Psychoacoustics publications

Background/Objectives: Tinnitus is a debilitating auditory disorder commonly described as a ringing in the ears in the absence of an external sound source. Sound trauma is considered a primary cause. Neuronal hyperactivity is one potential mechanism for the genesis of tinnitus and has been identified in the cochlear nucleus (CN) and the auditory cortex (AC), where there may be an imbalance of excitatory and inhibitory neurotransmissions. However, no study has directly correlated tinnitus with the extracellular levels of amino acids in the CN and the AC using microdialysis, which reflects the functions of these neurochemicals. In the present study, rats were exposed to acoustic trauma and then subjected to behavioural confirmation of tinnitus after one month, followed by microdialysis. Methods: Rats were divided into sham (aged, n = 6; young, n = 6); tinnitus-positive (aged, n = 7; young, n = 7); and tinnitus-negative (aged, n = 3; young, n = 3) groups. In vivo microdialysis was utilized to collect samples from the CN and the AC, simultaneously, in the same rat. Extracellular levels of amino acids were quantified using high-performance liquid chromatography (HPLC) coupled with an electrochemical detector (ECD). The effects of sound stimulation and age on neurochemical changes associated with tinnitus were also examined. Results: There were no significant differences in either the basal levels or the sound stimulation-evoked changes of any of the amino acids examined in the CN and the AC between the sham and tinnitus animals. However, the basal levels of serine and threonine exhibited age-related alterations in the AC, and significant differences in threonine and glycine levels were observed in the responses to 4 kHz and 16 kHz stimuli in the CN. Conclusions: These results demonstrate the lack of a direct link between extracellular levels of amino acids in the CN and the AC and tinnitus perception in a rat model of tinnitus.

Thalamic brain areas play an important role in adaptive behaviors. Nevertheless, the population dynamics of thalamic relays during learning across sensory modalities remain unknown. Using a cross-modal sensory reward-associative learning paradigm combined with deep brain two-photon calcium imaging of large populations of auditory thalamus (medial geniculate body, MGB) neurons in male mice, we identified that MGB neurons are biased towards reward predictors independent of modality. Additionally, functional classes of MGB neurons aligned with distinct task periods and behavioral outcomes, both dependent and independent of sensory modality. During non-sensory delay periods, MGB ensembles developed coherent neuronal representation as well as distinct co-activity network states reflecting predicted task outcome. These results demonstrate flexible cross-modal ensemble coding in auditory thalamus during adaptive learning and highlight its importance in brain-wide cross-modal computations during complex behavior.

The neural mechanisms of novelty detection, especially in relation to behavior, are currently poorly understood. Here, we present a protocol for recording neuronal activity in macaque auditory cortex during novelty detection tasks. We describe steps for behavioral training, surgical headpost implantation, MRI-based electrode targeting, and electrophysiological recording. These steps allow direct assessment of the correlation between novelty detection behavior and neuronal activity. For complete details on the use and execution of this protocol, please refer to Gong et al.1.

Background Prepulse inhibition (PPI) is a phenomenon where a weak prepulse stimulus inhibits the startle reflex to a subsequent stronger stimulus, which can be induced by various sensory stimulus modalities such as visual, tactile, and auditory stimuli. Methods This study investigates the neural mechanisms underlying auditory PPI by focusing on the deep layers of the superior colliculus (deepSC) and the inferior colliculus (IC) in rats. Nineteen male Sprague-Dawley rats were implanted with electrodes in the left deepSC and the right IC, and electrophysiological recordings were conducted under anesthesia to observe the frequency following responses (FFRs) to startle stimuli with and without prepulse stimuli. Results Our results showed that in the deepSC, narrowband noise as a prepulse stimulus significantly inhibited the envelope component of the startle response, while the fine structure component remained unaffected. However, this inhibitory effect was not observed in the IC or when the prepulse stimulus was a gap. Conclusion These findings suggest that the deepSC plays a crucial role in the neural circuitry of PPI, particularly in the modulation of the envelope component of the startle response. The differential effects of narrowband noise and gap as prepulse stimuli also indicate distinct neural pathways for sound-induced PPI and Gap-PPI. Understanding these mechanisms could provide insights into sensory processing and potential therapeutic targets for disorders involving impaired PPI, such as tinnitus.

