Abstracts

Rationale: Coupling of gamma events recorded between different brain areas is a measure of functional connectivity between brain areas via interneuronal networks. Epileptic activity may cause alterations of local and distant gamma event functional connectivity within neuronal circuits. The goal of these experiments is to investigate the long-term changes of coupling of local field potentials (LFP) in the frequency band 30-55Hz after kainic acid (KA) injection in rats that later develop and do not develop epilepsy. Methods: Experiments were conducted on adult male Sprague-Dawley rats. 16 tungsten microelectrodes (50 um O/D) and screw electrodes were implanted 1 week in symmetrical sites of prefrontal cortex, motor cortex, hippocampus and thalamus. KA was injected either in the left anterior hippocampus (group 1) or left neocortex (group 2). Two-month continuous EEG recordings were performed with sampling frequencies from 1k to 10k Hz. Maxima for gamma activity waves were detected and Shannon entropy was applied to determine the functional connectivity between different brain regions as peri-event histograms for each pair of channels. Connectivity index (CI) represented by normalized Shannon entropy values between areas of interest, was then compared to distinguish the connectivity differences between rats that developed seizures within two months after brain lesioning, and rats that did not. Results: Long-term continuous decrease of averaged gamma event couplings were observed in both groups after KA injection. Specifically, rats without seizure showed a decreased CI between the peri-lesion site and the left prefrontal cortex and the right thalamus, and an increased CI between the peri-lesion site and right prefrontal cortex, right hippocampus and left thalamus. Rats with seizures showed a decreased CI between the lesion site and most of the ipsilateral regions, and an increase CI between the lesion site and contralateral regions. Overall, rats without seizures formed a balanced gamma event coupling strength between the left and right sides of the brain, and rats with seizures developed an unbalanced shift of gamma event coupling strength to the side opposite the lesion. Conclusions: We observed a difference in spatial patterns of gamma event functional connectivity in rats that developed and did not develop epilepsy after KA status epilepticus. The rats that developed epilepsy had unbalanced gamma event coupling suggesting improper synaptic reorganization after the brain lesion. Funding: NIH grant, NS065877 NIH grant, NS033310