Investigating emotional reactivity in depression using event-related potentials

描述(由申请人提供)：严重抑郁障碍(MDD)具有巨大的公共卫生重要性，因为它具有高患病率、早发性、慢性和功能障碍。虽然行为和外周生理学研究已发现与MDD相关的情绪反应性缺陷，导致情绪环境不敏感(ECI)理论模型，但神经成像研究已发现根据感兴趣区域和所使用的情感刺激类型的不同，存在活动不足和活动过度的证据。一种可能性是，MDD的情绪反应性受到个人刺激相关性的影响，因此对标准刺激的反应性减弱，对具体刺激的反应性增加，尽管这一点尚未在单一样本中进行测试。这项拟议的研究试图使用三种直接测量大脑活动的方法来研究这一问题：事件相关电位(ERPs)、脑电(EEG)的频谱分析和功能磁共振成像(FMRI)。通过整合这三种方法，这项研究将有助于我们更好地理解MDD情绪异常加工的病理生理机制，这与国家精神卫生研究所神经科学和基础行为科学部的使命是一致的。此外，通过寻求系统地表征MDD的特定神经异常，本研究可能提供客观的生物学措施，为未来在临床问题上的工作提供信息，如治疗选择、跟踪治疗进展和预测康复。为了检验个人相关性对MDD中异常情绪处理的影响，拟议的研究将考虑30名患有当前MDD的成年人和30名从未抑郁的对照组的神经活动，具体目的有三：(A)比较ERP/EEG对规范和具体情绪刺激的反应；(B)比较ERP/EEG对基于奖励和基于绩效的反馈的反应；以及(C)使用功能磁共振检查神经对情绪面孔和奖励的激活。这项研究还结合了几个基本的培训内容，将为申请人提供机会，以获得在几个领域的进一步临床和方法学专业知识。作为该应用程序的联合发起人，Daniel Klein博士将提供情绪障碍评估方面的高级培训。Lilianne Mujica-Parodi博士也是赞助商之一，他将提供有关获取、分析和解释功能磁共振数据的培训。这项建议还包括两位提供高级统计培训的顾问：Joseph Dien博士在将主成分分析和源定位技术应用于ERP/EEG数据集方面拥有专业知识，Andreas Keil博士拥有使用时频方法分析振荡EEG数据的专业知识。最后，建议的研究和培训的实施将由Greg Hajcak博士监督，他是这项提议的发起人，也是申请者的主要学术导师。 公共卫生相关性：严重抑郁障碍(MDD)是一种对公共卫生具有巨大重要性的疾病，因为其患病率高、发病早、慢性和功能障碍。目前的项目试图用来研究大脑活动对情绪刺激的特定模式，以阐明MDD情绪异常反应的神经机制。通过这样做，这将有助于最近的研究工作，以确定与MDD相关的生物标记物，这些标记物可用于促进有效的治疗选择、跟踪治疗进展和预测康复。

DESCRIPTION (provided by applicant): Major depressive disorder (MDD) is of immense public health importance because of its high prevalence, early onset, chronicity, and functional impairment. While behavioral and peripheral physiological studies have identified a deficit in emotional reactivity associated with MDD, leading to an emotion context insensitivity (ECI) theoretical model, neuro imaging studies have yielded evidence of both hypo- and hyperactivity depending on the region of interest and the type of affective stimuli used. One possibility is that emotional reactivity in MDD is moderated by the personal relevance of stimuli, such that reactivity to normative stimuli is blunted and reactivity to idiographic stimuli is increased, although this has yet to be tested within a single sample. The proposed study seeks to examine this issue using three direct measures of brain activity: event-related potentials (ERPs), spectral analysis of the electroencephalogram (EEG), and functional magnetic resonance imaging (fMRI). By integrating these three methods, this study will be well-equipped to enhance our understanding of the pathophysiological mechanisms underlying abnormal emotional processing in MDD, which is consistent with the mission of the Division of Neuroscience and Basic Behavioral Science at the National Institute of Mental Health. Further, by seeking to systematically characterize specific neural abnormalities in MDD, the current study may provide objective biological measures that can inform future work on clinical issues such as treatment selection, tracking treatment progress, and predicting recovery. To examine the influence of personal relevance on abnormal emotional processing in MDD, the proposed research will consider neural activity among 30 adults with current MDD and 30 never-depressed controls, with three specific aims: (a) to compare ERP/EEG responses to normative and idiographic emotional stimuli; (b) to compare ERP/EEG responses to reward- and performance-based feedback; and (c) to use fMRI to examine neural activation to emotional faces and rewards. This research also incorporates several essential training components that will provide the opportunity for the applicant to attain further clinical and methodological expertise in several domains. As a co-sponsor of this application, Dr. Daniel Klein will provide advanced training in the assessment of mood disorders. Dr. Lilianne Mujica-Parodi, also a co-sponsor, will provide training in the acquisition, analysis, and interpretation of fMRI data. Two consultants are also included in this proposal to provide advanced statistical training: Dr. Joseph Dien has expertise in the application of principal components analysis and source localization techniques to ERP/EEG data sets, and Dr. Andreas Keil has expertise in using time-frequency approaches to analyze oscillatory EEG data. Finally, the implementation of the proposed research and training will be overseen by Dr. Greg Hajcak, the sponsor of this proposal and the primary academic mentor of the applicant. PUBLIC HEALTH RELEVANCE: Major depressive disorder (MDD) is an illness that is of immense public health importance because of its high prevalence rate, early onset, chronicity, and functional impairment. The current project seeks to use examine specific patterns of brain activity in response to emotional stimuli, in order to shed light on the neural mechanisms underlying abnormal emotional reactivity in MDD. In doing so, this will aid recent research efforts to identify biological markers associated with MDD that can be used to facilitate effective treatment selection, track treatment progress, and predict recovery.