@article{d53e8c7fa32a4c4e8e730659a2ca4465,
title = "Functional Connectivity of Vermis Correlates with Future Gait Impairments in Parkinson's Disease",
abstract = "Background: Dysfunction of cerebellar vermis contributes to gait abnormalities in multiple conditions and may play a key role in gait impairment in Parkinson's disease (PD). Objective: The purpose of this study was to investigate whether altered resting-state functional connectivity of the vermis relates to subsequent impairment of specific domains of gait in PD. Methods: We conducted morphometric and resting-state functional connectivity MRI analyses contrasting 45 PD and 32 age-matched healthy participants. Quantitative gait measures were acquired with a GAITRite walkway at varying intervals after functional connectivity data acquisition. Results: At baseline, PD participants had significantly altered functional connectivity between vermis and sensorimotor cortex compared with controls. Altered vermal functional connectivity with bilateral paracentral lobules correlated with subsequent measures of variability in stride length, step time, and single support time after controlling for confounding variables including the interval between imaging and gait measures. Similarly, altered functional connectivity between vermis and left sensorimotor cortex correlated with mean stride length and its variability. Vermis volume did not relate to any gait measure. PD participants did not differ from controls in vermis volume or cortical thickness at the site of significant regional clusters. Only altered lobule V:sensorimotor cortex functional connectivity correlated with subsequent gait measures in exploratory analyses involving all the other cerebellar lobules. Conclusions: These results demonstrate that abnormal vermal functional connectivity with sensorimotor cortex, in the absence of relevant vermal or cortical atrophy, correlates with subsequent gait impairment in PD. Our data reflect the potential of vermal functional connectivity as a novel imaging biomarker of gait impairment in PD.",
keywords = "Parkinson disease, cerebellum, functional connectivity, gait impairment, vermis",
author = "Baijayanta Maiti and Rawson, {Kerri S.} and Tanenbaum, {Aaron B.} and Koller, {Jonathan M.} and Snyder, {Abraham Z.} and Meghan Campbell and Gammon Earhart and Perlmutter, {Joel S.}",
note = "Funding Information: : This work was supported by NINDS/NIA at NIH RO1 NS075321‐02, NIH RO1 NS097437, P30 NS098577‐01, NS097799, KL2 TR002346 National Center for Advancing Translational Sciences of the NIH, American Academy of Neurology and American Brain Foundation Clinical Research Training Fellowship in Parkinson's disease, Parkinson Study Group, Parkinson's Disease Foundation Mentored Clinical Research Award, American Parkinson Disease Association (APDA); Greater St. Louis Chapter of APDA, Washington University ICTS/Barnes Jewish Hospital (BJH) Foundation Clinical Translation Award, the Jo Oertli Fund, BJH Foundation (Elliot Stein Family Fund & Parkinson disease research Fund) and Paula and Rodger Riney Foundation. Funding agencies Funding Information: Baijayanta Maiti has received funding from the National Center for Advancing Translational Sciences of the National Institutes of Health KL2 TR002346 and the Jo Oertli Fund and compensation for reviewing grants as a member of the Parkinson Study Group mentoring committee. Kerri S. Rawson has received funding from the National Institutes of Health NS075321, HD092444, and AT010753. Aaron B. Tanenbaum has received funding from the National Institutes of Health NS075321, NS107281, NS103957, NS110456, the Murphy Fund, Dystonia Medical Research Foundation, and National Center for Advancing Translational Sciences of the National Institutes of Health KL2 TR002346. Jonathan M. Koller has received research funding from the National Institutes of Health 5R01HD07085508, 5U01DA04112005, 1U01DA05103801, 5R01DK06483215, 5R01MH10403004, and 2R01MH0967730A1. Abraham Z. Snyder is supported by P30 NS098577‐01, R01 NS097437, and R01 NS10728101. Meghan C. Campbell receives research support from the National Institutes of Health (NS097437, NS075321‐02, NS097799, AG063974, AT010753‐01, AT010753‐02S1), the McDonnell Center for Systems Neuroscience, the Mallinckrodt Institute of Radiology at WUSTL, the Neuroimaging Labs Innovation Award, and honoraria from the Parkinson Foundation. Gammon M. Earhart has received research funding from the National Institutes of Health R01 HD092444, R61 AT114533, R61 AT114533‐S1, U01 NS113851 and National Endowment for the Arts 1880026‐31‐21. Joel S. Perlmutter has received research funding from National Institutes of Health NS075321, NS103957, NS107281, NS092865, U10NS077384, NS097437, U54NS116025, U19 NS110456, AG050263, AG‐64937, NS097799, NS075527, ES029524, NS109487, R61 AT010753 (NCATS, NINDS, NIA), Department of Defense (DOD W81XWH‐217‐1‐0393), Michael J. Fox Foundation, Barnes‐Jewish Hospital Foundation (Elliot Stein Family Fund and Parkinson disease research fund), American Parkinson Disease Association (APDA) Advanced Research Center at Washington University, Greater St. Louis Chapter of the APDA, Paula and Rodger Riney Fund, Jo Oertli Fund, Huntington Disease Society of America, Murphy Fund, and CHDI; honoraria from CHDI, Huntington Disease Study Group, Parkinson Study Group, Beth Israel Hospital (Harvard group), University of Pennsylvania, Stanford University; is also codirector for the Dystonia Coalition, which has received the majority of its support through the NIH (grants NS116025, NS065701 from the National Institutes of Neurological Disorders and Stroke TR 001456 from the Office of Rare Diseases Research at the National Center for Advancing Translational Sciences); serves as Director of Medical and Scientific Advisory Committee of the Dystonia Medical Research Foundation, Chair of the Scientific Advisory Committee of the Parkinson Study Group, Chair of the Standards Committee of the Huntington Study Group, member of the Scientific Advisory Board of the APDA, Chair of the Scientific and Publication Committee for ENROLL‐HD, and member of the Education Committee of the Huntington Study Group; and has provided medical legal consultation to Wood, Cooper and Peterson, LLC, and to Simmons and Simmons, LLP. Relevant conflicts of interest/financial disclosures: Publisher Copyright: {\textcopyright} 2021 International Parkinson and Movement Disorder Society.",
year = "2021",
month = nov,
doi = "10.1002/mds.28684",
language = "English",
volume = "36",
pages = "2559--2568",
journal = "Movement Disorders",
issn = "0885-3185",
number = "11",
}