Effects of anti-parkinsonian drugs on neural plasticity in human brain; new aspects of pathophysiological mechanisms underlying neurodegeneration.

• Project/Area Number: 26461308
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Kitasato University
• Principal Investigator: Hanajima Ritsuko 北里大学, 医学部, 准教授 (80396738)
• Co-Investigator(Kenkyū-buntansha): 寺尾 安生 杏林大学, 医学部, 教授 (20343139)
• Co-Investigator(Renkei-kenkyūsha): UGAWA Yoshikazu 福島県立医大, 医学部, 教授 (50168671)
• Research Collaborator: TANAKA Nobuyuki ; TSUTSUMI Ryousuke ; SHIIMIZU Takahiro ; ENOMOTO Hiroyuki ; SHIROTA Yuichiro ; TERADA Satomi ; MATSUDA Shunichi ; OOMINAMI Shinya ; HAMADA Masashi ; ABE Mitsuya
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 反復磁気刺激法 / 神経可塑性 / 長期増強 / パーキンソン病 / 神経変性疾患 / 神経生理学 / 反復磁気刺激 / 神経生理

Outline of Final Research Achievements

We studied the motor cortical synaptic plasticity in human to elucidate pathophysiological mechanisms underlying neurodegenerative disorders, using a new non-invasive repetitive transcranial magnetic stimulation technique, quadripulse magnetic stimulation (QPS). First, we showed that inter-individual variability was lower in the plasticity induced by QPS than those by the other non-invasive brain stimulations in healthy volunteers. Second, we revealed that the degree of long term potentiation (LTP)-like effects induced by QPS was significantly smaller in the older participants compared to the younger participants. Third, we presented that zonisamide, one of anti-parkinsonian drugs, enhanced LTP-like effect induced by QPS in non-responders to QPS. We presented these data in academic congresses and published those in international academic journals.

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: 印刷中 Issue: 7 Pages: 2103-2108
  • DOI: 10.1007/s00221-017-4953-0
  • Peer Reviewed / 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: 859-866
  • DOI: 10.1016/j.brs.2016.01.008
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Cerebellar dysfunction in essential tremor. (2016)
  • Author(s): Hanajima R, Tsutsumi R, Shirota Y, Shimizu T, Tanaka N, Ugawa Y.
  • Journal Title: Mov Disord Volume: 31 Pages: 1230-4
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Is multiple system atrophy with cerebellar ataxia (MSA-C) like spinocerebellar ataxia and multiple system atrophy with parkinsonism (MSA-P) like Parkinson's disease? - A saccade study on pathophysiology. (2016)
  • Author(s): Terao Y, Fukuda H, Tokushige S, Inomata-Terada S, Yugeta A, Hamada M, Ichikawa Y, Hanajima R, Ugawa Y.
  • Journal Title: Clin Neurophysiol. Volume: 127(2) Issue: 2 Pages: 1491-502
  • DOI: 10.1016/j.clinph.2015.07.035
  • Peer Reviewed
• [Journal Article] Somatosensory-evoked potential modulation by quadripulse transcranial magnetic stimulation in patients with benign myoclonus epilepsy. (2016)
  • Author(s): Nakatani-Enomoto S, Hanajima R, Hamada M, Terao Y, Matsumoto H, Shirota Y, Ohminami S, Okabe S, Hirose M, Nakamura K, Furubayashi T, Groiss SJ, Kobayashi S, Mochizuki H, Enomoto H, Ugawa Y.
  • Journal Title: Clin Neurophysiol Volume: 127(2) Issue: 2 Pages: 1560-7
  • DOI: 10.1016/j.clinph.2015.07.029
  • Peer Reviewed
• [Journal Article] Influence of Zonisamide on the LTP-like Effect Induced by Quadripulse Transcranial Magnetic Stimulation (QPS). (2015)
  • Author(s): Tanaka N, Hanajima R, Tsutsumi R, Shimizu T, Shirota Y, Terao Y, Ugawa Y.
  • Journal Title: Brain Stimul Volume: 8（6） Issue: 6 Pages: 1220-2
  • DOI: 10.1016/j.brs.2015.07.002
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Modulation of error-sensitivity during a prism adaptation task in people with cerebellar degeneration. (2015)
  • Author(s): Hanajima R, Shadmehr R, Ohminami S, Tsutsumi R, Shirota Y, Shimizu T, Tanaka N, Terao Y, Tsuji S, Ugawa Y, Uchimura M, Inoue M, Kitazawa S.
