Project 3: Modulating repetitive negative thinking related brain networks in young adults with depression

项目摘要：项目3--土司矢盖 重度抑郁障碍(MDD)是青壮年最常见的心理健康问题之一 (18-25岁)发生在11%，并对长期结果有严重影响，如共病精神 疾病、失业和自杀，如果得不到有效治疗的话。重复的消极思维(RNT)是 反复无常、难以控制的思维过程。RNT始终链接到一个 抑郁的频率、持续时间和严重程度更高，也预示着成年早期的自杀倾向。 尽管已经建立了治疗MDD的有效方法，但近三分之二的患者将不会有反应， 用目前可用的方法治疗MDD会留下高达90%的残留症状， 包括RNT。RNT越高，对这两种抗抑郁药的反应越慢，结果越差 药物和心理治疗。因此，RNT和潜在的神经回路将是理想的直接 有针对性的，它将促进相关的大脑调节功能。实时功能磁共振 成像神经反馈(rtfmri-nf)训练是一种理想的、非侵入性的翻译RNT相关脑的方法。 将这些网络转化为有针对性的疾病修正过程。这项建议建立在我们之前的工作基础上，在那里我们 确定了与RNT相关的脑功能连通性，即我们确定了 右前岛(RAI)与右颞上沟(RSTs)之间呈正相关 MDD患者具有较高的RNT。在这项建议中，我们使用rtfmri-nf来因果联系 RAI-RSTs的连通性与RNT的强度。我们将进行随机双盲、假对照研究。 RtfMRI-nf试验n=110(n=100完成者，假设自然损失率为10%)青壮年MDD患者(18岁- 25)有RNT症状。我们将评估如何使用rtfmri-nf来减弱RNT，从而减少 抑郁症。我们的目标是研究降低RAI-RSTS连通性在多大程度上缓解RNT和 接受活性rtfMRI-nf(n=55，50名完成者)的年轻MDD患者的抑郁症状与 Sham(人工产生反馈信号的神经反馈；n=55，50个完成者)组。具体目标 目的是确定(1)真实rtfMRI-nf与假rtfMRI-nf对RAI-RSTs功能连接的急性影响； RNT和抑郁症。一项探索性的目标将检查RAI-RST的急性调节程度 连通性导致RNT的变化以及抑郁症和亚急性RAI-RSTs连通性的变化 RtfMRI-nf治疗后一周。首要目标是确定(1)RNT中涉及RAI-RSTS连通性 可以作为MDD的靶向疾病修改过程来调节，以及(2)通过调节RAI-RST 连接减少RNT我们可以降低抑郁的严重程度。这项建议的系统性方法 通过确定跨诊断结构的神经靶点来体现NIH RDoC倡议的目标，以及 研究特定网络的直接调制下的大脑-行为功能关系。

PROJECT SUMMARY: Project 3 – Tsuchiyagaito Major Depressive disorder (MDD) is among the most common mental health conditions in young adulthood (ages 18-25) occurring in 11%, and has serious effects on long-term outcomes such as comorbid mental disorders, unemployment and suicide, if not effectively treated. Repetitive negative thinking (RNT) is a recurrent thought process which is negative in valence and difficult to control. RNT is consistently linked to a higher frequency, duration, and severity of depression, and also predicts suicidality in early adulthood. Although effective treatments for MDD have been established, nearly two-thirds of patients will not respond, and treatment of MDD with currently available modalities leave as many as 90% with residual symptoms, including RNT. Higher RNT is also linked to a slower response and poorer outcome to both antidepressant medication and psychotherapy. Thus, RNT and the underlying neural circuit would be ideal to be directly targeted and it would boost the relevant regulatory brain functions. Real-time functional Magnetic Resonance Imaging neurofeedback (rtfMRI-nf) training is an ideal, non-invasive method to translate RNT-related brain networks into a targetable disease-modifying process. This proposal builds on our previous work, in which we identified the brain functional connectivity associated with RNT, i.e., we determined that the connectivity between the right anterior insular (rAI) and the right superior temporal sulcus (rSTS) was positively correlated with higher RNT in individuals with MDD. In this proposal, we use rtfMRI-nf to causally relate the dysfunction of rAI-rSTS connectivity with the intensity of RNT. We will conduct a randomized double-blind, sham-controlled trial of rtfMRI-nf in n=110 (n=100 completers, assuming a 10% attrition) young adult MDD individuals (ages 18- 25) with RNT symptoms. We will evaluate how rtfMRI-nf can be used to attenuate RNT, and thereby reduce depression. We aim to investigate the degree to which reducing rAI-rSTS connectivity alleviates RNT and depressive symptoms in young adults with MDD receiving active rtfMRI-nf (n=55, 50 completers) compared to sham (neurofeedback with artificially generated feedback signals; n=55, 50 completers) groups. Specific aims are to determine (1) an acute effect of real vs. sham rtfMRI-nf on rAI-rSTS functional connectivity; (2) and on RNT and depression. An exploratory aim will examine the degree to which acute modulation of rAI-rSTS connectivity leads to changes in RNT as well as depression and sub-acute rAI-rSTS connectivity change one week after rtfMRI-nf. The overarching goal is to establish that (1) rAI-rSTS connectivity is involved in RNT and can be modulated as a targetable disease-modifying process of MDD, and (2) by modulating rAI-rSTS connectivity to reduce RNT we can reduce depression severity. The systematic approach of this proposal embodies the goals of the NIH RDoC Initiative by identifying a neural target for a transdiagnostic construct, and studying the brain-behavioral function relationships with the direct modulation of a specific network.