Responses In Inferior Colliculus Research Articles

Pairing tones with vagus nerve stimulation improves brain stem responses to speech in the valproic acid model of autism.

Receptive language deficits and aberrant auditory processing are often observed in individuals with autism spectrum disorders (ASD). Symptoms associated with ASD are observed in rodents prenatally exposed to valproic acid (VPA), including deficits in speech sound discrimination ability. These perceptual difficulties are accompanied by changes in neural activity patterns. In both cortical and subcortical levels of the auditory pathway, VPA-exposed rats have impaired responses to speech sounds. Developing a method to improve these neural deficits throughout the auditory pathway is necessary. The purpose of this study was to investigate the ability of vagus nerve stimulation (VNS) paired with sounds to restore degraded inferior colliculus (IC) responses in VPA-exposed rats. VNS paired with the speech sound "dad" was presented to a group of VPA-exposed rats 300 times per day for 20 days. Another group of VPA-exposed rats were presented with VNS paired with multiple tone frequencies for 20 days. The IC responses were recorded from 19 saline-exposed control rats and 18 VPA-exposed with no VNS, 8 VNS-speech paired VPA-exposed, and 7 VNS-tone paired VPA-exposed female and male rats. Pairing VNS with tones increased the IC response strength to speech sounds by 44% compared to VPA-exposed rats alone. Contrarily, VNS-speech pairing significantly decreased the IC response to speech compared with VPA-exposed rats by 5%. The present research indicates that pairing VNS with tones improved sound processing in rats exposed to VPA and suggests that auditory processing can be improved through targeted plasticity.NEW & NOTEWORTHY 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.

Combined-electrical optogenetic stimulation but not channelrhodopsin kinetics improves the fidelity of high rate stimulation in the auditory pathway in mice

Novel stimulation methods are needed to overcome the limitations of contemporary cochlear implants. Optogenetics is a technique that confers light sensitivity to neurons via the genetic introduction of light-sensitive ion channels. By controlling neural activity with light, auditory neurons can be activated with higher spatial precision. Understanding the behaviour of opsins at high stimulation rates is an important step towards their translation. To elucidate this, we compared the temporal characteristics of auditory nerve and inferior colliculus responses to optogenetic, electrical, and combined optogenetic-electrical stimulation in virally transduced mice expressing one of two channelrhodopsins, ChR2-H134R or ChIEF, at stimulation rates up to 400 pulses per second (pps). At 100 pps, optogenetic responses in ChIEF mice demonstrated higher fidelity, less change in latency, and greater response stability compared to responses in ChR2-H134R mice, but not at higher rates. Combined stimulation improved the response characteristics in both cohorts at 400 pps, although there was no consistent facilitation of electrical responses. Despite these results, day-long stimulation (up to 13 h) led to severe and non-recoverable deterioration of the optogenetic responses. The results of this study have significant implications for the translation of optogenetic-only and combined stimulation techniques for hearing loss.

The Neural Representation of Binaural Sound Localization Cues Across Different Subregions of the Chicken's Inferior Colliculus.

The sound localization behavior of the nocturnally hunting barn owl and its underlying neural computations is a textbook example of neuroethology. Differences in sound timing and level at the two ears are integrated in a series of well-characterized steps, from brainstem to inferior colliculus (IC), resulting in a topographical neural representation of auditory space. It remains an important question of brain evolution: How is this specialized case derived from a more plesiomorphic pattern? The present study is the first to match physiology and anatomical subregions in the non-owl avian IC. Single-unit responses in the chicken IC were tested for selectivity to different frequencies and to the binaural difference cues. Their anatomical origin was reconstructed with the help of electrolytic lesions and immunohistochemical identification of different subregions of the IC, based on previous characterizations in owl and chicken. In contrast to barn owl, there was no distinct differentiation of responses in the different subregions. We found neural topographies for both binaural cues but no evidence for a coherent representation of auditory space. The results are consistent with previous work in pigeon IC and chicken higher-order midbrain and suggest a plesiomorphic condition of multisensory integration in the midbrain that is dominated by lateral panoramic vision.

Dissociable Roles of the Auditory Midbrain and Cortex in Processing the Statistical Features of Natural Sound Textures.

