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
基本信息
- 批准号:7767672
- 负责人:
- 金额:$ 19.6万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:AcuteAddressAffectAgeAgitationAnimal ModelAnisotropyAnteriorAreaAttentionAttention ConcentrationAttentional deficitAuditoryBilateralBiological MarkersBlood flowBrainBrain InjuriesCephalicChronicChronic PhaseClinicalCognitiveCognitive deficitsComplexConflict (Psychology)Control GroupsCorpus callosum spleniumCraniocerebral TraumaCreatineCuesDataDelayed MemoryDevelopmentDiagnosisDiagnosticDifferential DiagnosisDiffuseDiffusionDiffusion Magnetic Resonance ImagingDiseaseDown-RegulationEmotionalEmployee StrikesExhibitsFailureFoundationsFrequenciesFunctional ImagingFunctional Magnetic Resonance ImagingFunctional disorderFutureGenderGlutamatesGray unit of radiation doseGroup ProcessesHealthHumanImageImaging TechniquesImpaired cognitionIndividualInferiorInjuryInterventionJointsKnowledgeLaboratoriesLobuleLongitudinal StudiesMagnetic Resonance ImagingMagnetic Resonance SpectroscopyMapsMeasurableMeasurementMeasuresMemoryMeta-AnalysisMetabolicMetabolismMinorityModalityModelingMotorMultimodal ImagingN-acetylaspartateNatureNeurologicNeuronal InjuryNeuronsNeuropsychological TestsOccupationalOutcomeParietalParticipantPathologyPatientsPerformancePhasePopulationPost-Concussion SyndromePrefrontal CortexProcessProtocols documentationProtonsPsyche structureReaction TimeRecoveryRecovery of FunctionRecruitment ActivityRegression AnalysisRelative (related person)ReportingResearchResidual stateResourcesRiskSample SizeSamplingSensoryServicesSeveritiesSignal TransductionSourceStagingStimulusStructureSumSymptomsSyndromeTBI PatientsTechniquesTestingTimeTissuesTrail Making TestTraumaTraumatic Brain InjuryUnited StatesUp-RegulationWorkX-Ray Computed Tomographybasebehavior measurementblood oxygenation level dependent responsecingulate gyruscognitive rehabilitationcostdisabilityexperiencegray matterhemodynamicsimaging modalityimprovedin vivoindexinginjuredinnovationmyoinositolneuroimagingneuromechanismneuropathologyneurophysiologyneuropsychologicalnoveloculomotorpublic health relevancerelating to nervous systemresponseselective attentionstandardize measuresuccesstoolwhite matter
项目摘要
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):最近一项涉及 1463 例轻度创伤性脑损伤 (TBI) 病例(39 项不同研究)的荟萃分析表明,认知功能障碍通常出现在损伤的半急性期(效应大小 d = 0.54),但在损伤后三个月内未观察到神经心理学缺陷。在轻度 TBI 后的所有认知缺陷中,注意力困难和注意力分散是最常报告和观察到的症状之一。然而,目前正在使用更新的神经影像技术对受伤最初几周注意力功能障碍和随后的恢复过程潜在的神经病理学进行深入研究。当前的申请建议使用神经心理学测试和两种实验室测量(定向和选择性注意任务)来量化这种注意力缺陷,并使用功能磁共振成像(FMRI)、扩散张量成像(DTI)和磁共振波谱(MRS)来量化轻度TBI中随时间变化而发生的潜在神经元变化。具体来说,27 名轻度 TBI 患者和 15 名非颅外伤对照者将在受伤后 3 周和 3-5 个月接受神经心理学测试和广泛的成像电池测试。在 FMRI 会议期间,参与者将被要求执行一项空间定向任务和一项要求他们处理来自两种感官模式(数字斯特鲁普)的冲突信息的任务。迄今为止,绝大多数 TBI 神经影像学研究仅采用单一成像方式(MRS 或 FMRI 或 DTI),选择患者时没有控制损伤后时间或损伤严重程度,并且没有对患者进行纵向研究。因此,当前提案的影响和创新在于几个层面。最重要的是,它解决了我们目前在开发标准化协议方面的知识中的一个重要差距,这些标准化协议能够捕获轻度 TBI 后发生的动态神经变化。常规临床成像方式(MRI 和 CT 扫描)通常对急性认知缺陷的神经病理学以及大多数 (80-90%) 患者随后发生的恢复过程不敏感。其次,每种选定的成像方式都包含有关不同类别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测量;DTI = 白质完整性的测量;MRS = 神经元和轴突健康的直接测量)。这三种不同成像技术的信息组合可能具有协同作用,并且超过每种单独成像技术的总和。我们将通过对采集的成像数据应用新颖的多元统计技术(联合独立成分分析;J-ICA)来直接检验这一假设。最后,使用这些神经影像学方法对半急性和慢性阶段的轻度 TBI 进行纵向研究将为 TBI 的人类恢复模型奠定基础。虽然单独的神经影像技术不太可能提供独立的客观诊断,但它们很可能提供增量信息,这对于鉴别诊断和未来结果的预测都很重要。重要的是,实现上述目标对于最终识别出少数有未来发生并发症风险的轻度 TBI 患者至关重要,以便在成功机会更大时立即进行干预。公共卫生相关性:仅在美国,每年就有大约 120 万例轻度创伤性脑损伤 (TBI) 病例,造成的损失估计达 560 亿美元。轻度 TBI 的症状范围从严重的身体和精神残疾到注意力、注意力或情绪控制方面的微妙问题。认知困难通常出现在受伤的最初几周内,但大多数(约 80-90%)患者通常会在受伤后 3-5 个月内缓解。了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。这不仅对于轻度 TBI 至关重要,而且对于更严重的 TBI 也至关重要。然而,对轻度 TBI 急性或慢性阶段认知缺陷的病理学识别通常很微妙,并且很难用 CT 或 MRI 等传统成像技术检测到。这表明需要探索更多基于研究的神经影像技术的诊断效用和预测有效性,例如功能磁共振成像(FMRI)、扩散张量成像(DTI)和磁共振波谱(MRS)。多种神经影像技术的使用至关重要,因为不同的模式测量源自大脑不同组织来源(例如白质与灰质)的不同信号(例如血流动力学、代谢或电生理),这对于识别头部外伤后可能发生的弥漫性损伤非常重要。潜在的急性病理学很可能是多方面的,涉及白质和灰质,这表明对神经元完整性的几个不同领域进行采样是了解急性认知缺陷以及随后的正常恢复过程的必要的第一步。此外,这些生物标志物可能有助于区分一小部分因损伤而继续存在认知问题的轻度 TBI 患者。
项目成果
期刊论文数量(0)
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Andrew Robert Mayer其他文献
Andrew Robert Mayer的其他文献
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{{ truncateString('Andrew Robert Mayer', 18)}}的其他基金
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