Publications using TDT

Kölliker's organ is a transient developmental structure in the mouse cochlea that undergoes significant remodeling postnatally. Utilizing an epithelial-specific conditional deletion mouse model of Prdm16 (marker and regulator of Kölliker's organ), we show that Prdm16 is required for interdental cell development, and thereby the development of the limbal domain of the tectorial membrane and its medial anchorage to the spiral limbus. Additionally, we show that Kölliker's organ is involved in normal tectorial membrane collagen fibril development and maturation. Interestingly, mesenchymal cells of the spiral limbus underneath Prdm16 -deficient Kölliker's organ failed to produce interstitial matrix proteins, resulting in a hypoplastic and truncated spiral limbus, indicating a non-cell autonomous role of Prdm16 in regulating spiral mesenchymal matrix development. Single-cell RNA sequencing identified differentially expressed genes in Prdm16 -deficient Kölliker's organ suggesting a role for connective tissue growth factor (CTGF) downstream Prdm16 in epithelial-mesenchymal signaling involved in spiral limbus matrix deposition. Prdm16 -deficient mice showed a hearing deficit, as indicated by elevated auditory brainstem response thresholds at most frequencies, consistent with the cochlear structural defects. Both sexes were studied. This work establishes Prdm16 as a deafness gene in mice through its role in regulating Kölliker's organ development. Such understanding recognizes Kölliker's organ as a developmental hub regulating multiple surrounding cochlear structures.

Alport syndrome (AS) is a genetic disorder marked by mutations in type IV collagen, leading to kidney glomerular dysfunction. AS also involves the cochlea, causing late-onset progressive hearing loss. Currently, there are no therapeutic drugs to protect hearing from AS. HDAC inhibitors (HDACis) are chemical compounds that block the activity of histone deacetylase and are known to exert diverse biologic effects. We investigated the effect of Trichostatin A (TSA), an HDACi, to assess its potential to inhibit hearing deterioration in AS. Col4a3 knockout (KO) mice were treated with TSA at 3 weeks of age, and hearing levels were measured using auditory brainstem response (ABR). The results demonstrate that TSA significantly protects the hearing of KO mice compared to the untreated group. The TSA-treated group exhibited a reduction in the levels of oxidative stress markers 4-Hydroxynonenal and 3-Nitrotyrosine, along with a decrease in inflammatory cytokines, in both the mouse cochlea and in vitro HEI-OC1 (House Ear Institute-Organ of Corti 1) cell and HEK (Human Embryonic Kidney)293T cells. AS demonstrated a thickening in the stria vascular vessels, a phenomenon that TSA attenuated. Col4α3 deficiency showed down-regulation of Hemeoxygenase-1 (HO-1), a key anti-inflammatory molecule. TSA treatment induced HO-1 signaling, which contributed to the inhibition of oxidative stress and inflammatory cytokines. These findings suggest that TSA represents a promising candidate molecule for mitigating the progression of hearing loss in AS.

Parkinson's disease (PD) is characterized by the degeneration of dopaminergic nigrostriatal inputs, which causes striatal network dysfunction and leads to pronounced motor deficits. Recent evidence highlights astrocytes as a potential local source for striatal neuromodulation. There is substantial evidence for norepinephrine‐mediated recruitment of cortical astrocyte activity during movement and locomotion. However, it is unclear how astrocytes in the striatum, a region devoid of norepinephrine neuromodulatory inputs, respond during locomotion. Moreover, it remains unknown how dopamine loss affects striatal astrocyte activity and whether astrocyte activity regulates behavioral deficits in PD. We addressed these questions by performing astrocyte‐specific calcium recordings and manipulations using in vivo fiber photometry and chemogenetics. We find that locomotion elicits astrocyte calcium activity over a slower timescale than neurons. Acute pharmacological blockade of dopamine receptors only moderately reduced locomotion‐related astrocyte activity. Yet, unilateral dopamine depletion significantly attenuated astrocyte calcium responses. Chemogenetic stimulation of G i ‐coupled receptors partially improved this functional astrocyte deficit in dopamine‐lesioned mice. In parallel, chemogenetic manipulation restored asymmetrical motor deficits and moderately improved open‐field exploratory behavior. Together, our results establish a novel role for functional striatal astrocyte signaling in modulating motor function in PD and highlight non‐neuronal targets for potential PD therapeutics.

