Estabilishing an artificial neural connection for improving voluntary locomotor function in individuals with spinal cord injury

• Project/Area Number: 18H03141
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 59010:Rehabilitation science-related
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: TAZOE Toshiki 公益財団法人東京都医学総合研究所, 脳・神経科学研究分野, 主席研究員 (60513017)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2021: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2020: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2019: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2018: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
• Keywords: 脊髄損傷 / 磁気刺激 / 歩行 / 人工神経接続 / 神経可塑性

Outline of Final Research Achievements

A non-invasive artificial neural connection using transvertebral magnetic stimulation was demonstrated to be an effective rehabilitation approach for inducing the recovery of voluntary locomotor function in individuals with chronic spinal cord injury. Residual function in the lumbar motor circuits receiving stimulation and the corticospinal pathways to the lumbar motor circuits was important to gain the rehabilitation effect of the non-invasive artificial neural connection.

Academic Significance and Societal Importance of the Research Achievements

脊髄損傷者に対する脊髄刺激リハビリテーションは外科手術を必要とする侵襲的な手法についてその有効性が示されていたが、本研究によって得られた成果は、磁気刺激のような非侵襲的な手技によっても、脊髄損傷者の脊髄機能を賦活化し歩行機能回復に寄与する手法となり得ることを実証することとなった。これにより、本研究で用いた非侵襲的な人工神経接続の技術は、幅広く実用的な歩行リハビリテーションの開発に大きく貢献する成果となった。

