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Multi-scale investigation of cerebral anatomo-functional changes induced by long-term electrical stimulation and surgical intervention

Research Project

Project/Area Number 20H03794
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 56010:Neurosurgery-related
Research InstitutionJichi Medical University

Principal Investigator

Kawai Kensuke  自治医科大学, 医学部, 教授 (70260924)

Co-Investigator(Kenkyū-buntansha) 石下 洋平  自治医科大学, 医学部, 講師 (30835632)
島崎 久仁子  自治医科大学, 医学部, 非常勤講師 (40142153)
手塚 正幸  自治医科大学, 医学部, 助教 (40721311)
中嶋 剛  自治医科大学, 医学部, 准教授 (60625995)
國井 尚人  東京大学, 医学部附属病院, 講師 (80713940)
佐藤 信  自治医科大学, 医学部, 助教 (80742345)
高橋 宏知  東京大学, 大学院情報理工学系研究科, 教授 (90361518)
大谷 啓介  自治医科大学, 医学部, 講師 (90790676)
大貫 良幸  自治医科大学, 医学部, 講師 (90835993)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2022: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2020: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
Keywords大脳電気刺激 / 迷走神経刺激 / 神経ネットワーク / てんかん / 記憶 / 大脳皮質ネットワーク / 多点脳表脳波 / てんかん外科 / 海馬
Outline of Research at the Start

本研究の目的は、大脳への電気刺激や外科的介入がもたらす機能的変化及び形態的変化を明らかにすることである。特に長期刺激や手術後長期の変化を、大脳皮質局所から大脳全体までマルチスケールに捉えることを目標とする。そのために、(1) ラット迷走神経刺激(VNS)長期刺激モデルを用いた聴覚野皮質と海馬における局所微小ネットワーク特性の変化と形態的変化、(2) ミニブタ脳表電気刺激モデルを用いた脳回単位での多点脳表脳波と functional NIRS による機能的ネットワーク特性の変化と形態的変化、(3) ヒトてんかん手術およびVNSによる大脳全体のネットワークと形態変化の検証を行う。

Outline of Final Research Achievements

We conducted research with the aim of elucidating the functional and morphological changes caused by electrical stimulation to the brain or surgical intervention. In rats, vagus nerve stimulation (VNS) was found to enhance the feedforward pathway through the cholinergic system and attenuate the feedback pathway through the noradrenergic system in the auditory cortex, suggesting the potential modulation of cortical gain through multiple neuromodulatory systems. Additionally, using fMRI, we examined the functional network (FC) changes in the human hippocampus after hippocampal transection. We observed a decrease in FC within the hippocampus corresponding to the transient decline in memory function at one month post-surgery, and a recovery of FC corresponding to the restoration of memory function at six months post-surgery. However, there was variability in the recovery of FC between the hippocampus and the prefrontal cortex or the cerebellum.

Academic Significance and Societal Importance of the Research Achievements

本研究は、大脳への電気刺激や外科的介入が大脳の機能的ネットワークにもたらす変化を明らかにすることによって、VNSや海馬多切術の効果発現機構の解明につながるものである。さらに自律神経系による大脳皮質機能の調節機構はいまだ不明な点が多く、その解明という学術的意義が大きい。また、欧米ではさまざまな精神・神経疾患に対するニューロモデュレーション治療が急激に進歩・普及しているが、日本への導入が大幅に遅れている。その背景には効果発現機構が未解明で至適刺激条件の合理的決定法が不明という課題があり、本研究の成果はこれらの課題解決の端緒となる点で臨床的・社会的にも有意義なものである。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (10 results)

All 2022 2021 2020

All Journal Article (10 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results)

  • [Journal Article] てんかんと自律神経2022

    • Author(s)
      川合謙介
    • Journal Title

      BRAIN and NERVE: 神経研究の進歩

      Volume: 74 Pages: 271-277

    • Related Report
      2022 Annual Research Report
  • [Journal Article] てんかん等に対する迷走神経刺激療法2022

    • Author(s)
      井林賢志、川合謙介
    • Journal Title

      自律神経

      Volume: 59 Pages: 212-220

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Vagus Nerve Stimulation Amplifies Task-Induced Cerebral Blood Flow Increase2021

    • Author(s)
      Kunii Naoto、Koizumi Tomoyuki、Kawai Kensuke、Shimada Seijiro、Saito Nobuhito
    • Journal Title

      Frontiers in Human Neuroscience

      Volume: 15 Pages: 726087-726087

    • DOI

      10.3389/fnhum.2021.726087

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Global and Parallel Cortical Processing Based on Auditory Gamma Oscillatory Responses in Humans2021

    • Author(s)
      Tada Mariko、Kirihara Kenji、Ishishita Yohei、Takasago Megumi、Kunii Naoto、Uka Takanori、Shimada Seijiro、Ibayashi Kenji、Kawai Kensuke、Saito Nobuhito、Koshiyama Daisuke、Fujioka Mao、Araki Tsuyoshi、Kasai Kiyoto
    • Journal Title

      Cerebral Cortex

      Volume: 31 Issue: 10 Pages: 4518-4532

    • DOI

      10.1093/cercor/bhab103

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Current Status and Future Objectives of Surgical Therapies for Epilepsy in Japan2021

    • Author(s)
      Mikuni N, Usui N, Otsubo H, Kawai K, Kishima H, Maehara T, Mine S, Yamamoto T.
    • Journal Title

      Neurologia medico-chirurgica

      Volume: 61 Issue: 11 Pages: 619-628

    • DOI

      10.2176/nmc.st.2021-0230

    • NAID

      130008116464

    • ISSN
      0470-8105, 1349-8029
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] てんかんにおける迷走神経刺激療法2021

    • Author(s)
      石下洋平、川合謙介
    • Journal Title

      最新精神医学

      Volume: 26 Pages: 419-425

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Journal Article] てんかんに対する植込型電気刺激療法の今後2021

    • Author(s)
      川合謙介
    • Journal Title

      Epilepsy

      Volume: 15 Pages: 79-83

    • NAID

      40022809346

    • Related Report
      2021 Annual Research Report
  • [Journal Article] AIによるてんかん発作の自動診断2021

    • Author(s)
      高橋宏知、川合謙介
    • Journal Title

      Clinical Neuroscience

      Volume: 39 Pages: 241-243

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Responsive Neurostimulation as a Novel Palliative Option in Epilepsy Surgery2020

    • Author(s)
      INAJI Motoki、YAMAMOTO Takamichi、KAWAI Kensuke、MAEHARA Taketoshi、DOYLE Werner K.
    • Journal Title

      Neurologia medico-chirurgica

      Volume: 61 Issue: 1 Pages: 1-11

    • DOI

      10.2176/nmc.st.2020-0172

    • NAID

      130007968989

    • ISSN
      0470-8105, 1349-8029
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Vagus nerve stimulation (VNS)-induced layer-specific modulation of evoked responses in the sensory cortex of rats2020

    • Author(s)
      Hirokazu Takahashi, Tomoyo I. Shiramatsu, Rie Hitsuyu, Kenji Ibayashi, and Kensuke Kawai
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 8932-8932

    • DOI

      10.1038/s41598-020-65745-z

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access

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Published: 2020-04-28   Modified: 2024-01-30  

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