  • Journal Title: J Neurophysiol Volume: 114(4) Issue: 4 Pages: 2460-71
  • DOI: 10.1152/jn.00145.2015
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Effects of rTMS of pre-supplementary motor area on fronto-basal-ganglia network activity during stop-signal task. (2015)
  • Author(s): Watanabe, T., Hanajima, R., Shirota, Y., Tsutsumi, R., Shimizu, T., Hayashi, T., Terao, Y., Ugawa, Y., Katsura, M., Kunimatsu, A., Ohtomo, K., Hirose, S., Miyashita, Y. and Konishi, S.
  • Journal Title: J. Neurosci. Volume: 35 Issue: 12 Pages: 4813-4823
  • DOI: 10.1523/jneurosci.3761-14.2015
  • Peer Reviewed / Open Access
• [Journal Article] Effects of L-Dopa and pramipexole on plasticity induced by QPS in human motor cortex. (2015)
  • Author(s): Enomoto H, Terao Y, Kadowaki S, Nakamura K, Moriya A, Nakatani-Enomoto S, Kobayashi S, Yoshihara A, Hanajima R, Ugawa Y.
  • Journal Title: J Neural Transm. Volume: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Different roles of pre-SMA and SMA in human visuomotor sequence learning: a TMS study (2017)
  • Author(s): T Shimizu, R Hanajima, R Tsutsumi, Y Shirota, N Tanaka, M Hamada, Y Ugawa.
  • Organizer: 2nd Brain Stimulation Conference
  • Place of Presentation: Barcelona (Spain)
  • Year and Date: 2017-03-05
  • Int'l Joint Research
• [Presentation] Inter-individual variability of quadri-pulse magnetic stimulation (QPS) (2016)
  • Author(s): 花島律子
  • Organizer: 第46回日本臨床神経生理学会学術大会
  • Place of Presentation: ホテルハマツ（福島県郡山市）
  • Year and Date: 2016-10-27
  • Invited
• [Presentation] Influence of Zonisamide on the LTP-like Effect Induced by Quadripulse Transcranial Magnetic Stimulation (2016)
  • Author(s): T Shimizu, R Hanajima, N Tanaka, R Tsutsumi, Y Shirota, Y Terao, Y Ugawa
  • Organizer: 6th International Conference on Transcranial Brain stimulation
  • Place of Presentation: Goettingen (Germany)
  • Year and Date: 2016-09-07
  • Int'l Joint Research
• [Presentation] Influence of anti-parkinson drugs on plastic changes induced by quadripulse transcranial magnetic stimulation (QPS) (2016)
  • Author(s): Hanajima R, Enomoto H, Tanaka N, Tsutusmi R, Shimizu T, Shirota Y, Tereo Y, Ugawa Y
  • Organizer: 6th International Conference on Transcranial Brain stimulation
  • Place of Presentation: Goettingen (Germany)
  • Year and Date: 2016-09-07
  • Int'l Joint Research / Invited
• [Presentation] M1 Interneuron function: SICI and pitfall. (2015)
  • Author(s): Hanajima R
  • Organizer: International Symposium on Magnetic Stimulation
  • Place of Presentation: 東京大学伊藤国際学研究センター（東京都文京区）
  • Year and Date: 2015-06-06
  • Int'l Joint Research / Invited
• [Presentation] Age dependency of the LTP like effect by quadri-pulse stimulation (QPS) over the primary motor cortex (2015)
  • Author(s): Hanajima R、 Tanaka N, Tsutsumi R, Enomoto H, Abe M, Nakamura K, Kobayashi S, Hamada M, Shimizu T, Terao Y, Ugawa Y.
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 朱鷺メッセ （新潟県新潟市）
  • Year and Date: 2015-05-20
• [Presentation] 連発磁気刺激(QPS)を用いたパーキンソン病患者におけるL-DOPAによる 大脳皮質可塑性変化の検討 (2015)
  • Author(s): 田中信行、堤涼介、清水崇宏、寺田 さとみ、 濱田 雅、寺尾 安生、宇川 義一、 花島 律子よる 大脳皮質可塑性変化の検討ra K, Kobayashi S, Hamada M, Shimizu T, Terao Y, Ugawa Y.