Background Plasticity from auditory experience shapes the brain’s encoding and perception of sound. Though prior research demonstrates that neural entrainment (i.e., brain-to-acoustic synchronization) aids speech perception, how long- and short-term plasticity influence entrainment to concurrent speech has not been investigated. Here, we explored neural entrainment mechanisms and the interplay between short- and long-term neuroplasticity for rapid auditory perceptual learning of concurrent speech sounds in young, normal-hearing musicians and nonmusicians. Method Participants learned to identify double-vowel mixtures during ∼45 min training sessions with concurrent high-density EEG recordings. We examined the degree to which brain responses entrained to the speech-stimulus train (∼9 Hz) to investigate whether entrainment to speech prior to behavioral decision predicted task performance. Source and directed functional connectivity analyses of the EEG probed whether behavior was driven by group differences auditory-motor coupling. Results Both musicians and nonmusicians showed rapid perceptual learning in accuracy with training. Interestingly, listeners’ neural entrainment strength prior to target speech mixtures predicted behavioral identification performance; stronger neural synchronization was observed preceding incorrect compared to correct trial responses. We also found stark hemispheric biases in auditory-motor coupling during speech entrainment, with greater auditory-motor connectivity in the right compared to left hemisphere for musicians (R>L) but not in nonmusicians (R=L). Conclusions Our findings confirm stronger neuroacoustic synchronization and auditory-motor coupling during speech processing in musicians. Stronger neural entrainment to rapid stimulus trains preceding incorrect behavioral responses supports the notion that alpha-band (∼10 Hz) arousal/suppression in brain activity is an important modulator of trial-by-trial success in perceptual processing.

Neuronal responses during behavior are diverse, ranging from highly reliable ‘classical’ responses to irregular ‘non-classically responsive’ firing. While a continuum of response properties is observed across neural systems, little is known about the synaptic origins and contributions of diverse responses to network function, perception, and behavior. To capture the heterogeneous responses measured from auditory cortex of rodents performing a frequency recognition task, we use a novel task-performing spiking recurrent neural network incorporating spike-timing-dependent plasticity. Reliable and irregular units contribute differentially to task performance via output and recurrent connections, respectively. Excitatory plasticity shifts the response distribution while inhibition constrains its diversity. Together both improve task performance with full network engagement. The same local patterns of synaptic inputs predict spiking response properties of network units and auditory cortical neurons from in vivo whole-cell recordings during behavior. Thus, diverse neural responses contribute to network function and emerge from synaptic plasticity rules.

Many animals can extract useful information from the vocalizations of other species. Neuroimaging studies have evidenced areas sensitive to conspecific vocalizations in the cerebral cortex of primates, but how these areas process heterospecific vocalizations remains unclear. Using fMRI-guided electrophysiology, we recorded the spiking activity of individual neurons in the anterior temporal voice patches of two macaques while they listened to complex sounds including vocalizations from several species. In addition to cells selective for conspecific macaque vocalizations, we identified an unsuspected subpopulation of neurons with strong selectivity for human voice, not merely explained by spectral or temporal structure of the sounds. The auditory representational geometry implemented by these neurons was strongly related to that measured in the human voice areas with neuroimaging and only weakly to low-level acoustical structure. These findings provide new insights into the neural mechanisms involved in auditory expertise and the evolution of communication systems in primates.

Salicylate is commonly used to induce tinnitus in animals, but its underlying mechanism of action is still debated. We therefore tested its effects on the firing properties of neurons in the mouse inferior colliculus (IC). Salicylate induced a large decrease in the spontaneous activity and an increase of ∼20 dB SPL in the minimum threshold of single units. In response to sinusoidally modulated noise (SAM noise) single units showed both an increase in phase locking and improved rate coding. Mice also became better at detecting amplitude modulations, and a simple threshold model based on the IC population response could reproduce this improvement. The responses to dynamic random chords (DRCs) suggested that the improved AM encoding was due to a linearization of the cochlear output, resulting in larger contrasts during SAM noise. These effects of salicylate are not consistent with the presence of tinnitus, but should be taken into account when studying hyperacusis.

