Hearing, Balance, Taste, and Smell

Plastic changes along auditory pathway during salicylate-induced ototoxicity: Hyperactivity and CF shifts

Event Abstract Back to Event Causal role of auditory cortex in mediating attention to moments in time Attention is the means by which the brain selects and highlights important sensory information for further processing, ignoring or suppressing the rest. The earliest single unit studies revealed that neural activity in the first stages of cortical sensory processing is modulated by attention (Hubel et al., 1959). To date, most of what is known about the neural mechanisms underlying attention is based on correlations between neural activity and behavior. Here we establish for the first time that not only is neural activity in the auditory cortex correlated with attention, but that the auditory cortex is causally involved in mediating the behavioral advantages conferred by attention. We first developed a rodent behavioral paradigm in which we could demonstrate that attention enhanced performance on a sensory discrimination task. The task was an auditory two-alternative choice paradigm, modeled after a related visual paradigm in humans (Coull and Nobre, 1998), in which we manipulated attention to moments in time. Rats were required to detect a frequency-modulated target sound immersed in a train of pure tone distractors. Performance varied systematically with task difficulty, manipulated by the varying modulation depth of the target. Behavioral analysis showed a clear improvement in both reaction times and correct discrimination whenever the target appeared at an expected moment, compared to the same target appearing unexpectedly. These results show that attention improved performance. We next used tetrodes to record responses from single neurons in the primary auditory cortex of rats performing this task. The majority of responsive neurons showed an increase evoked response to tones immediately preceding the expected appearance of the target when compared against responses to the same tones occurring long before the expected target location. These results show that attention to moments in time modulates changes in neural activity in the auditory cortex. Finally, we assessed the effect on performance of pharmacological inactivation of the auditory cortex. We used the GABA-A receptor agonist muscimol to reversibly inactivate the auditory cortex bilaterally. Muscimol inactivation impaired performance compared with control application of saline, implying that the auditory cortex plays an important role in this task under normal conditions. Furthermore, inactivation of the auditory cortex significantly reduced the improvements in performance associated with attention. These results suggest that the auditory cortex is required to mediate the behavioral advantage conferred by attention. In summary, we have shown that: (1) attention to moments in time can lead to improved performance on a two-alternative choice auditory detection/discrimination task in rats; (2) neural activity in the primary auditory cortex is correlated with attention to moments in time; and (3) the auditory cortex plays a causal role in mediating the behavioral advantage conferred by attention.

Reliability and Representational Bandwidth in the Auditory Cortex

SUMMARYNeuronal oscillations are suggested to play an important role in auditory working memory (WM), but their contribution to content-specific representations has remained unclear. Here, we measure magnetoencephalography during a retro-cueing task with parametric ripple-sound stimuli, which are spectrotemporally similar to speech but resist non-auditory memory strategies. Using machine learning analyses, with rigorous between-subject cross-validation and non-parametric permutation testing, we show that memorized sound content is strongly represented in phase-synchronization patterns between subregions of auditory and frontoparietal cortices. These phase-synchronization patterns predict the memorized sound content steadily across the studied maintenance period. In addition to connectivity-based representations, there are indices of more local, “activity silent” representations in auditory cortices, where the decoding accuracy of WM content significantly increases after task-irrelevant “impulse stimuli.” Our results demonstrate that synchronization patterns across auditory sensory and association areas orchestrate neuronal coding of auditory WM content. This connectivity-based coding scheme could also extend beyond the auditory domain.

