The auditory steady-state response (ASSR) is a cortical oscillation induced by trains of 40 Hz acoustic stimuli. While the ASSR has been widely used in clinic measurement, the underlying neural mechanism remains poorly understood. In this study, we investigated the contribution of different stages of auditory thalamocortical pathway-medial geniculate body (MGB), thalamic reticular nucleus (TRN), and auditory cortex (AC)-to the generation and regulation of 40 Hz ASSR in C57BL/6 mice of both sexes. We found that the neural response synchronizing to 40 Hz sound stimuli was most prominent in the GABAergic neurons in the granular layer of AC and the ventral division of MGB (MGBv), which were regulated by optogenetic manipulation of TRN neurons. Behavioral experiments confirmed that disrupting TRN activity has a detrimental effect on the ability of mice to discriminate 40 Hz sounds. These findings revealed a thalamocortical mechanism helpful to interpret the results of clinical ASSR examinations.Significance Statement Our study contributes to clarifying the thalamocortical mechanisms underlying the generation and regulation of the auditory steady-state response (ASSR), which is commonly used in both clinical and neuroscience research to assess the integrity of auditory function. Combining a series of electrophysiological and optogenetic experiments, we demonstrate that the generation of cortical ASSR is dependent on the lemniscal thalamocortical projections originating from the ventral division of medial geniculate body to the GABAergic interneurons in the granule layer of the auditory cortex. Furthermore, the thalamocortical process for ASSR is strictly regulated by the activity of thalamic reticular nucleus (TRN) neurons. Behavioral experiments confirmed that dysfunction of TRN would cause a disruption of mice\'s behavioral performance in the auditory discrimination task.

As the human auditory system is highly malleable in infancy, perinatal risk factors, such as preterm birth, may affect auditory development. In comparison to healthy full-term infants, preterm infants show abnormal auditory brain responses at term age, which may have long-term detrimental outcomes. To achieve an optimal neonatal care environment for preterm-born infants, many early interventions have been developed. Musical interventions developed for neonatal intensive care units (NICUs) have shown beneficial effects on vital functions and weight gain of preterm infants and might also influence basic auditory processing and thereby enhance outcomes. In the present study, we tested the effect of parental singing during kangaroo care on auditory processing of standardized audio stimuli. Preterm infants (born between 24 and 32 weeks of gestation) were randomized to singing intervention (n = 13) or control (n = 8) groups. The auditory processing was tested using two audio paradigms assessed with magnetoencephalography (MEG) at term corresponding age. To verify that the paradigms elicit responses in MEG, we studied 12 healthy full-term infants. In the singing intervention group, parents were instructed by a music therapist twice a week for 4 weeks to sing or hum during kangaroo care in an infant-directed way. The control group received standard kangaroo care. The results show that the infants in the singing intervention group show larger neural responses than those in the control group when controlling for the total amount of singing during kangaroo care. Our findings suggest that incorporating singing into kangaroo care may be beneficial for preterm infants, but the effect may not be due to exposure to singing but instead positive parenting, improved parental self-esteem and improved caregiver sensitivity.

Patients with schizophrenia exhibit impaired performance in tone-matching or voice discrimination tests. However, there is no animal model recapitulating these pathophysiological traits. Here, we tested the representation of auditory recognition deficits in an animal model of schizophrenia. We established a rat model for schizophrenia using a perinatal challenge of epidermal growth factor (EGF), exposed adult rats to 55 kHz sine tones, rat calls (50-60 kHz), or reversely played calls, analyzed electrocorticography (ECoG) of the auditory and frontal cortices. Grand averages of event-related responses (ERPs) in the auditory cortex showed between-group size differences in the P1 component, whereas the P2 component differed among sound stimulus types. In EGF model rats, gamma band amplitudes were decreased in the auditory cortex and were enhanced in the frontal cortex with sine stimulus. The model rats also exhibited a reduction in rat call-triggered intercortical phase synchrony in the beta range. Risperidone administration restored normal phase synchrony. These findings suggest that perinatal exposure to the cytokine impairs tone/call recognition processes in these neocortices. In conjunction with previous studies using this model, our findings indicate that perturbations in ErbB/EGF signaling during development exert a multiscale impact on auditory functions at the cellular, circuit, and cognitive levels.