Animal psychophysics can generate rich behavioral datasets, often comprised of many 1000s of trials for an individual subject. Gradient-boosted models are a promising machine learning approach for analyzing such data, partly due to the tools that allow users to gain insight into how the model makes predictions. We trained ferrets to report a target word’s presence, timing, and lateralization within a stream of consecutively presented non-target words. To assess the animals’ ability to generalize across pitch, we manipulated the fundamental frequency (F0) of the speech stimuli across trials, and to assess the contribution of pitch to streaming, we roved the F0 from word token to token. We then implemented gradient-boosted regression and decision trees on the trial outcome and reaction time data to understand the behavioral factors behind the ferrets’ decision-making. We visualized model contributions by implementing SHAPs feature importance and partial dependency plots. While ferrets could accurately perform the task across all pitch-shifted conditions, our models reveal subtle effects of shifting F0 on performance, with within-trial pitch shifting elevating false alarms and extending reaction times. Our models identified a subset of non-target words that animals commonly false alarmed to. Follow-up analysis demonstrated that the spectrotemporal similarity of target and non-target words rather than similarity in duration or amplitude waveform was the strongest predictor of the likelihood of false alarming. Finally, we compared the results with those obtained with traditional mixed effects models, revealing equivalent or better performance for the gradient-boosted models over these approaches.

Hearing is an active process in which listeners must detect and identify sounds, segregate and discriminate stimulus features, and extract their behavioral relevance. Adaptive changes in sound detection can emerge rapidly, during sudden shifts in acoustic or environmental context, or more slowly as a result of practice. Although we know that context- and learning-dependent changes in the spectral and temporal sensitivity of auditory cortical neurons support many aspects of flexible listening, the contribution of subcortical auditory regions to this process is less understood. Here, we recorded single- and multi-unit activity from the central nucleus of the inferior colliculus (ICC) and the ventral subdivision of the medial geniculate nucleus (MGV) of Mongolian gerbils under two different behavioral contexts: as animals performed an amplitude modulation (AM) detection task and as they were passively exposed to AM sounds. Using a signal detection framework to estimate neurometric sensitivity, we found that neural thresholds in both regions improved during task performance, and this improvement was driven by changes in firing rate rather than phase locking. We also found that ICC and MGV neurometric thresholds improved and correlated with behavioral performance as animals learn to detect small AM depths during a multi-day perceptual training paradigm. Finally, we reveal that in the MGV, but not the ICC, context-dependent enhancements in AM sensitivity grow stronger during perceptual training, mirroring prior observations in the auditory cortex. Together, our results suggest that the auditory midbrain and thalamus contribute to flexible sound processing and perception over rapid and slow timescales. Significance statement What a listener hears depends on several factors, such as whether the listener is attentive or distracted, and whether the sound is meaningful or irrelevant. Practice can also shape hearing by improving the detection of particular sound features, as occurs during language or musical learning. Understanding how changes in sound perception are implemented in the brain is important for developing strategies to optimize healthy hearing, and for treating disorders in which these processes go awry. We report that neurons in auditory midbrain and thalamus exhibit rapid shifts in sound sensitivity that depend on the sound’s behavioral relevance, and slower improvements that emerge over several days of training. Our results suggest that subcortical areas make an important contribution to flexible hearing.

