Tourette syndrome is characterised by atypical activation within the mentalizing network

Background: The neuropsychiatric condition Tourette syndrome (TS) frequently involves complex tics with social relevance, including echophenomena (i.e. tics involving imitation) and socially inappropriate behaviors. Recent studies have indicated that these patients can exhibit subtle reasoning differences on tasks involving theory of mind (ToM): the ability to reason about mental states. Objective: We investigated the neural correlates of mentalizing in TS. Methods: Twenty-five adults with TS (but no comorbid disorders) and twenty-five healthy controls underwent fMRI during an established ToM false-belief paradigm. Patients and controls were matched for age and gender and neuropsychological profiles were similar. Tic symptoms, premonitory urges, echophenomena, impulsive and obsessive-compulsive behaviors were assessed for covariate analysis. Results: There were no group differences in behavioral performance on the false-belief task. However, when contrasting neural activation across mentalizing and nonmentalizing conditions and comparing the two groups, patients with TS exhibited abnormalities of up and down-regulation of key nodes within the mentalizing network, including right temporo-parietal junction, right amygdala bordering the temporal pole, and posterior cingulate cortex. Group comparisons collapsed across conditions revealed additional activation differences in the inferior parietal region, part of the human mirror neuron system. In TS, inferior parietal activation covaried with a measure of echophenomena. Conclusion: The observed pattern of altered activation within the mentalizing network may reflect a functional neural biomarker specific to TS, which could underpin the reported differences in reasoning about ToM, and perhaps socially inappropriate behaviors. Furthermore, our findings highlight dysfunction within the mirror neuron system as the likely mechanism driving echophenomena.