The Neuronal Correlates of Theory of Mind in Schizophrenia

精神分裂症心理理论的神经元相关性

• 批准号: 7256676
• 负责人: Michal Assaf
• 金额: $ 8.2万
• 依托单位: HARTFORD HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7256676
• 关键词: Area; Attention; Behavior; Brain; Chronic Schizophrenia; Cognitive; Cognitive deficits; Computers; Development; Disease; Emotions; Functional Magnetic Resonance Imaging; Functional disorder; Fusiform gyrus; Future; Genetic; Goals; Heterogeneity; Human; Impairment; Individual; Intelligence; Life; MRI Scans; Magnetic Resonance Imaging; Measures; Medial; Mediating; Mind; Neurocognition; Neurocognitive; Neurons; Participant; Patients; Pattern; Performance; Persons; Play; Prefrontal Cortex; Probability; Process; Punishment; Rehabilitation therapy; Research; Research Personnel; Rewards; Risk; Scanning; Schizophrenia; Score; Severities; Short-Term Memory; Social Adjustment; Social Functioning; Social Interaction; Social isolation; Specificity; Subgroup; Symptoms; Testing; Thinking; Unemployment; base; design; desire; executive function; experience; hemodynamics; neuropathology; outcome forecast; remediation; response; social; social cognition; social skills; theories; tool

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.

描述（由申请人提供）：社会功能缺陷是精神分裂症（SZ）最严重的特征之一，也是导致许多患者经历社会孤立和失业的一个重要因素。由于最近的研究表明，SZ 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，因此推测“心理理论”(ToM) 推理过程中的特定缺陷是 SZ 社交功能障碍的神经病理学基础。 ToM 推理或“心智化”是指将心理状态（包括情感、欲望和目标）归因于他人的关键社会过程，以允许预测和解释他人的行为并随后调整自己的行为。有强有力的证据表明，精神化功能异常是深圳社会功能障碍的根源。尽管研究人员已经开始探索健康个体中处理内隐心理化的神经元网络，但 SZ 社会认知缺陷背后的神经病理学尚不清楚。使用功能性 MRI (fMRI)，我们将测量定义的大脑网络中的大脑激活模式，该模式有助于 30 名慢性精神分裂症患者和 30 名仔细匹配的健康对照 (HC) 在社交互动任务（即多米诺骨牌任务）中的内隐心智化。在接受功能磁共振成像扫描时，参与者将与人类和计算机对手平均玩 12 场多米诺骨牌游戏。前者独特地涉及将一种心态归因于另一个人（即预测他们的策略），并处理与奖励和惩罚相关的情绪，同时参与社交两人竞争游戏。为了获胜，玩家有时不得不选择吓唬对手，从而冒着被抓住和惩罚的风险（就像在扑克中一样）。当玩家公平竞争时，如果受到对手的挑战，他们就会获得奖励。我们将分析游戏过程中玩家试图预测人类对手（相对于计算机对手）的反应以避免惩罚并获得奖励（即隐式心智化过程）的关键间隔。我们将估计 SZ 大脑激活模式和 HC 大脑激活模式之间与此过程相关的差异。功能磁共振成像概率预测范式将评估多米诺骨牌范式到心智化期间激活模式的特异性，而不是概率预测。此外，我们将探讨患者在内隐心智化过程中的激活模式与其社交能力、症状异质性和四个领域的认知能力之间的关系：注意力、工作记忆、智力和执行功能。本研究旨在探讨 SZ 社交功能障碍的神经病理学及其与患者神经认知能力、社交能力和症状的关系。这反过来将是识别 SZ 患者亚组的重要一步，该亚组有可能从专门针对 ToM 社会认知的认知和药物康复疗法中获益最多，从而推进未来新治疗工具开发的研究（包括遗传学）。深圳。本研究旨在探讨这样一种假设：心智化过程的缺陷（即，将情绪、欲望和目标等心理状态归因于他人）是深圳社会功能障碍的神经病理学基础。它还将评估与心智化相关的大脑激活异常与患者的神经认知能力、社交能力和症状之间的关系。这些分析的结果将帮助我们确定一个 SZ 患者亚群，他们有可能从专门针对 ToM 社会认知的认知和药物康复疗法中获益最多，从而为未来开发新疗法的研究（包括遗传）铺平道路。 SZ 的治疗工具。