex differences in neural circuit activity in response to stress. The neuropeptide Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) and its receptor have been implicated in specific PTSD symptoms in women. In rats, the PACAP system appears to play a sex-specific role in fear. Blocking the PAC1 PACAP receptor impairs fear learning in female but not male animals. The mechanisms behind this sex-specific effect remain unclear. Here we use RNAscope to investigate how cycling ovarian hormones affect PAC1R co-expression with estrogen receptors in prefrontal cortical cell types. In this study, we tracked estrous stage prior to euthanasia in 28 female rats, along with a comparison group of six males (mock lavage). A probe mixture targeting PAC1R with either VGAT and ER beta or VGLUT and ER alpha was applied to 20μm sections of the PL. Preliminary results suggest that prelimbic expression of PAC1R mRNA varies across estrous cycle stage. To identify potential source regions of PACAP to the PL during aversive learning, we inject a fluorescent retrograde virus into the PL of male and female rats (n=12). We then use immunohistochemistry to identify PACAP isoforms in the virus target regions. The outcome of this work is expected to shed light on how PACAP in the PL influences other regions to affect fear memory formation as well as how changes in PACAP signaling could contribute to PTSD susceptibility.

Name: Mohsen Poorganji, PhD – Travel Award Winner
University: University of California San Diego
Department: Psychiatry
Program or Lab: Interventional Psychiatry
Mentor or PI: Dr. Zafiris J. Daskalakis

Poster Title: “Treatment Prediction for Repetitive Transcranial Magnetic Stimulation in Major Depressive Disorder using rest EEG and Convolution Neural Network”

The development of objective, physiological biomarkers of treatment response is lacking for patients major depressive disorder (MDD). Resting-state electroencephalography (rsEEG) is a non-invasive and cost-effective imaging modality that holds promise in this regard. This study investigates whether rsEEG connectivity, calculated using inter-site phase clustering (ISPC), could differentiate MDD patients from healthy controls. Using convolution neural networks (CNN), a deep learning neural network algorithm, this study also investigated whether rsEEG connectivity prior to repetitive transcranial magnetic stimulation (rTMS) treatment could discriminate treatment responders from non-responders. Network analysis was conducted on the publicly available Two Decades-Brainclinics Research Archive for Insights in Neurophysiology (TDBRAIN) database. This study included 129 MDD patients who had undergone rTMS treatment and 45 healthy controls (HC). Patients received rTMS treatment over the left dorsolateral prefrontal cortex. Results demonstrated significant differences in connectivity patterns between HC and MDD patients within theta and alpha frequency bands. Significant pre-treatment differences in connectivity were also observed between rTMS responders and non-responders in the delta band. The CNN demonstrated reasonable performance in predicting treatment response. Across 50 iterations of cross-validation (using a 90% training and 10% hold-out split), the model achieved an average accuracy of 78%. The model also performed reasonably well on internal hold-out datasets, which were never exposed to the model, achieving an accuracy of 69%. These findings demonstrate the potential of incorporating rsEEG, in conjunction with machine learning, as an objective biomarker into clinical decision-making for MDD.

Name: Rachel Puralewski, PhD
University: University of Wisconsin-Madison
Department: Psychiatry
Program or Lab: Kalin Lab
Mentor or PI: Dr. Ned Kalin

Poster Title: “Divergent developmental trajectories of regional brain metabolism across the first year of life in rhesus monkeys”

Nonhuman primates are important translational models for understanding the development of anxiety-related brain function. Threat-related neural responses are trait-like, emerge early in life, and predict later psychopathology. However, little is known about how brain metabolism in response to threat changes across early development. This longitudinal study investigated threat-related brain metabolism across the first year of life in 35 rhesus monkeys (Macaca mulatta; 24F/11M). At five ages (1.5, 6, 12, 24, 52 weeks), subjects were injected with ¹⁸fluorodeoxyglucose and exposed to 30 minutes of the No Eye Contact (NEC) condition of the Human Intruder Paradigm while anxiety-related behaviors were scored. Post-NEC, subjects had blood drawn for cortisol assays, and Positron Emission Tomography was used to assess brain metabolism during threat exposure. MRI scans were collected for anatomical references. Voxel-wise linear mixed effects models examined age-related changes and associations with Anxious Temperament (AT), derived from NEC-related freezing, cooing, and cortisol. Results revealed dynamic, region-specific changes in NEC-related metabolism across development (p<2.2×10⁻⁸). Cortical regions (prefrontal, temporal, cingulate) showed age-related increases, while subcortical regions (amygdala, hippocampus, thalamus, brainstem, cerebellum) showed decreases. NEC-related metabolism in the bed nucleus of the stria terminalis (BST) was positively associated with AT across ages (p<0.005). Age- and AT-associated changes in visual cortices varied by region. These findings highlight a developmental shift in threat-processing, suggesting increasing cortical activity and decreasing subcortical activity with age. This may reflect the maturation of regulatory mechanisms underlying adaptive anxiety responses, though additional work is needed to disentangle threat-specific changes from general brain maturation.

