Use of Novel Neuroimaging, Neuropsychological Methods, and Retrograde Memory Test to Detect Cognitive and Cerebral Disruption in Veterans with Mild Traumatic Brain Injury

使用新的神经影像学、神经心理学方法和逆行记忆测试来检测患有轻度创伤性脑损伤的退伍军人的认知和大脑障碍

• 批准号: 10696693
• 负责人: Lisa Marie Delano-Wood
• 金额: --
• 依托单位: VA SAN DIEGO HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10696693
• 关键词: Acute; Address; Affect; Anisotropy; Area; Assessment tool; Attenuated; Axon; Biological Markers; Brain; Brain Injuries; Brain region; Caring; Cerebrum; Characteristics; Chronic; Clinical; Clinical Trials; Cognitive; Cognitive deficits; Complex; Confusion; Conscious; Control Groups; Craniocerebral Trauma; Detection; Diffusion; Diffusion Magnetic Resonance Imaging; Disparate; Distal; Equilibrium; Evaluation; Event; Exhibits; Fiber; Foundations; Future; Glean; Goals; Heterogeneity; Image; Impairment; Individual; Individuation; Injury; Investigation; Joints; Literature; Magnetic Resonance Imaging; Measures; Memory; Methods; Nervous System Trauma; Neurobiology; Neurocognitive; Neuropsychological Tests; Neuropsychology; Outcome; Participant; Patients; Performance; Physiologic pulse; Population; Post-Concussion Syndrome; Post-Traumatic Stress Disorders; Predisposition; Probability; Property; Protocols documentation; Quality of life; Recording of previous events; Reporting; Research; Sampling; Scanning; Site; Techniques; Testing; Time; Tissues; Unconscious State; Veterans; Work; brain behavior; clinical decision-making; cognitive ability; cognitive performance; cognitive testing; comparison control; comparison group; frontal lobe; functional outcomes; gray matter; imaging approach; imaging modality; improved; individual variation; mild traumatic brain injury; multidisciplinary; neural; neuroimaging; neuroimaging marker; news; novel; research clinical testing; simulation; tool; treatment response; white matter; white matter damage

Identification of neuroimaging-based markers sensitive to mild neurotrauma and neuropsychological markers of cognitive disruption is vital toward addressing the complex treatment needs of the large number of Veterans with histories of mild traumatic brain injury (mTBI). Although neuroimaging methods, particularly in the area of diffusion imaging (dMRI) continue to show promise, there are significant limitations in the traditional, diffusion tensor imaging (DTI) based approach in white matter (WM). Specifically, a high degree of heterogeneity of WM axon orientations and sampling from disparate tissue types within a voxel contribute to inaccurate estimates of tissue properties. These limitations, inherent in standard and widely used DTI methods, likely attenuate DTI sensitivity in the detection of mild forms of neurotrauma, particularly in key, complex WM regions shown to be most susceptible to mTBI. Likewise, cognitive research findings in mTBI have been mixed, with conflicting reports and unclear cognitive outcomes that likely cloud and confuse clinical decision-making. The heterogeneity of TBI, differences in injury characteristics, and a non-uniform cognitive profile among affected Veterans likely contribute to the decreased sensitivity and inconsistency shown across studies that have leveraged traditional means- based comparisons of traditional neuropsychological test scores. Indeed, indicators of mTBI often fail to align with imaging findings, cognitive reports, and functional outcomes reported by Veterans with histories of mTBI. In the proposed study, we will apply new tools and methods in order to more sensitively examine WM disruption and neuropsychological performance in 60 Veterans with mTBI and 60 Veterans without a history of TBI. Participants will complete a broad neurocognitive assessment, including a novel test of retrograde memory for news facts, and will undergo a dMRI scan. We propose that leveraging a novel neuroimaging approach—one that is robust to the limitations inherent in standard DTI protocols—will enable investigation of WM proximal to the sulcal depths where all-cause mTBI is thought to inflict the greatest damage given shearing effects at the gray matter-white matter border. We will use dMRI acquisition and analysis methods which combine single and double pulsed field gradient dMRI acquisitions via a novel technique called Joint Estimation Diffusion Imaging (JEDI) to integrate diffusion information at the voxel and subvoxel level. Equilibrium probability (EP), an anisotropy measure that is more robust to the complexities of crossing fibers and partial voluming effects, will be calculated using JEDI. In particular, we will interrogate EP of voxels residing in the sulci at the gray matter-white matter border in the frontal lobe. Simulation and histopathological studies show these regions to be most susceptible to acute and distal effects of mild neurotrauma given the shearing effects that are particularly damaging because of differing tissue densities of the gray-white border. Second, given our recent work showing the sensitivity of newer cognitive methods to detect neuropsychological deficits in mTBI and others with mild cognitive difficulties, we will investigate intra-individuation cognitive performance variability (IIV) as a marker of cognitive disruption in order to enhance brain-behavior associations in Veterans compared to traditional comparison of group means. We will also administer a new cognitive tool, the retrograde memory news events test (RM-NET) to determine if it is sensitive to the cognitive deficits and TBI characteristics in Veterans with chronic mTBI. Taken together, the proposed study presents an opportunity to investigate WM disruption within brain regions vulnerable to mTBI using a novel neuroimaging approach (JEDI), further assess a promising cognitive concept (IIV) and new cognitive test (RM-NET), which may improve the evaluation of clinical outcomes following mTBI, and examine potential associations between IIV and WM disruption in Veterans with mTBI. Such cutting-edge work can lay the foundation for enhanced understanding of the neurobiological underpinnings of mTBI and persisting postconcussive symptoms in Veterans with neurotrauma and may identify neuroimaging biomarkers and cognitive abilities useful to evaluate treatment response in future clinical trials.

