Pathophysiology of motor symptoms in Parkinson's disease: Role of primary motor cortex

Parkinson's disease, the most common movement disorder, is a progressive neurodegenerative disease clinically characterized by prominent motor symptoms, e.g., bradykinesia, rigidity, and tremor in addition to postural and gait disorders and, in some cases, levodopa-induced dyskinesia (LID). From a pathophysiological point of view, the motor symptoms of Parkinson's disease are traditionally considered to reflect dopaminergic denervation of the basal ganglia, with only a few exceptions. Changes in neuronal activity, abnormal oscillations, and altered plasticity, and sensorimotor integration mechanisms have been described at the level of basal ganglia. However, numerous studies have emerged in recent years in support of a pathophysiological role played by different brain areas in Parkinson's disease, particularly the motor cortical areas. It has increasingly been demonstrated that the primary motor cortex plays a relevant role in the pathophysiology of bradykinesia. Available evidence also emphasizes the possible role of the primary motor cortex in the pathophysiology of resting tremor and LID. In contrast, experimental data regarding the pathophysiology of rigidity and postural and gait disorders are limited. Delineating the pathophysiological involvement of the primary motor cortex in Parkinson's disease has several implications, including a better understanding and characterization of the remarkable heterogeneity of motor symptoms in this condition. Finally, delineating the pathophysiological role of the primary motor cortex in Parkinson's disease could lead to the more appropriate use of non-invasive brain stimulation techniques for therapeutic purposes. While many knowledge gaps remain, further studies can help better define the pathophysiological role of cortical motor areas in Parkinson's disease.