Pallidal stimulation that improves parkinsonian motor symptoms also modulates neuronal firing patterns in primary motor cortex in the MPTP-treated monkey

Abstract

Deep brain stimulation (DBS), a surgical therapy for advanced Parkinson's disease (PD), is known to change neuronal activity patterns in the pallidothalamic circuit. Whether these effects translate to the motor cortex and, if so, how they might modulate the functional responses of individual neurons in primary motor cortex remains uncertain. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkey was implanted with a DBS lead spanning internal and external segments of globus pallidus. During therapeutic stimulation (135 Hz) for rigidity and bradykinesia, neurons in primary motor cortex (M1) exhibited an inhibitory phase-locking (2–5 ms) to the stimulus, an overall decrease in mean discharge rate, and an increase in response specificity to passive limb movement. Sub-therapeutic DBS (30 Hz) still produced entrainment to the stimulation, but the mean discharge rate and specificity to movement were not changed. Lower stimulation intensities (at 135 Hz), which no longer improved motor symptoms, had little effect on M1 activity. These findings suggest that DBS improves parkinsonian motor symptoms by inducing global changes in firing pattern and rate along the pallido-thalamocortical sensorimotor circuit.