title: Abnormal striatal dopaminergic neurotransmission during rest and task production in spasmodic dysphonia.
abstract: Spasmodic dysphonia is a primary focal dystonia characterized by involuntary spasms in the laryngeal muscles during speech production. The pathophysiology of spasmodic dysphonia is thought to involve structural and functional abnormalities in the basal ganglia-thalamo-cortical circuitry; however, neurochemical correlates underpinning these abnormalities as well as their relations to spasmodic dysphonia symptoms remain unknown. We used positron emission tomography with the radioligand [(11)C]raclopride (RAC) to study striatal dopaminergic neurotransmission at the resting state and during production of symptomatic sentences and asymptomatic finger tapping in spasmodic dysphonia patients. We found that patients, compared to healthy controls, had bilaterally decreased RAC binding potential (BP) to striatal dopamine D2/D3 receptors on average by 29.2%, which was associated with decreased RAC displacement (RAC ΔBP) in the left striatum during symptomatic speaking (group average difference 10.2%), but increased RAC ΔBP in the bilateral striatum during asymptomatic tapping (group average difference 10.1%). Patients with more severe voice symptoms and subclinically longer reaction time to initiate the tapping sequence had greater RAC ΔBP measures, while longer duration of spasmodic dysphonia was associated with a decrease in task-induced RAC ΔBP. Decreased dopaminergic transmission during symptomatic speech production may represent a disorder-specific pathophysiological trait involved in symptom generation, whereas increased dopaminergic function during unaffected task performance may be explained by a compensatory adaptation of the nigrostriatal dopaminergic system possibly due to decreased striatal D2/D3 receptor availability. These changes can be linked to the clinical and subclinical features of spasmodic dysphonia and may represent the neurochemical basis of basal ganglia alterations in this disorder.
authors.affiliation: Departments of Neurology and Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, Department of Neurology, University of Colorado Anschutz Medical Campus, Denver, Colorado 80045, and PET Department, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Kristina
authors.initials: K
authors.lastname: Simonyan
authors.forename: Brian D
authors.initials: BD
authors.lastname: Berman
authors.forename: Peter
authors.initials: P
authors.lastname: Herscovitch
authors.forename: Mark
authors.initials: M
authors.lastname: Hallett
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; D055154:Dysphonia / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology*; D005260:Female; D006801:Humans; D007818:Laryngeal Diseases / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011597:Psychomotor Performance; D020891:Raclopride; D011877:Radionuclide Imaging; D012146:Rest; D013068:Speech Production Measurement
chemical_list: D018492:Dopamine Antagonists; D020891:Raclopride; D004298:Dopamine
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