fMRI During Simulated Social Interactions in Schizophrenia: Emotion and Cognition

描述(申请人提供)：在许多精神分裂症患者中，甚至在他们的疾病还没有表现出来并被诊断出来之前，他们的童年时期就已经出现了社会互动的异常。社交联系的局限性、社交互动中的不适、社交技能发育不良、迟钝和/或社交不当的情绪，以及情绪相关的认知障碍，这些都是精神分裂症一旦表现出来并被诊断出来的特征。尽管人们认识到这种复杂的社会、情感和认知障碍的重要性，但相关的神经生物学异常一直很少被研究，也很少被理解。我们开发了一种新的范式，用功能磁共振成像研究模拟情绪唤起社会互动过程中的区域大脑激活。我们制作了演员直接与受试者谈论快乐或悲伤的个人经历的录像带，并展示了情感的各种面部、声音和身体表现。这种多维的、动态的和与社会背景相关的刺激比连续呈现人们面部的静态照片具有更大的现实世界有效性，这些照片通常用于社交-情绪激活的大脑成像研究。通过将健康受试者在这些录像带中的大脑激活与演员谈论情绪中性体验时的激活进行比较，我们确定了社交情绪共同的区域大脑激活以及每种情绪特有的激活。我们还制作了录像带，让演员假装吸食可卡因或准备赌博，并要求受试者加入他们的行列。通过这些和原始磁带，我们确定了可卡因成瘾者和病态赌徒的大脑激活异常，这些异常与他们的主要病理行为和引发情绪的社会互动有关。这项申请中提出的研究将是第一次将这种方法应用于精神分裂症的研究。在早期的工作中，我们证明了精神分裂症患者的认知和大脑偏侧性受到负面情绪的异常影响。为了进一步研究这一点，我们在模拟的唤起情绪的社交互动的录像带中加入了一项工作记忆任务。在对健康受试者的初步研究中，我们已经证明，快乐的情绪会增强与认知相关的基底节-丘脑皮质回路的激活。我们还建议使用这种新的方法来研究社会产生的情绪对精神分裂症患者认知相关大脑激活的影响。我们预测，引发积极情绪的社会互动不会像在健康人中那样，增强精神分裂症患者与认知相关的大脑活动。许多精神分裂症患者在表达和理解社交中必不可少的情绪方面存在问题。这些问题在疾病诊断之前，在一定程度上存在于家庭成员中，限制了患者的生活质量，甚至限制了患者参与治疗的能力。在这个项目中，我们将使用社会神经科学研究的新知识和新开发的脑成像程序来研究患者在社会情绪功能方面的大脑问题。

DESCRIPTION (provided by applicant): Social interactions are abnormal in many people with schizophrenia even during childhood before their illnesses are manifest and diagnosed. Limitations in social connectedness discomfort in social interactions poorly developed social skills, blunted and/or socially inappropriate emotion, and emotion- related disturbances of cognition are all features of schizophrenia once manifest and diagnosed. Despite the recognized importance of this complex of social, affective and cognitive disturbances, the associated neurobiological abnormalities have been little studied and are poorly understood. We have developed a new paradigm for studying regional brain activations with fMRI during simulated emotion-evoking social interactions. We created video tapes of actors talking directly to the subjects about happy or sad past personal experiences, and displaying the full range of facial, voice and body manifestations of the emotion. This multidimensional, dynamic and socially contextualized stimulation has greater real world validity than the sequential presentation of still photographs of people's faces typically used in brain imaging studies of social-emotional activation. By comparing brain activations in healthy subjects during these tapes to activations when the actors talked about emotionally-neutral experiences, we identified regional brain activations common to both socially generated emotions and activations specific to each emotion. We also created tapes in which actors pretended to use cocaine or prepare to gamble and asked the subjects to join them as they did. With these and the original tapes we identified brain activation abnormalities in cocaine addicts and pathological gamblers related to their primary pathological behaviors and to emotion-evoking social interactions. The studies proposed in this application would be the first to apply this method to the study of schizophrenia. In earlier work, we demonstrated that cognition and brain laterality were abnormally affected by negative emotion in people with schizophrenia. To investigate this further, we incorporated a working memory task within the video tapes of simulated emotion-evoking social interactions. In preliminary studies of healthy subjects we have demonstrated that happy emotion leads to enhanced cognition-related activation of basal ganglia-thalamocortical circuits. We also propose to use this new methodology to study the effects of socially generated emotion on cognition related brain activation in people with schizophrenia. We predict that positive emotion-evoking social interactions will not enhance cognition-related brain activity in people with schizophrenia as it does in healthy people. Many people with schizophrenia have problems with the expression and understanding of emotion essential in social interactions. These problems precede the diagnosis of illness, are present to some degree in family members, limit patient quality of life and even the ability to participate in treatments. In this project we will use new knowledge from social neuroscience research and newly developed brain imaging procedures to study brain aspects of the patient problems in social-emotional function.