The Interictal Suppression Hypothesis in focal epilepsy: network-level supporting evidence

Area of Science:

• Neuroscience
• Epileptology
• Network Science

Background:

• Focal epilepsy involves intermittent seizures, suggesting active suppression mechanisms beyond simple neurotransmitter balance.
• Previous research indicated altered connectivity in seizure-onset zones, hinting at network involvement in seizure control.
• The hypothesis posits that widespread brain networks actively suppress seizure-onset zones during interictal periods.

Purpose of the Study:

• To investigate the role of distributed brain networks in actively suppressing seizure-onset zones during interictal states.
• To evaluate network connectivity patterns in seizure onset, early propagation, and non-involved zones using intracranial electrography.
• To develop a classification model for identifying seizure-onset and propagation zones.

Main Methods:

• Intracranial electrographic recordings (resting-state and neurostimulation) in 81 individuals with drug-resistant focal epilepsy.
• Diffusion imaging to assess white-matter connectivity and structure-function coupling.
• Development and validation of a resting-state classification model.

Main Results:

• Seizure onset and early propagation zones exhibited significantly increased inward and decreased outward connectivity (P < 3.13 × 10-13).
• Enhanced structure-function coupling (hypercoupling) was observed in seizure-onset zones compared to healthy tissue (P < 9.76 × 10-21).
• Classification models achieved 92.0 ± 2.2% accuracy in identifying seizure-onset and propagation zones.

Conclusions:

• Seizure-onset zones are actively suppressed and segregated by widespread brain networks, a process disproportionate to structural changes.
• Findings support the interictal suppression hypothesis, highlighting functional network alterations in focal epilepsy.
• This research offers potential for improved presurgical evaluation and novel therapeutic strategies for drug-resistant epilepsy.