The technology for large-scale electrical recordings is rapidly improving, and extracellular recordings with multielectrode arrays now offer a unique window into neural activity at the population level. The high-frequency part of the recorded signal (MUA; multi-unit activity) is a measure of action-potential firing of neurons in the immediate vicinity of the electrode contacts, while the low-frequency part (LFP; local-field potential) appears to mainly be a measure of subthreshold dendritic activity of surrounding neurons [1,2]. The interpretation of MUA and LFP signals in terms of neural circuit activity is not straightforward, however, and new analysis methods are needed to take full advantage of the technological developments. Laminar population analysis (LPA) [1] was introduced a few years ago as a new method for extracting information about population activity. Based on physiologically-constrained joint modeling of the MUA and LFP signals, both the (i) laminar organization and time-resolved firing rates of the main cortical populations, and (ii) the functional synaptic connection patterns between these populations, were estimated. Later, the population firing-rates extracted by means of LPA were used to specify mathematical neural-network models describing thalamocortical and intracortical connections between neural populations in the rat somatosensory (barrel) system [3]. In Ref. [1] LPA was used to analyze stimulus-averaged laminar (linear) electrode data from the rat barrel system, and the predicted time-resolved population firing rates and synaptic connection patterns were found to be in qualitative agreement with previous experimental findings. Here we apply LPA to recently recorded laminar-electrode data from the primary auditory cortex of rats [4]. In this study the rats were exposed to a large variety of different auditory stimuli to investigate the phenomenon known as ‘stimulus-specific adaptation’, i.e., that neurons respond stronger to unexpected stimuli. Such rich data sets where the cortical neural circuits of interest potentially exhibit a large variety of activation patterns, are particularly well suited for analysis by means of LPA. Results from LPA analysis will be presented, highlighting the differences and similarities seen between the sensory-evoked cortical response patterns in primary auditory and somatosensory cortices of rats.

A fundamental task faced by the auditory system is the detection of events that are signaled by fluctuations in sound. Spiking in auditory cortical neurons is critical for sound detection, but the causal roles of specific cell types and circuits are still mostly unknown. Here we tested the role of a genetically identified population of layer 4 auditory cortical neurons in sound detection. We measured sound detection using a common variant of pre-pulse inhibition of the acoustic startle response, in which a silent gap in background noise acts as a cue that attenuates startle. We used a Gpr26-Cre driver line, which we found expressed predominantly in layer 4 of auditory cortex. Photostimulation of these cells, which were responsive to gaps in noise, was sufficient to attenuate the startle reflex. Photosuppression of these cells reduced neural responses to gaps throughout cortex, and impaired behavioral gap detection. These data demonstrate that cortical Gpr26 neurons are both necessary and sufficient for top–down modulation of the acoustic startle reflex, and are thus likely to be involved in sound detection.

In this paper, mathematical models for the auditory system were derived to characterize the impact of anesthesia on auditory systems and mechanism of hearing damage. The auditory system was represented by a model with external sound stimuli as the input and the neuron firing rates as the output, and represented as a black-box input-output system. Two parallel subsystem models were developed: an ARX model for the auditory system under external stimuli and an ARMA model for the spontaneous activities of the neurons in primary auditory cortex. The models provide a quantitative characterization of anesthesia’s impacts and describe the mechanism of hearing loss on auditory transmission channels.KeywordsFiring RateAuditory SystemARMA ModelBroadband NoisePrimary Auditory CortexThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

During early development, peripheral sensory systems generate physiological activity prior to exposure to normal environmental stimuli. This activity is thought to facilitate maturation of these neurons and their connections, perhaps even promoting efficacy or modifying downstream circuitry. In the mammalian auditory system, initial connections form at embryonic ages, but the functional characteristics of these early neural connections have not been assayed. We investigated processes of embryonic auditory development using a whole-head slice preparation that preserved connectivity between peripheral and brainstem stations of the auditory pathway. Transgenic mice expressing fluorescent protein provided observation of spiral ganglion and cochlear nucleus neurons to facilitate targeted electrophysiological recording. Here we demonstrate an apparent peripheral-to-central order for circuit maturation. Spiral ganglion cells acquire action potential-generating capacity at embryonic day 14 (E14), the earliest age tested, and action potential waveforms begin to mature in advance of comparable states for neurons of the ventral cochlear nucleus (VCN) and medial nucleus of the trapezoid body (MNTB). In accordance, auditory nerve synapses in the VCN are functional at E15, prior to VCN connectivity with the MNTB, which occurs at least 1 day later. Spiral ganglion neurons exhibit spontaneous activity at least by E14 and are able to drive third-order auditory brainstem neurons by E17. This activity precedes cochlear-generated wave activity by 4 days and ear canal opening by at least 2 weeks. Together, these findings reveal a previously unknown initial developmental phase for auditory maturation, and further implicate the spiral ganglion as a potential controlling centre in this process.

