To test the hypothesis that focal and parafocal neocortical tissue from pediatric patients with intractable epilepsy exhibits cellular and synaptic differences, the authors characterized the propensity of these neurons to generate (a) voltage-dependent bursting and (b) synaptically driven paroxysmal depolarization shifts. Neocortical slices were prepared from tissue resected from patients with intractable epilepsy. Multiunit network activity and simultaneous whole-cell patch recordings were made from neurons from three patient groups: (1) those with normal histology; (2) those with mild and severe cortical dysplasia; and (3) those with abnormal pathology but without cortical dysplasia. Seizure-like activity was characterized by population bursting with concomitant bursting in intracellularly recorded cortical neurons (n = 59). The authors found significantly more N-methyl-d-aspartic acid-driven voltage-dependent bursting neurons in focal versus parafocal tissue in patients with severe cortical dysplasia (P < 0.01). Occurrence of paroxysmal depolarization shifts and burst amplitude and burst duration were significantly related to tissue type: focal or parafocal (P < 0.05). The authors show that functional differences between focal and parafocal tissue in patients with severe cortical dysplasia exist. There are functional differences between patient groups with different histology, and bursting properties can be significantly associated with the distinction between focal and parafocal tissue.
From the Departments of *Neurology, †Neurosurgery, and ‡Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin; §Department of Pediatrics, The University of Chicago, Chicago, Illinois; ∥Department of Neurological Surgery and ¶Center for Integrative Brain Research, Seattle Children's Research Institute, University of Washington, Seattle, Washington, U.S.A.; #Laboratoire Plasticité et Physio-Pathologie de la Motricité, UMR 6196 CNRS-Aix Marseille University, Marseille, France; **Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Boulevard Juriquilla, Querétaro, México; Departments of ††Organismal Biology and Anatomy and ‡‡Pathology, The University of Chicago, Chicago, Illinois; §§Center for Clinical Research and Evidence-Based Medicine, The University of Texas-Houston Medical School, Houston, Texas; and ∥∥Department of Neurosurgery, The University of Chicago, Chicago, Illinois, U.S.A.
The first three authors contributed equally to this work.
Supported by Dr. Ralph and Marian Falk Medical Research Trust, Parents Against Childhood Epilepsy, K12 award (NIH HD043387), the Brain Research Foundation, Emory T. Clark Foundation, Advancing a Healthier Wisconsin, the Linn family, the Tarrson family, and the Dodd Family.
Address correspondence and reprint requests to Charles J. Marcuccilli, Department of Neurology, The Medical College of Wisconsin, 9000 W. Wisconsin Ave., PO Box 1997, Milwaukee, WI 53201, U.S.A.; e-mail: firstname.lastname@example.org.