Cognitive-pharmacologic functional magnetic resonance imaging in Tourette syndrome: A pilot study

Background Dopamine agonists and antagonists can reduce abnormal movements and vocalizations (tics) in Tourette syndrome (TS); however, dopamine-responsive abnormal function in specific brain regions has not been directly demonstrated in TS. We sought to identify dopamine-modulated brain regions that function abnormally in TS by combining functional magnetic resonance imaging (fMRI), a working memory (WM) task, and infusion of the dopamine prodrug levodopa (while blocking dopamine production outside the brain). Methods We obtained complete fMRI data in 8 neuroleptic-naive adults with a chronic tic disorder and in 10 well-matched tic-free control subjects. Results Different task-sensitive brain regions responded differently to the WM task depending on levodopa status and diagnostic group (analysis of variance [ANOVA], p < .001). Four regions showed interactions with diagnosis (ANOVA, p < .001). In TS subjects, the task induced excessive brain activity in parietal cortex, medial frontal gyrus, and thalamus. Levodopa normalized the excess activity. In left parietal cortex, the degree of normalization was greater in patients with higher levodopa plasma concentrations (n = 6; Spearman's r = -.84, p = .04) and a greater degree of diagnostic confidence of TS (r = -.71, p = .05). Conclusions These results are consistent with a dopamine-influenced functional abnormality of brain response in TS and suggest testable hypotheses about the mechanism by which dopamine antagonists and agonists alleviate tics.