Interictal epileptiform discharges induce hippocampal-cortical coupling in temporal lobe epilepsy.
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.
The Neuroscience Institute, New York University, School of Medicine, New York, New York, USA.
Jennifer N
JN
Gelinas
The Neuroscience Institute, New York University, School of Medicine, New York, New York, USA.
Dion
D
Khodagholy
Department of Neurology, Comprehensive Epilepsy Center, New York University, School of Medicine, New York, New York, USA.
Thomas
T
Thesen
Department of Neurology, Comprehensive Epilepsy Center, New York University, School of Medicine, New York, New York, USA.
Orrin
O
Devinsky
The Neuroscience Institute, New York University, School of Medicine, New York, New York, USA.|Center for Neural Science, New York University, School of Medicine, New York, New York, USA.
György
G
Buzsáki
D000328:Adult; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000503:physiopathology; D058256:Brain Waves / Q000502:physiology; D002540:Cerebral Cortex / Q000503:physiopathology; D004195:Disease Models, Animal; D000069280:Electrocorticography; D004569:Electroencephalography; D004828:Epilepsies, Partial / Q000503:physiopathology; D004833:Epilepsy, Temporal Lobe / Q000150:complications / Q000503:physiopathology*; D005260:Female; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000503:physiopathology*; D008875:Middle Aged; D010865:Pilot Projects; D017397:Prefrontal Cortex / Q000503:physiopathology*; D051381:Rats; D012890:Sleep / Q000502:physiology