Target variability and stability for precision fMRI-guided TMS of the amygdala circuitry in a clinical trial for PTSD

Target definition in functional magnetic resonance imaging (fMRI)-guided transcranial magnetic stimulation (TMS) has unresolved methodological, neurobiological, and clinical questions. In a randomized clinical trial for post-traumatic stress disorder (PTSD; n=50), topographic variability and stability of patient-specific right dorsolateral prefrontal cortex (rDLPFC) targets with the strongest functional connectivity to the right amygdala were analyzed. There was significant target variability between participants and between targeting methods, but each individual target was stable after engaging the amygdala circuitry with behavioral threat-related tasks. Target topography did not change after 20 sessions of sham TMS. However, after active TMS (1Hz, 36,000 pulses) target topography was significantly different. A larger change in the medial-anterior direction correlated with greater PTSD symptom improvement, suggesting neuroplastic adaptations in the targeted networks and a possible treatment-dependent shift towards more medial prefrontal control over amygdala regulation. These findings are important for fMRI-guided precision neuromodulation therapy development, particularly for the amygdala circuitry.