An interdisciplinary computational model for predicting traumatic brain injury: Linking biomechanics and functional neural networks.

The brain is a complex network consisting of neuron cell bodies in the gray matter and their axonal projections, forming the white matter tracts. These neurons are supported by an equally complex vascular network as well as glial cells. Traumatic brain injury (TBI) can lead to the disruption of the structural and functional brain networks due to disruption of both neuronal cell bodies in the gray matter as well as their projections and supporting cells. To explore how an impact can alter the function of brain networks, we integrated a finite element (FE) brain mechanics model with linked models of brain dynamics (Kuramoto oscillator) and vascular perfusion (Balloon-Windkessel) in this study. We used empirical resting-state functional magnetic resonance imaging (MRI) data to optimize the fit of our brain dynamics and perfusion models to clinical data. Results from the FE model were used to mimic injury in these optimized brain dynamics models: injury to the nodes (gray matter) led to a decrease in the nodal oscillation frequency, while damage to the edges (axonal connections/white matter) progressively decreased coupling among connected nodes. A total of 53 cases, including 33 non-injurious and 20 concussive head impacts experienced by professional American football players were simulated using this integrated model. We examined the correlation of injury outcomes with global measures of structural connectivity, neural dynamics, and functional connectivity of the brain networks when using different lesion methods. Results show that injurious head impacts cause significant alterations in global network topology regardless of lesion methods. Changes between the disrupted and healthy functional connectivity (measured by Pearson correlation) consistently correlated well with injury outcomes (AUC≥0.75), although the predictive performance is not significantly different (p>0.05) to that of traditional kinematic measures (angular acceleration). Intriguingly, our lesion model for gray matter damage predicted increases in global efficiency and clustering coefficient with increases in injury risk, while disrupting axonal connections led to lower network efficiency and clustering. When both injury mechanisms were combined into a single injury prediction model, the injury prediction performance depended on the thresholds used to determine neurodegeneration and mechanical tolerance for axonal injury. Together, these results point towards complex effects of mechanical trauma to the brain and provide a new framework for understanding brain injury at a causal mechanistic level and developing more effective diagnostic methods and therapeutic interventions.