Seizure suppression by EEG-guided repetitive transcranial magnetic stimulation in the rat

Abstract

Objective-To test the anticonvulsive potential of a range of repetitive transcranial magnetic stimulation (rTMS) frequencies by novel methods for simultaneous EEG and rTMS in a rat seizure model. Methods-Seizureswere triggered by intraperitoneal kainic acid (KA; 10 mg/kg). Rats (n = 21) were divided into three groups in which individual seizures were treated with rTMS trains at one of three frequencies: 0.25, 0.5 or 0.75 Hz. EEG was continuously viewed by an operator who identified each seizure onset. Consecutive seizures in each animal were (1) treated with active rTMS, (2) treated with sham rTMS, or (3) were untreated. EEG was re-analyzed post hoc by visual inspection, and seizure durations were compared within and between treatment groups.Results-KA-induced seizures were abbreviated by 0.75 Hz (P = 0.019) and 0.5 Hz (P = 0.033) active EEG-guided rTMS. In contrast, neither active 0.25 Hz rTMS nor the control conditions affected seizure duration (P > 0.2).Conclusions-We demonstrate that EEG-guided rTMS can suppress seizures in the rat KA epilepsy model, and that the effect is frequency dependent, with 0.75 and 0.5 Hz rTMS being superior to 0.25 Hz rTMS.Significance-These data support the use of rat seizure models in translational research aimed at evaluation and development of effective rTMS anticonvulsive protocols. We also offer a proof of principle that real-time analysis of EEG can be used to guide rTMS to suppress individual seizures.

Transcranial magnetic stimulation with electroencephalography: methodology, applications for research and cilinics

“…При низкочастотной ритмиче-ской ТМС (рТМС) у крыс была показана связь эф-фекта долговременного торможения с работой глута-матергических рецепторов НМДА-типа [43]. Возможности ТМС-ЭЭГ пока еще не достаточно изучены на грызунах, хотя в отдельных работах метод уже использовали, например, для анализа противо-судорожного эффекта рТМС у крыс [44]. В перспек-тиве ТМС-ЭЭГ может стать мощным инструментом трансляционных исследований.…”

Neuromodulatory Treatment of Medically Refractory Epilepsy

“…(Godlevsky et al 2006) A more recent study suggests that TMS can suppress kainate-induced seizures in rats at frequencies of 0.5 and 0.75Hz though not at 0.25 Hz, demonstrating a frequency dependence on seizure control. (Rotenberg et al 2008) On the other hand, higher frequency stimulation has been shown to have confounding effects. Using male Wistar rats, it was shown that in the pentylenetrazole model of clonic seizures, chronic high-frequency stimulation (50Hz) may induce kindling of seizure activity, though this effect was not appreciated with acute-only stimulation.…”

New Perspectives in Transcranial Magnetic Stimulation: Epilepsy, Consciousness and the Perturbational Approach

“…TMS-EEG also detects seizure improvement or exacerbation, making it a valuable clinical tool for everyday practice. TMS-EEG was recently applied in a small series of epilepsia partialis continua (EPC) to detect seizure suppression and to exclude seizure exacerbation during rTMS in animal models [144][145][146] and in humans [147][148][149][150]. Encouragingly, rTMS did not induce seizures, while seizure suppression was detected in some instances.…”