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 朱鷺メッセ （新潟県新潟市）
  • Year and Date: 2015-05-20
• [Presentation] 前補足運動野・補足運動野に対する経頭蓋反復磁気刺激が視覚運動系列学習に与える影響 大脳皮質可塑性変化の検討 (2015)
  • Author(s): 清水崇宏、花島律子、代田悠一郎、堤涼介、田中信行、徳重真一、宇川義一濱田雅、寺尾安生
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 朱鷺メッセ （新潟県新潟市）
  • Year and Date: 2015-05-20
• [Presentation] カフェインの反復単相性四連発磁気刺激法（QPS）による長期効果への影響 (2015)
  • Author(s): 堤涼介、田中信行、清水崇宏、寺尾安生、宇川義一、花島律子
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 朱鷺メッセ （新潟県新潟市）
  • Year and Date: 2015-05-20
• [Presentation] Physiology and modeling of non-invasive brain stimulation of the human motor cortex (2015)
  • Author(s): Hanajima R
  • Organizer: 1st International Taiwanese Congress of Neurology
  • Place of Presentation: Taipei International Convention Center (Taipei, Taiwan)
  • Year and Date: 2015-05-07
  • Int'l Joint Research / Invited
• [Presentation] Age influence on the quadri-pulse stimulation (QPS) induced LTP like effect (2015)
  • Author(s): Hanajima R, Tanaka N, Tsutsumi R, Enomoto H, Abe M, Nakamura K, Kobayashi S, Hamada M, Shimizu T, Terao Y, Ugawa Y
  • Organizer: 1st Brain stimulation conference
  • Place of Presentation: Singapore（シンガポール）
  • Year and Date: 2015-03-02 – 2015-03-04
• [Presentation] Effects of caffeine on the quadripulse transcranial magnetic stimulation (QPS) induced long-term potentiation (LTP) (2015)
  • Author(s): Tsutsumi R, Tanaka N, Shimizu T, Terao Y, Ugawa Y, Hanajima R
  • Organizer: 1st Brain stimulation conference
  • Place of Presentation: Singapore（シンガポール）
  • Year and Date: 2015-03-02 – 2015-03-04
• [Presentation] The inter-individual variability of quadripulse stimulation (QPS) (2015)
  • Author(s): Enomoto H, Kadowaki S, Abe M, Nakamura K, Kobayashi S, Hanajima R, Terao Y, Hamada M, Ugawa Y
  • Organizer: 1st Brain stimulation conference
  • Place of Presentation: Singapore（シンガポール）
  • Year and Date: 2015-03-02 – 2015-03-04
• [Presentation] The effect of antiParkinsonian drugs on the motor cortical plasticity induced by quadri-pulse magnetic stimulation (QPS) (2014)
  • Author(s): Hanajima R, Tanaka N, Tsutsumi R , Shimizu T, Matsuda S, Terada S, Terao Y, Enomoto H, Ugawa Y
  • Organizer: 第37回日本神経科学大会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] 4連発磁気刺激(QPS)を用いたゾニサミドによる大脳皮質可塑性変化の検討 (2014)
  • Author(s): 田中信行,堤涼介,清水崇宏,松田俊一,寺田さとみ, 濱田 雅,花島律子,寺尾安生,宇川義一
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡国際会議場他（福岡県福岡市）
  • Year and Date: 2014-05-21 – 2014-05-24
• [Presentation] 前補足運動野に対する四連発経頭蓋反復磁気刺激がヒト視覚運動系列学習に与える影響 (2014)
  • Author(s): 清水崇宏, 花島律子, 堤涼介, 代田悠一郎, 田中信行, 松田俊一, 寺尾安生, 宇川義一
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡国際会議場他（福岡県福岡市）
  • Year and Date: 2014-05-21 – 2014-05-24
• [Presentation] 一次運動野の反復単相性4連発経頭蓋磁気刺激QPSによる対側一次運動野への可塑性誘導 (2014)
  • Author(s): 堤涼介、花島律子、寺尾安生、代田悠一郎、大南伸也、清水崇弘、田中信行、宇川義一
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡国際会議場他（福岡県福岡市）
  • Year and Date: 2014-05-21 – 2014-05-24