Neuroimaging of Food Reinforcer Processing in Schizophrenia

描述（由申请人提供）：众所周知，精神分裂症（SZ）患者表现出参与可能导致奖励的目标导向行为的倾向降低。人们通常认为精神分裂症的动机缺陷源于体验快乐的能力降低，称为快感缺乏。然而，最近的一些研究挑战了这一观点，发现SZ患者经常报告正常的享乐体验。因此，精神分裂症患者寻求奖励行为的减少可能有一个更复杂的解释，可能与奖励处理的生理学有关。事实上，从精神分裂症的神经影像学研究中可以明显看出，大脑中涉及奖赏处理的区域出现了异常。这些发现指出了文献中的一个重要矛盾：精神分裂症患者报告正常的享乐体验，但往往表现出与奖励处理相关的异常生理证据。为了研究这种明显矛盾的原因，我们建议采用一种实验文献中的范式，该范式已被用于与功能性磁共振成像（fMRI）相结合，以确定大脑（眶额皮质）的活动最密切跟踪食物奖励的报告经验的部分。在这种模式中，参与者在MRI扫描仪中接受少量液体食物奖励，如番茄汁和巧克力牛奶，同时定期在视觉模拟量表上评估与每种食物相关的快乐体验。这种范式将使我们能够以更分级的方式确定精神分裂症患者大脑生理学与报告的享乐体验之间的对应关系，以及这些关系与健康志愿者中观察到的关系相似的程度。我们的预测是，精神分裂症患者自我报告的快乐和眶额皮层对食物奖励的神经反应之间的对应关系将明显弱于健康志愿者。此外，我们假设MRI对食物奖励的反应将更系统地与精神分裂症阴性症状的临床评级（如无意识）相关。这些结果可能对理解患者的动机缺陷以及开发更好的精神分裂症阴性症状治疗方法具有重要意义。 公共卫生相关性：精神分裂症是一种复杂的精神障碍，影响约1%的人口，导致超过3%的受影响个体在其成年生活中慢性残疾，以及巨大的公共卫生负担，就精神分裂症患者的极高失业率和公共卫生保健系统的巨大财务成本而言。由于精神分裂症的功能障碍与该疾病的阴性症状（如快感缺乏（无法体验快乐）和意志丧失（动机降低））之间的密切关系，因此在理解和开发治疗此类症状的治疗机制方面取得进展至关重要。该项目的目标是研究与精神分裂症患者的快乐体验相关的神经过程，以增加我们对阴性症状起源的了解，并确定潜在的治疗目标。

DESCRIPTION (provided by applicant): It is widely known that patients with schizophrenia (SZ) show a reduced tendency to engage in goal- directed behavior that could lead to rewards. It has often been thought that motivational deficits in schizophrenia stem from a reduced ability to experience pleasure, called anhedonia. A number of recent studies challenge this view, however, finding that SZ patients frequently report normal hedonic experience. The reduction in reward-seeking behavior in schizophrenia is thus likely to have a more complicated explanation, possibly related to the physiology of reward processing. Abnormalities in brain regions involved in reward processing are, in fact, evident from neuroimaging studies of schizophrenia. These findings point to an important contradiction in the literature: schizophrenia patients report normal hedonic experience, but often show evidence of abnormal physiological associated with reward processing. In order to investigate the reasons for this apparent contradiction, we propose to adapt a paradigm from the experimental literature, which has been used, in conjunction with functional magnetic resonance imaging (fMRI), to identify the part of the brain (orbitofrontal cortex) whose activity most closely tracks the reported experience of food rewards. In this paradigms, participants receive small squirts of liquid food rewards, like tomato juice and chocolate milk, in the MRI scanner, while periodically rating the experience of pleasure associated with each food on a visual analog scale. This paradigm will allow us to determine, in a more graded fashion, correspondences between brain physiology and reported hedonic experience in schizophrenia, and the extent to which these relationships resemble those observed in healthy volunteers. Our prediction is that the correspondence between self- reports of pleasure and neural responses to food rewards in orbitofrontal cortex will be significantly weaker in schizophrenia patients than in healthy volunteers. Furthermore, we hypothesize that MRI responses to food rewards will relate more systematically to clinical ratings of negative symptoms, such as avolition, in schizophrenia. These results would potentially have important implications for understanding motivational deficits in patients, and for developing better treatments for the negative symptoms of schizophrenia. PUBLIC HEALTH RELEVANCE: Schizophrenia is a complex mental disorder affecting approximately 1% of the population, that results in chronic disability for more than 3 of affected individuals through their adult lives, as well as a tremendous public health burden, in terms of the extremely high rate of unemployment in individuals with schizophrenia and the enormous financial costs to public health care system. Because of the close relationship between functional disability in schizophrenia and negative symptoms of the disorder, such as anhedonia (the inability to experience pleasure) and avolition (reduced motivation), it is critical that progress be made in understanding and developing therapeutic mechanisms for treating this class of symptoms. The goal of the proposed project is to investigate the neural processes associated with the experience of pleasure in schizophrenia, in order to increase our knowledge of the origins of negative symptoms, and to identify potential treatment targets.