@article{1c4cf63be18541229b36323f2c955dc6,
title = "The relevance of rich club regions for functional outcome post-stroke is enhanced in women",
abstract = "This study aimed to investigate the influence of stroke lesions in predefined highly interconnected (rich-club) brain regions on functional outcome post-stroke, determine their spatial specificity and explore the effects of biological sex on their relevance. We analyzed MRI data recorded at index stroke and ~3-months modified Rankin Scale (mRS) data from patients with acute ischemic stroke enrolled in the multisite MRI-GENIE study. Spatially normalized structural stroke lesions were parcellated into 108 atlas-defined bilateral (sub)cortical brain regions. Unfavorable outcome (mRS > 2) was modeled in a Bayesian logistic regression framework. Effects of individual brain regions were captured as two compound effects for (i) six bilateral rich club and (ii) all further non-rich club regions. In spatial specificity analyses, we randomized the split into “rich club” and “non-rich club” regions and compared the effect of the actual rich club regions to the distribution of effects from 1000 combinations of six random regions. In sex-specific analyses, we introduced an additional hierarchical level in our model structure to compare male and female-specific rich club effects. A total of 822 patients (age: 64.7[15.0], 39% women) were analyzed. Rich club regions had substantial relevance in explaining unfavorable functional outcome (mean of posterior distribution: 0.08, area under the curve: 0.8). In particular, the rich club-combination had a higher relevance than 98.4% of random constellations. Rich club regions were substantially more important in explaining long-term outcome in women than in men. All in all, lesions in rich club regions were associated with increased odds of unfavorable outcome. These effects were spatially specific and more pronounced in women.",
keywords = "Bayesian hierarchical modeling, functional outcome, lesion-symptom mapping, rich club, sex differences",
author = "{The MRI-GENIE and GISCOME Investigators and the International Stroke Genetics Consortium} and Bonkhoff, {Anna K.} and Schirmer, {Markus D.} and Martin Bretzner and Sungmin Hong and Regenhardt, {Robert W.} and Donahue, {Kathleen L.} and Nardin, {Marco J.} and Dalca, {Adrian V.} and Giese, {Anne Katrin} and Etherton, {Mark R.} and Hancock, {Brandon L.} and Mocking, {Steven J.T.} and McIntosh, {Elissa C.} and John Attia and Cole, {John W.} and Amanda Donatti and Griessenauer, {Christoph J.} and Laura Heitsch and Lukas Holmegaard and Katarina Jood and Jordi Jimenez-Conde and Kittner, {Steven J.} and Robin Lemmens and Levi, {Christopher R.} and McDonough, {Caitrin W.} and Meschia, {James F.} and Phuah, {Chia Ling} and Stefan Ropele and Jonathan Rosand and Jaume Roquer and Tatjana Rundek and Sacco, {Ralph L.} and Reinhold Schmidt and Pankaj Sharma and Agnieszka Slowik and Alessandro Sousa and Stanne, {Tara M.} and Daniel Strbian and Turgut Tatlisumak and Vincent Thijs and Achala Vagal and Johan Wasselius and Daniel Woo and Ramin Zand and McArdle, {Patrick F.} and Worrall, {Bradford B.} and Christina Jern and Lindgren, {Arne G.} and Jane Maguire and Ona Wu and Rost, {Natalia S.}",
note = "Funding Information: A.K.B. is supported by a MGH ECOR Fund for Medical Discovery (FMD) Clinical Research Fellowship Award. M.B. acknowledges support from the Soci{\'e}t{\'e} Fran{\c c}aise de Neuroradiologie, Soci{\'e}t{\'e} Fran{\c c}aise de Radiologie, Fondation ISITE‐ULNE. A.V. is in part supported by NIH‐NINDS (R01 NS103824, RF1 NS117643, R01 NS100417, U01NS100699, U01NS110772). C.J. acknowledges support from the Swedish Research Council (2021‐01114), the Swedish state under the agreement between the Swedish government and the county councils, the “Avtal om L{\"a}karutbildning och Medicinsk Forskning” (ALF) agreement (ALFGBG‐965328); the Swedish Heart and Lung Foundation (20190203). A.G.L. is funded by: The Swedish Research Council (2019‐01757), The Swedish Government (under the “Avtal om L{\"a}karutbildning och Medicinsk Forskning, ALF”), The Swedish Heart and Lung Foundation, The Swedish Stroke Association, Region Sk{\aa}ne, Lund University, Sk{\aa}ne University Hospital, Sparbanksstiftelsen F{\"a}rs och Frosta, Fremasons Lodge of Instruction Eos in Lund. N.S.R. is in part supported by NIH‐NINDS (R01NS082285, R01NS086905, U19NS115388). Funding Information: M.E. has received personal fees for consulting from Astra Zeneca and WorldCare Clinical Group. C.G. has received consulting honoraria from Microvention and Strykere and research funding from Medtronic and Penumbra. A.V. has received research funding from Cerenovus. A.G.L. reports personal fees from Bayer, NovoNordisk, Astra Zeneca, and BMS Pfizer outside this work. T.T. has served/serves on scientific advisory boards for Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Inventiva, Portola Pharm, and PHRI; has/has had research contracts with Bayer, Boehringer Ingelheim, and Bristol Myers Squibb. N.S.R. has received compensation as scientific advisory consultant from Omniox, Sanofi Genzyme and AbbVie Inc. Funding Information: MGH ECOR Fund for Medical Discovery (FMD) Clinical Research Fellowship; NIH‐NINDS, Grant/Award Numbers: R01NS082285, R01NS086905, U19NS115388; Soci{\'e}t{\'e} Fran{\c c}aise de Neuroradiologie, Soci{\'e}t{\'e} Fran{\c c}aise de Radiologie, Fondation ISITE‐ULNE; Swedish Research Council, Grant/Award Numbers: 2019‐01757, 2021‐01114; Swedish Heart and Lung Foundation, Grant/Award Number: 20190203; The Swedish Government; The Swedish Heart and Lung Foundation; Swedish Stroke Association Funding information Publisher Copyright: {\textcopyright} 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.",
year = "2023",
month = mar,
doi = "10.1002/hbm.26159",
language = "English",
volume = "44",
pages = "1579--1592",
journal = "Human Brain Mapping",
issn = "1065-9471",
number = "4",
}