Psychoacoustics publications

The auditory system has exquisite temporal coding in the periphery which is transformed into a rate-based code in central auditory structures, like auditory cortex. However, the cortex is still able to synchronize, albeit at lower modulation rates, to acoustic fluctuations. The perceptual significance of this cortical synchronization is unknown. We estimated physiological synchronization limits of cortex (in humans with electroencephalography) and brainstem neurons (in chinchillas) to dynamic binaural cues using a novel system-identification technique, along with parallel perceptual measurements. We find that cortex can synchronize to dynamic binaural cues up to approximately 10 Hz, which aligns well with our measured limits of perceiving dynamic spatial information and utilizing dynamic binaural cues for spatial unmasking, i.e. measures of binaural sluggishness. We also find that the tracking limit for frequency modulation (FM) is similar to the limit for spatial tracking, demonstrating that this sluggish tracking is a more general perceptual limit that can be accounted for by cortical temporal integration limits.

Social learning (SL) through experience with conspecifics can facilitate the acquisition of many behaviors. Thus, when Mongolian gerbils are exposed to a demonstrator performing an auditory discrimination task, their subsequent task acquisition is facilitated, even in the absence of visual cues. Here, we show that transient inactivation of auditory cortex (AC) during exposure caused a significant delay in task acquisition during the subsequent practice phase, suggesting that AC activity is necessary for SL. Moreover, social exposure induced an improvement in AC neuron sensitivity to auditory task cues. The magnitude of neural change during exposure correlated with task acquisition during practice. In contrast, exposure to only auditory task cues led to poorer neurometric and behavioral outcomes. Finally, social information during exposure was encoded in the AC of observer animals. Together, our results suggest that auditory SL is supported by AC neuron plasticity occurring during social exposure and prior to behavioral performance.

Objectives This study investigated the effect of synchronized activation of automatic gain control (AGC) on sound-localization and speech-recognition performance in cochlear implant users who use a contralateral hearing aid (bimodal listeners). Bimodal listeners often have poor spatial-hearing abilities, which could be partly due to perturbed interaural spatial acoustic cues from the two devices, as these act independently and provide incongruent or mismatched information. Synchronized AGC activation may remove this perturbation and improve spatial hearing. Design Ten bimodal listeners were fitted with a bimodal prototype allowing real-time communication between hearing aid and CI. They were tested for their horizontal localization ability of brief (150 ms) noise bursts presented in the frontal hemisphere. To test for frequency- and level-specific effects, sounds were band-passed (broadband 0.25-6 kHz, high-pass 1.5-6 kHz, and low-pass 0.25-0.85 kHz) and presented at levels of 50 and 80 dBA (i.e., below and above AGC activation threshold). Speech-in-noise recognition was assessed for short sentences presented at 75 dBA with a noise-adaptive algorithm. Sentences were presented from the front, with the noise presented either from the front or at a horizontal angle of ±70 deg. The sound-localization and speech-recognition tests were performed both with independently acting and synchronized AGC settings. Results Localization bias (mean error [95% confidence interval lower, upper range]) varied with sound type: -46 [-53, -38], -31 [-37, -23] and -2 [-16, 10] deg for high-pass, broadband and low-pass sounds, respectively. AGC synchronization did not systematically affect bias (paired difference in mean error with independent and synchronized AGCs: 6 [-3, 20] deg). However, AGC synchronization did reduce sound-localization error variability for 80-dB broadband sounds by 15 [6, 26] deg from an error standard deviation of 67 [63, 77] to 52 [45, 59] deg for independent and synchronized AGCs, respectively (no systematic difference was found for 50-dB and the high-pass and low-pass sounds). Speech-in-noise thresholds differed for noise presented from the front (0.3 [-1.3, 1.1] dB), implanted side (0.6 [-1.3, 2.3] dB), and non-implanted side (-2.4 [-4.6, 0.1] dB), but synchronization did not have an effect in these conditions. However, spatial release from masking thresholds did improve with synchronization when the noise was presented at the hearing-aid side: -2.7 [-4.5, -0.6] dB. Conclusions AGC synchronization improved the localization of broadband sounds presented above the AGC activation threshold in bimodal listeners. This is in line with the hypothesis that bimodal interaural level differences can be preserved for loud broadband sounds through AGC synchronization. Synchronization did not compromise the listener’s speech perception abilities, despite the reduction of the level of speech when AGC kicks in. Moreover, spatial release from masking was enhanced, suggesting that improved spatial hearing benefits speech recognition in noise