Name: Colleen Rooney, BA
University: Marquette University
Department: Psychology
Program or Lab: Age, Imaging, and Memory
Mentor or PI: Dr. Kristy Nielson

Poster Title: “Alexithymia and Source Localized Activation During Go/No-Go Inhibitory”

Alexithymia is a personality characteristic determined by three facets: difficulty identifying feelings (DIF), difficulty describing feelings (DDF), and externally oriented thinking (EOT), via the Toronto Alexithymia Scale-20 (TAS-20). High alexithymia is associated with poor emotional awareness (EA) and impaired executive functioning (EF), including inhibitory control. This is especially true in older adults, who tend to have reduced EF and elevated alexithymia. Elders also frequently exhibit greater neural activity during cognitive processes to compensate for neurodegeneration. Yet, the neural basis of these cognitive correlates of alexithymia, particularly in older age, are largely unknown. The frontal lobes, specifically the inferior frontal gyri (IFG), are crucial for response inhibition. Thus, we examined alexithymia and IFG activity during a ‘no-go’ inhibitory control task using electroencephalography (EEG) with source localization. We hypothesized greater bilateral IFG activation during no-go trials in those with higher DIF. We also hypothesized greater bilateral no-go IFG activation with lower EA, as measured by the Levels of Emotional Awareness Scale (LEAS) scale. Using Pearson’s correlations, we found a significant positive correlation between activation in the left-IFG and DIF scores. As predicted, those with greater DIF had greater left-IFG activation during no-go inhibition trials. However, there was no significant correlation between IFG activation and LEAS scores. Our findings suggest that DIF contributes to compensatory activation during inhibition, but this is not synonymous with EA. Thus, in older adults, high DIF may exacerbate the effects of age-related neurodegeneration, thereby contributing to age-related cognitive decline.

Name: Laura Schwager, BS
University: University of Iowa
Department: Health and Human Physiology
Program or Lab: Integrative Laboratory of Applied Physiology and Lifestyle Medicine
Mentor or PI: Dr. Nathaniel Jenkins

Poster Title: “Cognitive Reappraisal may be a Modifiable Target to Improve Vascular Function in Young Adults with Adverse Childhood Experiences: A Cross-Sectional, Pilot Study”

Introduction. Individuals with adverse childhood experiences (ACEs) are at increased risk for cardiovascular diseases (CVD), the leading cause of premature death in the United States. Our team has observed reduced vascular endothelial function (VEF), a subclinical pathophysiological mechanism contributing to CVD, among individuals with high ACE exposure. Here, we explored the association between cognitive reappraisal, a key component of emotional regulation, and VEF in individuals with and without ACE exposure.

Methods. Twenty-four healthy young adults (16F/8M; age=23±3 y) with either 0 ACEs (no-ACE, n=12) or ≥4 ACEs (high-ACE, n=12) were assessed. Cognitive reappraisal was measured with the Emotional Regulation Questionnaire, and VEF was measured using the brachial artery flow-mediated dilation technique. Group differences in VEF and cognitive reappraisal were examined using independent samples t-tests and Hedge’s g effect sizes. Pearson’s correlations were used to examine relations between cognitive reappraisal and VEF in the whole sample and within groups. Results. In high-ACE, VEF was lower (–3.2±1.1%; p=0.007; g=1.1), and cognitive reappraisal was moderately, but not significantly, lower (–5.1±2.8 a.u.; p=0.09; g=0.67). Cognitive reappraisal was positively associated with VEF in the whole (r=0.59, p=0.001) and high-ACE (r=0.53, p=0.0395) samples, and was not significantly associated in no-ACE (r=0.49, p=0.052). Conclusion. Young adults with high ACE exposure have lower VEF and tend to have lower cognitive reappraisal. Critically, a higher capacity to reframe emotional experiences is associated with greater vascular function independent of ACE exposure. Future studies should examine whether cognitive-behavioral therapy, which fosters this skill, can improve VEF among high-ACE individuals.

