Real-time fMRI Neurofeedback as a Tool to Mitigate Auditory Hallucinations in Patients with Schizophrenia

实时功能磁共振成像神经反馈作为减轻精神分裂症患者幻听的工具

• 批准号: 10615478
• 负责人: MARGARET A NIZNIKIEWICZ
• 金额: $ 102.95万
• 依托单位: BOSTON VA RESEARCH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10615478
• 关键词: Address; Adopted; Auditory Hallucination; Auditory Perception; Auditory area; Benchmarking; Brain; Brain region; Chronic Schizophrenia; Clinical; Cognitive; DSM-IV; Data; Delusions; Diagnostic; Dose; Feedback; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Gur; Impaired cognition; Intervention; Investigation; Lead; Literature; Measurable; Measures; Medial; Mediating; Methods; Modeling; Monitor; Motor Cortex; Neuropsychology; Outcome; Paper; Patients; Pharmaceutical Preparations; Phase; Prefrontal Cortex; Randomized; Resistance; Rest; Sampling; Schizophrenia; Severities; Short-Term Memory; Signal Transduction; Structure; Superior temporal gyrus; Symptoms; Therapeutic Effect; Time; Transcranial magnetic stimulation; Verbal Auditory Hallucinations; Voice; arm; base; cingulate cortex; cognitive function; design; disabling symptom; group intervention; improved; neurofeedback; novel; placebo group; primary outcome; randomized trial; relating to nervous system; response; severe mental illness; success; tool; treatment arm; trial comparing

This is a resubmission application, originally in response to RFA-MH-16-406 and consists of R61 and R33 phases. Auditory verbal hallucinations (AH) have long been a hallmark of schizophrenia (SZ) and are one of its major diagnostic features Andreasen and Flaum 1991; DSM-IV). They are difficult to manage with existing treatment options. Here, we propose that neurofeedback aimed to regulate the superior temporal gyrus (STG) activation will not only lead to activation changes in the STG, but also to changes in the default mode network (DMN) (R61), as well as to reductions in AH (R33), and that the brain and clinical changes will be correlated (R33). The theoretical framework for the current proposal is an AH model that assumes that AH result from abnormalities in a network of regions including STG, and medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC), the two latter regions are core medial hubs of DMN that are related to self-referential processing. This model is supported by theoretical papers Northoff and Qin 2010, Alderson-Day,2016, and experimental evidence Gur 1995, Liddle 1992, Dierks 1999 as well as our preliminary data (PD). In both R61 and R33 we will study SZ patients with medication resistant AH in the rt-fMRI intervention arm and in the sham-rt-fMRI arm. In both arms, the task and the rt-fMRI session structure will be identical. The SZ-intervention group will receive feedback from the STG while SZ-sham group will receive feedback from the motor cortex. In addition, 2 functional fMRI tasks will examine the effect of rt-fMRI neurofeedback and of sham-rt-fMRI on brain response. In the R61, we will randomly assign 48 SZ patients to either SZ-intervention (n=24) or SZ-sham-rtfMRI (n=24). The STG targeted neurofeedback is predicted to bring changes in brain regions involved in AH (STG and DMN) in SZ-intervention group only. The R61 GO criterion will be BOLD signal reduction in the STG, and resting state connectivity reduction between MPFC-PCC, post rt-fMRI-feedback in SZ-intervention group. In the R33, SZ-intervention group (random n=52) will receive 5 sessions of rt-fMRI feedback targeting STG, while SZ-sham group (random n=52) will receive 5 sham-rt-fMRI sessions. Based on our PD, we predict that rt-fMRI feedback aimed at STG will reduce AH which will be, in turn, associated with reductions in the STG activation and in the DMN connectivity (i.e., brain changes achieved in R61 and replicated in R33) in SZ- intervention group only. Five sessions of rt-fMRI feedback will address the question of dose response at brain and clinical levels. The impact of rt-fMRI neurofeedback and of sham-rt-fMRI on AH (primary outcome), and on delusions, negative symptoms and working memory (WM) (exploratory outcome) will be assessed with clinical and neuropsychological measures. In an exploratory aim, based on the existing literature Garrity 2007; Whitfield-Gabrieli 2009; Rotarska-Jagiela 2010, we predict the improvement in delusions, negative symptoms and in WM score, only post-rt-fMRI neurofeedback targeting the STG and not post-sham-rt-fMRI.

这是一份重新提交申请，最初是为了响应 RFA-MH-16-406，由 R61 和 R33相。幻听 (AH) 长期以来一直是精神分裂症 (SZ) 的一个标志，也是其中之一。 其主要诊断特征 Andreasen 和 Flaum 1991； DSM-IV）。他们很难用现有的 治疗方案。在这里，我们提出神经反馈旨在调节颞上回（STG） 激活不仅会导致STG的激活变化，还会导致默认模式网络的变化 (DMN) (R61)，以及 AH (R33) 的减少，并且大脑和临床变化将相关 （R33）。当前提案的理论框架是一个 AH 模型，假设 AH 的结果是 区域网络异常，包括 STG、内侧前额叶皮层 (MPFC) 和后部 扣带皮层 (PCC)，后两个区域是 DMN 的核心内侧中枢，与自我参照相关 加工。该模型得到理论论文 Northoff 和qin 2010、Alderson-Day,2016 和实验的支持 证据 Gur 1995、Liddle 1992、Dierks 1999 以及我们的初步数据 (PD)。 在 R61 和 R33 中，我们将在 rt-fMRI 干预中研究患有耐药性 AH 的 SZ 患者 臂和假 rt-fMRI 臂。在两组中，任务和 rt-fMRI 会话结构将是相同的。这 SZ-干预组将收到 STG 的反馈，而 SZ-sham 组将收到来自 STG 的反馈 运动皮层。此外，2 项功能性 fMRI 任务将检查 rt-fMRI 神经反馈和 假实时功能磁共振成像对大脑反应的影响。 在 R61 中，我们将随机分配 48 名 SZ 患者接受 SZ 干预 (n=24) 或 SZ-sham-rtfMRI （n=24）。 STG 靶向神经反馈预计会给涉及 AH 的大脑区域带来变化（STG 和 DMN）仅适用于 SZ 干预组。 R61 GO 标准将是 STG 中的 BOLD 信号减少，并且 SZ 干预组中 rt-fMRI 反馈后 MPFC-PCC 之间的静息态连接减少。 在 R33 中，SZ 干预组（随机 n=52）将接受 5 次 rt-fMRI 反馈靶向治疗 STG，而 SZ-sham 组（随机 n=52）将接受 5 次 sham-rt-fMRI 会话。根据我们的 PD，我们预测 针对 STG 的 rt-fMRI 反馈将减少 AH，这反过来又与 STG 的减少相关 SZ-中的激活和 DMN 连接（即 R61 中实现的大脑变化并在 R33 中复制） 仅干预组。五次 rt-fMRI 反馈将解决大脑剂量反应问题 和临床水平。 rt-fMRI 神经反馈和假 rt-fMRI 对 AH 的影响（主要结果），以及 将评估妄想、阴性症状和工作记忆 (WM)（探索性结果） 临床和神经心理学措施。出于探索性目的，基于现有文献 Garrity 2007； 惠特菲尔德-加布里埃利 2009； Rotarska-Jagiela 2010，我们预测妄想、阴性症状和 WM 评分的改善， 仅针对 STG 的 rt-fMRI 后神经反馈，而不是 sham-rt-fMRI 后。