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The middle-ear system relies on a balance of mass and stiffness characteristics for transmitting sound from the external environment to the cochlea and auditory neural pathway. Phase is one aspect of sound that, when transmitted and encoded by both ears, contributes to binaural cue sensitivity and spatial hearing. The study aims were (i) to investigate the effects of middle-ear stiffness on the auditory brainstem neural encoding of phase in human adults with normal pure-tone thresholds and (ii) to investigate the relationships between middle-ear stiffness-induced changes in wideband acoustic immittance and neural encoding of phase. The auditory brainstem neural encoding of phase was measured using the auditory steady-state response (ASSR) with and without middle-ear stiffness elicited via contralateral activation of the middle-ear muscle reflex (MEMR). Middle-ear stiffness was quantified using a wideband acoustic immittance assay of acoustic absorbance. Statistical analyses demonstrated decreased ASSR phase lag and decreased acoustic absorbance with contralateral activation of the MEMR, consistent with increased middle-ear stiffness changing the auditory brainstem neural encoding of phase. There were no statistically significant correlations between stiffness-induced changes in wideband acoustic absorbance and ASSR phase. The findings of this study may have important implications for understanding binaural cue sensitivity and horizontal plane sound localization in audiologic and otologic clinical populations that demonstrate changes in middle-ear stiffness, including cochlear implant recipients who use combined electric and binaural acoustic hearing and otosclerosis patients.

Neurodevelopmental disorders are on the rise worldwide, with diagnoses that detect derailment from typical milestones by 3-4.5 years of age. By then, the circuitry in the brain has already reached some level of maturation that inevitably takes neurodevelopment through a different course. There is a critical need then to develop analytical methods that detect problems much earlier and identify targets for treatment. We integrate data from multiple sources, including neonatal auditory brainstem responses (ABR), clinical criteria detecting autism years later in those neonates, and similar ABR information for young infants and children who also received a diagnosis of autism spectrum disorders, to produce the earliest known digital screening biomarker to flag neurodevelopmental derailment in neonates. This work also defines concrete targets for treatment and offers a new statistical approach to aid in guiding a personalized course of maturation in line with the highly nonlinear, accelerated neurodevelopmental rates of change in early infancy.Significance StatementAutism is currently detected on average after 4.5 years of age, based on differences in social interactions. Yet basic building blocks that develop to scaffold social interactions are present at birth and quantifiable at clinics. Auditory Brainstem Response tests, routinely given to neonates, infants, and young children, contain information about delays in signal transmission important for sensory integration. Although currently discarded as gross data under traditional statistical approaches, new analytics reveal unambiguous differences in ABR signals’ fluctuations between typically developing neonates and those who received an autism diagnosis. With very little effort and cost, these new analytics could be added to the clinical routine testing of neonates to create a universal screening tool for neurodevelopmental derailment and prodrome of autism.