Bursts of vagus nerve stimulation paired with auditory rehabilitation fail to improve speech sound perception in rats with hearing loss.

Hearing loss can lead to long-lasting effects on the central nervous system, and current therapies, such as auditory training and rehabilitation, show mixed success in improving perception and speech comprehension. Vagus nerve stimulation (VNS) is an adjunctive therapy that can be paired with rehabilitation to facilitate behavioral recovery after neural injury. However, VNS for auditory recovery has not been tested after severe hearing loss or significant damage to peripheral receptors.

Degraded inferior colliculus responses to complex sounds in prenatally exposed VPA rats.

Background: Individuals with autism spectrum disorders (ASD) often exhibit altered sensory processing and deficits in language development. Prenatal exposure to valproic acid (VPA) increases the risk for ASD and impairs both receptive and expressive language. Like individuals with ASD, rodents prenatally exposed to VPA exhibit degraded auditory cortical processing and abnormal neural activity to sounds.

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.

Degraded inferior colliculus responses to complex sounds in prenatally exposed VPA rats.

Background: Individuals with autism spectrum disorders (ASD) often exhibit altered sensory processing and deficits in language development. Prenatal exposure to valproic acid (VPA) increases the risk for ASD and impairs both receptive and expressive language. Like individuals with ASD, rodents prenatally exposed to VPA exhibit degraded auditory cortical processing and abnormal neural activity to sounds.

Auditory Brainstem Responses Predict Behavioral Deficits in Rats with Varying Levels of Noise-Induced Hearing Loss.

Intense noise exposure is a leading cause of hearing loss, which results in degraded speech sound discrimination ability, particularly in noisy environments. The development of an animal model of speech discrimination deficits due to noise induced hearing loss (NIHL) would enable testing of potential therapies to improve speech sound processing. Rats can accurately detect and discriminate human speech sounds in the presence of quiet and background noise.

Vagus nerve stimulation paired with tones restores auditory processing in a rat model of Rett syndrome.

Background: Rett syndrome is a rare neurological disorder associated with a mutation in the X-linked gene MECP2. This disorder mainly affects females, who typically have seemingly normal early development followed by a regression of acquired skills. The rodent Mecp2 model exhibits many of the classic neural abnormalities and behavioral deficits observed in individuals with Rett syndrome.

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.

Vagus Nerve Stimulation Rate and Duration Determine whether Sensory Pairing Produces Neural Plasticity.

Repeatedly pairing a brief train of vagus nerve stimulation (VNS) with an auditory stimulus drives reorganization of primary auditory cortex (A1), and the magnitude of this VNS-dependent plasticity is dependent on the stimulation parameters, including intensity and pulse rate. However, there is currently little data to guide the selection of VNS train durations, an easily adjusted parameter that could influence the effect of VNS-based therapies. Here, we tested the effect of varying the duration of the VNS train on the extent of VNS-dependent cortical plasticity.

Varying Stimulation Parameters to Improve Cortical Plasticity Generated by VNS-tone Pairing.

Pairing vagus nerve stimulation (VNS) with movements or sounds can direct robust plasticity in motor or auditory cortex, respectively. The degree of map plasticity is influenced by the intensity and pulse width of VNS, number of VNS-event pairings, and the interval between each pairing. It is likely that these parameters interact, influencing optimal implementation of VNS pairing protocols.

The interaction of pulse width and current intensity on the extent of cortical plasticity evoked by vagus nerve stimulation.

Background: Repeatedly pairing a tone with a brief burst of vagus nerve stimulation (VNS) results in a reorganization of primary auditory cortex (A1). The plasticity-enhancing and memory-enhancing effects of VNS follow an inverted-U response to stimulation intensity, in which moderate intensity currents yield greater effects than low or high intensity currents. It is not known how other stimulation parameters effect the plasticity-enhancing effects of VNS.

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.

Shank3-deficient rats exhibit degraded cortical responses to sound.

Unlabelled: Individuals with SHANK3 mutations have severely impaired receptive and expressive language abilities. While brain responses are known to be abnormal in these individuals, the auditory cortex response to sound has remained largely understudied. In this study, we document the auditory cortex response to speech and non-speech sounds in the novel Shank3-deficient rat model.

Degraded neural and behavioral processing of speech sounds in a rat model of Rett syndrome.

Individuals with Rett syndrome have greatly impaired speech and language abilities. Auditory brainstem responses to sounds are normal, but cortical responses are highly abnormal. In this study, we used the novel rat Mecp2 knockout model of Rett syndrome to document the neural and behavioral processing of speech sounds.

Vagal nerve stimulation blocks interleukin 6-dependent synaptic hyperexcitability induced by lipopolysaccharide-induced acute stress in the rodent prefrontal cortex.

The ratio between synaptic inhibition and excitation (sI/E) is a critical factor in the pathophysiology of neuropsychiatric disease. We recently described a stress-induced interleukin-6 dependent mechanism leading to a decrease in sI/E in the rodent temporal cortex. The aim of the present study was to determine whether a similar mechanism takes place in the prefrontal cortex, and to elaborate strategies to prevent or attenuate it.

Behavioral and neural discrimination of speech sounds after moderate or intense noise exposure in rats.

Objectives: Hearing loss is a commonly experienced disability in a variety of populations including veterans and the elderly and can often cause significant impairment in the ability to understand spoken language. In this study, we tested the hypothesis that neural and behavioral responses to speech will be differentially impaired in an animal model after two forms of hearing loss.

Design: Sixteen female Sprague-Dawley rats were exposed to one of two types of broadband noise which was either moderate or intense.

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.

Reversing pathological neural activity using targeted plasticity.

Brain changes in response to nerve damage or cochlear trauma can generate pathological neural activity that is believed to be responsible for many types of chronic pain and tinnitus. Several studies have reported that the severity of chronic pain and tinnitus is correlated with the degree of map reorganization in somatosensory and auditory cortex, respectively. Direct electrical or transcranial magnetic stimulation of sensory cortex can temporarily disrupt these phantom sensations.