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.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Transition Award (R00)
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Special Emphasis Panel (NSS)
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Shekim, Lana O
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Icahn School of Medicine at Mount Sinai
Schools of Medicine
New York
United States
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Simonyan, Kristina (2014) The laryngeal motor cortex: its organization and connectivity. Curr Opin Neurobiol 28:15-21
F├╝rtinger, Stefan; Zinn, Joel C; Simonyan, Kristina (2014) A neural population model incorporating dopaminergic neurotransmission during complex voluntary behaviors. PLoS Comput Biol 10:e1003924
Horwitz, Barry; Simonyan, Kristina (2014) PET neuroimaging: plenty of studies still need to be performed: comment on Cumming: "PET neuroimaging: the white elephant packs his trunk?". Neuroimage 84:1101-3
Simonyan, Kristina; Berman, Brian D; Herscovitch, Peter et al. (2013) Abnormal striatal dopaminergic neurotransmission during rest and task production in spasmodic dysphonia. J Neurosci 33:14705-14
Simonyan, Kristina; Herscovitch, Peter; Horwitz, Barry (2013) Speech-induced striatal dopamine release is left lateralized and coupled to functional striatal circuits in healthy humans: a combined PET, fMRI and DTI study. Neuroimage 70:21-32
Simonyan, Kristina; Horwitz, Barry; Jarvis, Erich D (2012) Dopamine regulation of human speech and bird song: a critical review. Brain Lang 122:142-50
Simonyan, Kristina; Horwitz, Barry (2011) Laryngeal motor cortex and control of speech in humans. Neuroscientist 17:197-208
Simonyan, Kristina; Ludlow, Christy L (2010) Abnormal activation of the primary somatosensory cortex in spasmodic dysphonia: an fMRI study. Cereb Cortex 20:2749-59