基于神经影像学的轻度神经创伤敏感标志物和神经心理学标志物的鉴定 认知中断对于解决大量退伍军人的复杂治疗需求至关重要 有轻度创伤性脑损伤（mTBI）病史。尽管神经成像方法，特别是在神经成像领域， 弥散成像（dMRI）继续显示出希望，但传统的弥散成像存在显着的局限性， 基于张量成像（DTI）的方法在白色物质（WM）。具体来说，WM的高度异质性 轴突取向和从体素内的不同组织类型的采样导致对轴突的不准确估计。 组织特性。这些局限性，固有的标准和广泛使用的DTI方法，可能会削弱DTI 检测轻度神经创伤的敏感性，特别是在关键的复杂WM区域， 最易受mTBI影响。同样，mTBI的认知研究结果也是喜忧参半，报告相互矛盾 以及不清楚的认知结果，可能会影响和混淆临床决策。TBI的异质性， 受伤特征的差异，以及受影响的退伍军人之间的非统一认知特征可能有助于 在利用传统方法的研究中显示出的灵敏度下降和不一致性- 基于传统神经心理学测试分数的比较。事实上，mTBI的指标往往无法与 有mTBI病史的退伍军人报告的影像学结果、认知报告和功能结局。 在这项研究中，我们将采用新的工具和方法，以便更敏感地检查工作记忆 60名mTBI退伍军人和60名无mTBI病史的退伍军人的中断和神经心理学表现 创伤性脑损伤参与者将完成一项广泛的神经认知评估，包括一项新的逆行记忆测试 接受核磁共振成像扫描我们建议利用一种新的神经成像方法--一种 这是鲁棒的固有局限性，在标准的DTI协议-将使调查WM近端 在脑沟深度处，考虑到剪切效应，全因mTBI被认为会造成最大的损伤， 灰质-白质边界。我们将使用dMRI采集和分析方法，该方法将联合收割机单个和 通过称为联合估计扩散成像的新技术进行双脉冲场梯度dMRI采集 （JEDI）以在体素和亚体素水平上整合扩散信息。平衡概率（EP） 对于交叉纤维和部分体积效应的复杂性更鲁棒的各向异性测量将是 使用JEDI计算。特别是，我们将询问EP的体素居住在沟在灰色物质-白色 额叶的物质边界模拟和组织病理学研究表明，这些地区是最 由于剪切效应， 由于灰白色边界的不同组织密度而造成损害。第二，鉴于我们最近的工作表明， 新的认知方法检测mTBI和其他轻度TBI患者神经心理学缺陷的敏感性 认知困难，我们将调查内个性化认知表现变异性（IIV）作为一个标志， 认知中断，以增强退伍军人的大脑行为协会相比，传统 组平均值比较。我们还将管理一个新的认知工具，逆行记忆新闻事件 测试（RM-NET），以确定它是否对退伍军人的认知缺陷和TBI特征敏感， 慢性mTBI综上所述，拟议的研究提供了一个机会，调查WM中断内 大脑区域易受mTBI使用一种新的神经成像方法（JEDI），进一步评估一个有前途的 认知概念（IIV）和新的认知测试（RM-NET），这可能会改善临床结局的评估 在mTBI之后，并检查患有mTBI的退伍军人中IIV和WM中断之间的潜在关联。等 尖端的工作可以为增强对神经生物学基础的理解奠定基础， 神经创伤退伍军人的mTBI和持续性脑震荡后症状，可识别神经影像学 生物标志物和认知能力，可用于在未来的临床试验中评估治疗反应。