Neuroimaging Studies of Reward Processing in Depression

抑郁症奖励处理的神经影像学研究

• 批准号: 7069040
• 负责人: Diego A Pizzagalli
• 金额: $ 30.71万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-07 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7069040
• 关键词: behavioral /social science research tag; bioimaging /biomedical imaging; biomarker; brain imaging /visualization /scanning; brain morphology; clinical research; cues; evoked potentials; functional magnetic resonance imaging; gray matter; human subject; magnetic resonance imaging; major depression; negative reinforcements; neuroanatomy; nucleus accumbens; patient oriented research; phenotype; prefrontal lobe /cortex; psychological stressor; reinforcer

DESCRIPTION (provided by applicant): The aim of this proposal is to investigate the functional neuroanatomy of depression. A promising strategy for parsing the heterogeneity of Major Depressive Disorder (MDD) is to identify phenotypes characterized by reliable functional brain abnormalities. Anhedonia, the lack of reactivity to pleasurable stimuli, is considered a trait marker for depression. Preclinical work suggests links among phenomena associated with depression - decreased hedonic responsiveness, exaggerated stress responsiveness, and dysfunction in the dopaminergic mesolimbic system - but in humans the neural underpinnings are largely unknown. Using behavioral, event-related potential (ERP), and functional magnetic resonance imaging (fMRI) techniques, this proposal aims to investigate these processes. A monetarily reinforced button-press task will be used to dissociate the neural circuitry involved in anticipation of and reactivity to reward or punishment. Experiment 1 addresses the spatio-temporal dynamics of brain mechanisms underlying anticipation of and reactivity to reward and punishment in subjects differing on objective measures of anhedonia, operationalized as decreased responsiveness to reward-related cues in a separate signal-detection task. Compared to controls, subjects with impaired reward responsiveness (n=20) are predicted to show lower activation in regions subserving reward processing (e.g., nucleus accumbens, medial prefrontal cortex) to reward-related, but not to punishment-related, cues. In the ERP data, decreased late frontal negativity wave to reward cues, and decreased medial-frontal negativity and P3 to reward feedbacks, are hypothesized. Experiment 2 extends this paradigm to subjects with a DSM-IV diagnosis of MDD. These subjects (n=23) are expected to show lower activation in regions subserving reward processing than controls (n=23) in response to reward-related cues, and higher activation in regions subserving processing of withdrawal-related cues. In the ERP data, medial-frontal negativity and P3 are predicted to differentiate the subject groups. Experiment 3 addresses the effects of mental stress on reward processing in MDD. Compared to controls (n=21), depressed subjects (n=21) are expected to show a larger stress-induced reduction of activation in regions subserving reward processing, and a larger activation in regions subserving punishment processing. Decreased gray matter density in medial and subgenual prefrontal regions, as assessed by voxel-based MRI morphometrical analyses, is expected to be associated with the detrimental effect of stress on reward responsiveness. Overall, the integration of techniques with high temporal (ERP) and spatial (fMRI) resolution will enhance understanding of the functional neuroanatomy of depression.

描述（由申请人提供）：本提案的目的是研究抑郁症的功能神经解剖学。解析重度抑郁症（MDD）异质性的一个有前途的策略是识别以可靠的功能性大脑异常为特征的表型。快感缺乏，即对愉悦刺激缺乏反应，被认为是抑郁症的一个特征标志。 临床前研究表明，与抑郁症相关的现象之间存在联系——享乐反应性降低、应激反应性过度以及多巴胺能中脑边缘系统功能障碍——但在人类中，神经基础在很大程度上是未知的。该提案旨在利用行为、事件相关电位（ERP）和功能磁共振成像（fMRI）技术来研究这些过程。金钱强化的按钮按下任务将用于分离参与奖励或惩罚的预期和反应的神经回路。实验1探讨了不同快感缺失客观测量的受试者对奖励和惩罚的预期和反应的大脑机制的时空动态，具体表现为在单独的信号检测任务中对奖励相关线索的反应性降低。与对照组相比，奖励反应能力受损的受试者（n = 20）预计在促进奖励处理的区域（例如伏核、内侧前额叶皮层）对奖励相关但与惩罚相关的线索表现出较低的激活。在 ERP 数据中，假设奖励线索的晚期额叶负波减少，奖励反馈的内侧额叶负波和 P3 减少。实验 2 将这一范例扩展到 DSM-IV 诊断为 MDD 的受试者。预计这些受试者（n = 23）在响应与奖励相关的线索时，在支持奖励处理的区域中表现出比对照组（n = 23）更低的激活，并且在支持与戒断相关线索的处理的区域中表现出更高的激活。在 ERP 数据中，预测内侧额叶负性和 P3 可以区分受试者组。实验 3 探讨了 MDD 中精神压力对奖励处理的影响。与对照组（n = 21）相比，抑郁受试者（n = 21）预计在支持奖励处理的区域中表现出更大的压力诱导的激活减少，并且在支持惩罚处理的区域中显示出更大的激活。通过基于体素的 MRI 形态测量分析评估，内侧和膝下前额叶区域灰质密度的降低预计与压力对奖励反应性的有害影响有关。总体而言，将技术与高时间（ERP）和空间（fMRI）分辨率相结合将增强对抑郁症功能神经解剖学的理解。