Lasting cortical activation after repetitive TMS of the motor cortex

OBJECTIVE: Cerebral [18F]fluorodeoxy-D-glucose PET ([18F]FDG-PET) was used to visualize the lasting neuronal activation after repetitive transcranial magnetic stimulation (rTMS) over the left hand area of the primary motor cortex (M1HAND). BACKGROUND: Applied over M1HAND, rTMS has been shown to produce a modulation of corticomotor excitability beyond the time of stimulation itself. METHODS: Eight right-handed subjects underwent nonquantitative [18F]FDG-PET measurements during two experimental conditions: at rest and after focal subthreshold 5-Hz rTMS over the left M1HAND. In the post-rTMS condition, [18F]FDG was injected immediately after the administration of 1,800 magnetic pulses over the left M1HAND. Relative differences in normalized regional cerebral metabolic rate of glucose (normalized rCMRglc) between conditions were determined using a voxel-by-voxel Student's t-test and volume-of-interest (VOI) analysis. Analysis was a priori restricted to the M1HAND, the supplementary motor area (SMA), and the primary auditory cortex of both hemispheres. RESULTS: A 5-Hz rTMS of the left M1HAND caused a lasting relative increase in normalized rCMRglc within the M1HAND bilaterally and the SMA. The magnitude and the topographic pattern of persisting relative rCMRglc increases within these motor cortical areas demonstrated considerable interindividual variations. CONCLUSIONS: Subthreshold 5-Hz repetitive transcranial magnetic stimulation (rTMS) over the hand area of the primary motor cortex is associated with a persisting neuronal activation in a distinct set of motor cortical areas beyond the time of stimulation. The current findings demonstrate that [18F]FDG-PET can localize and quantify regional net changes in synaptic cortical activity after rTMS and thus might elucidate the mechanisms underlying rTMS-associated therapeutic effects.