Abstracts

Rationale: Seizure-induced impaired awareness contributes to significant morbidity, mortality, and decreased quality of life. The neural underpinnings of impaired awareness during a temporal lobe seizure are poorly understood, but one proposed mechanism is the network inhibition hypothesis. According to this hypothesis, temporal lobe seizures inhibit the subcortical arousal systems that led to sleep or coma-like slow-wave activity in broad regions of the bilateral fronto-parietal association cortex, producing impaired awareness. Preclinical, human electrophysiological, and functional imaging studies support the hypothesis, but to date, no study has demonstrated the thalamic subnuclei-specific changes in neural activity in human temporal lobe epilepsy (TLE). The centromedian (CeM), being a higher-order nucleus, is rich in widely projecting matrix cells that facilitate interactions across cortical regions and is implicated in regulating states of vigilance, including arousal. In contrast, the anterior nucleus of the thalamus (ANT) is a first-order nucleus with brainstem-limbic connectivity. Based on these anatomical properties, we hypothesize that during seizure-induced impaired awareness, the neural activity across thalamic subnuclei will be diverse, with CeM demonstrating maximum inhibition and sleep spindle-like activity.

Methods: A single-center, cross-sectional study involving consenting adults with TLE undergoing stereo-EEG exploration for epilepsy surgery. Limbic thalami (either ANT or CeM) was sampled with modified implantation trajectory. Power spectral density, phase synchrony, 1/f for excitability, and directional connectivity between the thalamo-frontal region were performed in selected hippocampal onset seizures with impaired awareness (FIAS). Epochs analyzed were: a) awake baseline, b) during emergence of frontal delta after seizure onset, and c) preceding emergence of the frontal delta. The study was approved by the IRB.

Results: We analyzed 26 FIAS- 16 seizures (8 patients ANT), 10 seizures (4 patients CeM)). During FIAS, there was a significant increase in delta-theta power in the frontal region and increased overall power in the thalamic subnuclei. However, CeM had significantly higher power in the delta to beta bands and decreased excitability due to increased low-frequency oscillations. The ANT showed increased power across broadband (delta to low-gamma), representing seizure activity. Reciprocal functional connectivity between thalamic subnuclei and the frontal region was significantly decreased for ANT, while for CeM it was higher in 5-30 Hz in the direction from CeM to the frontal region.

Conclusions: During FIAS, the thalamic subnuclei showed diverse neural activity, with CeM showing decreased excitability and transition to a state similar to sleep-like activity with increased power in delta to beta. There was a breakdown in functional connectivity between ANT and cortex, while for CeM, there was a pathologically increased feedforward connectivity to the frontal region.

Funding: Please list any funding that was received in support of this abstract.: No funding.