The emotional sequelae of combat and other trauma exposure primarily give rise to five core symptom clusters: re-experiencing, avoidance, emotional numbing/dysphoria, dysphoric arousal, and anxious arousal. This approach to characterizing trauma-related symptomatology is inherently transdiagnostic and dimensional in nature and accords with the NIMH Research Domain Criteria (RDoC) project, which seeks to classify individuals with respect to unique behavioral and neural patterns irrespective of DSM diagnosis. Although these factors constitute a sound phenotypic model of trauma-induced psychopathology, little is known about the neural circuitry that underlies these dimensions or how characteristics of trauma-related psychopathology, such as fear learning, relate to component aspects of this heterogeneous phenotype. Elucidation of links between phenotypic characteristics of trauma-induced psychopathology, based on dimensions of observable behavior and neurobiological measures, could uncover individual differences and promote personally- tailored clinical interventions. We propose to assess these associations in trauma-exposed individuals using two highly validated protocols: reversal learning and retrieval-extinction. In reversal learning, participants first undergo fear acquisition where they encounter two stimuli and learn that one of them terminates with threat, whereas the other one does not. In the subsequent reversal phase, participants learn that the formerly safe stimulus now predicts threat, and the fearful one is now safe. In the retrieval-extinction paradigm, extinction training occurs after memory reactivation, i.e., during reconsolidation, allowing the updating of the fear memory with the safety information learned in extinction, which was shown to successfully prevent old fear memories from resurfacing. These paradigms provides a unique platform to investigate the neurocircuitry and psychophysiology of fear and safety learning and memory modification, and their relation to phenotypic measures of negative valence systems implicated in threat, arousal and regulatory systems, and loss. In the proposed study, we aim to evaluate the neural, psychophysiological, and computational mechanisms that govern fear and safety learning and memory, and their association to stress related psychopathology as expressed in combat veterans presenting with a transdiagnostic and full dimensional range of associated psychiatric symptoms.

Public Health Relevance

In line with the RDoC project, the proposed study aims to characterize the neural, psychophysiological, and computational mechanisms that govern fear and safety learning, and their association with negative valence systems implicated in threat, hyperarousal, and loss symptomatology, in combat veterans presenting with a transdiagnostic and full dimensional range of stress-related symptomatology. Such analyses will provide a more refined and nuanced approach to understanding the relation between neural and behavioral markers of these negative valence systems associated with trauma exposure that is less encumbered by the prevailing diagnostic nosology.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Borja, Susan
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Icahn School of Medicine at Mount Sinai
Schools of Medicine
New York
United States
Zip Code
Hu, Jingchu; Wang, Zijie; Feng, Xiaoyi et al. (2018) Post-retrieval oxytocin facilitates next day extinction of threat memory in humans. Psychopharmacology (Berl) :
Hu, Jingchu; Wang, Wenqing; Homan, Philipp et al. (2018) Reminder duration determines threat memory modification in humans. Sci Rep 8:8848
Homan, Philipp; Lin, Qi; Murrough, James W et al. (2017) Prazosin during threat discrimination boosts memory of the safe stimulus. Learn Mem 24:597-601
Lee, Jonathan L C; Nader, Karim; Schiller, Daniela (2017) An Update on Memory Reconsolidation Updating. Trends Cogn Sci 21:531-545
Homan, Philipp; Schiller, Daniela (2016) Neuroscience: This Is Not a Spider. Curr Biol 26:R898-R900
Clem, Roger L; Schiller, Daniela (2016) New Learning and Unlearning: Strangers or Accomplices in Threat Memory Attenuation? Trends Neurosci 39:340-351
Pietrzak, Robert H; Averill, Lynnette A; Abdallah, Chadi G et al. (2015) Amygdala-hippocampal volume and the phenotypic heterogeneity of posttraumatic stress disorder: a cross-sectional study. JAMA Psychiatry 72:396-8