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Decoding threat neurocircuitry representations during traumatic memory recall in PTSD

Abstract

The neurocircuitry mechanisms underlying recall of traumatic memories remain unclear. This study investigated whether traumatic memory recall engages neurocircuitry representations that mirror activity patterns engaged during generalized threat stimulus processing in Post Traumatic Stress Disorder (PTSD). Multivariate pattern analysis was used to train 3 decoders. A “trauma” decoder was trained on fMRI patterns during idiographic trauma versus neutral narratives in a sample of 73 adult women with PTSD. A separate cohort of 125 adult participants completed a reward and threat learning task, from which “shock” and “reward loss” decoders were trained on neural patterns during threat or reward outcome delivery, respectively. These decoders were then cross-tested on the alternative datasets, allowing analyses of the degree to which traumatic memory recall engaged neurocircuitry representations that overlap with more general aversive stimuli. Decoders were trained and tested in four networks related to salience processing as well bilateral amygdala and hippocampal masks. The shock decoder trained in a midcingulate / posterior insula network demonstrated elevated predictions for shock during traumatic versus neutral memory recall. Similarly, the trauma decoder made elevated predictions about trauma recall during shock versus no shock delivery across multiple networks related to salience processing. There was no overlap between reward loss decoder predictions and trauma memory recall or vice versa. PTSD participants with elevated re-experiencing symptoms demonstrated the highest engagement of shock activity patterns during trauma memory recall. These results suggest that trauma memory recall engages neurocircuitry representations that overlap with threat, specifically painful, stimulus delivery.

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Fig. 1: Depiction of analytical approach.
Fig. 2: Mean decoder accuracies and feature weight map.
Fig. 3: Shock decoder and reward decoder predictions.
Fig. 4: Trauma decoder predictions.
Fig. 5: Comparison of shock decoder predictions in memory recall task for high versus low re-experiencing symptoms.

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Data availability

De-identified data have been deposited at Open Science Framework and are publicly available as of the date of publication. DOIs are listed in the key resources table. All original code has been deposited at Open Science Framework and is publicly available as of the date of publication. DOIs are listed in the key resources table. Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

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Funding

J.M.C. is supported by MH119132, MH108753, MH132784, MH132722, and AA030740. J.E.D. is supported by MH122387. ZNS is supported by MH119132, MH108753.

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Conceptualization, KRM, JED, JMC; Methodology, KRM, JED, JMC; Data Curation KRM, JMC, MJ, ZNS; Investigation, KRM, JED, ZNS, JMC; Writing – Original Draft, KRM, JMC; Writing – Reviewing & Editing, KRM, JED, ZNS, MJ, JMC; Resources JMC, JED, ZNS, Funding Acquisition, JMC, JED, ZNS, Supervision, JMC.

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Correspondence to Josh M. Cisler.

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Dr Stowe reported receiving consultant fees from the CDC during the conduct of the study and being on the advisory board of Reunion Neuroscience outside the submitted work. The other authors declare no competing interests.

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Morris, K.R., Jaeb, M., Dunsmoor, J.E. et al. Decoding threat neurocircuitry representations during traumatic memory recall in PTSD. Neuropsychopharmacol. 50, 568–575 (2025). https://doi.org/10.1038/s41386-024-02028-5

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