Previous work has demonstrated that performance in an auditory selective attention task can be enhanced or impaired, depending on whether a task-irrelevant visual stimulus is temporally coherent with a target auditory stream or with a competing distractor. However, it remains unclear how audiovisual (AV) temporal coherence and auditory selective attention interact at the neurophysiological level. Here, we measured neural activity using EEG while human participants (men and women) performed an auditory selective attention task, detecting deviants in a target audio stream. The amplitude envelope of the two competing auditory streams changed independently, while the radius of a visual disk was manipulated to control the AV coherence. Analysis of the neural responses to the sound envelope demonstrated that auditory responses were enhanced largely independently of the attentional condition: both target and masker stream responses were enhanced when temporally coherent with the visual stimulus. In contrast, attention enhanced the event-related response evoked by the transient deviants, largely independently of AV coherence. These results provide evidence for dissociable neural signatures of bottom-up (coherence) and top-down (attention) effects in AV object formation. SIGNIFICANCE STATEMENT Temporal coherence between auditory stimuli and task-irrelevant visual stimuli can enhance behavioral performance in auditory selective attention tasks. However, how audiovisual temporal coherence and attention interact at the neural level has not been established. Here, we measured EEG during a behavioral task designed to independently manipulate audiovisual coherence and auditory selective attention. While some auditory features (sound envelope) could be coherent with visual stimuli, other features (timbre) were independent of visual stimuli. We find that audiovisual integration can be observed independently of attention for sound envelopes temporally coherent with visual stimuli, while the neural responses to unexpected timbre changes are most strongly modulated by attention. Our results provide evidence for dissociable neural mechanisms of bottom-up (coherence) and top-down (attention) effects on audiovisual object formation.

Tinnitus is an unpleasant symptom characterized by detective hearing without the actual sound input. Despite numerous studies elucidating a variety of pathomechanisms inducing tinnitus, the pathophysiology of tinnitus is not fully understood. The genes that are closely associated with this subtype of the auditory hallucination that could be utilized as potential treatment targets are still unknown. In this study, we explored the transcriptional profile changes of the auditory cortex after noise-induced tinnitus in rats using high throughput sequencing and verification of the detected genes using quantitative PCR (qPCR). Tinnitus models were established by analyzing startle behaviors through gap pre-pulse inhibition (PPI) of the acoustic startle. Two hundred and fifty-nine differential genes were identified, of which 162 genes were up-regulated and 97 genes were down-regulated. Analysis of the pathway enrichment indicated that the tinnitus group exhibited increased gene expression related to neurodegenerative disorders such as Huntington’s disease and Amyotrophic lateral sclerosis. Based on the identified genes, networks of protein–protein interaction were established and five hub genes were identified through degree rank, including Fos, Nr4a1, Nr4a3, Egr2, and Egr3. Therein, the Fos gene ranked first with the highest degree after noise exposure, and may be a potential target for the modulation of noise-induced tinnitus.

