TY - JOUR
T1 - Regional, not global, functional connectivity contributes to isolated focal dystonia
AU - Norris, Scott A.
AU - Morris, Aimee E.
AU - Campbell, Meghan C.
AU - Karimi, Morvarid
AU - Adeyemo, Babatunde
AU - Paniello, Randal C.
AU - Snyder, Abraham Z.
AU - Petersen, Steven E.
AU - Mink, Jonathan W.
AU - Perlmutter, Joel S.
N1 - Funding Information:
S.A. Norris received research support from NIH T32NS007205 and U54NS116025 as well as the Dystonia Medical Research Foundation Clinical Fellowship for portions of this work. A.E. Morris received research support from NIH T32 GM07356, the Geoffery Wassdorp Pediatric Neurology Fund (University of Rochester), Wilbur Smith Pediatric Neurology fund (University of Rochester), and Schmidt Foundation for Integrative Brain Research (University of Rochester). M.C. Campbell receives NIH research support and a Veterens Affairs Department stipend and travel for grant review. M. Karimi is deceased and unable to report disclosures. A. Babatunde, R.C. Paniello, A.Z. Snyder, and S.E. Petersen report no disclosures relevant to the manuscript. J.W. Mink reports grants from Abeona Inc, consultant fees from Neurogene Inc, Amicus Inc, and is chair/DSMB for Censa Inc, J.S. Perlmutter reports grants from NIH, including U54NS116025 and NS075321; grants from American Parkinson Disease Association (including Greater St. Louis Chapter); research support from the Murphy Fund, Paula C & Rodger O Riney Fund, and Jo Oerteli Fund; and serves as the Scientific Director of the Dystonia Medical Research Foundation (unpaid). Go to Neurology.org/N for full disclosures.
Funding Information:
NIH: T32NS007205, T32 GM07356, U54NS116025 (Dystonia Coalition), a part of the Rare Diseases Clinical Research Network, an initiative of the Office of Rare Diseases Research through collaboration between National Center for Advancing Translational Sciences and the National Institute of Neurologic Diseases and Stroke; Dystonia Medical Research Foundation Clinical Fellowship; American Parkinson Disease Association (APDA) Advanced Research Center for PD at WUSTL; Greater St. Louis Chapter of the APDA; Murphy fund; Jo Oertli fund; Schmidt Foundation for Integrative Brain Research; Geoffrey Waasdorp Pediatric Neurology Fund; and the Wilbur Smith Pediatric Neurology Fund.
Publisher Copyright:
© American Academy of Neurology.
PY - 2020/10/20
Y1 - 2020/10/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85093891030&partnerID=8YFLogxK
U2 - 10.1212/WNL.0000000000010791
DO - 10.1212/WNL.0000000000010791
M3 - Article
C2 - 32913023
AN - SCOPUS:85093891030
SN - 0028-3878
VL - 95
SP - E2246-E2258
JO - Neurology
JF - Neurology
IS - 16
ER -