Purpose: Auditory perceptual and cognitive tasks can be useful as a long-term goal in guiding rehabilitation and intervention strategies in audiology clinics that mostly operate at a faster pace and on strict timelines. The rationale of this study was to assess test–retest reliability of an abbreviated test battery and evaluate age-related auditory perceptual and cognitive effects on these measures. Method: Experiment 1 evaluated the test–retest repeatability of an abbreviated test battery and its use in an adverse listening environment. Ten participants performed two visits, each including four conditions: quiet, background noise, external noise, and background mixed with external noise. In Experiment 2, both auditory perceptual and cognitive assessments were collected from younger adults with normal hearing and older adults with and without hearing loss. The full test battery included measures of frequency selectivity, temporal fine structure and envelope processing, spectrotemporal and spatial processing and cognition, and an external measure of tolerance to background noise. Results: Results from Experiment 1 showed good test–retest repeatability and nonsignificant effects from background or external noise. In Experiment 2, effects of age and hearing loss were shown across auditory perceptual and cognitive measures, except in measures of temporal envelope perception and tolerance to background noise. Conclusions: These data support the use of an abbreviated test battery in relatively uncontrolled listening environments such as clinic waiting rooms. With an efficient test battery, perceptual and cognitive deficits can be assessed with minimal resources and little clinician involvement due to the automated nature of the test and the use of consumer-grade technology. Supplemental Material: https://doi.org/10.23641/asha.28021070

Activating transcription factor 6 (ATF6) is a key regulator of the unfolded protein response (UPR) and is important for ER function and protein homeostasis in metazoan cells. Patients carrying loss-of-function ATF6 disease alleles develop the cone dysfunction disorder achromatopsia. The effect of loss of ATF6 function on other cell types, organs, and diseases in people remains unclear. Here, we report that progressive sensorineural hearing loss was a notable complaint in some patients carrying ATF6 disease alleles and that Atf6 –/– mice also showed progressive auditory deficits affecting both sexes. In mice with hearing deficits, we found disorganized stereocilia on hair cells and focal loss of outer hair cells. Transcriptomics analysis of Atf6 –/– cochleae revealed a marked induction of the UPR, especially through the protein kinase RNA-like endoplasmic reticulum kinase (PERK) arm. These findings identify ATF6 as an essential regulator of cochlear health and function. Furthermore, they support the idea that ATF6 inactivation in people causes progressive sensorineural hearing loss as part of a blindness-deafness genetic syndrome targeting hair cells and cone photoreceptors. Last, our genetic findings indicate that ER stress is an important pathomechanism underlying cochlear damage and hearing loss, with clinical implications for patient lifestyle modifications that minimize environmental and physiological sources of ER stress to the ear.

According to the World Health Organization, more than 12% of the world’s population suffers from noise-induced hearing loss (NIHL). Oxidative stress-mediated damage to the stria vascularis (SV) is one of the pathogenic mechanisms of NIHL. Recent studies indicate that glycolysis plays a critical role in endothelial cells (ECs)-related diseases. However, the specific role of glycolysis in dysfunction of SV-ECs remain largely unknown. In this study, we investigated the effects of glycolysis on SV-ECs in vitro and on the SV in vivo. Our previous research identified the glycolysis pathway as a potential mechanism underlying the SV-ECs injuries induced by oxidative stress. We further examined the expression levels of glycolytic genes in SV-ECs under H 2 O 2 stimulation and in noise-exposed mice. We found that the gene and protein expression levels of glycolytic-related enzyme LDHA significantly decreased at early phase after oxidative stress injury both in vitro and in vivo, and exhibited anti-inflammatory effects on macrophages (Mφ). Moreover, we analyzed the differential secretomes of SV-ECs with and without inhibition of LDHA using LC-MS/MS technology, identifying CX3CL1 as a candidate mediator for cellular communication between SV-ECs and Mφ. We found that CX3CL1 secretion from SV-ECs was decreased following LDHA inhibition and exhibited anti-inflammatory effects on Mφ via the CX3CR1 pathway. Similarly, the pro-inflammatory effect of LDHA-overexpressing SV-ECs was attenuated following inhibition of CX3CL1. In conclusion, our study revealed that glycolysis-related LDHA was reduced in oxidative stress-induced SV-ECs, and that LDHA inhibition in SV-ECs elicited anti-inflammatory effects on Mφ, at least partially through the CX3CL1-CX3CR1 pathway. These findings suggest that LDHA represent a novel therapeutic strategy for the treatment of NIHL.

