Different Trajectories of Functional Connectivity Captured with Gamma-Event Coupling and Broadband Measures of Electroencephalographic in the Rat Fluid Percussion Injury Model

Functional connectivity (FC) after traumatic brain injury (TBI) is affected by an altered excitatory-inhibitory balance due to neuronal dysfunction, and the mechanistic changes observed could be reflected differently by contrasting methods. Local gamma event coupling FC (GEC-FC) is believed to represent multiunit fluctuations due to inhibitory dysfunction, and we hypothesized that FC derived from widespread, broadband amplitude signal (BBA-FC) would be different, reflecting broader mechanisms of functional disconnection. We tested this during sleep and active periods defined by high delta and theta electroencephalographic activity, respectively, at 1, 7, and 28 d after rat fluid-percussion-injury or sham injury (n = 6/group) using 10 indwelling, bilateral cortical, and hippocampal electrodes. We also measured seizure and high-frequency oscillatory activity (HFOs) as markers of electrophysiological burden. BBA-FC analysis showed early hyperconnectivity constrained to ipsilateral sensory-cortex-to-CA1-hippocampus that transformed to mainly ipsilateral FC deficits by 28 d compared with shams. These changes were conserved over active epochs, except at 28 d when there were no differences to shams. In comparison, GEC-FC analysis showed large regions of hyperconnectivity early after injury within similar ipsilateral and intra-hemispheric networks. GEC-FC weakened with time, but hyperconnectivity persisted at 28 d compared with sham. Edge and global connectivity measures revealed injury-related differences across time in GEC-FC as compared with BBA-FC, demonstrating greater sensitivity to FC changes post-injury. There was no significant association between sleep fragmentation, HFOs, or seizures with FC changes. The within-animal, spatial-temporal differences in BBA-FC and GEC-FC after injury may represent different mechanisms driving FC changes as a result of primary disconnection and interneuron loss.