Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

Abstract

Pathological neural activity could be treated by directing specific plasticity to renormalize circuits and restore function. Rehabilitative therapies aim to promote adaptive circuit changes after neurological disease or injury, but insufficient or maladaptive plasticity often prevents a full recovery. The development of adjunctive strategies that broadly support plasticity to facilitate the benefits of rehabilitative interventions has the potential to improve treatment of a wide range of neurological disorders. Recently, stimulation of the vagus nerve in conjunction with rehabilitation has emerged as one such potential targeted plasticity therapy. Vagus nerve stimulation (VNS) drives activation of neuromodulatory nuclei that are associated with plasticity, including the cholinergic basal forebrain and the noradrenergic locus coeruleus. Repeatedly pairing brief bursts of VNS sensory or motor events drives robust, event-specific plasticity in neural circuits. Animal models of chronic tinnitus, ischemic stroke, intracerebral hemorrhage, traumatic brain injury, and post-traumatic stress disorder benefit from delivery of VNS paired with successful trials during rehabilitative training. Moreover, mounting evidence from pilot clinical trials provides an initial indication that VNS-based targeted plasticity therapies may be effective in patients with neurological diseases and injuries. Here, I provide a discussion of the current uses and potential future applications of VNS-based targeted plasticity therapies in animal models and patients, and outline challenges for clinical implementation.

Parametric characterization of neural activity in the locus coeruleus in response to vagus nerve stimulation

“…This rapid recruitment of LC neurons likely mediates the memory- and plasticity-enhancing effects of VNS. We speculate that the short latency increase in LC activity drives a phasic release of norepinephrine which acts to facilitate plasticity specific to ongoing experience (Hays., 2016). The role of the LC in plasticity is supported by evidence that antagonism of β-adrenergic receptors blocks VNS-dependent plasticity (Shen et al, 2012).…”

“…Targeted plasticity therapies using short bursts of VNS paired with rehabilitative training regimens have emerged as potential treatments for a variety of neurological disorders (Hays., 2016). Preclinical studies demonstrate that VNS paired with rehabilitative training improves recovery in models of tinnitus, ischemic and hemorrhagic stroke, and traumatic brain injury (Engineer et al, 2011, Khodaparast et al, 2013, Khodaparast et al, 2014, Hays et al, 2014, Pruitt et al, 2016, Khodaparast et al, 2016, Hays et al, 2016).…”

“…Emerging studies provide evidence that VNS paired with rehabilitative training may be useful in the treatment of additional neurological disorders, including tinnitus and stroke (Dawson et al, 2016, De Ridder et al, 2014, Hays., 2016). Despite the widespread use of VNS, there is relatively little consensus on the optimal stimulation methods, perhaps owing to incomplete knowledge of the effects of VNS on structures throughout the brain.…”

Effects of chronic abdominal vagal stimulation of small-diameter neurons on brain metabolism and food intake

“…Furthermore, we also observed an activation of the cingular cortex irrespective of the stimulation pattern, which is compatible with DVC projection (20,22). Finally, the activation of the prefrontal cortex could reflect its connectivity with the thalamo-insular pathway, which is altered during VNS-dependent alterations in synaptic plasticity (30). Undoubtedly, the activation of the medulla in the vicinity of the DVC was an important observation that was found with the S2 and S3 stimulation patterns only.…”

Neural Circuits Catch Fire

“…Section 4 presents an alternative approach-create a heightened state of plasticity generally and then use task-specific training to target select circuits. In the first paper in this section, Dr. Seth Hays [11] discusses combining vagus nerve stimulation, which alters cortical plasticity, with task-specific rehabilitation of motor skill for recovery of movement or auditory experience to treat tinnitus. Finally, this issue ends with a discussion by Dr. Dale Corbett and colleagues [12] on how environmental enrichment and exercise enhance many of the changes associated with spontaneous recovery.…”