Mapping the functional connectome in traumatic brain injury: What can graph metrics tell us?

Objective: Traumatic brain injury (TBI) is associated with cognitive and motor deficits, and poses a significant personal, societal, and economic burden. One mechanism by which TBI is thought to affect cognition and behavior is through changes in functional connectivity. Graph theory is a powerful framework for quantifying topological features of neuroimaging-derived functional networks. The objective of this paper is to review studies examining functional connectivity in TBI with an emphasis on graph theoretical analysis that is proving to be valuable in uncovering network abnormalities in this condition. Methods: We review studies that have examined TBI-related alterations in different properties of the functional brain network, including global integration, segregation, centrality and resilience. We focus on functional data using task-related fMRI or resting-state fMRI in patients with TBI of different severity and recovery phase, and consider how graph metrics may inform rehabilitation and enhance efficacy. Moreover, we outline some methodological challenges associated with the examination of functional connectivity in patients with brain injury, including the sample size, parcellation scheme used, node definition and subgroup analyses. Results: The findings suggest that TBI is associated with hyperconnectivity and a suboptimal global integration, characterized by increased connectivity degree and strength and reduced efficiency of functional networks. This altered functional connectivity, also evident in other clinical populations, is attributable to diffuse white matter pathology and reductions in gray and white matter volume. These functional alterations are implicated in post-concussional symptoms, posttraumatic stress and neurocognitive dysfunction after TBI. Finally, the effects of focal lesions have been found to depend critically on topological position and their role in the network. Conclusion: Graph theory is a unique and powerful tool for exploring functional connectivity in brain-injured patients. One limitation is that its results do not provide specific measures about the biophysical mechanism underlying TBI. Continued work in this field will hopefully see graph metrics used as biomarkers to provide more accurate diagnosis and help guide treatment at the individual patient level.