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.
Highlights
The assessment of functional connectivity based on the temporal correlation of ongoing blood-oxygen-level-dependent (BOLD) fluctuations has transformed our understanding of the brain's reorganization and recovery after injury (Carter et al, 2012; Fornito and Bullmore, 2010, 2015; Fox, 2010; Gillebert and Mantini, 2013; Zhang and Raichle, 2010)
Based on previous findings in discrete networks (Baldassarre et al, 2014; Carter et al, 2010; He et al, 2007; Nomura et al, 2010; OvadiaCaro et al, 2013; Siegel et al, 2016a, 2016b; Wang et al, 2010; Warren et al, 2009) and computational models (Alstott et al, 2009; Honey and Sporns, 2008; van Dellen et al, 2013; Young et al, 2000), we hypothesized that a lesion in continuous connectivity space would induce a gradual impact on the whole connectome and that this would be most pronounced in areas that share a similar functional connectivity pattern with the lesion
Two analyses were performed using the clinical scores data; an analysis testing for the link between changes in functional connectivity and changes in clinical scores, and an analysis to test whether individual differences between distance-to-lesion and changes in functional connectivity over time along individual gradients are associated with clinical status at admission and discharge separately
Summary
The assessment of functional connectivity based on the temporal correlation of ongoing blood-oxygen-level-dependent (BOLD) fluctuations (resting-state functional magnetic resonance imaging; rs-fMRI) has transformed our understanding of the brain's reorganization and recovery after injury (Carter et al, 2012; Fornito and Bullmore, 2010, 2015; Fox, 2010; Gillebert and Mantini, 2013; Zhang and Raichle, 2010). Based on previous findings in discrete networks (Baldassarre et al, 2014; Carter et al, 2010; He et al, 2007; Nomura et al, 2010; OvadiaCaro et al, 2013; Siegel et al, 2016a, 2016b; Wang et al, 2010; Warren et al, 2009) and computational models (Alstott et al, 2009; Honey and Sporns, 2008; van Dellen et al, 2013; Young et al, 2000), we hypothesized that a lesion in continuous connectivity space would induce a gradual impact on the whole connectome and that this would be most pronounced in areas that share a similar functional connectivity pattern with the lesion
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