Semantic encoding of trauma memories in the hippocampus among individuals with PTSD

The recall of traumatic memories is central to clinical and neurobiological models of PTSD, yet neurocircuitry mechanisms underlying traumatic memory recall remain elusive. Recent advances in natural language processing and large language models enable complex semantic quantification of autobiographical memories. Here, we leveraged these analytic approaches to define the neurocircuitry encoding the semantic content of traumatic autobiographical narratives among individuals with PTSD. 79 women with PTSD related to interpersonal violence listened to traumatic and neutral autobiographical narratives during fMRI. Sentence-level brain activity and semantic embeddings were quantified for each script and participant. Neurocircuitry encoding semantic content of the narratives was defined through cross-validation across participants. A priori regions of interest included the hippocampus, superior temporal gyrus (STG), and posterior cingulate cortex (PCC). Our approach detected significant hippocampal sensitivity for semantic content of both trauma and neutral narratives; however, spatial encoding patterns of semantic content within the hippocampus differed between trauma and neutral narratives. Specifically, spatial encoding patterns in CA1 and dentate gyrus differentiated narrative type. Regardless of narrative type, PTSD symptom severity was positively associated with semantic encoding across the hippocampus and its subfields, except for the subiculum. For trauma narratives, semantic sensitivity was greater within the left STG and decreased in the PCC and broader default mode network. Encoding in neither region tracked with PTSD symptom severity. These results reveal a hippocampal role in mediating recall of specific semantic content for traumatic and neutral autobiographical narratives and suggest hippocampal sensitivity to autobiographical semantic content underlies greater PTSD symptom severity. Clinical trial registration information: Improving Therapeutic Learning for PTSD, Study Details | NCT04558112 | Improving Therapeutic Learning for PTSD | ClinicalTrials.gov, NCT04558112.