Abnormal neuronal activity in Tourette syndrome and its

27 Tourette syndrome (TS) is a common childhood-onset disorder characterized by motor and vocal 28 tics that are typically accompanied by a multitude of comorbid symptoms. Pharmacological 29 treatment options are limited, which has led to the exploration of deep brain stimulation (DBS) 30 as a possible treatment for severe cases. Multiple lines of evidence have linked TS with 31 abnormalities in the motor and limbic cortico-basal ganglia (CBG) pathways. 32 Neurophysiological data have only recently started to slowly accumulate from multiple sources: 33 noninvasive imaging and electrophysiological techniques, invasive electrophysiological 34 recordings in TS patients undergoing DBS implantation surgery and animal models of the 35 disorder. These converging sources point to system level physiological changes throughout the 36 CBG pathway including both general altered baseline neuronal activity patterns and specific tic 37 related activity. DBS has been applied to different regions along the motor and limbic pathways, 38 primarily to the globus pallidus internus, thalamic nuclei and nucleus accumbens. In line with the 39 findings that also draw on the more abundant application of DBS to Parkinson’s disease, this 40 stimulation is assumed to result in changes in the neuronal firing patterns and the passage of 41 information through the stimulated nucleus. We present an overview of recent experimental 42 findings on abnormal neuronal activity associated with TS and the changes in this activity 43 following DBS. These findings are then discussed in the context of current models of CBG 44 function in the normal state, during TS, and finally in the wider context of DBS in CBG-related 45 disorders. 46