ognitive-Pharmacologic Functional Magnetic esonance Imaging in Tourette Syndrome: Pilot Study

ackground: 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 o 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 he brain). ethods: We obtained complete fMRI data in 8 neuroleptic-naive adults with a chronic tic disorder and in 10 well-matched tic-free ontrol subjects. esults: Different task-sensitive brain regions responded differently to the WM task depending on levodopa status and diagnostic roup (analysis of variance [ANOVA], p .001). Four regions showed interactions with diagnosis (ANOVA, p .001). In TS subjects, he task induced excessive brain activity in parietal cortex, medial frontal gyrus, and thalamus. Levodopa normalized the excess ctivity. In left parietal cortex, the degree of normalization was greater in patients with higher levodopa plasma concentrations (n ; Spearman’s r .84, p .04) and a greater degree of diagnostic confidence of TS (r .71, p .05). onclusions: These results are consistent with a dopamine-influenced functional abnormality of brain response in TS and suggest estable hypotheses about the mechanism by which dopamine antagonists and agonists alleviate tics.