Abstracts

Decreased Thalamo-Hippocampal Functional Connectivity Underlies the Paradoxical Sleep-Wake Dependence of Interictal Epileptiform Discharges and Seizures

Abstract number : 3.446
Submission category : 3. Neurophysiology / 3G. Computational Analysis & Modeling of EEG
Year : 2023
Submission ID : 1431
Source : www.aesnet.org
Presentation date : 12/4/2023 12:00:00 AM
Published date :

Authors :
Presenting Author: Yurui Cao, BS – University of Illinois Urbana Champaign

Vaclav Kremen, PhD – Mayo Clinic; Krishnakant Saboo, PhD – University of Illinois Urbana Champaign; Filip Mivalt, MS – Mayo Clinic; Vladimir Sladky, MS – Mayo Clinic; Aisha Abdul Razaq, MD – Mayo Clinic; Jordan Bilderbeek, Student – University of Chicago; Jamie Van Gompel, MD – Mayo Clinic; Kai Miller, MD, PhD – Mayo Clinic; Dora Hermes, PhD – Mayo Clinic; Paul Arnold, MD – Carle Foundation Hospital; Suguna Pappu, MD, PhD – Carle Foundation Hospital; Ravishankar Iyer, PhD – University of Illinois Urbana Champaign; Gregory Worrell, MD, PhD – Mayo Clinic

Rationale:
In mesial temporal lobe epilepsy (mTLE), seizures primarily occur in wakefulness. Paradoxically, interictal epileptiform discharges (IEDs) are highest in non-rapid-eye-movement (NREM) sleep when seizures are less likely to occur. We hypothesize that reduced Thalamo-Hippocampal Functional Connectivity (THFC) impedes IEDs propagation and seizure organization, and underlies reduced seizures in NREM despite increased hippocampal IEDs.

Methods:
Using a novel investigational brain sensing and stimulation device, we tracked seizures, IEDs, and behavioral states over several months in ambulatory patients with mTLE. In four patients with mTLE, we obtained continuous local field potential (LFP) recordings from bilateral anterior nuclei of the thalamus and hippocampi, enabling THFC measurements. To quantify functional connectivity, we investigated (1) relative entropy (REN), which assesses dissimilarities between LFP distributions, thereby reflecting variations in neurodynamics across brain regions, (2) phase locking value (PLV), which quantifies the integral of phase differences between LFP signals, indicating the degree of synchronization between brain regions, and (3) Thalamo-Hippocampal evoked potentials. To compare functional connectivity in NREM sleep and wakefulness, we aggregated the computed features separately for NREM sleep and wakefulness. We employed the Mann-Whitney U test to assess the statistical significance of differences.

Results:
Our study encompassed data analysis from iEEG recordings in four patients spanning 56 days. Notably, we identified a marked decrease of THFC (p < 0.001) in NREM sleep compared to wakefulness in REN, PLV, and Thalamo- Hippocampal evoked responses. Thalamo-Hippocampal evoked responses have shorter latency in wakefulness relative to NREM sleep (with an average difference of 11.75 +/- 3.3 milliseconds), suggesting that limbic network excitability and connectivity are reduced in NREM sleep.
Neurophysiology