A closed-loop brain stimulation for reinforcing hyper-adaptability

• Project Area: Hyper-adaptability for overcoming body-brain dysfunction: Integrated empirical and system theoretical approaches
• Project/Area Number: 22H04762
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Complex systems
• Research Institution: Hokkaido University
• Principal Investigator: 竹内 雄一 北海道大学, 薬学研究院, 准教授 (70588384)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2023: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2022: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 脳波 / 機械学習 / 閉ループ制御 / 脳深部刺激 / 強化

Outline of Research at the Start

運動・感覚疾患、神経・精神疾患は、脳―身体―環境システムの変化に我々が上手く適応できずに障害が生じている状態である。当該疾患を克服するためには、脳に潜在する冗長ネットワークの探索・再動員により、ネットワーク構造を再構成する「超適応現象」を適切に誘導する必要がある。もし超適応現象が不適切に生じた場合は例えば幻肢痛のような病態に陥ってしまう可能性があるが、これまで超適応現象を適切にガイドする方法は存在しなかった。本研究では、時間特異的な報酬系脳領域刺激によって好ましい脳状態を強化することで、超適応現象を適切に誘導する新しい脳刺激法の開発に挑む。

Outline of Annual Research Achievements

運動・感覚疾患、神経・精神疾患は、脳―身体―環境システムの変化に我々が上手く適応できずに障害が生じている状態である。当該疾患を克服するためには、脳に潜在する冗長ネットワークの探索・再動員によるネットワーク構造の再構成、即ち”超適応現象”を適切に誘導する必要がある。一方、もし超適応現象が不適切に生じた場合は例えば幻肢痛のような病態に陥ってしまう可能性がある。しかしながらこれまで超適応現象を適切に誘導する方法は存在しなかった。こうした状況下最近研究代表者らは、心的外傷後ストレス障害（PTSD）モデル動物において、時間特異的報酬系脳領域刺激による恐怖消去学習の適切な強化にプレリミナリに成功した。そこで本研究では、時間特異的報酬系脳領域刺激がPTSDのみならず他の神経・精神疾患の症状も制御可能か検討することで、超適応現象の適切な誘導法を確立することを目的とした。
本年度は、神経・精神疾患モデル動物（うつ病、アルツハイマー型認知症）において、時間特異的脳深部刺激による症状制御実験に成功した。具体的には、まず、うつ病モデルラットにおいて、減弱した嗅球―梨状皮質間におけるガンマ周波帯脳活動を時間特異的脳深部刺激で増強することで、うつ病様行動を寛解できることを見出した。さらに、家族性アルツハイマー病患者由来変異を有するヒト化アミロイド前駆タンパク質のノックインマウスにおいて、時間特異的報酬系脳領域刺激で、一度障害された認知機能を回復させることに成功した。

