Chronic Stroke Sensorimotor Impairment Is Related to Smaller Hippocampal Volumes: An ENIGMA Analysis

• Type of Material: Article
• Authors: Artemis Zavaliangos-Petropulu, University of Southern California; Bethany Lo, University of Southern California; Miranda R Donnelly, University of Southern California; Nicholas Schweighofer, University of Southern California; Keith Lohse, Washington University in St. Louis; Neda Jahanshad, University of Southern California; Guiseppe Barisano, University of Southern California; Nerisa Banaj, IRCCS Santa Lucia Foundation; Michael Borich, Emory University; Lara A Boyd, University of British Columbia; Cathrin Buetefisch, Emory University; Winston D Byblow, University of Auckland; Jessica M Cassidy, University of North Carolina; Charalambos C Charalambous, University of Nicosia Medical School; Adriana B Conforto, São Paulo University; Julie A DiCarlo, Massachusetts General Hospital; Adrienne N Dula, University of Texas Austin; Natalia Egorova-Brumley, University of Melbourne; Mark R Etherton, Massachusetts General Hospital; Wuwei Feng, Duke University; Kelene A Fercho, University of South Dakota; Fatemeh Geranmayeh, Imperial College London; Collen A Hanlon, Wake Forest School of Medicine; Kathryn S Hayward, University of Melbourne; Brenton Hordacre, University of South Australia; Steven A Kautz, Ralph H Johnson Veterans Affairs Medical Center; Mohamed Salah Khlif, The Florey Institute of Neuroscience and Mental Health; Hosung Kim, University of Southern California; Amy Kuceyeski, Weill Cornell Medicine; David J Lin, Massachusetts General Hospital; Jingchun Liu, Tianjin Medical University General Hospital; Martin Lotze, University Medicine Greifswald; Bradley J MacIntosh, Sunnybrook Research Institute; John L Margetis, University of Southern California; Feroze B Mohamed, Thomas Jefferson University; Fabrizio Piras, IRCCS Santa Lucia Foundation; Ander Ramos-Murguialday, University of Tübingen; Kate P Revill, Emory University; Pamela S Roberts, University of Southern California; Andrew D Robertson, University of Waterloo; Heidi M Schambra, NYU Langone; Na Jin Seo, Ralph H Johnson Veterans Affairs Medical Center; Mark S Shiroishi, University of Southern California; Cathy M Stinear, University of Auckland; Surjo R Soekadar, Charité ‐ Universitätsmedizin Berlin; Gianfranco Spalletta, IRCCS Santa Lucia Foundation; Myriam Taga, NYU Langone; Wai Kwong Tang, Chinese University of Hong Kong; Gregory T Thielman, University of the Sciences, Philadelphia; Daniela Vecchio, IRCCS Santa Lucia Foundation; Nick S Ward, University College London; Lars T Westlye, University of Oslo; Emilio Werden, University of Melbourne; Carolee Winstein, University of Southern California; George F Wittenberg, University of Pittsburgh; Steven Wolf, Emory University; Kristin A Wong, University of Texas Austin; Chunshui Yu, Tianjin Medical University General Hospital; Amy Brodtmann, The Florey Institute of Neuroscience and Mental Health; Steven C Cramer, University of California Los Angeles; Paul M Thompson, University of Southern California; Sook-Lei Liew, University of Southern California
• Language: English
• Date: 2022-05-17
• Publisher: WILEY
• Publication Version: Final Published Version
• Copyright Statement: © 2022 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1161/JAHA.121.025109
• Title of Journal or Parent Work: JOURNAL OF THE AMERICAN HEART ASSOCIATION
• Volume: 11
• Issue: 10
• Start Page: e025109
• End Page: e025109
• Grant/Funding Information: N.J.S. is funded by NIH/National Institute of Child Health and Human Development (NICHD) 1R01HD094731‐01A1.; W.D.B. is supported by the Heath Research Council of New Zealand. J.M.C. is supported by NIH R00HD091375.; N.S. is supported by NIH R21NS120274. N.J.S. is supported by NIH/National Institute of General Medical Sciences (NIGMS) 2P20GM109040‐06, U54‐GM104941; S.A.K is supported by NIH P20 HD109040. F.B. is supported by Italian Ministry of Health, RC 20, 21.; M.T. is supported by National Institute of Neurological Disorders and Stroke (NINDS) R01 NS110696.; L.A.B. is supported by the Canadian Institutes of Health Research (CIHR). C.M.B. is supported by NIH R21 HD067906.; G.S. is supported by Italian Ministry of Health RC 18‐19‐20‐21A.; G.T.T. is supported by Temple University sub‐award of NIH R24 –NHLBI (Dr Mickey Selzer) Center for Experimental Neurorehabilitation Training.; F.G. is supported by Wellcome Trust (093957). B.H. is funded by and NHMRC fellowship (1125054).; S.‐L.L. is supported by NIH K01 HD091283; NIH R01 NS115845. A.B. and M.S.K. are supported by National Health and Medical Research Council (NHMRC) GNT1020526, GNT1045617 (A.B.), GNT1094974, and Heart Foundation Future Leader Fellowship 100784 (A.B.). P.M.T. is supported by NIH U54 EB020403.; A.B.C. is supported by NIH R01NS076348‐01, Hospital Israelita Albert Einstein 2250‐14, CNPq/305568/2016‐7.; S.R.S. is supported by European Research Council (ERC) (NGBMI, 759370); A.N.D. is supported by funding provided by the Texas Legislature to the Lone Star Stroke Clinical Trial Network. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the Government of the United States or the State of Texas.; N.E.‐B. is supported by Australian Research Council NIH DE180100893. W.F. is supported by NIH P20 GM109040.
• Keywords: DYSFUNCTION; Cardiovascular System & Cardiology; Cardiac & Cardiovascular Systems; hippocampus; REHABILITATION; REGIONS; MRI; TARGET; stroke; SEGMENTATION; sensorimotor impairment; Life Sciences & Biomedicine; RECOVERY; ATROPHY; Science & Technology; POSTSTROKE; ISCHEMIC-STROKE
• Research Categories: Health Sciences, Mental Health; Health Sciences, Radiology; Health Sciences, Medicine and Surgery; Health Sciences, Rehabilitation and Therapy