Background and Purpose Sphingosine‐1‐phosphate (S1P) receptor modulator (SRM) drugs suppress immune system function by disrupting lymphocyte trafficking, but SRMs are broadly immunosuppressive with on‐target liabilities. Another strategy to modulate the immune system is to block S1P transport. This study tests the hypothesis that blockers of S1P transport (STBs) mediated by Spinster homologue 2 (Spns2) approximate the efficacy of SRMs without their adverse events. Experimental Approach We have discovered and optimized STBs to enable investigations of S1P biology and to determine whether S1P transport is a valid drug target. The STB SLF80821178 was administered to rodents to assess its efficacy in a multiple sclerosis model and to test for toxicities associated with SRMs or Spns2‐deficient mice. Further, potential biomarkers of STBs, absolute lymphocyte counts (ALCs) in blood and S1P concentrations in plasma and lymph, were measured. Key Results SLF80821178 resembles SRMs in that it is efficacious in a standard multiple sclerosis model but does not evoke bradycardia or lung leakage, common to the SRM drug class. Also, chronic SLF80821178 administration does not affect auditory responses in adult mice despite the neurosensorial hearing defect observed in Spns2‐null mice. While both SRM and STB administration decrease ALCs, the maximal effect is less with an STB (45% vs. 90%). STBs have minimal effects on S1P concentration in plasma or thoracic duct lymph. Conclusion and Implications We found nothing to invalidate Spns2‐dependent S1P transport as a drug target. Indeed, STBs could be superior to SRMs as a therapy to modulate immune system function.

Transgenic mice provide unprecedented access to manipulate and visualize neural circuits; however, those on a C57BL/6 background develop progressive hearing loss, significantly confounding systems-level and behavioral analysis. While outbreeding can limit hearing loss, it introduces strain variability and complicates the generation of complex genotypes. Here, we propose an approach to preserve hearing by crossing transgenic mice with congenic B6.CAST- Cdh23 Ahl + mice, which maintain low-threshold hearing into adulthood. Widefield and two-photon imaging of the auditory cortex revealed that 2.5-month-old C57BL/6 mice exhibit elevated thresholds to high-frequency tones and widespread cortical reorganization, with most neurons responding best to lower frequencies. In contrast, Ahl+ C57BL/6 mice exhibited robust neural responses across tested frequencies and sound levels (4–64 kHz, 30–90 dB SPL) and retained low thresholds into adulthood. Our approach offers a cost-effective solution for generating complex genotypes and facilitates more interpretable systems neuroscience research by eliminating confounding effects from hearing loss.

Objective. In the present study, we examined the correlations between the recovery of stepping obtained with intrathecal brain derived neurotrophic factor (BDNF) delivery to the lumbar spinal cord and the firing of the lumbar spinal interneurons in a feline model of spinal cord injury (SCI). Approach. In-vivo extracellular recordings of spinal neurons were conducted using two 64-channel microelectrode arrays inserted in the intermediate zone of the L3–L7 segments of cats spinalized at the T11–T12 level that received either saline or BDNF delivered intrathecally to the lumbar cisterna via an implanted minipump. Interneuronal activity was explored in terms of averaged neuronal firing properties and in terms of spike train interactions. Main results. With respect to averaged neuronal firing properties, we observed a significant increase in firing frequency in BNDF-treated animals and a similar distribution of the units’ preferred phase of firing relative to the step cycle between the groups. With respect to spike train interactions, we observed higher synchrony of firing in BDNF-treated animals as well as less dependency on the unit’s past firing. Significance. Studies conducted in feline models of complete SCI show a gradual recovery of hindlimb stepping after intensive treadmill training. Similarly, delivery of neurotrophins such as BDNF or neurotrophin-3 to the injury site via cellular transplant or via implantable mini-pump to the lumbar cisterna has been shown to promote recovery of locomotor behavior in the absence of locomotor training. The results from this study suggest that BDNF treatment sets the overall population in a state of high excitability, which along with higher synchrony and ensemble-dependent behavior, allows for the proper integration of cutaneous and proprioceptive input resulting in treadmill locomotor recovery after SCI.

