Biology subjects

Mondul, J. A.

Publications and source records attributed to Mondul, J. A..

3 recordsLinked to original sources

bioRxiv2026

Noise-induced temporary threshold shift in macaques disrupts electrophysiological temporal processing despite recovery of cochlear sensitivity and preserved ribbon synapse counts

Noise exposure can produce lasting auditory dysfunction in the absence of permanent threshold shifts or hair cell loss, yet the functional consequences of temporary threshold shift (TTS) remain poorly defined in translational models. We assessed auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs) in rhesus macaques (n = 13) at 2 and 9-10 months following a single moderate noise exposure that induced TTS. Previous histological analyses of these macaques showed no significant loss of hair cells or ribbon synapses but revealed persistent broadening of inner and outer hair cell ribbon-volume distributions. After exposure, DPOAE amplitudes and thresholds and ABR thresholds returned to pre-exposure values and showed low-frequency enhancement at later time points. Suprathreshold click- and tone-evoked ABR amplitudes were largely preserved or enhanced after exposure, consistent with compensatory gain. In contrast, macaque-specific chirp-evoked ABRs showed modest amplitude reductions and latency prolongation across waves, indicating altered neural synchrony at standard stimulus presentation rates, but with variable time courses. More temporally demanding paradigms revealed persistent impairments. ABRs to faster click rates and shorter paired-click intervals showed reduced adaptability in response amplitude and timing after normalization, with deficits persisting through 9-10 months. Increased inner hair cell ribbon-volume variability was more consistently associated with temporal response measures, including latency, paired-click recovery, and rate adaptation, than with amplitude-based ABR measures. Together, these findings reveal a lasting dissociation between response magnitude and fidelity after TTS: suprathreshold responses may be preserved or enhanced, while neural synchrony and temporal adaptability remain impaired. Increased presynaptic ribbon volume variability may serve as a structural marker of synaptic remodeling accompanying hidden auditory dysfunction, rather than as a direct determinant of suprathreshold response magnitude. Temporally demanding ABR paradigms may supplement threshold-based diagnostics for detecting persistent noise-induced auditory dysfunction.

neuroscience↗

bioRxiv2026

Temporal integration in the subcortical auditory system and behavioral evidence of its dysfunction after "temporary" noise-induced hearing loss

How sensory information is processed over time is often conceptualized as a process of temporal integration. Recently, auditory temporal integration has received renewed attention as a potential assay of hidden hearing loss caused by cochlear synaptopathy in rodent and avian studies. How these results relate to human hearing is in question due to a lack of studies in primates, and, more generally, the neural basis of auditory temporal integration is unclear, as most subcortical studies of it have been conducted under anesthesia. We have recently introduced a nonhuman primate (NHP) model which can address translational questions about auditory temporal integration and hidden hearing loss. Thus, in this study, we utilized single-unit recordings and compared derived neurometric measures to psychometric measures of temporal integration in normal hearing NHPs performing a tone-in-noise detection task. We then assessed psychometric measures of temporal integration in NHPs before and after noise exposure. In normal hearing NHPs, cochlear nucleus and inferior colliculus (IC) integration rates were significantly greater than psychometric rates. However, in noise only, [~]25% of IC neurons exhibited similar integration rates to behavior. After noise exposure, psychometric integration was disrupted for brief stimuli presented in quiet, but not in noise. The dynamic range of the psychometric function reliably increased, months after recovery from the noise-induced temporary threshold shift (TTS). Together, these data identify a subcortical neural substrate for temporal integration in noisy environments and suggest that behavioral assays of temporal integration may serve as sensitive indicators of subclinical hearing loss.

neuroscience↗

bioRxiv2026

Persistent impairment of spatial hearing and neural binaural interaction after temporary noise-induced hearing loss

Many people have trouble understanding speech in noisy environments despite normal audiometric thresholds, a condition referred to as "hidden hearing loss." A leading hypothesis attributes this deficit to inner hair cell synaptic pathology (cochlear synaptopathy), which can persist after recovery from noise-induced temporary elevation of audiometric thresholds. This pathology impairs the temporally precise sound encoding necessary for spatial hearing, but direct evidence in primates, human or nonhuman, is lacking. Here, we show that a single noise exposure, producing only a temporary threshold elevation, induced long-lasting alterations in synaptic morphology, without synapse loss, resulting in persistent spatial hearing deficits for up to 11 months post-exposure in nonhuman primates of both sexes. These perceptual deficits were accompanied by a reduction in a neurophysiological measure of binaural processing - the binaural interaction component (BIC) of the auditory brainstem response (ABR). Both behavioral and neural deficits persisted despite full recovery of audiometric thresholds. Together, these findings provide the first evidence in primates that noise exposure disrupts spatial hearing and binaural neural circuit function without loss of hair cells or synapses. Because spatial hearing tests and the ABR/BIC are clinically accessible, this work also establishes translational biomarkers for early neural dysfunction underlying hidden hearing loss.

neuroscience↗