The CM‐aGPi Network in the Generation of Tics in Tourette Syndrome

Background Tourette syndrome (TS) is a neurodevelopmental disorder characterized by intermittent involuntary, repetitive movements and vocalizations collectively referred to as tics. For participants with severe tics who are resistant to medication and behavioral therapy, deep brain stimulation (DBS) has emerged as a potential treatment. Suboptimal animal models and shortcomings in anatomical imaging have collectively hindered progress in understanding the neurophysiological basis of human tic generation. Objectives This study investigates the mechanisms underlying tic generation across two DBS targets with simultaneous recordings—the centromedian thalamus (CM) and anterior globus pallidus internus (aGPi)—and their interactions. Methods Six participants with TS underwent bilateral implantation of four total CM and aGPi leads connected to two adaptive neurostimulators. Preoperative magnetic resonance imaging (MRI) and postoperative computed tomography (CT) scans localized lead and contact locations in CM and aGPi. Neural signals were recorded over nine consecutive monthly visits, encompassing both tic and symptom‐free states. No stimulation was applied during the recordings. Results Recordings from both human CM and aGPi revealed increased low‐frequency (<20 Hz) power during both motor and vocal tics. The pallido‐thalamic coherence in the pathological 1–10 Hz band was significantly greater during tics than in symptom‐free states. The phase difference between the two nuclei was reduced during tics, with higher internuclear phase differences observed in the left hemisphere. Conclusion These findings reveal distinct neural dynamics in the basal ganglia—thalamus network during tic generation, providing insight into the pathophysiology underlying human TS.