Vagus Nerve Stimulation Plus Sound May Improve Auditory Processing in Rett, Study Suggests

Stimulation of the vagus nerve, when paired with sound, could help people with Rett syndrome better process what they hear, a study in rats suggests.

The study, “Vagus nerve stimulation paired with tones restores auditory processing in a rat model of Rett syndrome,” was published in the journal Brain Stimulation.

People with Rett syndrome commonly experience difficulties with auditory processing, which refers to hearing and making sense of speech and other sounds. Previous research has indicated that such difficulties arise because of problems in the parts of the brain responsible for processing sound.

While interventions such as cognitive training can be partly beneficial, therapies that can significantly improve auditory processing in people with Rett syndrome are still needed.

Vagus nerve stimulation (VNS) involves electrical stimulation of one of the vagus nerves (one on each side of the body), which run from the head, down the neck, into the chest and abdomen. In the U.S., this approach is approved to treat depression and epilepsy.

VNS is believed to promote brain plasticity — the brain’s ability to “rewire” and form new connections. Previous research has suggested that pairing VNS with a sound can reverse damaging brain changes in a rat model of tinnitus.

“Thus, VNS may represent a means to influence plasticity in the auditory network in the context of Rett syndrome,” scientists from The University of Texas at Dallas wrote in their study.

To assess their hypothesis, the investigators used female rats with a mutation in the MECP2 gene, modeling Rett syndrome. A group of animals received VNS paired with sound cues, delivered 300 times per day for 20 days, while the others were untreated to serve as controls. An additional group of wild-type rats (without mutations) was also used.

An electrode was implanted around the left vagus nerve, and connected to wire leads placed under the skin between the eye and the ear, and to a head cap on top of the skull.

After seven days of recovery from surgery, the animals were placed in a cage within a sound-insulated chamber. The head cap was then connected to a pulse stimulator and sounds of multiple tone frequencies were presented from a speaker hanging above the cage.

One day after the last VNS-tone pairing session, the rats’ electrical activity in the primary auditory cortex was recorded in responses to sounds under anesthesia.

Relative to wild-type rats, untreated animals with MECP2 mutations showed a 29% decrease in the A1 response strength to speech sounds. Importantly, pairing VNS with sound in the rat model of Rett led to a significantly higher response strength than in untreated rats, which was similar to that observed in wild-type animals.

VNS treatment also partially normalized the speed with which A1 signals were fired (activated), and improved neural classifier performance, a measure of how well the brain can differentiate between similar sounds.

“In the current study, primary auditory cortex response deficits were confirmed in Mecp2 … rats. Moreover, presentation of a range of tones coincident with brief bursts of VNS partially restored these deficits,” the researchers concluded.

“These findings provide initial evidence that VNS-sound pairing can enhance cortical auditory processing in Mecp2 rats and lay the groundwork for future studies examining the functional consequences of these changes,” they added.