Research Products

• [Journal Article] Corticospinal interface to restore voluntary control of joint torque in a paralyzed forearm following spinal cord injury in non-human primates (2023)
  • Author(s): Obara Kei、Kaneshige Miki、Suzuki Michiaki、Yokoyama Osamu、Tazoe Toshiki、Nishimura Yukio
  • Journal Title: Frontiers in Neuroscience Volume: 17 Pages: 1127095-1127095
  • DOI: 10.3389/fnins.2023.1127095
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 特集 動的環境への適応系としての歩行 人工神経接続を用いた脳･脊髄損傷後の身体運動機能の再建 (2022)
  • Author(s): 田添 歳樹、西村 幸男
  • Journal Title: BRAIN and NERVE Volume: 74 Issue: 9 Pages: 1111-1116
  • DOI: 10.11477/mf.1416202190
  • ISSN: 1344-8129, 1881-6096
  • Year and Date: 2022-09-01
• [Journal Article] Tuning of motor outputs produced by spinal stimulation during voluntary control of torque directions in monkeys (2022)
  • Author(s): Kaneshige Miki、Obara Kei、Suzuki Michiaki、Tazoe Toshiki、Nishimura Yukio
  • Journal Title: eLife Volume: 11 Pages: 1-27
  • DOI: 10.7554/elife.78346
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Activation of human spinal locomotor circuitry using transvertebral magnetic stimulation (2022)
  • Author(s): Kawai Kazutake、Tazoe Toshiki、Yanai Toshimasa、Kanosue Kazuyuki、Nishimura Yukio
  • Journal Title: Frontiers in Human Neuroscience Volume: 16 Pages: 1016064-1016064
  • DOI: 10.3389/fnhum.2022.1016064
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Assessment of safety of self-controlled repetitive trans-vertebral magnetic stimulation (2021)
  • Author(s): Sasada S, Kadowaki S, Tazoe T, Murayama T, Kato K, Nakao Y, Matsumoto H, Nishimura Y, Ugawa Y
  • Journal Title: Clinical Neurophysiology Volume: 132（12） Issue: 12 Pages: 3166-3176
  • DOI: 10.1016/j.clinph.2021.09.016
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Abnormal changes in motor cortical maps in humans with spinal cord injury (2021)
  • Author(s): Tazoe Toshiki、Perez Monica A.
  • Journal Title: The Journal of Physiology Volume: 599 Issue: 22 Pages: 5031-5045
  • DOI: 10.1113/jp281430
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 閉回路型脊髄刺激によるニューロモジュレーションの誘導 (2021)
  • Author(s): 田添 歳樹、西村 幸男
  • Journal Title: 運動器リハビリテーション Volume: 32 Pages: 255-262
• [Journal Article] Arm cycling increases the short-latency reflex from ankle dorsiflexor afferents to knee extensor muscles. (2021)
  • Author(s): Sasada S, Tazoe T, Nakajima T, Omori S, Futatsubashi G, Komiyama T
  • Journal Title: Journal of Neurophysiology Volume: 125 Issue: 1 Pages: 110-119
  • DOI: 10.1152/jn.00299.2020
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 人工神経接続の臨床応用 (2020)
  • Author(s): 田添歳樹、加藤健治、西村幸男
  • Journal Title: 医学のあゆみ Volume: 275 Pages: 21569-21572
• [Journal Article] Non-invasive Neuromodulation―基礎・検査・治療 B.検査と治療 歩行障害 (2020)
  • Author(s): 田添歳樹、兼重美希、西村幸男
  • Journal Title: Clinical Neuroscience Volume: 38 Pages: 80-84
• [Journal Article] 特集 "スポーツ"を生み出す脳 アスリート脳の理解に向けて (2019)
  • Author(s): 横山修, 田添歳樹, 西村幸男
  • Journal Title: BRAIN and NERVE Volume: 71 Issue: 2 Pages: 99-103
  • DOI: 10.11477/mf.1416201228
  • ISSN: 1344-8129, 1881-6096
  • Year and Date: 2019-02-01
• [Journal Article] ヒト脊髄歩行中枢の入力出力関係 (2019)
  • Author(s): 河合一武、田添歳樹、彼末一之、西村幸男
  • Journal Title: スポーツ科学研究 Volume: 16 Pages: 49-61
  • NAID: 120006891844
• [Presentation] Reorganization of human spinal locomotor circuitry after spinal cord injury (2022)
  • Author(s): Toshiki Tazoe, Takashi Murayama, Tomonari Tosaka, Miki Kaneshige, Michiaki Suzuki, Naohisa Kikuchi, Yoshikazu Ugawa, Yukio Nishimura
  • Organizer: 51st annual meeting of Society for Neuroscience
  • Int'l Joint Research
• [Presentation] Stimulus intensity- and location-specific activation of human spinal locomotor circuitry by non-invasive transvertebral magnetic stimulation (2022)
  • Author(s): Kazutake Kawai, Toshiki Tazoe, Yukio Nishimura
  • Organizer: 51st annual meeting of Society for Neuroscience
  • Int'l Joint Research
• [Presentation] Adaptation to cortico-spinal interface to restore forearm paralysis in spinal cord injury (2022)
  • Author(s): Kei Obara, Miki Kaneshige, Michiaki Suzuki, Toshiki Tazoe, Yukio Nishimura
  • Organizer: 51st annual meeting of Society for Neuroscience
  • Int'l Joint Research
• [Presentation] 脊髄損傷後の運動機能の回復過程において、増大した脊髄のアウトプットは、一次運動野神経細胞活動の変調の減少と関連する (2022)
  • Author(s): 兼重 美希、尾原 圭、鈴木 迪諒、田添 歳樹、西村 幸男
  • Organizer: 第16回モーターコントロール研究会