Research Progress Status

令和5年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和5年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] ニューヨーク大学(米国)
• [Int'l Joint Research] セゲド大学(ハンガリー)
• [Int'l Joint Research] セゲド大学(ハンガリー)
• [Int'l Joint Research] ニューヨーク大学(米国)
• [Journal Article] TRPC6 is a mechanosensitive channel essential for ultrasound neuromodulation in mammalian brain (2024)
  • Author(s): Matsushita YM, Yoshida K, Yoshiya M, Shimizu T, Tsukamoto S, Takeuchi Y, Higuchi M, Shimojo M
  • Journal Title: bioRxiv Volume: 2024
  • DOI: 10.1101/2024.03.06.583779
  • Open Access / Int'l Joint Research
• [Journal Article] Reinstating olfactory bulb-derived limbic gamma oscillations alleviates depression-like behavioral deficits in rodents (2023)
  • Author(s): Li, Q.*, Takeuchi, Y.*, Wang, J., Barcsai, L., Pedraza, L.K., Kozak, G., Nakai, S., Kato, S., Kobayashi, K., Ohsawa, M., Lorincz, M.L., Devinsky, O., Buzsaki, G. and Berenyi, A. * Equal contribution
  • Journal Title: Neuron Volume: 111 Issue: 13 Pages: 2065
  • DOI: 10.1016/j.neuron.2023.04.013
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Closed-loop brain stimulation augments fear extinction in male rats (2023)
  • Author(s): Sierra RO, Pedraza LK, Barcsai L, Peijin A, Li Q, Kozak G, Takeuchi Y, Nagy AJ, Lorincz ML, Devinsky O, Buzsaki G, Berenyi A
  • Journal Title: Nature Communications Volume: 14 Issue: 1 Pages: 3972-3972
  • DOI: 10.1038/s41467-023-39546-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Toward non-invasive, precise control of internal organs via ultrasound neuromodulation of the autonomic nervous system (2023)
  • Author(s): Xu Y, Yoshida K, Takeuchi Y
  • Journal Title: Proc SPIE Volume: 12608 Pages: 59-59
  • DOI: 10.1117/12.3008167
  • Peer Reviewed
• [Journal Article] Time-targeted stimulation of the bran rewarding system as a novel brain disorder treatment (2023)
  • Author(s): Hara K, Takeuchi Y
  • Journal Title: Medical Science Digest Volume: 49 Pages: 154-156
• [Journal Article] Editorial: Oscillotherapeutics - Toward real-time control of pathological oscillations in the brain (2022)
  • Author(s): Takeuchi Y, Li Q, Kawano T, Nagai J, Mima T
  • Journal Title: Front Behav Neurosci Volume: 16 Pages: 1021616-1021616
  • DOI: 10.3389/fnbeh.2022.1021616
  • Open Access / Int'l Joint Research
• [Journal Article] Closed-loop brain stimulation to reduce pathologic fear (2022)
  • Author(s): Sierra RO, Pedraza LK, Barcsai L, Peijin A, Kozak G, Takeuchi Y, Lorincz ML, Devinsky O, Buzsaki G, Berenyi A
  • Journal Title: bioRxiv Volume: - Pages: 501314-501314
  • DOI: 10.1101/2022.07.24.501314
  • Open Access / Int'l Joint Research
• [Presentation] A closed-loop sonogenetic control of absence epilepsy (2024)
  • Author(s): Yoshida K, Minami M, Takeuchi Y
  • Organizer: The 101st Annual Meeting of The Physiological Society of Japan
  • Invited
• [Presentation] A non-invasive gene transfection technology using transcranial focused ultrasound irradiation (2024)
  • Author(s): Mimura T, Chan M, Minami M, Kudo N, Takeuchi Y
  • Organizer: The 101st Annual Meeting of The Physiological Society of Japan
• [Presentation] Reinstating olfactory bulb-derived limbic gamma oscillations alleviates depression-like behavioral deficits in rodents (2024)
  • Author(s): Takeuchi Y
  • Organizer: The 101st Annual Meeting of The Physiological Society of Japan
• [Presentation] Reinstating olfactory bulb derived limbic gamma oscillations alleviates depression-like behavioral deficits in rodents (2024)
  • Author(s): Li Q, Takeuchi Y, Wang J, Gellert L, Barcsai L, Pedraza LK, Nagy AJ, Kozak G, Nakai S, Kato S, Kobayashi K, Ohsawa M, Horvath G, Kekesi G, Lorincz ML, Devinsky O, Buzsaki G, Berenyi A
  • Organizer: The 2nd International Symposium Hyper-Adaptability
  • Int'l Joint Research
• [Presentation] Transcranial sonoporation technology for non-invasive gene transfection (2023)
  • Author(s): Mimura T, Chan M, Minami M, Omata D, Suzuki R, Takeuchi Y
  • Organizer: The 150th Annual Meeting of the Hokkaido Branch of the Pharmaceutical Society of Japan
