Continuous theta burst stimulation to the frontal pole durably decreases medial frontoamygdala connectivity

The frontal pole is a transdiagnostic target for affective disorders, perhaps through its connectivity with affective regions like the amygdala. Recent work shows that single-pulse or single-session transcranial magnetic stimulation (TMS) to the frontal pole (FP) modulates amygdala activity and frontoamygdala connectivity. In a secondary analysis of a double-blind, Sham-controlled clinical trial, 17 participants with alcohol use disorder (10 Real, 7 Sham; 24% Female; age 46 ± 13 years) received 10 sessions of continuous theta burst stimulation (cTBS) to the left frontal pole (FP1). Resting-state fMRI was acquired pre-treatment, post-treatment (within one week of treatment completion), and 1 month after treatment. Voxelwise mixed-effects modeling revealed that Real cTBS, compared to Sham, selectively decreased connectivity between the frontal pole and the medial amygdala. Using an ANCOVA approach to account for regression to the mean, this reduction was confirmed to be durable over the 1-month follow-up and was most pronounced in participants exhibiting the highest baseline connectivity. These results extend knowledge on amygdala modulation and set the stage for future work to access the amygdala through the frontal pole for affective disorders marked by amygdala dysregulation.