Pairing vagus nerve stimulation with tones drives plasticity across the auditory pathway.

Previous studies have demonstrated that pairing vagus nerve stimulation (VNS) with sounds can enhance the primary auditory cortex (A1) response to the paired sound. The neural response to sounds following VNS-sound pairing in other subcortical and cortical auditory fields has not been documented. We predicted that VNS-tone pairing would increase neural responses to the paired tone frequency across the auditory pathway. In this study, we paired VNS with the presentation of a 9-kHz tone 300 times a day for 20 days. We recorded neural responses to tones from 2,950 sites in the inferior colliculus (IC), A1, anterior auditory field (AAF), and posterior auditory field (PAF) 24 h after the last pairing session in anesthetized rats. We found that VNS-tone pairing increased the percentage of IC, A1, AAF, and PAF that responds to the paired tone frequency. Across all tested auditory fields, the response strength to tones was strengthened in VNS-tone paired rats compared with control rats. VNS-tone pairing reduced spontaneous activity, frequency selectivity, and response threshold across the auditory pathway. This is the first study to document both cortical and subcortical plasticity following VNS-sound pairing. Our findings suggest that VNS paired with sound presentation is an effective method to enhance auditory processing.NEW & NOTEWORTHY Previous studies have reported primary auditory cortex plasticity following vagus nerve stimulation (VNS) paired with a sound. This study extends previous findings by documenting that fields across the auditory pathway are altered by VNS-tone pairing. VNS-tone pairing increases the percentage of each field that responds to the paired tone frequency. This is the first study to document both cortical and subcortical plasticity following VNS-sound pairing.

Precise sound characteristics drive plasticity in the primary auditory cortex with VNS-sound pairing.

Introduction: Repeatedly pairing a tone with vagus nerve stimulation (VNS) alters frequency tuning across the auditory pathway. Pairing VNS with speech sounds selectively enhances the primary auditory cortex response to the paired sounds. It is not yet known how altering the speech sounds paired with VNS alters responses. In this study, we test the hypothesis that the sounds that are presented and paired with VNS will influence the neural plasticity observed following VNS-sound pairing. Methods: To explore the relationship between acoustic experience and neural plasticity, responses were recorded from primary auditory cortex (A1) after VNS was repeatedly paired with the speech sounds 'rad' and 'lad' or paired with only the speech sound 'rad' while 'lad' was an unpaired background sound. Results: Pairing both sounds with VNS increased the response strength and neural discriminability of the paired sounds in the primary auditory cortex. Surprisingly, pairing only 'rad' with VNS did not alter A1 responses. Discussion: These results suggest that the specific acoustic contrasts associated with VNS can powerfully shape neural activity in the auditory pathway. Methods to promote plasticity in the central auditory system represent a new therapeutic avenue to treat auditory processing disorders. Understanding how different sound contrasts and neural activity patterns shape plasticity could have important clinical implications.

The Interval Between VNS-Tone Pairings Determines the Extent of Cortical Map Plasticity.

Repeatedly pairing vagus nerve stimulation (VNS) with a tone or movement drives highly specific and long-lasting plasticity in auditory or motor cortex, respectively. Based on this robust enhancement of plasticity, VNS paired with rehabilitative training has emerged as a potential therapy to improve recovery, even when delivered long after the neurological insult. Development of VNS delivery paradigms that reduce therapy duration and maximize efficacy would facilitate clinical translation. The goal of the current study was to determine whether primary auditory cortex (A1) plasticity can be generated more quickly by shortening the interval between VNS-tone pairing events or by delivering fewer VNS-tone pairing events. While shortening the inter-stimulus interval between VNS-tone pairing events resulted in significant A1 plasticity, reducing the number of VNS-tone pairing events failed to alter A1 responses. Additionally, shortening the inter-stimulus interval between VNS-tone pairing events failed to normalize neural and behavioral responses following acoustic trauma. Extending the interval between VNS-tone pairing events yielded comparable A1 frequency map plasticity to the standard protocol, but did so without increasing neural excitability. These results indicate that the duration of the VNS-event pairing session is an important parameter that can be adjusted to optimize neural plasticity for different clinical needs.

Speech discrimination after early exposure to pulsed-noise or speech.

Early experience of structured inputs and complex sound features generate lasting changes in tonotopy and receptive field properties of primary auditory cortex (A1). In this study we tested whether these changes are severe enough to alter neural representations and behavioral discrimination of speech. We exposed two groups of rat pups during the critical period of auditory development to pulsed-noise or speech. Both groups of rats were trained to discriminate speech sounds when they were young adults, and anesthetized neural responses were recorded from A1. The representation of speech in A1 and behavioral discrimination of speech remained robust to altered spectral and temporal characteristics of A1 neurons after pulsed-noise exposure. Exposure to passive speech during early development provided no added advantage in speech sound processing. Speech training increased A1 neuronal firing rate for speech stimuli in naïve rats, but did not increase responses in rats that experienced early exposure to pulsed-noise or speech. Our results suggest that speech sound processing is resistant to changes in simple neural response properties caused by manipulating early acoustic environment.