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Estimating the activities in the three neurotransmission systems for clarifying the mechanisms of cognitive dysfunction in schizophrenia

Research Project

Project/Area Number 20K03490
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 10040:Experimental psychology-related
Research InstitutionNational Center of Neurology and Psychiatry

Principal Investigator

Shirama Aya  国立研究開発法人国立精神・神経医療研究センター, 精神保健研究所 児童・予防精神医学研究部, 室長 (50738127)

Co-Investigator(Kenkyū-buntansha) 住吉 太幹  国立研究開発法人国立精神・神経医療研究センター, 精神保健研究所 児童・予防精神医学研究部, 部長 (80286062)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2021: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2020: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Keywords統合失調症 / 認知機能障害 / 自律神経系 / 瞳孔計測 / 神経伝達系
Outline of Research at the Start

従来,統合失調症はドーパミン(DA)過剰状態の表れであるとされてきた。D2受容体の発見や抗精神病薬,DA作動薬を用いた研究から,皮質におけるDA活性の不足と,皮質下における過剰を想定した統合失調症モデルが考案された(Davis et al., 1991)。一方,DA系に作用する抗精神病薬だけでは,統合失調症の認知機能障害を十分に改善できず,非 DA系の寄与を含めた包括的な理解が必要である。そこで本研究では,瞳孔径および網膜電図からDA,NA,Achの3系を非侵襲的に推定し,統合失調症の認知機能障害に各系が及ぼす影響を検討する。

Outline of Final Research Achievements

The underlying mechanisms of cognitive dysfunction including impairments of verbal memory, attention, executive function, problem solving, and processing speed in schizophrenia are thought to be involved with different neurotransmission systems. In order to understand the cognitive dysfunction in schizophrenia, the present study invented a new method for estimating activities in several neurotransmission systems non-invasively. We analyzed the complexity and symmetricity of the temporal behavior of pupil size in order to estimate the activities of the sympathetic/parasympathetic (NA/ACh) systems and the locus coeruleus. Also, we examined the efficacy of ERG (electroretinogram) for estimating the DA system activity. In addition, we measured pupil size during an inference task and found that prediction uncertainty mediated by the arousal system is not efficiently utilized in patients with schizophrenia.

Academic Significance and Societal Importance of the Research Achievements

統合失調症では,記憶,注意,作業記憶,問題解決,処理速度などの広範な認知機能に障害が見られる。認知機能障害は患者の生活能力や機能的転帰に対して陽性症状や陰性症状と比べ強い影響力をもち,統合失調症の中心的特徴と考えられている。統合失調症における認知機能障害には複数の神経伝達系が複雑に関与しているのみられるが,従来の手法ではこれらを同時に評価することは難しかった。本研究では,アイトラッカーやERGといった非侵襲的な計測方法を用いて神経伝達系の活動を評価する手法を考案した。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (13 results)

All 2022 2021 2020

All Journal Article (7 results) (of which Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (5 results) (of which Int'l Joint Research: 2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Asymmetric Complexity in a Pupil Control Model With Laterally Imbalanced Neural Activity in the Locus Coeruleus: A Potential Biomarker for Attention-Deficit/Hyperactivity Disorder2022

    • Author(s)
      Hiraku Kumano, Sou Nobukawa, Aya Shirama, Tetsuya Takahashi, Toshinobu Takeda, Ohta Haruhisa, Mitsuru Kikuchi, Akira Iwanami, Nobumasa Kato, Shigenobu Toda
    • Journal Title

      Neural Computation

      Volume: 34 Issue: 12 Pages: 2388-2407

    • DOI

      10.1162/neco_a_01545

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ADHDの瞳孔径制御モデルにより生成された瞳孔径時系列の複雑性解析2022

    • Author(s)
      熊野 開, 信川 創, 白間 綾, 高橋 哲也, 戸田 重誠
    • Journal Title

      信学技法

      Volume: 121 Pages: 1-14

    • Related Report
      2021 Research-status Report
  • [Journal Article] Pupil Diameter Control Model Focusing on the Left-Right Difference of the Neural Activity Locus Coeruleus of ADHD2021