Introduction Subjective tinnitus, the perception of sound without an external acoustic source, is often subsequent to noise-induced hearing loss or ototoxic medications. The condition is believed to result from neuroplastic alterations in the auditory centers, characterized by heightened spontaneous neural activities and increased synchrony due to an imbalance between excitation and inhibition. However, the role of the thalamic reticular nucleus (TRN), a structure composed exclusively of GABAergic neurons involved in thalamocortical oscillations, in the pathogenesis of tinnitus remains largely unexplored. Methods We induced tinnitus in mice using sodium salicylate and assessed tinnitus-like behaviors using the Gap Pre-Pulse Inhibition of the Acoustic Startle (GPIAS) paradigm. We utilized combined viral tracing techniques to identify the neural circuitry involved and employed immunofluorescence and confocal imaging to determine cell types and activated neurons. Results Salicylate-treated mice exhibited tinnitus-like behaviors. Our tracing clearly delineated the inputs and outputs of the auditory-specific TRN. We discovered that chemogenetic activation of the auditory TRN significantly reduced the salicylate-evoked rise in c-Fos expression in the auditory cortex. Discussion This finding posits the TRN as a potential modulatory target for tinnitus treatment. Furthermore, the mapped sensory inputs to the auditory TRN suggest possibilities for employing optogenetic or sensory stimulations to manipulate thalamocortical activities. The precise mapping of the auditory TRN-mediated neural pathways offers a promising avenue for designing targeted interventions to alleviate tinnitus symptoms.

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. This study investigated the utility of pairing VNS with passive or active auditory rehabilitation in a rat model of noise-induced hearing loss. Although auditory rehabilitation helped rats improve their frequency discrimination, learn novel speech discrimination tasks, and achieve speech-in-noise performance similar to normal hearing controls, VNS did not enhance recovery of speech sound perception. These results highlight the limitations of VNS as an adjunctive therapy for hearing loss rehabilitation and suggest that optimal benefits from neuromodulation may require restored peripheral signaling.

Tinnitus is a disturbing condition defined as the occurrence of acoustic hallucinations with no actual sound. Although the mechanisms underlying tinnitus have been explored extensively, the pathophysiology of the disease is not completely understood. Moreover, genes and potential treatment targets related to auditory hallucinations remain unknown. In this study, we examined transcriptional-profile changes in the medial geniculate body after noise-induced tinnitus in rats by performing RNA sequencing and validated differentially expressed genes via quantitative polymerase chain reaction analysis. The rat model of tinnitus was established by analyzing startle behavior based on gap-pre-pulse inhibition of acoustic startles. We identified 87 differently expressed genes, of which 40 were upregulated and 47 were downregulated. Pathway-enrichment analysis revealed that the differentially enriched genes in the tinnitus group were associated with pathway terms, such as coronavirus disease COVID-19, neuroactive ligand-receptor interaction. Protein–protein-interaction networks were established, and two hub genes (Rpl7a and AC136661.1) were identified among the selected genes. Further studies focusing on targeting and modulating these genes are required for developing potential treatments for noise-induced tinnitus in patients.

Introduction The voice and hearing can be affected to different degrees by aging, which can cause communication difficulties for elderly people. Vocal production requires effective temporal auditory processing at central levels within the nervous system, which can be compromised by the aging process. Objective To analyze the correlation between voice and temporal auditory processing in older adults. Materials and Methods A total of 40 elderly people aged 60 years or older were subdivided into 2 groups according to the presence or absence of vocal symptoms measured by the Voice Symptom Scale. All of the participants were submitted to auditory temporal tests, vocal self-assessment, and acoustic and perceptual auditory analyses of voice. Results Most of the subjects assessed had decreased voice intensity and normal variability in terms of vocal quality. The performance was normal in the Pitch Pattern Sequence test and altered in the Random Gap Detection test. In the Masking Period Pattern test, the detection thresholds for the target signal were increased in the presence of masking in different temporal target signal positions. Only pitch differed between the two groups. There were differences between the genders regarding frequency, shimmer, the overall severity of the alteration, and roughness. There was a correlation regarding temporal resolution ability and the overall severity of the alteration and roughness of the voice. Conclusion There is a central auditory impairment in temporal resolution which is correlated with vocal alterations in the elderly.

