Developing Cognitive Training and Rehabilitation Paradigms for Experimental TBI

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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.