神経修飾法による新しい運動障害治療の開発

• Project Area: Understanding brain plasticity on body representations to promote their adaptive functions
• Project/Area Number: 15H01658
• 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: The University of Tokyo
• Principal Investigator: 濱田 雅 東京大学, 医学部附属病院, 助教 (40708054)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000); Fiscal Year 2016: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
• Keywords: 経頭蓋磁気刺激法 / 神経修飾 / 運動障害 / 経頭蓋磁気刺激

Outline of Annual Research Achievements

本研究では神経修飾法による新しい運動障害治療の開発を目的とした。初年度は申請者が開発した強力な神経修飾法Quadripulse stimulation (QPS)について、効果が多数例でも安定していることを示し、またこれまでの研究をまとめ高齢者では反応率が下がることを示した。ＱＰＳ以外でもより強力な効果が得られることを想定しtheta burst stimulation (ＴＢＳ)という方法を用いて障害された神経ネットワークに関わる脳領域の多数部位同時/逐次刺激により神経ネットワークモデュレーションを行った。残念ながら多数部位刺激でもＴＢＳではやはりばらつきが大きく、より強力な効果を得ることはできなかった。この原因としては同時部位刺激により得られる効果はあまり大きくなく、刺激プロトコール自体のeffect sizeのほうが勝っている可能性が示唆された。神経修飾法による新しい運動障害治療開発の一環として、その機序の解明に関する研究も行った。磁気刺激による治療効果の一部は運動学習を介して発現している可能性を考えその機序の解明のためにＱＰＳや連合性ペア刺激による運動学習への効果を検討した。結果としては連合性ペア刺激では小脳適応学習阻害効果は刺激されている細胞集団特性よりも末梢神経刺激と磁気刺激によるタイミングがより重要な要素であること、使用依存学習では刺激細胞集団特性が重要であることを示した。以上から運動学習ごとに磁気刺激による効果発現機序が異なっており、治療応用を考える上では、目的とする運動・症状の発現機序の違いにより磁気刺激プロトコールを変える必要性があることが示唆された。

