Electrical Stimulation publications

Introduction Prenatal exposure to valproic acid (VPA) is a common environmental cause of autism spectrum disorder (ASD) and often leads to expressive and receptive language impairments. Similar communication difficulties among individuals with ASD are often linked to abnormal subcortical and cortical sound processing. Rodents prenatally exposed to VPA exhibit degraded cortical responses to speech and an impaired ability to behaviorally discriminate speech sounds. Methods We sought to determine whether sound processing could be restored with paired vagus nerve stimulation (VNS). In a first experiment, we evaluated whether sound-paired VNS would alter in vivo extracellular multi-unit responses to tones, noise burst trains, and speech sounds from the anterior auditory field. We next sought to evaluate whether improvements to neural sound processing led to improvements in sound discrimination ability. In a second experiment, rats underwent go/no-go sound discrimination testing where VNS was paired with successful trials. Results We found that VPA-exposed rats had degraded spectral, temporal, and speech sound processing compared to saline-exposed control rats. VPA-exposed rats which received sound-paired VNS exhibited a partial or full restoration of processing across sound types. However, across several sound discrimination tasks, we did not observe changes in behavioral performance in response to prenatal exposure to VPA or VNS. Discussion Our study is the first to show that speech-paired VNS leads to a generalized improvement in cortical sound processing across sound types, rescuing neural processing among VPA-exposed rats. These results provide a framework for future studies to develop VNS-based interventions for communication disorders.

Pairing vagus nerve stimulation (VNS) with sounds has improved auditory processing in the auditory cortex of normal-hearing rats and autism models of rats. This study tests the ability of VNS-sound pairing to restore auditory processing in the inferior colliculus (IC) of valproic acid (VPA)-exposed rats. Pairing VNS with tones significantly reversed the degraded sound processing in the IC in VPA-exposed rats. The findings provide evidence that auditory processing in autism rat models can be improved through VNS.

Spatial hearing in cochlear implant (CI) patients remains a major challenge, with many early deaf users reported to have no measurable sensitivity to interaural time differences (ITDs). Deprivation of binaural experience during an early critical period is often hypothesized to be the cause of this shortcoming. However, we show that neonatally deafened (ND) rats provided with precisely synchronized CI stimulation in adulthood can be trained to lateralize ITDs with essentially normal behavioral thresholds near 50 μs. Furthermore, comparable ND rats show high physiological sensitivity to ITDs immediately after binaural implantation in adulthood. Our result that ND-CI rats achieved very good behavioral ITD thresholds, while prelingually deaf human CI patients often fail to develop a useful sensitivity to ITD raises urgent questions concerning the possibility that shortcomings in technology or treatment, rather than missing input during early development, may be behind the usually poor binaural outcomes for current CI patients.

Corticofugal modulation of auditory responses in subcortical nuclei has been extensively studied whereas corticofugal synaptic transmission must still be characterized. This study examined postsynaptic potentials of the corticocollicular system, i.e., the projections from the primary auditory cortex (AI) to the central nucleus of the inferior colliculus (ICc) of the midbrain, in anesthetized C57 mice. We used focal electrical stimulation at the microampere level to activate the AI (ESAI) and in vivo whole-cell current-clamp to record the membrane potentials of ICc neurons. Following the whole-cell patch-clamp recording of 88 ICc neurons, 42 ICc neurons showed ESAI-evoked changes in the membrane potentials. We found that the ESAI induced inhibitory postsynaptic potentials in 6 out of 42 ICc neurons but only when the stimulus current was 96 μA or higher. In the remaining 36 ICc neurons, excitatory postsynaptic potentials (EPSPs) were induced at a much lower stimulus current. The 36 ICc neurons exhibiting EPSPs were categorized into physiologically matched neurons (n = 12) when the characteristic frequencies of the stimulated AI and recorded ICc neurons were similar (≤1 kHz) and unmatched neurons (n = 24) when they were different (>1 kHz). Compared to unmatched neurons, matched neurons exhibited a significantly lower threshold of evoking noticeable EPSP, greater EPSP amplitude, and shorter EPSP latency. Our data allow us to propose that corticocollicular synaptic transmission is primarily excitatory and that synaptic efficacy is dependent on the relationship of the frequency tunings between AI and ICc neurons.

