Neuroimaging of the mood change induced by rTMS: Primate model study

• Project/Area Number: 26560455
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Basic / Social brain science
• Research Institution: Tohoku University
• Principal Investigator: Tsutsui Ken-Ichiro 東北大学, 生命科学研究科, 教授 (90396466)
• Co-Investigator(Kenkyū-buntansha): 林 拓也 国立研究開発法人理化学研究所, ライフサイエンス技術基盤研究センター, チームリーダー (50372115) ; 尾上 浩隆 国立研究開発法人理化学研究所, ライフサイエンス技術基盤研究センター, チームリーダー (80214196)
• Research Collaborator: NAKAMURA Shinya
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 脳・神経 / 抑うつ / サルうつ病モデル / 経頭蓋磁気刺激

Outline of Final Research Achievements

We applied low-frequency repetitive trans-cranial magnetic stimulation (lf-rTMS) to the ventral part of the medial prefrontal cortex (vmPFC) in rhesus monkeys. After the stimulation, all these monkeys fell into a severe depressive state, which lasted for 1 - 3 days. Such state could be characterized by reduction of within-cage spontaneous activity, reduction of motivation to perform behavioral tasks, and increase in the blood cortisol level. On the other hand, similar stimulation on the posterior part of the anterior cingulate cortex (pACC), or any other cortical regions, did not induce such drastic change in mood. We performed functional MR imaging (fMRI) to measure the resting-state whole brain activity after lf-rTMS to vmPFC and pACC, and sham stimulation to vmPFC. The data is now being analyzed to reveal the difference of the brain activity between the depressive and normal state.

Research Products

• [Journal Article] Oral Administration of Methylphenidate (Ritalin) Affects Dopamine Release Differentially Between the Prefrontal Cortex and Striatum: A Microdialysis Study in the Monkey (2017)
  • Author(s): Kodama T, Kojima T, Honda Y, Hosokawa T, Tsutsui KI, Watanabe M
  • Journal Title: Journal of Neuroscience Volume: 37 Issue: 9 Pages: 2387-2394
  • DOI: 10.1523/jneurosci.2155-16.2017
  • Peer Reviewed
• [Journal Article] A dynamic code for economic object valuation in prefrontal cortex neurons (2016)
  • Author(s): Tsutsui KI, Grabenhorst F, Kobayashi S, Schultz W
  • Journal Title: Nature Communications Volume: 7 Issue: 1 Pages: 12554-12554
  • DOI: 10.1038/ncomms12554
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Neck collar for restraining head and body movements in rats for behavioral task performance and simultaneous neural activity recording. (2016)
  • Author(s): Tateyama Y, Oyama K, Lo CW, Iijima T, Tsutsui KI
  • Journal Title: Journal of Neruoscience Methods Volume: 263 Pages: 68-74
  • DOI: 10.1016/j.jneumeth.2016.02.005
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Comparative Overview of Visuospatial Working Memory in Monkeys and Rats (2016)
  • Author(s): Tsutsui KI, Oyama K, Nakamura S, Iijima T
  • Journal Title: Frontiers of Systems Neuroscience Volume: 10 Pages: 99-99
  • DOI: 10.3389/fnsys.2016.00099
  • Peer Reviewed / Open Access
• [Journal Article] Similarity in neuronal firing regimes across mammalian species (2016)
  • Author(s): Yasuhiro Mochizuki, ..., Ichiro Fujita, et al.
  • Journal Title: Journal of Neuroscience Volume: 36 Issue: 21 Pages: 5736-5747
  • DOI: 10.1523/jneurosci.0230-16.2016
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Representation of Functional Category in the Monkey Prefrontal Cortex and Its Rule-Dependent Use for Behavioral Selection. (2016)
  • Author(s): Tsutsui KI, Hosokawa T, Yamada M, Iijima T
  • Journal Title: Journal of Neuroscience Volume: 36 Issue: 10 Pages: 3038-3048
  • DOI: 10.1523/jneurosci.2063-15.2016
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Discrete coding of stimulus value, reward expectation, and reward prediction error in the dorsal striatum. (2015)
  • Author(s): Oyama K, Tateyama Y, Hernadi I, Tobler PN, Iijima T, Tsutsui KI
  • Journal Title: Journal of Neurophysiology Volume: 114 Issue: 5 Pages: 2600-2615
  • DOI: 10.1152/jn.00097.2015
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Effects of G-gene Deletion and Replacement on Rabies Virus Vector Gene Expression. (2015)
  • Author(s): Sato S, Ohara S, Tsutsui KI, Iijima T
  • Journal Title: PLoS One Volume: 10 Issue: 5 Pages: e0128020-e0128020
  • DOI: 10.1371/journal.pone.0128020
  • Peer Reviewed / Open Access
• [Journal Article] Dopaminergic and serotonergic modulation of anterior insular and orbitofrontal cortex function in risky decision making. (2015)
  • Author(s): Ishii H, Ohara S, Tobler PN, Tsutsui KI, Iijima T.
