Impact of Posttraumatic Stress Disorder on the Behavioral and Multivariate Neural Correlates of Contextual Fear Learning

Biol Psychiatry Cogn Neurosci Neuroimaging. 2026 Apr 29:S2451-9022(26)00125-4. doi: 10.1016/j.bpsc.2026.04.010. Online ahead of print.

ABSTRACT

BACKGROUND: Posttraumatic stress disorder (PTSD) is linked with impairments of fear learning, particularly context and safety cue discrimination. However, it remains unclear whether alterations in distinguishing threat and safety stem from trauma exposure itself or from anxiety-related pathology more generally. This study used multiple control groups to disentangle the impact of PTSD on behavioral and neural indices of fear learning.

METHODS: Four groups of participants were recruited: PTSD related to interpersonal violence (n = 21), trauma exposed- (n = 46), anxiety- (n = 19), and healthy-controls (n = 34). Participants completed a contextual fear conditioning task while undergoing fMRI. Multivariate pattern analysis was used to decode the anticipatory neural representation of the unconditioned stimulus (i.e., electric shock) when participants were presented with conditioned stimuli.

RESULTS: Behaviorally, PTSD participants showed poorer discrimination between high- and low-threat conditioned stimuli in trial-by-trial shock predictions relative to all control groups, with a convergent pattern in shock likelihood estimates. Neural shock reinstatement in the salience network discriminated between high- and low-threat stimuli to a greater extent among healthy-controls compared to the PTSD group. Shock representations in the medial prefrontal cortex and inferior frontal networks were more strongly coupled with shock likelihood estimates among healthy-controls and anxiety-controls, respectively, compared to the PTSD group.

CONCLUSIONS: PTSD is uniquely associated with poorer threat discrimination during fear learning. Neural networks that encode differential threat expectation for conditioned stimuli among healthy participants do not discriminate threat magnitude among PTSD participants.

PMID:42067061 | DOI:10.1016/j.bpsc.2026.04.010