Abstracts

Previously we have shown that cortex (CTX) shows strong electrical association with anterior thalamus (AN) during the early portion of clonic seizures in the rat pentylenetetrazol (PTZ) model. EEG is not silent during the build-up to a seizure. Interchannel EEG bursting events occur which gradually increase to the climactic ictal event. During the actual pre-ictal build-up to a seizure, there are strong communication networks established early between cortical and thalamic channels. Pre-ictally we believe that AN has a larger mutual information (MI) with CTX than does posterior thalamus (PT), an unaffiliated nucleus. Modulation of this MI after ethosuximide (ESM) infusion is examined.
We implant cortical screws and unilateral AN, PT and hippocampal electrodes in N=9 (5 experimental; 4 control) rats. In day 2 field potential baseline recordings are made after jugular catheterization. Prior to PTZ infusion, a 100 mg/kg bolus dose of iv ESM is given. After 15 min, the slow PTZ infusion (5.5 mg/kg/min) begins and we see a steady growth of bursting events. MI processing is done through the method of adaptive partitioning. Our MI measurement utilize a frequency band from 0 to 30 Hz with 1 min sections overlapping by 50%. We wish to evaluate AN vs. PT thalamocortical channel MI differences during the 6 min pre-ictal period and the subsequent ictus.
Average time-to-clonic for controls is 12.5 ([plusmn]2.34 SD) min vs 23.5 ([plusmn]10.4) min for ESM animals (p[le]0.04). During the pre-clonic phase, MI between AN-CTX was markedly enhanced by prior administration of ESM. During the pre-ictal period using multi-variate ANOVA, we see a significant increase in CTX-AN MI due to the treatment effect of the administration of ESM (p[le]0.05). ESM exacerbates the difference between CTX-AN and CTX-PT MI, i.e. accentuates AN-CTX and diminishes CTX-PT interaction during the pre-ictal state. Consideration of results within the ESM group showed (from paired-sample T-tests) that CTX-AN MI is larger than CTX-PT MI pre-ictally (p[le]0.02). During the clonic seizure CTX-AN MI is larger than CTX-PT MI (p[le]0.02) without any significant ESM effect.
ESM enhances thalamocortical communication between AN, a chief epileptic network gating center and CTX. ESM maintains the animal in an extended [ldquo]threshold state[rdquo] before the ultimate seizure arises from accumulating PTZ. During this time it effectively helps to electrically highlight AN[apos]s selective interaction with CTX. ESM affects differential MI only during the pre-ictal state and does not extend to the clonic seizure. This is an excellent example of how field potential thalamocortical communication between sites is not purely localized in time to seizure events, but extends to information exchange between AN and CTX during the preparatory bursting events prior to a seizure. MI may be a key seizure indicator when AEDs fail and a seizure occurs.
[Supported by: NIH NS35528 [amp] EFA Health Sciences Student Fellowship]