  • Journal Title: Neurosci Res Volume: 92 Pages: 53-61
  • DOI: 10.1016/j.neures.2014.11.009
  • Peer Reviewed
• [Presentation] Decision related activities of anterior insular and orbitofrontal cortex in a gambling behavior of rats. (2016)
  • Author(s): Ishii H, Kaizu Y, Takahashi S, Ohara S, Tobler PN, Tsutsui KI，Iijima T
  • Organizer: Society for Neuroscience Annual Meeting
  • Place of Presentation: San Diego USA
  • Year and Date: 2016-11-14
  • Int'l Joint Research
• [Presentation] Efferent projections of the calbindinpositive entorhinal neurons in the rat: Connectional differences between the medial and lateral entorhinal cortex. (2016)
  • Author(s): Ohara S, Itou K, Shiraishi M, Gianatti M，Sota Y，Kabashima S, Onodera M，Tsutsui KI，Witter M，Iijima T
  • Organizer: Society for Neuroscience Annual Meeting
  • Place of Presentation: San Diego USA
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] ｒTMSの作用機序解明および臨床利用における刺激条件最適化に向けて (2016)
  • Author(s): 筒井健一郎
  • Organizer: 脳科学研究戦略推進プログラム「ＢＭＩ技術」報告会
  • Place of Presentation: 東京
  • Year and Date: 2016-11-10
  • Invited
• [Presentation] Using transcranial magnetic stimulation (TMS) as a tool for primate neuroscience research (2016)
  • Author(s): Tsutsui KI
  • Organizer: 31st International Congress of Psychology (ICP2016)
  • Place of Presentation: 横浜
  • Year and Date: 2016-07-25
• [Presentation] Connectional differences between calbindin positive neurons in the medial and lateral entorhinal cortex of the rat. (2016)
  • Author(s): Ohara S，Itou K，Shiraishi M，Gianatti M，Sota Y，Kabashima S, Onodera M，Tsutsui KI，Witter M，Iijima T
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2016-07-22
  • Int'l Joint Research
• [Presentation] Connectional differences between layer Va and Vb neurons in the lateral entorhinal cortex of the rat. (2016)
  • Author(s): Onodera M, Ohara S，Shiraishi M, Itou K，Tsutsui KI, Witter M，Iijima T
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2016-07-22
  • Int'l Joint Research
• [Presentation] Inactivation of rat dorsomedial prefrontal cortex or posterior parietal cortex, but not ventromedial prefrontal cortex, impairs the performance of the visuospatial delayed response task. (2016)
  • Author(s): Oyama K，Lo CW，Tateyama Y，Iijima T，Tsutsui KI
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2016-07-21
  • Int'l Joint Research
• [Presentation] Neural correlates of abstract thought process in monkey prefrontal cortex. (2016)
  • Author(s): Hosokawa T，Nakamura S，Yamada M，Iijima T，Tsutsui KI
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2016-07-21
  • Int'l Joint Research
• [Presentation] Reduction of spontaneous physical activity and sociability induced by low-frequency repetitive transcranial stimulation (rTMS) to the lower part of the medial frontal cortex in monkeys. (2016)
  • Author(s): Nakamura S，Ogawa K，Goto Y，Hosokawa T，Iijima T，Tsutsui KI
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2016-07-21
  • Int'l Joint Research
• [Presentation] Sustained delay activity in mPFC and PPC of head-fixed rats performing delayed pro-/anti-response task. (2016)
  • Author(s): Tateyama Y，Oyama K，Lo CW，Iijima T，Tsutsui KI
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2016-07-21
  • Int'l Joint Research
• [Presentation] 反復経頭蓋磁気刺激（rTMS）によるサル内側前頭葉の情動・気分調節機能の検証 (2016)
  • Author(s): 筒井健一郎
  • Organizer: 第57回日本心身医学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2016-06-05
  • Invited
• [Presentation] 経頭蓋時期刺激（TMS）で拓く霊長類研究の新展開 (2015)
  • Author(s): 筒井健一郎
  • Organizer: ナショナルバイオリソース第12回公開シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2015-12-11
  • Invited
• [Presentation] Cortical and subcortical projections of the entorhinal layer III neurons of the rat. (2015)
  • Author(s): Ohara S., Ito, K., Sota, Y., Tsutsui, K-I., Witter, P. M., Iijima, T.
