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

项目 3：调节患有抑郁症的年轻人的重复消极思维相关的大脑网络

• 批准号: 10711141
• 负责人: Aki Tsuchiyagaito
• 金额: $ 27.3万
• 依托单位: LAUREATE INSTITUTE FOR BRAIN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10711141
• 关键词: Acute; Adult; Age; Anterior; Antidepressive Agents; Area; Attenuated; Back; Behavioral; Brain; Brain region; Data; Detection; Diagnostic; Disease; Double-Blind Method; Emotional; Episodic memory; Equipment and supply inventories; Event; Feedback; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Individual; Individual Differences; Informal Social Control; Insula of Reil; Language; Link; Major Depressive Disorder; Measurable; Measures; Mediating; Mental Depression; Mental Health; Mental disorders; Methods; Modality; Montgomery and Asberg depression rating scale; Neurosciences; Outcome; Participant; Patients; Pharmaceutical Preparations; Play; Process; Prognosis; Psychotherapy; Randomized; Recovery; Recurrence; Regulation; Research Domain Criteria; Residual state; Role; Running; Severities; Signal Transduction; Speech; Structure of superior temporal sulcus; Suicide; Symptoms; Thinking; Time; Training; Translating; Unemployment; United States National Institutes of Health; Visit; Work; arm; cognitive process; comorbidity; depressive symptoms; effective therapy; efficacy study; emerging adult; experience; health assessment; heuristics; indexing; language processing; neural; neural circuit; neurobiological mechanism; neurofeedback; neuroregulation; novel; placebo group; primary outcome; response; rumination; secondary analysis; secondary outcome; suicidal; theories; therapy design; therapy resistant; tool; trait; young adult

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.

项目摘要：项目3 - Tsuchiyagaito 重度抑郁症（MDD）是年轻成年中最常见的心理健康状况之一 （18-25岁）发生在11％，并对合并症等长期结局产生严重影响 疾病，失业和自杀，即使没有有效治疗。重复的负面思维（RNT）是 经常性的思考过程，价值为负，难以控制。 rnt始终链接到 抑郁症的频率更高，持续时间和严重程度，还可以预测成年初期的自杀性。 尽管已经建立了对MDD的有效治疗方法，但几乎三分之二的患者不会反应 与当前可用方式的MDD处理多达90％，残留症状， 包括rnt。较高的RNT也与较慢的响应和对两种抗抑郁药的较差的结果有关 药物和心理治疗。 RNT和基础神经回路将是直接的理想 有针对性的，它将促进相关的调节大脑功能。实时功能磁共振 成像神经反馈（RTFMRI-NF）训练是一种理想的，无创的方法，用于翻译与RNT相关的大脑 网络进入一个可定位的疾病改良过程。这项建议是建立在我们以前的工作的基础上的 确定了与RNT相关的大脑功能连接性，即我们确定了连接性 右前岛（RAI）和右上临时沟（RST）之间 MDD的个体中的RNT较高。在此提案中，我们使用RTFMRI-NF将其与功能障碍有关 RAI-RST与RNT强度的连通性。我们将进行随机的双盲，假对照 n = 110（n = 100个完成者，假设损耗率为10％）的RTFMRI-NF试验年轻成人MDD个体（18岁以上 25）带有rnt符号。我们将评估如何使用RTFMRI-NF来衰减RNT，从而减少 沮丧。我们旨在调查降低rai-rsts连接性的程度减轻rnt和 MDD年轻人的抑郁症状接受活性RTFMRI-NF（n = 55，50个完成者） 假（神经反馈具有人为产生的反馈信号； n = 55，50个完成者）组。具体目标 确定（1）真实与假rtfmri-nf对RAI-RST功能连接的急性影响； （2）和 RNT和抑郁。探索性目的将检查RAI-RST的急性调节程度 连通性导致RNT以及抑郁和亚急性RAI-RST连接变化变化一个 RTFMRI-NF后一周。总体目标是确定（1）rai-rsts连接涉及RNT，并且 可以调制为MDD的可靶向疾病改良过程，（2）通过调节RAI-RSTS 连通性以降低RNT，我们可以减轻抑郁症的严重程度。该提议的系统方法 通过识别转诊构造的神经目标，体现NIH RDOC倡议的目标，并 研究大脑行为功能关系与特定网络的直接调节。