Closed-loop brain stimulation can improve Parkinsonian gait disturbance

• Project/Area Number: 19K11351
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59010:Rehabilitation science-related
• Research Institution: Nagoya City University
• Principal Investigator: Ueki Yoshino 名古屋市立大学, 医薬学総合研究院(医学), 教授 (40467478)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: neuromodulation / ニューロリハビリテーション / パーキンソン病 / tACS / closed loop stimulation / 歩行

Outline of Research at the Start

パーキンソン病 (PD)の治療は、急速に進歩しており、ドパミン補充療法のみならずiPS細胞移植療法も現実化してきている。しかしながら、PDおよびその関連疾患の病態首座が脳内ネットワークであるとの観点から非侵襲的治療を試みるケースは国内外でも類を見ない。そこで、本研究では、①患者個人での最適歩行リズム（周波数）に合致させたパターン直流刺激を脳に与えることで歩行リズムを正常化する新規リハビリテーション法を開発する、②介入による脳内ネットワークおよび可塑性変容を非侵襲的脳機能画像法を用いて捉える、③介入効果を介入前の客観的評価法で予測をできるか指標を抽出することを目的とする。

Outline of Final Research Achievements

Gait disturbance lowers activities of daily living in patients with Parkinson's disease (PD) and related disorders. We recently developed a novel neuromodulation approach using gait-combined closed-loop transcranial electrical stimulation (tES). Here, we tested the efficacy of this intervention in patients with Parkinsonian gait disturbances. Twenty-three patients were randomly assigned to a real intervention group using gait-combined closed loop oscillatory tES over the cerebellum at the frequency of individualized comfortable gait rhythm, and to a sham control group. Ten intervention sessions were completed for all patients and showed that the gait speed and stride length were significantly increased after tES. Moreover, gait symmetry and subjective feelings about freezing were significantly improved. These findings showed that gait-combined closed-loop tES improved Parkinsonian gait disturbances, possibly through the modulation of brain networks generating gait rhythms.

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的独自性・独創的な点は、PD関連疾患をネットワーク病態としてとらえ、患者個々人に適応させた最新のニューロモデュレーションを用いたネットワーク介入を行い、その行動学的変化のみならずネットワークに与える効果を非侵襲的脳機能計測法を用いて明らかにするものである。この様なPD関連疾患の歩行障害をネットワーク病態の観点から非侵襲的に介入し、さらに患者個人の脳内リズムに個別化したオーダーメイドリハビリテーションは国内外に例がなく、非常に斬新的である。PDにおける新たなリハビリテーション法として社会的意義も高い。

