title: Electric stimulation of the tuberomamillary nucleus affects epileptic activity and sleep-wake cycle in a genetic absence epilepsy model.
abstract: Deep brain stimulation (DBS) is a promising approach for epilepsy treatment, but the optimal targets and parameters of stimulation are yet to be investigated. Tuberomamillary nucleus (TMN) is involved in EEG desynchronization-one of the proposed mechanisms for DBS action. We studied whether TMN stimulation could interfere with epileptic spike-wave discharges (SWDs) in WAG/Rij rats with inherited absence epilepsy and whether such stimulation would affect sleep-wake cycle. EEG and video registration were used to determine SWD occurrence and stages of sleep and wake during three-hours recording sessions. Stimulation (100Hz) was applied in two modes: closed-loop (with previously determined interruption threshold intensity) or open-loop mode (with 50% or 70% threshold intensity). Closed-loop stimulation successfully interrupted SWDs but elevated their number by 148 ± 54% compared to baseline. It was accompanied by increase in number of episodes but not total duration of both active and passive wakefulness. Open-loop stimulation with amplitude 50% threshold did not change measured parameters, though 70% threshold stimulation reduced SWDs number by 40 ± 9%, significantly raised the amount of active wakefulness and decreased the amount of both slow-wave and rapid eye movement sleep. These results suggest that the TMN is unfavorable as a target for DBS as its stimulation may cause alterations in sleep-wake cycle. A careful choosing of parameters and control of sleep-wake activity is necessary when applying DBS in epilepsy.
authors.affiliation: Lomonosov Moscow State University, Moscow, Russia; Institute of Higher Nervous Activity and Neurophysiology RAS, Moscow, Russia. Electronic address: vitaliyablik@gmail.com.
authors.forename: Vitaliya
authors.initials: V
authors.lastname: Blik
mesh_terms: D000818:Animals; D004558:Electric Stimulation / Q000379:methods*; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000235:genetics / Q000503:physiopathology* / Q000628:therapy; D007026:Hypothalamic Area, Lateral / Q000503:physiopathology*; D008297:Male; D051381:Rats; D012890:Sleep / Q000502:physiology*; D014741:Video Recording; D014851:Wakefulness / Q000502:physiology*
keywords: Deep brain stimulation; EEG desynchronization; Epilepsy; Sleep–wake cycle; Spike-wave discharges; Tuberomamillary nucleus