Enhancing Neural Circuit Plasticity to Promote Recovery After TBI



 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.