Fig. 2: Closed-loop VNS restores cortical motor maps after nerve damage.

a Intracortical microstimulation reveals that, despite extensive rehabilitative training, nerve injury results in a substantial reduction in motor cortical area evoking movements of the denervated digit flexors and an increase in motor cortical area that evokes extension movements (Rehab, n = 11). CL-VNS (n = 8) reverses these lesion-induced cortical map changes, restoring the digit flexion representations and reducing the aberrant expansion of extensor representations. Delayed VNS (n = 7) failed to restore motor map representations, demonstrating that VNS relies on timed engagement with rehabilitation. b Bubble plots detailing the cortical locations of digit flexion and wrist extension movements across animals in each experimental group. The size of each bubble represents the proportion of subjects that the stimulation evoked a digit flexion or wrist extension movement at each cortical site. Note that CL-VNS significantly increases the denervated digit flexion representation and reduces the lesion-induced expansion of extension compared to Rehab and Delayed VNS. Same group sizes as in (a). c Due to misdirected reinnervation, nerve damage results in a substantial increase in the percentage of sites that generate multi-joint movements involving simultaneous digit and elbow flexion. CL-VNS reduced the percentage of sites that simultaneously elicit both movements compared to Rehab or Delayed VNS, suggesting the restoration of independent muscle control. Same group sizes as in a. d Bubble plots illustrating the stimulation site locations that generate the simultaneous digit and elbow flexion movements. Same group sizes as in a. Circles depict individual subjects in a, c. 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.