Sound texture perception takes advantage of a hierarchy of time-averaged statistical features of acoustic stimuli, but much remains unclear about how these statistical features are processed along the auditory pathway. Here, we compared the neural representation of sound textures in the inferior colliculus (IC) and auditory cortex (AC) of anesthetized female rats. We recorded responses to texture morph stimuli that gradually add statistical features of increasingly higher complexity. For each texture, several different exemplars were synthesized using different random seeds. An analysis of transient and ongoing multiunit responses showed that the IC units were sensitive to every type of statistical feature, albeit to a varying extent. In contrast, only a small proportion of AC units were overtly sensitive to any statistical features. Differences in texture types explained more of the variance of IC neural responses than did differences in exemplars, indicating a degree of "texture type tuning" in the IC, but the same was, perhaps surprisingly, not the case for AC responses. We also evaluated the accuracy of texture type classification from single-trial population activity and found that IC responses became more informative as more summary statistics were included in the texture morphs, while for AC population responses, classification performance remained consistently very low. These results argue against the idea that AC neurons encode sound type via an overt sensitivity in neural firing rate to fine-grain spectral and temporal statistical features.

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

BackgroundIndividuals 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. Disrupted neuronal morphology has been documented in earlier processing areas of the auditory pathway in VPA-exposed rodents, but there are no studies documenting early auditory pathway physiology. Therefore, the objective of this study is to characterize inferior colliculus (IC) responses to different sounds in rats prenatally exposed to VPA compared to saline-exposed rats.MethodsIn vivo extracellular multiunit recordings from the inferior colliculus were collected in response to tones, speech sounds, and noise burst trains.ResultsOur results indicate that the overall response to speech sounds was degraded in VPA-exposed rats compared to saline-exposed controls, but responses to tones and noise burst trains were unaltered.ConclusionsThese results are consistent with observations in individuals with autism that neural responses to complex sounds, like speech, are often altered, and lays the foundation for future studies of potential therapeutics to improve auditory processing in the VPA rat model of ASD.

Sensitivity to direction and velocity of fast frequency chirps in the inferior colliculus of awake rabbit

Neurons in the mammalian inferior colliculus (IC) are sensitive to the velocity (speed and direction) of fast frequency chirps contained in Schroeder-phase harmonic complexes (SCHR). However, IC neurons are also sensitive to stimulus periodicity, a prominent feature of SCHR stimuli. Here, to disentangle velocity sensitivity from periodicity tuning, we introduced a novel stimulus consisting of aperiodic random chirps. Extracellular, single-unit recordings were made in the IC of Dutch-belted rabbits in response to both SCHR and aperiodic chirps. Rate-velocity functions were constructed from aperiodic-chirp responses and compared to SCHR rate profiles, revealing interactions between stimulus periodicity and neural velocity sensitivity. A generalized linear model analysis demonstrated that periodicity tuning influences SCHR response rates more strongly than velocity sensitivity. Principal component analysis of rate-velocity functions revealed that neurons were more often sensitive to the direction of lower-velocity chirps and were less often sensitive to the direction of higher-velocity chirps. Overall, these results demonstrate that sensitivity to chirp velocity is common in the IC. Harmonic sounds with complex phase spectra, such as speech and music, contain chirps, and velocity sensitivity would shape IC responses to these sounds.

Gradients of response latencies and temporal precision of auditory neurons extend across the whole inferior colliculus.

Neural responses to acoustic stimulation have long been studied throughout the auditory system to understand how sound information is coded for perception. Within the inferior colliculus (IC), a majority of the studies have focused predominantly on characterizing neural responses within the central region (ICC), as it is viewed as part of the lemniscal system mainly responsible for auditory perception. In contrast, the responses of outer cortices (ICO) have largely been unexplored, though they also function in auditory perception tasks. Therefore, we sought to expand on previous work by completing a three-dimensional (3-D) functional mapping study of the whole IC. We analyzed responses to different pure tone and broadband noise stimuli across all IC subregions and correlated those responses with over 2,000 recording locations across the IC. Our study revealed there are well-organized trends for temporal response parameters across the full IC that do not show a clear distinction at the ICC and ICO border. These gradients span from slow, imprecise responses in the caudal-medial IC to fast, precise responses in the rostral-lateral IC, regardless of subregion, including the fastest responses located in the ICO. These trends were consistent at various acoustic stimulation levels. Weaker spatial trends could be found for response duration and spontaneous activity. Apart from tonotopic organization, spatial trends were not apparent for spectral response properties. Overall, these detailed acoustic response maps across the whole IC provide new insights into the organization and function of the IC.NEW & NOTEWORTHY Study of the inferior colliculus (IC) has largely focused on the central nucleus, with little exploration of the outer cortices. Here, we systematically assessed the acoustic response properties from over 2,000 locations in different subregions of the IC. The results revealed spatial trends in temporal response patterns that span all subregions. Furthermore, two populations of temporal response types emerged for neurons in the outer cortices that may contribute to their functional roles in auditory tasks.

