Substantial reorganization occurs throughout spared brain regions following stroke or traumatic brain injury. These neuroplastic mechanisms are thought to underlie functional behavioral recovery, but our understanding of the electrophysiological activity associated with this reorganization is incomplete. Characterizing the changes in neural activity during recovery from brain injury would allow us to better target and develop new therapies. One such therapy that has been recently proposed is activity-dependent stimulation (ADS), designed to artificially connect two sites within the nervous system. Our long-term goal is to understand the mechanisms of ADS that drive functional improvements after cortical lesions in order to translate ADS paradigms into clinical populations. The overall objective for the current project is to determine how patterns of local field potential (LFP) signals change during recovery from brain injury, how these signals are altered through ADS, and to determine if they can be used effectively to trigger ADS and drive behavioral recovery. Specifically, our central hypothesis is that the movement-related spectral power and functional connectivity of LFP signals are dysfunctional after brain injury and will be normalized after either recovery or ADS. The rationale for the proposed research is that the LFP changes that occur after a brain injury and after single-unit driven ADS, will be pathway-specific candidate features for LFP-triggered ADS algorithms. While single-unit driven ADS has shown benefits in a rodent model of brain injury, success demonstrating that LFP signals can be used to drive ADS paradigms in animal models may result in more effective translation into patient populations due to the increased longevity of LFP-driven interfaces. We will seek to accomplish these goals through the following specific aims: 1) identify alterations in movement-related spectral power changes and movement-related functional connectivity that occur in LFP signals after a cortical lesion; 2) identify alterations in movement-related spectral power changes and functional connectivity that occur after single-unit triggered ADS in brain-injured animals; and 3) demonstrate the ability to use LFP-triggered ADS to generate changes in functional connectivity. We will test these aims using chronic recordings in awake behaving healthy rodents, brain-injured rodents, and brain-injured rodents undergoing an ADS protocol. Additionally, we will use chronic LFP-driven ADS paradigms to determine if these algorithms can alter cortical functional connectivity. This project is innovative because it proposes a new paradigm positing that LFP signal components have the fidelity to be used to trigger activity-dependent stimulation protocols altering cortical connectivity. Furthermore, this project is significant because it will generate a greater understanding of the dynamics of neural activity associated with motor behavior after a brain injury and with recovery of motor function.
The proposed research is relevant to public health because acquired brain injuries, including stroke and traumatic brain injury, leave a large number of survivors with chronic motor disabilities, necessitating long-term medical and institutional care. The proposed studies seek to develop a greater understanding of the functional correlates of motor behavior after brain injury. This project will enable the development of new therapies, such as activity-dependent stimulation paradigms, designed to maximize function in survivors of brain injuries.
