Ongoing challenges in diagnosing focal cortical dysplasia (FCD) mandate continuous research and consensus agreement to improve disease definition and classification. An International League Against Epilepsy (ILAE) Task Force (TF) reviewed the FCD classification of 2011 to identify existing gaps and provide a timely update. The following methodology was applied to achieve this goal: a survey of published literature indexed with ((Focal Cortical Dysplasia) AND (epilepsy)) between 01/01/2012 and 06/30/2021 (n = 1349) in PubMed identified the knowledge gained since 2012 and new developments in the field. An online survey consulted the ILAE community about the current use of the FCD classification scheme with 367 people answering. The TF performed an iterative clinico‐pathological and genetic agreement study to objectively measure the diagnostic gap in blood/brain samples from 22 patients suspicious for FCD and submitted to epilepsy surgery. The literature confirmed new molecular‐genetic characterizations involving the mechanistic Target Of Rapamycin (mTOR) pathway in FCD type II (FCDII), and SLC35A2 in mild malformations of cortical development (mMCDs) with oligodendroglial hyperplasia (MOGHE). The electro‐clinical‐imaging phenotypes and surgical outcomes were better defined and validated for FCDII. Little new information was acquired on clinical, histopathological, or genetic characteristics of FCD type I (FCDI) and FCD type III (FCDIII). The survey identified mMCDs, FCDI, and genetic characterization as fields for improvement in an updated classification. Our iterative clinico‐pathological and genetic agreement study confirmed the importance of immunohistochemical staining, neuroimaging, and genetic tests to improve the diagnostic yield. The TF proposes to include mMCDs, MOGHE, and “no definite FCD on histopathology” as new categories in the updated FCD classification. The histopathological classification can be further augmented by advanced neuroimaging and genetic studies to comprehensively diagnose FCD subtypes; these different levels should then be integrated into a multi‐layered diagnostic scheme. This update may help to foster multidisciplinary efforts toward a better understanding of FCD and the development of novel targeted treatment options.

Brain-derived neurotrophic factor (BDNF) is transported anterogradely in neurons of the CNS and can be released by activity-dependent mechanisms to regulate synaptic plasticity. However, few neural networks have been identified in which the production, transport, and effects of BDNF on postsynaptic neurons can be analyzed in detail. In this study, we have identified such a network. BDNF has been colocalized by immunocytochemistry with tyrosine hydroxylase (TH) in nerve fibers and nerve terminals within the lateral septum of rats. BDNF-containing nerve fibers terminate on a population of calbindin-containing neurons in lateral septum that contain TrkB, the high-affinity receptor for BDNF. Overexpression of BDNF in noradrenergic neurons increased levels of calbindin in septum, as well as in whole-brain lysates. Septal levels of calbindin and BDNF partially decreased after unilateral lesions of the medial forebrain bundle (MFB), induced with 6-hydroxydopamine, a treatment that abolished TH staining. These data suggest that BDNF is anterogradely transported within the MFB in catecholaminergic neurons arising from brainstem nuclei. To determine whether BDNF affects the production of calbindin in lateral septal neurons directly, we tested the effects of BDNF on cultures of septal neurons from embryonic day 16–17 rats. BDNF promoted the expression of calbindin, as well as the arborization of calbindin-containing neurons, but BDNF had no effect on cell division or survival. Together, these results suggest that BDNF, anterogradely transported in catecholaminergic neurons, regulates calbindin expression within the lateral septum.