Primary motor cortex in Parkinson's disease: Functional changes and opportunities for neurostimulation.

Movement abnormalities of Parkinson's disease (PD) arise from disordered neural activity in multiple interconnected brain structures. The planning and execution of movement requires recruitment of a heterogeneous collection of pyramidal projection neurons in the primary motor cortex (M1). The neural representations of movement in M1 single-cell and field potential recordings are directly and indirectly influenced by the midbrain dopaminergic neurons that degenerate in PD. This review examines M1 functional alterations in PD as uncovered by electrophysiological recordings and neurostimulation studies in patients and experimental animal models. Dysfunction of the parkinsonian M1 depends on the severity and/or duration of dopamine-depletion and the species examined, and is expressed as alterations in movement-related firing dynamics; functional reorganisation of local circuits; and changes in field potential beta oscillations. Neurostimulation methods that modulate M1 activity directly (e.g., transcranial magnetic stimulation) or indirectly (subthalamic nucleus deep brain stimulation) improve motor function in PD patients, showing that targeted neuromodulation of M1 is a realistic therapy. We argue that the therapeutic profile of M1 neurostimulation is likely to be greatly enhanced with alternative technologies that permit cell-type specific control and incorporate feedback from electrophysiological biomarkers measured locally.