Merri J. Rosen - US grants

[unreadable] Description (provided by applicant): Many auditory perceptual skills mature over a surprisingly long time course (in humans), well into the teenage years. If hearing is disrupted during development, there may be long-lasting deficits in auditory perception and language acquisition. Surprisingly, maturation of the auditory coding properties that support these emerging perceptual skills are largely unknown; what little we do know is based solely on recordings from anesthetized animals. This is also why our understanding of the effect of hearing loss (HL) on central auditory maturation is unsettled. These studies will thus examine functional development in awake animals for the first time, and explore how coding properties are influenced by sensory experience. The central hypothesis of this proposal is that mild to moderate conductive HL during development permanently disrupts coding properties in the auditory cortex, leading to measurable deficits in perceptual performance. There are three related experimental aims. The FIRST AIM will determine whether HL during development disrupts the perceptual abilities of adult animals. Animals will be tested on a psychophysical task known to mature gradually and to be affected by hearing loss in humans: detection of modulation depth in sinusoidally amplitude modulated (SAM) signals. The SECOND AIM will characterize the normal rate of development of neural coding properties in auditory cortex. Those percepts measured behaviorally in Aim 1 will be examined along with other percepts similarly susceptible to developmental perturbation. Single unit recordings will be obtained in awake control animals during the period of development that follows maturation of the cochlea (thus, peripheral processing will not be assessed). The broad goals are to determine whether coding properties mature at different rates, as suggested by human behavioral studies, and to search for neural correlates underlying SAM detection. Finally, the THIRD AIM will assess whether these coding properties are perturbed in a manner that correlates with perceptual deficits in animals reared with conductive HL, measured in Aim 1. Together, these data will provide the first analysis of auditory coding in awake developing animals, and reveal whether HL disrupts both perceptual skills and the coding properties that support them. These studies have direct clinical relevance. By first determining when the central auditory system reaches maturity, it will be possible to determine whether coding properties fail to develop normally, or reach maturity early but begin to regress due to hearing loss. This knowledge will be important in informing clinicians for intervention in cases of early hearing impairment. [unreadable] [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): The long-term goal of this work is to identify neural mechanisms that limit perceptual abilities as a result of developmental hearing loss. In the auditory system, chronic middle ear infections (otitis media) in children result in fluctuating conductive hearing loss (HLC) during development. The duration of hearing loss is correlated with persistent perceptual problems including speech processing deficits. Processing of time-varying auditory signals is particularly vulnerable to early hearing loss. Recent work in an animal model of conductive hearing loss shows that early hearing impairment shifts both synaptic properties and responses to sound in auditory cortex. However, it is unknown how altered synaptic elements shape cortical tuning, or how altered cortical tuning contributes to impaired perception. To address these issues, this project examines the chain of events initiated by hearing loss in order to establish the links between synaptic changes in auditory cortical neurons, their effects on the sound-evoked responses of these neurons, and impaired perception. Aim 1 will determine response properties that are vulnerable to early hearing loss. Aim 2 will determine the synaptic mechanisms that shape altered response properties of neurons in auditory cortex. Aim 3 will identify how cortical responses to auditory stimuli that are altered by hearing loss relate to perceptual impairments. The degree to which early hearing loss causes a simple maturational delay or novel pathology is unknown. Several neural changes due to early hearing loss indicate a delayed maturation of synaptic components and auditory responses. However, temporal response properties in hearing-impaired animals are not uniformly immature, and Aim 1 will identify those elements of time-varying stimuli that are susceptible to the effects of auditory deprivation. In particular, early hearing loss impairs processing of slow but not fast amplitude modulations (AM). However, preliminary data indicate that it may be the rate of the amplitude rise in AM signals, rather than the frequency of the modulations, that elicits abnormal neural responses. This distinction is important: speech is composed of periodic amplitude and frequency modulations with a variety of slow and fast rise times. Studies of dyslexia and specific language impairment indicate that the neural processing of a subset of these speech components is impaired, which has led to directed therapeutic interventions. This proposal will identify which stimulus parameters elicit responses that are altered by early hearing loss. Understanding the neural basis of impairments resulting from chronic conductive hearing loss is a necessary step toward providing targets for intervention and remediation.