Hyper-adaptability to altered musculoskeletal system: cortical and subcortical mechanism.

• Project Area: Hyper-adaptability for overcoming body-brain dysfunction: Integrated empirical and system theoretical approaches
• Project/Area Number: 19H05724
• 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: National Center of Neurology and Psychiatry
• Principal Investigator: 関 和彦 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 モデル動物開発研究部, 部長 (00226630)
• Project Period (FY): 2019-06-28 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥94,120,000 (Direct Cost: ¥72,400,000、Indirect Cost: ¥21,720,000); Fiscal Year 2023: ¥15,730,000 (Direct Cost: ¥12,100,000、Indirect Cost: ¥3,630,000); Fiscal Year 2022: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000); Fiscal Year 2021: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2020: ¥12,610,000 (Direct Cost: ¥9,700,000、Indirect Cost: ¥2,910,000); Fiscal Year 2019: ¥32,110,000 (Direct Cost: ¥24,700,000、Indirect Cost: ¥7,410,000)
• Keywords: マカクサル / 可塑性 / 筋シナジー / 筋電図 / 筋再配置 / tendon transfer / macaque monkey / muscle synergy / sensorimotor / ECoG / EMG / 超適応 / 霊長類 / 運動 / 感覚予測誤差 / 身体改変

Outline of Research at the Start

身体の障害や疾病などによってヒトの身体構造が急激に変化する場合がある。そのような状態でも短時間のリハビリテーション訓練などによって意図したとおりに運動を行うことができるのは，身体運動に関わる脳神経構造が、変化した身体に適応して再構成されているからである。身体の急激な変化は後天的で個体にとって未経験の現象であり、それに対する適応は超適応として定義することができる。この、超適応時の脳神経構造の再構成のメカニズムは明らかでない。そこで、本研究ではヒトと筋骨格構造が類似しているサルを対象に、身体構造を変化させ、それに対する中枢神経系の適応を神経細胞レベルで神経生理学的に評価する。

Outline of Annual Research Achievements

当該年度は、マカクサルを対象とした筋再配置の術式を用いて作成した動物モデルを対象に、精密把握運動時の筋電図記録を新たな視点から解析し、超適応現象の背景にある中枢神経系適応の時定数を推定した。その結果、筋再配置に対する適応には早い時定数を有するfast適応、遅い時定数をもつslow適応が存在し、それらの連関によって説明できることが明らかになった。つまり、腱再配置による劇的な感覚運動連関への介入は、早い時定数の変化を誘発し（筋シナジーの逆転現象）、誘発された変化が十分大きい場合に、遅いダイナミクスの変化（逆転シナジーの連続活動）を誘発された。またその遅い時定数の変化が蓄積して閾値に到達した場合、新たな早い時定数の変化（筋シナジーの再逆転現象）を生み、それが新たな遅い時定数の変化(trick motionの獲得と熟達）を誘発する現象を定量化した。つまり、身体改変への中枢神経系の適応は異なった時定数を有する変化の連鎖モデルで説明できる可能性を示した。またこのような感覚運動変換過程の可塑性の基盤となる神経メカニズムを解明した。つまり、固有感覚入力の変化の際の感覚予測誤差の増大が、ナプス前抑制によって、また脳幹においては楔状束核における感覚ゲーティングによって、それぞれ対応できる可能性を示した。

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

• [Journal Article] Modulation of somatosensory signal transmission in the primate cuneate nucleus during voluntary hand movement (2024)
  • Author(s): Kubota Shinji、Sasaki Chika、Kikuta Satomi、Yoshida Junichiro、Ito Sho、Gomi Hiroaki、Oya Tomomichi、Seki Kazuhiko
  • Journal Title: Cell Reports Volume: 43 Issue: 3 Pages: 113884-113884
  • DOI: 10.1016/j.celrep.2024.113884
  • Peer Reviewed / Open Access
• [Journal Article] Unraveling Neural Mechanisms of Upper Limb Motor Dysfunction after Stroke and Novel Evaluation Methods for Functional Recovery (2023)
  • Author(s): Kosugi Akito、Funato Tetsuro、Seki Kazuhiko
  • Journal Title: The Japanese Journal of Rehabilitation Medicine Volume: 60 Issue: 9 Pages: 754-761
  • DOI: 10.2490/jjrmc.60.754
  • ISSN: 1881-3526, 1881-8560
  • Year and Date: 2023-09-18
• [Journal Article] Presynaptic gating of monkey proprioceptive signals for proper motor action (2023)
  • Author(s): Tomatsu Saeka、Kim GeeHee、Kubota Shinji、Seki Kazuhiko
  • Journal Title: Nature Communications Volume: 14 Issue: 1
  • DOI: 10.1038/s41467-023-42077-w
  • Peer Reviewed / Open Access
• [Journal Article] Time course of recovery of different motor functions following a reproducible cortical infarction in non-human primates (2023)
  • Author(s): Kosugi Akito、Saga Yosuke、Kudo Moeko、Koizumi Masashi、Umeda Tatsuya、Seki Kazuhiko
