大学院特別講義

新潟脳神経研究会特別例会
オンラインセミナーの御案内
日時：令和 3 年 2 月 3 日(水) 14:00〜

開催方法：Zoom による配信

オンデマンド脳活動介入によるてんかん発作制御とその応用
On-demand intervention of epileptic
seizures and beyond

竹内 雄一 先生

Dr.Yuichi Takeuchi
大阪市立大学大学院医学研究科 神経生理学
Department of Physiology, Osaka City University Graduate School of Medicine
Approximately 1% of world population have epilepsy and more than 30% of them are
drug-resistant; therefore, a new therapeutic approach is desired. We have previously
developed a closed-loop transcranial electrical stimulation (TES) technique to control
absence (petit mal) seizures using rats1. Non-invasive and time-targeting natures of theclosed-loop TES technique will diminish risks associated with intracranial electrodeimplantations and disturbance of normal brain functions. We have also developed
another technique for controlling secondary generalized, grand-mal seizures of temporal
lobe epilepsy (TLE) using a ‘proxy’ intervention strategy2. As seizure generator network
of TLE is often distributed over bilateral hippocampi and para-hippocampal gyri, directintervention on these structures is not technically feasible. Thus, we stimulated themedial septum (MS) to modulate highly synchronous hippocampal oscillations inseizures of TLE harnessing the MS’s diffuse bilateral connections to the hippocampi andpara-hippocampal structures, which govern oscillatory activities there. We found thatclosed-loop MS electrical stimulation effectively terminated electrographic and motor
seizures of hippocampally-kindled rats whereas open-loop MS stimulation did not. Celltype specific optogenetic stimulation of MS neurons revealed that precisely timed
activation of MS GABAergic neurons could underlie the MS-mediated seizure terminatingeffects. To translate these findings into clinical practice, we have then developed a new
TES technology to spatially target brain regions: Intersectional Short Pulse stimulation3.
To focus intensity of electrical stimulation to an intracranial region, we placed multiple
pairs of stimulus electrodes over the head of rats, human cadavers, and healthy
volunteers. We found that the focused electrical stimulation could successfully modulate
neural activities and oscillatory brain activities in the focused region. Our seizure
intervention techniques with non-invasive, time-, spatial-, and proxy-targeting natures
would be useful to control refractory epilepsy. In addition, I’m going to discuss possible

applications of our technique to other neurological and psychiatric disorders4.
1. Berényi A, Belluscio M, Mao D, Buzsáki G, Closed-loop control of epilepsy by transcranialelectrical stimulation. Science 337: 735–737, 2012.
2. Takeuchi Y, Harangozó M, Pedraza L, Földi T, Kozák G, Li Q, Berényi A, Closed-loop
stimulation of the medial septum terminates epileptic seizures, Brain, in press.
3. Vöröslakos M, Takeuchi Y, Brinyiczki K, Zombori T, Oliva A, Fernández-Ruiz A, Kozák G,Kincses ZT, Iványi B, Buzsáki G, Berényi A, Direct effects of transcranial electric stimulationon brain circuits in rats and humans. Nat Commun 9: 483, 2018.
4. Takeuchi Y, Berényi A, Oscillotherapeutics – Time-targeted interventions in epilepsy andbeyond.
Neurosci Res 152: 87-107, 2020.

どうぞ奮ってご参加ください。
担当：システム脳病態学分野／田井中研究室