rCBF changes elicited by rTMS over DLPFC in humans

Recently, repetitive TMS (rTMS) has been used as a potential treatment for depression. Several studies have shown antidepressant effects of rapid rTMS over the left dorsolateral prefrontal cortex (DLPFC), whereas some studies suggested the effectiveness of slow rTMS over the right DLPFC. Despite the growing interest in therapeutic application of rTMS, the precise mechanisms for rTMS over the DLPFC are still unknown. To clarify these mechanisms for slow rTMS over the right prefrontal cortex, we measured regional cerebral blood flow (rCBF) during real or sham rTMS and after stimulation using repeated l5O-labeled H2O PET scanning in seven healthy subjects. We found that slow rTMS over the right DLPFC could produce significant rCBF increase in the ipsilateral anterior cingulate cortex (ACC) during stimulation as compared with sham stimulation. The lasting activation occurred in the ipsilateral medial prefrontal cortex, contralateral ventrolateral PFC, and the contralateral ventral striatum. These data indicate that slow rTMS is able to produce rCBF changes in the paralimbic system and frontal cortex. We conclude that the lasting effect on the ventral striatum should reflect modulatory effects of rTMS over the DLPFC on the meso-limbic dopaminergic system that must play critical roles in antidepressant effects.