Deep Brain Stimulation Reduces Tic-Related Neural Activity via Temporal Locking with Stimulus Pulses

A neurosurgical intervention that has shown potential for treating basal ganglia (BG) mediated motor tics involves high-frequency deep brain stimulation (HF-DBS) targeted to the output nucleus of the BG: the globus pallidus internus (GPi). This study used a nonhuman primate (Macaca fuscata) model of BG-meditated motor tics, and investigated the short-term neuronal mechanism that might underlie the beneficial effects of GPi-HF-DBS. In parallel with behavioral tic expressions, phasic alterations of neuronal activity emerged in the pallidum following focal disinhibition of the striatum with bicuculline. We delivered HF-DBS in the GPi in such a way that on-stimulation and off-stimulation conditions alternated every 30 s. Analysis of electromyographic (EMG) records showed that during on-stimulation, there were significant reductions in tic-related EMG amplitude. Analysis of pallidal activity showed that GPi-HF-DBS induced both sustained and transient patterns of excitation and inhibition in both segments of the GP. Population-scale firing rates were initially raised relative to baseline, but were not significantly different by the time stimulation ceased. Modulation of behavior and neuronal firing rates were associated with the reduction of tic-related phasic activity in pallidal cells. Examination of short-latency responses showed that firing rate changes were strongly associated with locking of the cells' activity with the HF-DBS pulse. This temporal locking often induced multiphasic changes of firing rates in individual cells, which dynamically changed across the stimulation period. These results support clinical studies that reported success in treating motor tics with GPi-HF-DBS, and demonstrate that the underlying local mechanism within the GP is suppression of tic-related activity through temporal locking with the stimulation pulse.