Attentional Dysfunction and Recovery in Traumatic Brain Injury (TBI)

创伤性脑损伤 (TBI) 中的注意力障碍和恢复

• 批准号: 7767672
• 负责人: Andrew Robert Mayer
• 金额: $ 19.6万
• 依托单位: THE MIND RESEARCH NETWORK
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7767672
• 关键词: Acute; Address; Affect; Age; Agitation; Animal Model; Anisotropy; Anterior; Area; Attention; Attention Concentration; Attentional deficit; Auditory; Bilateral; Biological Markers; Blood flow; Brain; Brain Injuries; Cephalic; Chronic; Chronic Phase; Clinical; Cognitive; Cognitive deficits; Complex; Conflict (Psychology); Control Groups; Corpus callosum splenium; Craniocerebral Trauma; Creatine; Cues; Data; Delayed Memory; Development; Diagnosis; Diagnostic; Differential Diagnosis; Diffuse; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Down-Regulation; Emotional; Employee Strikes; Exhibits; Failure; Foundations; Frequencies; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Future; Gender; Glutamates; Gray unit of radiation dose; Group Processes; Health; Human; Image; Imaging Techniques; Impaired cognition; Individual; Inferior; Injury; Intervention; Joints; Knowledge; Laboratories; Lobule; Longitudinal Studies; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Maps; Measurable; Measurement; Measures; Memory; Meta-Analysis; Metabolic; Metabolism; Minority; Modality; Modeling; Motor; Multimodal Imaging; N-acetylaspartate; Nature; Neurologic; Neuronal Injury; Neurons; Neuropsychological Tests; Occupational; Outcome; Parietal; Participant; Pathology; Patients; Performance; Phase; Population; Post-Concussion Syndrome; Prefrontal Cortex; Process; Protocols documentation; Protons; Psyche structure; Reaction Time; Recovery; Recovery of Function; Recruitment Activity; Regression Analysis; Relative (related person); Reporting; Research; Residual state; Resources; Risk; Sample Size; Sampling; Sensory; Services; Severities; Signal Transduction; Source; Staging; Stimulus; Structure; Sum; Symptoms; Syndrome; TBI Patients; Techniques; Testing; Time; Tissues; Trail Making Test; Trauma; Traumatic Brain Injury; United States; Up-Regulation; Work; X-Ray Computed Tomography; base; behavior measurement; blood oxygenation level dependent response; cingulate gyrus; cognitive rehabilitation; cost; disability; experience; gray matter; hemodynamics; imaging modality; improved; in vivo; indexing; injured; innovation; myoinositol; neuroimaging; neuromechanism; neuropathology; neurophysiology; neuropsychological; novel; oculomotor; public health relevance; relating to nervous system; response; selective attention; standardize measure; success; tool; white matter

DESCRIPTION (provided by applicant): A recent meta-analysis involving 1463 cases (39 different studies) of mild traumatic brain injury (TBI) indicated that cognitive dysfunction was typically present in the semi-acute phase of injury (effect size d = .54) but that no neuropsychological deficits were observable at three months post-injury. Of all cognitive deficits following mild TBI, difficulties with attention and distractibility are one of the most commonly reported, and observed, symptoms. However, the neuropathology underlying attentional dysfunction in the first few weeks of injury and the subsequent recovery process are currently understudied using newer neuroimaging techniques. The current application proposes to use neuropsychological testing and two laboratory measures (orienting and selective attention tasks) to quantify this attentional deficit, and functional magnetic resonance imaging (FMRI), diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) to quantify the underlying neuronal changes that occur as a function of time in mild TBI. Specifically, 27 mild TBI patients and 15 non-cranial trauma controls will undergo neuropsychological testing and an extensive imaging battery 3 weeks and 3-5 months post injury. During the FMRI session, participants will be asked to perform a spatial orienting task and a task that requires them to process conflicting information from two sensory modalities (Numeric Stroop). To date, the vast majority of TBI neuroimaging studies have employed only a single imaging modality (MRS or FMRI or DTI), have selected patients without controlling for time post-injury or severity of injury, and have not studied patients longitudinally. Thus, the impact and innovation of the current proposal therefore lies on several levels. Foremost, it addresses an important gap in our current knowledge regarding the development of standardized protocols that are capable of capturing the dynamic neurological changes that occur after a mild TBI. Routine clinical imaging modalities (MRI and CT scans) are usually insensitive to both the neuronal pathology underlying acute cognitive deficits as well as to the subsequent recovery process that occurs in the majority (80-90%) of patients. Second, each of the selected imaging modalities contains different information about the functioning of different classes of neuronal tissues (i.e., FMRI = indirect measure of gray matter functioning and vasculature; DTI = measure of white matter integrity; MRS = direct measure of neuronal and axonal health). The combination of information from these three different imaging techniques is likely to be synergistic and exceed the sum of each individual modality alone. We will directly test this hypothesis by applying novel multivariate statistical techniques (joint independent component analyses; J-ICA) to the acquired imaging data. Finally, a longitudinal study of mild TBI during both the semi-acute and chronic phase using these neuroimaging modalities will provide the foundation for a human recovery model in TBI. While it is unlikely that neuroimaging techniques alone will ever be able to provide an independent objective diagnosis, it is likely that they will provide incremental information that will be important for both differential diagnosis and predictions about future outcome. Importantly, the realization of the above will be critical for eventually identifying the minority of mild TBI patients at risk for developing future complications so that intervention can occur acutely, when there is a better chance of success. PUBLIC HEALTH RELEVANCE: In the United States alone, there are approximately 1.2 million mild traumatic brain injury (TBI) cases per year that result in an estimated cost of $56 billion dollars. The symptoms of mild TBI can range from severe physical and mental disability to subtle problems with attention, concentration, or emotional control. Cognitive difficulties are often present in the first few weeks of injury, but typically remit 3-5 months post injury in the majority (approximately 80-90%) of patients. The first step for understanding these cognitive difficulties is to develop biomarkers that are sensitive to neuronal injury and the subsequent recovery process. This will be critical not only for mild TBI, but also for more severe forms of TBI as well. However, the identification of the pathology underlying cognitive deficits in the acute or chronic phases of mild TBI is often subtle, and hard to detect with conventional imaging techniques such as CT or MRI. This suggests that the diagnostic utility and predictive validity of more research-based neuroimaging techniques, such as functional magnetic resonance imaging (FMRI), diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) needs to be explored. The use of multiple neuroimaging techniques is crucial because different modalities measure different signals (e.g., hemodynamic, metabolic or electrophysiological) that originate from different tissue sources in the brain (e.g., white versus gray matter), which will be important for identifying the diffuse injuries that may occur following head trauma. It is likely that the underlying acute pathology is multifaceted and involves both white and gray matter, suggesting that sampling several different domains of neuronal integrity is a necessary first step to understanding the acute cognitive deficits as well as the subsequent normal recovery process. Moreover, these bio- markers may be useful for distinguishing the small percentage of mild TBI patients who continue to have cognitive problems due to the injury.