• [Presentation] 人工的な皮質ー脊髄路に対して脊髄損傷モデルサルは大脳皮質運動野のニューロン群を適応させる (2022)
  • Author(s): 尾原 圭、兼重 美希、鈴木 迪諒、横山 修、田添 歳樹、西村 幸男
  • Organizer: 第16回モーターコントロール研究会
• [Presentation] Aberrant activity of spinal locomotor circuitry in humans with complete spinal cord injury (2022)
  • Author(s): Toshiki Tazoe, Takashi Murayama, Tomonari Tosaka, Miki Kaneshige, Michiaki Suzuki, Naohisa Kikuchi, Yoshikazu Ugawa, Yukio Nishimura
  • Organizer: 第45回日本神経科学大会
• [Presentation] Enhanced spinal outputs are associated with compensatory changes in cell activities of monkey motor cortex through motor recovery after spinal cord injury (2022)
  • Author(s): Miki Kaneshige, Kei Obara, Michiaki Suzuki, Toshiki Tazoe, Yukio Nishimura
  • Organizer: 第45回日本神経科学大会
• [Presentation] An ensemble tuning of the macaque primary motor cortex during adaptation to the artificial corticospinal pathway after spinal cord injury (2022)
  • Author(s): Kei Obara, Miki Kaneshige, Michiaki Suzuki, Toshiki Tazoe, Yukio Nishimura
  • Organizer: 第45回日本神経科学大会
• [Presentation] Location specific excitation of human spinal locomotor circuitry by transvertebral magnetic stimulation (2021)
  • Author(s): Toshiki Tazoe, Yukio Nishimura
  • Organizer: 1st China-Japan-Korea International Meeting（第44回日本神経科学大会共催）
  • Int'l Joint Research
• [Presentation] Activation of human spinal locomotor circuitry using transvertebral magnetic stimulation (2021)
  • Author(s): Kazutake Kawai, Toshiki Tazoe, Kazuyuki Kanosue, Yukio Nishimura
  • Organizer: 1st China-Japan-Korea International Meeting（第44回日本神経科学大会共催）
  • Int'l Joint Research
• [Presentation] Bypassing spinal lesion via artificial cortico-spinal pathway induces task-related modulations in an ensemble of M1 neurons (2021)
  • Author(s): Kei Obara, Miki Kaneshige, Michiaki Suzuki, Toshiki Tazoe, Yukio Nishimura
  • Organizer: 1st China-Japan-Korea International Meeting（第44回日本神経科学大会共催）
  • Int'l Joint Research
• [Presentation] Boosting motor outputs and inducing cortical adaptation via artificial neural connection (2021)
  • Author(s): Miki Kaneshige, Kei Obara, Michiaki Suzuki, Toshiki Tazoe, Yukio Nishimura
  • Organizer: 1st China-Japan-Korea International Meeting（第44回日本神経科学大会共催）
  • Int'l Joint Research
• [Presentation] Activation of human spinal locomotor circuitry using transvertebral magnetic stimulation (2020)
  • Author(s): Kazutake Kawai, Toshiki Tazoe, Kazuyuki Kanosue, Yukio Nishimura
  • Organizer: 第97回日本生理学会大会
• [Presentation] Non-invasive transvertebral magnetic stimulation discloses residual motor function of sublesional spinal circuitry in humans with spinal cord injury (2019)
  • Author(s): Toshiki Tazoe, Michiaki Suzuki, Miki Kaneshige, Koichi Iwatsuki, Yukio Nishimura
  • Organizer: 49th annual meeting of Society for Neuroscience
  • Int'l Joint Research
• [Presentation] Spinal stimulus effects altered by voluntary muscle activity in monkeys (2019)
  • Author(s): Miki Kaneshige, Kei Obara, Michiaki Suzuki, Toshiki Tazoe, Yukio Nishimura
  • Organizer: 29th annual meeting of Nueral Control of Movement
  • Int'l Joint Research
• [Presentation] ヒトの粗大把持運動に貢献する一次運動野活動 (2019)
  • Author(s): 田添歳樹
  • Organizer: 身体運動制御の会
  • Invited
• [Presentation] Functional organization of spinal motor map in sport athletes (2019)
  • Author(s): Toshiki Tazoe
  • Organizer: 9th Federation of the Asian and Oceanian Physiological Societies Congress
  • Int'l Joint Research
• [Presentation] Muscle representations in spinal motor circuitry in intact humans and an individual with SCI (2019)
  • Author(s): Toshiki Tazoe, Koichi Iwatsuki, Yukio Nishimura
  • Organizer: 9th Federation of the Asian and Oceanian Physiological Societies Congress
  • Int'l Joint Research
• [Presentation] 皮質内介在ニューロン回路の粗大把握運動への選択的関与 (2018)
  • Author(s): 田添歳樹
  • Organizer: 第12回モーターコントロール研究会
• [Presentation] Early limb unloading elicits long-term motor deficits involving hyperexcitability underlying persist glutamatergic synaptic plasticity in spinal cord injury (2018)
  • Author(s): Morioka K, Tazoe T, Huie JR, Haefeli J, Almeida CA, Sacramento JA, Bresnahan JC, Beattie MS, Tanaka S, Ogata T, Ferguson AR
  • Organizer: 48th annual meeting of Society for Neuroscience
  • Int'l Joint Research
• [Presentation] 経脊椎磁気刺激によるヒト脊髄神経回路の体部位局在 (2018)
  • Author(s): 田添歳樹，岩月幸一，西村幸男
  • Organizer: 次世代脳プロジェクト冬のシンポジウム
• [Presentation] 磁気刺激による脊髄歩行中枢の刺激強度特性 (2018)
  • Author(s): 河合一武，田添歳樹，西村幸男
  • Organizer: 次世代脳プロジェクト冬のシンポジウム