Alterations in Network Connectivity after Traumatic Brain Injury in Mice.

Abstract

Victims of mild traumatic brain injury (mTBI) usually do not display clear morphological brain defects, but frequently have long-lasting cognitive deficits, emotional difficulties, and behavioral disturbances. In the present study we used diffusion magnetic resonance imaging (dMRI) combined with graph theory measurements to investigate the effects of mTBI on brain network connectivity. We employed a non-invasive closed-head weight-drop mouse model to produce mTBI. Mice were scanned at two time points, 24 h before the injury and either 7 or 30 days following the injury. Connectivity matrices were computed for each animal at each time point, and these were subsequently used to extract graph theory measures reflecting network integration and segregation, on both the global (i.e., whole brain) and local (i.e., single regions) levels. We found that cluster coefficient, reflecting network segregation, decreased 7 days post-injury and then returned to baseline level 30 days following the injury. Global efficiency, reflecting network integration, demonstrated opposite patterns in the left and right hemispheres, with an increase of right hemisphere efficiency at 7 days and then a decrease in efficiency following 30 days, and vice versa in the left hemisphere. These findings suggest a possible compensation mechanism acting to moderate the influence of mTBI on the global network. Moreover, these results highlight the importance of tracking the dynamic changes in mTBI over time, and the potential of structural connectivity as a promising approach for studying network integrity and pathology progression in mTBI.