Multimodal Imaging of NeuroHIV Dynamics (MIND): An Omaha-Pittsburgh Consortium

NeuroHIV 动力学 (MIND) 的多模态成像：奥马哈-匹兹堡联盟

基本信息

批准号：
9919644
负责人：
JAMES T. BECKER
金额：
$ 94.17万
依托单位：
UNIVERSITY OF NEBRASKA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2021-01-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9919644
关键词：
AIDS dementia AIDS/HIV problem Acquired Immunodeficiency Syndrome Adult Affect Architecture Area Attention Behavioral Brain Brain Mapping Brain region Chronic Code Cognition Disorders Cognitive Cognitive Science Collection Complication Custom Data Data Analyses Databases Development Disease Economics Electrophysiology (science)Etiology Exhibits Functional Magnetic Resonance Imaging Functional disorder General Population Goals HIV HIV Infections HIV-associated cognitive impairment HIV-associated neurocognitive disorder Human Image Impaired cognition Impairment Individual Knowledge Life Expectancy Literature Magnetic Resonance Imaging Magnetoencephalography Maps Measures Mediator of activation protein Medical History Medical center Memory impairment Methods Modality Monitor Motor Motor Cortex Multimodal Imaging National NeuroAids Tissue Consortium Nature Nebraska Neurobiology Neurologic Neurons Neuropsychological Tests Parietal Lobe Participant Patients Penetration Performance Persons Physiological Physiology Play Prevalence Publishing Quality of life Request for Applications Request for Proposals Research Research Domain Criteria Resources Rest Risk Role Sampling Short-Term Memory Source Structure Targeted Research Techniques Terminal Disease The Multicenter AIDS Cohort Study Thick Time Series Analysis Unemployment Universities Viral Visual Perception Visual attention Western World Work antiretroviral therapy cognitive control cognitive function cognitive system cognitive task comorbidity gamma-Aminobutyric Acid hemodynamics imaging approach imaging modality imaging study innovation instrumentation interest lifestyle factors magnetic resonance spectroscopic imaging medication compliance motor disorder multimodality neural circuit neuroAIDS neuroimaging neuromechanism neuronal circuitry novel receptor relating to nervous system response

项目摘要

Project Summary/Abstract HIV-infected adults in the western world have a life expectancy near that of the general population, but are at a significantly elevated risk of developing cognitive impairments. Such impairments are the most common neurological complication of HIV disease, with prevalence estimates ranging from 35-70% of all HIV-infected individuals. Research targeting such comorbidities has been identified as a top priority by the Office of AIDS Research (NOT-OD-15-137). While the mechanisms underlying these deficits are not well understood, numerous human neuroimaging studies have examined the brain areas that may be involved, and overall these studies have been largely successful in identifying the critical hubs and networks. However, many questions remain regarding basic circuit dysfunction within these brain regions, and consequently there is a clear and common need to further investigate the neural dynamics and connectivity, as well as other key physiological parameters that may underlie the development and progression of HIV-related cognitive dysfunction. This proposal responds to RFA-MH-18-610, which requests proposals that “advance knowledge of the etiology of mild to moderate forms of HIV-related cognitive dysfunction by clarifying the role played by altered neuronal circuits, receptors, and networks,” using “novel neuro-electrophysiological and neuroimaging techniques.” The Multimodal Imaging of NeuroHIV Dynamics (MIND) Consortium responds to this call with an innovative, large- scale multimodal neuroimaging study that uses the latest breakthroughs in instrumentation and data analyses to identify the pathophysiology of neuroHIV in virally-suppressed adults. Specifically, the consortium will use advanced magnetoencephalographic (MEG) imaging to quantify the region- and circuit-level neural dynamics serving cognitive processing, 3-Tesla MRI and multimodal parcellation methods to map areal brain architecture, functional MRI (fMRI) for hemodynamics and intrinsic networks, and 7-Tesla magnetic resonance spectroscopic imaging (MRSI) to quantify GABA levels in multi-voxel slabs of interest identified by the functional modalities. The investigative team includes a unique combination of experts in MEG, MRI/fMRI, MRSI, and cognitive psychology from the University of Nebraska and University of Pittsburgh Medical Centers (UNMC/UPMC). In addition, this consortium will harness existing resources such as the Multicenter AIDS Cohort Study (MACS) database and the National NeuroAIDS Tissue Consortium (NNTC) and, consistent with the RFA, will follow the Research Domain Criteria (RDoC) framework to define cognitive constructs. The consortium’s overarching hypothesis is that HIV-infected adults will exhibit aberrations in local inhibitory circuits, and that these deficits will alter gamma oscillations and thereby impair neuronal coding and interregional functional connectivity in the theta range. Such gamma deficits would provide robust explanatory power for the breadth of pathophysiological findings in the existent literature, and the MIND study is uniquely powered to investigate the underlying sources of these deficits, which are likely multifactorial (e.g., medical history, lifestyle factors, CNS viral penetration).

项目概要/摘要西方世界感染艾滋病毒的成年人的预期寿命接近普通人群，但仍处于发生认知障碍的风险显着升高。此类障碍是最常见的。 HIV 疾病的神经系统并发症，患病率估计占所有 HIV 感染者的 35-70% 针对此类合并症的研究已被艾滋病办公室确定为首要任务。研究（NOT-OD-15-137）虽然这些缺陷的机制尚不清楚，许多人类神经影像学研究已经检查了可能涉及的大脑区域，总体而言，这些区域研究在确定关键枢纽和网络方面已取得很大成功，但仍存在许多问题。仍然存在关于这些大脑回路内的基本回路功能障碍的问题，因此有一个清晰且明确的共同需要进一步研究神经动力学和连接性，以及其他关键的生理学可能是 HIV 相关认知功能障碍发生和进展的参数。该提案是对 RFA-MH-18-610 的回应，该提案要求“增进对病因学的了解” 通过阐明神经元所起的作用来治疗轻度至中度的 HIV 相关认知功能障碍电路、受体和网络”，使用“新颖的神经电生理学和神经影像技术”。 NeuroHIV 动力学 (MIND) 联盟的多模态成像以创新的、大型的大规模多模式神经影像研究，利用仪器和数据分析的最新突破具体来说，该联盟将使用这种方法来确定病毒抑制的成人中神经艾滋病毒的病理生理学。先进的脑磁图 (MEG) 成像可量化区域和电路级神经动力学服务于认知处理、3-特斯拉 MRI 和多模态分割方法来绘制区域大脑结构，用于血流动力学和内在网络的功能 MRI (fMRI) 以及 7-特斯拉磁共振波谱成像（MRSI）来量化由功能模式识别的感兴趣的多体素板中的 GABA 水平。调查团队由脑磁图 (MEG)、磁共振成像/功能磁共振成像 (MRI/fMRI)、磁共振成像 (MRSI) 和认知方面的专家组成的独特组合内布拉斯加大学和匹兹堡大学医学中心 (UNMC/UPMC) 的心理学。此外，该联盟将利用现有资源，例如多中心艾滋病队列研究（MACS）数据库和国家神经艾滋病组织联盟 (NNTC)，并且根据 RFA，将遵循定义认知结构的研究领域标准 (RDoC) 框架。假设感染艾滋病毒的成年人会在局部抑制回路中表现出异常，并且这些缺陷将改变伽马振荡，从而损害神经编码和区域间功能连接这种伽玛缺陷将为病理生理学的广度提供强有力的解释力。存在主义文献中的发现，而 MIND 研究具有独特的能力来调查潜在的来源这些缺陷可能是多因素造成的（例如病史、生活方式因素、中枢神经系统病毒渗透）。