Aperiodic Activity Indexes Neural Hyperexcitability in Generalized Epilepsy.

Area of Science:

• Neuroscience
• Epileptology
• Computational Neuroscience

Background:

• Generalized epilepsy (GE) is a complex neurological disorder characterized by widespread brain hyperexcitability and seizures.
• Magneto- and electroencephalography (M/EEG) reveal large-scale brain activity patterns, including interictal epileptic discharges (IEDs), associated with hyperexcitability.
• The relationship between cellular-level hyperexcitability and large-scale M/EEG signatures, particularly aperiodic brain activity, remains incompletely understood.

Purpose of the Study:

• To investigate whether aperiodic activity in resting-state magnetoencephalography (MEG) can serve as a whole-brain index of neural hyperexcitability in generalized epilepsy.
• To determine if the characteristics of aperiodic brain activity change systematically in patients with GE compared to healthy controls.
• To explore the dynamic changes in aperiodic activity in relation to the occurrence of interictal epileptic discharges (IEDs).

Main Methods:

• Resting-state MEG data were acquired from 51 patients with GE and 49 age-matched healthy controls.
• The power spectra of MEG data were analyzed using the FOOOF algorithm to differentiate oscillatory activity from aperiodic (1/f) activity.
• Aperiodic activity parameters were compared between GE patients and controls, and their temporal dynamics around IEDs were quantified.

Main Results:

• Aperiodic activity in MEG recordings significantly indexed whole-brain hyperexcitability in GE patients, particularly during periods without IEDs (p=0.0130, d=0.52).
• During the occurrence of IEDs, large-scale neural circuits transiently shifted towards a less excitable network state (p=0.001, d=0.68).
• These findings suggest that MEG background activity reflects the current brain state of hyperexcitability.

Conclusions:

• Aperiodic brain activity, as measured by MEG, serves as a reliable indicator of generalized epilepsy-related hyperexcitability at the whole-brain level.
• The brain's network state dynamically influences excitability, with a shift towards reduced excitability during interictal epileptic discharges.
• MEG background activity offers a valuable, state-dependent biomarker for neural hyperexcitability in GE, independent of overt epileptic waveform presence.