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Real-time closed-loop interventions of epileptic seizures by non-invasive deep brain stimulation

Research Project

Project/Area Number 18KK0236
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 51:Brain sciences and related fields
Research InstitutionHokkaido University (2021)
Osaka City University (2020)
Nagoya City University (2018-2019)

Principal Investigator

Takeuchi Yuichi  北海道大学, 薬学研究院, 准教授 (70588384)

Co-Investigator(Kenkyū-buntansha) 大澤 匡弘  名古屋市立大学, 医薬学総合研究院(薬学), 准教授 (80369173)
McHugh Thomas  国立研究開発法人理化学研究所, 脳神経科学研究センター, チームリーダー (50553731)
河野 剛士  豊橋技術科学大学, 工学(系)研究科(研究院), 准教授 (70452216)
春田 牧人  奈良先端科学技術大学院大学, 先端科学技術研究科, 助教 (40733663)
Lin ChiaWen  国立研究開発法人理化学研究所, 脳神経科学研究センター, 研究員 (20730253)
Project Period (FY) 2018-10-09 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2021: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Keywordsてんかん / 実時間シグナル処理 / 脳深部刺激 / 光遺伝学 / 非侵襲的脳刺激 / 超音波 / 実時間処理 / 脳波 / 前脳基底部 / 前脳基底核 / 大脳辺縁系
Outline of Final Research Achievements

Drug-resistant epilepsy lacks effective treatments other than highly invasive surgical resections of seizure foci. Therefore, novel therapeutic technologies that address drug-resistant epilepsy have been desired. We had found that deep brain stimulation targeting the basal forebrain can alleviate seizure symptoms as a potential medical technology to overcome drug-resistant epilepsy in preclinical studies. However, the disruption of normal brain functions by continuous stimulation and the high invasiveness of electrode penetration had been major challenges in research and development of the deep brain stimulation toward clinical application. In this study, found that these challenges can be overcome through time-targeted stimulus deliveries during seizures and novel non-invasive brain stimulation technologies.

Academic Significance and Societal Importance of the Research Achievements

世界5000万人のてんかん患者のうち約30%が薬剤抵抗性である。特に側頭葉てんかんは難治性である割合が高い。難治性側頭葉てんかんは就学就労妊娠制限により社会に損失を生じるのみならず、発作により患者の日常生活に著しく支障をきたし、発作の二次性全般化によって突然死のリスクを高めるため、適切に制御する必要がある。本研究により、前脳基底部GABA作動性神経の新規抗てんかん作用が報告され、新しい非侵襲的かつ時空間特異的な脳刺激法が創出された。当該法の臨床実装は薬物抵抗性てんかんの克服に寄与し得る。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (54 results)

All 2022 2021 2020 2019 2018 Other

All Int'l Joint Research (11 results) Journal Article (12 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 8 results,  Open Access: 9 results) Presentation (23 results) (of which Int'l Joint Research: 11 results,  Invited: 5 results) Book (4 results) Remarks (3 results) Funded Workshop (1 results)

  • [Int'l Joint Research] セゲド大学(ハンガリー)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] ニューヨーク大学/ハーバード大学(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] セゲド大学(ハンガリー)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] ニューヨーク大学/デューク大学/ハーバード大学(米国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] シンガポール国立大学(シンガポール)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] セゲド大学(ハンガリー)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] ニューヨーク大学/デューク大学/ハーバード大学(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] シンガポール国立大学(シンガポール)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] セゲド大学(ハンガリー)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] シンガポール国立大学(シンガポール)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] ハーバード大学/デューク大学(米国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] 超音波ニューロモデュレーション2022

    • Author(s)
      竹内雄一、関和彦
    • Journal Title

      Clinical Neuroscience

      Volume: 40 Pages: 249-253

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Reinstating olfactory bulb derived limbic gamma oscillations alleviates depression2022

