BOLD MRI responses to repetitive TMS over human dorsal premotor cortex

Functional magnetic resonance imaging (fMRI) studies in humans have hitherto failed to demonstrate activity changes in the direct vicinity of transcranial magnetic stimulation (TMS) that cannot be attributed to re-afferent somatosensory feedback or a spread of excitation. In order to investigate the underlying activity changes at the site of stimulation as well as in remote connected regions, we applied short trains of high-intensity (110% of resting motor threshold) and low-intensity (90% of active motor threshold) repetitive TMS (rTMS; 3 Hz, 10 s duration) over the presumed location of the left dorsal premotor cortex (PMd) during fMRI. Signal increases in the direct vicinity of the stimulated PMd were observed during rTMS at 110% RMT. However, positive BOLD MRI responses were observed with rTMS at both 90% and 110% RMT in connected brain regions such as right PMd, bilateral PMv, supplementary motor area, somatosensory cortex, cingulate motor area, left posterior temporal lobe, cerebellum, and caudate nucleus. Responses were generally smaller during low-intensity rTMS. The results indicate that short trains of TMS can modify local hemodynamics in the absence of overt motor responses. In addition, premotor rTMS cannot only effectively stimulate cortico-cortical but also cortico-subcortical connections even at low stimulation intensities.