Acoustic environments are composed of complex overlapping sounds that the auditory system is required to segregate into discrete perceptual objects. The functions of distinct auditory processing stations in this challenging task are poorly understood. Here we show a direct role for mouse auditory cortex in detection and segregation of acoustic information. We measured the sensitivity of auditory cortical neurons to brief tones embedded in masking noise. By altering spectrotemporal characteristics of the masker, we reveal that sensitivity to pure tone stimuli is strongly enhanced in coherently modulated broadband noise, corresponding to the psychoacoustic phenomenon comodulation masking release. Improvements in detection were largest following priming periods of noise alone, indicating that cortical segregation is enhanced over time. Transient opsin-mediated silencing of auditory cortex during the priming period almost completely abolished these improvements, suggesting that cortical processing may play a direct and significant role in detection of quiet sounds in noisy environments.SIGNIFICANCE STATEMENT Auditory systems are adept at detecting and segregating competing sound sources, but there is little direct evidence of how this process occurs in the mammalian auditory pathway. We demonstrate that coherent broadband noise enhances signal representation in auditory cortex, and that prolonged exposure to noise is necessary to produce this enhancement. Using optogenetic perturbation to selectively silence auditory cortex during early noise processing, we show that cortical processing plays a crucial role in the segregation of competing sounds.

The auditory system of many mammalian species is immature at the time of birth. Peripheral elements, particularly the middle ear and cochlea, account for much of the physiological immaturity observed in central auditory structures. However, there is now considerable evidence that the central pathway undergoes developmental changes that, at least partially, occur in parallel with peripheral development. Auditory nerve fibres and their terminals have been shown to be of smaller diameter and less extensively arborized in neonatal than in adult cats. These factors almost certainly contribute to many of the sluggish physiological properties of neurones in the kitten auditory nerve and cochlear nucleus. At higher levels of the cat auditory system (inferior colliculus, auditory cortex) mechanisms subserving binaural interaction also undergo a period of postnatal development. Recent studies of sound deprivation produced by either deafferentation or a conductive hearing loss have demonstrated that alteration of cochlear output during the immediate postnatal period may change the normal development of the central auditory system.

Vibration-induced auditory-cortex activation in a congenitally deaf adult

Auditory fear conditioning elicits plastic changes specific to a conditioning tonal stimulus (CS) in the central auditory system.Gao and Suga (1998) proposed the neural circuit for producing these tone-specific changes, represented by best frequency (BF) shifts.The Gao-Suga model (Fig. 1, solid arrows), elaborated upon by Suga et al. (2000Suga et al. ( , 2002)), states that small (or subthreshold) short-term cortical and collicular BF shifts specific to tone bursts (CS) are evoked by the neural circuit within the auditory cortex (Chowdhury and Suga 2000;

An essential task of the auditory system is to discriminate between different communication signals, such as vocalizations. In everyday acoustic environments, the auditory system needs to be capable of performing the discrimination under different acoustic distortions of vocalizations. To achieve this, the auditory system is thought to build a representation of vocalizations that is invariant to their basic acoustic transformations. The mechanism by which neuronal populations create such an invariant representation within the auditory cortex is only beginning to be understood. We recorded the responses of populations of neurons in the primary and nonprimary auditory cortex of rats to original and acoustically distorted vocalizations. We found that populations of neurons in the nonprimary auditory cortex exhibited greater invariance in encoding vocalizations over acoustic transformations than neuronal populations in the primary auditory cortex. These findings are consistent with the hypothesis that invariant representations are created gradually through hierarchical transformation within the auditory pathway.

