Transcranial magnetic stimulation of the human motor cortex influences the neuronal activity of subthalamic nucleus.

The critical role of the subthalamic nucleus (STN) in the control of movement and parkinsonian symptoms is well established. Research in animals suggests that the cerebral cortex plays an important role in regulating the activity of the STN but this control is not known in humans. The most extensive cortical innervation of the STN originates from motor areas. Here, we used transcranial magnetic stimulation (TMS) during intraoperative single-unit recordings from STN, in six patients with Parkinson's disease (PD) undergoing implantation of deep brain stimulators, to determine whether TMS of the motor cortex (MC) modulates the activity of STN and to investigate in vivo the functional organization of the corticosubthalamic circuit in the human brain. Single-pulse TMS of the MC induced an excitation in 74.9% of neurons investigated. This activation was followed by a long-lasting inhibition of the STN neuronal activity that did not correlate with PD severity. Responsive neurons to TMS of the hand area of motor cortex were located mainly in the lateral and dorsal region of the subthalamus while unresponsive cells had a prevalently medial distribution. This is the first report of TMS-induced modulation of STN neuronal activity in humans. These findings open up new avenues for in vivo studies of corticosubthalamic interactions in human brain and PD.