The medial olivocochlear reflex strength is modulated during a visual working memory task.

Top-down modulation of sensory responses to distracting stimuli by selective attention has been proposed as an important mechanism by which our brain can maintain relevant information during working memory tasks. Previous works in visual working memory (VWM) have reported modulation of neural responses to distracting sounds at different levels of the central auditory pathways. Whether these modulations occur also at the level of the auditory receptor is unknown. Here, we hypothesize that cochlear responses to irrelevant auditory stimuli can be modulated by the medial olivocochlear system during VWM. Twenty-one subjects (13 males, mean age 25.3 yr) with normal hearing performed a visual change detection task with different VWM load conditions (high load = 4 visual objects; low load = 2 visual objects). Auditory stimuli were presented as distractors and allowed the measurement of distortion product otoacoustic emissions (DPOAEs) and scalp auditory evoked potentials. In addition, the medial olivocochlear reflex strength was evaluated by adding contralateral acoustic stimulation. We found larger contralateral acoustic suppression of DPOAEs during the visual working memory period (n = 21) compared with control experiments (n = 10), in which individuals were passively exposed to the same experimental conditions. These results show that during the visual working memory period there is a modulation of the medial olivocochlear reflex strength, suggesting a possible common mechanism for top-down filtering of auditory responses during cognitive processes.NEW & NOTEWORTHY The auditory efferent system has been proposed to function as a biological filter of cochlear responses during selective attention. Here, we recorded electroencephalographic activity and otoacoustic emissions in response to auditory distractors during a visual working memory task in humans. We found that the olivocochlear efferent activity is modulated during the visual working memory period suggesting a common mechanism for suppressing cochlear responses during selective attention and working memory.

Medial olivocochlear reflex effects on amplitude growth functions of long- and short-latency components of click-evoked otoacoustic emissions in humans.

Functional outcomes of medial olivocochlear reflex (MOCR) activation, such as improved hearing in background noise and protection from noise damage, involve moderate to high sound levels. Previous noninvasive measurements of MOCR in humans focused primarily on otoacoustic emissions (OAEs) evoked at low sound levels. Interpreting MOCR effects on OAEs at higher levels is complicated by the possibility of the middle-ear muscle reflex and by components of OAEs arising from different locations along the length of the cochlear spiral. We overcame these issues by presenting click stimuli at a very slow rate and by time-frequency windowing the resulting click-evoked (CE)OAEs into short-latency (SL) and long-latency (LL) components. We characterized the effects of MOCR on CEOAE components using multiple measures to more comprehensively assess these effects throughout much of the dynamic range of hearing. These measures included CEOAE amplitude attenuation, equivalent input attenuation, phase, and slope of growth functions. Results show that MOCR effects are smaller on SL components than LL components, consistent with SL components being generated slightly basal of the characteristic frequency region. Amplitude attenuation measures showed the largest effects at the lowest stimulus levels, but slope change and equivalent input attenuation measures did not decrease at higher stimulus levels. These latter measures are less commonly reported and may provide insight into the variability in listening performance and noise susceptibility seen across individuals.NEW & NOTEWORTHY The auditory efferent system, operating at moderate to high sound levels, may improve hearing in background noise and provide protection from noise damage. We used otoacoustic emissions to measure these efferent effects across a wide range of sound levels and identified level-dependent and independent effects. Previous reports have focused on level-dependent measures. The level-independent effects identified here may provide new insights into the functional relevance of auditory efferent activity in humans.

Functional MRI evidence of the cortico-olivary efferent pathway during active auditory target processing in humans.

Auditory target detection has been explored by a number of studies, but none have demonstrated activity in the auditory subcortical centers evoked by the top-down attentional mechanism related to target detection in humans. We applied functional magnetic resonance imaging (fMRI) with sparse sampling to explore activity in the auditory centers, particularly in the subcortex, during an active auditory target detection task. Fourteen healthy subjects with normal hearing tapped the left index finger in response to target tonal stimuli presented among other (non-target) stimuli during continuous white noise stimulation. General linear model, region-of-interest, and connectivity analyses were performed. In the cortex, bilateral auditory cortices as well as the cingulate gyrus, thalamus, and supramarginal gyrus were activated to target stimuli and functionally connected to each other. In the subcortex, the superior olivary complex (SOC) and locus coeruleus were activated to the target but not to the non-target or background noise stimuli. The SOC was the only auditory subcortical center that displayed connectivity to the auditory cortical areas as well as the cingulate and supramarginal gyri during target presentation but not during other conditions. SOC activation appears to be the first fMRI evidence of direct cortico-olivary projections in the human brain as well as SOC participation in auditory target detection. Our results may be an initial step towards developing a noninvasive methodology to evaluate the functional integrity of the auditory efferent system in humans.

