title: Phenotype- and genotype-specific structural alterations in spasmodic dysphonia.
abstract: Spasmodic dysphonia is a focal dystonia characterized by involuntary spasms in the laryngeal muscles that occur selectively during speaking. Although hereditary trends have been reported in up to 16% of patients, the causative etiology of spasmodic dysphonia is unclear, and the influences of various phenotypes and genotypes on disorder pathophysiology are poorly understood. In this study, we examined structural alterations in cortical gray matter and white matter integrity in relationship to different phenotypes and putative genotypes of spasmodic dysphonia to elucidate the structural component of its complex pathophysiology.
  
  
  
  Eighty-nine patients with spasmodic dysphonia underwent high-resolution magnetic resonance imaging and diffusion-weighted imaging to examine cortical thickness and white matter fractional anisotropy in adductor versus abductor forms (distinct phenotypes) and in sporadic versus familial cases (distinct genotypes).
  
  
  
  Phenotype-specific abnormalities were localized in the left sensorimotor cortex and angular gyrus and the white matter bundle of the right superior corona radiata. Genotype-specific alterations were found in the left superior temporal gyrus, supplementary motor area, and the arcuate portion of the left superior longitudinal fasciculus.
  
  
  
  Our findings suggest that phenotypic differences in spasmodic dysphonia arise at the level of the primary and associative areas of motor control, whereas genotype-related pathophysiological mechanisms may be associated with dysfunction of regions regulating phonological and sensory processing. Identification of structural alterations specific to disorder phenotype and putative genotype provides an important step toward future delineation of imaging markers and potential targets for novel therapeutic interventions for spasmodic dysphonia. © 2017 International Parkinson and Movement Disorder Society.
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Serena
authors.initials: S
authors.lastname: Bianchi
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Battistella
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Hailey
authors.initials: H
authors.lastname: Huddleston
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Scharf
authors.affiliation: Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Lazar
authors.initials: L
authors.lastname: Fleysher
authors.affiliation: School of Health and Rehabilitation Sciences, Speech Pathology, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Anna F
authors.initials: AF
authors.lastname: Rumbach
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Frucht
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Head and Neck Surgical Group, New York, New York, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Blitzer
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Ozelius
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Department of Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Kristina
authors.identifier: 0000-0001-7444-0437
authors.initials: K
authors.lastname: Simonyan
mesh_terms: D000328:Adult; D000368:Aged; D016880:Anisotropy; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics; D056324:Diffusion Tensor Imaging; D055154:Dysphonia / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D005260:Female; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D012720:Severity of Illness Index; D015898:Tomography Scanners, X-Ray Computed; D014404:Tubulin / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; D044385:GTP-Binding Protein alpha Subunits; D018832:Molecular Chaperones; D009687:Nuclear Proteins; C474080:THAP1 protein, human; C108175:TOR1A protein, human; C582076:TUBB4A protein, human; D014404:Tubulin; C084618:olfactory G protein subunit alpha olf
keywords: cortical thickness; diffusion-weighted imaging; genetics; laryngeal dystonia