Development of neuroimaging-based, translatable biomarkers applicable to both human and mouse

• Project/Area Number: 25461752
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: National Institute of Radiological Sciences (2015); The University of Tokyo (2013-2014)
• Principal Investigator: Yahata Noriaki 国立研究開発法人放射線医学総合研究所, 分子イメージング研究センター, 研究員 (70409150)
• Co-Investigator(Renkei-kenkyūsha): KASAI Kiyoto 東京大学, 医学部附属病院, 教授 (80322056) ; JINDE Seiichiro 東京大学, 医学部附属病院, 講師 (30376454) ; TANAKA Shinji 東京大学, 医学部, 助教 (60548494) ; AOKI Ichio 放射線医学総合研究所, 分子イメージング研究センター, チームリーダー (10319519)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 脳・神経 / 精神疾患 / 安静時脳機能画像 / 自発的脳活動 / 機能的結合 / 自閉症 / 疾患モデル動物 / 機械学習 / 脳画像

Outline of Final Research Achievements

We aimed to establish a neuroimaging-based biomarker that allows quantitative characterization of autism in the mouse-to-human translational research. Specifically, by using magnetic resonance imaging, we conducted longitudinal measurements of mouse brains (C57BL/6J) and thereby explored differential characteristics of the structure and spontaneous activity between autism model and wild-type mice. Conducting voxel-based morphometry on the structural images, inter-regional functional connectivity analysis on the resting-state functional images, as well as comparison of these findings with independent human studies, we have identified that gray matter volume and functional connectivity involving the limbic system through basal ganglia are candidate biomarkers of autism that are common to both human and mouse. Future investigation on their relationship with autism-specific behavioral phenotypes (such as socio-communicative deficits) is required to further clarify the clinical implication.

Research Products

• [Journal Article] A Small Number of Abnormal Brain Connections Predicts Adult Autism Spectrum Disorder. (2015)
  • Author(s): .Yahata N, Morimoto J, Hashimoto R, Lisi G, Shibata K, Kawakubo Y, Kuwabara H, Kuroda M, Yamada T, Megumi F, Imamizu H, Náñez J, Takahashi H, Okamoto Y, Kasai K, Kato N, Sasaki Y, Watanabe T, Kawato M
  • Journal Title: Nat. Commun. Volume: 7 Issue: 1 Pages: 11254-11254
  • DOI: 10.1038/ncomms11254
  • NAID: 120005770754
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] rs-fcMRIを用いた精神疾患の判別 (2015)
  • Author(s): 森本淳, 八幡憲明, 橋本龍一郎, 川人光男
  • Journal Title: Clinical Neuroscience Volume: 33 Pages: 1192-1194
  • Acknowledgement Compliant
• [Journal Article] 脳活動ビッグデータ解析による病態理解に向けた疾患判別. (2015)
  • Author(s): 森本淳, 八幡憲明, 橋本龍一郎, 川人光男
  • Journal Title: 分子精神医学 Volume: 15 Pages: 2-6
• [Presentation] 安静時脳機能結合を通じた自閉スペクトラム症の神経基盤理解と臨床応用の可能性 (2016)
  • Author(s): 八幡憲明
  • Organizer: 第112回日本精神神経学会学術総会
  • Place of Presentation: 幕張
  • Year and Date: 2016-06-02
• [Presentation] 安静時脳機能結合に基づく精神疾患の理解と今後の展望 (2015)
  • Author(s): 八幡憲明
  • Organizer: 第43回日本磁気共鳴医学会大会
  • Place of Presentation: 東京
  • Year and Date: 2015-09-10
• [Presentation] 安静時脳機能結合に基づく精神疾患の理解と今後の展望 (2015)
  • Author(s): 八幡憲明
  • Organizer: 第18回日本薬物脳波学会学術集会
  • Place of Presentation: 和歌山
  • Year and Date: 2015-06-26
  • Invited
• [Presentation] A machine-learning-based study on the neural substrates of autism spectrum disorder using resting-state fMRI. (2014)
  • Author(s): Yahata, N., Morimoto, J., Hashimoto, R., Shibata, K., Imamizu, H., Fukuda, M,. Kawakubo, Y., Kuwabara, H., Kuroda, M., Yamada, T., Kato, N., Sasaki, Y., Watanabe, T., Kasai, K. & Kawato, M.
  • Organizer: 第36回日本生物学的精神医学会
  • Place of Presentation: 奈良
  • Year and Date: 2014-09-30
• [Presentation] A machine-learning-based investigation on the neural substrates of autism spectrum disorder using resting-state fMRI. (2014)
  • Author(s): Yahata, N., Morimoto, J., Hashimoto, R., Shibata, K., Imamizu, H., Fukuda, M,. Kawakubo, Y., Kuwabara, H., Kuroda, M., Yamada, T., Kato, N., Sasaki, Y., Watanabe, T., Kasai, K. & Kawato, M.
  • Organizer: 第37回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-12
• [Presentation] A machine-learning-based biomarker for autism spectrum disorder using resting-state functional MRI. (2013)
  • Author(s): Yahata, N., Morimoto, J., Hashimoto, R., Shibata, K., Imamizu, H., Fukuda, M., Kawakubo, Y., Yamada, T., Sasaki, Y., Kato, N., Watanabe, T., Kasai, K. & Kawato, K.
  • Organizer: 第36回日本神経科学大会（Neuro2013）
  • Place of Presentation: 京都
• [Presentation] A machine-learning-based biomarker for autism spectrum disorder using resting-state functional MRI. (2013)
  • Author(s): Yahata, N., Morimoto, J., Hashimoto, R., Shibata, K., Imamizu, H., Fukuda, M., Kawakubo, Y., Yamada, T., Sasaki, Y., Kato, N., Watanabe, T., Kasai, K. & Kawato, K.
  • Organizer: 11th World Congress of Biological Psychiatry (WFSBP)
  • Place of Presentation: 京都