Alterations in topology, cost, and dynamics of gamma-band EEG functional networks in a preclinical model of traumatic brain injury.

Abstract

Traumatic brain injury (TBI) is a major cause of disability leading to multiple sequelae in cognitive, sensory, and physical domains, including posttraumatic epilepsy. Despite extensive research, our understanding of its impact on macroscopic brain circuitry remains incomplete. We analyzed electrophysiological functional connectomes in the gamma band from an animal model of blast-induced TBI over multiple time points after injury. We revealed differences in small-world propensity and rich-club structure compared with age-matched controls, indicating functional reorganization following injury. We further investigated cost-efficiency trade-offs, propose a computationally efficient normalization procedure for quantifying the cost of spatially embedded networks that controls for connectivity strength differences, and observed dynamic changes across the injury timeline. To explore potential links between altered network topology and epileptic activity, we employed a brain-wide computational model of seizure dynamics and attribute brain reorganization to a homeostatic mechanism of activity regulation with the potential unintended consequence of driving generalized seizures. Finally, we demonstrated post-injury hyperexcitability that manifests as an increase in sound-evoked response amplitudes at the cortical level. Our work characterizes, for the first time, gamma-band functional network reorganization in a model of brain injury and proposes potential causes of these changes, thus identifying targets for future therapeutic interventions.