Neural Correlates of Proactive Control in Major Depressive Disorder

抑郁症是一种终生患病率很高的精神疾病，社会成本巨大。抑郁症中的认知缺陷已经被观察到无数次。先前的研究已经报道了认知控制的缺陷，即基本认知和运动过程的灵活，目标导向的控制。在这种情况下，特别重要的是研究结果表明，在认知控制的性能可以影响所使用的刺激的情感效价。例如，抑郁症患者的认知控制缺陷在处理负价信息时表现得尤为突出。这些发现不仅有助于提高我们对抑郁症认知缺陷机制的理解，而且还为认知行为治疗方法的进一步发展提供了重要基础。在本申请中，我们建议在波恩（埃廷格）和蒂罗尔（杜舍克）并行进行两项研究，以大大扩展这一领域的先前研究。首先，我们旨在将抑郁症的认知控制研究整合到Braver（2012）的双重控制机制模型的理论框架中。该模型已被证明在认知心理学和认知神经科学研究中具有影响力，它区分了主动和被动控制模式，并允许对精神障碍控制方面的选择性障碍进行预测。第二，系统研究了情感调节对主动控制的影响。最后，我们希望研究这些过程的神经相关性;在波恩，我们建议使用功能性磁共振成像（fMRI），在蒂罗尔，我们将使用脑电图（EEG）。在研究I（波恩）中，50名DSM 5诊断为抑郁症的门诊患者和50名健康对照（男/女）将在fMRI中执行抑制控制任务（antisaccades）。在抑制扫视中的主动控制将通过施加情绪负面（愤怒、恐惧、悲伤的面孔）、积极和中性刺激来调制。在研究II（Tirol）中，将在50名门诊抑郁症患者和50名健康对照（男/女）中同时应用antisaccade任务和事件相关电位记录。总的来说，这两项研究将提供一个全面和详细的表征抑郁症的前摄认知控制，其调制的情感因素和神经相关。这两项研究在认知控制的选定方面和选定的神经科学方法方面相互补充，这使得研究空间（fMRI）和时间（EEG）方面的神经相关的主动控制。

Depression is a mental disorder with high lifetime prevalence and enormous societal costs. Cognitive deficits in depression have been observed numerous times. Previous studies have reported well-replicated deficits in cognitive control, i.e. the flexible, goal-oriented control of basic cognitive and motor processes. Particularly important in this context are findings which demonstrate that performance in cognitive control can be influenced by the affective valence of the utilised stimuli. For example, deficits in cognitive control in depression have been found to be particularly strong when negatively valenced information has to be processed. These findings are of importance not only as they help to improve our understanding of the mechanisms of cognitive deficits in depression; they also provide an important basis for further development of cognitive behavioural therapy approaches. In this application, we propose two studies to be run in parallel in Bonn (Ettinger) and Tirol (Duschek), in order to substantially extend prior research in this area. First, we aim to integrate the study of cognitive control in depression into the theoretical framework of the Dual Mechanisms of Control Model by Braver (2012). This model, which has proven influential in cognitive psychology and cognitive neuroscience research, distinguishes between proactive and reactive modes of control and allows making predictions regarding selective impairments in those aspects of control in mental disorders. Second, we aim to systematically study the influence of affective modulation on proactive control. Finally, we wish to characterise the neural correlates of these processes; in Bonn we proposed to use functional magnetic resonance imaging (fMRI) and in Tirol we will use electroencephalography (EEG). In Study I (Bonn), 50 outpatients with a DSM 5 diagnosis of depression and 50 healthy controls (m/f) will perform an inhibitory control task (antisaccades) in fMRI. Proactive control in the inhibition of saccades will be modulated through the application of emotionally negative (angry, fearful, sad faces), positive and neutral stimuli. In Study II (Tirol), the antisaccade task will be applied simultaneously with recordings of event-related potentials in 50 outpatients with depression and 50 healthy controls (m/f). Overall, the two studies will provide a comprehensive and detailed characterisation of proactive cognitive control in depression, its modulation by affective factors and its neural correlates. The two studies ideally complement each other in terms of the selected aspects of cognitive control and the chosen neuroscientific methods, which allow investigation of both spatial (fMRI) and temporal (EEG) aspects of the neural correlates of proactive control.