AMPA-type glutamate receptors (AMPARs) mediate excitatory cochlear transmission. However, unique roles of AMPAR subunits are unresolved. Lack of subunit GluA3 (Gria3 KO ) in male mice reduced cochlear output by 8 postnatal weeks. Here, we studied the role of X-linked Gria3 in cochlear function and synapse anatomy in females. Auditory brainstem responses (ABRs) were similar in 3-week-old female Gria3 WT and Gria3 KO mice raised in quiet. However, after switching to ambient sound, ABR thresholds were elevated and wave-1 amplitudes were diminished at 5-week and older in Gria3 KO . A quiet vivarium precluded this effect. Paired synapses were similar in number, but lone ribbons and ribbonless synapses were more frequent, and swollen afferent terminals were observed only in female Gria3 KO mice in ambient sound. Synaptic GluA4:GluA2 ratios increased relative to Gria3 WT , particularly in ambient sound, suggesting an activity-dependent increase in calcium-permeable AMPARs in Gria3 KO . We propose that lack of GluA3 induces a sex-dependent vulnerability to AMPAR-mediated excitotoxicity.

The macaque cerebral cortex contains concentrations of neurons that prefer faces over inanimate objects. Although these so-called face patches are thought to be specialized for the analysis of facial signals, their exact tuning properties remain unclear. For example, what happens when an object by chance resembles a face? Everyday objects can sometimes, through the accidental positioning of their internal components, appear as faces. This phenomenon is known as face pareidolia. Behavioral experiments have suggested that macaques, like humans, perceive illusory faces in such objects. However, it is an open question whether such stimuli would naturally stimulate neurons residing in cortical face patches. To address this question, we recorded single unit activity from four fMRI-defined face-selective regions: the anterior medial (AM), anterior fundus (AF), prefrontal orbital (PO), and perirhinal cortex (PRh) face patches. We compared neural responses elicited by images of real macaque faces, pareidolia-evoking objects, and matched control objects. Contrary to expectations, we found no evidence of a general preference for pareidolia-evoking objects over control objects. Although a subset of neurons exhibited stronger responses to pareidolia-evoking objects, the population responses to both categories of objects were similar, and collectively much less than to real macaque faces. These results suggest that neural responses in the four regions we tested are principally concerned with the analysis of realistic facial characteristics, whereas the special attention afforded to face-like pareidolia stimuli is supported by activity elsewhere in the brain.

Perception of the environment is multimodal in nature, with sensory systems intricately interconnected. The ability to integrate multimodal sensations while preserving the distinct characteristics of each sensory modality is crucial, and the underlying mechanisms of the organization that facilitate this process require further elucidation. In the auditory system, although the concept of core and shell pathways is well established, the brain-wide input/output relationships of thalamic regions projecting to auditory-responsive cortical areas remain insufficiently studied, particularly in relation to non-auditory structures. In this study, we utilized functional imaging and viral tracing techniques to map the brain-wide connections of core and shell pathways. We identified three distinct shell pathways, in addition to a core pathway, each exhibiting unique associations with non-auditory structures involved in behavior, emotion, and other functions. This architecture suggests that these pathways contribute differentially to various aspects of multimodal sensory integration.

The neural basis of perceptual distortions induced by psychedelics remains poorly understood. This study demonstrates that the serotonergic psychedelic DOI increases neural response variability and impairs deviance detection in the auditory cortex by reducing sensitivity to unexpected sounds. These findings provide new insights into how psychedelics disrupt sensory processing and alter the balance between bottom-up and top-down neural signaling, contributing to our understanding of altered perception in the psychedelic state.

Cricket song recognition is thought to evolve through modifications of a shared neural network. However, the species Anurogryllus muticus has an unusual recognition pattern that challenges this view: females respond to both normal male song pulse periods and periods twice as long. Of the three minimal models tested, only a single-neuron model with an oscillating membrane could explain this unusual behavior. A minimal model of the cricket's song network reproduced the behavior after adding a mechanism that, while present in the full network, is not crucial for song recognition in other species. This shows how a shared neural network can produce diverse behaviors and highlights how different computations contribute to evolution. Our results also demonstrate how nonlinear computations can lead to rapid behavioral changes during evolution because small changes in network parameters can lead to large changes in behavior.

