Auditory Research publications

Cochlear hair cells (HCs) sense sound waves and allow us to hear. Loss of HCs will cause irreversible sensorineural hearing loss. It is well known that DNA damage repair plays a critical role in protecting cells in many organs. However, how HCs respond to DNA damage and how defective DNA damage repair contributes to hearing loss remain elusive. In this study, we showed that cisplatin induced DNA damage in outer hair cells (OHCs) and promoted OHC loss, leading to hearing loss in mice of either sex. Cisplatin induced the expression of Brca1, a DNA damage repair factor, in OHCs. Deficiency of Brca1 induced OHC and hearing loss, and further promoted cisplatin-induced DNA damage in OHCs, accelerating OHC loss. This study provides the first in vivo evidence demonstrating that cisplatin mainly induces DNA damage in OHCs and that BRCA1 promotes repair of DNA damage in OHCs and prevents hearing loss. Our findings not only demonstrate that DNA damage–inducing agent generates DNA damage in postmitotic HCs but also suggest that DNA repair factors, like BRCA1, protect postmitotic HCs from DNA damage–induced cell death and hearing loss.

Macrophages serve as the primary immune cell population and assume a pivotal role in the immune response within the damaged cochleae. Yet, the origin and role of macrophages in response to noise exposure remain controversial. Here, we take advantage of Ccr2RFP/+ Cx3cr1GFP/+ dual-reporter mice to identify the infiltrated and tissue-resident macrophages. After noise exposure, we reveal that activated resident macrophages change in morphology, increase in abundance, and migrate to the region of hair cells, leading to the loss of outer hair cells and the damage of ribbon synapses. Meanwhile, peripheral monocytes are not implicated in the noise-induced hair cell insults. These noise-induced activities of macrophages are abolished by inhibiting TLR4 signaling, resulting in alleviated insults of hair cells and partial recovery of hearing. Our findings indicate cochlear resident macrophages are pro-inflammatory and detrimental players in acoustic trauma and introduce a potential therapeutic target in noise-induced hearing loss.

We investigated how neural oscillations code the hierarchical nature of stress rhythms in speech and how stress processing varies with language experience. By measuring phase synchrony of multilevel EEG-acoustic tracking and intra-brain cross-frequency coupling, we show the encoding of stress involves different neural signatures (delta rhythms = stress foot rate; theta rhythms = syllable rate), is stronger for amplitude vs. duration stress cues, and induces nested delta-theta coherence mirroring the stress-syllable hierarchy in speech. Only native English, but not Mandarin, speakers exhibited enhanced neural entrainment at central stress (2 Hz) and syllable (4 Hz) rates intrinsic to natural English. English individuals with superior cortical-stress tracking capabilities also displayed stronger neural hierarchical coherence, highlighting a nuanced interplay between internal nesting of brain rhythms and external entrainment rooted in language-specific speech rhythms. Our cross-language findings reveal brain-speech synchronization is not purely a "bottom-up" but benefits from "top-down" processing from listeners' language-specific experience.

Cortical processing of auditory information can be affected by interspecies differences as well as brain states. Here we compare multifeature spectro-temporal receptive fields (STRFs) and associated input/output functions or nonlinearities (NLs) of neurons in primary auditory cortex (AC) of four mammalian species. Single-unit recordings were performed in awake animals (female squirrel monkeys, female, and male mice) and anesthetized animals (female squirrel monkeys, rats, and cats). Neuronal responses were modeled as consisting of two STRFs and their associated NLs. The NLs for the STRF with the highest information content show a broad distribution between linear and quadratic forms. In awake animals, we find a higher percentage of quadratic-like NLs as opposed to more linear NLs in anesthetized animals. Moderate sex differences of the shape of NLs were observed between male and female unanesthetized mice. This indicates that the core AC possesses a rich variety of potential computations, particularly in awake animals, suggesting that multiple computational algorithms are at play to enable the auditory system’s robust recognition of auditory events.