  • Journal Title: Frontiers in Neurology Volume: 14 Pages: 1094774-1094774
  • DOI: 10.3389/fneur.2023.1094774
  • Peer Reviewed / Open Access
• [Journal Article] Muscle synergy analysis yields an efficient and physiologically relevant method of assessing stroke (2022)
  • Author(s): Funato Tetsuro、Hattori Noriaki、Yozu Arito、An Qi、Oya Tomomichi、Shirafuji Shouhei、Jino Akihiro、Miura Kyoichi、Martino Giovanni、Berger Denise、Miyai Ichiro、Ota Jun、Ivanenko Yury、d’Avella Andrea、Seki Kazuhiko
  • Journal Title: Brain Communications Volume: 4 Issue: 4
  • DOI: 10.1093/braincomms/fcac200
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Musculoskeletal Modeling and Inverse Dynamic Analysis of Precision Grip in the Japanese Macaque (2021)
  • Author(s): Saito Tsuyoshi、Ogihara Naomichi、Takei Tomohiko、Seki Kazuhiko
  • Journal Title: Frontiers in Systems Neuroscience Volume: 15 Pages: 774596-774596
  • DOI: 10.3389/fnsys.2021.774596
  • Peer Reviewed / Open Access
• [Journal Article] Distribution of Large and Small Dorsal Root Ganglion Neurons in Common Marmosets (2021)
  • Author(s): Kudo Moeko、Wupuer Sidikejiang、Kubota Shinji、Seki Kazuhiko
  • Journal Title: Frontiers in Systems Neuroscience Volume: 15
  • DOI: 10.3389/fnsys.2021.801492
  • Peer Reviewed
• [Journal Article] Specific gene expression in unmyelinated dorsal root ganglion neurons in nonhuman primates by intranerve injection of adeno-associated virus 6 vector. (2021)
  • Author(s): Kudo M, Wupuer S, Fujiwara M, Saito Y, Kubota S, Inoue K, Takada M, Seki K
  • Journal Title: Molecular Therapy - Methods & Clinical Development Volume: 23 Pages: 11-22
  • DOI: 10.1016/j.omtm.2021.07.009
  • Peer Reviewed / Open Access
• [Journal Article] Approaches to Revealing the Neural Basis of Muscle Synergies: A Review and A Critique (2021)
  • Author(s): Cheung Vincent C. K.、Seki Kazuhiko
  • Journal Title: Journal of Neurophysiology Volume: - Issue: 5 Pages: 1580-1597
  • DOI: 10.1152/jn.00625.2019
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Forelimb force direction and magnitude independently controlled by spinal modules in the macaque (2020)
  • Author(s): Yaron Amit、Kowalski David、Yaguchi Hiroaki、Takei Tomohiko、Seki Kazuhiko
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 117 Issue: 44 Pages: 27655-27666
  • DOI: 10.1073/pnas.1919253117
  • NAID: 120006892060
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Distinct sensorimotor feedback loops for dynamic and static control of primate precision grip (2020)
  • Author(s): Tomomichi Oya, Tomohiko Takei, and Kazuhiko Seki
  • Journal Title: Communications Biology Volume: 3 Issue: 1 Pages: 156-156
  • DOI: 10.1038/s42003-020-0861-0
  • NAID: 120006823945
  • Peer Reviewed / Open Access
• [Journal Article] Characterization of Brain-Targeted Drug Delivery Enhanced by a Combination of Lipid-Based Microbubbles and Non-Focused Ultrasound (2020)
  • Author(s): Omata Daiki、Hagiwara Fumiko、Munakata Lisa、Shima Tadamitsu、Kageyama Saori、Suzuki Yuno、Azuma Takashi、Takagi Shu、Seki Kazuhiko、Maruyama Kazuo、Suzuki Ryo
  • Journal Title: Journal of Pharmaceutical Sciences Volume: 109 Issue: 9 Pages: 2827-2835
  • DOI: 10.1016/j.xphs.2020.06.008
  • Peer Reviewed / Open Access
• [Journal Article] Decoding of muscle activity from the sensorimotor cortex in freely behaving monkeys (2019)
  • Author(s): Umeda Tatsuya、Koizumi Masashi、Katakai Yuko、Saito Ryoichi、Seki Kazuhiko
