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.

鉴定对轻度神经创伤和神经心理学标记敏感的基于神经影像的标记 认知破坏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。尽管神经影像学方法，特别是在 扩散成像（dMRI）继续展现出前景，但传统的扩散成像技术存在显着的局限性 基于张量成像（DTI）的白质（WM）方法。具体来说，WM 的高度异质性 轴突方向和体素内不同组织类型的采样会导致不准确的估计 组织特性。标准和广泛使用的 DTI 方法固有的这些限制可能会削弱 DTI 检测轻度神经创伤的敏感性，特别是在关键、复杂的 WM 区域 最容易受到 mTBI 的影响。同样，mTBI 的认知研究结果也很复杂，报告相互矛盾 不明确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的认知状况不一致可能是造成这种情况的原因 利用传统手段的研究显示出敏感性降低和不一致的情况—— 基于传统神经心理学测试分数的比较。事实上，mTBI 的指标常常无法协调一致 包括有 mTBI 病史的退伍军人报告的影像学结果、认知报告和功能结果。 在拟议的研究中，我们将应用新的工具和方法，以便更敏感地检查 WM 60 名患有 mTBI 的退伍军人和 60 名没有 mTBI 病史的退伍军人的破坏和神经心理学表现 创伤性脑损伤。参与者将完成广泛的神经认知评估，包括一项新颖的逆行记忆测试 了解新闻事实，并将接受 dMRI 扫描。我们建议利用一种新颖的神经影像方法—— 这对标准 DTI 协议固有的限制具有鲁棒性，将能够对接近的 WM 进行调查 考虑到切变效应，全因 mTBI 被认为造成最大损伤的脑沟深度 灰质-白质边界。我们将使用 dMRI 采集和分析方法，将单一和 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）集成体素和亚体素级别的扩散信息。平衡概率 (EP) 对交叉纤维的复杂性和部分体积效应更稳健的各向异性测量将是 使用 JEDI 计算。特别是，我们将询问位于灰质白色脑沟中的体素的 EP 额叶的物质边界。模拟和组织病理学研究表明这些区域是最 由于剪切效应特别严重，因此容易受到轻度神经创伤的急性和远端影响 由于灰白色边界的组织密度不同而造成损害。其次，鉴于我们最近的工作表明 新认知方法检测 mTBI 和其他轻度脑损伤患者神经心理缺陷的敏感性 认知困难，我们将研究个体内认知表现变异性（IIV）作为 与传统方法相比，认知干扰可以增强退伍军人的大脑行为关联 组均值比较。我们还将使用一种新的认知工具，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研究 WM 破坏的机会 使用新型神经成像方法 (JEDI) 进一步评估易受 mTBI 影响的大脑区域 认知概念（IIV）和新认知测试（RM-NET），可以改善临床结果的评估 继 mTBI 后，并检查患有 mTBI 的退伍军人中 IIV 和 WM 破坏之间的潜在关联。这样的 前沿工作可以为增强对神经生物学基础的理解奠定基础 患有神经外伤的退伍军人中的 mTBI 和持续性脑震荡后症状可能会通过神经影像学来识别 生物标志物和认知能力有助于评估未来临床试验中的治疗反应。