Right vagus nerve stimulation promotes motor cortical plasticity

Stimulation of the left cervical vagus nerve (l-VNS) paired with motor training is FDA-approved to improve upper limb function after stroke. However, recent preclinical studies have revealed a striking asymmetry in engagement of the midbrain dopaminergic reward system by right versus left VNS. Unlike l-VNS, right VNS (r-VNS) reinforces behavior and drives activation of midbrain dopaminergic neurons. These findings raise the possibility that r-VNS may provide therapeutic advantages by engaging plasticity- or motivation-enhancing dopaminergic signaling. In the current study, we tested whether r-VNS enhances VNS-driven motor cortical plasticity or behavioral performance compared to traditional l-VNS. Healthy rats were trained on a stimulation-paired lever-pressing task previously shown to predict the efficacy of l-VNS treatment post-stroke. Both l-VNS and r-VNS significantly expanded the representation of task-relevant musculature in the motor cortex, with no differences observed between stimulation groups. Like l-VNS, r-VNS was not accompanied by increases in task engagement or percent correct performance in healthy subjects. Combined, our findings do not support the hypothesis that r-VNS provides significant benefit over l-VNS through differential engagement of motor learning or motivational circuits. However, our results suggest that r-VNS, like l-VNS, is highly effective at inducing cortical neuroplasticity, which is associated with enhanced stroke recovery.