Abstract

BACKGROUND: Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is vulnerable to poststroke secondary degeneration and is involved in sensorimotor behavior but has not been widely studied within the context of poststroke upper-limb sensorimotor impairment. We investigated associations between non-lesioned hippocampal volume and upper limb sensorimotor impairment in people with chronic stroke, hypothesizing that smaller ipsilesional hippocampal volumes would be associated with greater sensorimotor impairment. METHODS AND RESULTS: Cross-sectional T1-weighted magnetic resonance images of the brain were pooled from 357 participants with chronic stroke from 18 research cohorts of the ENIGMA (Enhancing NeuoImaging Genetics through Meta-Analysis) Stroke Recovery Working Group. Sensorimotor impairment was estimated from the FMA-UE (Fugl-Meyer Assessment of Upper Extremity). Robust mixed-effects linear models were used to test associations between poststroke sensorimotor impairment and hippocampal volumes (ipsilesional and contralesional separately; Bonferroni-corrected, P<0.025), controlling for age, sex, lesion volume, and lesioned hemisphere. In exploratory analyses, we tested for a sensorimotor impairment and sex interaction and relationships between lesion volume, sensorimotor damage, and hippocampal volume. Greater sensorimotor impairment was significantly associated with ipsilesional (P=0.005; β=0.16) but not contralesional (P=0.96; β=0.003) hippocampal volume, independent of lesion volume and other covariates (P=0.001; β=0.26). Women showed progressively worsening sensorimotor impairment with smaller ipsilesional (P=0.008; β=-0.26) and contralesional (P=0.006; β=-0.27) hippocampal volumes compared with men. Hippocampal volume was associated with lesion size (P<0.001; β=-0.21) and extent of sensorimotor damage (P=0.003; β=-0.15). CONCLUSIONS: The present study identifies novel associations between chronic poststroke sensorimotor impairment and ipsilesional hippocampal volume that are not caused by lesion size and may be stronger in women.