Functional neuroimaging of reward and motivation deficits in schizophrenia

描述（由申请人提供）：此职业发展奖申请题为“奖励和动机缺陷的功能性神经iniaging精神分裂症。“候选人将是宾夕法尼亚大学精神病学助理教授。他将由Raquel Gur和Ruben Gur博士指导，他们以研究精神分裂症的情感和认知缺陷而闻名。该提案的动机是候选人以前的经验，研究奖励的神经化学作为一个MD-PhD学生，照顾精神分裂症患者作为精神科医生，并使用功能性MRI（fMRI）研究精神分裂症的病理生理学作为博士后研究员。精神分裂症的阴性症状（社交、动机和情感缺陷）对功能障碍有很大影响。他们迫切需要更好的理解和更有效的治疗。这项研究将集中在腹侧纹状体（VS），它在将奖励经验转化为未来动机方面起着关键作用。候选人的初步数据将VS功能减退与阴性症状的总体严重程度联系起来。拟议的研究将测试候选人的假设，即VS功能减退将具体涉及低动机和降低期望的快乐。当受试者执行简单的社会和非社会奖励任务时，将使用fMRI测量VS活动。将获得详细的阴性症状特征，以及尼古丁依赖和抑郁的指标，因为这些常见的合并症也会影响VS功能。一级家庭成员，谁往往表现出消极的精神病学，将与患者本身一起研究。这将使研究结果能够独立于药物和慢性疾病的影响进行探索。该研究是专门设计来发展候选人的科学专业知识和独立的研究轨迹符合他的职业目标。此外，候选人将通过以下领域的课程和指导学习进行专业培训：功能磁共振成像技术，情感神经科学，药理学，统计学以及有效，道德临床试验的设计。拟议的工作将为候选人准备一个独立的研究生涯，重点是提高对精神分裂症的理解和治疗。精神分裂症是一种常见的脑部疾病，给患者、家庭和社会带来巨大的成本。缺乏动力和快乐减少的症状会导致慢性社会和职业障碍。该提案旨在澄清这些缺陷的神经生物学，并为候选人的职业生涯做好准备，使用强大的脑成像技术为精神分裂症患者开发更有效的治疗方法。

DESCRIPTION (provided by applicant): This Career Development Award application is entitled "Functional Neuroiniaging of Reward and Motivation Deficits in Schizophrenia." The candidate will be an Assistant Professor of Psychiatry at the University of Pennsylvania. He will be mentored by Drs. Raquel Gur and Ruben Gur, renowned for their research on emotional and cognitive deficits of schizophrenia. The proposal is motivated by the candidate's prior experiences studying the neurochemistry of reward as an MD-PhD student, caring for patients with schizophrenia as a psychiatrist, and using functional MRI (fMRI) to study schizophrenia pathophysiology as a postdoctoral fellow. Negative symptoms (social, motivational, and emotional deficits) of schizophrenia have a strong impact on functional disability. They present an urgent need for better understanding and more effective treatments. The study will focus on the ventral striatum (VS), which plays a key role in converting rewarding experiences into future motivation. The candidate's preliminary data links VS hypofunction to global severity of negative symptoms. The proposed study will test the candidate's hypothesis that VS hypofunction will be specifically related to low motivation and reduced expectations of pleasure. VS activity will be measured using fMRI while subjects perform simple social and nonsocial reward tasks. A detailed negative symptom profile will be obtained, together with measures of nicotine dependence and depression, as these common comorbidities also impact VS function. First-degree family members, who often exhibit negative symptomatology, will be studied alongside the patients themselves. This will allow findings to be explored independently of medication and chronic illness effects. The study is specifically designed to develop the candidate's scientific expertise and independent research trajectory in line with his career goals. In addition, the candidate will pursue specialized training through coursework and mentored learning in the following areas: fMRI techniques, affective neuroscience, pharmacology, statistics, and the design of effective, ethical clinical trials. The proposed work will prepare the candidate for an independent research career focused on improving the understanding and treatment of schizophrenia. PUBLIC HEALTH RELEVANCE: Schizophrenia is a common brain disorder that imposes enormous costs on patients, families, and society. Symptoms of low motivation and reduced pleasure contribute to chronic social and occupational impairment. This proposal aims to clarify the neurobiology of these deficits, and prepare the candidate for a career using powerful brain imaging technology to develop more effective treatments for patients with schizophrenia.