Prepulse inhibition of the acoustic startle reflex impairment by 5-HT2A receptor activation in the inferior colliculus is prevented by GABAA receptor blockade in the pedunculopontine tegmental nucleus

The relationship between serotonin dysfunction and schizophrenia commenced with the discovery of the effects of lysergic acid diethylamide (LSD) that has high affinity for 5-HT2A receptors. Activation of these receptors produces perceptual and behavioural changes such as illusions, visual hallucinations and locomotor hyperactivity. Using prepulse inhibition (PPI) of the acoustic startle, which is impaired in schizophrenia,we aimed to investigate:i) the existence of a direct and potentially inhibitory neural pathway between the inferior colliculus (IC) and the pedunculopontine tegmental nucleus (PPTg) involved in the mediation of PPI responses by a neural tract tracing procedure;ii) if the microinjection of the 5-HT2A receptors agonist DOI in IC would activate neurons in this structure and in the PPTg by a c-Fos protein immunohistochemistry study;iii) whether the deficits in PPI responses, observed after the administration of DOI in the IC, could be prevented by the concomitant microinjection of the GABAA receptor antagonist bicuculline in the PPTg.Male Wistar rats were used in this study. An IC-PPTg reciprocated neuronal pathway was identified by neurotracing. The number of c-Fos labelled cells was lower in the DOI group in IC and PPTg, suggesting that this decrease could be due to the high levels of GABA in both structures. The concomitant microinjections of bicuculline in PPTg and DOI in IC prevented the PPI deficit observed after the IC microinjection of DOI. Our findings suggest that IC 5-HT2A receptors may be at least partially involved in the regulation of inhibitory pathways mediating PPI response in IC and PPTg structures.

Incorporating models of subcortical processing improves the ability to predict EEG responses to natural speech

The goal of describing how the human brain responds to complex acoustic stimuli has driven auditory neuroscience research for decades. Often, a systems-based approach has been taken, in which neurophysiological responses are modeled based on features of the presented stimulus. This includes a wealth of work modeling electroencephalogram (EEG) responses to complex acoustic stimuli such as speech. Examples of the acoustic features used in such modeling include the amplitude envelope and spectrogram of speech. These models implicitly assume a direct mapping from stimulus representation to cortical activity. However, in reality, the representation of sound is transformed as it passes through early stages of the auditory pathway, such that inputs to the cortex are fundamentally different from the raw audio signal that was presented. Thus, it could be valuable to account for the transformations taking place in lower-order auditory areas, such as the auditory nerve, cochlear nucleus, and inferior colliculus (IC) when predicting cortical responses to complex sounds. Specifically, because IC responses are more similar to cortical inputs than acoustic features derived directly from the audio signal, we hypothesized that linear mappings (temporal response functions; TRFs) fit to the outputs of an IC model would better predict EEG responses to speech stimuli. To this end, we modeled responses to the acoustic stimuli as they passed through the auditory nerve, cochlear nucleus, and inferior colliculus before fitting a TRF to the output of the modeled IC responses. Results showed that using model-IC responses in traditional systems analyzes resulted in better predictions of EEG activity than using the envelope or spectrogram of a speech stimulus. Further, it was revealed that model-IC derived TRFs predict different aspects of the EEG than acoustic-feature TRFs, and combining both types of TRF models provides a more accurate prediction of the EEG response.

