Role of inhibitory control in modulating focal seizure spread

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Classical, Jacksonian-like focal seizure propagation. The purple zone is the ictal core, surrounded by the ictal wavefront (orange), slowly expanding toward adjacent cortical circuitry. The yellowish area surrounding the ictal core represents the ‘ictal penumbra’, an area that receives massive synaptic barrages from the ictal core and demonstrates epileptiform EEGs but has not been recruited into the seizing territory. B. The epileptic network. Several disparate ictogenic zones (purple) are recurrently conn

Focal seizure propagation is classically thought to be spatially contiguous. However, distribution of seizures through a large-scale epileptic network has been theorized. Here, we used a multielectrode array, wide field calcium imaging, and two-photon calcium imaging to study focal seizure propagation pathways in an acute rodent neocortical 4-aminopyridine model. Although ictal neuronal bursts did not propagate beyond a 2–3-mm region, they were associated with hemisphere-wide field potential fluctuations and parvalbumin-positive interneuron activity outside the seizure focus. While bicuculline surface application enhanced contiguous seizure propagation, focal bicuculline microinjection at sites distant to the 4-aminopyridine focus resulted in epileptic network formation with maximal activity at the two foci. Our study suggests that both classical and epileptic network propagation can arise from localized inhibition defects, and that the network appearance can arise in the context of normal brain structure without requirement for pathological connectivity changes between sites.

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Publication Name: 
Jyun-you Liou, Hongtao Ma, Michael Wenzel, Mingrui Zhao, Eliza Baird-Daniel, Elliot H Smith, Andy Daniel, Ronald Emerson, Rafael Yuste, Theodore H Schwartz, Catherine A Schevon