Towards physiologically-informed rehabilitation therapies

I propose multi-modal, cross-species experiments to first determine the neurophysiological mechanisms underpinning motor plasticity, and then to develop approaches that drive plasticity to enhance behaviour. I will focus on the role of neural dynamics, particularly on phase-amplitude coupling of θ- and γ-activity (θ-γ PAC), in two key nodes of the motor network: the primary motor cortex (M1) and thalamus, to address these key aims: - Decoding the neurochemical and circuit underpinnings of M1 θ-γ PAC and how it modulates network connectivity during motor plasticity - Driving motor network connectivity to optimise motor plasticity - Determining clinical relevance: the role of GABAergic signalling and θ-γ PAC in stroke recovery I will capitalise on the advantages of cross-species investigations to determine the causality and cell-type specificity of neural dynamics underpinning plasticity. I will drive plasticity using novel human neurophysiological tools to stimulate, and record from, deep brain structures to enhance behaviour. Finally, I will translate the physiologically defined stimulation approach developed in the fellowship to enhance behaviour in chronic stroke survivors. Taken together, this work will provide an essential understanding of the physiological changes underpinning motor skill acquisition, as well as resulting in putative therapeutic interventions to enhance stroke recovery: a substantial, under-met, clinical need.