Abstracts

Rationale: Studies suggest that frequency of interictal spiking may be correlated with an increase of cognitive and memory deficits in individuals with temporal lobe epilepsy (TLE). Traumatic brain injury (TBI) significantly increases the risk of TLE development, however it is not established if rate of interictal spiking predicts cognitive performance following TBI. Furthermore, the severity of injury may play a role in modulating spiking properties such as density, width and amplitude, as well as power within standard frequency bands. Using care to determine an accurate electrographic baseline across inherently variable EEG records, we examined spiking and frequency patterns in an animal model of TBI using two different severities of injury and their association with memory and motor deficits. Methods: Adult mice were subjected to Controlled Cortical Impact (CCI), producing either moderate (CCI-M; 1 mm depth, 3.5 m/sec velocity, 400 msec duration) or severe (CCI-S; 2 mm depth, 5 m/sec velocity, 199 msec duration) brain injury. These animals, including uninjured shams, were implanted with cortical electrodes at 7 weeks post-injury, and EEG and video were recorded for 5-6 weeks. Using LabChart Pro v.7.3.7, interictal spike density analysis was performed at 11 weeks post-CCI. Resulting data from EEG analysis was compared to performance on behavioral Novel Object Recognition (NOR) and Rotarod experiments to examine potential associations. Results: Interictal spike density is significantly higher (ANOVA p < 0.001) in CCI-S mice (2601 ± 498 spikes/day) compared to sham controls (1403 ± 145 spikes/day) and not statistically different between sham and CCI-M mice (2087 ± 333 spikes/day), nor different between CCI groups. Memory performance on NOR testing was also not different between sham control and CCI-M animals, while CCI-S mice showed significant impairment of memory performance compared to controls (ANOVA; p=0.015). Similarly, vestibulomotor performance on Rotarod testing was not different between sham control and CCI-M animals, while CCI-S mice showed significant impairment of memory performance compared to both controls and CCI-M mice (ANOVA; p<0.001). Conclusions: Preliminary results suggest that at the level of group analysis, interictal spike density does correlate with degree of memory and motor deficits in mice following CCI of differing severity, with CCI-S mice demonstrating both the highest interictal spike density as well as the most severe impairments in memory and motor performance. Further studies will be required to determine if interictal spike density, and/or other characteristics of the interictal EEG, might be useful biomarkers to prospectively predict behavioral performance after TBI. Studies were supported by a DOD grant W81XWH-11-1-0501