title: Neural correlates of abnormal sensory discrimination in laryngeal dystonia.
abstract: Aberrant sensory processing plays a fundamental role in the pathophysiology of dystonia; however, its underpinning neural mechanisms in relation to dystonia phenotype and genotype remain unclear. We examined temporal and spatial discrimination thresholds in patients with isolated laryngeal form of dystonia (LD), who exhibited different clinical phenotypes (adductor vs. abductor forms) and potentially different genotypes (sporadic vs. familial forms). We correlated our behavioral findings with the brain gray matter volume and functional activity during resting and symptomatic speech production. We found that temporal but not spatial discrimination was significantly altered across all forms of LD, with higher frequency of abnormalities seen in familial than sporadic patients. Common neural correlates of abnormal temporal discrimination across all forms were found with structural and functional changes in the middle frontal and primary somatosensory cortices. In addition, patients with familial LD had greater cerebellar involvement in processing of altered temporal discrimination, whereas sporadic LD patients had greater recruitment of the putamen and sensorimotor cortex. Based on the clinical phenotype, adductor form-specific correlations between abnormal discrimination and brain changes were found in the frontal cortex, whereas abductor form-specific correlations were observed in the cerebellum and putamen. Our behavioral and neuroimaging findings outline the relationship of abnormal sensory discrimination with the phenotype and genotype of isolated LD, suggesting the presence of potentially divergent pathophysiological pathways underlying different manifestations of this disorder.
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, USA.
authors.forename: Pichet
authors.initials: P
authors.lastname: Termsarasab
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, USA.
authors.forename: Ritesh A
authors.initials: RA
authors.lastname: Ramdhani
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, 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, USA.
authors.forename: Estee
authors.initials: E
authors.lastname: Rubien-Thomas
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Choy
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, USA.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Farwell
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, USA.
authors.forename: Miodrag
authors.initials: M
authors.lastname: Velickovic
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, USA ; Head and Neck Surgical Group, New York, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Blitzer
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Frucht
authors.affiliation: Trinity Centre for Bioengineering, Trinity College Dublin, Ireland.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Reilly
authors.affiliation: Department of Neurology, St. Vincent's University Hospital, Dublin, Ireland.
authors.forename: Michael
authors.initials: M
authors.lastname: Hutchinson
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Charlestown, MA, 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, USA ; Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, USA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Simonyan
mesh_terms: D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D001931:Brain Mapping; D004192:Discrimination, Psychological / Q000502:physiology*; D004421:Dystonia / Q000473:pathology* / Q000503:physiopathology*; D058068:Endophenotypes; D005260:Female; D005838:Genotype; D066128:Gray Matter / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007830:Larynx / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012684:Sensory Thresholds / Q000502:physiology*; D013060:Speech / Q000502:physiology*; D055698:Touch Perception / Q000502:physiology; D014796:Visual Perception / Q000502:physiology
keywords: Brain imaging; Endophenotype; Sensory processing