Cortical-subcortical structural connections support transcranial magnetic stimulation engagement of the amygdala

The amygdala processes valenced stimuli, influences emotion, and exhibits aberrant activity across anxiety disorders, depression, and PTSD. Interventions modulating amygdala activity hold promise as transdiagnostic psychiatric treatments. In 45 healthy participants, we investigated whether transcranial magnetic stimulation (TMS) elicits indirect changes in amygdala activity when applied to ventrolateral prefrontal cortex (vIPFC), a region important for emotion regulation. Harnessing in-scanner interleaved TMS/functional MRI (fMRI), we reveal that vIPFC neuro-stimulation evoked acute and focal modulations of amygdala fMRI BOLD signal. Larger TMS-evoked changes in the amygdala were associated with higher fiber density in a vIPFC-amygdala white matter pathway when stimulating vIPFC but not an anatomical control, suggesting this pathway facilitated stimulation-induced communication between cortex and subcortex. This work provides evidence of amygdala engagement by TMS, highlighting stimulation of vIPFC-amygdala circuits as a candidate treatment for transdiagnostic psychopathology. More broadly, it indicates that targeting cortical-subcortical structural connections may enhance the impact of TMS on subcortical neural activity and, by extension, subcortex-subserved behaviors.

Automated summary

The amygdala processes valenced stimuli and influences emotion. This study found that transcranial magnetic stimulation (TMS) can indirectly change amygdala activity when applied to ventrolateral prefrontal cortex (vIPFC). TMS stimulation of vIPFC was associated with acute and focal modulations of amygdala activity. Higher fiber density in the vIPFC-amygdala white matter pathway was also related to larger TMS-induced changes in the amygdala, indicating the importance of this pathway for cortical-subcortical communication.