In an effort to help elucidate the neural mechanisms underlying tinnitus in humans, researchers have often relied on animal models; a preclinical approach which ultimately required that behavioral paradigms be designed to reliably screen animals for tinnitus. Previously, we developed a two-alternative forced-choice (2AFC) paradigm for rats that allowed for the simultaneous recording of neural activity at the very moments when they were reporting the presence/absence of tinnitus. Because we first validated our paradigm in rats experiencing transient tinnitus following a high-dose of sodium salicylate, the present study now sought to evaluate its utility to screen for tinnitus caused by intense sound exposure; a common tinnitus-inducer in humans. More specifically, through a series of experimental protocols, we aimed to (1) conduct sham experiments to ensure that the paradigm was able to correctly classify control rats as not having tinnitus, (2) confirm the time course over which the behavioral testing could reliably be performed post-exposure to assess chronic tinnitus, and (3) determine if the paradigm was sensitive to the variable outcomes often observed after intense sound exposure (e.g., hearing loss with our without tinnitus). Ultimately, in accordance with our predictions, the 2AFC paradigm was indeed resistant to false-positive screening of rats for intense sound-induced tinnitus, and it was able to reveal variable tinnitus and hearing loss profiles in individual rats following intense sound exposure. Taken together, the present study documents the utility of our appetitive operant conditioning paradigm to assess acute and chronic sound-induced tinnitus in rats. Finally, based on our findings, we discuss important experimental considerations that will help ensure that our paradigm is able to provide a suitable platform for future investigations into the neural basis of tinnitus.

Listeners use the spatial location or change in spatial location of coherent acoustic cues to aid in auditory object formation. From stimulus-evoked onset responses in normal-hearing listeners using electroencephalography (EEG), we have previously shown measurable tuning to stimuli changing location in quiet, revealing a potential window into the cortical representations of auditory scene analysis. These earlier studies used non-fluctuating, spectrally narrow stimuli, so it was still unknown whether previous observations would translate to speech stimuli, and whether responses would be preserved for stimuli in the presence of background maskers. To examine the effects that selective auditory attention and interferers have on object formation, we measured cortical responses to speech changing location in the free field with and without background babble (+6 dB SNR) during both passive and active conditions. Active conditions required listeners to respond to the onset of the speech stream when it occurred at a new location, explicitly indicating ‘yes’ or ‘no’ to whether the stimulus occurred at a block-specific location either 30 degrees to the left or right of midline. In the aggregate, results show similar evoked responses to speech stimuli changing location in quiet compared to babble background. However, the effect of the two background environments diverges somewhat when considering the magnitude and direction of the location change and where the subject was attending. In quiet, attention to the right hemifield appeared to evoke a stronger response than attention to the left hemifield when speech shifted in the rightward direction. No such difference was found in babble conditions. Therefore, consistent with challenges associated with cocktail party listening, directed spatial attention could be compromised in the presence of stimulus noise and likely leads to poorer use of spatial cues in auditory streaming.

Differences in the timing and intensity of sounds arriving at the two ears provide fundamental binaural cues that help us localize and segregate sounds in the environment. Neural encoding of these cues is commonly represented asymmetrically in the cortex with stronger activation in the hemisphere contralateral to the perceived spatial location. Although advancing age is known to degrade the perception of binaural cues, less is known about how the neural representation of such cues is impacted by age. Here, we use electroencephalography (EEG) to investigate age-related changes in the hemispheric distribution of interaural time difference (ITD) encoding based on cortical auditory evoked potentials (CAEPs) and derived binaural interaction component (BIC) measures in ten younger and ten older normal-hearing adults. Sensor-level analyses of the CAEP and BIC showed age-related differences in global field power, where older listeners had significantly larger responses than younger for both binaural metrics. Source-level analyses showed hemispheric differences in auditory cortex activity for left and right lateralized stimuli in younger adults, consistent with a contralateral activation model for processing ITDs. Older adults, however, showed reduced hemispheric asymmetry across ITDs, despite having overall larger responses than younger adults. Further, when averaged across ITD condition to evaluate changes in cortical asymmetry over time, there was a significant shift in laterality corresponding to the peak components (P1, N1, P2) in the source waveform that also was affected by age. These novel results demonstrate across-hemisphere cortical dynamics during binaural temporal processing that are altered with advancing age.

