Quantitative Behavioral and Imaging Phenotypes of Amotivation in Schizophrenia

描述(申请人提供)：这项拟议的研究旨在发现导致精神分裂症无动力的神经回路异常，并确定无动力的定量行为和成像测量，以加速未来的翻译和治疗研究。病理性的动力丧失是精神分裂症的“消极症状”之一，它涉及到情感和社会能力的缺陷。与其他负面症状，如快感缺乏(快感降低)、无社交(社交动力降低)和表现力下降，运动障碍是精神分裂症导致残疾的主要原因。与通常对抗精神病药物有反应的阳性症状(幻觉、妄想)不同，包括运动障碍在内的阴性症状对当前的治疗反应很差，因此构成了精神病学中一个主要的未得到满足的治疗需求。尽管这一点很重要，但精神分裂症的运动一直没有得到充分的研究，导致这种缺陷的大脑异常在很大程度上仍不清楚。精神分裂症实验室动机范式的验证和应用落后于享乐性和情绪处理缺陷的研究，缩小这一差距是本提案的主要目标。在四年的时间里，这项拟议的研究将评估80名患有广泛阴性症状的成人精神分裂症患者的动机，以及40名健康对照受试者。具体目标是：1)使用转译实验室任务来量化精神分裂症的动机缺陷，2)确定精神分裂症中与动机缺陷相关的神经回路功能障碍，以及3)定义 复杂的全脑表型预测运动严重程度。为了实现这些目标，我们将应用新的行为和功能成像任务以及先进的多变量模式分析技术。这项研究将提供一个预测运动严重程度的详细的脑行为模式，这将有助于促进对精神分裂症的理解、治疗和预防。

DESCRIPTION (provided by applicant): The proposed study aims to discover the neural circuit abnormalities contributing to amotivation in schizophrenia, and identify quantitative behavioral and imaging measures of amotivation that can accelerate future translational and therapeutic research. A pathological loss of motivation is one of the "negative symptoms" of schizophrenia, which involve deficits in emotional and social capacities. Together with other negative symptoms such as anhedonia (reduced pleasure), asociality (reduced social drive), and reduced expressivity, amotivation contributes strongly to the disability caused by schizophrenia. Unlike positive symptoms (hallucinations, delusions) which are generally responsive to antipsychotic medications, negative symptoms including amotivation respond poorly to current treatments, and therefore constitute a major unmet therapeutic need in psychiatry. Despite this importance, amotivation in schizophrenia has been understudied and the brain abnormalities causing this deficit remain largely unknown. Validation and application of laboratory motivation paradigms in schizophrenia has lagged behind research in hedonic and emotion- processing deficits, and narrowing this gap is a major aim of this proposal. Over four years, the proposed study will evaluate motivation in 80 adults with schizophrenia with a wide range of negative symptoms, as well as 40 healthy control subjects. The specific aims are: 1) To quantify motivational deficits in schizophrenia using translational laboratory tasks, 2) To identif neural circuit dysfunction associated with motivation deficits in schizophrenia, and 3) To define a complex whole-brain phenotype predicting amotivation severity. To achieve these aims we will apply novel behavioral and functional imaging tasks together with advanced multivariate pattern analysis techniques. This study will provide a detailed brain-behavior pattern predicting amotivation severity which will help advance the understanding, treatment, and prevention of schizophrenia.