  • Journal Title: NeuroImage Volume: 197 Pages: 512-526
  • DOI: 10.1016/j.neuroimage.2019.04.045
  • Peer Reviewed
• [Journal Article] Optogenetic recruitment of spinal reflex pathways from large‐diameter primary afferents in non‐transgenic rats transduced with AAV9/Channelrhodopsin 2 (2019)
  • Author(s): Kubota Shinji、Sidikejiang Wupuer、Kudo Moeko、Inoue Ken‐ichi、Umeda Tatsuya、Takada Masahiko、Seki Kazuhiko
  • Journal Title: The Journal of Physiology Volume: 597 Issue: 19 Pages: 5025-5040
  • DOI: 10.1113/jp278292
  • Peer Reviewed / Open Access
• [Presentation] Somatosensory gain modulation in primate hand movement (2024)
  • Author(s): Seki K
  • Organizer: Sensorimotor circuits for limb control
  • Int'l Joint Research / Invited
• [Presentation] 霊長類における体性感覚運動統合の神経メカニズム (2024)
  • Author(s): 関和彦
  • Organizer: 京都大学ヒト行動進化研究センター国際脳科学シンポジウム
  • Invited
• [Presentation] Modulation of cutaneous sensory signal transmission in the primate cuneate nucleus during voluntary hand movement (2024)
  • Author(s): Kubota S, Kudo M, Kikuta S, Yoshida J, Oya T, Watakabe A, Inoue K, Takada M. Seki K
  • Organizer: Sensorimotor circuits for limb control
  • Int'l Joint Research
• [Presentation] High-density neural recording reveals populational dynamics of the cervical spinal cord in rats performing target-reaching task. Sensorimotor circuits for limb control (2024)
  • Author(s): 江川史朗
  • Organizer: Sensorimotor circuits for limb control
  • Int'l Joint Research
• [Presentation] Muscle synergy analysis yields an efficient and physiologically relevant way of assessing stroke (2023)
  • Author(s): Seki K
  • Organizer: 26th Thai Neuroscience Society International Conference
  • Int'l Joint Research / Invited
• [Presentation] Centrally generated presynaptic inhibition selectively modulates proprioceptive and tactile reafferent signals at the spinal cord of behaving monkeys (2023)
  • Author(s): Seki K
  • Organizer: Motor Control: Spinal Circuits and Beyond2023
  • Int'l Joint Research / Invited
• [Presentation] Neural Adaptation in Response to Tendon Transfer in the Primate Forearm (2023)
  • Author(s): Philipp R, Uchida N, Ohta N, Oya T, Hara Y, Funato T, Seki K
  • Organizer: The 2nd International Symposium on Hyper-Adaptability 2023
  • Int'l Joint Research
• [Presentation] Neural adaptation to a physically-modified body in non-human primates (2023)
  • Author(s): Seki K
  • Organizer: The 2nd International Symposium on Hyper-Adaptability 2023
  • Int'l Joint Research
• [Presentation] Neuropixels recording in the Spinal Cord of Behaving Rats (High-density neural recording reveals cervical spinal cord neuronal circuits in awake behaving rats) (2023)
  • Author(s): Egawa S, Kosugi A, Maeda K, Yaron A, Seki K
  • Organizer: Neuroscience 2023
  • Int'l Joint Research
• [Presentation] Development of a novel behavioral task paradigm for somatosensory-guided motor learning in macaque monkeys (2023)
  • Author(s): Yoshida J, Kubota S, Seki K
  • Organizer: The 2nd International Symposium on Hyper-Adaptability 2023
  • Int'l Joint Research
• [Presentation] Optogenetic activation of somatosensory afferents in non-human primates by systemic AAV administration (2023)
  • Author(s): Kosugi A, Kudo M, Inoue K, Takada M, Seki K
  • Organizer: Motor Control: Spinal Circuits and Beyond2023
  • Int'l Joint Research
• [Presentation] Modulation of somatosnesory signals through a cortico-cuneate pathway during voluntary hand movement (2023)
