Neuromodulation trials for the treatment of posttraumatic stress disorder (PTSD) have yielded mixed results, and the optimal neuroanatomical target remains unclear. Here we analyzed three datasets to study brain circuitry causally linked to PTSD in military veterans. In veterans with penetrating traumatic brain injury, lesion locations that reduced probability of PTSD were preferentially connected to a circuit including the medial prefrontal cortex, amygdala and anterolateral temporal lobe. In veterans without lesions, PTSD was specifically associated with increased connectivity within this circuit. Reduced functional connectivity within this circuit after transcranial magnetic stimulation correlated with symptom reduction, even though the circuit was not directly targeted. This lesion-based 'PTSD circuit' may serve as a target for clinical trials of neuromodulation in veterans with PTSD.
© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.