Untangling neurophysiology of Tourette syndrome using dual-target bi-pallidal deep brain stimulation

Tourette syndrome is a neurodevelopmental disorder characterized by motor and vocal tics, often accompanied by psychiatric comorbidities. Deep brain stimulation (DBS) may be recommended for medication-refractory severe cases, but optimal stimulation targets and the mechanisms underlying DBS effects remain uncertain.

This pilot study aimed to investigate the clinical and neurophysiological effects of dual-target DBS involving both the anterior and posterior globus pallidus internus (GPi) in patients with severe Tourette syndrome.

Three patients with severe, medication-refractory Tourette syndrome underwent dual-target GPi DBS. Local field potentials (LFPs) were recorded postoperatively under different stimulation conditions. Clinical outcomes, including tic severity, psychiatric symptoms, and patient-reported quality of life, were assessed longitudinally.

High-beta oscillations (20-35 Hz) were prominent in the posterior GPi of two patients who exhibited the most pronounced tic reduction. Stimulation of one GPi region did not produce consistent cross-modulatory spectral changes in the other region, suggesting limited acute cross-modulatory effects between anterior and posterior GPi under the present recording conditions. Clinically, two patients experienced substantial tic reduction and consistent psychiatric improvements, including decreased irritability, improved mood, and resolution of self-injurious behaviors. Patient-reported outcomes indicated enhanced social reintegration and quality of life, even in the patient with limited tic suppression.

These findings provide insight into the functional interactions and clinical correlates of globus pallidus internus subregions, and support the potential utility of dual-target deep brain stimulation for both motor and non-motor symptoms in Tourette syndrome.