Fear learning–induced brain dynamics predict individual extinction memory expression following transcranial magnetic stimulation

Fear learning and extinction unfold as time-dependent processes. Herein, we examined whether fear learning dynamically reorganizes brain activity and whether such reorganization predicts subsequent extinction-memory expression under transcranial magnetic stimulation (TMS)-modulated extinction. Eighty-seven healthy adults completed a three-day Pavlovian threat-learning protocol with resting-state fMRI, TMS-modulated extinction, and extinction-memory fMRI.

Using coactivation pattern analysis with a hidden Markov model, we identified a fear-learning–induced brain state characterized by increased engagement and transition uncertainty after conditioning. Functional connectivity reorganization within this state predicted individual differences in extinction recall- and renewal-related brain activation under TMS-modulated extinction (cross-validated; recall r = 0.47, p = 0.001; renewal r = 0.37, p = 0.01; permutation-tested), but not natural extinction. In separate brain–behavior correlation analyses, the neural variates identified in the TMS-modulated extinction were associated with behavioral expression.

These findings demonstrate that fear learning reshapes brain-state dynamics and identifies a candidate biomarker of neuromodulation-linked extinction-memory expression. We thank Joe Borrelli for his assistance with data management and information technology support throughout this study. M.R.M was supported by the National Institute of Mental Health (R01MH123736 and R01MH125198).

Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA Kai Zhang, Lihan Cui, B.Isabel Moallem, Hani Meelad, Zakiya Atiyah, Muhammad Badarnee, Isabella Mason, Zhenfu Wen & Mohammed R. Milad Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA Ralph H. Johnson VA Medical Center, Charleston, SC, USA Correspondence to Zhenfu Wen or Mohammed R.

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