Research Progress Status

28年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

28年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] The effect of age on the homotopic motor cortical long-term potentiation-like effect induced by quadripulse stimulation (2017)
  • Author(s): Hanajima R, Tanaka N, Tsutsumi R, Enomoto H, Abe M, Nakamura K, Kobayashi S, Hamada M, Shimizu T, Terao Y, Ugawa Y
  • Journal Title: Exp Brain Res Volume: 235 Issue: 7 Pages: 2103
  • DOI: 10.1007/s00221-017-4953-0
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Development of a novel system to quantify the spatial temporal parameters for crutch-assisted quadrupedal gait. (2017)
  • Author(s): Yozu A, Hamada M, Sasaki T, Tokushige SI, Tsuji S, Haga N
  • Journal Title: Advanced Robotics Volume: 31 Issue: 1-2 Pages: 80-87
  • DOI: 10.1080/01691864.2016.1244489
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Variability in neural excitability and plasticity induction in the human cortex: A brain stimulation study. (2017)
  • Author(s): Hordacre B, Goldsworthy MR, Vallence AM, Darvishi S, Moezzi B, Hamada M, Rothwell JC, Ridding MC.
  • Journal Title: Brain Stimulation Volume: 10 Issue: 3 Pages: 588-595
  • DOI: 10.1016/j.brs.2016.12.001
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Variability in Response to Quadripulse Stimulation of the Motor Cortex (2016)
  • Author(s): Nakamura K., Groiss S.J., Hamada M., Enomoto H., Kadowaki S., Abe M., Murakami T., Wiratman W., Chang F., Kobayashi S., Hanajima R., Terao Y., Ugawa Y.
  • Journal Title: Brain Stimulation Volume: 9 Issue: 6 Pages: 859
  • DOI: 10.1016/j.brs.2016.01.008
  • URL: https://pure.teikyo.jp/en/publications/e43b4d03-2322-4e3d-b65d-94790ac9e329
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Variability in response to quadripulse stimulation of the motor cortex (2016)
  • Author(s): Nakamura K, Groiss SJ, Hamada M, Enomoto H, Kadowaki S, Abe M, Murakami T, Wiratman W, Chang F, Kobayashi S, Hanajima R, Terao Y, Ugawa Y
  • Journal Title: Brain Stimulation Volume: 未定
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Current direction - basic physiology and plasticity (2017)
  • Author(s): Hamada M
  • Organizer: 2nd International Brain Stimulation Conference
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2017-03-05
  • Int'l Joint Research / Invited
• [Presentation] Effect of subthreshold paired associative stimulation during voluntary contraction on motor learning (2017)
  • Author(s): Sasaki T, Tokushige S, Togashi N, Inomata-Terada S,, Terao Y, Ugawa Y, Hamada M.
  • Organizer: 2nd International Brain Stimulation Conference
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2017-03-05
  • Int'l Joint Research
• [Presentation] Brain stimulation and neuromodulation of neurodegenerative disorders. (2016)
  • Author(s): Hamada M
  • Organizer: 2016 Japanese-American Kavli Frontiers of Science symposium
  • Place of Presentation: Irvine, California
  • Year and Date: 2016-12-02
  • Int'l Joint Research / Invited
• [Presentation] Influence of the difference of induced current direction on measurement of corticospinal excitability changes after continuous and intermittent theta burst stimulation (2016)
  • Author(s): Takuya Sasaki, Shin-ichi Tokushige, Satomi Terada, Akihiro Yugeta, Yasuo Terao, Yoshikazu Ugawa, Masashi Hamada
  • Organizer: 6th International Conference on Transcranial Brain Stimulation 2016
  • Place of Presentation: Goettingen, Germany
  • Year and Date: 2016-09-07
  • Int'l Joint Research
• [Presentation] Variability in response to theta burst stimulation (2016)
  • Author(s): Masashi Hamada
  • Organizer: 6th International Conference on Transcranial Brain Stimulation 2016
  • Place of Presentation: Goettingen, Germany
  • Year and Date: 2016-09-07
  • Int'l Joint Research / Invited
• [Presentation] Determinants of the induction of cortical plasticity by theta burst stimulation. (2016)
  • Author(s): Hamada M
  • Organizer: 6th International Conference on Transcranial Brain Stimulation
  • Place of Presentation: Goettingen, Germany
  • Int'l Joint Research / Invited
• [Presentation] Plasticity of human motor and sensory cortices induced by non-invasive brain stimulation. (2016)
  • Author(s): Hamada M
  • Organizer: 10th ICME International Conference on Complex Medical Engineering (CME2016)
  • Place of Presentation: Utsunomiya, Japan
  • Int'l Joint Research / Invited
• [Presentation] Influence of the difference of induced current direction on measurement of corticospinal excitability changes after continuous and intermittent theta burst stimulation. (2016)
  • Author(s): Sasaki T, Tokushige S, Terada S, Yugeta A, Terao Y, Ugawa Y, Hamada M.
  • Organizer: 6th International Conference on Transcranial Brain Stimulation
  • Place of Presentation: Goettingen, Germany
  • Int'l Joint Research
• [Presentation] Variability in response to non-invasive brain stimulation (2015)
  • Author(s): Masashi Hamada
  • Organizer: 5th Annual Symposium for Exploring neuroplasticity and connectivity of the human brain
  • Place of Presentation: Taichung, Taiwan
  • Year and Date: 2015-11-14
  • Int'l Joint Research / Invited
• [Presentation] 非侵襲的脳刺激法の現状と課題 (2015)
  • Author(s): 濱田 雅
  • Organizer: 第45回日本臨床神経学会学術大会
  • Place of Presentation: 大阪
  • Year and Date: 2015-11-05
  • Invited
• [Presentation] Quadripulse stimulation (2015)
  • Author(s): Masashi Hamada
  • Organizer: International Symposium on Magnetic Stimulation
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2015-06-06
  • Int'l Joint Research / Invited