Neural implants that deliver multi-site electrical stimulation to the nervous systems are no longer the last resort but routine treatment options for various neurological disorders. Multi-site electrical stimulation is also widely used to study nervous system function and neural circuit transformations. These technologies increasingly demand dynamic electrical stimulation and closed-loop feedback control for real-time assessment of neural function, which is technically challenging since stimulus-evoked artifacts overwhelm the small neural signals of interest. We report a novel and versatile artifact removal method that can be applied in a variety of settings, from single- to multi-site stimulation and recording and for current waveforms of arbitrary shape and size. The method capitalizes on linear electrical coupling between stimulating currents and recording artifacts, which allows us to estimate a multi-channel linear Wiener filter to predict and subsequently remove artifacts via subtraction. We confirm and verify the linearity assumption and demonstrate feasibility in a variety of recording modalities, including in vitro sciatic nerve stimulation, bilateral cochlear implant stimulation, and multi-channel stimulation and recording between the auditory midbrain and cortex. We demonstrate a vast enhancement in the recording quality with a typical artifact reduction of 25-40 dB. The method is efficient and can be scaled to arbitrary number of stimulus and recording sites, making it ideal for applications in large-scale arrays, closed-loop implants, and high-resolution multi-channel brain-machine interfaces.

The primary auditory cortex (AI) modulates the sound information processing in the lemniscal subcortical nuclei, including the anteroventral cochlear nucleus (AVCN), in a frequency-specific manner. The dorsal cochlear nucleus (DCN) is a non-lemniscal subcortical nucleus but it is tonotopically organized like the AVCN. However, it remains unclear how the AI modulates the sound information processing in the DCN. This study examined the impact of focal electrical stimulation of AI on the auditory responses of the DCN neurons in mice. We found that the electrical stimulation induced significant changes in the best frequency (BF) of DCN neurons. The changes in the BFs were highly specific to the BF differences between the stimulated AI neurons and the recorded DCN neurons. The DCN BFs shifted higher when the AI BFs were higher than the DCN BFs and the DCN BFs shifted lower when the AI BFs were lower than the DCN BFs. The DCN BFs showed no change when the AI and DCN BFs were similar. Moreover, the BF shifts were linearly correlated to the BF differences. Thus, our data suggest that corticofugal modulation of the DCN is also highly specific to frequency information, similar to the corticofugal modulation of the AVCN. The frequency-specificity of corticofugal modulation does not appear limited to the lemniscal ascending pathway.

Auditory cortical plasticity can be induced through various approaches. The medial geniculate body (MGB) of the auditory thalamus gates the ascending auditory inputs to the cortex. The thalamocortical system has been proposed to play a critical role in the responses of the auditory cortex (AC). In the present study, we investigated the cellular mechanism of the cortical activity, adopting an in vivo intracellular recording technique, recording from the primary auditory cortex (AI) while presenting an acoustic stimulus to the rat and electrically stimulating its MGB. We found that low-frequency stimuli enhanced the amplitudes of sound-evoked excitatory postsynaptic potentials (EPSPs) in AI neurons, whereas high-frequency stimuli depressed these auditory responses. The degree of this modulation depended on the intensities of the train stimuli as well as the intervals between the electrical stimulations and their paired sound stimulations. These findings may have implications regarding the basic mechanisms of MGB activation of auditory cortical plasticity and cortical signal processing.

Background: Cortical neurons implement a high frequency-specific modulation of subcortical nuclei that includes the cochlear nucleus. Anatomical studies show that corticofugal fibers terminating in the auditory thalamus and midbrain are mostly ipsilateral. Differently, corticofugal fibers terminating in the cochlear nucleus are bilateral, which fits to the needs of binaural hearing that improves hearing quality. This leads to our hypothesis that corticofugal modulation of initial neural processing of sound information from the contralateral and ipsilateral ears could be equivalent or coordinated at the first sound processing level. Methodology/principal findings: With the focal electrical stimulation of the auditory cortex and single unit recording, this study examined corticofugal modulation of the ipsilateral cochlear nucleus. The same methods and procedures as described in our previous study of corticofugal modulation of contralateral cochlear nucleus were employed simply for comparison. We found that focal electrical stimulation of cortical neurons induced substantial changes in the response magnitude, response latency and receptive field of ipsilateral cochlear nucleus neurons. Cortical stimulation facilitated auditory response and shortened the response latency of physiologically matched neurons whereas it inhibited auditory response and lengthened the response latency of unmatched neurons. Finally, cortical stimulation shifted the best frequencies of cochlear neurons towards those of stimulated cortical neurons. Conclusion: Our data suggest that cortical neurons enable a high frequency-specific remodelling of sound information processing in the ipsilateral cochlear nucleus in the same manner as that in the contralateral cochlear nucleus.