  • Organizer: Society for Neuroscience Annual Meeting
  • Place of Presentation: Chicago (USA)
  • Year and Date: 2015-10-21
  • Int'l Joint Research
• [Presentation] Rabies virus vector with improved transgene expression level for transsynaptic tracing. (2015)
  • Author(s): Sota, Y., Ohara, S., Sato, S., Ito, K., Tsutsui, K-I., Iijima, T.
  • Organizer: Society for Neuroscience Annual Meeting
  • Place of Presentation: Chicago (USA)
  • Year and Date: 2015-10-21
  • Int'l Joint Research
• [Presentation] The effect of bimodal value representation on goal directed behavior and reflective choice in behaving macaque. (2015)
  • Author(s): Yasuda M, Nakamura S, Okada KI, Kobayashi Y, Tsutsui KI, Nakamura K.
  • Organizer: Society for Neuroscience Annual Meeting
  • Place of Presentation: Chicago (USA)
  • Year and Date: 2015-10-20
  • Int'l Joint Research
• [Presentation] Comparison of neural representations between rat anterior insular and orbitofrontal cortex in risky decision making. (2015)
  • Author(s): Ishii, H., Kaizu, Y., Takahashi, S., Ohara, S., Tobler, N. P., Tsutsui, K-I., Iijima, T.
  • Organizer: Society for Neuroscience Annual Meeting
  • Place of Presentation: Chicago (USA)
  • Year and Date: 2015-10-20
  • Int'l Joint Research
• [Presentation] Neural responses observed only in a gambling task in the rat anterior insular cortex. (2015)
  • Author(s): Kaizu, Y., Ishii, H., Takahashi, S., Ohara, S., Tobler, N. P., Tsutsui, K-I., Iijima, T.
  • Organizer: Society for Neuroscience Annual Meeting
  • Place of Presentation: Chicago (USA)
  • Year and Date: 2015-10-20
  • Int'l Joint Research
• [Presentation] Cytoarchitectonic information of rat medial prefrontal “delay” neurons revealed by single-neuron electroporation. (2015)
  • Author(s): Oyama, K., Tateyama, Y., Lo, CW., Ohara, S., Karube, F., Fujiyama, F., Iijima, T., Tsutsui, K-I.
  • Organizer: Society for Neuroscience Annual Meeting
  • Place of Presentation: Chicago (USA)
  • Year and Date: 2015-10-20
  • Int'l Joint Research
• [Presentation] Inactivation of rat dorsomedial prefrontal cortex impairs delayed response performance under head fixation (2015)
  • Author(s): Lo C, Tateyama Y, Oyama K, T. Iijima T, Tsutsui KI
  • Organizer: Society for Neuroscience Annual Meeting
  • Place of Presentation: Chicago (USA)
  • Year and Date: 2015-10-19
  • Int'l Joint Research
• [Presentation] Comparing the impact of online and low-frequency offline rTMS over the unilateral dorsolateral prefrontal cortex on the delayed response task performance. (2015)
  • Author(s): Ogawa K, Nakamura S, Hosokawa T, Iijima T, Tsutsui KI.
  • Organizer: Society for Neuroscience Annual Meeting
  • Place of Presentation: Chicago (USA)
  • Year and Date: 2015-10-19
  • Int'l Joint Research
• [Presentation] Neck collar: A novel non-invasive system for restricting head and body movements in rats for behavioral task performance and simultaneous neuron activity recording (2015)
  • Author(s): Tateyama Y, Oyama K, Lo C, Iijima T, Tsutsui KI
  • Organizer: Society for Neuroscience Annual Meeting
  • Place of Presentation: Chicago (USA)
  • Year and Date: 2015-10-18
  • Int'l Joint Research
• [Presentation] Ventrolateral prefrontal activity reflects increases in object value induced by larger choice sets. (2015)
  • Author(s): Fujiwara J, Usui N, Eifuku S, Iijima T, Taira M, Tsutsui KI, Tobler P
  • Organizer: Society for Neuroscience Annual Meeting
  • Place of Presentation: Chicago (USA)
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] Morphological identification of rat medial prefrontal neurons showing sustained activity during a delay period of a delayed response task by single-neuron electroporation. (2015)
  • Author(s): Oyama, K., Tateyama, Y., Lo, CW., Ohara, S., Karube, F., Fujiyama, F., Iijima, T., Tsutsui, K-I.
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-07-30
• [Presentation] Afferents and Efferents of the Commissural Projection Neurons in Enthorinal Cortex Layer 3 of the Rat. (2015)
  • Author(s): Ohara, S., Itou, K., Sota, Y., Sato, S., Tsutsui, K-I., Iijima, T.
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-07-30
• [Presentation] Ventrolateral prefrontal activity reflects increases in object value induced by larger choice sets. (2015)
  • Author(s): Fujiwara J, Usui N, Eifuku S, Iijima T, Taira M, Tsutsui KI, Tobler PN.
