Evidence for a relationship between the suppression of distortion product otoacoustic emissions and hearing threshold

Sensory neural pathways develop through a combination of "pre-wiring" by innate processes and "re-wiring" by the external environment ("nature and nurture"). However, there is increasing evidence that the development of the systematic (topographic) representation of receptor space in the visual pathway (retinotopic map) does not require external light, but rather gradients of chemical markers and waves of spontaneous activity. Is the same true of the development of topographic sound frequency (tonotopic) maps in the auditory pathway? Single-unit responses to tone pip stimuli were isolated from numerous microelectrode penetrations of auditory cortex (under ketamine anesthesia) in the developing chinchilla ('laniger'), a precocious mammal. Results are reported at postnatal day 3 (P3), P15, P30 and from adult animals. Hearing sensitivity and spike firing rates were mature in the youngest group. Tonotopic maps in primary and secondary auditory cortex were also well-ordered and sharply tuned by P3. The representation of sound frequency in the chinchilla auditory pathway thus appears to reach maturity 'in utero', where external (and maternal) sounds are considerably attenuated, and might not contribute to the mechanism(s) involved. On the other hand, the spectral-temporal complexity of cortical receptive fields increased progressively (past P30) to adulthood. Increasing fractions of neurons responded to multiple frequency bands, distinct in space and/or time. This likely reflects the continuing postnatal emergence of lateral connections between cortical columns, perhaps to confer selectivity for recurring fragments of species-specific vocalizations, such as frequency stacks and glides. There are several key parallels in the timelines of chinchilla and human auditory system development. It may be, therefore, that inadequate sound stimulation in early infancy (e.g. due to chronic middle ear disease) does not affect the sensorineural machinery required for precise frequency resolution, but may prevent the emergence of more complex sound feature selectivity, and so contribute to impaired speech perception., Otoacoustic emissions are sounds produced by the cochlea of the inner ear. For example, if two tonal stimuli at frequencies f1 and f 2 are presented to the ear, a third spectral component can be measured in the ear canal at frequency 2f1-f2, named the cubic distortion product otoacoustic emission (DPOAE). For low levels of f 1 and f2, the dominant cause of distortion is believed to be the nonlinear operation of the cochlear amplifier, the biochemically-powered internal motor behind the ear's remarkable frequency selectivity and sensitivity. Since most cases of hearing loss result from an impairment of this amplification process, DPOAEs provide a fast, objective test of hearing status. However, because their levels correlate only weakly with audiometric thresholds, use of DPOAEs in the clinic is limited to a pass or fail screening for hearing defects. In a recent paper, David Mills (J Acoust Soc Am 103:507-523) proposed a novel algorithm for estimating the gain of the cochlear amplifier, not from DPOAE level, but from the manner in which the level decreased when a third stimulus tone, the suppressor, was applied simultaneously with f1 and f2. In this thesis, the validity of Mills' algorithm is investigated using two approaches. First, a relationship between suppression and gain is derived on the basis of a small number of assumptions motivated by established empirical findings. Second, it is shown, to a very high degree of certainty, that there exists a relationship between DPOAE suppressibility and hearing threshold (an indirect measure of active gain) in humans. It is concluded that DPOAE suppression is a direct, noninvasive window on the gain of the cochlear amplifier. It has tangible diagnostic potential and warrants further study.