Longitudinal increases in structural connectome segregation and functional connectome integration are associated with better recovery after mild TBI

Traumatic brain injury damages white matter pathways that connect brain regions, disrupting transmission of electrochemical signals and causing cognitive and emotional dysfunction. Connectome-level mechanisms for how the brain compensates for injury have not been fully characterized. Here, we collected serial MRI-based structural and functional connectome metrics and neuropsychological scores in 26 mild traumatic brain injury subjects (29.4{+/-}8.0 years, 20 male) at 1 and 6 months post-injury. We quantified the relationship between functional and structural connectomes using network diffusion model propagation time, a measure that can be interpreted as how much of the structural connectome is being utilized for the spread of functional activation, as captured via the functional connectome. Overall cognition showed significant improvement from 1 to 6 months (t25=-2.15, p=0.04). None of the structural or functional global connectome metrics were significantly different between 1 and 6 months, or when compared to 34 age- and gender-matched controls (28.6{+/-}8.8 years, 25 male). We predicted longitudinal changes in overall cognition from changes in global connectome measures using a partial least squares regression model (cross-validated R2 = 0.27). We observe that increased network diffusion model propagation time, increased structural connectome segregation and increased functional connectome integration were related to better cognitive recovery. We interpret these findings as suggesting two connectome-based post-injury recovery mechanisms: one of neuroplasticity that increases functional connectome integration and one of remote white matter degeneration that increases structural connectome segregation. We hypothesize that our inherently multi-modal measure of network diffusion model propagation time captures the interplay between these two mechanisms.\n\nAbbreviationsmild traumatic brain injury (mTBI), structural connectome (SC), functional connectome (FC), network diffusion (ND), functional MRI (fMRI), diffusion MRI (dMRI), principal component analysis (PCA), partial least squares regression (PLSR), confidence interval (CI), Attention Network Test (ANT), California Verbal Learning Test II (CVLT-II), Coma Recovery Scale - Revised (CRS-R)