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Developing Cognitive Training and Rehabilitation Paradigms for Experimental TBI

开发实验性 TBI 的认知训练和康复范例

基本信息

批准号：
8449189
负责人：
AMY K WAGNER
金额：
$ 17.97万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-04-01 至 2014-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8449189
关键词：
Affect Arousal Attention Behavior Clinic Clinical Cognition Cognitive Cognitive deficits Conscious Cues Data Dose Elements Failure Feedback Functional disorder Hippocampus (Brain)Impaired cognition Injury Intervention Learning Life Link Literature Location Maps Memory Memory impairment Methods Modeling Neuropsychology Performance Physiological Plastics Public Health Rattus Recovery Relative (related person)Reporting Response to stimulus physiology Retrieval Rewards Rodent Model Shapes Solid Structure Structure-Activity Relationship Testing Time Tissues Training Translations Traumatic Brain Injury Unconscious State Work base clinically relevant cognitive function cognitive recovery cognitive rehabilitation cognitive training community reintegration controlled cortical impact disability executive function flexibility high reward high risk implicit memory improved injured morris water maze neurogenesis novel regenerative skill acquisition skills skills training tool way finding

项目摘要

DESCRIPTION (provided by applicant): The neurobiologic basis of physiologic cognitive function and traumatic brain injury (TBI) induced cognitive dysfunction is not well understood. Dissociable explicit-implicit learning and memory networks exist in which each network can work to either facilitate or inhibit memory function. After TBI, the clinical literature suggests that implicit networks are relatively preserved over explicit networks, but explicit feedback can impair the use of implicitly learned information. Therefore, the types of strategies used in rehabilitatio to promote learning and memory after TBI are critically important in optimizing recovery. In our rodent model of experimental TBI, we have taken this clinical framework and linked spatial navigation to explicit, and search strategy to implicit, learning and memory. We propose that controlled cortical impact (CCI) injury can be used to model implicit and explicit learning and memory deficits of TBI. In the Morris water maze (MWM) task, rats have difficulty mastering the spatial components of task, and a reduced capability to learn the general strategies needed locate the platform. Repetitive non-spatial looping behavior, or thigmotaxis, predominates after TBI. However, our recent results show that providing pre-injury training on the non-spatial components of the MWM task to rats before CCI reduces thigmotaxis and improves overall place learning when tested 2 weeks later. In fact this implicit pre-training completely eliminated the apparent injury place learning deficits typically observed during spatial acquisition and retention trials between untrained CCI and sham injured rats, and implicit memory remains largely intact after CCI. Currently, no experimental cognitive rehabilitation models exist for TBI. Such models could transform our ability to examine mechanisms of learning and memory dysfunction after TBI and help develop and optimize cognitive training tools for translation to the clinic. Importantly, our new preliminary data suggests that 1 wk of non-spatial cognitive training AFTER injury leads to large reductions in cognitive deficits; and reduced thigmotaxis, demonstrating the feasibility of our proposed model. This high-risk/high reward R21 proposal explores post-CCI implicit learning methods in the MWM to improve spatial learning, memory, and search strategy. We will develop a model of cognitive rehabilitation in CCI by adapting clinically relevant approaches like Overtraining, Errorless Learning, and the Method of Vanishing Cues to enhance learning and memory in the MWM. We will also assess static vs. flexible implicit learning methods for their ability to improve carryover to novel task conditions n the MWM and to facilitate incorporation of explicit feedback. We will also explore relationships with hippocampal (HP) damage, neurogenesis, and plasticity and MWM performance. We hypothesize that, after CCI, implicit training paradigms (cog-training) will enhance performance in the MWM, we can exploit implicit learning approaches to facilitate explicit learning and memory, and that post-CCI cog-training effects on behavior may, in part, be related to HP neurogenesis and plasticity as well as the skill specific benefits from the intervention.

描述（由申请人提供）：生理认知功能和创伤性脑损伤（TBI）诱导的认知功能障碍的神经生物学基础尚未得到充分理解。分离的外显-内隐学习和记忆网络存在，其中每个网络都可以促进或抑制记忆功能。临床文献表明，TBI后，内隐网络相对于外显网络保留，但外显反馈会损害内隐网络。使用隐式学习的信息。因此，TBI后促进学习和记忆的康复策略类型对优化恢复至关重要。在我们的实验性TBI的啮齿动物模型中，我们采用了这种临床框架，并将空间导航与外显联系起来，将搜索策略与内隐联系起来，学习和记忆。我们建议，控制性皮质撞击（CCI）损伤可用于模拟TBI的内隐和外显学习和记忆缺陷。在Morris水迷宫（MWM）任务中，大鼠难以掌握任务的空间成分，并且学习定位平台所需的一般策略的能力降低。重复性非空间循环行为，或趋触性，TBI后占主导地位。然而，我们最近的研究结果表明，在CCI之前对大鼠进行MWM任务的非空间成分的损伤前训练，可以减少趋触性，并在2周后进行测试时改善整体位置学习。事实上，这种内隐预训练完全消除了在未训练的CCI和假损伤大鼠之间的空间获取和保留试验期间通常观察到的明显损伤位置学习缺陷，并且内隐记忆在CCI后基本上保持完整。目前，还没有实验性的认知康复模型存在TBI。这些模型可以改变我们检查TBI后学习和记忆功能障碍机制的能力，并帮助开发和优化认知训练工具，诊所重要的是，我们的新的初步数据表明，损伤后1周的非空间认知训练导致认知缺陷大幅减少;并减少趋触性，证明了我们提出的模型的可行性。这个高风险/高回报的R21建议探索后CCI内隐学习方法在MWM，以改善空间学习，记忆和搜索策略。我们将通过调整临床相关方法（如过度训练，无错学习和消失线索法）来开发CCI的认知康复模型，以增强MWM中的学习和记忆。我们还将评估静态与灵活的内隐学习方法的能力，以提高结转到新的任务条件下的MWM，并促进纳入明确的反馈。我们还将探讨海马（HP）损伤，神经发生，可塑性和MWM性能的关系。我们假设，CCI后，内隐训练范式（认知训练）将提高MWM的性能，我们可以利用内隐学习方法来促进外显学习和记忆，CCI后认知训练对行为的影响可能部分与HP神经发生和可塑性以及干预的技能特异性益处有关。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Visual Priming Enhances the Effects of Nonspatial Cognitive Rehabilitation Training on Spatial Learning After Experimental Traumatic Brain Injury.

DOI：
10.1177/1545968315570326
发表时间：
2015-10
期刊：
Neurorehabilitation and neural repair
影响因子：
4.2
作者：
Edwards CM;Kumar K;Koesarie K;Brough E;Ritter AC;Brayer SW;Thiels E;Skidmore ER;Wagner AK
通讯作者：
Wagner AK

Non-spatial pre-training in the water maze as a clinically relevant model for evaluating learning and memory in experimental TBI.

DOI：
10.1016/j.nlm.2013.07.006
发表时间：
2013-11
期刊：
NEUROBIOLOGY OF LEARNING AND MEMORY
影响因子：
2.7
作者：
Wagner, Amy K.;Brayer, Samuel W.;Hurwitz, Max;Niyonkuru, Christian;Zou, Huichao;Failla, Michelle;Arenth, Patricia;Manole, Mioara D.;Skidmore, Elizabeth;Thiels, Edda
通讯作者：
Thiels, Edda

Training to Optimize Learning after Traumatic Brain Injury.

脑外伤后优化学习的培训。