Preterm birth carries a risk for adverse neurodevelopment. Cognitive dysfunctions, such as language disorders may manifest as atypical sound discrimination already in early infancy. As infant-directed singing has been shown to enhance language acquisition in infants, we examined whether parental singing during skin-to-skin care (kangaroo care) improves speech sound discrimination in preterm infants. Forty-five preterm infants born between 26 and 33 gestational weeks (GW) and their parents participated in this cluster-randomized controlled trial (ClinicalTrials ID IRB00003181SK). In both groups, parents conducted kangaroo care during 33-40 GW. In the singing intervention group (n = 24), a certified music therapist guided parents to sing or hum during daily kangaroo care. In the control group (n = 21), parents conducted standard kangaroo care and were not instructed to use their voices. Parents in both groups reported the duration of daily intervention. Auditory event-related potentials were recorded with electroencephalogram at term age using a multi-feature paradigm consisting of phonetic and emotional speech sound changes and a one-deviant oddball paradigm with pure tones. In the multi-feature paradigm, prominent mismatch responses (MMR) were elicited to the emotional sounds and many of the phonetic deviants in the singing intervention group and in the control group to some of the emotional and phonetic deviants. A group difference was found as the MMRs were larger in the singing intervention group, mainly due to larger MMRs being elicited to the emotional sounds, especially in females. The overall duration of the singing intervention (range 15-63 days) was positively associated with the MMR amplitudes for both phonetic and emotional stimuli in both sexes, unlike the daily singing time (range 8-120 min/day). In the oddball paradigm, MMRs for the non-speech sounds were elicited in both groups and no group differences nor connections between the singing time and the response amplitudes were found. These results imply that repeated parental singing during kangaroo care improved auditory discrimination of phonetic and emotional speech sounds in preterm infants at term age. Regular singing routines can be recommended for parents to promote the development of the auditory system and auditory processing of speech sounds in preterm infants.

Autism spectrum disorder (ASD) is increasingly common with 1 in 59 children in the United States currently meeting the diagnostic criteria. Altered sensory processing is typical in ASD, with auditory sensitivities being especially common; in particular, people with ASD frequently show heightened sensitivity to environmental sounds and a poor ability to tolerate loud sounds. These sensitivities may contribute to impairments in language comprehension and to a worsened ability to distinguish relevant sounds from background noise. Event-related potential tests have found that individuals with ASD show altered cortical activity to both simple and speech-like sounds, which likely contribute to the observed processing impairments. Our goal in this review is to provide a description of ASD-related changes to the auditory system and how those changes contribute to the impairments seen in sound discrimination, sound-in-noise performance, and language processing. In particular, we emphasize how differences in the degree of cortical activation and in temporal processing may contribute to errors in sound discrimination.

To learn speech-sound categories, infants must identify the acoustic dimensions that differentiate categories and selectively attend to them as opposed to irrelevant dimensions. Variability on irrelevant acoustic dimensions can aid formation of robust categories in infants through adults in tasks such as word learning (e.g., Rost and McMurray, 2009) or speech-sound learning (e.g., Lively et al., 1993). At the same time, variability sometimes overwhelms learners, interfering with learning and processing. Two prior studies (Kuhl & Miller, 1982; Jusczyk, Pisoni, & Mullennix, 1992) found that irrelevant variability sometimes impaired early sound discrimination. We asked whether variability would impair or facilitate discrimination for older infants, comparing 7.5-month-old infants\' discrimination of an early acquired native contrast, /p/ vs. /b/ (in the word forms /pIm/ vs. /bIm/), in Experiment 1, with an acoustically subtle, non-native contrast, /n/ vs. /ŋ/ (in /nIm/ vs. /ŋIm/), in Experiment 2. Words were spoken by one or four talkers. Infants discriminated the native but not the non-native contrast, and there were no significant effects of talker condition. We discuss implications for theories of phonological learning and avenues for future research.

Previous neuroimaging studies have shown that sounds can be discriminated due to living-related or man-made-related characteristics and involve different brain regions. However, these studies have mainly provided source space analyses, which offer simple maps of activated brain regions but do not explain how regions of a distributed system are functionally organized under a specific task. In the present study, we aimed to further examine the functional connectivity of the auditory processing pathway across different categories of non-speech sounds in healthy adults, by means of MEG. Our analyses demonstrated significant activation and interconnection differences between living and man-made object sounds, in the prefrontal areas, anterior-superior temporal gyrus (aSTG), posterior cingulate cortex (PCC), and supramarginal gyrus (SMG), occurring within 80-120 ms post-stimulus interval. Current findings replicated previous ones, in that other regions beyond the auditory cortex are involved during auditory processing. According to the functional connectivity analysis, differential brain networks across the categories exist, which proposes that sound category discrimination processing relies on distinct cortical networks, a notion that has been strongly argued in the literature also in relation to the visual system.

