Predicting Recovery of Cognitive Control Deficits in Traumatic Brain Injury

预测创伤性脑损伤中认知控制缺陷的恢复

• 批准号: 9315179
• 负责人: JAMES F CAVANAGH
• 金额: $ 27.13万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9315179
• 关键词: Acute; Address; Assessment tool; Behavior; Behavior assessment; Behavioral; Biological Markers; Biological Neural Networks; Brain; Brain Injuries; Centers of Research Excellence; Chronic; Classification; Clinical; Common Data Element; Communication; Data Analytics; Development; Diagnosis; Diffusion; Diffusion Magnetic Resonance Imaging; Effectiveness; Electrophysiology (science); Emergency Medicine; Exhibits; Failure; Goals; Grant; Hospitals; Image; Image Analysis; Impaired cognition; Impulsivity; Individual; Injury; Intervention; Knowledge; Lesion; Life; Link; Measures; Mediating; Monitor; Neurons; New Mexico; Occupational; Outcome; Pathology; Patients; Pattern; Performance; Phase; Population; Process; Psyche structure; Questionnaires; Reaction Time; Recovery; Recovery of Function; Recruitment Activity; Rehabilitation therapy; Reporting; Resolution; Sensitivity and Specificity; Services; Signal Transduction; Statistical Models; Structural defect; Survivors; Symptoms; System; Techniques; Testing; Tissues; Translating; Traumatic Brain Injury; Treatment Efficacy; United States National Institutes of Health; Universities; Work; X-Ray Computed Tomography; anatomic imaging; base; behavior measurement; clinical development; clinical practice; clinically relevant; cognitive control; cognitive recovery; cost; disability; experience; frontal lobe; improved; injured; innovation; multimodality; neurobehavioral; neurosurgery; novel; novel therapeutics; operation; outcome forecast; prognostic; relating to nervous system; repaired; response; restoration; therapy development; white matter

Approximately 400,000-500,000 patients remain chronically symptomatic every year following mild or moderate traumatic brain injury (mmTBI) according to latest estimates. To optimally treat these patients, we must first understand the underlying neuropathological changes after injury rather than relying on clinical observations and patient-reported symptoms (i.e. current clinical practice). Our central hypothesis is that structural damage to white matter following injury will be functionally expressed as a deficiency in the long-distance EEG signals that underlie cognitive control over behavior. Our preliminary work establishes that theta band synchrony underlies various forms of cognitive control, providing a common mechanism for understanding the most prevalent deficits (i.e. distractibility, impulsivity, irritability) following injury. This work will capitalize on our recent findings that white matter abnormalities are reliably present in mmTBI patients and contribute to deficiencies in cognitive control. To test our central hypotheses, 100 mmTBI patients (18-55 years) will be recruited from the Departments of Neurosurgery and Emergency Medicine from our local hospitals. All patients will undergo a thorough neurobehavioral exam during the early semi-acute (<2 weeks), late semi-acute (2 months) and early chronic (four months) injury stages. Advanced behavioral measures of cognitive control developed at NIH (EXAMINER battery) and recommended measures from Common Data Elements will be used to characterize neurobehavioral deficits. Electrophysiology (EEG) will be used to characterize theta band synchrony during cognitive control and high angular resolution diffusion imaging (HARDI) will be used to determine white matter abnormalities between the main nodes of the cognitive control network. Finally, in addition to CT scans, extensive anatomical imaging (T1, T2, FLAIR and SWI) will be conducted to identify patients with focal lesions. The current grant is innovative both in our multimodal longitudinal approach, as well as two of our selected biomarkers (white matter and EEG synchrony) for understanding cognitive control deficits in mmTBI. Novel data analytic techniques (pattern classifiers) will be applied to objectively determine the bias-free predictive power of these biomarkers on the course of recovery. Following this study, clinicians will be able to understand the neuronal mechanisms mediating a failure to recover following mmTBI, and ultimately utilize these biomarkers to determine which patient will require additional rehabilitative services. This represents a crucial first step for improving diagnosis and developing novel therapeutic options, key components for other projects on our COBRE application.

轻度或中度后，每年约有400,000-500,000名患者每年长期症状 根据最新估计，创伤性脑损伤（MMTBI）。为了最佳治疗这些患者，我们必须首先 了解受伤后的潜在神经病理学变化，而不是依靠临床观察 和患者报告的症状（即当前的临床实践）。我们的中心假设是结构性损害 受伤后的白质将在功能上表达为长途脑电图的缺陷 这是对行为的认知控制。我们的初步工作确定Theta乐队同步 构成了各种形式的认知控制，提供了一种共同理解的共同机制 受伤后普遍缺陷（即分散性，冲动性，易怒）。这项工作将利用我们的 最近的发现，MMTBI患者可靠地存在白质异常，并有助于 认知控制中的缺陷。为了检验我们的中心假设，将有100名MMTBI患者（18-55岁） 从我们当地医院的神经外科和急诊医学部门招募。所有患者 在半急性早期（<2周），半急性晚期（2 几个月）和慢性（四个月）伤害阶段。认知控制的先进行为度量 在NIH（审查员电池）开发的，并从共同数据元素中采取建议的措施是 用于表征神经行为缺陷。电生理学（EEG）将用于表征theta带 认知对照过程中的同步和高角度分辨率扩散成像（HARDI）将用于 确定认知控制网络的主要节点之间的白质异常。最后，在 除CT扫描外，还将进行广泛的解剖成像（T1，T2，Flair和SWI）以识别 患有局灶性病变的患者。当前的赠款在我们的多模式纵向方法中都是创新的 作为我们选择的两个生物标志物（白质和脑电图同步），以理解认知控制 MMTBI的缺陷。新颖的数据分析技术（模式分类器）将应用于客观确定 这些生物标志物在恢复过程中的无偏见预测能力。在这项研究之后，临床医生 将能够理解MMTBI后介导的介导的神经元机制，并且 最终利用这些生物标志物来确定哪个患者需要额外的康复服务。这 这是改善诊断和开发新型治疗选择的关键第一步，关键 在我们的毛绒应用程序上的其他项目的组件。