The Cerebellum's Contribution to Working Memory Following Traumatic Brain Injury

脑外伤后小脑对工作记忆的贡献

• 批准号: 8526842
• 负责人: John Medaglia
• 金额: $ 0.37万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8526842
• 关键词: Accounting; Affect; American; Anterior; Area; Behavior; Behavioral; Biological Neural Networks; Brain; Brain Injuries; Brain region; Cerebellum; Clinical; Cognition; Cognitive; Cognitive deficits; Complex; Data; Detection; Diffuse Axonal Injury; Diffusion Magnetic Resonance Imaging; Equation; Event; Exposure to; Fiber; Funding; Future; Goals; Graph; Housing; Impaired cognition; Individual; Injury; Learning; Lesion; Lobule; Memory impairment; Methods; Modeling; Neurocognitive; Neurosciences Research; Parietal; Parietal Lobe; Pattern; Performance; Pharmaceutical Preparations; Play; Pontine structure; Prefrontal Cortex; Process; Prosencephalon; Reaction Time; Recovery; Recruitment Activity; Request for Applications; Research; Resources; Role; Sampling; Short-Term Memory; Signal Transduction; Site; Speed; System; Task Performances; Techniques; Testing; Thalamic structure; Time; Training; Traumatic Brain Injury; base; career; cingulate cortex; classical conditioning; cognitive control; cognitive recovery; cognitive rehabilitation; coping; cost; data modeling; density; information processing; insight; joint function; neuroimaging; neurosurgery; novel; pre-doctoral; processing speed; public health relevance; regional difference; response; theories

DESCRIPTION (provided by applicant): This application requests 2 years of funding to support John Medaglia's pre-doctoral training in functional neuroimaging data modeling and clinical neuroscience research. The proposed research will apply novel techniques to understand the role of the cerebellum as a latent support mechanism for working memory performance following moderate-to-severe traumatic brain injury (TBI) to better understand the processes underlying cognitive deficits and recovery. This project is distinct from traditional fMR research that attempts to isolate regional differences between individuals with TBI and matched healthy controls in that it affords explicit quantitative and qualitative examinations of how neura networks are affected by injuries. This proposal consists of 3 aims, each with an associated experimental approach. Specific Aim 1 is to examine the role of a traditionally understudied region, the cerebellum, in a distributed working memory (WM) system with a critical role in learned timing, pattern detection, associative learning, and speed of information processing. It is hypothesized that the cerebellum will be highly related to previously identified regions involved in WM (i.e., the dorsolateral prefrontal cortex, anterior cingulate cortex, and parietal cortex) during task performance and that the strengths of these relationships will predict performance, particularly those between the cerebellum and the prefrontal cortex. Specific Aim 2 is to test the hypothesis that the primary large-scale networks observed during WM tasks (i.e., involving the dorsolateral prefrontal cortex, anterior cingulate cortex, parietal cortex, and cerebellum) in controls will be disrupted in TBI and that disruption will predict behavioral performance. Importantly, this extends beyond Aim 1 by considering the joint functions of large networks as important to behavior as opposed to each part in isolation. It is hypothesized that controls will have more closely interrelated functional networks loosely constrained by anatomical connections, whereas individuals with TBI will have fractionated networks with specific disruptions in cerebellar and prefrontal functional connections that are predictive of cognitive dysfunction. Aim 3 will seek to corroborate functional findings in brain structural connectivity using diffusion tensor imaging. It is hypothesized that anatomical integrity will predict the degre of functional connectivity across the brain as well as specific functional relationships between the dorsolateral prefrontal cortex and parietal cortex, which have anatomical connections with the cerebellum. The results from this proposal will advance our understanding of the mechanisms of how the brain responds to injury as a neurocognitive system as opposed to previous findings that do not account for the complex relationships among regions in the brain during cognitive processing. This is a critical step toward future aggressive treatment of severe injury because it will aid our understanding of how disrupted activity in certain parts of the neurl system affects others, which may have critical implications for neurosurgery, medication, and cognitive rehabilitation. This proposal will also prepare the Applicant with advanced expertise in signal analysis, linear and nonlinear equation modeling, the utility of graph theory in understanding the brain, and structural connectivity techniques which will provide the basis for a productive independent research career.

描述（由申请人提供）：本申请需要 2 年的资金来支持 John Medaglia 在功能神经影像数据建模和临床神经科学研究方面的博士前培训。拟议的研究将应用新技术来了解小脑作为中度至重度创伤性脑损伤（TBI）后工作记忆表现的潜在支持机制的作用，以更好地了解认知缺陷和恢复的过程。该项目与传统的 fMR 研究不同，传统的 fMR 研究试图隔离 TBI 个体和匹配的健康对照之间的区域差异，因为它提供了神经网络如何受损伤影响的明确的定量和定性检查。该提案包含 3 个目标，每个目标都有相关的实验方法。具体目标 1 是检查传统上研究不足的区域小脑在分布式工作记忆 (WM) 系统中的作用，该系统在学习计时、模式检测、联想学习和信息处理速度方面发挥着关键作用。这是 假设在任务执行过程中，小脑将与先前确定的参与 WM 的区域（即背外侧前额叶皮层、前扣带皮层和顶叶皮层）高度相关，并且这些关系的强度将预测性能，特别是小脑之间的关系和前额皮质。具体目标 2 是检验以下假设：在 WM 任务期间观察到的主要大规模网络（即，涉及背外侧前额叶皮层、前扣带皮层、顶叶皮层和小脑）将在 TBI 中受到破坏，并且该破坏将预测行为表现。重要的是，这超出了目标 1，因为考虑到大型网络的联合功能对行为的重要性，而不是孤立的每个部分。据推测，对照者将具有更紧密相关的功能网络，不受解剖学连接的松散约束，而患有 TBI 的个体将具有分裂的网络，小脑和前额叶功能连接会出现特定的中断，这可以预测认知功能障碍。目标 3 将寻求使用扩散张量成像来证实大脑结构连接的功能发现。据推测，解剖完整性将预测整个大脑的功能连接程度以及背外侧前额叶皮层和顶叶皮层之间的特定功能关系，这些皮层与小脑有解剖学联系。该提案的结果将促进我们对大脑作为神经认知系统如何应对损伤的机制的理解，而不是之前的研究结果没有解释认知处理过程中大脑区域之间的复杂关系。这是未来积极治疗严重损伤的关键一步，因为它将帮助我们了解神经系统某些部分的活动中断如何影响其他部分，这可能对神经外科、药物治疗和认知康复产生重要影响。该提案还将为申请人提供信号分析、线性和非线性方程建模、图论在理解大脑方面的实用性以及结构连接技术方面的先进专业知识，这将为富有成效的独立研究生涯奠定基础。