    • Author(s)
      Li Q, Takeuchi Y, Wang J, Barcsai L, Pedraza L, Kozak G, Nakai S, Kato S, Kobayashi K, Ohsawa M, Lorincz ML, Devinsky O, Buzsaki G, Berenyi A
    • Journal Title

      bioRxiv

      Volume: 2022.02.01 Pages: 478683-478683

    • DOI

      10.1101/2022.02.01.478683

    • Related Report
      2021 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Reduced MC4R signaling alters nociceptive thresholds associated with red hair2021

    • Author(s)
      Robinson KC, Kemeny LV, Fell GL, Hermann AL, Allouche J, Ding W, Yekkirala A, Hsiao JJ, Su MY, Theodosakis N, Kozak G, Takeuchi Y, Shen S, Berenyi A, Mao J, Woolf CJ, Fisher DE
    • Journal Title

      Sci Adv

      Volume: 7 Issue: 14

    • DOI

      10.1126/sciadv.abd1310

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Medial Septum as a Potential Target for Treating Brain Disorders Associated With Oscillopathies2021

    • Author(s)
      Takeuchi Yuichi、Nagy Anett J.、Barcsai Livia、Li Qun、Ohsawa Masahiro、Mizuseki Kenji、Berenyi Antal
    • Journal Title

      Frontiers in Neural Circuits

      Volume: 15 Pages: 701080-701080

    • DOI

      10.3389/fncir.2021.701080

    • URL

      https://localhost/en/publications/890e390b-0ec7-42a7-8ede-1dd1abbecf91

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] オシレーション治療2021

    • Author(s)
      竹内雄一
    • Journal Title

      Clinical Neuroscience

      Volume: 39 Pages: 847-851

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Closed-loop stimulation of the medial septum terminates epileptic seizures2021

    • Author(s)
      Takeuchi Y, Harangozo M, Pedraza L, Foldi T, Kozak G, Li Q, Berenyi A
    • Journal Title

      Brain

      Volume: 114 Issue: 3 Pages: 885-908

    • DOI

      10.1093/brain/awaa450

    • NAID

      130008001593

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Development of a neural probe integrated with high-efficiency MicroLEDs for in vivo application2020

    • Author(s)
      Yasunaga H, Takagi T, Shinko D, Nakayama Y, Takeuchi Y, Nishikawa A, Loesing A, Ohsawa M, Sekiguchi H
    • Journal Title

      Jpn J Appl Phys

      Volume: 60 Issue: 1 Pages: 16503-16503

    • DOI

      10.35848/1347-4065/abcffa

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Oscillotherapeutics - Time-targeted interventions in epilepsy and beyond2020

    • Author(s)
      Takeuchi Y, Berenyi A
    • Journal Title

      Neurosci Res

      Volume: 152 Pages: 87-107

    • DOI

      10.1016/j.neures.2020.01.002

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Closed-loop stimulation of the medial septum terminates epileptic seizures2020

    • Author(s)
      Takeuchi Y, Harangozo M, Pedraza L, Foldi T, Kozak G, Berenyi A
    • Journal Title

      bioRxiv

      Volume: 3

    • DOI

      10.1101/2020.03.09.982827

    • NAID

      130008001593

    • Related Report
      2019 Research-status Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Tonic GABAergic Inhibition Is Essential for Nerve Injury-Induced Afferent Remodeling in the Somatosensory Thalamus and Ectopic Sensations2020

    • Author(s)
      Nagumo Y, Ueta Y, Nakayama H, Osaki H, Takeuchi Y, Uesaka N, Kano M, Miyata M
    • Journal Title

      Cell Rep

      Volume: 31 Issue: 12 Pages: 107797-107797

    • DOI

      10.1016/j.celrep.2020.107797

    • NAID

      120007053424

    • URL

      https://localhost/en/publications/8d597353-cfc5-42f1-beb8-16cc959f03b5

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The metabotropic glutamate receptor subtype 1 regulates development and maintenance of lemniscal synaptic connectivity in the somatosensory thalamus2019

    • Author(s)
      Narushima M, Yagasaki Y, Takeuchi Y, Aiba A, Miyata M
    • Journal Title

      PLoS ONE

      Volume: 14 Issue: 12 Pages: 820-820

    • DOI

      10.1371/journal.pone.0226820

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A collagen-coated PGA conduit for interpositional-jump graft with end-to-side neurorrhaphy for treating facial nerve paralysis in rat2018

