A concept in Parkinson's disease postulates that motor cortex may pattern abnormal rhythmic activities in the basal ganglia, underlying the genesis of observed motor symptoms. We conducted a preclinical study of electrical interference in the primary motor cortex using a chronic MPTP primate model in which dopamine depletion was progressive and regularly documented using 18F-DOPA positron tomography. High-frequency motor cortex stimulation significantly reduced akinesia and bradykinesia. This behavioral benefit was associated with an increased metabolic activity in the supplementary motor area as assessed with 18-F-deoxyglucose PET, a normalization of mean firing rate in the internal globus pallidus (GPi) and the subthalamic nucleus (STN), and a reduction of synchronized oscillatory neuronal activities in these two structures. Motor cortex stimulation is a simple and safe procedure to modulate subthalamo-pallido-cortical loop and alleviate parkinsonian symptoms without requiring deep brain stereotactic surgery.