Rumination, arousal and cognition in depression: an fMRI/EEG study

描述（由申请人提供）：我认为在抑郁症中，过度的反刍和失调的觉醒会破坏一般的认知能力和功能。我的目标是在行为和神经层面探索这一假设。反刍是抑郁症的核心特征（Nolen-Hoeksema 2000），并预测了抑郁症精神病理的许多指标（Miranda and Nolen-Hoeksema 2007）。目的1：默认模式网络的激活将与反刍相关，并且在抑郁症中增加。我提出反刍，正如默认模式网络的过度活跃所反映的那样，干扰了支撑正确执行的要求性认知活动的任务积极网络的功能。目的2：在正确的试验中，默认模式网络过度活跃将与抑郁症的任务正性网络活动减弱相关。我认为，抑郁症的觉醒是失调的，表现为临床症状，如兴趣减退、疲劳、精神运动激动/迟钝、失眠/嗜睡，并将导致对唤醒事件的异常心理生理和神经反应，如认知任务中的错误。目标3。在错误试验中，抑郁症患者的神经和心理生理唤醒指标会增加。最后，我提出失调的觉醒也与任务正性网络的最佳功能减弱有关。目标4。在错误后的实验中，基于觉醒的任务正性网络的增强会在抑郁症中减弱。这个应用程序将测试这些假设使用a)注意力任务（埃里克森侧卫任务）；b)多模态成像，包括快速呈现事件相关功能磁共振成像（er-fMRI）和高密度（128通道）脑电图（EEG）；C)并发心理生理指标（瞳孔测量）；d)症状和反刍倾向的测量。我们拟招募30名重度抑郁症患者和30名健康对照。重度抑郁症（MDD）终生患病率为10-25%，死亡率高（1997年美国第八大死因），社会经济成本非常高（1990年美国为440亿美元），是一个重大的公共卫生问题。我们假设反刍、觉醒和认知网络的失调是抑郁症病理生理学的基础。这种功能障碍的特征可以改善新的神经治疗方法，例如重复经颅磁刺激（rTMS），以治疗这种具有如此高的个人和社会成本的疾病。

DESCRIPTION (provided by applicant): I propose that in depression, excessive rumination and dysregulated arousal serve to undermine general cognitive ability and functioning. I aim to explore this hypothesis at the behavioral and neural level. Rumination is a core feature of depression (Nolen-Hoeksema 2000), and predicts numerous indices of depressive psychopathology (Miranda and Nolen-Hoeksema 2007). Aim 1: Default mode network activation will be associated with rumination, and increased in depression. I propose that rumination, as reflected in hyperactivity of the default mode network, interferes with the functioning of a task-positive network underpinning correctly-performed demanding cognitive activity. Aim 2: During correct trials, default mode network hyperactivity will correlate with attenuated task-positive network activity in depression. I propose that arousal is dysregulated in depression, manifested in clinical symptoms such as diminished interest, fatigue, psychomotor agitation/retardation, and insomnia/hypersomnia, and will result in abnormal psychophysiological and neural responses to arousing events, such as errors on a cognitive task. Aim 3. During error trials, neural and psychophysiological measures of arousal will be increased in depression. Finally, I propose that dysregulated arousal also correlates with attenuated optimal functioning of the taskpositive network. Aim 4. During post-error trials, arousal-based enhancement of the task-positive network will be attenuated in depression. This application would test these hypotheses using a) an attentional task (Eriksen flanker task); b) multimodal imaging, including rapid presentation event-related functional magnetic resonance imaging (er-fMRI) and high density (128 channel) electroencephalography (EEG); c) concurrent psychophysiological indices (pupillometry); and d) measures of symptomatogloy and propensity to ruminate. We propose to recruit 30 patients with major depresive disorder (MOD) and 30 healthy control subjects. With 10-25% lifetime prevalence, high mortality (8th leading cause of death in the US in 1997), and a very high economic cost for society ($44 billion in the US in 1990), major depressive disorder (MDD) is a significant public health problem. We posit that dysregulation of networks involved in rumination, arousal and cognition are fundamental to the pathophysiology of depression. Characterization of this dysfunction could improve new neurotherapeutic treatments, such as repeated transcranial magnetic stimulation (rTMS,) for a disorder with such high individual and societal costs.