title: Striatal dopaminergic dysfunction at rest and during task performance in writer's cramp.
abstract: Writer's cramp is a task-specific focal hand dystonia characterized by involuntary excessive muscle contractions during writing. Although abnormal striatal dopamine receptor binding has been implicated in the pathophysiology of writer's cramp and other primary dystonias, endogenous dopamine release during task performance has not been previously investigated in writer's cramp. Using positron emission tomography imaging with the D2/D3 antagonist 11C-raclopride, we analysed striatal D2/D3 availability at rest and endogenous dopamine release during sequential finger tapping and speech production tasks in 15 patients with writer's cramp and 15 matched healthy control subjects. Compared with control subjects, patients had reduced 11C-raclopride binding to D2/D3 receptors at rest in the bilateral striatum, consistent with findings in previous studies. During the tapping task, patients had decreased dopamine release in the left striatum as assessed by reduced change in 11C-raclopride binding compared with control subjects. One cluster of reduced dopamine release in the left putamen during tapping overlapped with a region of reduced 11C-raclopride binding to D2/D3 receptors at rest. During the sentence production task, patients showed increased dopamine release in the left striatum. No overlap between altered dopamine release during speech production and reduced 11C-raclopride binding to D2/D3 receptors at rest was seen. Striatal regions where D2/D3 availability at rest positively correlated with disease duration were lateral and non-overlapping with striatal regions showing reduced D2/D3 receptor availability, except for a cluster in the left nucleus accumbens, which showed a negative correlation with disease duration and overlapped with striatal regions showing reduced D2/D3 availability. Our findings suggest that patients with writer's cramp may have divergent responses in striatal dopamine release during an asymptomatic motor task involving the dystonic hand and an unrelated asymptomatic task, sentence production. Our voxel-based results also suggest that writer's cramp may be associated with reduced striatal dopamine release occuring in the setting of reduced D2/D3 receptor availability and raise the possibility that basal ganglia circuits associated with premotor cortices and those associated with primary motor cortex are differentially affected in primary focal dystonias.
authors.affiliation: 1 Department of Neurology, University of Colorado Anschutz Medical Campus, Denver, CO USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Berman
authors.forename: Mark
authors.initials: M
authors.lastname: Hallett
authors.forename: Peter
authors.initials: P
authors.lastname: Herscovitch
authors.forename: Kristina
authors.initials: K
authors.lastname: Simonyan
mesh_terms: D000328:Adult; D000368:Aged; D001931:Brain Mapping; D016022:Case-Control Studies; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D020821:Dystonic Disorders / Q000473:pathology*; D005260:Female; D007839:Functional Laterality; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011597:Psychomotor Performance; D020891:Raclopride / Q000493:pharmacokinetics; D012146:Rest; D013223:Statistics as Topic
chemical_list: D018492:Dopamine Antagonists; D020891:Raclopride; D004298:Dopamine
keywords: PET; dopamine; dystonia; raclopride; striatum