The relevance of rich club regions for functional outcome post-stroke is enhanced in women
Authors
Anna K. Bonkhoff, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Markus D. Schirmer, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Martin Bretzner, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Sungmin Hong, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Robert W. Regenhardt, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Kathleen L. Donahue, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Marco J. Nardin, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Adrian V. Dalca, Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, Boston, Massachusetts, USA.
Anne-Katrin Giese, Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Mark R. Etherton, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Brandon L. Hancock, Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
Steven J. Mocking, Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
Elissa C. McIntosh, Department of Psychiatry, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
John Attia, Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
John W. Cole, Department of Neurology, University of Maryland School of Medicine and Veterans Affairs Maryland Health Care System, Baltimore, Maryland, USA.
Amanda Donatti, School of Medical Sciences, University of Campinas (UNICAMP) and the Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, Brazil.
Christoph J. Griessenauer, Department of Neurosurgery, Geisinger, Danville, Pennsylvania, USA.
Laura Heitsch, Department of Emergency Medicine, Washington University School of Medicine, St Louis, Missouri, USA.
Lukas Holmegaard, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Katarina Jood, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Jordi Jimenez-Conde, Department of Neurology, Neurovascular Research Group (NEUVAS), IMIM-Hospital del Mar (Institut Hospital del Mar d'Investigacions Mèdiques). Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra, Barcelona, Spain.
Steven J. Kittner, Department of Neurology, University of Maryland School of Medicine and Veterans Affairs Maryland Health Care System, Baltimore, Maryland, USA.
Robin Lemmens, Department of Neurosciences, KU Leuven - University of Leuven, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), Leuven, Belgium.
Christopher R. Levi, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.
Caitrin W. McDonough, Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, Florida, USA.
James F. Meschia, Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA.
Chia-Ling Phuah, Department of Neurology, Washington University School of Medicine & Barnes-Jewish Hospital, St Louis, Missouri, USA.
Stefan Ropele, Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Graz, Austria.
Jonathan Rosand, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Jaume Roquer, Department of Neurology, Neurovascular Research Group (NEUVAS), IMIM-Hospital del Mar (Institut Hospital del Mar d'Investigacions Mèdiques). Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra, Barcelona, Spain.
Tatjana Rundek, Department of Neurology and Evelyn F. McKnight Brain Institute, Miller School of Medicine, University of Miami, Miami, Florida, USA.
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.
Medical Subject Headings
Female; Humans; Male; Middle Aged; Bayes Theorem; Brain; Ischemic Stroke (diagnostic imaging, pathology); Models, Neurological; Stroke
Publication Date
3-1-2023
Publication Title
Human brain mapping
Digital Object Identifier (DOI)
10.1002/hbm.26159
Recommended Citation
Bonkhoff, Anna K.; Schirmer, Markus D.; Bretzner, Martin; Hong, Sungmin; Regenhardt, Robert W.; Donahue, Kathleen L.; Nardin, Marco J.; Dalca, Adrian V.; Giese, Anne-Katrin; Etherton, Mark R.; Hancock, Brandon L.; Mocking, Steven J.; McIntosh, Elissa C.; Attia, John; Cole, John W.; Donatti, Amanda; Griessenauer, Christoph J.; Heitsch, Laura; Holmegaard, Lukas; Jood, Katarina; Jimenez-Conde, Jordi; Kittner, Steven J.; Lemmens, Robin; Levi, Christopher R.; McDonough, Caitrin W.; Meschia, James F.; Phuah, Chia-Ling; Ropele, Stefan; Rosand, Jonathan; Roquer, Jaume; and Rundek, Tatjana, "The relevance of rich club regions for functional outcome post-stroke is enhanced in women" (2023). Neurology. 1735.
https://scholar.barrowneuro.org/neurology/1735
