Abstracts

Evidence has shown that anti-epileptic drugs (AEDs) can distinctively alter EEG rhythms and neuronal bursting in thalamocortical networks. We will show that anterior thalamus (AN) to cortex coherence is changed by ethosuximide (ESM) treatment prior to pentylenetetrazol (PTZ) seizures in rats. Coherence modulation is due to alpha wave generation in the cortex. Novel alpha wave production occurs locally without a concomitant presence thalamically. Prior work demonstrated the selective involvement of AN over the posterior thalamus (PT) in PTZ seizures with partial coherence spectral methods. Eight SD rats (4 exp [amp] 4 cntrl) were used for this experiment. After surgery to implant screw electrodes in the cranium and bipolar depth electrodes (AN and PT), rats are treated with an ESM bolus (100 mg/kg). Controls are given pure saline. After 15 minutes PTZ is infused at a rate of 5.5 mg/kg/min. Recording of field potenials/EEG is done through characteristic clonic [amp] tonic-clonic phases and digitized at 1000 Hz. A new method of coherence analysis is devised that is based on the cross-bispectrum. Only the first 8 seconds of the initial ictal episode was analyzed. This open-ended technique known as BISCOH (bispectrally-based coherence) helps isolate nonlinear frequency generation in the cortical endpoint in thalamocortical networks. Conventional coherence analysis does not distinguish between enhanced nonlinear behavior and other causes of lowered or dissociative connectivity. ESM causes a rise in seizure threshold (time-to-clonic: 738 vs 1219 s; p[lt]0.04). The growth in network coupling is evident particularly inside the alpha band frequency band. In the mid to high alpha rhythm there is a significant rise in AN-to-cortex BISCOH for ESM-treated animals. This suggests the presence of new alpha wave signaling in cortex. Simple t-tests show growth in AN to cortical BISCOH after ESM at 10 Hz: (0.579 vs 1.209; p[le]0.02) and 12 Hz: (0.63 vs 1.37; p[lt]0.007). MANOVA coupled with Bonferroni-Scheffe measures show differences at each frequency at the p[lt]0.05 level in AN. PT levels remain unchanged with the addition of the AED. AEDs can affect thalamocortical communication. Increases in EEG synchronization occur after AED treatment. Conventional coherence based on spectral measurements may register these changes as dissociative since they reflect harmonic generation at the cortical destination after propagation. Newer coherence measuring tools expand the notion of thalamocortical communication to include enhanced nonlinear coupling. Bispectral EEG methods remain useful tools for discriminating seizure states after AED treatment within specific functional epileptic networks. (Supported by NIH R01-NS35528 [amp] the Ganaway Fund.)