The process by which sensory evidence contributes to perceptual choices requires an understanding of its transformation into decision variables. Here, we address this issue by evaluating the neural representation of acoustic information in the auditory cortex-recipient parietal cortex, while gerbils either performed a two-alternative forced-choice auditory discrimination task or while they passively listened to identical acoustic stimuli. During task engagement, stimulus identity decoding performance from simultaneously recorded parietal neurons significantly correlated with psychometric sensitivity. In contrast, decoding performance during passive listening was significantly reduced. Principal component and geometric analyses revealed the emergence of low-dimensional encoding of linearly separable manifolds with respect to stimulus identity and decision, but only during task engagement. These findings confirm that the parietal cortex mediates a transition of acoustic representations into decision-related variables. Finally, using a clustering analysis, we identified three functionally distinct subpopulations of neurons that each encoded task-relevant information during separate temporal segments of a trial. Taken together, our findings demonstrate how parietal cortex neurons integrate and transform encoded auditory information to guide sound-driven perceptual decisions.

We hypothesized that auditory stimulation could reduce the progression of Alzheimer’s disease (AD), and that audiovisual stimulation could have additional effects through multisensory integration. We exposed 12 month old Apoetm1.1(APOE*4)Adiuj mice (a mouse model of sporadic AD) to auditory (A) or audiovisual stimulation (AV) at 40 Hz for 14 days in a soundproof chamber system (no stimulation, N). Behavioral tests were performed before and after each session, and their brain tissues were assessed for amyloid-beta expression and apoptotic cell death, after 14 days. Furthermore, brain levels of acetylcholine and apoptosis-related proteins were analyzed. In the Y-maze test, the percentage relative alternation was significantly higher in group A than in group N mice. Amyloid-beta and TUNEL positivity in the hippocampal CA3 region was significantly lower in group A and group AV mice than in group N mice (p < 0.05). Acetylcholine levels were significantly higher in group A and group AV mice than in group N mice (p < 0.05). Compared to group N mice, expression of the proapoptotic proteins Bax and caspase-3 was lower in group A, and expression of the antiapoptotic protein Bcl-2 was higher in group AV. In a mouse model of early-stage sporadic AD, auditory or audiovisual stimulation improved cognitive performance and neuropathology.

Hearing loss is a chronic health condition that affects millions of people worldwide. In addition to age-related hearing impairment, excessive noise exposure is a leading cause of hearing loss. Beyond the devastating effects of hearing impairment itself, epidemiological studies have identified hearing loss as a major risk factor for age-related cognitive decline, including dementia. At present, we currently lack a full understanding of the brain regions and underlying molecular changes that are responsible for mediating the link between hearing loss and cognitive impairment across aging. In the present study, we exposed 6-month-old rats to an occupational-like noise (100 dB SPL, 4 h/day × 30 days) or sham exposure and investigated both hippocampal-dependent (i.e., spatial learning and memory, assessed using the Morris water maze) and striatal-dependent (i.e., visuomotor associative learning, assessed using an operant-conditioning task) cognitive function across aging at 7, 10, and 13 months of age. We also investigated brain region-specific changes in microglial expression following noise/sham exposure in order to assess the potential contribution of this cell type to noise-induced cognitive impairments. Consistent with human studies, the occupational-like noise exposure resulted in high-frequency hearing loss, evidenced by a significant increase in hearing thresholds at 20 kHz. Ultimately, our results suggest that not all higher-level cognitive tasks or their associated brain regions appear to be equally susceptible to noise-induced deficits during aging, as the occupational-like noise exposure caused an age-dependent deficit in spatial but not visuomotor associative learning, as well as altered microglial expression in the hippocampus but not the striatum. Interestingly, we found no significant relationships between spatial learning ability and the level of hearing loss or altered microglial density in the hippocampus following noise exposure, suggesting that other changes in the brain likely contribute to hippocampal-dependent cognitive dysfunction following noise exposure. Lastly, we found that a subset of younger animals also showed noise-induced deficits in spatial learning; findings which suggest that noise exposure may represent an increased risk for cognitive impairment in vulnerable subjects. Overall, our findings highlight that even a mild occupational-like noise exposure earlier in adulthood can have long lasting implications for cognitive function later in life.

