PROJECT SUMMARY Stroke is a leading cause of death and disability worldwide. The most common post-stroke disability is weakness or paralysis in the opposite limbs, which persists chronically (more than 6 months post-stroke) in approximately 60% of patients. There is an ongoing need for more effective post-stroke motor recovery treatments. Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation tool that can increase cortical excitability by applying weak, uniform 1 or 2 milliamp (mA) currents through scalp electrodes. In some existing studies, tDCS has shown promise for treating post-stroke aphasia and motor impairments by applying stimulation to the perilesional cortex. However, tDCS outcomes in stroke patients have been inconsistent between individuals and across studies. This may be due to the lack of personalized dosing. Typically, tDCS studies apply the same mA dosage to each person. The current one-size fits all approach likely results in underdosing for many individuals. Early modeling studies on magnetic resonance imaging (MRI) scans, including those in our lab, have shown that applying a standard 2mA tDCS dose across healthy or stroke participants results in heterogenous cortical electric fields (E-fields) at the intended target. A solution for personalizing tDCS dose may be reverse-calculation E-field modeling. This approach accounts for anatomical differences by calculating the individualized mA dosage at the scalp needed to produce the same E-field in the brain between participants. Thus, using reverse-calculation E- field modeling could potentially make tDCS more effective for post-stroke motor rehabilitation by personalizing tDCS dose to ensure that each person gets the E-field they need at the cortical target. While this reverse- calculation approach is promising, it has only been tested retrospectively. This F31 proposes to prospectively test the within-subjects effects of personalizing tDCS dose, compared to standard 2mA and sham, on motor excitability in healthy adults (Aim 1) and chronic ischemic stroke patients (Aim 2). We hypothesize that personalizing dose with reverse-calculation E-field modeling will produce significantly more consistent tDCS- induced motor excitability changes (as measured by motor evoked potentials; MEPs) than a standard 2mA dose or sham stimulation will. An Exploratory Aim will investigate the relationship between baseline functional MRI (fMRI) measures (resting state functional connectivity strength within the targeted somatomotor network) and the degree of tDCS-induced motor excitability change. The proposed research will take place at the Medical University of South Carolina (MUSC) in the Brain Stimulation Lab (BSL), which has a long history of pioneering brain stimulation treatments for neurological and psychiatric conditions. This F31 proposal incorporates a wide breadth of training opportunities, including technical skill advancement in neuroimaging and E-field modeling, ...