Engaging Multiple Mechanisms of Plasticity to Promote Functional Recovery after Stroke

Abstract

The human brain is responsible for executing a vast range of functions such as movement, somatosensation, visual processing, and cognition. These and other abilities depend critically on a delicate balance between the stability and adaptability of neuronal connections. Neural injuries such as stroke disrupt these connections and often result in serious debilitating effects on the brain's ability to perform critical functions. A major challenge in developing effective rehabilitative treatments for stroke is the absence of a unifying framework for investigating multiple physiological processes in preclinical animal models. In this dissertation, I describe a framework by which we can study various aspects of cortical physiology in non-human primates (NHPs), a clinically relevant animal model, under healthy and stroke conditions (Chapter 2). Although neurons possess a diverse repertoire of plasticity mechanisms to modify and stabilize their connections, stimulation-based stroke therapies have largely focused on Hebbian forms of plasticity. Other mechanisms remain underexplored despite their potential relevance for recovery. I present two approaches to engage homeostatic and Hebbian plasticity mechanisms to induce targeted changes in functional connectivity in NHPs and rodents (Chapters 3 and 4). The combination of these tools and approaches can drive the development of effective rehabilitative stroke treatments to restore the loss of critical functions such as mobility, somatosensation, and visual processing.