Name: Nicole Stigler, BS
University: University of Wisconsin-Madison
Department: School of Pharmacy
Program or Lab: Wenthur Lab
Mentor or PI: Dr. Cody J. Wenthur

Poster Title: “Differentiating the Role of (2R,6R)-Hydroxynorketamine in Ketamine’s Rewarding and Fast-Acting Antidepressant Effects”

Ketamine, an N-methyl-D-aspartate receptor antagonist, has shown effectiveness in rapidly reducing symptoms of major depressive disorder relative to other approved therapeutics, but treatment is limited by its potentially addictive qualities. Due to different neural targets, ketamine metabolite (2R,6R)-hydroxynorketamine (2R,6R-HNK) has demonstrated antidepressant effects on rodent behavioral despair assays with less potential for abuse. We implemented the DISSECTIV method, in which we generated vaccines against 2R,6R-HNK to block the molecule from entering the central nervous system. To test the role of 2R,6R-HNK on ketamine’s rewarding effects, we performed a self-administration assay using male Sprague Dawley rats (n=6). Rats were trained to self-administer ketamine under an FR1 schedule by using a behavioral chamber that contained two levers, an active and inactive lever. Upon an active lever press, a 1mg/kg/infusion dose of ketamine was administered alongside the shine of a cue light, both lasting 4 seconds. Inactive lever presses did not provide drug infusions nor visual cues. We observed an interaction between time and active lever presses per hour with significant differences between day 1 and day 10-15 (p = 0.0215-<0.0001). After vaccination with a 2R,6R-HNK-CRM bioconjugate, rats decreased active lever pressing behavior (p = 0.0049). Results are likely due to cross-reactivity of the vaccine with ketamine and 2R,6R-HNK. To address this, we are currently focused on developing monoclonal antibodies that exhibit greater selectivity for 2R,6R-HNK.

Name: Nick Stowe
University: University of Wisconsin-Madison
Department: Psychiatry
Program or Lab: Neuroscience Training Program
Mentor or PI: Dr. Ned Kalin

Poster Title: “Single-Nucleus RNA Sequencing Exploration of Adolescent Rhesus Macaques in Relation to Anxious Temperament”

Anxiety disorders are among the most prevalent psychiatric disorders, with symptoms often beginning early in life, and the societal impact and severity of these disorders has been increasing. Therefore, there is a compelling need to develop novel treatments. To establish treatments, it is critical to identify the molecular substrates underlying these disorders. Nonhuman primates (NHP) provide an important translational bridge for exploring human psychopathology due to similarities to humans in brain morphology, social structure and behavior,2 and DNA and amino acid sequence. In collaboration with Dr. Elisabeth Binder’s laboratory at the Max Planck Institute in Germany, we have started to identify cell type-specific gene expression patterns in the amygdala and other components of the anxiety circuit towards understanding the cells and genes within cells that are related to the phenotype that confers risk to develop stress-related psychopathology, termed anxious temperament (AT). From a cohort of 72 preadolescent rhesus macaques, phenotyped for anxious temperament, brain function, and structure with multimodal imaging, we sampled tissue from the ventromedial region of the basal nucleus of the amygdalafor single nuclear RNA sequencing (snRNAseq) and bulk RNA sequencing (RNAseq). We describe the preliminary snRNAseq results, including quality control metrics and a characterization of the various cell types that comprise the cell types based on known marker genes revealed large proportions of excitatory and inhibitory neurons, and glia cells, including oligodendrocytes, microglia, astrocytes, and oligodendrocyte progenitor cells. Future work will aim to identify gene expression patterns related to various factors including age, cortisol levels, and AT.

Name: Ellie Thorstenson
University: Marquette University
Department: Psychology
Program or Lab: Translational Affective Neuroscience Lab
Mentor or PI: Dr. Jacklynn Fitzgerald

Poster Title: “Childhood Trauma and Physiological Response to Conditioned Fear and Unconditioned Threat”

Background: Childhood trauma (CT) is highly prevalent and has been linked to long-term psychological and physiological consequences, specifically hypo-responsivity to fear-conditioned stimuli (CS+). Yet, there are limited studies testing responses to threatening unconditioned stimuli (US) in this population, or examining whether hypo-responsivity is driven by accelerated habituation. We examined the relationship between CT and changes in psychophysiological response to CS+ and US and investigated how these responses changed over trials (e.g., habituation).