Animal research focused on chronic tinnitus associated with noise-induced hearing loss can be expensive and time-consuming as a result of the behavioral training required. Although there exist a number of behavioral tests for tinnitus; there have been few formal direct comparisons of these tests. Here, we evaluated animals in two different tinnitus assessment methods. CBA/CaJ mice were trained in an operant conditioning, active avoidance (AA) test, and a reflexive, gap-induced pre-pulse inhibition of acoustic startle (GPIAS) test, or both. Tinnitus was induced in awake mice by unilateral continuous sound exposure using a 2-kHz- or 1 2 octave-wide noise centered at 16 kHz and presented at 113- or 116-dB SPL. Tinnitus was assessed 8 weeks after sound overexposure. Most mice had evidence of tinnitus behavior in at least one of the two behaviors. Of the mice evaluated in AA, over half (55%) had tinnitus positive behavior. In GPIAS, fewer animals (13%) were positive than were identified using the AA test. Few mice were positive in both tests (10%), and only one was positive for tinnitus behavior at the same spectral frequency in both tests. When the association between tinnitus behavior and spontaneous activity recorded in the inferior colliculus was compared, animals with tinnitus behavior in AA exhibited increased spontaneous activity, while those positive in GPIAS did not. Thus, it appears that operant conditioning tests, like AA, maybe more reliable and accurate tests for tinnitus than reflexive tests.

The “cocktail party” problem—how a listener perceives speech in noisy environments—is typically studied using speech (multi-talker babble) or noise maskers. However, realistic cocktail party scenarios often include background music (e.g., coffee shops, concerts). Studies investigating music’s effects on concurrent speech perception have predominantly used highly controlled synthetic music or shaped noise, which do not reflect naturalistic listening environments. Behaviorally, familiar background music and songs with vocals/lyrics inhibit concurrent speech recognition. Here, we investigated the neural bases of these effects. While recording multichannel EEG, participants listened to an audiobook while popular songs (or silence) played in the background at a 0 dB signal-to-noise ratio. Songs were either familiar or unfamiliar to listeners and featured either vocals or isolated instrumentals from the original audio recordings. Comprehension questions probed task engagement. We used temporal response functions (TRFs) to isolate cortical tracking to the target speech envelope and analyzed neural responses around 100 ms (i.e., auditory N1 wave). We found that speech comprehension was, expectedly, impaired during background music compared to silence. Target speech tracking was further hindered by the presence of vocals. When masked by familiar music, response latencies to speech were less susceptible to informational masking, suggesting concurrent neural tracking of speech was easier during music known to the listener. These differential effects of music familiarity were further exacerbated in listeners with less musical ability. Our neuroimaging results and their dependence on listening skills are consistent with early attentional-gain mechanisms where familiar music is easier to tune out (listeners already know the song’s expectancies) and thus can allocate fewer attentional resources to the background music to better monitor concurrent speech material.

Voluntary stream segregation was investigated in cochlear implant (CI) users and normal-hearing (NH) listeners using a segregation-promoting objective approach which evaluated the role of spectral and amplitude-modulation (AM) rate separations on stream segregation and its build-up. Sequences of 9 or 3 pairs of A and B narrowband noise (NBN) bursts were presented which differed in either center frequency of the noise band, the AM-rate, or both. In some sequences (delayed sequences), the last B burst was delayed by 35 ms from their otherwise-steady temporal position. In the other sequences (no-delay sequences), the last B bursts were temporally advanced from 0 to 10 ms. A single interval yes/no procedure was utilized to measure participants’ sensitivity ( d ′ ) in identifying delayed vs. no-delay sequences. A higher d ′ value showed the higher ability to segregate the A and B subsequences. For NH listeners, performance improved with each spectral separation. However, for CI users, performance was only significantly better for the condition with the largest spectral separation. Additionally, performance was significantly poorer for the largest AM-rate separation than for the condition with no AM-rate separation for both groups. The significant effect of sequence duration in both groups indicated that listeners made more improvement with lengthening the duration of stimulus sequences, supporting the build-up effect. The results of this study suggest that CI users are less able than NH listeners to segregate NBN bursts into different auditory streams when they are moderately separated in the spectral domain. Contrary to our hypothesis, our results indicate that AM-rate separation may interfere with the segregation of streams of NBN. Additionally, our results add evidence to the literature that CI users build up stream segregation at a rate comparable to NH listeners, when the inter-stream spectral separations are adequately large.