Older adults with normal hearing or with age-related hearing loss face challenges when listening to speech in noisy environments. To better serve individuals with communication difficulties, precision diagnostics are needed to characterize individuals’ auditory perceptual and cognitive abilities beyond pure tone thresholds. These abilities can be heterogenous across individuals within the same population. The goal of the present study is to consider the suprathreshold variability and develop characteristic profiles for older adults with normal hearing (ONH) and with hearing loss (OHL). Auditory perceptual and cognitive abilities were tested on ONH ( n = 20) and OHL ( n = 20) on an abbreviated test battery using portable automated rapid testing. Using cluster analyses, three main profiles were revealed for each group, showing differences in auditory perceptual and cognitive abilities despite similar audiometric thresholds. Analysis of variance showed that ONH profiles differed in spatial release from masking, speech-in-babble testing, cognition, tone-in-noise, and binaural temporal processing abilities. The OHL profiles differed in spatial release from masking, speech-in-babble testing, cognition, and tolerance to background noise performance. Correlation analyses showed significant relationships between auditory and cognitive abilities in both groups. This study showed that auditory perceptual and cognitive deficits can be present to varying degrees in the presence of audiometrically normal hearing and among listeners with similar degrees of hearing loss. The results of this study inform the need for taking individual differences into consideration and developing targeted intervention options beyond pure tone thresholds and speech testing.

Tinnitus is a phantom auditory sensation often accompanied by hearing loss, cognitive impairments, and psychological disturbances in various populations. Dysfunction of KCNQ2 and KCNQ3 channels—voltage-dependent potassium ion channels—in the cochlear nucleus can cause tinnitus. Despite the recognized significance of KCNQ2 and KCNQ3 channels in the auditory cortex, their precise relationship and implications in the pathogenesis of tinnitus remain areas of scientific inquiry. This study aimed to elucidate the pathological roles of KCNQ2 and KCNQ3 channels within the auditory cortex in tinnitus development and examine the therapeutic potential of mid-infrared photons for tinnitus treatment. We utilized a noise-induced tinnitus model combined with immunofluorescence, electrophysiological recording, and molecular dynamic simulation to investigate the morphological and physiological alterations after inducing tinnitus. Moreover, in vivo irradiation was administered to verify the treatment effects of infrared photons. Tinnitus was verified by deficits of the gap ratio with similar prepulse inhibition ratio and auditory brainstem response threshold. We observed an important enhancement in neuronal excitability in the auditory cortex using patch-clamp recordings, which correlated with KCNQ2 and KCNQ3 channel dysfunction. After irradiation with infrared photons, excitatory neuron firing was inhibited owing to increased KCNQ2 current resulting from structural alterations in the filter region. Meanwhile, deficits of the acoustic startle response in tinnitus animals were alleviated by infrared photons. Furthermore, infrared photons reversed the abnormal hyperexcitability of excitatory neurons in the tinnitus group. This study provided a novel method for modulating neuron excitability in the auditory cortex using KCNQ2 channels through a nonthermal effect. Infrared photons effectively mitigated tinnitus-related behaviors by suppressing abnormal neural excitability, potentially laying the groundwork for innovative therapeutic approaches for tinnitus treatment.

We often exert greater cognitive resources (i.e., listening effort) to understand speech under challenging acoustic conditions. This mechanism can be overwhelmed in those with hearing loss, resulting in cognitive fatigue in adults, and potentially impeding language acquisition in children. However, the neural mechanisms that support listening effort are uncertain. Evidence from human studies suggest that the cingulate cortex is engaged under difficult listening conditions, and may exert top-down modulation of the auditory cortex (AC). Here, we asked whether the gerbil cingulate cortex (Cg) sends anatomical projections to the AC that facilitate perceptual performance. To model challenging listening conditions, we used a sound discrimination task in which stimulus parameters were presented in either ‘Easy’ or ‘Hard’ blocks (i.e., long or short stimulus duration, respectively). Gerbils achieved statistically identical psychometric performance in Easy and Hard blocks. Anatomical tracing experiments revealed a strong, descending projection from layer 2/3 of the Cg1 subregion of the cingulate cortex to superficial and deep layers of primary and dorsal AC. To determine whether Cg improves task performance under challenging conditions, we bilaterally infused muscimol to inactivate Cg1, and found that psychometric thresholds were degraded for only Hard blocks. To test whether the Cg-to-AC projection facilitates task performance, we chemogenetically inactivated these inputs and found that performance was only degraded during Hard blocks. Taken together, the results reveal a descending cortical pathway that facilitates perceptual performance during challenging listening conditions. Significance Statement Sensory perception often occurs under challenging conditions, such a noisy background or dim environment, yet stimulus sensitivity can remain unaffected. One hypothesis is that cognitive resources are recruited to the task, thereby facilitating perceptual performance. Here, we identify a top-down cortical circuit, from cingulate to auditory cortex in the gerbils, that supports auditory perceptual performance under challenging listening conditions. This pathway is a plausible circuit that supports effortful listening, and may be degraded by hearing loss.

