Callosal dysfunction explains injury sequelae in a computational network model of axonal injury.

Mild traumatic brain injury (mTBI) often results in neurobehavioral aberrations such as impaired attention and increased reaction time. Diffusion imaging and postmortem analysis studies suggest that mTBI primarily affects myelinated axons in white matter tracts. In particular, corpus callosum, mediating interhemispheric information exchange, has been shown to be affected in mTBI. Yet little is known about the mechanisms linking the injury of myelinated callosal axons to the neurobehavioral sequelae of mTBI. To address this issue, we devised and studied a large, biologically plausible neuronal network model of cortical tissue. Importantly, the model architecture incorporated intra- and interhemispheric organization, including myelinated callosal axons and distance-dependent axonal conduction delays. In the resting state, the intact model network exhibited several salient features, including alpha-band (8-12 Hz) collective activity with low-frequency irregular spiking of individual neurons. The network model of callosal injury captured several clinical observations, including 1) "slowing down" of the network rhythms, manifested as an increased resting-state theta-to-alpha power ratio, 2) reduced response to attention-like network stimulation, manifested as a reduced spectral power of collective activity, and 3) increased population response time in response to stimulation. Importantly, these changes were positively correlated with injury severity, supporting proposals to use neurobehavioral indices as biomarkers for determining the severity of injury. Our modeling effort helps to understand the role played by the injury of callosal myelinated axons in defining the neurobehavioral sequelae of mTBI.