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Neuroimage Clin. 2019 Jul 19;24:101947. doi: 10.1016/j.nicl.2019.101947. [Epub ahead of print]

The impact of ischemic stroke on connectivity gradients.

Author information

1
Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; Department of Cognitive Neurology, University Hospital Leipzig and Faculty of Medicine, University of Leipzig, Leipzig, Germany.
2
Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, Berlin, Germany; Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany.
3
Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, Berlin, Germany.
4
Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; Department of Cognitive Neurology, University Hospital Leipzig and Faculty of Medicine, University of Leipzig, Leipzig, Germany; Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, Berlin, Germany; Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany.
5
Centre National de la Recherche Scientifique (CNRS) UMR 7225, Frontlab, Institut du Cerveau et de la Moelle épinière, Paris, France. Electronic address: daniel.margulies@icm-institute.org.
6
Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany; Department of Neurology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Berlin, Germany. Electronic address: ovadia@cbs.mpg.de.

Abstract

The functional organization of the brain can be represented as a low-dimensional space that reflects its macroscale hierarchy. The dimensions of this space, described as connectivity gradients, capture the similarity of areas' connections along a continuous space. Studying how pathological perturbations with known effects on functional connectivity affect these connectivity gradients provides support for their biological relevance. Previous work has shown that localized lesions cause widespread functional connectivity alterations in structurally intact areas, affecting a network of interconnected regions. By using acute stroke as a model of the effects of focal lesions on the connectome, we apply the connectivity gradient framework to depict how functional reorganization occurs throughout the brain, unrestricted by traditional definitions of functional network boundaries. We define a three-dimensional connectivity space template based on functional connectivity data from healthy controls. By projecting lesion locations into this space, we demonstrate that ischemic strokes result in dimension-specific alterations in functional connectivity over the first week after symptom onset. Specifically, changes in functional connectivity were captured along connectivity Gradients 1 and 3. The degree of functional connectivity change was associated with the distance from the lesion along these connectivity gradients (a measure of functional similarity) regardless of the anatomical distance from the lesion. Together, these results provide support for the biological validity of connectivity gradients and suggest a novel framework to characterize connectivity alterations after stroke.

KEYWORDS:

Connectivity gradients; Connectome; Diaschisis; Diffusion embedding; Intrinsic functional connectivity; Resting-state fMRI

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