  • Author(s): Kubota S, Kudo M, Kikuta S, Yoshida J, Oya T, Seki K
  • Organizer: NCM2023
  • Int'l Joint Research
• [Presentation] Analysis of muscle activity related to long-term adaptation after tendon-transfer in a macaque monkey (2023)
  • Author(s): Ota N, Philipp R, Hara Y, Funato T, Seki K
  • Organizer: NCM2023
  • Int'l Joint Research
• [Presentation] Neural adaptation in response to a tendon cross-union of an antagonistic muscle pair in the forearm of the macaque: An EMG and EGoG study (2023)
  • Author(s): Philipp R, Ohta N, Takayama Y, Hara Y, Funato T, Seki K
  • Organizer: 第46回日本神経科学大会
• [Presentation] Modulation of sensory evoked potentials in the sensory motor cortex during voluntary movement (2023)
  • Author(s): Yoshida J, Kubota S, Kikuta S, Seki K
  • Organizer: 第46回日本神経科学大会
• [Presentation] Spinal motor modules for primate arm and hand movement. (2022)
  • Author(s): Seki K
  • Organizer: WCB2022
  • Int'l Joint Research / Invited
• [Presentation] Gating of Somatosensory Signals in the Primate Cuneate Nucleus During Voluntary Hand Movement (2022)
  • Author(s): Kubota S, Sasaki C, Kikuta S, Oya T, Seki K
  • Organizer: Motor Systems Symposium 2022 - Salk Institute for Biological Studies,
  • Int'l Joint Research
• [Presentation] Neural adaptation in response to tendon cross-union of an antagonistic muscle pair in the primate forearm (2022)
  • Author(s): Philipp R, Uchida N, Hara Y, Funato T, Seki K
  • Organizer: Neuroscience 2022
  • Int'l Joint Research
• [Presentation] Proprioceptive sensory attenuation in area 3a during voluntary movement and action observation in macaque (2022)
  • Author(s): Seki K, Kikuta S, Kubota S, Confais J, Yaron A, Oya T
  • Organizer: Neuroscience 2022
  • Int'l Joint Research
• [Presentation] Gating of proprioceptive signals in the primate cuneate nucleus during voluntary hand movement (2022)
  • Author(s): Kubota S, Sasaki C, Kikuta S, Oya T, Seki K
  • Organizer: Neuroscience 2022
  • Int'l Joint Research
• [Presentation] 筋シナジー及びその制御の神経機構 (2022)
  • Author(s): 関和彦
  • Organizer: 第20回日本神経理学療法学会学術大会
  • Invited
• [Presentation] パネルディスカッション3「骨を繋ぎ、稼働させる筋と腱を俯瞰する」 (2022)
  • Author(s): 関和彦
  • Organizer: 第40回日本骨代謝学会
  • Invited
• [Presentation] 無意識下でつながる感覚と運動 (2022)
  • Author(s): 関和彦
  • Organizer: さきがけ「生体多感覚システム」領域公開シンポジウム
  • Invited
• [Presentation] Sensory gain modulation at the primate cuneate nucleus; top-down and bottom-up neural mechanisms. (2021)
  • Author(s): Seki K
  • Organizer: NCM2021
  • Int'l Joint Research / Invited
• [Presentation] Modulation of somatosensory signal transmission in the primate cuneate nucleus during voluntary hand movement. (2021)
  • Author(s): Kubota S, Sasaki C, Ito S, Gomi H, Oya T, Seki K
  • Organizer: NCM2021
  • Int'l Joint Research
• [Presentation] Elucidation of neural mechanisms of hyper-adaptabilityto body change (2021)
  • Author(s): Seki K
  • Organizer: 1st International Symposium on Hyper-Adaptability
  • Int'l Joint Research
• [Presentation] Hyper-adaptation after tendon transfer of upper limb: Neural mechanisms inducing hyper-adaptation (2021)
  • Author(s): Philipp R, Uchida N, Hara Y, Funato T, Seki K
  • Organizer: 第44回日本神経科学大会 シンポジウム「脳の超適応」
• [Presentation] マカクサルの上肢筋腱移植手術に伴う中枢神経系の長期適応様式 (2021)
  • Author(s): 関和彦
  • Organizer: 令和3年度 京都大学 霊長類研究所 共同利用研究会
  • Invited
• [Presentation] 随意運動の制御における脊髄神経回路の新機能 (2021)
  • Author(s): 関和彦
  • Organizer: 日本脊髄外科学会
  • Invited
