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We present the implementation and efficacy of an open-source closed-loop neurofeedback (CLNF) and closed-loop movement feedback (CLMF) system. In CLNF, we measure mm-scale cortical mesoscale activity with GCaMP6s and provide graded auditory feedback (within ~63 ms) based on changes in dorsal-cortical activation within regions of interest (ROIs) and with a specified rule. Single or dual ROIs (ROI1, ROI2) on the dorsal cortical map were selected as targets. Both motor and sensory regions supported closed-loop training in male and female mice. Mice modulated activity in rule-specific target cortical ROIs to get increasing rewards over days (repeated-measures ANOVA [RM-ANOVA], p=2.83e-5) and adapted to changes in ROI rules (RM-ANOVA, p=8.3e-10, Table 4 for different rule changes). In CLMF, feedback (within ~67 ms) was based on tracking a specified body movement, and rewards were generated when the behavior reached a threshold. For movement training, the group that received graded auditory feedback performed significantly better (RM-ANOVA, p=9.6e-7) than a control group (RM-ANOVA, p=0.49) within 4 training days. Additionally, mice can learn a change in task rule from left forelimb to right forelimb within a day, after a brief performance drop on day 5. Offline analysis of neural data and behavioral tracking revealed changes in the overall distribution of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    fluorescence values in CLNF and body-part speed values in CLMF experiments. Increased CLMF performance was accompanied by a decrease in task latency and cortical \u0394\n                    <jats:italic>F<\/jats:italic>\n                    \/\n                    <jats:italic>F<\/jats:italic>\n                    <jats:sub>0<\/jats:sub>\n                    amplitude during the task, indicating lower cortical activation as the task gets more familiar.\n                  <\/jats:p>","DOI":"10.7554\/elife.105070","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T13:25:29Z","timestamp":1736169929000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.105070","source":"Crossref","is-referenced-by-count":0,"title":["Real-time closed-loop feedback system for mouse mesoscale cortical signal and movement control"],"prefix":"10.7554","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6814-2812","authenticated-orcid":true,"given":"Pankaj 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