Viral-mediated transduction of auditory neurons with opsins for optical and hybrid activation

Optical stimulation is a paradigm-shifting approach to modulating neural activity that has the potential to overcome the issue of current spread that occurs with electrical stimulation by providing focused stimuli. But optical stimulation either requires high power infrared light or genetic modification of neurons to make them responsive to lower power visible light. This work examines optical activation of auditory neurons following optogenetic modification via AAV injection in two species (mouse and guinea pig). An Anc80 viral vector was used to express the channelrhodopsin variant ChR2-H134R fused to a fluorescent reporter gene under the control of the human synapsin-1 promoter. The AAV was administered directly to the cochlea (n = 33) or posterior semi-circular canal of C57BL/6 mice (n = 4) or to guinea pig cochleae (n = 6). Light (488 nm), electrical stimuli or the combination of these (hybrid stimulation) was delivered to the cochlea via a laser-coupled optical fibre and co-located platinum wire. Activation thresholds, spread of activation and stimulus interactions were obtained from multi-unit recordings from the central nucleus of the inferior colliculus of injected mice, as well as ChR2-H134R transgenic mice (n = 4). Expression of ChR2-H134R was examined by histology. In the mouse, transduction of auditory neurons by the Anc80 viral vector was most successful when injected at a neonatal age with up to 89% of neurons transduced. Auditory neuron transductions were not successful in guinea pigs. Inferior colliculus responses to optical stimuli were detected in a cochleotopic manner in all mice with ChR2-H134R expression. There was a significant correlation between lower activation thresholds in mice and higher proportions of transduced neurons. There was no difference in spread of activation between optical stimulation and electrical stimulation provided by the light/electrical delivery system used here (optical fibre with bonded 25 µm platinum/iridium wire). Hybrid stimulation, comprised of sub-threshold optical stimulation to ‘prime’ or raise the excitability of the neurons, lowered the threshold for electrical activation in most cases, but the impact on excitation width was more variable compared to transgenic mice. This study demonstrates the impact of opsin expression levels and expression pattern on optical and hybrid stimulation when considering optical or hybrid stimulation techniques for neuromodulation.

Disparity in interaural time difference improves the accuracy of neural representations of individual concurrent narrowband sounds in rat inferior colliculus and auditory cortex.

The central mechanisms underlying binaural unmasking for spectrally overlapping concurrent sounds, which are unresolved in the peripheral auditory system, remain largely unknown. In this study, frequency-following responses (FFRs) to two binaurally presented independent narrowband noises (NBNs) with overlapping spectra were recorded simultaneously in the inferior colliculus (IC) and auditory cortex (AC) in anesthetized rats. The results showed that for both IC FFRs and AC FFRs, introducing an interaural time difference (ITD) disparity between the two concurrent NBNs enhanced the representation fidelity, reflected by the increased coherence between the responses evoked by double-NBN stimulation and the responses evoked by single NBNs. The ITD disparity effect varied across frequency bands, being more marked for higher frequency bands in the IC and lower frequency bands in the AC. Moreover, the coherence between IC responses and AC responses was also enhanced by the ITD disparity, and the enhancement was most prominent for low-frequency bands and the IC and the AC on the same side. These results suggest a critical role of the ITD cue in the neural segregation of spectrotemporally overlapping sounds.NEW & NOTEWORTHY When two spectrally overlapped narrowband noises are presented at the same time with the same sound-pressure level, they mask each other. Introducing a disparity in interaural time difference between these two narrowband noises improves the accuracy of the neural representation of individual sounds in both the inferior colliculus and the auditory cortex. The lower frequency signal transformation from the inferior colliculus to the auditory cortex on the same side is also enhanced, showing the effect of binaural unmasking.

Midbrain sensitivity to spectral cues for sound-source localization: A modeling study

