Elucidating the autism pathogenesis through brain networks of "theory of mind" and modeling autism in non-human primates

2018 Fiscal Year Final Research Report

• Project/Area Number: 26293261
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Niigata University
• Principal Investigator: Someya Toshiyuki 新潟大学, 医歯学系, 教授 (50187902)
• Co-Investigator(Kenkyū-buntansha): 長谷川 功 新潟大学, 医歯学系, 教授 (60282620) ; 飯島 淳彦 新潟大学, 自然科学系, 教授 (00377186) ; 川嵜 圭祐 新潟大学, 医歯学系, 准教授 (60511178) ; 江川 純 新潟大学, 医歯学総合研究科, 特任准教授 (80648527) ; 北村 秀明 新潟大学, 医歯学総合研究科, 非常勤講師 (00361923)
• Project Period (FY): 2014-04-01 – 2019-03-31
• Keywords: 心の理論 / 非言語的誤信念課題 / DREADD / マカクザル

Outline of Final Research Achievements

Human neuroimaging studies using various false-belief (FB) attribution tasks have revealed relationships between theory of mind (ToM) and brain networks, including the medial prefrontal cortex (mPFC). In the present study, we examined whether there was causation between neuronal activity in the macaque mPFC and the spontaneous gaze bias to FB targets. We injected hM4Di, an inhibitory DREADD , into the mPFC. We chemogenetically inactivated the mPFC using clozapine N-oxide, a specific ligand to hM4Di. We found that chemogenetic deactivation of the mPFC with CNO injection in monkeys expressing hM4Di specifically altered the gaze bias to the FB target. Thus, our results indicate that neural activity in the macaque mPFC plays a causal role in ToM. These findings suggest the novel possibility that macaques implicitly attribute mental states to others via the operation of neural circuits that are shared with humans, in which the mPFC plays a pivotal role.

Free Research Field

発達精神医学

Academic Significance and Societal Importance of the Research Achievements

本研究により、マカクザルには心の理論がある可能性、及び内側前頭前野が心の理論の脳回路の一部である可能性が示唆された。本研究成果により妥当性の高いASDモデル動物を作成することが可能となり、分子遺伝的基盤や生物学的治療の研究が飛躍的に推進されると考えられる。