Malformations-related neocortical circuits in focal seizures

Abstract

This review article gives an overview on the molecular, cellular and network mechanisms underlying focal seizures in neocortical networks with developmental malformations. Neocortical malformations comprise a large variety of structural abnormalities associated with epilepsy and other neurological and psychiatric disorders. Genetic or acquired disorders of neocortical cell proliferation, neuronal migration and/or programmed cell death may cause pathologies ranging from the expression of dysmorphic neurons and heterotopic cell clusters to abnormal layering and cortical misfolding. After providing a brief overview on the pathogenesis and structure of neocortical malformations in humans, animal models are discussed and how they contributed to our understanding on the mechanisms of neocortical hyperexcitability associated with developmental disorders. State-of-the-art molecular biological and electrophysiological techniques have been also used in humans and on resectioned neocortical tissue of epileptic patients and provide deep insights into the subcellular, cellular and network mechanisms contributing to focal seizures. Finally, a brief outlook is given how novel models and methods can shape translational research in the near future.

Keywords: Cortical malformation; Development; Focal epilepsy; Neocortex; Review.