Interictal epileptiform discharges induce hippocampal-cortical coupling in temporal lobe epilepsy

• Published in: Nature medicine Vol. 22; no. 6; pp. 641 - 648
• Main Authors: Gelinas, Jennifer N, Khodagholy, Dion, Thesen, Thomas, Devinsky, Orrin, Buzsáki, György
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.06.2016
• Subjects: Adult; Animals; Behavior, Animal; Brain - physiopathology; Brain Waves - physiology; Care and treatment; Cerebral Cortex - physiopathology; Convulsions & seizures; Development and progression; Diagnosis; Disease Models, Animal; Electrocorticography; Electroencephalography; Epilepsies, Partial - physiopathology; Epilepsy; Epilepsy, Temporal Lobe - complications; Epilepsy, Temporal Lobe - physiopathology; Female; Health aspects; Hippocampus - physiopathology; Humans; Male; Memory; Memory Disorders - etiology; Memory Disorders - physiopathology; Middle Aged; Neurobiology; Neurophysiology; Physiological aspects; Pilot Projects; Prefrontal Cortex - physiopathology; Rapid eye movement; Rats; Rodents; Sleep; Sleep - physiology; Temporal lobe epilepsy; United States
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/nm.4084

Interactions between the hippocampus and the cortex are critical for memory. Interictal epileptiform discharges (IEDs) identify epileptic brain regions and can impair memory, but the mechanisms by which they interact with physiological patterns of network activity are mostly undefined. We show in a rat model of temporal lobe epilepsy that spontaneous hippocampal IEDs correlate with impaired memory consolidation, and that they are precisely coordinated with spindle oscillations in the prefrontal cortex during nonrapid-eye-movement (NREM) sleep. This coordination surpasses the normal physiological ripple-spindle coupling and is accompanied by decreased ripple occurrence. IEDs also induce spindles during rapid-eye movement (REM) sleep and wakefulness-behavioral states that do not naturally express these oscillations-by generating a cortical 'down' state. In a pilot clinical examination of four subjects with focal epilepsy, we confirm a similar correlation of temporofrontal IEDs with spindles over anatomically restricted cortical regions. These findings imply that IEDs may impair memory via the misappropriation of physiological mechanisms for hippocampal-cortical coupling, which suggests a target for the treatment of memory impairment in epilepsy.