Across Species "Natural Ablation" Reveals the Brainstem Source of a Noninvasive Biomarker of Binaural Hearing.

The binaural interaction component (BIC) of the auditory brainstem response is a noninvasive electroencephalographic signature of neural processing of binaural sounds. Despite its potential as a clinical biomarker, the neural structures and mechanism that generate the BIC are not known. We explore here the hypothesis that the BIC emerges from excitatory-inhibitory interactions in auditory brainstem neurons. We measured the BIC in response to click stimuli while varying interaural time differences (ITDs) in subjects of either sex from five animal species. Species had head sizes spanning a 3.5-fold range and correspondingly large variations in the sizes of the auditory brainstem nuclei known to process binaural sounds [the medial superior olive (MSO) and the lateral superior olive (LSO)]. The BIC was reliably elicited in all species, including those that have small or inexistent MSOs. In addition, the range of ITDs where BIC was elicited was independent of animal species, suggesting that the BIC is not a reflection of the processing of ITDs per se. Finally, we provide a model of the amplitude and latency of the BIC peak, which is based on excitatory-inhibitory synaptic interactions, without assuming any specific arrangement of delay lines. Our results show that the BIC is preserved across species ranging from mice to humans. We argue that this is the result of generic excitatory-inhibitory synaptic interactions at the level of the LSO, and thus best seen as reflecting the integration of binaural inputs as opposed to their spatial properties.SIGNIFICANCE STATEMENT Noninvasive electrophysiological measures of sensory system activity are critical for the objective clinical diagnosis of human sensory processing deficits. The binaural component of sound-evoked auditory brainstem responses is one such measure of binaural auditory coding fidelity in the early stages of the auditory system. Yet, the precise neurons that lead to this evoked potential are not fully understood. This paper provides a comparative study of this potential in different mammals and shows that it is preserved across species, from mice to men, despite large variations in morphology and neuroanatomy. Our results confirm its relevance to the assessment of binaural hearing integrity in humans and demonstrates how it can be used to bridge the gap between rodent models and humans.

Physiological models of the lateral superior olive.

In computational biology, modeling is a fundamental tool for formulating, analyzing and predicting complex phenomena. Most neuron models, however, are designed to reproduce certain small sets of empirical data. Hence their outcome is usually not compatible or comparable with other models or datasets, making it unclear how widely applicable such models are. In this study, we investigate these aspects of modeling, namely credibility and generalizability, with a specific focus on auditory neurons involved in the localization of sound sources. The primary cues for binaural sound localization are comprised of interaural time and level differences (ITD/ILD), which are the timing and intensity differences of the sound waves arriving at the two ears. The lateral superior olive (LSO) in the auditory brainstem is one of the locations where such acoustic information is first computed. An LSO neuron receives temporally structured excitatory and inhibitory synaptic inputs that are driven by ipsi- and contralateral sound stimuli, respectively, and changes its spike rate according to binaural acoustic differences. Here we examine seven contemporary models of LSO neurons with different levels of biophysical complexity, from predominantly functional ones ('shot-noise' models) to those with more detailed physiological components (variations of integrate-and-fire and Hodgkin-Huxley-type). These models, calibrated to reproduce known monaural and binaural characteristics of LSO, generate largely similar results to each other in simulating ITD and ILD coding. Our comparisons of physiological detail, computational efficiency, predictive performances, and further expandability of the models demonstrate (1) that the simplistic, functional LSO models are suitable for applications where low computational costs and mathematical transparency are needed, (2) that more complex models with detailed membrane potential dynamics are necessary for simulation studies where sub-neuronal nonlinear processes play important roles, and (3) that, for general purposes, intermediate models might be a reasonable compromise between simplicity and biological plausibility.

Efferent modulation of pre-neural and neural distortion products.

Distortion product otoacoustic emissions (DPOAEs) and distortion product frequency following responses (DPFFRs) are respectively pre-neural and neural measurements associated with cochlear nonlinearity. Because cochlear nonlinearity is putatively linked to outer hair cell electromotility, DPOAEs and DPFFRs may provide complementary measurements of the human medial olivocochlear (MOC) reflex, which directly modulates outer hair cell function. In this study, we first quantified MOC reflex-induced DPOAE inhibition at spectral fine structure peaks in 22 young human adults with normal hearing. The f1 and f2 tone pairs producing the largest DPOAE fine structure peak for each subject were then used to evoke DPFFRs with and without MOC reflex activation to provide a related neural measure of efferent inhibition. We observed significant positive relationships between DPOAE fine structure peak inhibition and inhibition of DPFFR components representing neural phase locking to f2 and 2f1-f2, but not f1. These findings may support previous observations that the MOC reflex inhibits DPOAE sources differentially. That these effects are maintained and represented in the auditory brainstem suggests that the MOC reflex may exert a potent influence on subsequent subcortical neural representation of sound.