描述（由申请人提供）：涉及轻度创伤性脑损伤（TBI）的1463例（39例不同的研究）的最新荟萃分析表明，通常在三个月后三个月的神经性心理学缺乏症的半急性损伤（效应大小d = .54）中通常存在认知功能障碍（效应大小d = .54）。在轻度TBI之后的所有认知缺陷中，注意力和分散性的困难是最常见，观察到的症状之一。但是，目前使用较新的神经影像技术在受伤的前几周和随后的恢复过程中的注意力障碍以及随后的恢复过程中的神经病理学的基础。当前的应用建议使用神经心理学测试和两项实验室措施（定向和选择性注意任务）来量化这种注意力缺陷，以及功能性磁共振成像（FMRI），扩散张量成像（DTI）和磁性恢复光谱（MRS），以量化潜在的神经元更改的神经元更改。具体而言，27例轻度TBI患者和15例非颅骨创伤控制将接受神经心理学测试，并在受伤后3周零3-5个月进行大量的成像电池。在fMRI会议期间，将要求参与者执行一个空间定向任务，并要求他们从两种感觉方式（Numeric Stroop）处理冲突的信息。迄今为止，绝大多数TBI神经影像学研究仅采用了单个成像方式（MRS或fMRI或DTI），选择了患者而没有控制伤害后或受伤的严重程度，并且没有纵向研究患者。因此，当前提案的影响和创新在于多个级别。最重要的是，它解决了我们目前关于标准化方案的发展的重要差距，这些方案能够捕获轻度TBI后发生的动态神经系统变化。常规的临床成像方式（MRI和CT扫描）通常对急性认知缺陷的神经元病理不敏感，以及大多数患者（80-90％）发生的随后恢复过程。其次，每种选定的成像方式都包含有关不同类别的神经元组织功能的不同信息（即fMRI =灰质功能和脉管系统的间接度量； dti =白质完整性的度量； MRS = MRS =直接测量神经元和轴突健康）。来自这三种不同成像技术的信息的组合可能是协同作用的，并且仅超过了每种单独方式的总和。我们将通过应用新颖的多元统计技术（联合独立组件分析； J-KIA）直接检验这一假设。最后，使用这些神经影像学方式对半急性和慢性期的轻度TBI进行纵向研究将为TBI的人类恢复模型提供基础。尽管仅神经影像技术就不太可能能够提供独立的客观诊断，但它们很可能会提供增量信息，这对于差异诊断和对未来结果的预测至关重要。重要的是，上述实现对于最终确定有少数有可能发展未来并发症的风险的温和的TBI患者至关重要，因此，当成功的机会更大的机会时，干预措施可能会急剧进行。公共卫生相关性：仅在美国，每年大约有120万例轻度创伤性脑损伤（TBI）病例，估计成本为560亿美元。轻度TBI的症状范围从严重的身体和精神残疾到关注，集中或情绪控制的微妙问题。认知困难通常在受伤的头几周内出现，但通常在大多数患者（约80-90％）受伤后3-5个月汇率。理解这些认知困难的第一步是开发对神经元损伤和随后的恢复过程敏感的生物标志物。这不仅对轻度TBI至关重要，而且对于更严重的TBI也是至关重要的。然而，在轻度TBI的急性或慢性阶段中鉴定出认知缺陷的病理通常是微妙的，并且很难用常规成像技术（例如CT或MRI）检测。这表明需要探索更多基于研究的神经影像学技术的诊断效用和预测有效性，例如功能性磁共振成像（FMRI），扩散张量成像（DTI）和磁共振光谱（MRS）需要探索。多种神经影像技术的使用至关重要，因为不同的模态测量了不同的信号（例如，血液动力学，代谢或电生理学）源自大脑中不同组织源（例如，白色与灰色物质），这对于识别可能在头部创伤后可能发生的差异受伤很重要。潜在的急性病理可能是多方面的，并且涉及白物质和灰质，这表明对几个不同的神经元完整性进行采样是理解急性认知缺陷以及随后的正常恢复过程的必要第一步。此外，这些生物标志物可能有助于区分由于受伤而继续存在认知问题的轻度TBI患者的较小比例。