Noise-induced cochlear synaptopathy has been studied for over 25 years with no known diagnosis for this disorder in humans. This type of "hidden hearing loss" induces a loss of synapses in the inner ear but no change in audiometric thresholds. Recent studies have shown that by two months post synaptopathy-inducing noise exposure, synapses in some animal species can regenerate. Animal studies to date have focused primarily on peripheral hearing measures to diagnose ribbon synapse loss, while suggesting binaural listening deficits such as speech-reception-in-noise result from this disorder, but haven't accounted for the possible regeneration of synapses. To address this, we measured binaural physiological and behavioral function, the latter utilizing the pre-pulse inhibition of acoustic startle method, in both male and female adult guinea pigs following exposure to noise that has been shown to induce cochlear synaptopathy. Physiological measurements extended to 2 months post noise exposure to characterize any deficit and subsequent recovery. While common audiological assessments showed temporary threshold shift, reduced evoked potential amplitudes indicative of synaptopathy and measurable binaural electrophysiological hearing deficits post exposure, all measures recovered by 2 months. Suspected regeneration of synaptic ribbons occurred by 2 months post exposure and cochlear histology revealed no synaptic loss 4 months post exposure. Our results show that the same noise exposure protocol demonstrated to cause synaptic loss in prior studies causes physiological binaural processing deficits in the brainstem and that the recovery of neural binaural processing coincides with the regeneration of synapses shown in previous studies and normal binaural hearing behavior.

Multiple studies suggest that Parkinson's disease (PD) is associated with changes in neuronal activity throughout the basal ganglia-thalamocortical motor circuit. There are limited electrophysiological data, however, describing how parkinsonism impacts neuronal activity in the presupplementary motor area (pre-SMA), an area in the medial frontal cortex involved in movement planning and motor control. In this study, single unit activity was recorded in the pre-SMA of two female nonhuman primates during a visually cued reaching task in both the naive and parkinsonian state using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of parkinsonism. In the naive state, neuronal discharge rates were dynamically modulated prior to the presentation of the instructional go-cue. In a subset of these modulated cells, the magnitude of modulation correlated linearly with reaction time (RT). In the parkinsonian state, however, modulation of discharge rates in the pre-SMA was disrupted, and the predictive encoding of RT was significantly diminished. These findings add to our understanding of the role of pre-SMA in motor behavior and suggest that disrupted encoding in this cortical region contributes to the alteration of early preparatory and premovement processes present in Parkinson's disease.

The structure of local circuits is highly conserved across the cortex, yet the spatial and temporal properties of population activity differ fundamentally in sensory-level and association-level areas. In the sensory cortex, population activity has a shorter timescale and decays sharply over distance, supporting a population code for the fine-scale features of sensory stimuli. In the association cortex, population activity has a longer timescale and spreads over wider distances, a code that is suited to holding information in memory and driving behavior. We tested whether these differences in activity dynamics could be explained by differences in network structure. We targeted photostimulations to single excitatory neurons of layer 2/3, while monitoring surrounding population activity using two-photon calcium imaging. Experiments were performed in the auditory (AC) and posterior parietal cortex (PPC) within the same mice of both sexes, which also expressed a red fluorophore in somatostatin-expressing interneurons (SOM). In both cortical regions, photostimulations resulted in a spatially restricted zone of positive influence on neurons closely neighboring the targeted neuron and a more spatially diffuse zone of negative influence affecting more distant neurons (akin to a network-level “suppressive surround”). However, the relative spatial extents of positive and negative influence were different in AC and PPC. In PPC, the central zone of positive influence was wider, but the negative suppressive surround was more narrow than in AC, which could account for the larger-scale network dynamics in PPC. The more narrow central positive influence zone and wider suppressive surround in AC could serve to sharpen sensory representations.

