Causal Connectivity Maps Derived from Single-Pulse Interleaved TMS/fMRI.

Here we employed interleaved single-pulse transcranial magnetic stimulation with functional MRI (spTMS/fMRI) to generate causal activation maps targeting the left hemisphere according to two sets of personalized resting connectivity targeting approaches in over 80 participants. Voxelwise event-related fMRI BOLD maps quantified TMS-evoked brain responses to each stimulation site. Group-level maps controlled for head motion, scalp discomfort, and somatosensory effects, ensuring specificity of the intended brain responses to stimulation. Stimulation of frontal regions targeting the subgenual anterior cingulate cortex (sgACC) induced BOLD responses in the sgACC and modulated distributed cortical and subcortical regions. Similarly, ventrolateral targets led to an average negative BOLD response in the amygdala target and numerous other distributed brain regions. ROI-based analyses revealed no significant group differences (depressed vs. healthy control) in evoked responses within the sgACC or amygdala. These results validate that image-guided TMS can causally engage distributed brain regions, supporting its utility for circuit and network-based neuromodulation. The publicly available causal connectivity maps might be used to guide future research linking cortical circuit maps with fMRI and/or behavioral outcomes.