Evaluating the impact of intracortical microstimulation on distant cortical brain regions for neuroprosthetic applications

Enhancing functional motor recovery after localized brain injury is a widely recognized priority in healthcare as disorders of the nervous system that cause motor impairment, such as stroke, are among the most common causes of adult-onset disability. Restoring physiological function in a dysfunctional brain to improve quality of life is a primary challenge in scientific and clinical research and could be driven by innovative therapeutic approaches. Recently, techniques using brain stimulation methodologies have been employed to promote post-injury neuroplasticity for the restitution of motor function. One type of closed-loop stimulation, i.e., activity-dependent stimulation (ADS), has been shown to modify existing functional connectivity within either healthy or injured cerebral cortices and used to increase behavioral recovery following cortical injury. The aim of this PhD thesis is to characterize the electrophysiological correlates of such behavioral recovery in both healthy and injured cortical networks using in vivo animal models. We tested the ability of two different intracortical micro-stimulation protocols, i.e., ADS and its randomized open-loop version (RS), to potentiate cortico-cortical connections between two distant cortical locations in both anaesthetized and awake behaving rats. Thus, this dissertation has the following three main goals: 1) to investigate the ability of ADS to induce changes in intra-cortical activity in healthy anesthetized rats, 2) to characterize the electrophysiological signs of brain injury and evaluate the capability of ADS to promote electrophysiological changes in the damaged network, and 3) to investigate the long-term effects of stimulation by repeating the treatment for 21 consecutive days in healthy awake behaving animals. The results of this study indicate that closed-loop activity-dependent stimulation induced greater changes than open-loop random stimulation, further strengthening the idea that Hebbian-inspired protocols might potentiate cortico-cortical connections between distant brain areas. The implications of these results have the potential to lead to novel treatments for various neurological diseases and disorders and inspire new neurorehabilitation therapies.