Methods: Participants (N = 129) completed the Fear, Reward, and Neutral Discrimination task; geometric shapes were associated with fear (aversive noise), reward (monetary incentive), or safety (no outcome); 8 trials of each cue. Skin conductance responses (SCR) provided a measure of physiological arousal. The Childhood Trauma Questionnaire (CTQ) was used to assess severity of CT. A linear mixed-effects model tested the association between CTQ and SCR amplitudes in response to the CS+ and US; trial-by-CTQ interactions were tested.

Results: No significant main effects of trial, CTQ, or trial-by-CTQ interactions were observed for the CS+ (p’s > 0.05). With respect to the fear US, results demonstrated a significant main effect of CTQ, such that higher CTQ severity was associated with increased SCR (p=0.009). This was qualified by a significant CTQ – by – trial interaction (p = 0.019); individuals with greater CTQ severity (p<0.001) exhibited a heightened initial response followed by rapid decline over repeated trials.

Conclusions
Findings suggest that individuals with greater CT exhibit a distinct physiological response to known threat characterized by heightened initial arousal followed by quicker habituation.

Name: Aasrita Tulluri
University: Loyola University Chicago
Department: Neuroscience
Program or Lab: Memory & Neuromodulatory Mechanisims Lab (MNEME LAB)
Mentor or PI: Dr. Stephanie L. Grella

Poster Title: “Memory-Updating Impairments in Stress-Related Memory Disorders: Differences in the Vulnerability to Post-Traumatic Stress Disorder”

Post Traumatic Stress Disorder (PTSD) is a psychiatric condition that can develop after experiencing a traumatic event. It is twice as prevalent in females as it is in males. A hallmark symptom of PTSD is fear generalization, where individuals transfer fear responses from a specific cue or context to unrelated stimuli or contexts. We hypothesize that this arises from impaired memory-updating processes, where a failure to remap trauma-related memory traces in the presence of new information, and the persistent recall of these memories in non-trauma-related contexts occurs. To examine these remapping deficits at the engram level, we studied male and female C57BLS/6 mice using a viral-based neuronal tagging strategy (i.e., Tet-tag) combined with immunohistochemistry and fluorescent confocal microscopy to examine the stability and flexibility of fear-related memory traces in the dorsal dentate gyrus of the hippocampus. Additionally, we tested whether fear generalization or remapping deficits could be predicted using acoustic startle reflex (ASR) as a pre-screen, where mice were parsed into susceptible and resilient populations. Contrary to our hypothesis, males exhibited higher startle reactivity, while females demonstrated a more adaptive fear response, reaching peak freezing arlier in a manner predictive of shock intensity. All mice generalized fear, and pre-exposure to a safe context reinforced this effect. Generalization corresponded with overlapping neural activity in safe and fear contexts, supporting the role of impaired memory-updating in PTSD. Finally, females showed a significant positive correlation between ASR and freezing in the safe context, suggesting ASR may predict PTSD susceptibility in humans.

Name: Kenneth Wang, BA – Travel Award Winner
University: The University of Chicago
Department: Biological Sciences Department
Program or Lab: Pritzker School of Medicine
Mentor or PI: Royce Lee, MD

Poster Title: “Electrophysiological Measures of Error Processing Following Low-Dose LSD Administration”

Classic psychedelics have demonstrated promise in elucidating neuropharmacological mechanisms and in treating psychiatric disorders such as depression, which may involve overactive error processing. Administration of low doses of psychedelics reportedly improves cognition and mood. However, the effects of psychedelics on error processing, in particular the error-related negativity (ERN), correct-related negativity (CRN), and error-related positivity (Pe), have not been examined. The present study investigated how administration of low doses of LSD modulates electrophysiological correlates of error processing. We conducted a within-subject, double-blind study of 18 healthy adults, using electroencephalogram to measure neural responses to error during the electrophysiological monetary incentive delay (eMID) task. Participants completed the task after drug administration of, in randomized order, placebo, 13 µg LSD (LSD-13), or 26 µg LSD (LSD-26). The ERN/CRN and Pe were measured during response processing. Compared to placebo, LSD-13 and LSD-26 attenuated Pe difference wave amplitude but had no effect on ERN/CRN. Pe amplitude was greater for the Hit (vs. Miss) outcome, while ERN/CRN amplitudes were similar across outcomes. Thus, both doses of LSD reduced the ERP component associated with conscious error processing (Pe) without affecting those reflecting automatic error detection (ERN/CRN). These results are the first to demonstrate that low-dose LSD may decrease neural correlates of error processing, with implications for treatment of psychiatric disorders. This is the first study to utilize the eMID to examine error-related brain activity, which may explain the unusual similarity of ERN/CRN amplitude across Hit and Miss conditions, and the unexpected direction of Pe amplitude difference.

