Fig. 3: Closed-loop VNS delivered during rehabilitative training improves motor and sensory function after nerve damage.

a, b Closed-loop VNS paired with rehabilitation (CL-VNS, n = 10) significantly enhances recovery of volitional forelimb function compared to equivalent rehabilitation without CL-VNS (Rehab, n = 13). Consistent with the failure to restore cortical motor maps, Delayed VNS (n = 11) fails to improve recovery compared to CL-VNS. c Plots depicting the proportion of subjects in each group sorted by percentage of pull force recovery. All CL-VNS subjects recovered at least 80% of pre-injury function by the end of therapy. Subjects receiving either Rehab or Delayed VNS exhibited substantially reduced levels of recovery, with many subjects demonstrating < 50% recovery. Same group sizes as in a, b. d CL-VNS (n = 7) significantly improved tactile sensation in the denervated forepaw compared to both Rehab (n = 7) and Delayed VNS (n = 7) groups. In a, b asterisks indicate significant differences using t-tests across groups at each time point. The color of the asterisk denotes the group compared to CL-VNS (blue indicates CL-VNS v. Rehab, and black indicates CL-VNS v. Delayed VNS). Circles depict individual subjects in d. Error bars indicate S.E.M. All comparisons represent Bonferroni-corrected t-tests to CL-VNS, ***p < 0.0005, **p < 0.005, *p < 0.025. Source data are provided as a Source Data file.