Enhancing Neural Circuit Plasticity to Promote Recovery After TBI

 描述（由申请人提供）： 创伤性脑损伤（TBI）被称为伊拉克和阿富汗战争的标志性损伤。这些损伤导致各种问题，包括感觉、行动和认知方面的障碍。重要的是，即使是轻微的创伤性脑损伤也会导致认知和执行功能问题。虽然这些症状的确切原因尚未完全确定，但它们可能是由白质纤维束的破坏引起的，这些纤维束有助于连接复杂认知操作背后的大规模神经网络。不幸的是，目前没有可以有效修复这些神经回路的治疗方法。事实上，甚至没有这些回路功能障碍的有效临床前模型来开始测试和开发用于TBI的新的基于回路的治疗方法。在这项研究计划中，我的目标是开发一个临床前模型的微观和宏观电路功能障碍后，创伤性脑损伤的啮齿动物。我将首先通过记录TBI损伤后的运动前区、运动区和感觉皮层来描述损伤如何破坏感觉运动功能的皮层网络。我将研究这些区域内的局部电路和这些区域之间的远程耦合。此外，我还将研究在促进运动恢复的治疗后，这些网络中发生的生理变化。在这一系列研究中，我将试图清楚地 了解TBI如何破坏感觉运动皮层网络;以及治疗驱动受影响网络可塑性的具体方式。接下来，我将测试一种特定的神经工程方法来增强受影响网络的可塑性，并研究这是否可以增强可塑性并诱导运动恢复。具体来说，我将使用脑机接口技术来增强感觉运动皮层网络节点内的连通性，从而“修复”断裂的电路。我将评估这种BMI方法如何用于驱动生理，解剖和皮质运动地图可塑性和诱导运动恢复。如果成功的话，这一提议可能预示着一种从根本上改善TBI后认知和行为功能障碍的新方法，以及一系列其他神经和精神疾病。

 DESCRIPTION (provided by applicant): Traumatic brain injuries (TBI) have been called the signature injury from the Iraq and Afghanistan wars. These injuries result in a variety of problems, including impairments in sensation, action and cognition. Importantly, even mild traumatic brain injuries can result in cognitive and executive function problems. Though the exact cause of these symptoms have not been completely worked out, they are likely caused by a break-down in white-matter fiber tracts that help to connect large-scale neural-networks underlying complex cognitive operations. Unfortunately, there are no treatments that can effectively repair these neural circuits at present Indeed, there are no valid pre-clinical models of these circuit dysfunctions to even begin to test and develop novel circuit-based treatment approaches for TBI. In this research proposal, I aim to develop a pre-clinical model of micro and macro-circuit dysfunction following traumatic-brain injury in rodents. I will first characterize how injury disrupts cortical networks underlying sensorimotor function, by recording from premotor, motor and sensory cortex after TBI-injury. I will study both local circuits within these regions and long-range coupling between these regions. In addition, I will study how physiological changes that occur in these networks following treatments that promote motor recovery. In this set of studies, I will attempt to clearly understand both how TBI disrupts sensorimotor cortical networks; and the specific ways in which treatments drives plasticity in the affected networks. Next, I will test one specific neuro-engineering approach to enhancing plasticity in affected networks, and will study whether this can enhance plasticity and induce motor recovery. Specifically, I will use brain-computer-interface technologies to enhance connectivity within nodes of the sensorimotor cortical network, thus "repairing" the broken circuit. I will assess how this BMI-approach can be used to drive physiologic, anatomic and cortical motor map plasticity and induce motor recovery. If successful, this proposal could herald a fundamentally new approach for ameliorating cognitive and behavioral dysfunction after TBI, as well as a host of other neurologic and psychiatric illnesses.