Tinnitus is the phantom perception of sound that has no external source. A neurological signature of tinnitus, and the frequently associated hyperacusis, is an imbalance between excitatory and inhibitory activity in the central auditory system (CAS), leading to dysregulated network excitability. The large conductance, calcium-activated potassium (BK) channel is a key player in pre- and post-synaptic excitability through its mediation of K + currents. Changes in BK channel activity are associated with aberrant network activity in sensory regions of the CNS, raising the possibility that BK channel modulation could regulate activity associated with tinnitus and hyperacusis. To test whether BK channel openers are able to suppress biomarkers of drug-induced tinnitus and hyperacusis, the 1,3,4 oxadiazole BMS-191011 was given to young adult CBA mice that had been administered 250 mg/kg sodium salicylate (SS). Systemic treatment with BMS-191011 reduced behavioral manifestations of SS-induced tinnitus, but not hyperacusis, probed via the gap-in-noise startle response method. Systemic BMS-191011 treatment did not influence SS-induced increases in auditory brainstem response functions, but local application at the inferior colliculus did reverse SS-suppressed spontaneous activity, particularly in the frequency region of the tinnitus percept. Thus, action of BMS-191011 in the inferior colliculus may contribute to the reduction in behaviorally measured tinnitus. Together, these findings support the utility of BK channel openers in reducing central auditory processing changes associated with the formation of the tinnitus percept.

Maternal infections during pregnancy are linked with an increased risk for disorders like Autism Spectrum Disorder and schizophrenia in the offspring. Although precise mechanisms are still unclear, clinical and preclinical evidence suggest a strong role for maternal immune activation (MIA) in the neurodevelopmental disruptions caused by maternal infection. Previously, studies using the Polyinosinic:Polycytidylic (Poly I:C) MIA preclinical model showed that cytokines like Interleukin 6 (Il6) are important mediators of MIA's effects. In this study, we hypothesized that Il15 may similarly act as a mediator of Poly I:C MIA, given its role in the antiviral immune response. To test this hypothesis, we induced Poly I:C MIA at gestational day 9.5 in wildtype (WT) and Il15 -/- rat dams and tested their offspring in adolescence and adulthood. Poly I:C MIA and Il15 knockout produced both independent and synergistic effects on offspring behaviour. Poly I:C MIA decreased startle reactivity in adult WT offspring but resulted in increased adolescent anxiety and decreased adult locomotor activity in Il15 -/- offspring. In addition, Poly I:C MIA led to genotype-independent effects on locomotor activity and prepulse inhibition. Finally, we showed that Il15 -/- offspring exhibit distinct phenotypes that were unrelated to Poly I:C MIA including altered startle reactivity, locomotion and signal transduction in the auditory brainstem. Overall, our findings indicate that the lack of Il15 can leave offspring either more or less susceptible to Poly I:C MIA, depending on the phenotype in question. Future studies should examine the contribution of fetal versus maternal Il15 in MIA to determine the precise developmental mechanisms underlying these changes.

Elevated neural plasticity during development contributes to dramatic improvements in perceptual, motor, and cognitive skills. However, malleable neural circuits are vulnerable to environmental influences that may disrupt behavioral maturation. While these risks are well-established prior to sexual maturity (i.e., critical periods), the degree of neural vulnerability during adolescence remains uncertain. Here, we induce transient hearing loss (HL) spanning adolescence in gerbils, and ask whether behavioral and neural maturation are disrupted. We find that adolescent HL causes a significant perceptual deficit that can be attributed to degraded auditory cortex processing, as assessed with wireless single neuron recordings and within-session population-level analyses. Finally, auditory cortex brain slices from adolescent HL animals reveal synaptic deficits that are distinct from those typically observed after critical period deprivation. Taken together, these results show that diminished adolescent sensory experience can cause long-lasting behavioral deficits that originate, in part, from a dysfunctional cortical circuit.

