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）：本申请要求提供2年的资金，以支持John Medaglia在功能性神经成像数据建模和临床神经科学研究方面的博士前培训。拟议的研究将采用新颖的技术来了解小脑作为中度到重度创伤性脑损伤（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，该研究试图隔离TBI和匹配的健康对照者之间的区域差异，因为它可以对神经网络受伤的影响进行明确的定量和定性检查。该提案由3个目标组成，每个目标都采用相关的实验方法。具体目的1是检查传统研究的区域，即小脑在分布式工作记忆（WM）系统中的作用，在学习的时间安排，模式检测，关联学习和信息处理速度中起着至关重要的作用。这是 假设小脑将与WM先前鉴定的区域高度相关（即，在任务性能过程​​中，背侧外侧前额叶皮层，前扣带回皮质和顶叶皮层），并且这些关系的优势将预测性能，尤其是在Cerebellum和Frothental前细胞之间的表现。具体目的2是测试以下假设：在WM任务中观察到的主要大规模网络（即涉及背外侧前额叶皮层，前扣带回皮质，顶叶皮层和小脑在对照组中都会在TBI中受到干扰，并且在TBI中会受到干扰。重要的是，通过考虑大型网络的关节功能对行为很重要，而不是孤立的每个部分，这超出了目标1。假设控件将具有由解剖连接的更加紧密相互关联的功能网络，而具有TBI的个体将具有分馏网络，具有小脑和前额叶功能连接的特定干扰，可以预测认知功能障碍。 AIM 3将寻求使用扩散张量成像来证实大脑结构连通性的功能发现。假设解剖完整性将预测整个大脑的功能连通性，以及背外侧前额叶皮层和顶叶皮层之间的特定功能关系，这些关系与小脑具有解剖学连接。该提案的结果将促进我们对大脑如何应对损伤作为神经认知系统的机制的理解，而不是先前的发现，这些发现没有说明认知处理过程中大脑区域之间的复杂关系。这是朝着对严重伤害进行积极对待的关键一步，因为它将有助于我们理解神经系统某些部位的活动如何影响他人的活动，这可能对神经外科手术，药物和认知康复具有至关重要的影响。该建议还将为申请人提供信号分析，线性和非线性方程建模，图理论在理解大脑方面的实用性以及结构连接技术方面的高级专业知识，并为生产性独立研究职业提供基础。