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

## TL;DR

This study explores how traumatic brain injury alters brain network structures and may lead to epilepsy, using an animal model and gamma-band EEG data.

## Contribution

The paper introduces a novel computational normalization method for network cost and identifies gamma-band network reorganization in TBI for the first time.

## Key findings

- TBI alters small-world propensity and rich-club structure in gamma-band functional networks.
- Post-injury hyperexcitability is observed as increased cortical sound-evoked response amplitudes.
- Altered network topology is linked to potential mechanisms of posttraumatic epilepsy.

## 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.

Traumatic brain injury (TBI) is a prevalent neurological disorder caused by factors such as accidents, contact sports, or military conflict. While animal studies have provided detailed insights into the molecular and cellular mechanisms underlying TBI, and clinical research has revealed its effects on large-scale brain network organization, these findings often lack integration. Our research seeks to address this gap by examining large-scale brain activity in an animal model of TBI. By analyzing brain network structures, we identify reorganization, highlighting novel connections to weight gain and posttraumatic epilepsy. Further exploration using this model may deepen our understanding of cross-scale mechanisms and inform the development of therapeutic interventions.