The role of subcortical structures in human epilepsy

Like normal cerebral function, epileptic seizures involve widespread network interactions between cortical and subcortical structures. Although the cortex is often emphasized as the site of seizure origin, accumulating evidence points to a crucial role for subcortical structures in behavioral manifestations, propagation, and, in some cases, initiation of epileptic seizures. Extensive previous studies have shown the importance of subcortical structures in animal seizure models, but corresponding human studies have been relatively few. We review the existing evidence supporting the importance of the thalamus, basal ganglia, hypothalamus, cerebellum, and brain stem in human epilepsy. We also propose a "network inhibition hypothesis" through which focal cortical seizures disrupt function in subcortical structures (such as the medial diencephalon and pontomesencephalic reticular formation), leading secondarily to widespread inhibition of nonseizing cortical regions, which may in turn be responsible for behavioral manifestations such as loss of consciousness during complex partial seizures.