Name: Kylee West, MS – Travel Award Winner
University: University of Iowa
Department: Department of Health and Human Physiology
Program or Lab: Integrative Laboratory of Applied Physiology & Lifestyle Medicine
Mentor or PI: Dr. Nathaniel Jenkins

Poster Title: “Psychological Resilience Modulates the Effect of Adverse Childhood Experiences on Endothelial Function and Mitochondrial Reactive Oxygen Species in Young Adults”

Adverse childhood experiences (ACEs) are severe psychosocial stressors during childhood that promote impaired vascular endothelial function (VEF) and are associated with reduced psychological resilience. Chronic psychosocial stress induces metabolic and neurohumoral mediators that functionally alter mitochondria, which could promote generation of mitochondrial reactive oxygen species (mtROS) that impair VEF. Purpose: To examine the role of psychological resilience on VEF and mtROS in young adults with versus without prior ACE exposure. Methods: Apparently healthy, young adults (age=24±5 y; BMI=26±5 kg/m2) with ≥3 ACEs (ACE+) and without ACEs (ACE-; n=11) completed the Connor-Davidson Resilience Scale. ACE+ individuals were grouped into high (ACE+HR; n=6) and low (ACE+LR; n=6) resilience groups using median split. In vivo VEF was assessed using the flow mediated dilation technique. In ex vivo experiments, human aortic endothelial cells were cultured with 10% participant serum, stained with CellROX, and imaged to measure mtROS. CD-RISC scores, VEF, and mtROS were compared among groups using one-way ANOVAs with post-hoc comparisons. Results: Compared to ACE–, resilience was lower in ACE+LR (mean±SE difference = -17±6 au; p=0.03) but wasn’t different in ACE+HR (-2±6; p=0.93). Compared to ACE–, VEF (-4.9±1%; p=0.0099) and mtROS (-191±60 au; p=0.012) were lower in ACE+LR, whereas VEF (-1.9±1%; p=0.44) and mtROS (-71±60 au; p=0.47) were not different in ACE+HR. Conclusions: These data provide initial evidence supporting impaired VEF and paradoxical reductions in mtROS in individuals with prior ACE exposure and low psychological resilience. However, high psychological resilience may buffer the physiological effects of ACE exposure.

Name: Louis Zielinski, BA
University: Marquette University
Department: Department of Psychology
Program or Lab: Translational Affective Neuroscience Lab
Mentor or PI: Dr. Jacklynn Fitzgerald

Poster Title: “Sociodemographic Correlates of Learned Fear: Preliminary Results from a Conditional Fear, Reward, and Neutral Discrimination Task”

Background: Contingency awareness — recognizing that a conditioned stimulus (CS) predicts threat — is critical for shaping conditioned fear responses. However, only limited research has examined sociodemographic differences in awareness. Such information may be critical to understanding factors associated with successful fear learning.

Methods: Participants (N = 93) completed a Fear, Reward, and Neutral Discrimination task; geometric shapes (CS) were associated with fear (aversive noise unconditioned stimulus [US]), reward (monetary US), or neutral (no outcome). Skin conductance responses (SCR) provided a measure of physiological response to the CS; self-reported likeability provided a measure of contingency awareness such that fear learners were those who rated the fear cue aversively. Chi-square and t-tests were used to test sociodemographic differences fear learning status. Moderated linear regressions tested whether fear learning status moderated the relationship between sociodemographic predictors and SCR to conditioned fear cues.

Results: Fear learner status was related to ethnoracial minoritized identity (p = 0.037). Ethnoracial minoritized individuals comprised 29% of the sample but were disproportionately represented as non-fear learners (50% of non-fear learners). Fear learning status was unrelated to gender (p = 0.451) and age (p = 0.945). Being a non-fear learner was associated with less SCR to the conditioned fear cue (p = 0.023), but fear learning status did not moderate the relationship between race and SCR to conditioned fear cues (p = .16).

Conclusions: Results support limited prior work that also found ethnoracial minoritized individuals do not form a learned fear response as readily as their white non-Hispanic peers.