基于博弈论的精神分裂症心理理论障碍及其脑网络关联研究

Impaired theory of mind is one of traits of schizophrenia and is a critical factor to predict functional outcome of patients with schizophrenia. Current theory of mind tasks fail to capture the ability to infer mental states of others in real-life situations. Furthermore, almost all of studies investigating the neural basis of impaired theory of mind in schizophrenia focus on activation in an individual brain region, but leave the functional interactions among brain regions behind. This project aims to study characteristics of impaired theory of mind using paradigms based on game theory and explore the neural basis behind the impaired theory of mind from the perspective of brain network both in schizophrenic patients with negative symptoms and patients with positive symptoms. Specifically, in study 1, we will use theory of mind paradigms based on game theory to study whether patients can appropriately infer mental states of their partners in social interaction situations, and then to find the relationships between the impaired theory of mind and the clinical characteristics, cognition and social function in both of the two groups of schizophrenic patients. In study 2, we will investigate the brain network relevant to theory of mind based on game theory and explore the relationship between abnormalities in brain networks and the impaired theory of mind in these schizophrenic patients using task-state functional magnetic resonance imaging (fMRI) and resting-state fMRI. This project will clarify the characteristics of theory of mind based on game theory and its neural basis in schizophrenic patients with negative symptoms and patients with positive symptoms. Finally, this project will improve our understanding on psychopathology of schizophrenia, will be helpful to find a new biomarker for early diagnosis and prognosis evaluation of schizophrenia, and will provide evidences for improving therapy and intervention of schizophrenia.

心理理论障碍是精神分裂症特征性表现，是决定患者功能预后程度的关键因素。传统心理理论任务不能真实刻画现实社会个体探测他人意图的能力，且现有研究绝大部分仅关注孤立脑区活动，忽略脑区之间的功能交互。本项目采用博弈论研究范式和脑网络研究方法，研究阴性症状为主型和阳性症状为主型精神分裂症患者的心理理论障碍及其神经基础。研究1采用基于博弈论的心理理论任务范式，研究这两类患者在社会互动中能否正确理解他人意图，并探索其与患者临床特征、认知与社会功能的关系；研究2结合任务态/静息态功能磁共振成像技术，探究这两类患者博弈互动脑网络和静息态脑网络异常模式及其与心理理论障碍的关联。本项目预期将明确博弈互动中阴性和阳性症状为主精神分裂症患者心理理论障碍的各自表现形式及其神经基础，将增进对精神分裂症精神病理机制的理解，发现可用于精神分裂症早期诊断、预后评估的新影像学标记，为改善精神分裂症治疗和干预方式提供理论依据。

心理理论障碍是精神分裂症特征性表现，是决定患者功能预后程度的关键因素。传统心理理论任务不能真实刻画现实社会个体探测他人意图的能力，且现有研究绝大部分仅关注孤立脑区活动，忽略了脑区之间的功能交互。本项目采用博弈论研究范式和脑网络研究方法，研究精神分裂症患者的心理理论障碍及其神经基础，以及这些异常与阳性症状、阴性症状的关系。本项目组研究发现，（1）精神分裂症患者在基于博弈论的心理理论任务范式下，表现出异常的社会互动行为，提示患者“在线”心理理论能力障碍；并发现患者的“离线”心理理论能力，而不是其认知功能，介导了患者的博弈互动行为异常；患者的阳性症状与患者的异常行为有显著相关。（2）精神分裂症患者在迷你最后通牒博弈任务中，表现出异常的脑激活模式，主要表现在楔叶与右侧壳核活动异常。（3）精神分裂症患者在静息状态下，心理理论网络重要脑区即左侧颞顶结合部的功能连接异常。（4）采用最新的动态因果模型分析方法，我们可以发现精神分裂症患者核心脑网络效应连接模式异常，并且异常连接的连接强度与患者临床症状严重程度及认知功能相关。这些研究成果，增进了我们对精神分裂症心理理论障碍及其神经基础的理解。