Spasmodic dysphonia (SD) is a primary focal dystonia with selective impairment of voluntary control of voice production. Despite the recent progress in elucidating the brain abnormalities within the basal gangliathalamo-motor cortical circuitry in this disorder, there is a fundamental gap in understanding the neurochemical correlates underpinning these changes. The objective of this application is to determine the role played by major basal ganglia neurotransmitters in normal and altered voluntary voice production. The central hypothesis is that changes in neurotransmission contribute to altered functional brain activity in SD. Using neuroimaging techniques (PET and fMRI), this hypothesis will be tested by pursuing two specific aims: (1) to identify GABAergic and dopaminergic function in healthy subjects and SD patients;and (2) to determine correlations between the neurotransmitters and network functional activity during speech production and at rest. This approach is innovative, because it will be among the first detailed investigations designed to determine neurotransmitter contribution to the control of normal voice production and to the pathophysiology of SD. The proposed research is significant, because it is expected to advance our understanding of how voluntary voice control system is organized in healthy and diseased individuals as a first step in identifying the mechanisms for neuropharmacological interventions in patients with neurological voice and speech disorders. Thus, the proposed research is relevant to that part of NIH's mission that pertains to developing fundamental knowledge, which will potentially help to reduce the burdens of human disability. During the mentored K99 phase of this award, the applicant will develop expertise in PET imaging using radioligands and will continue to hone her skills in fMRI and neuroimaging data analysis to facilitate her development in the ROO phase of the award as an independent investigator in the field of neurological voice and speech disorders.
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