Circadian Rhythms of Human Brain - Electrical Impedance

presentation, poster

English

Rationale: Long-term data collection using implantable neural sense and stimulation (INSS) devices in patients with epilepsy enables investigation of ultradian, circadian and infradian rhythms in sleep, seizures, interictal epileptiform discharges (IED), and brain impedance. It has long been recognized that IED and seizures have circadian patterns. Recent studies also highlight the importance of circadian changes in brain extracellular space, and the functional role of slow-wave sleep and the associated increase in extracellular space volume that is hypothesized to provide improved metabolite and protein clearance. The direct evidence for increased extracellular space volume during sleep primarily comes from rodent studies, and a few human imaging studies with limited temporal sampling. Here we investigate a potential surrogate of extracellular volume, the brain electrical impedance in hippocampus (HPC) and anterior nucleus of thalamus (ANT) over multiple months in four ambulatory humans with drug resistant epilepsy. Methods: We collected several months of continuous iEEG and impedance measurements from each of 4 patients with drug resistant epilepsy implanted with an investigational INSS and living in their normal home environments. Continuous iEEG was used to precisely assess sleep states using machine learning algorithms. Impedance was measured in 15-minute intervals in bilateral ANT and HPC to analyze the relationship between sleep states and impedance cycles (Pearson’s Correlation Coefficient and Mann-Whitney U test) using 31 days and nights of data. Results: The ANT and HPC electrical impedance followed a distinct circadian rhythm with period ranging between 23.36 and 24.81 hours. We observed a phase shift in the maximum and minimum between ANT and HPC impedance with Pearson’s Correlation Coefficient of 0.604 (p < .001), while the left and right HPC shows a high correlation 0.700 (p < .001) without any phase shift. Moreover, impedances of both HPC and ANT shows a distinct correlation with sleep (0.504 and 0.507 both p < .001) with the average absolute impedance change, across all measured leads, between wake and sleep 26.3 ± 13.2 Ω (p < .001). Conclusion: We show human brain impedance cycles with a circadian rhythm that varies across different behavioral states and brain locations. Further research of this phenomena and the relationship of impedance to sleep, seizures, epileptiform interictal discharges may prove useful for understanding the role of the extracellular space in seizure generation in temporal lobe epilepsy.

brain; epilepsy; implantable neural stimulator; impedance; extracellular environment

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

8. 11. 2021

Society for Neuroscience

Chicago, USA