title: Thalamocortical Connectivity Correlates with Phenotypic Variability in Dystonia.
abstract: Dystonia is a brain disorder characterized by abnormal involuntary movements without defining neuropathological changes. The disease is often inherited as an autosomal-dominant trait with incomplete penetrance. Individuals with dystonia, whether inherited or sporadic, exhibit striking phenotypic variability, with marked differences in the somatic distribution and severity of clinical manifestations. In the current study, we used magnetic resonance diffusion tensor imaging to identify microstructural changes associated with specific limb manifestations. Functional MRI was used to localize specific limb regions within the somatosensory cortex. Microstructural integrity was preserved when assessed in subrolandic white matter regions somatotopically related to the clinically involved limbs, but was reduced in regions linked to clinically uninvolved (asymptomatic) body areas. Clinical manifestations were greatest in subjects with relatively intact microstructure in somatotopically relevant white matter regions. Tractography revealed significant phenotype-related differences in the visualized thalamocortical tracts while corticostriatal and corticospinal pathways did not differ between groups. Cerebellothalamic microstructural abnormalities were also seen in the dystonia subjects, but these changes were associated with genotype, rather than with phenotypic variation. The findings suggest that the thalamocortical motor system is a major determinant of dystonia phenotype. This pathway may represent a novel therapeutic target for individuals with refractory limb dystonia.
authors.affiliation: Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
authors.forename: An
authors.initials: A
authors.lastname: Vo
authors.affiliation: Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
authors.forename: Wataru
authors.initials: W
authors.lastname: Sako
authors.affiliation: Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Niethammer
authors.affiliation: Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
authors.forename: Maren
authors.initials: M
authors.lastname: Carbon
authors.affiliation: Mirken Department of Neurology, Beth Israel Medical Center, New York, NY 10003, USA.
authors.forename: Susan B
authors.initials: SB
authors.lastname: Bressman
authors.affiliation: Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA Department of Radiology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Aziz M
authors.initials: AM
authors.lastname: Uluğ
authors.affiliation: Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
authors.forename: David
authors.initials: D
authors.lastname: Eidelberg
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000098:blood supply / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging; D004421:Dystonia / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000098:blood supply / Q000502:physiology; D010100:Oxygen / Q000097:blood; D010641:Phenotype; D012720:Severity of Illness Index; D013223:Statistics as Topic; D013788:Thalamus / Q000098:blood supply / Q000473:pathology*
chemical_list: D010100:Oxygen
keywords: diffusion tensor imaging (DTI); dystonia; motor system; tractography