Multivariate Brain Representations of the Traumatic Memory in PTSD: Changes Across Exposure Sessions and Impact of...

Understanding how exposure-based trauma treatment modifies neural representations of trauma memory may lead to optimized and targeted interventions for posttraumatic stress disorder. Although exposure therapies reliably reduce symptoms, the neural mechanisms through which repeated trauma memory retrieval and processing reshape representational structure, and whether such changes can be bolstered through pharmacological agents shown to enhance extinction learning, remain poorly understood.

Women with PTSD related to interpersonal violence (N=80) completed two days of repeated exposure to an individualized trauma and neutral narrative during fMRI. Immediately after Day 1 exposures, participants were randomized to placebo (n=37) or 100mg Levodopa (L-DOPA; n=43), targeting dopaminergic enhancement of memory consolidation. Support vector machines characterized multivariate neural representations of distinct aversive cognitive states: painful stimulus delivery, trauma memory recall, self-reported anxiety during memory recall. To test generalization of representational changes across contexts, the Day 2 narratives were presented in either the same or different sensory context compared to Day 1.

Across participants, medial prefrontal cortex (mPFC) network representations for each aversive state reduced from Day 1 to Day 2. There was no impact of L-DOPA on self-reported anxiety to the trauma memory or on neural representations of trauma memory recall or painful stimulus delivery. L-DOPA was associated with attenuated anxiety representations in the mPFC under a changed context, potentially consistent with enhanced generalization of representational updating.

These findings highlight that trauma memory representations in the mPFC are malleable with repeated exposure. The augmenting effect of L-DOPA was mostly null, except for decreased mPFC representations for anxiety in a changed context.