Subthalamic nucleus neurons are synchronized to primary motor cortex local field potentials in Parkinson's disease

Abstract

In Parkinson's disease (PD), striatal dopamine denervation results in a cascade of abnormalities in the single-unit activity of downstream basal ganglia nuclei that include increased firing rate, altered firing patterns, and increased oscillatory activity. However, the effects of these abnormalities on cortical function are poorly understood. Here, in humans undergoing deep brain stimulator implantation surgery, we use the novel technique of subdural electrocortico graphy in combination with subthalamic nucleus (STN) single-unit recording to study basal ganglia-cortex interactions at the millisecond time scale. We show that in patients with PD, STN spiking is synchronized with primary motor cortex (M1) local field potentials in two distinct patterns: first, STN spikes are phase-synchronized with M1 rhythms in the theta, alpha, or beta (4-30 Hz) bands. Second, STN spikes are synchronized with M1 gamma activity over a broad spectral range (50-200Hz).The amplitude of STN spike-synchronized gammaactivity in M1is itself rhythmically modulated by the phase of alower-frequency rhythm (phase-amplitude coupling), such that "waves" of phase-synchronized gamma activity precede the occurrence of STN spikes. Weshow the disease specificity of the sephenomenain PD, by comparison with STN-M1pairedre cordingsper form edina group of patients with adifferent disorder, primary craniocervical dystonia. Our findings support a model of the basal ganglia-thalamocorticalloopin PD in which gamma activity in primary motor cortex, modulated by the phase of low-frequency rhythms, drives STN unit discharge. ©2013 the authors.