Spontaneous otoacoustic emission recordings during contralateral pure-tone activation of medial olivocochlear reflex.

We hypothesized that cochlear frequency discrimination occurs through medial olivocochlear efferent (MOCE)-induced alterations in outer hair cell (OHC) electromotility, which is independent from basilar membrane traveling waves. After obtaining informed consent, volunteers with normal hearing (n = 10; mean age: 20.6 ± 1.2 years) and patients with unilateral deafness (n = 10; mean age: 30.2 ± 17.9 years) or bilateral deafness (n = 8; mean age: 30.7 ± 13.8 years) underwent a complete physical and audiological examination, and audiological tests including transient evoked otoacoustic emission and spontaneous otoacoustic emission (TEOAE and SOAE, respectively). SOAE recordings were performed during contralateral pure-tone stimuli at 1 and 3 kHz. SOAE recordings in the presence of contralateral pure-tone stimuli showed frequency-specific activation out of the initial frequency range of SOAE responses. Basilar membrane motion during pure-tone stimulation results from OHC activation by means of MOCE neurons rather than from a traveling wave. Eventually, frequency-specific responses obtained from SOAEs suggested that OHC electromotility may be responsible for frequency discrimination of the cochlea independently from basilar membrane motion.

Dopaminergic projections of the subparafascicular thalamic nucleus to the auditory brainstem.

Neuromodulators can alter the response properties of sensory neurons, including those in the auditory system. Dopamine, which plays a major role in reward and movement, has been shown to alter neural responses in the auditory brainstem and midbrain. Recently we identified the subparafascicular thalamic nucleus (SPF), part of the A11 dopaminergic cell group, as the source of dopamine to the inferior colliculus (IC). The superior olivary complex (SOC) is also a likely target of dopaminergic projections from the SPF because it receives projections from the SPF and contains fibers and terminals immunoreactive for tyrosine hydroxylase, the rate limiting enzyme in dopamine synthesis. However, it is unknown if the projections from the SPF to SOC are dopaminergic, and if single neurons in the SPF project to both the IC and SOC. Using anterograde tracing combined with fluorescent immunohistochemistry, we found that the SPF sends dopaminergic projections to the superior paraolivary nucleus and the medial nucleus of the trapezoid body, but not the lateral superior olive. We confirmed these projections using a retrograde tracer. By making dual retrograde deposits in the IC and SOC, we found that individual dopaminergic cells innervate both the IC and SOC. These results suggest dopaminergic innervation, likely released in a context dependent manner, occurs at multiple levels of the auditory pathway.

The medial olivocochlear reflex in children during active listening.

OBJECTIVE: To determine if active listening modulates the strength of the medial olivocochlear (MOC) reflex in children. DESIGN: Click-evoked otoacoustic emissions (CEOAEs) were recorded from the right ear in quiet and in four test conditions: one with contralateral broadband noise (BBN) only, and three with active listening tasks wherein attention was directed to speech embedded in contralateral BBN. STUDY SAMPLE: Fifteen typically-developing children (ranging in age from 8 to14 years) with normal hearing. RESULTS: CEOAE levels were reduced in every condition with contralateral acoustic stimulus (CAS) when compared to preceding quiet conditions. There was an additional systematic decrease in CEOAE level with increased listening task difficulty, although this effect was very small. These CEOAE level differences were most apparent in the 8-18 ms region after click onset. CONCLUSIONS: Active listening may change the strength of the MOC reflex in children, although the effects reported here are very subtle. Further studies are needed to verify that task difficulty modulates the activity of the MOC reflex in children.

The superior paraolivary nucleus shapes temporal response properties of neurons in the inferior colliculus.

The mammalian superior paraolivary nucleus (SPON) is a major source of GABAergic inhibition to neurons in the inferior colliculus (IC), a well-studied midbrain nucleus that is the site of convergence and integration for the majority ascending auditory pathways en route to the cortex. Neurons in the SPON and IC exhibit highly precise responses to temporal sound features, which are important perceptual cues for naturally occurring sounds. To determine how inhibitory input from the SPON contributes to the encoding of temporal information in the IC, a reversible inactivation procedure was conducted to silence SPON neurons, while recording responses to amplitude-modulated tones and silent gaps between tones in the IC. The results show that SPON-derived inhibition shapes responses of onset and sustained units in the IC via different mechanisms. Onset neurons appear to be driven primarily by excitatory inputs and their responses are shaped indirectly by SPON-derived inhibition, whereas sustained neurons are heavily influenced directly by transient offset inhibition from the SPON. The findings also demonstrate that a more complete dissection of temporal processing pathways is critical for understanding how biologically important sounds are encoded by the brain.