    • Author(s)
      Niimi Yosuke、Matsumine Hajime、Takeuchi Yuichi、Osaki Hironobu、Tsunoda Satoshi、Miyata Mariko、Yamato Masayuki、Sakurai Hiroyuki
    • Journal Title

      Microsurgery

      Volume: Epub ahead of print Issue: 1 Pages: 70-80

    • DOI

      10.1002/micr.30291

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Reinstating olfactory bulb derived limbic gamma oscillations alleviates depression2022

    • Author(s)
      Li Q, Takeuchi Y, Wang J, Barcsai L, Pedraza KL, Kozak G, Nakai S, Kato S, Kobayashi K, Ohsawa M, Lorincz ML, Berenyi A
    • Organizer
      IBRO Workshop 2022
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Controlling pathological fear expression through closed-loop brain stimulation2022

    • Author(s)
      Barcsai L, Sierra R, Pedraza L, Lakos B, Pejin A, Kozak G, Takeuchi Y, Foldi T, Lorincz M, Berenyi A
    • Organizer
      IBRO Workshop 2022
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Closed-loop stimulation of the medial septum terminates epileptic seizures2021

    • Author(s)
      Takeuchi Y
    • Organizer
      The 44th Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Closed-loop brain stimulation for controlling epileptic seizures2021

    • Author(s)
      Takeuchi Y
    • Organizer
      The 51st Annual Meeting of the Japanese Society of Clinical Neurophysiology
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Closed-loop stimulation of the medial septum terminates epileptic seizures2021

    • Author(s)
      Takeuchi Y
    • Organizer
      The 94th Annual Meeting of the Japan Pharmacological Society
    • Related Report
      2020 Research-status Report
  • [Presentation] Closed-loop brain stimulation for epileptic seizures and beyond2021

    • Author(s)
      Takeuchi Y
    • Organizer
      The 98th Annual Meeting of the Physiological Society of Japan
    • Related Report
      2020 Research-status Report
  • [Presentation] The metabotropic glutamate receptor subtype 1 regulates development and maintenance of lemniscal synaptic connectivity through cortical activity in the somatosensory thalamus2020

    • Author(s)
      Narushima M, Yagasaki Y, Takeuchi Y, Aiba A, Miyata M
    • Organizer
      FENS Meeting 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Controlling fear expression through closed-loop intervention: Sharp-waves ripples triggering medial forebrain bundle stimulation enhance extinction and induce long-lasting fear attenuation2020

    • Author(s)
      Pedraza L, Sierra R, Takeuchi Y, Kozak G, Peijin A, Berenyi A
    • Organizer
      FENS Meeting 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Controlling fear expression through closed-loop intervention: Sharp-waves ripples triggering medial forebrain bundle stimulation enhance extinction and induce long-lasting fear attenuation2020

    • Author(s)
      Pedraza L, Sierra R, Takeuchi Y, Kozak G, Peijin A, Berenyi A
    • Organizer
      The 43rd Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2020 Research-status Report
  • [Presentation] On-demand interventions of epileptic seizures and beyond2020

    • Author(s)
      Takeuchi Y
    • Organizer
      The 43rd Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2020 Research-status Report
  • [Presentation] Closed-loop stimulation of the medial septum terminates epilepsy seizures in rats2020

    • Author(s)
      Takeuchi Y, Harangozo M, Pedraza L, Foldi T, Kozak G, Berenyi A
    • Organizer
      The 93th Annual Meeting of the Japan Pharmacological Society
    • Related Report
      2019 Research-status Report
  • [Presentation] 時空間特異的な脳活動介入によるてんかんの制御2020

    • Author(s)
      竹内雄一
    • Organizer
      第29回神経行動薬理学若手研究者の集い
    • Related Report
      2019 Research-status Report
  • [Presentation] A closed-loop proxy-intervention of epileptic seizures2020

    • Author(s)
      Takeuchi Y, Harangozo; M, Pedraza L, Foldi T, Kozak G, Berenyi A
    • Organizer
      IBRO Workshop 2020
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] The functional role of altered olfactory network synchrony in the development of depression2020