    • Author(s)
      Kumano, H., Nobukawa, S., Shirama, A., Takahashi, T., & Toda, S.
    • Journal Title

      Proceedings of The 2021 NonLinear Science Workshop

      Volume: ID: 36 Pages: 1-1

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] 青斑核活動の非対称性に着目したADHDの瞳孔径制御モデルの構築2021

    • Author(s)
      熊野 開, 信川 創, 白間 綾, 高橋 哲也, 戸田 重誠
    • Journal Title

      インテリジェント・システム・シンポジウム2021講演論文集

      Volume: 2021/9/21-23 Pages: 219-223

    • Related Report
      2021 Research-status Report
  • [Journal Article] Identification of attention-deficit hyperactivity disorder based on the complexity and symmetricity of pupil diameter2021

    • Author(s)
      Nobukawa Sou、Shirama Aya、Takahashi Tetsuya、Takeda Toshinobu、Ohta Haruhisa、Kikuchi Mitsuru、Iwanami Akira、Kato Nobumasa、Toda Shigenobu
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 1-14

    • DOI

      10.1038/s41598-021-88191-x

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pupillometric Complexity and Symmetricity Follow Inverted-U Curves Against Baseline Diameter Due to Crossed Locus Coeruleus Projections to the Edinger-Westphal Nucleus2021

    • Author(s)
      Nobukawa Sou、Shirama Aya、Takahashi Tetsuya、Takeda Toshinobu、Ohta Haruhisa、Kikuchi Mitsuru、Iwanami Akira、Kato Nobumasa、Toda Shigenobu
    • Journal Title

      Frontiers in Physiology

      Volume: 12 Pages: 614479-90

    • DOI

      10.3389/fphys.2021.614479

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Atypical alert state control in adult patients with ADHD: A pupillometry study2020

    • Author(s)
      Shirama Aya、Takeda Toshinobu、Ohta Haruhisa、Iwanami Akira、Toda Shigenobu、Kato Nobumasa
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 12 Pages: e0244662-e0244662

    • DOI

      10.1371/journal.pone.0244662

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Predictive inference and pupil-linked arousal systems in schizophrenia2022

    • Author(s)
      Shirama, A., & Sumiyoshi, T.
    • Organizer
      NEURO 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 左右瞳孔径挙動に基づくADHDの判別の検討と数理モデルによる神経活動推定2022

    • Author(s)
      1)信川創, 熊野開, 白間綾, 髙橋哲也, 武田俊信, 太田晴久, 菊知充, 岩波明, 加藤進昌, 戸田重誠
    • Organizer
      日本成人期発達障害臨床医学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Pupil diameter control model focusing on the left-right difference of the neural activity locus coeruleus of ADHD2021

    • Author(s)
      Kumano, H. Nobukawa, S. Shirama, A. Takahashi, T. Toda, S.
    • Organizer
      The 2021 Nonlinear Science Workshop
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] ADHDにおける瞳孔制御モデルの構築2021

    • Author(s)
      熊野 開, 信川 創, 白間 綾, 高橋 哲也, 戸田 重誠
    • Organizer
      第20回情報科学技術フォーラム
    • Related Report
      2021 Research-status Report
  • [Presentation] 青斑核活動の非対称性に着目したADHDの瞳孔径制御モデルの構築2021

    • Author(s)
      熊野 開, 信川 創, 白間 綾, 高橋 哲也, 戸田 重誠
    • Organizer
      インテリジェント・システム・シンポジウム2021
    • Related Report
      2021 Research-status Report
  • [Patent(Industrial Property Rights)] 精神活動推定装置2020

    • Inventor(s)
      2020
    • Industrial Property Rights Holder
      国立精神・神経医療研究センター、千葉工業大学、福井大学、昭和大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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