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: 10019700
• 负责人: MARGARET A NIZNIKIEWICZ
• 金额: $ 101.96万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10019700
• 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.

这是一个重新提交的申请，最初是对RFA-MH-16-406的响应，由R61和 R33期。听觉言语幻觉(AH)长期以来一直是精神分裂症(SZ)的特征之一 其主要诊断特征为Andreasen和Flaum，1991；DSM-IV)。它们很难使用现有的设备进行管理 治疗方案。在这里，我们提出了神经反馈的目的是调节颞叶上回。 激活不仅会导致STG中的激活更改，还会导致默认模式网络中的更改 (DMN)(R61)，以及AH(R33)的减少，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，该模型假设AH产生于 包括STG、内侧前额叶皮质(MPFC)和后部的区域网络异常 扣带回皮质(PCC)后两个区域是DMN与自我参照相关的核心内侧中枢 正在处理。该模型得到了理论论文Northoff和Qin 2010、2016年的Alderson-Day和实验的支持 证据Gur 1995年、利德尔1992年、Dierks 1999年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SZ药物耐药的AH患者 手臂和假RT-fMRI手臂中。在两个手臂中，任务和RT-fMRI会话结构将是相同的。这个 SZ-干预组将收到STG的反馈，而SZ-Sham组将收到STG的反馈 运动皮质。此外，两项功能性核磁共振任务将检验rt-fmri神经反馈和 Sham-RT-fMRI对脑反应的影响。 在R61中，我们将48名SZ患者随机分配到SZ-干预(n=24)或SZ-Sham-rtfMRI (n=24)。STG靶向神经反馈可引起AH(STG)相关脑区的改变 和DMN)，仅为SZ干预组。R61 GO标准将是STG中的大胆信号减少，以及 SZ干预组RT-fMRI反馈后MPFC-PCC之间的静息状态连接性降低。 在R33中，SZ干预组(随机n=52)将接受5次RT-fMRI反馈靶向 SZ-Sham组(随机n=52)接受5次Sham-RT-fMRI治疗。根据我们的PD，我们预测 针对STG的RT-fMRI反馈将减少AH，这反过来将与STG的减少相关 激活和DMN连接(即在R61中实现的脑变化和在R33中复制的脑变化)在SZ- 仅限干预组。五次RT-fMRI反馈将解决大脑的剂量响应问题 和临床水平。RT-fMRI神经反馈和Sham-RT-fMRI对AH(主要结局)的影响 对于妄想症、阴性症状和工作记忆(WM)(探索性结果)，将用 临床和神经心理测量。在探索性目的上，立足于已有的文学作品《Garrity 2007》； Whitfield-Gabrieli 2009；Rotarska-Jagiela 2010，我们预测妄想症、阴性症状和WM评分的改善， 仅针对STG的RT-fMRI后的神经反馈，而不是Sham-RT-fMRI后的神经反馈。