Developmental dyslexia is a common neurodevelopmental disorder characterized by difficulties in reading and writing. Although underlying biological and genetic mechanisms remain unclear, anomalies in phonological processing and auditory processing have been associated with dyslexia. Several candidate risk genes have also been identified, with KIAA0319 as a main candidate. Animal models targeting the rodent homolog ( Kiaa0319 ) have been used to explore putative behavioral and anatomic anomalies, with mixed results. For example after downregulation of Kiaa0319 expression in rats via shRNA, significant adult rapid auditory processing impairments were reported, along with cortical anomalies reflecting atypical neuronal migration. Conversely, Kiaa0319 knockout (KO) mice were reported to have typical adult auditory processing, and no visible cortical anomalies. To address these inconsistencies, we tested Kiaa0319 KO mice on auditory processing tasks similar to those used previously in rat shRNA knockdown studies. Subsequent neuroanatomic analyses on these same mice targeted medial geniculate nucleus (MGN), a receptive communication‐related brain structure. Results confirm that Kiaa0319 KO mice exhibit significant auditory processing impairments specific to rapid/brief stimuli, and also show significant volumetric reductions and a shift toward fewer large and smaller neurons in the MGN. The latter finding is consistent with post mortem MGN data from human dyslexic brains. Combined evidence supports a role for KIAA0319 in the development of auditory CNS pathways subserving rapid auditory processing functions critical to the development of speech processing, language, and ultimately reading. Results affirm KIAA0319 variation as a possible risk factor for dyslexia specifically via anomalies in central acoustic processing pathways.

Background To localize sound sources accurately in a reverberant environment, human binaural hearing strongly favors analyzing the initial wave front of sounds. Behavioral studies of this “precedence effect” have so far largely been confined to human subjects, limiting the scope of complementary physiological approaches. Similarly, physiological studies have mostly looked at neural responses in the inferior colliculus, the main relay point between the inner ear and the auditory cortex, or used modeling of cochlear auditory transduction in an attempt to identify likely underlying mechanisms. Studies capable of providing a direct comparison of neural coding and behavioral measures of sound localization under the precedence effect are lacking. Results We adapted a “temporal weighting function” paradigm previously developed to quantify the precedence effect in human for use in laboratory rats. The animals learned to lateralize click trains in which each click in the train had a different interaural time difference. Computing the “perceptual weight” of each click in the train revealed a strong onset bias, very similar to that reported for humans. Follow-on electrocorticographic recording experiments revealed that onset weighting of interaural time differences is a robust feature of the cortical population response, but interestingly, it often fails to manifest at individual cortical recording sites. Conclusion While previous studies suggested that the precedence effect may be caused by early processing mechanisms in the cochlea or inhibitory circuitry in the brainstem and midbrain, our results indicate that the precedence effect is not fully developed at the level of individual recording sites in the auditory cortex, but robust and consistent precedence effects are observable only in the auditory cortex at the level of cortical population responses. This indicates that the precedence effect emerges at later cortical processing stages and is a significantly “higher order” feature than has hitherto been assumed.

Offset responses in auditory processing appear after a sound terminates. They arise in neuronal circuits within the peripheral auditory system, but their role in the central auditory system remains unknown. Here, we ask what the behavioral relevance of cortical offset responses is and what circuit mechanisms drive them. At the perceptual level, our results reveal that experimentally minimizing auditory cortical offset responses decreases the mouse performance to detect sound termination, assigning a behavioral role to offset responses. By combining in vivo electrophysiology in the auditory cortex and thalamus of awake mice, we also demonstrate that cortical offset responses are not only inherited from the periphery but also amplified and generated de novo. Finally, we show that offset responses code more than silence, including relevant changes in sound trajectories. Together, our results reveal the importance of cortical offset responses in encoding sound termination and detecting changes within temporally discontinuous sounds crucial for speech and vocalization.