• [Presentation] Bio-Electrical Signals for Motor Control in Robotics: Standardization of Muscle Synergy Analysis (2021)
  • Author(s): Alvaro Costa, Massimo Sartori, Qi An, Kazuhiko Seki, Andrea d`Avella, Diego Torricelli, Yuri Ivanenko, Andres Ubeda, Fady Alnajjar, Emel Demircan, Juan C. Moreno, Shingo Shimoda
  • Organizer: 2021 IEEE/RSJ International conference on intelligent robots and systems
  • Int'l Joint Research / Invited
• [Presentation] Hyper-adaptation after tendon transfer of upper limb: Neural mechanisms inducing hyper-adaptation (2021)
  • Author(s): Philipp R, Uchida N, Hara Y, Funato T, Seki K
  • Organizer: 1st International Symposium on Hyper-Adaptability
  • Int'l Joint Research
• [Presentation] Are primates just big frogs? Forelimb force direction and amplitude are independently controlled by spinal motor modules (2020)
  • Author(s): Yaron A, Kowalski D, Yaguchi H, Takei T, Seki K
  • Organizer: Neuromatch meeting
  • Int'l Joint Research
• [Presentation] 自由行動下における皮質脳波から筋活動情報を解読する ―野生型及び脳梗塞モデルサルにおける検討例― (2020)
  • Author(s): 関和彦
  • Organizer: 第22回日本ヒト脳機能マッピング学会
  • Invited
• [Presentation] 生物の感覚運動機能を左右する閉ループ神経回路とその非侵襲的制御 (2020)
  • Author(s): 関和彦、高木周、東隆、丸山和雄、鈴木亮
  • Organizer: 第43回日本神経科学大会
  • Invited
• [Presentation] Modular control of limb movement: from neural correlates to clinical relevance (2019)
  • Author(s): Seki K
  • Organizer: WORKSHOP on NEUROROBOTICS
  • Int'l Joint Research / Invited
• [Presentation] Neural adaptation to surgical relocation of primate hand muscles (2019)
  • Author(s): Seki K
  • Organizer: Tokyo Hand Meeting(NCM Ancillary Meeting)
  • Int'l Joint Research
• [Presentation] Spinal and cortical neural mechanism for active inference in volitional movement. (2019)
  • Author(s): Seki K
  • Organizer: The Satellite Meeting/29th NCM Annual Meeting
  • Int'l Joint Research
• [Presentation] Decoding muscle activity using electrocorticographic signals in freely behaving marmosets (2019)
  • Author(s): Umeda T, Koizumi M, Katakai Y, Saito R, Seki K
  • Organizer: 29th NCM Annual Meeting
  • Int'l Joint Research
• [Presentation] Emergence of spinomuscular and corticomuscular loops in dynamic vs. static phases of precision grip. (2019)
  • Author(s): Oya T, Takei T, Seki K
  • Organizer: 29th NCM Annual Meeting
  • Int'l Joint Research
• [Presentation] Linear summation of spinally-induced forearm force field in macaque monkeys. (2019)
  • Author(s): Yaron A, Yaguchi H, Kowalski D, Takei T, Seki K
  • Organizer: 29th NCM Annual Meeting
  • Int'l Joint Research / Invited
• [Presentation] Gain control of spinal proprioceptive reflex in awake, behaving monkeys. (2019)
  • Author(s): Seki K
  • Organizer: Neuroscience 2019
  • Int'l Joint Research / Invited
• [Presentation] Mini-symposium “Gain Control in the Sensorimotor System: From Neural Circuit Organization to Behavioral Function (2019)
  • Author(s): Seki K, E. Azim
  • Organizer: Neuroscience 2019
  • Int'l Joint Research
• [Presentation] 協調的筋活動を作り出す神経機構 (2019)
  • Author(s): 関 和彦
  • Organizer: 第58回日本運動障害研究会
  • Invited
• [Presentation] 自由行動下における皮質脳波から筋活動のデコーディング (2019)
  • Author(s): 梅田 達也, 小泉 昌司 , 片貝 祐子, 齋藤 亮一, 関 和彦
  • Organizer: 第42回日本神経科学大会
• [Presentation] 後根神経節（DRG）細胞への細胞種特異的遺伝子導入法: 齧歯類と霊長類における比較 (2019)
  • Author(s): 工藤もゑこ, Wupuer Sidikejiang, 井上 謙一, 高田 昌彦, 関 和彦
  • Organizer: 第42回日本神経科学大会
• [Presentation] 筋電解析による身体変化に対する神経適応メカニズムの解明 (2019)
  • Author(s): 内田直輝, Roland Philipp, 大屋知徹, 舩戸徹郎, 関和彦
  • Organizer: 第13回Motor Control研究会