Some species have evolved the ability to use the sense of hearing to modify existing vocalizations, or even create new ones, which enlarges their repertoires and results in complex communication systems.1 This ability corresponds to various forms of vocal production learning that are all possessed by humans and independently displayed by distantly related vertebrates.1,2,3,4,5,6,7 Among mammals, a few species, including the Egyptian fruit bat,8,9,10 would possess such vocal production learning abilities.7 Yet the necessity of an intact auditory system for the development of the Egyptian fruit bat typical vocal repertoire has not been tested. Furthermore, a systematic causal examination of learned and innate aspects of the entire repertoire has never been performed in any vocal learner. Here we addressed these gaps by eliminating pups' sense of hearing at birth and assessing its effects on vocal production in adulthood. The deafening treatment enabled us to both causally test these bats' vocal learning ability and discern learned from innate aspects of their vocalizations. Leveraging wireless individual audio recordings from freely interacting adults, we show that a subset of the Egyptian fruit bat vocal repertoire necessitates auditory feedback. Intriguingly, these affected vocalizations belong to different acoustic groups in the vocal repertoire of males and females. These findings open the possibilities for targeted studies of the mammalian neural circuits that enable sexually dimorphic forms of vocal learning.

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.

Mammalian cochlea spiral ganglion neurons (SGNs) are crucial for sound transmission, they can be damaged by chemotherapy drug cisplatin and lead to irreversible sensorineural hearing loss (SNHL), while such damage can also render cochlear implants ineffective. However, the mechanisms underlying cisplatin‐induced SGNs damage and subsequent SNHL are still under debate and there is no currently effective clinical treatment. Here, this study demonstrates that ferroptosis is triggered in SGNs following exposure to cisplatin. Inhibiting ferroptosis protects against cisplatin‐induced SGNs damage and hearing loss, while inducing ferroptosis intensifies these effects. Furthermore, cisplatin prompts nuclear receptor coactivator 4 (NCOA4)‐mediated ferritinophagy in SGNs, while knocking down NCOA4 mitigates cisplatin‐induced ferroptosis and hearing loss. Notably, the upstream regulator of NCOA4 is identified and transcription factor forkhead box O1 (FOXO1) is shown to directly suppress NCOA4 expression in SGNs. The knocking down of FOXO1 amplifies NCOA4‐mediated ferritinophagy, increases ferroptosis and lipid peroxidation, while disrupting the interaction between FOXO1 and NCOA4 in NCOA4 knock out mice prevents the cisplatin‐induced SGN ferroptosis and hearing loss. Collectively, this study highlights the critical role of the FOXO1‐NCOA4 axis in regulating ferritinophagy and ferroptosis in cisplatin‐induced SGNs damage, offering promising therapeutic targets for SNHL mitigation.

Background: There exists an unfulfilled requirement for effective cochlear pharmacotherapy. Controlled local drug delivery could lead to effective bioavailability. The round window niche (RWN), a cavity in the middle ear, is connected to the cochlea via a membrane through which drug can diffuse. We are developing individualized drug-eluting RWN implants (RNIs). To test their effectiveness in guinea pigs, a commonly used model in cochlear pharmacology studies, it is first necessary to develop guinea pig RNIs (GP-RNI). Methods: Since guinea pigs do not have a RWN such as it is present in humans and to reduce the variables in in vivo studies, a one-size-fits-all GP-RNI model was designed using 12 data sets of Dunkin-Hartley guinea pigs. The model was 3D-printed using silicone. The accuracy and precision of printing, distribution of the sample ingredient dexamethasone (DEX), biocompatibility, bio-efficacy, implantability and drug release were tested in vitro. The GP-RNI efficacy was validated in cochlear implant-traumatized guinea pigs in vivo. Results: The 3D-printed GP-RNI was precise, accurate and fitted in all tested guinea pig RWNs. DEX was homogeneously included in the silicone. The GP-RNI containing 1% DEX was biocompatible, bio-effective and showed a two-phase and sustained DEX release in vitro, while it reduced fibrous tissue growth around the cochlear implant in vivo. Conclusions: We developed a GP-RNI that can be used for precise inner ear drug delivery in guinea pigs, providing a reliable platform for testing the RNI's safety and efficacy, with potential implications for future clinical translation.