    • Author(s)
      Li Q, Takeuchi Y, Kozak G, Ohsawa M, Harangozo M, Berenyi A
    • Organizer
      IBRO Workshop 2020
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Closed-loop manipulation of hippocampal ripples reduce persistent fear expression in animal model of posttraumatic-stress disorder2020

    • Author(s)
      Pedraza L, Sierra R, Takeuchi Y, Kozak G, Peijin A, Barcsai L, Berenyi A
    • Organizer
      IBRO Workshop 2020
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Coding of self-motion-induced and self-independent visual motion in the rat dorsomedial striatum2020

    • Author(s)
      Nagy A, Takeuchi Y, Berenyi A
    • Organizer
      IBRO Workshop 2020
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Controlling hippocampal and temporal lobe seizures through medial septum using electrical and optogenetic techniques2019

    • Author(s)
      Takeuchi Y.
    • Organizer
      セゲド大学 部門公開セミナー
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] オンデマンド脳深部刺激によるてんかん発作のリアルタイム制御2019

    • Author(s)
      竹内雄一
    • Organizer
      第28回神経行動薬理学若手研究者の集い
    • Related Report
      2018 Research-status Report
  • [Presentation] Automated, closed-loop stimulation of the medial septum alleviates temporal lobe epilepsy in rats.2019

    • Author(s)
      Takeuchi Y., Harangozo; M., Pedraza L., Foldi T., Kozak G., and Berenyi A.
    • Organizer
      The 9th FAOPS Congress
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 精神・神経疾患のリアルタイム制御にむけて2018

    • Author(s)
      竹内雄一
    • Organizer
      大阪市立大学 部門公開セミナー
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Real-time closed-loop interventions of epileptic seizures2018

    • Author(s)
      竹内雄一
    • Organizer
      生理学研究所 部門公開セミナー
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 神経精神疾患のリアルタイム制御に向けて2018

    • Author(s)
      竹内雄一
    • Organizer
      日本薬学会東海支部 特別講演会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Closed-loop stimulation of the medial septum alleviates temporal lobe epilepsy in rats.2018

    • Author(s)
      Takeuchi Y., Harangozo; M., Pedraza L., Foldi T., Kozak G., and Berenyi A.
    • Organizer
      The 49th NIPS International Symposium
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Book] タウ・バイオロジー(細胞 2021.1)2021

    • Author(s)
      竹内雄一(分担執筆)
    • Total Pages
      68
    • Publisher
      北隆館
    • Related Report
      2020 Research-status Report
  • [Book] 神経難病の治療開発update(BIO Clinica 2020.8)2020

    • Author(s)
      竹内雄一(分担執筆)
    • Total Pages
      106
    • Publisher
      北隆館
    • Related Report
      2020 Research-status Report
  • [Book] てんかんの進歩(Medical Science Digest 2020.2)2020

    • Author(s)
      竹内雄一(分担執筆)
    • Total Pages
      60
    • Publisher
      北隆館
    • Related Report
      2019 Research-status Report
  • [Book] 神経精神疾患のイメージング(Medical Science Digest 2020.6)2020

    • Author(s)
      竹内雄一(分担執筆)
    • Total Pages
      88
    • Publisher
      北隆館
    • Related Report
      2019 Research-status Report
  • [Remarks] researchmap

    • URL

      https://researchmap.jp/ytake/

    • Related Report
      2021 Annual Research Report 2020 Research-status Report 2019 Research-status Report 2018 Research-status Report
  • [Remarks] 個人ウェブサイト

    • URL

      https://ytake.org/

    • Related Report
      2021 Annual Research Report
  • [Remarks] 個人ホームページ

    • URL

      https://ytake.org/

    • Related Report
      2020 Research-status Report 2019 Research-status Report
  • [Funded Workshop] Symposium: Cutting-edge closed-loop and non-invasive brain stimulation technologies for neurological and psychiatric disorders2020

    • Related Report
      2020 Research-status Report

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Published: 2018-10-12   Modified: 2023-01-30  

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