Neuronal Firing and Waveform Alterations through Ictal Recruitment in Humans.

Area of Science:

• Neuroscience
• Epilepsy Research
• Computational Neuroscience

Background:

• Analyzing neuronal activity during human seizures is crucial for understanding seizure onset and propagation.
• Extracellular recordings are hindered by ionic changes and hypersynchronous firing, complicating single-neuron detection.
• Prior animal studies show action potential waveform changes during seizures, but human data is limited.

Purpose of the Study:

• To develop a novel spike sorting method for analyzing neuronal activity during human seizures.
• To investigate single-neuron activity patterns in seizure-invaded versus penumbral regions in human epilepsy.
• To identify neuron-intrinsic hallmarks of seizure invasion.

Main Methods:

• Developed a novel template-matching-based spike sorting method.
• Analyzed microelectrode array recordings from 27 patients with intractable focal epilepsy.
• Tracked 1239 single neurons throughout multiple seizures.

Main Results:

• Identified distinct neuronal activity patterns in seizure-invaded ('core') versus penumbral regions.
• Neurons in seizure-invaded tissue exhibited increased action potential duration (p < 0.001) and reduced amplitude (p < 0.001).
• Neurons in penumbral regions maintained stable action potential waveforms; all returned to baseline post-seizure.

Conclusions:

• A distinction between seizure core and penumbral territories is evident at the single-neuron level.
• Altered action potential waveforms (longer duration, reduced amplitude) are neuron-intrinsic hallmarks of seizure invasion.
• These waveform changes impede traditional spike sorting but can define local neuronal recruitment during seizures.