• [Presentation] A closed-loop transcranial ultrasound irradiation system for an awake rat model of absence epilepsy (2023)
  • Author(s): Yoshida K, Minami M, Takeuchi Y
  • Organizer: The 46th Annual Meeting of the Japan Neuroscience Society
• [Presentation] Non-invasive gene transfection to neurons in the cortex using transcranial ultrasound irradiation (2023)
  • Author(s): Chan M, Mimura T, Minami M, Takeuchi Y
  • Organizer: The 46th Annual Meeting of the Japan Neuroscience Society
• [Presentation] A neural basis of decision-making when faced with contradictory predictions of reward and punishment (2023)
  • Author(s): Yoshida K, Chan M, Minami M, Takeuchi Y
  • Organizer: CogFeel@ALIFE2023
  • Int'l Joint Research
• [Presentation] Non-invasive, spatiotemporal control of internal organs via sonogenetic stimulation of the autonomic nervous system (2023)
  • Author(s): Yoshida K, Xu Y, Mimura T, Chan M, Kudo N, Minami M, Takeuchi Y
  • Organizer: JNNS2023
• [Presentation] Toward non-invasive, precise control of internal organs via ultrasound neuromodulation of the autonomic nervous system (2023)
  • Author(s): Xu Y, Yoshida K, Takeuchi Y
  • Organizer: 9th Biomedical Imaging and Sensing Conference. Yokohama, Japan
  • Int'l Joint Research / Invited
• [Presentation] Bidirectional GABAergic and cholinergic modulation of delta-band activities in a hippocampal-like circuit in silico (2023)
  • Author(s): Itagaki K, Minami M, Takeuchi Y
  • Organizer: The 100th Anniversary Annual Meeting of The Physiological Society of Japan
• [Presentation] Transcranial sonoporation technology for non-invasive gene transfection to neurons in the cerebral cortex (2023)
  • Author(s): Mimura T, Chan M, Minami M, Takeuchi Y
  • Organizer: The 143rd Annual Meeting of the Pharmaceutical Society of Japan
• [Presentation] Controlling pathologic fear expression through closed-loop brain stimulation (2022)
  • Author(s): Sierra RO, Pedraza LK, Barcsai L, Peijin A, Kozak G, Takeuchi Y, Lorincz M, Berenyi A
  • Organizer: The 52nd SfN Annual Meeting
  • Int'l Joint Research
• [Presentation] Reinstating olfactory bulb derived limbic gamma oscillations alleviates depression-like behavioral deficits in rodents (2022)
  • Author(s): Li Q, Takeuchi Y, Wang J, Barcsai L, Pedraza KL, Kozak G, Nakai S, Kato S, Kobayashi K, Ohsawa M, Lorincz ML, Devinsky O, Buzsaki G, Berenyi A
  • Organizer: The 52nd SfN Annual Meeting
  • Int'l Joint Research
• [Presentation] A neural basis of decision-making under conflicting predictions of reward and punishment (2022)
  • Author(s): Yoshida K, Chan M, Li Q, Pedraza L, Sierra R, Minami M, Berenyi A, Takeuchi Y
  • Organizer: The 52nd SfN Annual Meeting
  • Int'l Joint Research
• [Presentation] A neural basis of decision-making under conflicting predictions of reward and punishment (2022)
  • Author(s): Yoshida K, Chan M, Li Q, Pedraza L, Sierra R, Berenyi A, Minami M, Takeuchi Y
  • Organizer: The 45th Annual Meeting of the Japan Neuroscience Society
• [Presentation] Decoding and quantification of seizure susceptibility with cross-regional oscillatory brain activity patterns in a rat model of temporal lobe epilepsy (2022)
  • Author(s): Takeuchi Y, Li Q, Berenyi A, Minami M
  • Organizer: The 45th Annual Meeting of the Japan Neuroscience Society
• [Presentation] Reduced operant task engagement and altered neural oscillations in a triple-hit rat model of schizophrenia (2022)
  • Author(s): Chan M, Li Q, Horvath G, Berenyi A, Minami M, Takeuchi Y
  • Organizer: The 45th Annual Meeting of the Japan Neuroscience Society
• [Presentation] Closed-loop control of neurological and psychiatric disorders (2022)
  • Author(s): Takeuchi Y
  • Organizer: BPCNPNPPP4
  • Invited
• [Book] Oscillotherapeutics - Toward Real-Time Control of Pathological Oscillations in the Brain (2022)
  • Author(s): Takeuchi Y, Kawano T, Li Q, Mima T, Nagai J
  • Total Pages: 109
  • Publisher: Lausanne: Frontiers Media SA.
  • ISBN: 9782889764587
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