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

Abstract

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.

Tic related local field potentials in the thalamus and the effect of deep brain stimulation in Tourette syndrome: Report of three cases

“…This has been reported also in human and non-human studies (McCairn et al, 2013a). Although the DBS effect ipsilaterally was not recorded, due to the excessive electrical artefact of DBS, it may be inferred from the observed inhibition of the contralateral thalamic activity, that ipsilaterally to the applied DBS side an inhibition of thalamic alpha activity may have occurred at least as strong as on the contralateral side of stimulation.…”

Pallidal stimulation suppresses pathological dysrhythmia in the parkinsonian motor cortex

“…Our artifact subtraction method makes it possible to identify short-latency responses (0 -3 ms) in close spatial proximity to the stimulating electrode (McCairn and Turner 2009;McCairn et al 2013). Using this technique, we found only one M1 cell (out of 132 cells studied) that responded at a short fixed latency as would be expected of antidromic driving.…”

Pathophysiology of tic disorders

“…The striatal disinhibition model has been applied in multiple studies in both rodents [33][34][35][36] and non human primates. [37][38][39][40][41] Multiple studies that have revealed finely timed tic-related changes in neuronal activity throughout the CBG circuit, including the striatum, cortex, thalamus, GPe, GPi, and SNr. 37,38,[42][43][44] Whereas each of the areas displayed tic-related modulations in neuronal activity in short (subsecond) time scales around tic onset, the modulation type differed substantially (Fig.…”