Background/Purpose: The purpose of this study was (1) to identify changes in structural connectivity after stroke and (2) to relate changes in indirect connectivity to post-stroke impairment. Methods: A novel measure of indirect connectivity was implemented to assess the impact of stroke on brain connectivity. Probabilistic tractography was performed on 13 chronic stroke and 16 control participants to estimate connectivity between gray matter (GM) regions. The Fugl-Meyer assessment of motor impairment was measured for stroke participants. Network measures of direct and indirect connectivity were calculated, and these measures were linearly combined with measures of white matter integrity to predict motor impairment. Results: We found significantly reduced indirect connectivity in the frontal and parietal lobes, ipsilesional subcortical regions, and bilateral cerebellum after stroke. When added to the regression analysis, the volume of GM with reduced indirect connectivity significantly improved the correlation between image parameters and upper extremity motor impairment (R2 = 0.71, p < 0.05). Conclusion: This study provides evidence of changes in indirect connectivity in regions remote from the lesion, particularly in the cerebellum and regions in the fronto-parietal cortices, and these changes correlate with upper extremity motor impairment. These results highlight the value of using measures of indirect connectivity to identify the effect of stroke on brain networks. Impact statement Changes in indirect structural connectivity occur in regions distant from a lesion after stroke, highlighting the impact that stroke has on brain functional networks. Specifically, losses in indirect structural connectivity occur in hubs with high centrality, including the fronto-parietal cortices and cerebellum. These losses in indirect connectivity more accurately reflect motor impairments than measures of direct structural connectivity. As a consequence, indirect structural connectivity appears to be important to recovery after stroke and imaging biomarkers that incorporate indirect structural connectivity might improve prognostication of stroke outcomes.
Keywords: diffusion imaging; indirect connectivity; stroke; structural connectivity; tractography; whole brain.