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

Abstract

Traumatic brain injury is a major cause of disability leading to multiple sequelae in cognitive, sensory, and physical domains, including post-traumatic epilepsy. Despite extensive research, our understanding of its impact on macroscopic brain circuitry remains incomplete. We analyzed electrophysiological functional connectomes in the gamma band using a preclinical model of blast-induced traumatic brain injury over multiple time points after injury. We revealed differences in small-world propensity and rich-club structure compared to age-matched controls, indicating functional reorganization following injury. We further investigated cost-efficiency trade-offs, propose a computationally efficient normalization procedure for quantifying cost of spatially embedded networks that controls for connectivity strength differences, and suggest metabolic drivers as a candidate for the observed differences. Furthermore, 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.