The numerical sense of animals includes identifying the numerosity of a sequence of events that occur with specific intervals, e.g., notes in a call or bar of music. Across nervous systems, the temporal patterning of spikes can code these events, but how this information is decoded (counted) remains elusive. In the anuran auditory system, temporal information of this type is decoded in the midbrain, where “interval-counting” neurons spike only after at least a threshold number of sound pulses have occurred with specific timing. We show that this decoding process, i.e., interval counting, arises from integrating phasic, onset-type and offset inhibition with excitation that augments across successive intervals, possibly due to a progressive decrease in “shunting” effects of inhibition. Because these physiological properties are ubiquitous within and across central nervous systems, interval counting may be a general mechanism for decoding diverse information coded/encoded in temporal patterns of spikes, including “bursts,” and estimating elapsed time.

While soundscapes shape the structure and function of auditory systems over evolutionary timescales, there is limited information regarding the adaptation of wild fish populations to their natural acoustic environments. This is particularly relevant for freshwater ecosystems, which are extremely diverse and face escalating pressures from human activities and associated noise pollution. The Siamese fighting fish Betta splendens is one of the most important cultured species in the global ornamental fish market and is increasingly recognized as a model organism for genetics and behavioural studies. This air-breathing species (Anabantoidei ) , characterized by the presence of a suprabranchial labyrinth organ, is native to Southeast Asia and inhabits low flow freshwater ecosystems that are increasingly threatened due to habitat destruction and pollution. We characterized the underwater soundscape, along with various ecological parameters, across five marshland habitats of B. splendens , from lentic waterbodies to small canals near a lake in Chiang Rai province (Thailand). All habitats exhibited common traits of low dissolved oxygen and dense herbaceous vegetation. Soundscapes were relatively quiet with Sound Pressure Level (SPL) around 102-105 dB re 1 µPa and most spectral energy below 1000 Hz. Sound recordings captured diverse biological sounds, including potential fish vocalizations, but primarily insect sounds. Based on Auditory Evoked Potential (AEP) recordings, we identified sex-specific differences and a best hearing range within 100-400 Hz. This low-frequency tuning highlights the potential susceptibility of B. splendens to anthropogenic noise activities. This study provides first characterization of the auditory sensitivity and natural soundscape of B. splendens, establishing an important ground for future hearing research in this species. The information provided on the auditory sensory adaptation of B. splendens emphasizes the importance of preserving quiet soundscapes from lentic freshwater ecosystems.

Age‐related hearing loss (AHL) is the most common sensory disorder amongst the older population. Inflammaging is a ≈chronic low‐grade inflammation that worsens with age and is an early sign of AHL; however, the underlying mechanisms remain unclear. We used electrophysiological and genetic approaches to establish the importance of interleukin 6 (IL‐6)‐dependent inflammation in AHL. Elevated IL‐6 in the cochlea enhanced Ca v 1.3 calcium channel function in the inner hair cell (IHC) synapse in mice with AHL. IL‐6 upregulated the Ca v 1.3 channel via the Janus kinase‐mitogen activated kinase pathway, causing neurotransmitter excitotoxicity and synapse impairment; IL‐6 deficiency or the administration of a Ca v 1.3 channel blocker attenuated this age‐related damage, and rescued hearing loss. Thus, IL‐6‐dependent inflammaging upregulated the Ca v 1.3 channel in IHCs, contributing to AHL. Our findings could help the comprehensive understanding of inflammaging's effects on AHL, aiding in early intervention to protect against hearing decline.

