The Neuronal Correlates of Theory of Mind in Schizophrenia

描述（由申请人提供）：社会功能缺陷是精神分裂症（SZ）最严重的残疾特征之一，也是导致许多患者社会孤立和失业的重要因素。由于最近的研究表明，SZ患者常见的一般神经认知障碍并不能完全解释患者的社交缺陷，因此有人假设，“心智理论”（ToM）推理过程的特定缺陷是SZ患者社交功能障碍的神经病理学基础。ToM推理，或“心理化”，指的是将心理状态（包括情绪、欲望和目标）归因于他人的关键社会过程，以便预测和解释他人的行为，并相应地调整自己的行为。有强有力的证据表明，异常的心理功能是SZ社会功能障碍的基础。尽管研究人员已经开始探索健康个体中处理内隐心智化的神经网络，但SZ社会认知缺陷背后的神经病理学尚不清楚。使用功能磁共振成像（fMRI），我们将测量30名慢性SZ患者和30名精心匹配的健康对照（HC）在社会互动任务（Domino任务）中提供内隐心智化的定义脑网络中的大脑激活模式。在接受功能磁共振成像扫描的同时，参与者将与人类和电脑对手平均玩12次多米诺骨牌游戏。前者独特地涉及到将心理状态归因于另一个人（即预测他们的策略），并处理与奖励和惩罚相关的情绪，同时参与社交双人竞争游戏。为了获胜，玩家有时不得不选择欺骗对手，从而冒着被抓住并受到惩罚的风险（就像在扑克中一样）。当玩家公平地进行游戏时，他们便会受到对手的挑战而获得奖励。我们将分析游戏中的关键时间间隔，即玩家试图预测其人类对手（vs.计算机对手）的反应以避免惩罚并获得奖励（即内隐心理过程）。我们将估计SZ与HC相关的大脑激活模式之间的差异。fMRI概率预测范式将评估多米诺骨牌范式中激活模式对心智化的特异性，而不是概率预测。此外，我们将探讨内隐心智化过程中患者的激活模式与社会能力、症状异质性和注意力、工作记忆、智力和执行功能四个领域的认知能力之间的关系。本研究旨在探讨SZ患者社交功能障碍的神经病理学基础及其与患者神经认知能力、社交能力和症状的关系。反过来，这将是确定有可能从认知和药物康复治疗中获益最多的SZ患者亚群的重要一步，特别是针对ToM社会认知，从而推进未来SZ新治疗工具的研究（包括遗传）。本研究旨在探讨心理化过程的缺陷（即将心理状态，包括情绪，欲望和目标，归因于他人）是SZ社交功能障碍的神经病理学基础的假设。它还将评估与精神化相关的大脑激活异常与患者的神经认知能力、社会能力和症状之间的关系。这些分析的结果将帮助我们确定有可能从认知和药物康复治疗中获益最多的SZ患者亚组，特别是针对ToM社会认知，从而为未来研究（包括遗传学）开发新的SZ治疗工具铺平道路。

DESCRIPTION (provided by applicant): Social function deficits are among the most disabling features of schizophrenia (SZ) and are a significant factor in the resulting social isolation and unemployment experienced by many patients. Since recent studies show that general neurocognitive impairments commonly seen in SZ do not fully explain patients' social deficiencies, it has been postulated that specific deficits in the 'Theory of Mind' (ToM) reasoning process underlie the neuropathology of social dysfunction in SZ. ToM reasoning, or 'mentalizing', refers to the crucial social process of attributing states of mind (including emotions, desires and goals) to other people to allow prediction and interpretation of others' behavior and consequent adjustment of one's own behavior. There is strong evidence that abnormal mentalizing functions underlie the social dysfunction in SZ. Although researchers have started to explore the neuronal networks that process implicit mentalizing in healthy individuals, the neuropathology that underlies this social cognitive deficit in SZ is not yet understood. Using functional MRI (fMRI), we will measure brain activation patterns in a defined brain network that subserves implicit mentalizing in 30 chronic SZ patients and 30 carefully matched healthy controls (HC) during a social interaction task, the Domino task. While undergoing the fMRI scans, participants will play an average of 12 Domino games against a human- and a computer-opponent. The former uniquely involves attributing a state of mind to another person (i.e. predicting their strategy), and processing emotions associated with reward and punishment, while being involved in a social two-player competitive game. In order to win, players occasionally have to choose to bluff their opponent, and thus risk being caught and punished (as in poker). When players play fairly they are rewarded if challenged by the opponent. We will analyze the critical intervals during the game when players are engaged in trying to predict their human-opponent's responses (vs. computer-opponent) to avoid punishments and gain rewards (i.e. implicit mentalizing process). We will estimate the differences between SZ brain activation patterns and those of HC related to this process. An fMRI probability prediction paradigm will evaluate the specificity of activation patterns during the domino paradigm to mentalization as opposed to probability prediction. Additionally, we will explore the relationship between patients' activation patterns during implicit mentalization and their social competence, symptoms heterogeneity and cognitive abilities in four domains: attention, working memory, intelligence, and executive functions. This study is designed to explore the neuropathology underlying social dysfunction in SZ and its association with patients' neurocognitive abilities, social competence and symptomatology. This in turn will be an essential step in identifying a subgroup of SZ patients that has the potential to benefit the most from cognitive and pharmacological rehabilitation remedies specifically targeting ToM social cognition and thus advancing future research (including genetic) of development of new treatment tools for SZ. This study is designed to explore the hypothesis that deficits in mentalizing processes (i.e. attributing states of mind, including emotions, desires and goals, to other people) underlie the neuropathology of social dysfunction in SZ. It will also assess the relationship between brain activations abnormalities associated with mentalizing and patients' neurocognitive abilities, social competence and symptomatology. The results of these analyses will help us in identifying a subgroup of SZ patients that has the potential to benefit the most from cognitive and pharmacological rehabilitation remedies specifically targeting ToM social cognition and thus pave the way for future research (including genetic) of development of new treatment tools for SZ.