Figure 1: Schematic diagram of the major anatomical pathways affected by deep brain stimulation and motor cortex stimulation. Left: Both the Subthalamic Nucleus (STN) and Zona Incerta (ZI) receive heavy projections from a subgroup of layer V neurons in the cerebral cortex. The external pallidal segment (GPe) receives inputs from the neostriatum (caudate nucleus and putamen) and the STN. The internal pallidal segment (GPi) is the main output structure of the basal ganglia (the other being the substantia nigra reticulata) and projects to the nuclei of the motor thalamus (ventral anterior nucleus and ventral lateral nucleus). The subthalamic region is a white matter area abutting the STN and encompassing the ZI. Right: Epidural electrodes are targeted to the primary motor cortex contralateral to the site of the defect and connected to a stimulator. Stimulation intensity ranges from 0 to 75 μA, frequency from 0 to 75 Hz, and duration from 0 to 90 minutes [6]. In a neuropathic pain model, MCS enhanced the activity of inhibitory nucleus ZI neurons and suppressed the activity of posterior thalamic nucleus (PO) neurons. Activity is decreased in the somatosensory cortex, a major projection target of the PO, diminishing pain. Excitatory (glutamatergic) pathways are shown as red lines, inhibitory (GABAergic) connections as blue lines. Abbreviation: Put: putamen.