Investigating the effects of subconcussion on functional connectivity using mass-univariate and multivariate approaches

There are concerns about the effects of subconcussive head impacts in sport, but the effects of subconcussion on brain connectivity are not well understood. We hypothesized that college football players experience changes in brain functional connectivity not found in athletes competing in lower impact sports or healthy controls. These changes may be spatially heterogeneous across participants, requiring analysis methods that go beyond mass-univariate approaches commonly used in functional MRI (fMRI). To test this hypothesis, we analyzed resting-state fMRI data from college football (n=15), soccer (n=12), and lacrosse players (n=16), and controls (n=29) collected at preseason and postseason time points. Regional homogeneity (ReHo) and degree centrality (DC) were calculated as measures of local and long-range functional connectivity, respectively. Standard voxel-wise analysis and paired support vector machine (SVM) classification studied subconcussion's effects on local and global functional connectivity. Voxel-wise analyses yielded minimal findings, but SVM classification had high accuracy for college football's ReHo (87%, p=0.009) and no other group. The findings suggest subconcussion results in spatially heterogeneous changes in local functional connectivity that may only be detectible with multivariate analyses. To determine if voxel-wise and SVM analyses had similar spatial patterns, region-average t-statistic and SVM weight values were compared using a measure of ranking distance. T-statistic and SVM weight rankings exhibited significantly low ranking distance values for all groups and metrics, demonstrating that the analyses converged on a similar underlying effect. Overall, this research suggests that subconcussion in football may produce local functional connectivity changes similar to concussion.