Scott A Norris1, Aimee E Morris2, Meghan C Campbell2, Morvarid Karimi2, Babatunde Adeyemo2, Randal C Paniello2, Abraham Z Snyder2, Steven E Petersen2, Jonathan W Mink2, Joel S Perlmutter2. 1. From the Departments of Neurology (S.A.N., M.C.C., M.K., A.B., A.Z.S., S.E.P., J.S.P.), Radiology (S.A.N., M.C.C., A.Z.S., S.E.P., J.S.P.), Otolaryngology (R.C.P.), Neuroscience (S.E.P., J.S.P.), Psychology (S.E.P.), Physical Therapy (J.S.P.), and Occupational Therapy (J.S.P.), Washington University School of Medicine, St. Louis, MO; University of Rochester Medical Scientist Training Program and Neurosciences Graduate Program (A.E.M.); and Departments of Neurology, Neuroscience, and Pediatrics (J.W.M.), University of Rochester, NY. norriss@wustl.edu. 2. From the Departments of Neurology (S.A.N., M.C.C., M.K., A.B., A.Z.S., S.E.P., J.S.P.), Radiology (S.A.N., M.C.C., A.Z.S., S.E.P., J.S.P.), Otolaryngology (R.C.P.), Neuroscience (S.E.P., J.S.P.), Psychology (S.E.P.), Physical Therapy (J.S.P.), and Occupational Therapy (J.S.P.), Washington University School of Medicine, St. Louis, MO; University of Rochester Medical Scientist Training Program and Neurosciences Graduate Program (A.E.M.); and Departments of Neurology, Neuroscience, and Pediatrics (J.W.M.), University of Rochester, NY.
Abstract
OBJECTIVE: To test the hypothesis that there is shared regional or global functional connectivity dysfunction in a large cohort of patients with isolated focal dystonia affecting different body regions compared to control participants. In this case-control study, we obtained resting-state MRI scans (three or four 7.3-minute runs) with eyes closed in participants with focal dystonia (cranial [17], cervical [13], laryngeal [18], or limb [10]) and age- and sex-matched controls. METHODS: Rigorous preprocessing for all analyses was performed to minimize effect of head motion during scan acquisition (dystonia n = 58, control n = 47 analyzed). We assessed regional functional connectivity by computing a seed-correlation map between putamen, pallidum, and sensorimotor cortex and all brain voxels. We assessed significant group differences on a cluster-wise basis. In a separate analysis, we applied 300 seed regions across the cortex, cerebellum, basal ganglia, and thalamus to comprehensively sample the whole brain. We obtained participant whole-brain correlation matrices by computing the correlation between seed average time courses for each seed pair. Weighted object-oriented data analysis assessed group-level whole-brain differences. RESULTS: Participants with focal dystonia had decreased functional connectivity at the regional level, within the striatum and between lateral primary sensorimotor cortex and ventral intraparietal area, whereas whole-brain correlation matrices did not differ between focal dystonia and control groups. Rigorous quality control measures eliminated spurious large-scale functional connectivity differences between groups. CONCLUSION: Regional functional connectivity differences, not global network level dysfunction, contributes to common pathophysiologic mechanisms in isolated focal dystonia. Rigorous quality control eliminated spurious large-scale network differences between patients with focal dystonia and control participants.
OBJECTIVE: To test the hypothesis that there is shared regional or global functional connectivity dysfunction in a large cohort of patients with isolated focal dystonia affecting different body regions compared to control participants. In this case-control study, we obtained resting-state MRI scans (three or four 7.3-minute runs) with eyes closed in participants with focal dystonia (cranial [17], cervical [13], laryngeal [18], or limb [10]) and age- and sex-matched controls. METHODS: Rigorous preprocessing for all analyses was performed to minimize effect of head motion during scan acquisition (dystonia n = 58, control n = 47 analyzed). We assessed regional functional connectivity by computing a seed-correlation map between putamen, pallidum, and sensorimotor cortex and all brain voxels. We assessed significant group differences on a cluster-wise basis. In a separate analysis, we applied 300 seed regions across the cortex, cerebellum, basal ganglia, and thalamus to comprehensively sample the whole brain. We obtained participant whole-brain correlation matrices by computing the correlation between seed average time courses for each seed pair. Weighted object-oriented data analysis assessed group-level whole-brain differences. RESULTS: Participants with focal dystonia had decreased functional connectivity at the regional level, within the striatum and between lateral primary sensorimotor cortex and ventral intraparietal area, whereas whole-brain correlation matrices did not differ between focal dystonia and control groups. Rigorous quality control measures eliminated spurious large-scale functional connectivity differences between groups. CONCLUSION: Regional functional connectivity differences, not global network level dysfunction, contributes to common pathophysiologic mechanisms in isolated focal dystonia. Rigorous quality control eliminated spurious large-scale network differences between patients with focal dystonia and control participants.
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