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.

对轻度神经损伤和神经心理学标志物敏感的神经影像学标志物的鉴定