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

Abstract

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 abnormalities of the NVS, mostly related to heightened threat processing, yet more recent work also suggests deficits in PVS functionality in PTSD, mainly in the form of reduced reward functioning. The current study examined the hypothesis that individuals' ability to recover from a potentially traumatic event relies on promoting reward-seeking behaviors (i.e., PVS) alongside diminished threat assessment (i.e., NVS), during the first year following trauma, a critical period for PTSD development or recovery. To do so, we longitudinally tracked behavioral and neural responses among 171 adult civilians with early post-traumatic stress symptoms at 1-, 6- and 14-months following trauma exposure (TP1, TP2, and TP3, respectively). At each time-point, participants played a naturalistic game encompassing dynamic provocation of risk-taking, punishments and rewards in an fMRI setting. Results showed that greater amygdala activation and functional connectivity with the lateral orbitofrontal cortex (lOFC) in response to punishments (i.e., hyperactive NVS) at TP1 were associated with more severe post-traumatic stress symptoms at both TP1 and TP3 (but not at TP2), and specifically with more hyperarousal and intrusion symptoms. On the other hand, decreased ventral striatum (VS) activity and functional connectivity with the ventromedial prefrontal cortex (vmPFC) in response to rewards (i.e., hypoactive PVS) at TP1 were associated with more severe post-traumatic stress symptoms at TP3 (but not at TP1 or TP2), and specifically with more avoidance symptoms. Explainable machine learning revealed the primacy of the PVS over the NVS at TP1 in predicting PTSD symptom development from TP1 to TP3. Behaviorally, fewer risky choices in the task were associated with more severe symptoms at TP1, but not at TP2 or TP3. Finally, an integrative exploratory analysis revealed that reduction in risky choices in the task (from TP1 to TP2) moderated the relation between NVS hyperactivity at TP1 and symptom severity at TP3. Altogether, our results support the idea that trauma exposure might alter both NVS and PVS processing. While NVS presents early heightened saliency processing in the immediate aftermath of trauma, early PVS only affects the long-term outcome of traumatic stress. These insights inform possible mechanism-driven therapeutic strategies for PTSD, addressing not only negative but also positive valence processing.

Angiotensin Antagonist Inhibits Preferential Negative Memory Encoding via Decreasing Hippocampus Activation and Its Coupling With the Amygdala

“…Neuroimaging studies in PTSD commonly linked symptoms in the domains of hyperarousal and emotional memory to dysregulations in the amygdala-hippocampal complex. Some evidence suggests that hyperarousal and emotional-reactivity symptoms in PTSD are strongly mediated by amygdalar dysregulations (61,62) while memory dysfunctions are associated with hippocampal dysregulations (63). However, during threat learning and encoding of negative emotional materials both regions have been found to be dysregulated in PTSD (26,52,64,65).…”