Stimulus responses and targeted plasticity of the macaque motor cortex using intracortical microstimulation

Abstract

Electrical stimulation is a commonly used tool for probing neural circuits in both research and clinical settings. Stimulation delivered directly to the cerebral cortex, intracortical microstimulation (ICMS), has often been used to induce targeted plasticity between a pre- and postsynaptic site. However, the results often require a long conditioning period, are highly variable, and depend on the cortical site pairs. The following dissertation describes experiments performed to better understand both the behavioral and neural effects of ICMS and utilizes that knowledge for a more effective spike-timing dependent plasticity (STDP) protocol. First, ICMS is delivered at different phases of unimanual movement to assess its effects beyond the stimulated hemisphere and dependence of the changes observed on the movement state. Next, gamma-triggered stimulation as a proxy for-population triggered stimulation is explored for inducing STDP. Then single neuron responses to ICMS and the dependencies of the responses to underlying spontaneous activity as well as how they change over time are characterized. The single neuron responses are subsequently used as a measure of connectivity in a paired stimulation paradigm to induce STDP. Finally, different behavioral states during sleep and waking are determined, and the underlying neural dynamics are compared to lay the groundwork for assessing plasticity throughout different brain states. The combined results strongly suggest the significance of specific timing in delivering ICMS, indicate the role of inhibitory responses, and provide insights for future applications of ICMS.