Excitatory-inhibitory mismatch shapes node recruitment in an epileptic network

Area of Science:

• Neuroscience
• Epilepsy Research
• Network Dynamics

Background:

• Focal epilepsy is increasingly viewed as a network disorder.
• Understanding how epileptiform activity spreads noncontiguously through brain networks is crucial.
• Animal models for studying focal epilepsy network dynamics are limited.

Purpose of the Study:

• To investigate the network spread of interictal spikes (IISs).
• To identify how distant brain nodes are recruited during IISs.
• To explore the role of excitatory and inhibitory cells in IIS propagation.

Main Methods:

• Injected bicuculline into the S1 barrel cortex of animal models.
• Utilized multisite local field potential and calcium imaging (Thy-1 and parvalbumin cells).
• Analyzed node participation using spike-triggered coactivity maps, repeating experiments with 4-aminopyridine.

Main Results:

• IISs reverberated throughout the studied network, recruiting both excitatory and inhibitory cells.
• The ipsilateral secondary motor area (iM2) showed the strongest response.
• Paradoxically, a disynaptically connected node (contralateral M2) was recruited more intensely than a monosynaptically connected node (contralateral S1), linked to node-specific excitatory/inhibitory balance.

Conclusions:

• IISs spread noncontiguously by utilizing interconnected brain pathways.
• Node-specific excitatory/inhibitory balance is critical for the recruitment of brain nodes in epilepsy networks.
• This study presents a multinodal IIS network model for investigating epileptiform activity propagation.