Project Summary/ Abstract Despite advances in gait research in the last decade, restoration of community walking continues to be an unaccomplished goal for over four million persons with stroke. Recent human studies have highlighted the significant involvement of the motor cortex in walking, emphasizing the need to develop research paradigms that provide a better understanding of cortical mechanisms in order to develop more effective walking training protocols. Transcranial direct current stimulation (tDCS) is emerging as a promising tool for enhancing task- oriented therapy of the upper limb. However, for the lower limb little is known regarding the role of the brain in gait recovery. The objective of this study is to develop a novel therapeutic intervention that is based on understanding neural adaptations to enhance gait in stroke survivors. In this study we propose that cortical priming combined with ankle motor control training is expected to improve volitional control of the paretic ankle and will enhance the beneficial effects of gait training. In this experiment, moderate to severely impaired post- stroke individuals will receive a fast treadmill training (FTT) protocol following the administration of one of three priming paradigms: facilitatory tDCS in combination with an ankle motor training task (tDCS-AMT), sham tDCS in combination with an ankle motor training task (sham-AMT) or facilitatory tDCS during rest (tDCS-rest). In addition, a control group of patients (CONT) will participate in the FTT protocol in the absence of any priming intervention. Aim 1 will identify the effectiveness of tDCS-AMT on gait speed, gait symmetry and ankle range of motion. Aim 2 will determine the effectiveness of tDCS-AMT on corticospinal mechanisms as measured by transcranial magnetic stimulation (TMS). Aim 3 will determine the effectiveness of tDCS-AMT on paretic ankle motor control and functional outcomes. With our mechanistic approach to enhance function, we seek to optimize gait rehabilitation post stroke and characterize relationships between neural mechanisms and functional recovery. Improved gait will enable stroke survivors to be more independent in the community and advance their quality of life, which is relevant to the mission of the NIH.