Circuits generating secondarily generalized seizures

Mapping the circuits underlying the generation and propagation of seizures is critically important for understanding their pathophysiology. We review evidence to suggest that circuits engaged in secondarily generalized seizures are likely to be more complex than those currently proposed. Focal seizures have been proposed to engage canonical thalamocortical circuits that mediate primarily generalized absence seizures, leading to secondarily generalized tonic-clonic seizures. In addition to traveling through the canonical thalamocortical circuits, secondarily generalized seizures could also travel through the striatum, globus pallidus, substantia nigra reticulata, and corpus callosum to the contralateral hemisphere. Recruitment of principal neurons in superficial layers 2/3 of the cortex can play a critical role in corticocortical seizure spread. Understanding the neuronal structures engaged in generating secondarily generalized seizures could provide novel targets for neuromodulation for the treatment of seizures. Furthermore, these sites may be loci of neuronal plasticity facilitating epileptogenesis. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".