Characterizing the behavioral and neural mechanisms of inhibitory control dysfunction in PTSD.

Va Boston Health Care System, Boston MA

Investigators

Abstract

Post-traumatic stress disorder (PTSD) is prevalent amongst post-9/11 Veterans and is associated with poor long-term outcomes. Limitations of current PTSD models (e.g., fear learning model) and their associated treatments (e.g., prolonged exposure) necessitate developing a richer mechanistic understanding of PTSD. One cognitive mechanism shown to be important to the development and maintenance of PTSD is inhibitory control, the ability to resist reflexive, prepotent actions (response inhibition), as well as external (distractor suppression) and internal distractions (memory suppression) that interfere with goal-directed behavior. Inhibitory control impairments, and dysfunction in the underlying neural circuits, have been linked to poor long-term outcomes and reduced treatment efficacy following traumatic stress. The goal of the current proposal is to better characterize the nature and specificity of inhibitory control deficits in PTSD as well as their neural basis. The first aim of this proposal is to examine whether PTSD-related inhibitory control dysfunction is distinct from other information processing deficits, including general executive dysfunction or reduced fear extinction. Additionally, inhibitory control can be exerted over emotional, i.e., “hot” information (threatening thoughts, memories, or environmental stimuli), or rather over emotionally neutral “cool” information and a goal is to determine whether these reflect independent or overlapping mechanisms. The second aim of this proposal is to better understand the neural underpinnings of inhibitory control deficits using task-based fMRI during hot and cool inhibitory control tasks. We propose to use sophisticated analytic approaches (e.g., representational similarity) and focus on frontal-parietal cognitive control and salience/limbic circuits, which have been consistently implicated in PTSD in our and others' previous work. A final exploratory aim is to use ecological momentary assessments (EMA) throughout daily life to examine whether momentary PTSD symptoms and momentary hot or cool inhibitory control predict or precede one another. This will help better understand the causal dynamics between PTSD symptoms and hot and cool inhibitory control. Together, these aims will answer core mechanistic questions about PTSD and will provide guidance for implementing existing treatments as well as targets for new treatments.