The features of head-related transfer functions (HRTFs) are a key topic in the field of spatial auditory displays. Neural encoding of HRTFs is not well understood; their sharp spectral peaks and notches are not well represented by average rates of relatively widely tuned auditory-nerve (AN) fibers, and phase-locking to the temporal fine structure is not adequate to encode features at high-frequencies. However, low-frequency fluctuations in cochlear responses to wideband stimuli are encoded in time-varying rates of AN fibers across all frequency channels. Here, we focus on modeling the profile of amplitude fluctuations in response to spectral cues across the population of AN channels. The fluctuation profile across AN responses sets up an average-rate profile across inferior colliculus (IC) neurons, which are sensitive to envelope-related low-frequency fluctuations. Both unilateral and bilateral IC model responses indicate that rather than responding to spectral peaks in a given HRTF, IC responses are more sensitive to fluctuations in frequency channels near steep spectral slopes. The influence of the spatial location and stimulus level on model IC responses was examined. Using statistical methods, psychoacoustical thresholds of discrimination of sounds that differ in the source location were estimated and compared to trends in the existing perceptual results. The features of head-related transfer functions (HRTFs) are a key topic in the field of spatial auditory displays. Neural encoding of HRTFs is not well understood; their sharp spectral peaks and notches are not well represented by average rates of relatively widely tuned auditory-nerve (AN) fibers, and phase-locking to the temporal fine structure is not adequate to encode features at high-frequencies. However, low-frequency fluctuations in cochlear responses to wideband stimuli are encoded in time-varying rates of AN fibers across all frequency channels. Here, we focus on modeling the profile of amplitude fluctuations in response to spectral cues across the population of AN channels. The fluctuation profile across AN responses sets up an average-rate profile across inferior colliculus (IC) neurons, which are sensitive to envelope-related low-frequency fluctuations. Both unilateral and bilateral IC model responses indicate that rather than responding to spectral peaks in a given HRTF, IC responses are mor...

Auditory brainstem stimulation with a conformable microfabricated array elicits responses with tonotopically organized components

Auditory brainstem implants (ABIs) restore hearing to deaf individuals not eligible for cochlear implants. Speech comprehension in ABI users is generally poor compared to that of cochlear implant users, and side effects are common. The poor performance may result from activating broad areas and multiple neuronal populations of the cochlear nucleus, however detailed studies of the responses to surface stimulation of the cochlear nucleus are lacking. A conformable electrode array was microfabricated to fit on the rat's dorsal cochlear nucleus (DCN). It hosts 20 small electrodes (each 100 μm diam.). The array was tested by recording evoked potentials and neural activity along the tonotopic axis of the inferior colliculus (IC). Almost all bipolar electrode pairs elicited responses, in some cases with an even, or relatively constant, pattern of thresholds and supra-threshold measures along the long axis of the array. This pattern suggests that conformable arrays can provide relatively constant excitation along the surface of the DCN and thus might decrease the ABI side effects caused by spread of high current to adjacent structures. We also examined tonotopic patterns of the IC responses. Compared to sound-evoked responses, electrically-evoked response mappings had less tonotopic organization and were broader in width. They became more tonotopic when the evoked activity common to all electrodes and the late phase of response were subtracted out, perhaps because the remaining activity is from tonotopically organized principal cells of the DCN. Responses became less tonotopic when inter-electrode distance was increased from 400 μm to 800 μm but were relatively unaffected by changing to monopolar stimulation. The results illustrate the challenges of using a surface array to present tonotopic cues and improve speech comprehension in humans who use the ABI.

Intracochlear near infrared stimulation: Feasibility of optoacoustic stimulation in vivo

Intracochlear optical stimulation has been suggested as an alternative approach to hearing prosthetics in recent years. This study investigated the properties of a near infrared laser (NIR) induced optoacoustic effect. Pressure recordings were performed at the external meatus of anaesthetized guinea pigs during intracochlear NIR stimulation. The sound pressure and power spectra were determined. The results were compared to multi unit responses in the inferior colliculus (IC). Additionally, the responses to NIR stimulation were compared to IC responses induced by intracochlear electric stimulation at the same cochlear position to investigate a potentially confounding contribution of direct neural NIR stimulation. The power spectra of the sound recorded at the external meatus (n = 7) had most power at frequencies below 10 kHz and showed little variation for different stimulation sites. The mean spike rates of IC units responding to intracochlear NIR stimulation (n = 222) of 17 animals were significantly correlated with the power of the externally recorded signal at frequencies corresponding to the best frequencies of the IC units. The response strength as well as the sound pressure at the external meatus depended on the pulse peak power of the optical stimulus. The sound pressure recorded at the external meatus reached levels above 70 dB SPL peak equivalent. In hearing animals a cochlear activation apical to the location of the fiber was found. The absence of any NIR responses after pharmacologically deafening and the comparison to electric stimulation at the NIR stimulation site revealed no indication of a confounding direct neural NIR stimulation. Intracochlear optoacoustic stimulation might become useful in combined electro-acoustic stimulation devices in the future.

