PROJECT SUMMARY / ABSTRACT Hemiparesis of the upper-limb is one of the most serious impairments resulting from stroke. Paresis of finger and thumb extensors is a frequently persisting consequence of stroke, and causes loss of hand function. We have developed contralaterally controlled functional electrical stimulation (CCFES), a novel neuromuscular electrical stimulation (NMES) therapy that gives the patient intimate control of both timing and intensity of stimulation to their finger and thumb extensors and thereby enables intention-driven hand opening and enhanced functional task practice. Several clinical trials of CCFES-assisted therapy have shown that it reduces impairment and improves function of the affected upper-limb, and it improves dexterity more than conventional NMES. The main objective of this study is to build upon the benefits of CCFES-assisted therapy for chronic stroke motor recovery. One strategy to improve rehabilitation outcomes is to combine treatments that may have synergistic effects. Therefore, this study applies transcranial direct current stimulation (tDCS) to the motor cortex during CCFES to determine if the combination of the two will improve outcomes over those achieved by CCFES alone. TDCS and CCFES may work in synergy to improve outcomes by increasing the concurrent activity of the cortical neurons within the ipsilesional motor network (conventional tDCS montage) or by exciting the contralesional networks (unconventional tDCS montage), as suggested by our pilot single-session cross-over study. The specific aims of the study are: 1) Determine if the addition of tDCS during CCFES improves motor outcomes over CCFES alone, 2) Estimate the relative effects of two tDCS electrode arrangements on motor outcomes, and 3) Estimate the relative effects of two tDCS electrode arrangements on neurophysiologic outcomes. We will conduct a randomized controlled trial in which 63 stroke survivors 6 to 24 months post-stroke will be randomly assigned to 12 weeks of: a) conventional tDCS during CCFES, b) unconventional tDCS during CCFES, or c) sham tDCS during CCFES. Upper extremity impairment, activity limitation and neurophysiologic assessment will be made at baseline, 6, 12, 24, and 36 weeks. This study is the first RCT of tDCS during CCFES in chronic upper extremity hemiplegia. The information learned in this study will serve to accelerate the development of treatments for reducing post-stroke disability.