Sensory organ damage induces a host of cellular and physiological changes in the periphery and the brain. Here, we show that some aspects of auditory processing recover after profound cochlear denervation due to a progressive, compensatory plasticity at higher stages of the central auditory pathway. Lesioning >95% of cochlear nerve afferent synapses, while sparing hair cells, in adult mice virtually eliminated the auditory brainstem response and acoustic startle reflex, yet tone detection behavior was nearly normal. As sound-evoked responses from the auditory nerve grew progressively weaker following denervation, sound-evoked activity in the cortex – and to a lesser extent the midbrain – rebounded or surpassed control levels. Increased central gain supported the recovery of rudimentary sound features encoded by firing rate, but not features encoded by precise spike timing such as modulated noise or speech. These findings underscore the importance of central plasticity in the perceptual sequelae of cochlear hearing impairment.

Decades of clinical and basic research in visual system development have shown that degraded or imbalanced visual inputs can induce a long-lasting visual impairment called amblyopia. In the auditory domain, it is well established that inducing a conductive hearing loss (CHL) in young laboratory animals is associated with a panoply of central auditory system irregularities, ranging from cellular morphology to behavior. Human auditory deprivation, in the form of otitis media (OM), is tremendously common in young children, yet the evidence linking a history of OM to long-lasting auditory processing impairments has been equivocal for decades. Here, we review the apparent discrepancies in the clinical and basic auditory literature and provide a meta-analysis to show that the evidence for human amblyaudia, the auditory analog of amblyopia, is considerably more compelling than is generally believed. We argue that a major cause for this discrepancy is the fact that most clinical studies attempt to link central auditory deficits to a history of middle ear pathology, when the primary risk factor for brain-based developmental impairments such as amblyopia and amblyaudia is whether the afferent sensory signal is degraded during critical periods of brain development. Accordingly, clinical studies that target the subset of children with a history of OM that is also accompanied by elevated hearing thresholds consistently identify perceptual and physiological deficits that can endure for years after peripheral hearing is audiometrically normal, in keeping with the animal studies on CHL. These studies suggest that infants with OM severe enough to cause degraded afferent signal transmission (e.g., CHL) are particularly at risk to develop lasting central auditory impairments. We propose some practical guidelines to identify at-risk infants and test for the positive expression of amblyaudia in older children.

Understanding the biology of the previously underappreciated sensitivity of cochlear synapses to noise insult, and its clinical consequences, is becoming a mission for a growing number of auditory researchers. In addition, several research groups have become interested in developing therapeutic approaches that can reverse synaptopathy and restore hearing function. One of the major challenges to realizing the potential of synaptopathy rodent models is that current clinical audiometric approaches cannot yet reveal the presence of this subtle cochlear pathology in humans. This has catalyzed efforts, both from basic and clinical perspectives, to investigate novel means for diagnosing synaptopathy and to determine the main functional consequences for auditory perception and hearing abilities. Such means, and a strong concordance between findings in pre-clinical animal models and clinical studies in humans, are important for developing and realizing therapeutics. This paper frames the key outstanding translational questions that need to be addressed to realize this ambitious goal.

All sensory systems face the fundamental challenge of encoding weak signals in noisy backgrounds. Although discrimination abilities can improve with practice, these benefits rarely generalize to untrained stimulus dimensions. Inspired by recent findings that action video game training can impart a broader spectrum of benefits than traditional perceptual learning paradigms, we trained adult humans and mice in an immersive audio game that challenged them to forage for hidden auditory targets in a 2D soundscape. Both species learned to modulate their angular search vectors and target approach velocities based on real-time changes in the level of a weak tone embedded in broadband noise. In humans, mastery of this tone in noise task generalized to an improved ability to comprehend spoken sentences in speech babble noise. Neural plasticity in the auditory cortex of trained mice supported improved decoding of low-intensity sounds at the training frequency and an enhanced resistance to interference from background masking noise. These findings highlight the potential to improve the neural and perceptual salience of degraded sensory stimuli through immersive computerized games.foraging | hearing | cortical | gradient search | noise suppression E fficient search for resources is critical to the survival of most species. As such, foraging represents a conserved, adaptive behavior that drives decision making under the types of naturalistic contexts for which brains have evolved. Efficient foraging involves the dynamic integration of sensory cues, memory, and the costs and values associated with foraging decisions (1-3). The sensory cues used to guide foraging can be either discrete or gradient-based. For instance, moths, dogs, and humans navigate odor gradients using characteristic casting and zigzagging behaviors in response to dynamic somatosensory and olfactory cues (4-6). Although the successful execution of these behaviors would be expected to strongly rely on the integration of rapidly changing, weak and noisy sensory information, previous work has primarily focused on computations involved in cost/value decisions related to the exploration/exploitation trade-off (1, 2, 7-9), rather than whether and how foraging behavior is refined through learned associations between these dynamic sensory cues and reinforcement signals (but see refs. 10-12).Accumulating evidence suggests that sensory learning in mature animals reflects the coordinated activation of sensory brain areas and neuromodulatory control nuclei (13). Of these neuromodulatory systems, cholinergic and dopaminergic neurons in the nucleus basalis and ventral tegmental area, respectively, have been observed to code cognitive operations of cue detection (14, 15) and reward prediction (16) associated with behaviorally relevant sensory stimuli and to subserve learning in complex sensory-guided tasks (17). Theoretically, these learning systems are maximally engaged by tasks that require the continuous interplay of sensory cues, dynamically updated motor action program...