Suprathreshold processing and binaural interaction in rhesus macaques with cochlear synaptopathy

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ABSTRACT As many as 15% of patients in audiology clinics have normal hearing thresholds, but struggle to understand speech in noise. Understanding speech in noisy environments requires perceptual analysis of suprathreshold sound features, in contrast to audiometric threshold, which is an estimate of the softest sound a listener can detect. These suprathreshold processing deficits that normal hearing patients exhibit cannot be treated currently because their basis in the auditory pathway is not well established. A promising explanation is cochlear synaptopathy, which refers to inner hair cell synapse loss. Synaptopathy leaves thresholds unaffected, but degrades the encoding of suprathreshold sounds as measured by the auditory brainstem response (ABR), and alters excitatory-inhibitory balance in the auditory pathway, which is required for encoding spatial and temporal sound features. Corroborating evidence from the human literature comes in the form of studies showing that normal hearing subjects display substantial individual differences in neurophysiological and behavioral measures of spatial and temporal processing. In particular, the binaural interaction component (BIC) of the ABR is compromised in patients with this profile. Importantly, the BIC may depend on subcortical inhibition, which is compromised by synaptopathy. Despite these compelling links between suprathreshold processing deficits and the neurophysiological effects of synaptopathy, there is no direct evidence that synaptopathy causes perceptual deficits. This is largely because synaptopathy can only be verified via post-mortem cochlear histology, and perceptual measures have rarely been used in animal studies of synaptopathy. Moreover, studies of synaptopathy have only used rodents, which differ from primates in their inhibitory neurotransmission, and perceptual measures of spatial and temporal processing. Such differences could complicate the translation of neurophysiological and behavioral findings into diagnostic and therapeutic innovations. It is for these reasons that we propose using our nonhuman primate model of cochlear synaptopathy to link anatomical, neurophysiological, and perceptual effects of synaptopathy. We propose studying the effects of synaptopathy on temporal and spatial processing to establish synaptopathy's perceptual effects (Aim 1), and linking those effects with a neurophysiological correlate of spatial hearing – the BIC of the ABR (Aim 2). Both temporal and spatial processing will be studied in detection and discrimination paradigms, with the expectation the discrimination tasks will show the largest deficits, and that synaptopathy, and degraded BIC, will correlate with these deficits. These links will provide an explanation of how synaptopathy and its neural consequences can cause deficits in normal hearing subjects, and will form the basis for noninvasive diagnostic tests for synaptopathy in humans.