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Andrew Hooyman, Alexander Garbin and Beth Fisher

Recent neuroimaging research has demonstrated that resting-state intracortical connectivity (i.e., the shared communication between two brain regions) can serve as a robust predictor of motor performance and learning. Theoretically, direct modulation of resting-state intracortical connectivity within the motor system could then improve motor performance and learning. However, previous neuromodulation techniques such as repetitive Transcranial Magnetic Stimulation may be limited in the capacity to modulate targeted intracortical connectivity. Paired Associative Stimulation (PAS) has shown efficacy in facilitating connectivity primarily between the central and peripheral nervous system based on the neuroplasticity mechanism of Spike Timing Dependent Plasticity. It may therefore be plausible for a reconfigured corticocortical PAS paradigm to modulate resting-state intracortical connectivity using a dual stimulator methodology over specific cortical nodes. However, potential theoretical and technological considerations of such a paradigm first need to be addressed prior to application for the purposes of manipulating motor behavior. We posit a corticocortical PAS paradigm used in conjunction with resting-state electroencephalography to demonstrate efficacy of potentiating motor learning associated resting-state intracortical connectivity within the human brain. Here we provide a precise PAS/EEG experimental design, details on data analysis, recommendations for maintaining scientific rigor, and preliminary proof of principle within a single-subject.