Auditory central gain compensates for changes in cochlear output after prolonged low-level noise exposure

Remarkably, the central auditory system can modify the strength of its sound-evoked neural response based on prior acoustic experiences, a phenomenon referred to as central gain. Gain changes are well documented following traumatic noise exposure, but much less is known about central gain dynamics following prolonged exposure to low-level noise, a common acoustic experience in many urban and work environments. We recently reported that the neural output of the cochlea is reduced, while gain was enhanced in the inferior colliculus (IC) following a 5-week exposure to 75 dB noise. To determine if similar effects were present at even lower intensities, we exposed rats to a 65 dB noise expecting to see little to no change in the cochlea or IC. The exposure had little effect on distortion product otoacoustic emissions and did not cause any hair cell loss. However, the amplitude of the CAP, which reflects the neural output of cochlea, was depressed by 50–75%. Surprisingly, neural responses from the IC were enhanced up to 70%, mainly at frequencies within the noise exposure band. One-week post-exposure, CAP amplitudes returned to normal at frequencies within or above the exposure band, whereas responses evoked by frequencies below the exposure band were enhanced by more than 80%. In contrast, IC responses below the exposure frequency were depressed 10–20% whereas responses within the exposure frequency band were enhanced 10–20%. Thus, the central auditory system dynamically up- and down-regulates its gain to maintain supra-threshold neural responses within a narrow homeostatic range; a function that likely contributes to the prevention of sounds from being perceived as muffled or too loud.

Stimulus-specific adaptation in the anesthetized mouse revealed by brainstem auditory evoked potentials

Neural responses to sensory inputs in a complex and natural environment must be weighted according to their relevance. To do so, the brain needs to be able to deal with sudden stimulus fluctuations in an ever-changing acoustic environment. Stimulus-specific adaptation (SSA) is a phenomenon of some neurons along the auditory pathway that show a reduced response to repetitive sounds while responsive to those that occur rarely. SSA has been shown from the inferior colliculus to auditory cortex, but has not been detected in the cochlear nucleus. To discover where SSA is first generated along the auditory pathway, auditory brainstem responses (ABRs) to pure tones were evaluated in anesthetized mice using an oddball paradigm. Using a typical narrow band-pass filter, changes in the ABRs suggest unspecific short-term adaptation may occur as early as the auditory nerve fibers. Furthermore, after applying a wide band-pass filter –allowing the visualization of a late slow wave in the ABR– we found a reduction of the amplitude of the response to repetitive sounds, compared to rare ones, in the slow wave component P0 that follow the fast wave V. Previous studies have shown the P0 shows temporal correlation with the sustained responses of inferior colliculus, thus we suggest that this nucleus is the first to show stimulus specific adaptation in the auditory pathway.

Design, Fabrication, and Evaluation of a Parylene Thin-Film Electrode Array for Cochlear Implants.

To improve the existing manually assembled cochlear implant electrode arrays, a thin-film electrode array (TFEA) was microfabricated having a maximum electrode density of 15 sites along an 8-mm length, with each site having a 75 μm × 1.8 μm (diameter× height) disk electrode. The microfabrication method adopted photoresist transferring, lift-off, two-step oxygen plasma etching, and fuming nitric acid release to reduce lift-off complexity, protect the metal layer, and increase the release efficiency. Systematic in vitro characterization showed that the TFEA's bending stiffness was 6.40 × 10-10 N·m2 near the base and 1.26 × 10-10N·m2 near the apex. The TFEA electrode produced an average impedance of 16 kΩ and a maximum current limit of 800 μA, measured with 1-kHz sinusoidal current using monopolar stimulation in saline. A TFEA prototype was implanted in a cat cochlea to obtain in vivo measurements of electrically evoked auditory brainstem and inferior colliculus responses to monopolar stimulation with 41-μs/phase biphasic pulses. Both physiological responses produced a threshold of ∼300 μA and a dynamic range of 5-8 dB above the threshold. Compared with existing arrays, the present TFEA had 104 times less bending stiffness, 97% less electrode area, and comparable physiological thresholds. Using a simplified structure and stable fabrication method, the present TEFA produced physical and physiological performance comparable to existing commercial devices. The present TFEA represents a step closer toward an automated process replacing the labor-intensive and expensive manual assembly of the cochlear implant electrode arrays.

