Multimodal Neural Investigation of Reward Processing in Schizophrenia

描述(由申请人提供)： 精神分裂症的“消极”症状，如快感缺失和运动障碍，标志着缺乏典型的享乐性和激励性输出，可能反映了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与奖励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表现。特别是，前额叶-纹状体连接的障碍可能会导致精神分裂症患者更高级别的奖赏加工缺陷，例如缺乏奖赏的表示和价值，以及优化奖赏寻求的目标导向行为的动机和执行方面的缺陷。几项功能磁共振研究报告称，精神分裂症患者纹状体大脑对奖励性刺激的激活减少与更糟糕的阴性症状有关。此外，最近的发现表明，在健康的个体中，奖励的可用性增强了驱动Cognitiv控制的区域的功能活动，例如外侧前额叶皮质。表面上看，规范性控制相关的大脑反应会被激励情境放大，以增加行为输出，从而最大限度地获得奖励。综上所述，这些文献表明，为了更好地了解大脑奖励系统的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方面的现实世界缺陷，不仅有必要考虑奖励刺激引发的初始大脑反应，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，这项CDA研究将检验对奖励刺激的诱发大脑反应的基本特征，以及奖励激励对新近发病的精神分裂症年轻人认知控制功能的相互作用。培训计划将通过正式课程、方法学研讨会、研讨会以及与精神分裂症、奖励神经生物学和功能神经成像方法的整合方面的知名研究人员的合作，进一步发展PI在精神神经成像方面的专业知识。更具体地说，这项拟议的工作将结合神经成像手段(fMRI和EEG)来表征精神分裂症潜在的奖赏加工缺陷的神经生物学机制，因为它们与痛失和快感缺乏的临床特征有关。主要项目目标是告知 通过以下方式理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时的大脑功能，以及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的结合将使人们能够更全面地评估与奖励相关的大脑活动，这是拟议工作的重点。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有力预测因素，这表明对这类症状的有效干预可以明显改善临床预后。这项CDA项目的发现可以为精神分裂症奖赏加工异常的病理生理学提供有价值的见解，这反过来可能为与治疗动机和精神障碍相关的干预努力提供信息。 享乐主义的缺陷。

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.