Cortical Thickness and White Matter Surface Morphology in Tourette Syndrome: A Cohort Study

OBJECTIVE: To examine cortical thickness and white matter surface morphology in a large sample of individuals with Tourette syndrome (TS) and neurotypical controls across the lifespan, and to assess associations with symptom severity, comorbidities, and medication use. METHODS: Cross-sectional neuroimaging cohort study utilizing high-resolution, T1-weighted magnetic resonance imaging scans obtained in 264 participants (151 TS, 113 neurotypical controls), aged 6-63 years. Image processing included rigorous quality control and deformation-based morphometry. Voxel-wise measures of cortical thickness and white matter surface displacement from a template brain were calculated. General linear models applied voxel-wise tested group differences adjusted for age, sex, and socioeconomic status. Additional covariates in sensitivity analyses included full-scale IQ, comorbid illnesses, and medication use. Interactions of group with age and sex, as well as associations with symptom severity, were also evaluated. RESULTS: Compared with controls, TS participants showed extensive cortical thinning in precentral and postcentral gyri, inferior and middle frontal gyri, and inferior parietal lobule, as well as white matter surface displacement in overlapping regions. These effects remained significant after covarying for IQ, comorbidity, and medication use. Neither age nor sex significantly moderated these group differences. Attention deficit hyperactivity disorder symptom severity was associated with additional frontoparietal cortical thinning; obsessive-compulsive disorder severity showed no effect. Tic symptom severity did not associate significantly with brain measures anywhere. INTERPRETATION: These findings suggest that cortical thinning and associated white matter reductions in TS reflect stable neurodevelopmental traits rather than transient symptom states. These cortical portions of cortico-striato-thalamo-cortical circuits may serve as targets for future therapeutic interventions. ANN NEUROL 2026.