Adding vagus nerve stimulation to rehabilitation improves motor dysfunction after stroke

Vagus nerve stimulation (VNS) paired with rehabilitative training may enhance recovery of forelimb rotational function after stroke, according to research published in Stroke. This VNS-dependent enhancement of recovery also generalized to a similar, untrained task.

The improvements were shown in rats in which unilateral cortical and subcortical ischemic lesions were administered, reported researchers from The University of Texas at Dallas, led by Eric Meyers, PhD. According to the authors, the findings extend the viability of VNS as a safe, effective, and robust therapeutic strategy to improve motor dysfunction after stroke.

“We find that VNS paired with rehabilitative training more than doubles recovery of supination function compared with extensive rehabilitative training alone,” the authors wrote. “Furthermore, subjects that received VNS during training on a task emphasizing forelimb supination displayed significantly improved performance on a separate task measuring forelimb strength compared with subjects undergoing training without VNS.”

The recovery of supination function was found to persist for at least 7 weeks after cessation of VNS. The authors state that this is the first evidence that a combination of VNS with rehabilitative training promotes plasticity after stroke.

“These findings support VNS therapy as an effective post-stroke intervention and provide insight into the neural mechanisms that may subserve recovery,” they added.

For the study, 31 rats were trained on a fully automated, quantitative task that measured forelimb supination. When they were proficient at the task, unilateral ischemic lesions of primary motor cortex and dorsolateral striatum were administered.

One week later, rats were randomized to receive 6 weeks of rehabilitative training on the supination task with or without VNS. Rats then underwent 4 weeks of testing on a task assessing forelimb strength. The durability of the VNS benefits was tested on the supination task 2 months after VNS was stopped.

Ischemic lesions substantially reduced performance on the supination task. One week after lesions were administered, both groups had significant reductions in peak turn angle and success rate.

VNS plus rehabilitation significantly improved the recovery of peak turn angle compared with rehabilitation alone, consistent with an enhanced recovery of forelimb supination, the investigators found. Significantly improved performance was observed during all 6 weeks of therapy (P < 0.01). In addition, VNS plus rehabilitation improved the success rate compared with rehabilitation alone. Significant improvements occurred during all weeks of therapy.

The benefits of VNS also generalized to untrained tasks: rats that received VNS paired with rehabilitative training on the supination task performed significantly better on the isometric pull task compared with animals that underwent training alone.

Further, the benefits of VNS were maintained for multiple weeks. An additional 2 weeks of testing of the supination assessment task demonstrated no reduction in peak turn angle or success rate in the VNS plus rehabilitation group. “The durability of improvements after cessation of VNS is a key consideration in translating VNS therapy for stroke recovery to the clinic,” the researchers wrote.

VNS paired with rehabilitative training improved recovery by increasing synaptic connectivity within motor networks that control the grasping muscles of the forelimb. VNS resulted in a six-fold increase in labeled sensorimotor cortical neurons in the lesion brain hemisphere and a three-fold increase in the unlesioned hemisphere.

Loss of the ability to supinate the forearm is a major contributor to post-stroke disability, so strategies to improve recovery of forearm rotational function are critical, the authors suggest.

They concluded: “Adding VNS to rehabilitative training more than doubled recovery. These results suggest that pairing VNS with a range of rehabilitative exercises that incorporate rotational movements may be beneficial for patients.”

To read more about this study, click here.