Age-related hearing loss (ARHL) is a complex condition with genetic, aging, and environmental influences. Sirtuins, particularly SIRT1, are NAD-dependent protein deacetylases critical to aging and stress responses. SIRT1 is modulated by nicotinamide N-methyltransferase (NNMT) and its product, N 1 -methylnicotinamide (MNAM), which influence ARHL progression. While SIRT1 is protective under certain conditions, its overexpression may paradoxically exacerbate hearing loss. This study examines MNAM supplementation’s impact on SIRT1 expression and ARHL in low-fat diet (LFD)-fed B6 and CBA mice. Mice were divided into LFD and LFD + MNAM groups and evaluated for auditory function, cochlear morphology, metabolic profiles, and SIRT1 expression at 3, 6, and 12 months of age. MNAM supplementation accelerated ARHL in both strains, with B6 mice showing more pronounced and earlier disease progression. Auditory brainstem response (ABR) thresholds were significantly elevated, and distortion-product otoacoustic emissions (DPOAE) indicated outer hair cell dysfunction. Cochlear histology revealed reduced hair cell and spiral ganglion cell counts, as well as decreased Na + /K + -ATPase α1 expression and endocochlear potential. MNAM increased SIRT1 protein levels in the cochlea without altering Sirt1 mRNA, suggesting post-transcriptional regulation. Metabolomic analysis revealed disrupted mitochondrial and oxidative pathways, including fatty acid oxidation and gluconeogenesis. Tricarboxylic acid (TCA) cycle dysregulation was evident, particularly in B6 mice, with elevated pyruvate, fumarate, and lactate levels. Despite similar metabolic trends in CBA mice, their slower aging profiles mitigated ARHL progression. These results suggest that while moderate SIRT1 expression protects against ARHL, overexpression disrupts metabolic homeostasis, accelerating cochlear aging and dysfunction. The dual role of SIRT1 emphasizes the need for precise modulation of its expression for effective therapeutic interventions. Future research should explore mechanisms underlying SIRT1-induced cochlear damage and strategies to maintain balanced SIRT1 expression. This study highlights MNAM’s detrimental effects on ARHL, underscoring its significance for developing targeted approaches to delay ARHL onset and preserve auditory function.

Sound‐evoked wakefulness from sleep is crucial in daily life, yet its neural mechanisms remain poorly understood. It is found that CaMKIIα+ neurons in the temporal association cortex (TeA) of mice are not essential for natural awakening from sleep. However, optogenetic activation of these neurons reliably induces wakefulness from non‐rapid eye movement (NREM) sleep but not from rapid eye movement (REM) sleep. In vivo electrophysiological and calcium recordings further demonstrated that TeA neurons are monotonically tuned to sound intensity but not frequency. More importantly, it is found that the activity of CaMKIIα+ neurons in TeA can gate sound‐evoked arousal from NREM sleep, which is further confirmed by optogenetic manipulations. Further investigation reveals that the baseline excitability of TeA CaMKIIα+ neurons and the delta oscillations in the electroencephalogram are particularly important in regulating the evoked activity of TeA neurons. Anatomical and functional screening of downstream targets of TeA reveals that excitatory projections from TeA glutamatergic neurons to glutamatergic neurons in the basolateral/lateral amygdala are critical for modulating sound‐evoked arousal from NREM sleep. These findings uncover a top‐down regulatory circuit that selectively governs sound‐evoked arousal from NREM sleep, with the TeA functioning as a key connecting cortex to subcortical regions.

We aimed to test whether hearing speech in phonetic categories (as opposed to a continuous/gradient fashion) affords benefits to “cocktail party” speech perception. We measured speech perception performance (recognition, localization, and source monitoring) in a simulated 3D cocktail party environment. We manipulated task difficulty by varying the number of additional maskers presented at other spatial locations in the horizontal soundfield (1–4 talkers) and via forward vs. time-reversed maskers, the latter promoting a release from masking. In separate tasks, we measured isolated phoneme categorization using two-alternative forced choice (2AFC) and visual analog scaling (VAS) tasks designed to promote more/less categorical hearing and thus test putative links between categorization and real-world speech-in-noise skills. We first show cocktail party speech recognition accuracy and speed decline with additional competing talkers and amidst forward compared to reverse maskers. Dividing listeners into “discrete” vs. “continuous” categorizers based on their VAS labeling (i.e., whether responses were binary or continuous judgments), we then show the degree of release from masking experienced at the cocktail party is predicted by their degree of categoricity in phoneme labeling and not high-frequency audiometric thresholds; more discrete listeners make less effective use of time-reversal and show less release from masking than their gradient responding peers. Our results suggest a link between speech categorization skills and cocktail party processing, with a gradient (rather than discrete) listening strategy benefiting degraded speech perception. These findings suggest that less flexibility in binning sounds into categories may be one factor that contributes to figure-ground deficits.