Targeting Auditory Cortex Plasticity Using Vagus Nerve Stimulation

Abstract

Neuroplasticity refers to the ability of the nervous system to change in response to experience or injury. These changes can be positive (i.e., language acquisition) or negative (i.e., tinnitus). The release of neuromodulators like norepinephrine are critical for neuroplasticity, and regions responsible for their release are modulated by vagus nerve stimulation (VNS). When VNS is paired with a sensory stimulus, specific and lasting changes are observed in the nervous system. In addition, VNS is FDA-approved in the treatment of drug resistant epilepsy and depression, and has been proven to be safe and effective for thousands of patients. Several patients benefited from VNS tone-pairing therapy as a treatment for tinnitus in recent clinical trials. However, no patient was completely cured of his/her tinnitus. A potential reason for these results is that more plasticity must be driven in VNS tone-paired treatment for patients to have maximal benefit. Therefore, VNS parameters must be evaluated to ensure the best settings for driving plasticity are being used clinically. To accomplish this goal, the rate, train duration, and number of VNS pulses were evaluated. Results suggest that 30 Hz is better at driving plasticity than rates a much higher (120 Hz) or lower (7.5 Hz) levels. Longer (2000 ms) VNS pulse trains are not capable of driving plasticity. However, it is possible to drive plasticity using one-fourth of the stimulation used in previous experiments. These results suggest that the magnitude of plasticity driven by VNS is sensitive to changes in multiple stimulation parameters. The high temporal precision of VNS-tone pairing protocols may help to explain the cellular mechanisms responsible for the beneficial effects of precisely timed VNS during restoration of sensory or motor function