Discriminating biologically relevant sounds is crucial for survival. The neurophysiological mechanisms that mediate this process must register both the reward significance and the physical parameters of acoustic stimuli. Previous experiments have revealed that the primary function of the auditory cortex (AC) is to provide a neural representation of the acoustic parameters of sound stimuli. However, how the brain associates acoustic signals with reward remains unresolved. The amygdala (AMY) and medial prefrontal cortex (mPFC) play keys role in emotion and learning, but it is unknown whether AMY and mPFC neurons are involved in sound discrimination or how the roles of AMY and mPFC neurons differ from those of AC neurons. To examine this, we recorded neural activity in the primary auditory cortex (A1), AMY, and mPFC of cats while they performed a Go/No-go task to discriminate sounds with different temporal patterns. We found that the activity of A1 neurons faithfully coded the temporal patterns of sound stimuli; this activity was not affected by the cats\' behavioral choices. The neural representation of stimulus patterns decreased in the AMY, but the neural activity increased when the cats were preparing to discriminate the sound stimuli and waiting for reward. Neural activity in the mPFC did not represent sound patterns, but it showed a clear association with reward and was modulated by the cats\' behavioral choices. Our results indicate that the initial auditory representation in A1 is gradually transformed into a stimulus-reward association in the AMY and mPFC to ultimately generate a behavioral choice. NEW & NOTEWORTHY We compared the characteristics of neural activities of primary auditory cortex (A1), amygdala (AMY), and medial prefrontal cortex (mPFC) while cats were performing the same auditory discrimination task. Our results show that there is a gradual transformation of the neural code from a faithful temporal representation of the stimulus in A1, which is insensitive to behavioral choices, to an association with the predictive reward in AMY and mPFC, which, to some extent, is correlated with the animal\'s behavioral choice.

When complex sounds are reversed in time, the original and reversed versions are perceived differently in spectral and temporal dimensions despite their identical duration and long-term spectrum-power profiles. Spatiotemporal activation patterns evoked by temporally asymmetric sound pairs demonstrate how the temporal envelope determines the readout of the spectrum. We examined the patterns of activation evoked by a temporally asymmetric sound pair in the primary auditory field (AI) of anesthetized guinea pigs and determined how discrimination training modified these patterns. Optical imaging using a voltage-sensitive dye revealed that a forward ramped-down natural sound (F) consistently evoked much stronger responses than its time-reversed, ramped-up counterpart (revF). The spatiotemporal maximum peak (maxP) of F-evoked activation was always greater than that of revF-evoked activation, and these maxPs were significantly separated within the AI. Although discrimination training did not affect the absolute magnitude of these maxPs, the revF-to-F ratio of the activation peaks calculated at the location where hemispheres were maximally activated (i.e., F-evoked maxP) was significantly smaller in the trained group. The F-evoked activation propagated across the AI along the temporal axis to the ventroanterior belt field (VA), with the local activation peak within the VA being significantly larger in the trained than in the naïve group. These results suggest that the innate network is more responsive to natural sounds of ramped-down envelopes than their time-reversed, unnatural sounds. The VA belt field activation might play an important role in emotional learning of sounds through its connections with amygdala.

OBJECTIVE: Mismatch negativity (MMN), a component of the auditory event-related potential (ERP) in response to auditory-expectancy violation, is sensitive to central auditory processing deficits associated with several clinical conditions and to auditory skills deriving from musical expertise. This sensitivity is more evident for stimuli integrated in complex sound contexts. This study tested whether increasing magnitudes of deviation (levels) entail increasing MMN amplitude (or decreasing latency), aiming to create a balanced version of the musical multi-feature paradigm towards measurement of extensive auditory discrimination profiles in auditory expertise or deficits.
METHODS: Using electroencephalography, we measured MMNs in healthy young adults to six types of sound feature change (pitch, timbre, location, intensity, slide and rhythm) at three different magnitudes of deviation, embedded in a music-sounding context. We also behaviourally assessed the individual musical aptitude using the Musical Ear Test (MET).
RESULTS: 16 of 18 sound feature changes elicited significant MMNs. For pitch, intensity, location, and slide, the MMN amplitude increased with increasing magnitude of feature change. We observed a ceiling effect for rhythm, and a floor effect for timbre. The slide MMN amplitude correlated positively with MET melody score and negatively with MET rhythm score.
CONCLUSIONS: This novel paradigm provides an extensive, objective measure of auditory discrimination profile for different sound features embedded in a complex sound context.
CONCLUSIONS: The paradigm can be adopted to study the neurophysiology of individuals with music processing difficulties or with special musical skills, and may be a useful tool for investigating development, plasticity, and deficits of auditory processing.