Neural Representation Of Harmonic Single Sideband Encoder In Inferior Colliculus Of Guinea Pigs.

The supplement of harmonics and temporal fine structure (TFS) information has been verified to increase the tone recognition of cochlear implants (CIs) users. However, the limited resolution of spectral and temporal in electric hearing hindered the delivery of TFS information. Harmonic single sideband encoder (HSSE) can explicitly track the harmonics of complex sounds and linearly transform harmonics into modulators conveying both amplitude modulation (AM) and TFS information to electrodes. However, it keeps urgent to develop fast, objective and quantitative methods to evaluate the TFS representation in higher level centers of auditory pathway to HSSE strategy. The study built an IC mathematical model based on spectro-temporal receptive field (STRF) by recording the vivo neural responses of inferior colliculus (IC) to a couple of original Chinese Mandarin speech and analyzing the FS representation on IC. Finally the study predicted neural response to HSSE coded speech. The results showed that the IC neuronal response evoked by HSSE coded speech contained FS information.

The contribution of inferior colliculus activity to the auditory brainstem response (ABR) in mice

In mice, the auditory brainstem response (ABR) is frequently used to assess hearing status in transgenic hearing models. The diagnostic value of the ABR depends on knowledge about the anatomical sources of its characteristic waves. Here, we studied the contribution of the inferior colliculus (IC) to the click-evoked scalp ABR in mice. We demonstrate a non-invasive correlate of the IC response that can be measured in the scalp ABR as a slow positive wave P0 with peak latency 7–8 ms when recorded with adequate band-pass filtering. Wave P0 showed close correspondence in latency, magnitude and shape with the sustained part of evoked spiking activity and local field potentials (LFP) in the central nucleus of the IC. In addition, the onset peaks of the IC response were related temporally to ABR wave V and to some extent to wave IV. This relation was further supported by depth-dependent modulation of the shape of ABR wave IV and V within the IC suggesting generation within or in close vicinity to the IC. In conclusion, the slow ABR wave P0 in the scalp ABR may represent a complementary non-invasive marker for IC activity in the mouse. Further, the latency of synchronized click-evoked activity in the IC supports the view that IC contributes to ABR wave V, and possibly also to ABR wave IV.

Auditory midbrain processing is differentially modulated by auditory and visual cortices: An auditory fMRI study

The cortex contains extensive descending projections, yet the impact of cortical input on brainstem processing remains poorly understood. In the central auditory system, the auditory cortex contains direct and indirect pathways (via brainstem cholinergic cells) to nuclei of the auditory midbrain, called the inferior colliculus (IC). While these projections modulate auditory processing throughout the IC, single neuron recordings have samples from only a small fraction of cells during stimulation of the corticofugal pathway. Furthermore, assessments of cortical feedback have not been extended to sensory modalities other than audition. To address these issues, we devised blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) paradigms to measure the sound-evoked responses throughout the rat IC and investigated the effects of bilateral ablation of either auditory or visual cortices. Auditory cortex ablation increased the gain of IC responses to noise stimuli (primarily in the central nucleus of the IC) and decreased response selectivity to forward species-specific vocalizations (versus temporally reversed ones, most prominently in the external cortex of the IC). In contrast, visual cortex ablation decreased the gain and induced a much smaller effect on response selectivity. The results suggest that auditory cortical projections normally exert a large-scale and net suppressive influence on specific IC subnuclei, while visual cortical projections provide a facilitatory influence. Meanwhile, auditory cortical projections enhance the midbrain response selectivity to species-specific vocalizations. We also probed the role of the indirect cholinergic projections in the auditory system in the descending modulation process by pharmacologically blocking muscarinic cholinergic receptors. This manipulation did not affect the gain of IC responses but significantly reduced the response selectivity to vocalizations. The results imply that auditory cortical gain modulation is mediated primarily through direct projections and they point to future investigations of the differential roles of the direct and indirect projections in corticofugal modulation. In summary, our imaging findings demonstrate the large-scale descending influences, from both the auditory and visual cortices, on sound processing in different IC subdivisions. They can guide future studies on the coordinated activity across multiple regions of the auditory network, and its dysfunctions.