The relative importance or saliency of sensory inputs depend on the animal’s environmental context and the behavioural responses to these same inputs can vary over time. Here we show how freely moving rats, trained to discriminate between deviant tones embedded in a regular pattern of repeating stimuli and different variations of the classic oddball paradigm, can detect deviant tones, and this discriminability resembles the properties that are typical of neuronal adaptation described in previous studies. Moreover, the auditory brainstem response (ABR) latency decreases after training, a finding consistent with the notion that animals develop a type of plasticity to auditory stimuli. Our study suggests the existence of a form of long-term memory that may modulate the level of neuronal adaptation according to its behavioural relevance, and sets the ground for future experiments that will help to disentangle the functional mechanisms that govern behavioural habituation and its relation to neuronal adaptation.

Background: Commonly encountered nontraumatic, moderate noise is increasingly implicated in anxiety; however, the neural substrates underlying this process remain unclear. Objectives: We investigated the neural circuit mechanism through which chronic exposure to moderate-level noise causes anxiety-like behaviors. Methods: Mice were exposed to chronic, moderate white noise [85 decibel (dB) sound pressure level (SPL)], 4 h/d for 4 wk to induce anxiety-like behaviors, which were assessed by open field, elevated plus maze, light-dark box, and social interaction tests. Viral tracing, immunofluorescence confocal imaging, and brain slice patch-clamp recordings were used to characterize projections from auditory brain regions to the lateral amygdala. Neuronal activities were characterized by in vivo multielectrode and fiber photometry recordings in awake mice. Optogenetics and chemogenetics were used to manipulate specific neural circuitry. Results: Mice chronically (4 wk) exposed to moderate noise (85 dB SPL, 4 h/d) demonstrated greater neuronal activity in the lateral amygdala (LA), and the LA played a critical role in noise-induced anxiety-like behavior in these model mice. Viral tracing showed that the LA received monosynaptic projections from the medial geniculate body (MG) and auditory cortex (ACx). Optogenetic excitation of the MG→LA or ACx→LA circuits acutely evoked anxiety-like behaviors, whereas their chemogenetic inactivation abolished noise-induced anxiety-like behavior. Moreover, mice chronically exposed to moderate noise were more susceptible to acute stress, with more neuronal firing in the LA, even after noise withdrawal. Discussion: Mice exposed to 4 wk of moderate noise (85 dB SPL, 4 h/d) demonstrated behavioral and physiological differences compared to controls. The neural circuit mechanisms involved greater excitation from glutamatergic neurons of the MG and ACx to LA neurons under chronic, moderate noise exposure, which ultimately promoted anxiety-like behaviors. Our findings support the hypothesis that nontraumatic noise pollution is a potentially serious but unrecognized public health concern. https://doi.org/10.1289/EHP12532.

Human language follows statistical regularities or linguistic laws. For instance, Zipf's law of brevity states that the more frequently a word is used, the shorter it tends to be. All human languages adhere to this word structure. However, it is unclear whether Zipf's law emerged de novo in humans or whether it also exists in the non-linguistic vocal systems of our primate ancestors. Using a vocal conditioning paradigm, we examined the capacity of marmoset monkeys to efficiently encode vocalizations. We observed that marmosets adopted vocal compression strategies at three levels: (i) increasing call rate, (ii) decreasing call duration and (iii) increasing the proportion of short calls. Our results demonstrate that marmosets, when able to freely choose what to vocalize, exhibit vocal statistical regularities consistent with Zipf's law of brevity that go beyond their context-specific natural vocal behaviour. This suggests that linguistic laws emerged in non-linguistic vocal systems in the primate lineage.