Neural correlates of the oxytocin in the treatment of autism spectrum disorder based on aberrant neural network hypothesis

• Project/Area Number: 16K10206
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: University of Fukui
• Principal Investigator: Takahashi Tetsuya 福井大学, 学術研究院医学系部門, 客員准教授 (00377459)
• Co-Investigator(Kenkyū-buntansha): 菊知 充 金沢大学, 子どものこころの発達研究センター, 教授 (00377384) ; 平石 博敏 浜松医科大学, 光尖端医学教育研究センター, 特任研究員 (40643789) ; 山西 輝也 福井工業大学, 環境情報学部, 教授 (50298387)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2016: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: 自閉症スぺクトラム障害 / 神経ネットワーク / GABA神経活動 / 脳磁図 / オキシトシン / ネットワーク解析 / 自閉症スペクトラム障害 / 神経ネットワーク解析 / 自閉性スペクトラム障害 / GABA神経 / 自閉性障害 / 非線形・グラフ解析

Outline of Final Research Achievements

GABAergic dysfunction plays a crucial role in the pathogenesis of aberrant neural network hypothesis in autism spectrum disorder (ASD). The perinatal excitatory-to-inhibitory shift of GABA is mediated by oxytocin. The deficit of this oxytocin-mediated GABA inhibition reportedly associates with the prevalence of ASD. Therefore, oxytocin has been receiving great attention as a neuroprotective agent of ASD.
Gamma-band oscillatory activity is reportedly involved in mediating GABAergic activity. Additionally, complex network theory is a useful approach in understanding brain network. This research aimed to elucidate therapeutic mechanisms of oxytocin in ASD using MEG with newly developed analysis methods.

Academic Significance and Societal Importance of the Research Achievements

本研究課題で開発した、dynamical phase synchronization analysis（Nobukawa et al., 2018）は動的な位相同期現象を複雑性理論によって定量化するものであり、またtemporal-scale-specific fractal analysis（Nobukawa et al., 2019）は複数の時間軸を用いて、時系列上の複雑性を定量化するものである。
これらの解析法は、神経ネットワーク特性に新たな視点をもたらす先駆的な解析法であり、今後精神疾患における神経ネットワーク異常を理解する上で重要な役割を果たすと考えられる。

Research Products

• [Journal Article] Changes in functional connectivity dynamics with aging: A dynamical phase synchronization approach (2019)
  • Author(s): Sou Nobukawa, Mitsuru Kikuchi, Tetsuya Takahashi
  • Journal Title: NeuroImage Volume: 188 Pages: 357-368
  • DOI: 10.1016/j.neuroimage.2018.12.008
  • Peer Reviewed / Open Access
• [Journal Article] Atypical temporal-scale-specific fractal changes in Alzheimer's disease EEG and their relevance to cognitive decline (2019)
  • Author(s): Sou Nobukawa, Teruya Yamanishi, Haruhiko Nishimura, Yuji Wada, Mitsuru Kikuchi, Tetsuya Takahashi
  • Journal Title: Cognitive Neurodynamics Volume: 13 Issue: 1 Pages: 1-11
  • DOI: 10.1007/s11571-018-9509-x
  • Peer Reviewed / Open Access
• [Journal Article] Abnormal functional connectivity of high-frequency rhythms in drug-naïve schizophrenia. (2018)
  • Author(s): Takahashi T, Goto T, Nobukawa S, Tanaka Y, Kikuchi M, Higashima M, Wada Y.
  • Journal Title: Clin Neurophysiol. Volume: 129 Issue: 1 Pages: 222-231
  • DOI: 10.1016/j.clinph.2017.11.004
  • Peer Reviewed
• [Journal Article] Band-specific atypical functional connectivity pattern in childhood autism spectrum disorder. (2017)
  • Author(s): Takahashi T, Yamanishi T, Nobukawa S, Kasakawa S, Yoshimura Y, Hiraishi H, Hasegawa C, Ikeda T, Hirosawa T, Munesue T, Higashida H, Minabe Y, Kikuchi M.
  • Journal Title: Clin Neurophysiol. Volume: 128 Issue: 8 Pages: 45-50
  • DOI: 10.1016/j.clinph.2017.05.010
  • Peer Reviewed
• [Journal Article] Band-specific atypical functional connectivity pattern in childhood autism spectrum disorder (2017)
  • Author(s): Tetsuya Takahashi, Teruya Yamanishi, Sou Nobukawa, Shinya Kasakawa, Yuko Yoshimura, Hirotoshi Hiraishi, Chiaki Hasegawa, Takashi Ikeda, Tetsu Hirosawa, Toshio Munesue, Haruhiro Higashida, Yoshio Minabe, Mitsuru Kikuchi
  • Journal Title: Clinical Neurophysiology Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] How to characterize complex brain networks (2019)
  • Author(s): Tetsuya Takahashi
  • Organizer: Mechanism of Brain and Mind 19th Winter Workshop
  • Int'l Joint Research / Invited
• [Presentation] Childhood Brain Signal Complexity and Connectivity (2018)
  • Author(s): T Takahashi, T Ikeda, C Hasegawa, Y Yoshimura, Nobukawa, Y Minabe, M Kikuchi
  • Organizer: The 21st International Conference on Biomagnetism
  • Int'l Joint Research
• [Presentation] 神経ネットワークダイナミクスから探る精神疾患のメカニズム (2017)
  • Author(s): 高橋哲也
  • Organizer: 第1７回Ｋフォーラム
  • Invited
• [Presentation] Increasing Signal Variability During Development and Its Relevance to Autism Spectrum Disorders (2017)
  • Author(s): Tetsuya Takahashi
  • Organizer: World Federation of Societies of Biological Psychiatry
  • Int'l Joint Research
• [Presentation] The Emerging Field of E/MEG Analyses on Neural Network-Complexity and Connectivity- (2017)
  • Author(s): Tetsuya Takahashi
  • Organizer: Germany-Hong Kong Joint Workshop at the Hong Kong Baptist University
  • Invited
• [Patent(Industrial Property Rights)] 生体信号処理装置、生体信号処理システム、および制御プログラム (2017)
  • Inventor(s): 高橋哲也
  • Industrial Property Rights Holder: 高橋哲也
  • Industrial Property Rights Type: 特許
  • Filing Date: 2017