Keynan, N. J. | Search bioRxiv

bioRxiv2021

Differential Roles of Positive and Negative Valence Systems in the Development of Post-Traumatic Stress Psychopathology

Negative and positive valence systems (NVS and PVS) pertain to processing of aversive and rewarding stimuli, respectively. Post-Traumatic Stress Disorder (PTSD) has been typically associated with hyper-responsivity of the NVS, and more recently, with deficient PVS functionality. The respective roles of these systems in early PTSD development have yet to be resolved. Here, we assessed neurobehavioral indicators of PVS and NVS longitudinally among 171 adult civilians at 1-, 6-, and 14-months following trauma exposure (TP1, TP2, and TP3). Using the Safe or Risky Domino Choice (SRDC) game during fMRI, NVS and PVS functionality (i.e., activity and connectivity) were indicated by the amygdala and ventral striatum (VS) responses to punishments and rewards, respectively. The complementary functionality of these systems was behaviorally assessed as the percentage of risky choices taken during the game. Results revealed that increased amygdala functionality at TP1 was associated with greater PTSD severity at TP1 and TP3, specifically with hyperarousal and intrusion. Decreased VS functionality at TP1 was associated with greater PTSD severity at TP3, specifically with avoidance. Explainable machine learning revealed the primacy of PVS over NVS functionality at TP1 in predicting PTSD severity at TP3. Behaviorally, fewer risky choices were associated with more severe symptoms at TP1, especially with intrusion and avoidance. Overall, these results suggest a differential and potentially complementary involvement of NVS and PVS in PTSD development following trauma. Early therapeutics for PTSD in the immediate aftermath of trauma may thus target both negative and positive valence processing.

neuroscience↗

bioRxiv2019

Multi-Domain Potential Biomarkers for Post Traumatic Stress Disorder (PTSD) Severity in Recent Trauma Survivors

Contemporary symptom-based diagnosis of Post-traumatic Stress Disorder (PTSD) largely overlooks related neurobehavioral findings and rely entirely on subjective interpersonal reporting. Previous studies associating objective biomarkers with PTSD have mostly used the disorders symptom-based diagnosis as main outcome measure, overlooking the actual clustering and richness of phenotypical features associated with PTSD. Here, we aimed to computationally derive potential neurocognitive biomarkers that could efficiently differentiate PTSD subtypes, based on an observational cohort study of recent trauma survivors. A three-staged semi-unsupervised method ("3C") was used to categorize trauma survivors based on current PTSD diagnostics, derive clusters of PTSD based on features related to symptom load, and to classify participants cluster membership using objective features. A total of 256 features were extracted from psychometrics, cognitive, structural and functional neuroimaging data, obtained from 101 adult civilians (age=34.80{+/-}11.95, 51 females) evaluated within a month of trauma exposure. Multi-domain features that best differentiated cluster membership were indicated by using importance analysis, classification trees, and ANOVA. Results revealed that entorhinal and rostral anterior cingulate cortices volumes (structural domain), in-task amygdalas functional connectivity with the insula and thalamus (functional domain), executive function and cognitive flexibility (cognitive domain) best differentiated between two clusters related to PTSD severity. Cross-validation established the results robustness and consistency within this sample. Multi-domain biomarkers revealed by the 3C analytics offer objective classifiers of post-traumatic morbidity shortly following trauma. They also map onto previously documented neurobehavioral PTSD features, supporting the future use of standardized and objective measurements to more precisely identify psychopathology subgroups shortly after trauma.

neuroscience↗