Network Excitability in Human Mesial Temporal Lobe Epilepsy

presentation, poster

English

Objective: Seizures are a consequence of abnormal brain network excitability. Two fundamental electrophysiologic biomarkers of epilepsy and network excitability, interictal epileptiform spikes (IES) and seizures, show circadian patterns supporting behavioral state modulation of brain excitability. The circadian patterns of seizures and IES in mesial temporal lobe epilepsy (mTLE), however, differ as seizures show daytime peaks and IES show nocturnal peaks in occurrence. Methods: We investigated this paradox in mTLE brain excitability using a chronically implanted device enabling continuous intracranial EEG (iEEG), wireless data streaming, and electrical stimulation in four patients with electrodes targeting two key mTLE network nodes, the hippocampus (Hc) and anterior nucleus of the thalamus (ANT). Automated sleep staging, IES rates, and seizure detection iEEG classifiers provided dense behavioral state and brain excitability tracking. The Hc evoked responses to continuous ANT electrical stimulation were used to track ANT-Hc network excitability over multiple months in ambulatory subjects living in their natural environments. Results: Consistent with prior literature, seizure probability was highest during the day and average IES rates were highest at night. In particular, seizures had a daytime bimodal peak, increased in the morning and evening whereas IES had a unimodal nocturnal peak during non-REM slow wave sleep. Using continuous behavioral state, IES, seizure, and ANT-Hc evoked potential tracking, we show that mTLE seizures are increased in wakefulness, while IES are increased in slow-wave sleep. Tracking ANT-Hc evoked potentials we show that the ANT-Hc evoked responses have shorter latency in wakefulness relative to slow wave sleep, suggesting that limbic network excitability and connectivity are reduced in slow-wave sleep. Conclusion: We hypothesize that increased local Hc excitability in slow-wave sleep, as demonstrated by increased spike rates, is not associated with increased seizure probability due to reduced long-range limbic (ANT-Hc) effective connectivity. This reduced limbic effective connectivity in slow wave sleep may suppress the broader network activation required for initiation and propagation of mTLE seizures. These results help clarify a standing paradox of Hc excitability and seizure occurrence in mTLE and provide insights to the mechanism of therapeutic electrical brain stimulation. Furthermore, the ability to effectively track brain network connectivity and excitability in behaving humans may prove useful for adaptive electrical brain stimulation to improve electrical brain stimulation efficacy.

epilepsy; evoked response potential; excitability; behavioral state; sleep; non-REM

KŘEMEN, V.; GREGG, N.; SLADKÝ, V.; MÍVALT, F.; BALZEKAS, I.; MARKS, V.; LUNDSTROM, B.; NEJEDLÝ, P.; ATTIA, T.; CREPEAU, D.; ST LOUIS, E.; HERMES, D.; MESSINA, S.; DENISON, T.; MILLER, K.; VAN GOMPEL, J.; BRINKMANN, B.; WORRELL, G.

8. 11. 2021

Society for Neuroscience

Chicago, USA