Ribbon synapses of inner hair cells are uniquely designed for ultrafast and indefatigable neurotransmission of the sound. The molecular machinery ensuring the efficient, compensatory recycling of the synaptic vesicles, however, remains elusive. This study showed that hair cell knockout of murine Dmxl2 , whose human homolog is responsible for non-syndromic sensorineural hearing loss DFNA71, resulted in auditory synaptopathy by impairing synaptic endocytosis and recycling. The mutant mice in the C57BL/6J background of either sex had mild hearing loss with severely diminished wave-I amplitude of the auditory brainstem response. Membrane capacitance measurements of the inner hair cells revealed deficiency in sustained synaptic exocytosis and endocytic membrane retrieval. Consistent with the electrophysiological findings, 3D electron microscopy reconstruction showed reduced reserve pool of synaptic vesicles and endocytic compartments, while the membrane-proximal and ribbon-associated vesicles remain intact. Our results propose an important role of DMXL2 in hair cell endocytosis and recycling of the synaptic vesicles. Significance Statement The molecular basis underlying efficient recycling of the ribbon synaptic vesicles in cochlear hair cells remains elusive. In this study, investigation of a hair cell-specific knockout mouse for Dmxl2 identifies its import roles in endocytosis and recycling of the auditory synaptic vesicles. The mutant mice display auditory synaptopathy, a common feature for noise-induced hearing loss and age-related hearing loss. The inner hair cells show deficiency in sustained synaptic exocytosis and endocytic membrane retrieval with reduced reserve pool of synaptic vesicles and endocytic compartments. Our results provide new insights into the molecular machinery ensuring ultrafast and indefatigable neurotransmission of the sound.

Following up on our previous observation that early B cell factor (EBF) sites are enriched in open chromatin of the developing sensory epithelium of the mouse cochlea, we investigated the effect of deletion of Ebf1 on inner ear development. We used a Cre driver to delete Ebf1 at the otocyst stage before development of the cochlea. We examined the cochlea at postnatal day (P) 1 and found that the sensory epithelium had doubled in size but the length of the cochlear duct was unaffected. We also found that deletion of Ebf1 led to ectopic sensory patches in the Kölliker's organ. Innervation of the developing organ of Corti was disrupted with no obvious spiral bundles. The ectopic patches were also innervated. All the extra hair cells (HCs) within the sensory epithelium and Kölliker's organ contained mechanoelectrical transduction channels, as indicated by rapid uptake of FM1-43. The excessive numbers of HCs were still present in the adult Ebf1 conditional knockout (cKO) animal. The animals had significantly elevated auditory brainstem response thresholds, suggesting that this gene is essential for hearing development.

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 Methyltransferase-like 3 (METTL3), a component of the N6-methyladenosine (m6A) methyltransferase family, exhibits significant expression in HEI-OC1 cells and cochlear explants. Aminoglycoside antibiotics, known for their ototoxic potential, frequently induce irreversible auditory damage in hair cells, predominantly through oxidative stress mechanisms. However, the specific role of METTL3 in kanamycin-induced hair cell loss remains unclear. Objective This study aims to elucidate the mechanisms by which METTL3 contributes to kanamycin-induced ototoxicity. Methods and Results In vivo experiments demonstrated a notable reduction in METTL3 expression within cochlear explants following kanamycin administration, concomitant with the formation of stress granules (SGs). Similarly, a 24-hour kanamycin treatment led to decreased METTL3 expression and induced SG formation both in HEI-OC1 cells and neonatal cochlear explants, corroborating the in vivo observations. Lentivirus-mediated transfection was employed to overexpress and knockdown METTL3 in HEI-OC1 cells. Knockdown of METTL3 resulted in increased reactive oxygen species (ROS) levels and apoptosis induced by kanamycin, while concurrently reducing SG formation. Conversely, overexpression of METTL3 attenuated ROS generation, decreased apoptosis rates, and promoted SG formation induced by kanamycin. Therefore, METTL3-mediated SG formation presents a promising target for mitigating kanamycin-induced ROS generation and the rate of apoptosis. Conclusion This finding indicates that METTL3-mediated SG formation holds potential in mitigating kanamycin-induced impairments in cochlear hair cells by reducing ROS formation and apoptosis rates.

