Abstracts

Rationale: Development of post-traumatic epilepsy (PTE) after traumatic brain injury (TBI) is a major health concern (5% to 50% of TBI cases). PTE is a long-term process spanning months to years after TBI. We thus postulated that quantitative analysis of continuous long-term EEG after TBI might shed light into the underlying mechanisms of PTE and epileptogenesis. Methods: Six male Sprague-Dawley rats, weighing approximately 375 grams each, were subjected to a controlled cortical impact (CCI). A 6mm piston was pneumatically driven into the right parietal (RP) cortex to a depth of 3mm with velocity of 5.5m/s. The rats were subsequently implanted with a total of six EEG electrodes in the left thalamus (LT), hippocampus (LH), parietal (LP) and frontal (LF) cortex, and right occipital (RO) and frontal (RF) cortex (no electrodes in the ipsilateral to the impact hippocampus and temporal cortex). Following a two week recovery period, long-term (14-week) continuous EEG recordings were conducted (L.P. filtered up to 40Hz). Using linear (coherence) and non-linear (Lyapunov exponents STLmax) measures of EEG dynamics, we studied the evolution over time (at a ten sec resolution) of the global as well as the local functional connectivity between brain sites. Results: Four of the six TBI-induced rats developed PTE six to ten weeks after the initial insult to the brain. Analysis of the continuous EEG from these rats showed a gradual increase of the functional connectivity between critical brain sites in terms of their EEG dynamics, starting at least two weeks prior to their first spontaneous seizure and in some cases continuing long thereafter. In contrast, such an increase was not observed for the rats that did not develop epilepsy. The linear measure (coherence) provided evidence of an increased level of connectivity between the site closest to the impact (RO) and three distant brain sites (RF, LF, LP). These changes were observed mostly in the alpha, beta and gamma EEG frequency bands. The non-linear measure (STLmax entrainment) provided evidence of an increased level of connectivity over weeks similarly between RO and the contralateral frontal and parietal cortices. In addition, STLmax suggested an increase in functional connectivity between RO and the contralateral hippocampus. Consistent behavior of functional connectivity changes between brain sites and the "focus" (site of impact) over time was demonstrated for coherence in one out of the four epileptic and in both non-epileptic rats, while for STLmax in three out of the four epileptic and in both non-epileptic rats. Conclusions: Our preliminary results strongly support a network pathology in TBI that worsens with time. In rats that eventually developed PTE, long-term trends of increasing functional connectivity between the impaired cortex and the rest of the brain, both prior to and after the first spontaneous seizure, were observed. In those rats that did not develop PTE, no such increase was found. This research is supported by Department of Defense (DOD) PH/TBI Research Program, Office of Congressionally Directed Medical Research Programs (CDMRP) grant PT090712.