Multimodal Neural Investigation of Reward Processing in Schizophrenia

描述（由申请人提供）： 精神分裂症的“阴性”症状，如快感缺乏和动机丧失，表明缺乏典型的享乐和动机输出，并可能反映大脑处理奖励刺激方式的潜在变化。基础神经科学的最新进展为奖赏相关的神经回路提供了新的见解，当受到干扰时，可能会导致负面症状的表现。特别是，前额叶-纹状体连接的损伤可能会导致精神分裂症患者的高阶奖励处理缺陷，例如奖励如何表示和评价的缺陷，以及优化奖励寻求的目标导向行为的动机和执行的缺陷。一些功能磁共振成像研究报告说，减少纹状体的大脑激活奖励刺激与精神分裂症患者更糟糕的负性行为。此外，最近的研究结果表明，在健康的个体中，奖励的可获得性增强了诸如外侧前额叶皮层等区域的功能活动，这些区域驱动认知控制。从表面上看，规范控制相关的大脑反应被激励的环境放大，以增加行为输出，从而最大限度地获得奖励。总之，这些文献表明，为了更好地了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实现的真实的世界缺陷，不仅需要考虑奖励刺激引起的初始大脑反应，而且还需要考虑这些更基本的奖励信号如何与驱动动机行为的高阶认知特征相互作用。因此，本CDA研究将探讨诱发脑反应的奖励刺激的基本特征，以及奖励激励对近期发作的精神分裂症的年轻人的认知控制功能的相互作用。培训计划将进一步发展PI在精神病学神经影像学方面的专业知识，通过定制的正式课程、方法学讲习班、研讨会以及与精神分裂症、奖励神经生物学和功能性神经影像学方法整合方面的既定研究者的合作。更具体地说，拟议的工作将结合联合收割机神经成像方式（功能磁共振成像和脑电图），以表征神经生物学机制的基础上假定的奖励处理缺陷的精神分裂症，因为它们涉及到临床特征的无意志和快感缺乏。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）评估精神分裂症患者在被动预期、接受和失去金钱奖励期间的大脑功能; ii）确定精神分裂症患者在认知控制期间与奖励相关的大脑功能调节是否偏离健康控制模式。通过提供有关大脑活动的空间和时间特征的信息，fMRI和EEG的组合将能够更全面地评估奖励相关的大脑活动的各个方面，这些方面是拟议工作的重点。阴性症状是精神分裂症患者较差的社会和职业功能结局的强预测因子，这表明有效干预这类症状可以明显改善临床预后。这个CDA项目的发现可以为精神分裂症中奖励处理异常的病理生理学提供有价值的见解，这反过来可以为治疗动机和行为相关的干预工作提供信息。 享乐赤字

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.