Auditory space has been conceptualized as a matrix of systematically arranged combinations of binaural disparity cues that arise in the superior olivary complex (SOC). The computational code for interaural time and intensity differences utilizes excitatory and inhibitory projections that converge in the inferior colliculus (IC). The challenge is to determine the neural circuits underlying this convergence and to model how the binaural cues encode location. It has been shown that midbrain neurons are largely excited by sound from the contralateral ear and inhibited by sound leading at the ipsilateral ear. In this context, ascending projections from the lateral superior olive (LSO) to the IC have been reported to be ipsilaterally glycinergic and contralaterally glutamatergic. This study used CBA/CaH mice (3–6 months old) and applied unilateral retrograde tracing techniques into the IC in conjunction with immunocytochemical methods with glycine and glutamate transporters (GlyT2 and vGLUT2, respectively) to analyze the projection patterns from the LSO to the IC. Glycinergic and glutamatergic neurons were spatially intermixed within the LSO, and both types projected to the IC. For GlyT2 and vGLUT2 neurons, the average percentage of ipsilaterally and contralaterally projecting cells was similar (ANOVA, p = 0.48 ). A roughly equal number of GlyT2 and vGLUT2 neurons did not project to the IC. The somatic size and shape of these neurons match the descriptions of LSO principal cells. A minor but distinct population of small (< 40 μm 2 ) neurons that labeled for GlyT2 did not project to the IC; these cells emerge as candidates for inhibitory local circuit neurons. Our findings indicate a symmetric and bilateral projection of glycine and glutamate neurons from the LSO to the IC. The differences between our results and those from previous studies suggest that species and habitat differences have a significant role in mechanisms of binaural processing and highlight the importance of research methods and comparative neuroscience. These data will be important for modeling how excitatory and inhibitory systems converge to create auditory space in the CBA/CaH mouse.

This study aimed to investigate the effects of the intravenous administration of lidocaine in the auditory cortex after the systemic administration of salicylate. Healthy male albino Hartley guinea pigs were divided into two groups. The control group received only lidocaine, whereas the experimental group received lidocaine after checking for the effects of salicylate. Extracellular recordings of spikes in the primary auditory cortex and dorsocaudal areas in healthy albino Hartley guinea pigs were continuously documented (pre- and post-lidocaine, pre- and post-salicylate, and post-salicylate after adding lidocaine to post-salicylate). We recorded 160 single units in the primary auditory cortex from five guinea pigs and 155 single units in the dorsocaudal area from another five guinea pigs to confirm the effects of lidocaine on untreated animals. No significant change was detected in either the threshold or Q 10dB value after lidocaine administration in the primary auditory cortex and dorsocaudal areas. Spontaneous firing activity significantly decreased after lidocaine administration in the primary auditory cortex and dorsocaudal areas. Next, we recorded 160 single units in the primary auditory cortex from five guinea pigs and 137 single units in the dorsocaudal area from another five guinea pigs to determine the effects of lidocaine on salicylate-treated animals. The threshold was significantly elevated after salicylate administration; however, no additional change was detected after adding lidocaine to the primary auditory cortex and dorsocaudal areas. Regarding the Q 10dB value, lidocaine negated the significant changes induced by salicylate in the primary auditory cortex and dorsocaudal areas. Moreover, lidocaine negated the significant changes in spontaneous firing activities induced by salicylate in the primary auditory cortex and dorsocaudal areas. In conclusion, changes in the Q 10dB value and spontaneous firing activities induced by salicylate administration are abolished by lidocaine administration, suggesting that these changes are related to the presence of tinnitus.

Demyelination is a common pathological feature in a wide range of diseases, characterized by the loss of myelin sheath and myelin-supporting oligodendrocytes. These losses lead to impaired axonal function, increased vulnerability of axons to damage, and result in significant brain atrophy and neuro-axonal degeneration. Multiple pathomolecular processes contribute to neuroinflammation, oligodendrocyte cell death, and progressive neuronal dysfunction. In this study, we use the cuprizone mouse model of demyelination to investigate long-term non-invasive gamma entrainment using sensory stimulation as a potential therapeutic intervention for promoting myelination and reducing neuroinflammation in male mice. Here, we show that multisensory gamma stimulation mitigates demyelination, promotes oligodendrogenesis, preserves functional integrity and synaptic plasticity, attenuates oligodendrocyte ferroptosis-induced cell death, and reduces brain inflammation. Thus, the protective effects of multisensory gamma stimulation on myelin and anti-neuroinflammatory properties support its potential as a therapeutic approach for demyelinating disorders.

