Post-traumatic stress disorder (PTSD) is a highly prevalent and debilitating disorder. Despite
efforts to characterize PTSD pathophysiology, no biomarkers have been established to aid in
diagnosis, treatment development, and prediction of treatment response. New evidence poses
that PTSD is mediated by dysfunctional discrimination of context/cues in both threat and reward
processing, involving the hippocampus, nucleus accumbens, amygdala, and prefrontal cortex.
Still, the contextual component, or the formation of mental boundaries of the environment (mental
representations) that delineate threat/safety and reward/non-reward cues/signals within a single
environment, and the neural circuits of these processes are yet to be studied in PTSD where
contextual processing is often impaired.
I have developed two virtual reality (VR) tasks to examine threat and reward discrimination, to
assess the underlying mechanisms of learning valence discrimination within an environment using
location-specific information. Briefly, the task used for this study consists of neutral (CS-) and
threat or reward (CS+) areas, within a single environment, and participants must use spatial
information to learn to discriminate between both areas. The task is designed to reveal brain
regions involved in learning locations predictive of environmental reward.
This research proposal aims to investigate brain activity differences between patients with PTSD
(n=80), trauma-exposed controls without PTSD (TE; n=80), and healthy controls (HC; n=80).
Functional magnetic resonance imaging (fMRI) during the VR paradigm will be used to clarify the
neural mechanisms underlying threat and reward learning and discrimination processing across
groups. Multiple levels of assessment will include multimodal MRI, coupled with peripheral
measures of arousal (e.g., Skin Conductance Response), eye-tracking, and subjective ratings of
learning.
This is a first step to clarify the process of threat and reward discrimination learning within an
environment, particularly to elucidate if the neural signatures are specific to valence signaling or
to PTSD psychopathology in general. In the long term, this research will shed light on the specific
role of brain areas needed for discrimination learning within an environment which will advance
the development of effective diagnostics and treatments for PTSD and other psychopathologies.