重性抑郁障碍患者负性无关信息摆脱困难的神经振荡编码模式的脑电研究

The deficient control process that cannot rid memory of negative information in patients with major depressive disorder (MDD) contributes to severe rumination, which is defined as a recurrent, self-reflective, and unintentional focus on depressive symptomatology and its causes and consequences. High levels of rumination is not merely a symptom of depression, it maintains, exacerbates depressive symptoms and predicts the likelihood of recurrence of depressive episode. Therefore, for understanding the neural mechanism of occurrence and maintenance of rumination in MDD, it would be useful to explore the underlying pathologic mechanisms of the inability to disengage from negative irrelevant information. Numerous literatures have verified that various deficits in MDD are probably caused by the connectivity disturbance and functional abnormalities between limbic and cortex networks across left and right cerebral hemisphere, however, the underlying neural networks of difficulties expelling negative irrelevant information is still obscure. Considering that different frequency oscillations play critical roles in emotional arouse, cognitive control, learning and memory, as well as the broad scope of brain oscillations in MDD diagnosis and non-pharmacologic interventions, in the current study, with electroencephalography(EEG) study, which is a directly non-invasive recording technology of neuronal electrical activity along the scalp, as well as behavior psychological assessment, we investigate the time-frequency encoding features of disengaging from negative irrelevant information in MDD patients and healthy controls, respectively. By analysis of the wavelet power, phase synchronization, cross-frequency coupling and partial directed coherence, we will try to elaborate neural encoding pattern during spontaneous state and the condition on expelling negative irrelevant information from working memory in MDD from the perspective of oscillation coupling and synchronization. We hope to structure the underlying characteristic neural oscillation networks involved in the occurrence and maintenance of rumination in MDD, in order to explore more reliable and feasible EEG biomarker for MDD diagnosis and potential interventional target toward the aspect of neural oscillation for MDD treatment.

重性抑郁障碍（MDD）患者由于认知控制受损，无法摆脱既往无关的负性记忆的干扰，继而无法有效处理新信息，外在表现为反刍思维，其严重程度直接影响着MDD症状的持续、恶化以及复发。因此阐明MDD负性无关信息摆脱困难的机制对于探索其反刍思维的产生和维持乃至MDD的病理机制意义重大。尽管影像和电生理研究已表明MDD的众多病理缺陷来自于左右皮层-边缘系统网络的失能，但对其摆脱负性信息的神经网络机制尚未明了。考虑到不同神经节律振荡在情绪唤醒、认知控制和学习记忆中的作用以及其在疾病诊疗中广阔的应用前景，本项目中，我们将运用具有高时间敏感度的神经振荡无创检测技术——脑电，结合行为学，从神经振荡跨频耦合和同步网络的角度阐述MDD患者负性无关信息摆脱相关的静息和工作记忆任务的神经编码，希望找出患者反刍思维产生和维持的异常神经振荡网络，以探索MDD诊断的神经网络标记物的可能性并为非药物治疗寻求可能的神经振荡靶点。

重性抑郁障碍（MDD）患者普遍饱受着反刍思维的困扰，其严重程度直接影响着MDD症状的持续、恶化以及复发。尽管影像和电生理研究已表明MDD的众多病理缺陷来自于左右皮层-边缘系统网络的失能，但对其反刍思维的神经网络机制尚未明了。考虑到不同神经节律振荡在情绪唤醒、认知控制和学习记忆中的作用以及其在疾病诊疗中广阔的应用前景，本项目旨在从脑电节律振荡时频复杂度的角度探索MDD患者反刍思维相关的神经编码特征。我们收集了25例未经治疗的MDD患者和23例健康对照的神经认知评估数据和静息态、任务态下的脑电信号。目前对数据分析的结果显示，MDD患者的反刍思维较之健康对照更为严重，其严重程度与患者认知损害以及阻滞的程度呈显著正相关；通过对静息状态下脑电信号小波变换功率谱和排序熵的分析，我们发现MDD患者脑电信号的高频节律尤其是前额叶和部分额顶区gamma节律的功率显著增加，而且delta、theta以及beta节律的熵值显著增加。我们进一步对被试反刍思维的程度与脑电特征信号进行相关分析，结果显示MDD患者反刍思维中强迫思考的程度与额叶中央、左侧额顶区的高频尤其是Gamma功率成显著正相关，而健康被试强迫思考的程度则主要与顶枕区的高频（beta和gamma）节律功率成正相关。上述结果显示MDD患者较之健康对照，其静息状态下的神经节律振荡的复杂度更高，复杂度的增加往往反映了大脑信息加工的低效能，这可能与MDD患者情绪调节和认知功能的损害有关；而且两组人群反刍思维相关的的脑区并不重合，MDD患者反刍思维相关的脑区主要位于额、顶叶，这很可能提示MDD患者和健康人群反刍思维的神经网络机制是不同的，MDD患者不可控的思维反刍与额、顶叶的信息加工异常有关。这些结果既为MDD患者的异常脑功能网络提供了新的证据，也加深了对抑郁性反刍思维中枢机制的理解，同时为MDD患者反刍思维的神经调控探索潜在的靶点提供了依据。