Study on the Differences in Cortical Layers During Epileptic Seizure Onset and Spread

Epilepsy is a neurological disorder that severely impacts patients’ quality of life, affecting approximately 1% of the global population. Among all epilepsy patients, nearly one-third are resistant to pharmaceutical treatments, known as drug-resistant epilepsy. For these patients, the most effective treatment often involves surgical removal or destruction of the seizure onset zone (SOZ) in the brain, which is responsible for generating and spreading seizures. Thus, accurately locating the SOZ is key to successful epilepsy surgery. Despite decades of research, scientists have yet to fully understand the spontaneous seizures and their spread mechanisms at the neuronal microcircuit level.

Research Background and Motivation

The mechanisms of seizure onset and spread have long been a mystery in neuroscience. Traditional studies primarily focused on using intracranial electrodes to record seizures over long periods, monitoring local field potentials and widespread neuronal activity to determine the pathological networks in the brain. Therefore, recently, emerging research directions on the microcircuit mechanisms of seizures have garnered increasing attention.

The primary motivation of this research lies in the fact that, although existing studies provide critical insights into pathological activities at a large-scale neuronal network level, there is still a lack of in-depth understanding of the roles of cellular and small circuit elements in seizure generation and spread. Advances in technology have enabled new electrodes to record the activity of individual or small groups of neurons, especially laminar electrodes, which can penetrate the gray matter layers to record neuronal activities in various cortical regions. Hence, this study aims to achieve new breakthroughs in understanding the mechanisms of seizure onset and spread through the use of laminar electrodes.

Source of the Paper

This research paper was co-authored by Pierre Bourdillon, Liankun Ren, Mila Halgren, and several other scholars. The authors are from multiple renowned research institutions, including Massachusetts General Hospital and Harvard Medical School (USA), Hospital Foundation Adolphe de Rothschild (France), Xuanwu Hospital, National Center for Neurological Disorders (China), among others. The paper was published in the “Nature Communications” journal on May 10, 2024.

Research Process and Experimental Design

In this study, the authors used laminar microelectrodes to record seizures in 10 epilepsy patients, collecting data from 30 seizures in total. Detailed analysis of electrode recordings from both the seizure onset and spread zones revealed specific involvement across different cortical layers during seizures.

a) Detailed Introduction to the Research Process

1. Patient Selection and Electrode Implantation: The study selected 10 patients with drug-resistant focal epilepsy (2 females, 8 males). These patients underwent video EEG recordings as part of their pre-surgical evaluation. The patients came from Massachusetts General Hospital and Brigham and Women’s Hospital, New York University Medical Center, and the National Institute of Clinical Neurosciences.

2. Seizure Recording and Localization: A total of 30 seizures were recorded, with 5 out of 17 laminar electrodes located in the seizure onset zone. Seizures were identified using local field potentials (LFP) and multi-unit activity (MUA) recordings, identifying both onset and spread regions.

3. Data Processing and CSD Analysis: Local field potential data from each patient were pre-processed. Current source density (CSD) analysis was used to determine the flow direction of seizure discharges across different cortical layers, providing a spatiotemporal evolution analysis.

4. MUA Analysis: Besides LFP, multi-unit activity data were also analyzed to explore the activity of neurons in various cortical layers.

5. Independent Component Analysis (ICA): ICA was used to separate CSD patterns, identifying seizure discharge patterns and analyzing their dynamic changes during seizures.

b) Main Results

1. CSD Measurement Outcomes: Discharges in the seizure onset zone primarily occurred in the granular and infragranular layers, whereas in the spread zone, discharges mainly concentrated in the supragranular layers. During seizures, the discharge pattern in the seizure onset zone remained fixed in the granular and infragranular layers, while in the spread zone, discharges progressively extended to deeper cortical layers.

2. MUA Evolution Patterns: At the initial stage of the seizure, neuronal discharges in the seizure onset zone were concentrated in the deep granular layer. However, as the seizure progressed, this activity did not extend to the supragranular layers, indicating a critical role of the deeper cortical layers in seizure onset.

3. Seizure Spread Mechanism: Discharges in the spread zone were initially activated in the supragranular layers but gradually involved deeper cortical layers over time, showing a complex spread process.

c) Conclusions and Research Value

Through laminar electrode recordings, this study reveals the dominant role of the granular and infragranular layers in seizure onset, while the supragranular layers play a vital role in the spread of seizures. This provides a new perspective for understanding the cortical microcircuitry involved in epileptic seizures.

1. Scientific Significance: The study offers new insights into the involvement of cortical microcircuits in seizures, contributing to the development of new models to explain the physiological mechanisms of epilepsy.

2. Application Value: The findings can improve methods for localizing the seizure onset zone in epilepsy surgery and aid in the development of new neuromodulation techniques to prevent seizure generation and spread.

d) Research Highlights

1. Unique Experimental Methods: Utilizing laminar electrodes to record multi-layer cortical activity provides a novel data perspective for epilepsy research.

2. Detailed Result Analysis: CSD and MUA analyses detail the dynamic changes across different cortical layers during seizures, revealing specific roles of cortical microcircuits in seizures.

3. Broad Applicability and Future Research Directions: The findings are significant for understanding drug-resistant focal epilepsy and provide methodological references for other types of epilepsy and similar neurological disorders.

Through this study, not only do we gain deeper insights into the mechanisms of epileptic seizures, but we also provide theoretical foundations and technical support for future treatment strategies.