Hearing loss is a major health concern in our society, affecting more than 400 million people worldwide. Among the causes, aminoglycoside therapy can result in permanent hearing loss in 40% to 60% of patients receiving treatment, and despite these high numbers, no drug for preventing or treating this type of hearing loss has yet been approved by the US Food and Drug Administration. We have previously conducted high-throughput screenings of bioactive compounds, using zebrafish as our discovery platform, and identified piplartine as a potential therapeutic molecule. In the present study, we expanded this work and characterized piplartine’s physicochemical and therapeutic properties. We showed that piplartine had a wide therapeutic window and neither induced nephrotoxicity in vivo in zebrafish nor interfered with aminoglycoside antibacterial activity. In addition, a fluorescence-based assay demonstrated that piplartine did not inhibit cytochrome C activity in microsomes. Coadministration of piplartine protected from kanamycin-induced hair cell loss in zebrafish and protected hearing function, outer hair cells, and presynaptic ribbons in a mouse model of kanamycin ototoxicity. Last, we investigated piplartine’s mechanism of action by phospho-omics, immunoblotting, immunohistochemistry, and molecular dynamics experiments. We found an up-regulation of AKT1 signaling in the cochleas of mice cotreated with piplartine. Piplartine treatment normalized kanamycin-induced up-regulation of TRPV1 expression and modulated the gating properties of this receptor. Because aminoglycoside entrance to the inner ear is, in part, mediated by TRPV1, these results suggested that by regulating TRPV1 expression, piplartine blocked aminoglycoside’s entrance, thereby preventing the long-term deleterious effects of aminoglycoside accumulation in the inner ear compartment.

Objectives: Individuals with Down syndrome (DS) have a higher incidence of hearing loss (HL) compared with their peers without developmental disabilities. Little is known about the associations between HL and functional hearing for individuals with DS. This study investigated two aspects of auditory functions, “what” (understanding the content of sound) and “where” (localizing the source of sound), in young adults with DS. Speech reception thresholds in quiet and in the presence of interferers provided insight into speech recognition, that is, the “what” aspect of auditory maturation. Insights into “where” aspect of auditory maturation were gained from evaluating speech reception thresholds in colocated versus separated conditions (quantifying spatial release from masking) as well as right versus left discrimination and sound location identification. Auditory functions in the “where” domain develop during earlier stages of cognitive development in contrast with the later developing “what” functions. We hypothesized that young adults with DS would exhibit stronger “where” than “what” auditory functioning, albeit with the potential impact of HL. Considering the importance of auditory working memory and receptive vocabulary for speech recognition, we hypothesized that better speech recognition in young adults with DS, in quiet and with speech interferers, would be associated with better auditory working memory ability and receptive vocabulary. Design: Nineteen young adults with DS (aged 19 to 24 years) participated in the study and completed assessments on pure-tone audiometry, right versus left discrimination, sound location identification, and speech recognition in quiet and with speech interferers that were colocated or spatially separated. Results were compared with published data from children and adults without DS and HL, tested using similar protocols and stimuli. Digit Span tests assessed auditory working memory. Receptive vocabulary was examined using the Peabody Picture Vocabulary Test Fifth Edition. Results: Seven participants (37%) had HL in at least 1 ear; 4 individuals had mild HL, and 3 had moderate HL or worse. Participants with mild or no HL had ≥75% correct at 5° separation on the discrimination task and sound localization root mean square errors (mean ± SD: 8.73° ± 2.63°) within the range of adults in the comparison group. Speech reception thresholds in young adults with DS were higher than all comparison groups. However, spatial release from masking did not differ between young adults with DS and comparison groups. Better (lower) speech reception thresholds were associated with better hearing and better auditory working memory ability. Receptive vocabulary did not predict speech recognition. Conclusions: In the absence of HL, young adults with DS exhibited higher accuracy during spatial hearing tasks as compared with speech recognition tasks. Thus, auditory processes associated with the “where” pathways appear to be a relative strength than those associated with “what” pathways in young adults with DS. Further, both HL and auditory working memory impairments contributed to difficulties in speech recognition in the presence of speech interferers. Future larger-sized samples are needed to replicate and extend our findings.