Figure 4.

Proposed model of the STN‐DBS effective network. A, Alterations of brain activity by STN‐DBS. STN‐DNS mainly modulates the striato‐thalamo‐cortical pathway, showing remote effects in the cortical regions via network modulation as well as local effects in the target and nearby subcortical regions. For the local effects, STN‐DBS may affect (i) axon terminals synapsing on neurons of the STN, (ii) the dendrites or soma of neurons in the STN, (iii) the action potential‐initiating segment in the axon hillock or proximal axon of interneurons, (iv) efferent neurons residing in the STN, and (v) axons passing through or in the vicinity of the STN (gray arrow). For the remote effects, STN‐DBS reduces brain activity in the motor cortex, such as the M1 and caudal SMA (DOWN arrow in deep blue). Collectively, these data lead us to postulate that the STN‐DBS effective network, which is composed of the bilateral SMA and left M1 areas, and the bilateral thalamus/STN/GPi, may underlie the neural substrate of the therapeutic benefit of STN‐DBS. CAU, caudate nucleus; DA, dopamine; GABA, gamma amino butyric acid; Glu, glutamate; GPe, globus pallidus externus; GPi, globus pallidus internus; PUT, putamen; SNc, substantia nigra pars compacta; STN, subthalamic nucleus; THA, thalamus