title: Sleep states differentiate single neuron activity recorded from human epileptic hippocampus, entorhinal cortex, and subiculum.
abstract: Animal models of epilepsy have shown that synchronous burst firing is associated with epileptogenesis, yet the evidence from human studies linking neuronal synchrony and burst firing to epileptogenesis remains equivocal. Sleep-wake states have been shown to differentially modulate the generation of epileptiform EEG spikes between brain regions of greater and lesser seizure-generating potential, providing information that helps to identify the primary epileptogenic region. Using these state-dependent mechanisms to assist us in identifying neuronal correlates of human epilepsy, we recorded interictal neuronal activity from mesial temporal lobe (MTL) areas in epileptic patients implanted with depth electrodes required for medical diagnosis during polysomnographically defined sleep-wake states. Results show that single neurons recorded ipsilateral to seizure-initiating MTL ("epileptic") areas had significantly higher firing rates (p = 0.01) and burst propensity (p = 0.01) and greater synchrony of discharges (p = 0.003) compared with neurons recorded from contralateral non-seizure-generating MTL ("non-epileptic") areas. In particular, during episodes of slow wave sleep (SWS) and rapid eye movement (REM) sleep, epileptic hippocampal neurons had significantly higher burst rates compared with non-epileptic hippocampal neurons (both p = 0.01). In contrast, during episodes of wakefulness (Aw), no difference in burst firing between epileptic and non-epileptic hippocampal neurons was observed. Furthermore, synchronous firing was significantly higher between epileptic MTL neurons compared with non-epileptic MTL neurons during SWS (p = 0.04) and REM sleep (p = 0.02), but no difference in neuronal synchrony was found between epileptic and non-epileptic neurons during Aw. These results provide evidence that sleep states differentially modulate abnormal epileptogenic neuronal discharge properties within human MTL and confirm that neuronal burst firing and enhanced neuronal synchrony observed in experimental animal models of epilepsy characterizes human epilepsy as well.
authors.affiliation: Department of Neurobiology, David Greffen School of Medicine at University of California Los Angeles, Los Angeles, California 90095, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Staba
authors.forename: Charles L
authors.initials: CL
authors.lastname: Wilson
authors.forename: Anatol
authors.initials: A
authors.lastname: Bragin
authors.forename: Itzhak
authors.initials: I
authors.lastname: Fried
authors.forename: Jerome
authors.initials: J
authors.lastname: Engel
mesh_terms: D000200:Action Potentials; D001921:Brain / Q000033:anatomy & histology / Q000473:pathology / Q000503:physiopathology; D004569:Electroencephalography; D018728:Entorhinal Cortex / Q000503:physiopathology*; D004827:Epilepsy / Q000473:pathology / Q000503:physiopathology*; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D008839:Microelectrodes; D009474:Neurons / Q000502:physiology*; D017286:Polysomnography; D012890:Sleep / Q000502:physiology*; D012894:Sleep Stages / Q000502:physiology; D013702:Temporal Lobe / Q000503:physiopathology; D014851:Wakefulness