Multimodal Neural Investigation of Reward Processing in Schizophrenia

精神分裂症奖励加工的多模态神经研究

• 批准号: 9336853
• 负责人: SUSANNA FRYER
• 金额: --
• 依托单位: VETERANS AFFAIRS MED CTR SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9336853
• 关键词: Anhedonia; Award; Behavior; Behavior Control; Behavior Therapy; Behavioral; Belief; Brain; Clinical; Cognitive; Collaborations; Consensus; Corpus striatum structure; Coupling; Cues; Data; Development; Educational workshop; Electroencephalography; Electrophysiology (science); Event-Related Potentials; Failure; Feedback; Functional Magnetic Resonance Imaging; Functional disorder; Gambling; Goals; Healthcare; Impairment; Incentives; Individual; Intervention; Investigation; Knowledge; Lateral; Lead; Literature; Measures; Mental Health; Methodology; Methods; Modality; Motivation; Neurobiology; Neurosciences; Occupational; Outcome; Output; Patients; Pattern; Performance; Prefrontal Cortex; Process; Program Development; Psychotic Disorders; Reporting; Research; Research Personnel; Rewards; Schizophrenia; Scientist; Signal Transduction; Speed; Stimulus; Structure; Symptoms; System; Therapeutic; Training; Ventral Striatum; Veterans; Work; base; brain dysfunction; career development; cingulate cortex; cognitive control; experience; functional outcomes; health care delivery; hedonic; improved; insight; interest; motivated behavior; multimodality; neural circuit; neurobiological mechanism; neuroimaging; novel; outcome forecast; patient subsets; pleasure; public health relevance; relating to nervous system; response; reward processing; severe mental illness; social; symptomatology; tool; young adult

DESCRIPTION (provided by applicant): "Negative" symptoms of schizophrenia, such as anhedonia and amotivation, signal an absence of typical hedonic and motivational outputs, and may reflect underlying alterations in the way the brain processes rewarding stimuli. Recent advances in basic neuroscience are providing novel insights into reward-related neural circuitry that, when perturbed, could contribute to negative symptom manifestation. In particular, impairments in prefrontal-striatal connections may confer higher-order reward processing deficits in schizophrenia, such as deficits in how rewards are represented and valued, as well as in the motivation and execution of goal-directed behaviors that optimize reward seeking. Several fMRI studies have reported that reduced striatal brain activations to rewarding stimuli relate to worse negative symptomatology in schizophrenia patients. In addition, recent findings show that in healthy individuals reward availability enhances functional activity in regions, such as the lateral prefrontal cortex, that drive cognitiv control. Ostensibly, normative control-related brain responses are amplified by incentivized contexts in order to increase behavioral output and thereby maximize reward attainment. Together, these literatures suggest that to better understand the extent to which dysfunctions of the brain's reward system contribute to the real world deficits in goal pursuit and attainment associated with schizophrenia, it will be necessary to consider not only initial brain responses evoked by rewarding stimuli, but also how these more basic reward signals interact with higher-order cognitive features that drive motivated behaviors. Accordingly, this CDA study will examine basic features of evoked brain responses to rewarding stimuli, as well as the interaction of reward incentives on cognitive control functioning in young adults with recent-onset schizophrenia. The training plan will further develop the PI's expertise in psychiatric neuroimaging through a tailored combination of formal coursework, methodological workshops, seminars, and collaboration with established investigators in schizophrenia, reward neurobiology, and the integration of functional neuroimaging methods. More specifically, the proposed work will combine neuroimaging modalities (fMRI and EEG) to characterize neurobiological mechanisms underlying putative reward processing deficits in schizophrenia, as they relate to clinical features of avolition and anhedonia. Major project objectives are to inform understanding of the neurobiology of reward through: i) assessing brain functioning during passive anticipation, receipt and loss of monetary rewards in schizophrenia and ii) determining whether reward-related modulation of brain functioning during cognitive control deviates in schizophrenia from healthy control patterns. By providing information about both spatial and temporal features of brain activity, combination fMRI and EEG will enable a more comprehensive assessment of the aspects of reward-related brain activity that are the focus of the proposed work. Negative symptoms are strong predictors of poorer social and occupational functional outcomes in schizophrenia, suggesting that effectively intervening on this symptom class could demonstrably improve clinical prognosis. Findings from this CDA project could provide valuable insight into the pathophysiology of reward processing anomalies in schizophrenia, which may in turn, inform intervention efforts relevant to treating motivational and hedonic deficits.

描述（由申请人提供）： 精神分裂症的“阴性”症状，例如Anhedonia和动机，表明缺乏典型的享乐和动机产量，并且可能反映了大脑过程奖励刺激的方式的潜在改变。基本神经科学的最新进展正在为与奖励相关的神经回路提供新的见解，而当受到干扰时，可能会导致负面症状表现。特别是，前额叶 - 纹状体连接的损害可能会赋予精神分裂症中的高阶奖励处理缺陷，例如在奖励的代表和重视方面的缺陷以及目标指导行为的动机和执行，以优化奖励寻求奖励。一些功能磁共振成像研究报告说，降低纹状体脑的活化以奖励刺激，与精神分裂症患者的阴性症状较差有关。此外，最近的发现表明，在健康的个体中，奖励可用性增强了驱动认知控制的区域的功能活动，例如外侧前额叶皮层。表面上，与规范控制相关的大脑反应通过激励环境扩大，以增加行为产出并最大程度地提高奖励。这些文献共同表明，为了更好地理解大脑奖励系统功能障碍在多大程度上导致了与精神分裂症相关的目标追求和达到的现实世界中的缺陷，因此有必要不仅考虑到奖励刺激奖励的初始大脑反应，而且还必须考虑这些更多基本奖励信号如何与高级认知能力相互作用，使其与高级认知能力相互作用。因此，这项CDA研究将检查诱发大脑对奖励刺激的反应的基本特征，以及最近患有最近发作精神分裂症的年轻人对认知控制功能的奖励激励措施的相互作用。该培训计划将通过与精神分裂症，奖励神经生物学的既定研究者以及功能性神经成像方法的整合相结合，进一步发展PI在精神神经影像学方面的专业知识。更具体地说，拟议的工作将结合神经成像模式（fMRI和EEG），以表征精神分裂症中假定的奖励处理缺陷的神经生物学机制，因为它们涉及道理和Anhedonia的临床特征。主要项目目标是告知 通过以下方式了解奖励的神经生物学：i）评估精神分裂症中的被动预期，收到和货币奖励的损失和ii）确定精神分裂症与健康控制模式的认知控制偏差期间脑功能的奖励相关调节是否相关。通过提供有关大脑活动的空间和时间特征的信息，fMRI和EEG组合将对奖励相关的大脑活动的各个方面进行更全面的评估，这是拟议工作的重点。负面症状是精神分裂症中社会和职业功能结果较差的有力预测指标，这表明有效介入此症状类别可以明显地改善临床预后。该CDA项目的发现可以为精神分裂症的奖励处理异常的病理生理学提供宝贵的见解，这可能会为干预措施提供与治疗动机和动机有关的干预工作。 享乐不足。