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-07-29
• [Presentation] An integrated system for the quantitative measure of motivation and emotion in monkeys. (2015)
  • Author(s): Yasuda M, Nakamura S, Okada KI, Kobayashi Y, Tsutsui KI, Nakamura K.
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-07-29
• [Presentation] Risky choice selective neuron in rat anterior insular cortex. (2015)
  • Author(s): Ishii, H., Kaizu, Y., Takahashi, S., Ohara, S., Tobler, N. P., Tsutsui, K-I., Iijima, T.
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-07-29
• [Presentation] Different contributions of monkey frontal, premotor, and parietal corticies in spatial working memory task revealed by on-line rTMS. (2015)
  • Author(s): Tsutsui KI
  • Organizer: International Symposimu on Magnetic Stimulation: Past, Present and Future
  • Place of Presentation: 東京
  • Year and Date: 2015-06-06
  • Int'l Joint Research / Invited
• [Presentation] The effect of inactivation of prefrontal cortex on immediate behavioral adaptation in group reversal (2015)
  • Author(s): Hosokawa T, Nakamura S, Matsui Y, Yamada M, Iijima T, Tsutsui KI
  • Organizer: 1st International Brain Stimulation Conference
  • Place of Presentation: Singapore
  • Year and Date: 2015-03-02
• [Presentation] Different roles of the monkey dorsolateral prefrontal, premotor and posterior parietal cortices in a (2015)
  • Author(s): Nakamura S, Hosokawa T, Iijima T, Tsutsui KI
  • Organizer: 1st International Brain Stimulation Conference
  • Place of Presentation: Singapore
  • Year and Date: 2015-03-02
• [Presentation] Functional segregation of prefrontal and premotor cortices in a delayed response task: An rTMS study (2014)
  • Author(s): Nakamura S, Hosokawa T, Iijima T, Tsutsui KI
  • Organizer: Society for Neuroscience 2014
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2014-11-19
• [Presentation] Involvement of dorsolateral and ventrolateral prefrontal cortex in behavioral adaptation to group (2014)
  • Author(s): Hosokawa T, Nakamura S, Matsui Y, Yamada M, Iijima T, Tsutsui KI
  • Organizer: Society for Neuroscience 2014
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2014-11-19
• [Presentation] Sustained activity in mPFC of head-fixed rats performing delayed response task (2014)
  • Author(s): Tateyama Y, Oyama K, Omori K, Iijima T, Tsutsui KI
  • Organizer: Society for Neuroscience 2014
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2014-11-19
• [Presentation] Deleting G protein of rabies virus vector enhances transgene expression level via decreased cell (2014)
  • Author(s): Sato S, Ohara S, Tsutsui KI, Iijima T
  • Organizer: Society for Neuroscience 2014
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2014-11-19
• [Presentation] Dopaminergic and serotonergic modulation of anterior insular and orbitofrontal cortex in risky (2014)
  • Author(s): Ishii H, Ohara S, Kaizu Y, Tobler PN, Tsutsui KI, Iijima T
  • Organizer: Society for Neuroscience 2014
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2014-11-18
• [Presentation] Topographical organization of multisynaptic inputs to the hippocampus: Dual transsynaptic tracing (2014)
  • Author(s): Ohara S, Sato S, Tsutsui KI, Witter MP, Iijima T
  • Organizer: Society for Neuroscience 2014
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2014-11-15
• [Presentation] 遅延反応課題遂行中のラット頭頂連合野における感覚情報と運動情報 (2014)
  • Author(s): 舘山 幸菜 小山 佳 大森 和音 飯島 敏夫 筒井 健一郎
  • Organizer: 第37回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-13
• [Presentation] rTMSを用いた機能阻害によって明らかになった遅延反応課題における大脳皮質諸領野の役割分担 (2014)
  • Author(s): 中村 晋也 細川 貴之 飯島 敏夫 筒井 健一郎
  • Organizer: 第37回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-13
• [Presentation] グループ逆転課題遂行中のサル前頭連合野におけるカテゴリ情報の表現 (2014)
  • Author(s): 細川 貴之 中村 晋也 山田 宗和 飯島 敏夫 筒井 健一郎
  • Organizer: 第37回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-12
• [Presentation] 狂犬病ウイルスベクターを用いたラット海馬歯状回への投射経路の解析 (2014)
  • Author(s): 大原 慎也 佐藤 翔 筒井 健一郎 Witter Menno P 飯島 敏夫
  • Organizer: 第37回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-12
• [Presentation] Investigating the functional specialization within the monkey neocortex using TMS (2014)
  • Author(s): Tsutsui KI
  • Organizer: Magstim Neuroscience Conference 2014
  • Place of Presentation: Oxford, UK
  • Year and Date: 2014-05-10
  • Invited