Research Products

• [Journal Article] Hebb可塑性 (2022)
  • Author(s): 植木美乃、村上里奈、青山公紀
  • Journal Title: Journal of Clinical Rehabilitation Volume: 31(3) Pages: 247-251
• [Journal Article] Impairment of the visuospatial working memory in the patients with Parkinson's Disease: an fMRI study. (2021)
  • Author(s): Kawashima S, Shimizu Y, Ueki Y, Matsukawa N.
  • Journal Title: BMC Neurol. Volume: 21(1) Issue: 1 Pages: 335-335
  • DOI: 10.1186/s12883-021-02366-7
  • Peer Reviewed / Open Access
• [Journal Article] Occipital Tau Deposition and Astrogliosis After Traumatic Brain Injuries in a Kendo Player. (2021)
  • Author(s): Uchida Y, Horimoto Y, Shibata H, Kuno T, Usami T, Takada K, Iida A, Ueki Y, Okamura N, Matsukawa N.
  • Journal Title: Neurol Clin Pract. Volume: 11(4) Issue: 4 Pages: 579-581
  • DOI: 10.1212/cpj.0000000000000936
  • Peer Reviewed
• [Journal Article] 地域リハビリテーションの現場から (2021)
  • Author(s): 植木美乃
  • Journal Title: Journal of Clinical Rehabilitaiton Volume: 30(5) Pages: 475-481
• [Journal Article] Iron leakage owing to blood?brain barrier disruption in small vessel disease CADASIL (2020)
  • Author(s): Uchida Yuto、Kan Hirohito、Sakurai Keita、Arai Nobuyuki、Inui Shohei、Kobayashi Susumu、Kato Daisuke、Ueki Yoshino、Matsukawa Noriyuki
  • Journal Title: Neurology Volume: 95 Issue: 9
  • DOI: 10.1212/wnl.0000000000010148
  • Peer Reviewed
• [Journal Article] Corticobasal syndrome-Pick's disease: A clinicopathological study (2020)
  • Author(s): Uchida Y, Yoshida M, Takada K, Tsugu Y, Ueki Y, Matsukawa N.
  • Journal Title: J Neurol Sci Volume: 412 Pages: 116752-116752
  • DOI: 10.1016/j.jns.2020.116752
  • Peer Reviewed
• [Journal Article] Magnetic Susceptibility Associates with Dopaminergic Deficits and Cognition in Parkinson's Disease. (2020)
  • Author(s): Uchida Y, Kan H, Sakurai K, Inui S, Kobayashi S, Akagawa Y, Shibuya K, Ueki Y, Matsukawa N.
  • Journal Title: Mov Disord Volume: in press Issue: 8 Pages: 1396-1405
  • DOI: 10.1002/mds.28077
  • Peer Reviewed
• [Journal Article] Simultaneous voxel‐based magnetic susceptibility and morphometry analysis using magnetization‐prepared spoiled turbo multiple gradient echo (2020)
  • Author(s): Kan Hirohito、Uchida Yuto、Arai Nobuyuki、Ueki Yoshino、Aoki Toshitaka、Kasai Harumasa、Kunitomo Hiroshi、Hirose Yasujiro、Matsukawa Noriyuki、Shibamoto Yuta
  • Journal Title: NMR in Biomedicine Volume: in press Issue: 5
  • DOI: 10.1002/nbm.4272
  • Peer Reviewed
• [Journal Article] Treatment of patellar fractures using bioresorbable forged composites of raw particulate unsintered hydroxyapatite/poly-L-lactide cannulated screws and nonabsorbable sutures (2020)
  • Author(s): Usami Takuya、Takada Naoya、Sakai Hiroaki、Endo Shinichiro、Sekiya Isato、Ueki Yoshino、Murakami Hideki、Kuroyanagi Gen
  • Journal Title: Injury Volume: Dec 29 Issue: 6 Pages: 31045-7
  • DOI: 10.1016/j.injury.2020.12.015
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Simultaneous voxel-based magnetic susceptibility and morphometry analysis using magnetization-prepared spoiled turbo multiple gradient echo. (2020)
  • Author(s): Kan H, Uchida Y, Arai N, Ueki Y, Aoki T, Kasai H, Kunitomo H, Hirose Y, Matsukawa N, Shibamoto Y.
  • Journal Title: NMR Biomed Volume: 33(5)
  • Peer Reviewed
• [Journal Article] Anatomical Links between White Matter Hyperintensity and Medial Temporal Atrophy Reveal Impairment of Executive Functions. (2019)
  • Author(s): Yamanaka T, Uchida Y, Sakurai K, Kato D, Mizuno M, Sato T, Madokoro Y, Kondo Y, Suzuki A, Ueki Y, Ishii F, Borlongan CV, Matsukawa N
  • Journal Title: Aging Dis. Volume: 10(4) Issue: 4 Pages: 711-718
  • DOI: 10.14336/ad.2018.0929
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Nigrostriatal Dopaminergic Dysfunction And Altered Functional Connectivity In REM Sleep Behaviour Disorder With Mild Motor Impairment (2019)
  • Author(s): Yamada G, Ueki Y, Oishi N, Oguri T, Fukui A, Nakayama M, Kandori A, Sano Y, Kan H, Arai N, Sakurai K, Wada I, Matsukawa N
  • Journal Title: Front. Neurol. Volume: 10 Pages: 802-802
  • DOI: 10.3389/fneur.2019.00802
  • Peer Reviewed / Open Access
• [Journal Article] Impaired Motor Skill Acquisition Using Mirror Visual Feedback Improved by Transcranial Direct Current Stimulation (tDCS) in Patients With Parkinson's Disease (2019)
  • Author(s): Horiba M, Ueki Y, Nojima I, Shimizu Y, Sahashi K, Itamoto S, Suzuki A, Yamada G, Matsukawa N, Wada I
  • Journal Title: Front Neurosci Volume: 13 Pages: 602-602
  • DOI: 10.3389/fnins.2019.00602
  • Peer Reviewed / Open Access
• [Journal Article] Voxel-based quantitative susceptibility mapping in Parkinson's disease with mild cognitive impairment (2019)
  • Author(s): Uchida Y, Kan H, Sakurai K, Arai N, Kato D, Kawashima S, Ueki Y, Matsukawa N.
  • Journal Title: Mov Disord Volume: 34(8) Issue: 8 Pages: 1164-1173
  • DOI: 10.1002/mds.27717
  • Peer Reviewed
• [Journal Article] Tongue base retraction and airway obstruction in drug-induced oromandibular dystonia (2019)
  • Author(s): Yamada G, Ueki Y, Okita K, Matsukawa N.
  • Journal Title: Neurology Volume: 92(18) Pages: 859-859
  • Peer Reviewed
• [Journal Article] Differences in postural stability and dynamic visual acuity among healthy young adults in relation to sports activity: a cross sectional study (2019)
  • Author(s): Koide Y, Ueki Y, Asai Y, Morimoto H, Asai H, Johnson EG, Lohman EB, Sakuma E, Mizutani J, Ueki T, Wada I
  • Journal Title: Journal of Physical Therapy Science Volume: 31 Issue: 1 Pages: 53-56
  • DOI: 10.1589/jpts.31.53
  • NAID: 130007554849
  • ISSN: 0915-5287, 2187-5626
  • Peer Reviewed
• [Presentation] 神経疾患におけるニューロリハビリテーション (2021)
  • Author(s): 植木美乃
  • Organizer: 日本臨床神経性理学会
  • Invited
• [Presentation] リハビリテーション科における多職種連携の取り組み (2021)
  • Author(s): 植木美乃
  • Organizer: 第5回日本リハビリテーション医学会秋季学術集会
  • Invited
• [Presentation] 神経疾患におけるニューロリハビリテーション (2021)
  • Author(s): 植木美乃
  • Organizer: 第58回日本リハビリテーション医学会
  • Invited
• [Presentation] パーキンソン病のリハビリテーション (2021)
  • Author(s): 植木美乃
  • Organizer: 第49回日本リハビリテーション医学会中部東海地方会
  • Invited
• [Presentation] 神経疾患におけるリハビリテーション (2021)
  • Author(s): 植木美乃
  • Organizer: 第51回日本リハビリテーション医学会九州地方会
  • Invited
• [Book] リハビリテーション診療サポートガイド (2021)
  • Author(s): 植木美乃
  • Total Pages: 8
  • Publisher: 南山堂
• [Book] 現代医学68-1 (2021)
  • Author(s): 植木美乃
  • Total Pages: 4
  • Publisher: クリニコ出版