We tested the hypothesis that information is routed from one area of the auditory cortex (AC) to another via the dorsal division of the medial geniculate body (MGBd) by analyzing the degree of reciprocal connectivity between the auditory thalamus and cortex. Biotinylated dextran amine injected into the primary AC (AI) or anterior auditory field (AAF) of mice produced large, "driver-type" terminals primarily in the MGBd, with essentially no such terminals in the ventral MGB (MGBv). In contrast, small, "modulator-type" terminals were found primarily in the MGBv, and this coincided with areas of retrogradely labeled thalamocortical cell bodies. After MGBv injections, anterograde label was observed in layers 4 and 6 of the AI and AAF, which coincided with retrogradely labeled layer 6 cell bodies. After MGBd injections, thalamocortical terminals were seen in layers 1, 4, and 6 of the secondary AC and dorsoposterior AC, which coincided with labeled layer 6 cell bodies. Notably, after MGBd injection, a substantial number of layer 5 cells were labeled in all AC areas, whereas very few were seen after MGBv injection. Further, the degree of anterograde label in layer 4 of cortical columns containing labeled layer 6 cell bodies was greater than in columns containing labeled layer 5 cell bodies. These data suggest that auditory layer 5 corticothalamic projections are targeted to the MGBd in a nonreciprocal fashion and that the MGBd may route this information to the nonprimary AC.

<b>Purpose: </b>From an anthropological perspective of hominin communication, the human auditory system likely evolved to enable special sensitivity to sounds produced by the vocal tracts of human conspecifics whether attended or passively heard. While numerous electrophysiological studies have used stereotypical human-produced verbal (speech voice and singing voice) and nonverbal vocalizations to identify human voice–sensitive responses, controversy remains as to when (and where) processing of acoustic signal attributes characteristic of “human voiceness” per se initiate in the brain.<b>Method: </b>To explore this, we used animal vocalizations and human-mimicked versions of those calls (“mimic voice”) to examine late auditory evoked potential responses in humans.<b>Results: </b>Here, we revealed an N1b component (96–120 ms poststimulus) during a nonattending listening condition showing significantly greater magnitude in response to mimics, beginning as early as primary auditory cortices, preceding the time window reported in previous studies that revealed species-specific vocalization processing initiating in the range of 147–219 ms. During a sound discrimination task, a P600 (500–700 ms poststimulus) component showed specificity for accurate discrimination of human mimic voice. Distinct acoustic signal attributes and features of the stimuli were used in a classifier model, which could distinguish most human from animal voice comparably to behavioral data—though none of these single features could adequately distinguish human voiceness.<b>Conclusions:</b> These results provide novel ideas for algorithms used in neuromimetic hearing aids, as well as direct electrophysiological support for a neurocognitive model of natural sound processing that informs both neurodevelopmental and anthropological models regarding the establishment of auditory communication systems in humans.<br><b>Supplemental Material S1.</b>Part A: Error trial AEP data from Task condition.Part B: Machine learning classification of animal vocals and their human mimics. <br>Talkington, W. J., Donai, J., Kadner, A. S., Layne, M. L., Forino, A., Wen, S., Gao, S., Gray, M. M., Ashraf, A. J., Valencia, G. N., Smith, B. D., Khoo, S. K., Gray, S. J., Lass, N., Brefczynski-Lewis, J. A., Engdahl, S., Graham, D., Frum, C. A., &amp; Lewis, J. W. (2020). Electrophysiological evidence of early cortical sensitivity to human conspecific mimic voice as a distinct category of natural sound. <i>Journal of Speech, Language, and Hearing Research.</i> Advance online publication. https://doi.org/10.1044/2020_JSLHR-20-00063