PROJECT SUMMARY Knee osteoarthritis (KOA) is a common age-related disorder and a leading cause of long-term pain and disability, for which there is a substantial therapeutic gap. Baduanjin (BDJ) is a unique mind-body exercise consisting of eight movements that can be practiced at home with video guidance, thereby making it a suitable option for older adults with KOA. Our recent study showed that BDJ can significantly reduce pain in patients with KOA. However, responses to BDJ intervention are heterogeneous, and some individuals demonstrate only a moderate response. Thus, there is an urgent need for mechanistic research to enhance the modulation effect of this promising mind-body therapy. One characteristic of BDJ is the practice of controlled fine body/limb movements and muscle and tendon strengthening. This property suggests motor learning and control may play an important role in BDJ. Improving motor performance should enhance the modulation effect of this promising mind-body intervention. The primary motor cortex (M1) is the principal brain region of the motor system and integrates input from other cortical brain areas to generate neural impulses that pass down the spinal cord and control the execution of movement. Thus, M1 may play a crucial role in BDJ practice. Transcranial direct current stimulation (tDCS) is a safe and clinically applicable neuromodulation tool that can alter cortical excitability and has been used to investigate the causal relationship between brain and behavior. Studies have shown that tDCS at M1 can facilitate motor performance. Thus, increasing the excitability of M1 using tDCS should be able to improve performance of BDJ, increasing its modulation effects. Furthermore, M1 is the most commonly used neuromodulation target for pain management. This proposal aims to investigate whether we can enhance the modulation effects of BDJ mind-body intervention by enhancing the cortical excitability of bilateral M1 using multifocal tDCS in patients with knee osteoarthritis. Specifically, we will conduct a randomized study using a 2 x 2 factorial design in which 140 KOA patients will be randomized to one of four groups: 1) BDJ + real tDCS, 2) BDJ + sham tDCS, 3) stretching + real tDCS, and 4) stretching + sham tDCS. Multidisciplinary assessments will be evaluated at baseline and 12 weeks, with a follow-up at 24 weeks. Our expected outcome is significant and highly innovative in that the findings obtained will lead to the establishment of a new and clinically implementable treatment paradigm for KOA and be broadly applicable to the management of chronic musculoskeletal pain.