Combining Electrophysiological, Behavioral and Psychological Measures to Target Mechanisms of Emotion Processing and Regulation During Cognitive Behavior Therapy in Depression

项目摘要 这个R21应用程序旨在阐明认知过程中发生变化的神经生物学机制。 行为疗法（CBT）治疗重度抑郁症（MDD）。这项假设驱动的研究将探讨 心理正念（PM）和正念（M）的心理结构之间的关联 CBT治疗MDD的时间过程及其与自动神经电生理和行为测量的关系 (i.e.刺激驱动的或自下而上的）情绪处理。这一目标的动机是以下理由：PM 和M代表自我认知的不同元认知过程，被认为对情绪调节（ER）至关重要 CBT的成功显著情感图片的事件相关电位（ERP）反映了被试不同阶段的动机性 关注使用先进的分析EEG技术，我们将这些阶段与大脑皮层的分层激活联系起来。 "情绪"脑区沿着枕颞腹侧流，范围从前意识刺激 分类（右侧次级视觉皮层，右侧颞顶交界）到意识评价（后 扣带皮层、腹内侧皮层）。重要的是，对情绪刺激的ERP反应迟钝， 在临床抑郁症和右颞顶和背外侧前额叶激活减退中观察到 在成功的抗抑郁药或电休克治疗后，这些区域恢复正常。一种两分情感识别 测试，以左耳（右半球）的形式提供自下而上情绪处理的听觉测量 识别语音模式的情感语调的优势，揭示了MDD的行为缺陷 患者此外，在CBT中，对于言语刺激（左半球）的右耳优势增加 响应者。采用随机分配到CBT或非特异性支持治疗的60名MDD患者样本 （安慰剂），我们将获得心理，电生理，行为和临床结果的反应措施 至12周的CBT在治疗前后设计，以确定：（1）何时何地在大脑自动 情绪处理被CBT改变;（2）如果情绪反应的变化被元- 自我认识的认知过程;以及，（3）如果这些措施，单独或组合，有希望作为 CBT治疗反应的标志物。健康成年人（HC）的现有ERP和行为数据使用 相同的实验方案将提供标准（尺度）数据。这项研究汇集了经验丰富的临床 心理学家和精神病学家与具有专业知识的调查人员一起进行抑郁症的治疗和研究 在情感神经科学和电生理学研究中的应用。它将提供一个关键的新步骤， ER的情感认知和神经生理机制，通过CBT发生变化。除了 他们的理论相关性，该项目的研究结果也将有助于开发新的和更有针对性的 这些研究有助于确定可能从CBT治疗单相抑郁症中获益最多的患者。

PROJECT SUMMARY This R21 application aims to clarify the neurobiological mechanisms by which change occurs during cognitive behavior therapy (CBT) for major depressive disorder (MDD). This hypothesis-driven study will explore the association between the psychological constructs of psychological mindedness (PM) and mindfulness (M) during the time course of CBT for MDD, and its relationship to electrophysiological and behavioral measures of automatic (i.e. stimulus-driven or bottom-up) emotion processing. This objective is motivated by the following rationale: PM and M represent different meta-cognitive processes of self-knowledge deemed critical for emotion regulation (ER) and CBT success. Event-related potentials (ERPs) to salient affective pictures reflect different stages of motivated attention. Using advanced analytic EEG techniques, we have linked these stages to the hierarchical activation of `emotional' brain regions along the occipitotemporal ventral stream, ranging from preconscious stimulus categorization (right secondary visual cortex, right temporoparietal junction) to conscious appraisal (posterior cingulate cortex, ventromedial cortex). Importantly, blunted ERP responses to emotionally-arousing stimuli have been observed in clinical depression, and hypoactivation of right temporoparietal and dorsolateral prefrontal regions normalize after successful antidepressant or electroconvulsive treatment. A dichotic emotion recognition test, which provides an auditory measure of bottom-up emotion processing in form of a left ear (right hemisphere) advantage for recognizing the emotional intonation of speech patterns, has revealed behavioral deficits in MDD patients. Moreover, an increased right ear advantage for verbal stimuli (left hemisphere) is seen in CBT responders. Employing a sample of 60 MDD patients randomly assigned to CBT or nonspecific supportive therapy (placebo), we will obtain psychological, electrophysiological, behavioral and clinical outcome measures of response to 12 weeks of CBT in a pre-post treatment design to determine: (1) when and where in the brain automatic emotion processing is altered by CBT; (2) if changes in emotional responding are moderated or mediated by meta- cognitive processes of self-knowledge; and, (3) if these measures, alone or in combination, have promise as markers of CBT treatment response. Existing ERP and behavioral data for healthy adults (HC) obtained using the same experimental protocols will provide normative (yardstick) data. This study brings together experienced clinical psychologists and psychiatrists doing treatment and research in depression with investigators having expertise in affective neuroscience and electrophysiological studies in MDD. It will provide a critical new step for outlining the affective-cognitive and neurophysiological mechanisms of ER by which change through CBT occurs. Apart from their theoretical relevance, the findings of this project will also aid in developing novel and more targeted interventions and in identifying patients who may benefit most from CBT for unipolar depression.