Sharon Freeman

Development of hearing in neonatal rats: Air and bone conducted ABR thresholds

While the human full-term neonate can hear at birth, in the rat the onset of auditory function as monitored by recording auditory nerve-brainstem evoked responses (ABR) has been reported to begin on post-natal day (PND) 12-14 and reaches adult thresholds at about 22 days. In order to determine the factors involved in this late onset and then rapid threshold improvement in rats, the ABR to both air conducted (AC) and bone-conducted (BC) auditory stimulation was determined in neonatal rats. ABR to maximal intensity BC stimuli (55 dB above adult rat ABR threshold--55 dB HL*) could be recorded from PND 7-8 while AC responses to 80 dB HL* stimuli, only from PND 11. The air-bone gap (a measure of conductive immaturities only) disappeared on PND 15. This shows that there are both conductive (external and middle ear--Air-bone gap) and sensori-neural (inner ear--BC threshold) immaturities in the neonatal rat; the conductive factors are resolved by PND 15 while the sensori-neural continue after that. With respect to conductive factors, it seems that the state of the ear canal is not important while the chief conductive factors involved probably include mesenchyme resorption and/or ossicular ossification. The chief sensori-neural factor may be the development of the endocochlear potential. It is likely that the human fetus in-utero undergoes similar stages of development.

The depression of the auditory nerve-brain-stem evoked response in hypoxaemia — mechanism and site of effect ☆

During severe hypoxaemia in the cat the ABR was depressed in 2 different patterns: if mean arterial blood pressure (MAP) was maintained then all other evoked potentials (EPs--somatosensory and visual) remained. If MAP was not maintained, all of these EPs were depressed. This study sought to document these different patterns of ABR depression and to ascertain their mechanisms. When MAP fell, the ABR loss began with the later waves and progressed to the earlier waves. These are signs of a central brain lesion. The hypoxaemia, detrimental to normal function of the cardiovascular system, leads to depression of MAP, to a fall in cerebral perfusion pressure and blood flow, to cerebral ischaemia and ABR loss. On the other hand, when MAP was maintained, severe hypoxaemia was accompanied by a depression of all of the ABR waves at the same time. The cochlear microphonic potential was also simultaneously depressed. These are signs of a peripheral, cochlear effect similar to the demonstrated depression of the positive endocochlear resting potential of the scala media and of the cochlear microphonic potential during hypoxaemia. This leads to interference with the cochlear transduction mechanism so that all of the auditory evoked potentials, including the ABR, are simultaneously depressed. These results lead to the suggestion that the ABR abnormalities seen in patients who suffered a hypoxic (anoxic) insult or an ischaemic episode (prolonged interpeak latencies, loss of later waves and finally all waves absent or only the first wave remaining) is always due to ischaemia even when the initial insult was hypoxic.

Further evidence for a fluid pathway during bone conduction auditory stimulation.

This study was designed to evaluate the suggestion that during bone vibrator stimulation on skull bone (bone conduction auditory stimulation), a major connection between the site of the bone vibrator and the inner ear is a fluid pathway. A series of experiments were conducted on pairs of animals (rats or guinea pigs). The cranial cavities of each pair of animals were coupled by means of a saline filled plastic tube sealed into a craniotomy in the skull of each animal. In response to bone conduction click stimulation to the skull bone of animal I, auditory nerve-brainstem evoked responses could be recorded in animal II. Various procedures showed that these responses were initiated in animal II in response to audio-frequency sound pressures generated within the cranial cavity of animal I by the bone conduction stimulation and transferred to the cranial cavity of animal II through the fluid in the plastic tube: they were not responses to air conducted sounds generated by the bone vibrator, were not induced in animal II by vibrations conveyed to it by the plastic tube and were not electrically conducted activity from animal I. Exposing the fluid in the tube to air was not accompanied by any change in threshold. These experiments confirm that during bone conduction stimulation on the skull, audio-frequency sound pressures (alternating condensations and rarefactions) can be conveyed by a fluid pathway to the cochlea and stimulate it.

Multi-modality evoked potentials in hypoxaemia

The auditory nerve-brain-stem evoked response (ABR) has been shown to be insensitive to hypoxic inspiratory gas mixtures which severely depress the EEG. In order to determine the relative sensitivities of additional brain regions and pathways to hypoxaemia, anaesthetized paralysed cats were ventilated with various gas mixtures while recording the evoked responses of the auditory, somatosensory (including peripheral nerve, brain-stem and primary cortical components), visual and vestibular systems. Arterial blood pressure was maintained by dopamine infusion and pH was corrected with bicarbonate. Hypoxic gas mixtures (6-7% O2) presented for 60 min, causing severe hypoxaemia (paO2 20-30 mm Hg; O2 saturation 25-50%), were without effect on the somatosensory, vestibular and visual EPs while the auditory evoked potentials (ABR and cortical components) were depressed. However, if arterial blood pressure was allowed to fall, all of the evoked potentials became severely depressed and isoelectric. These results and others indicate that the cortical components are qualitatively similar to the more peripheral evoked potentials. The resistance of these evoked potentials to controlled hypoxaemia is probably due to their generation by oligosynaptic pathways and to a compensatory switch to anaerobic metabolism and to an elevation of cerebral blood flow.

Short and middle latency vestibular evoked responses to acceleration in man

We have succeeded in recording short and middle latency vestibular evoked responses in human subjects. The head was held rigidly in a special, patented head holder, constructed individually for each subject, which gripped the teeth of the upper jaw. The stimulus consisted of 2/sec steps of angular acceleration impulses produced by a special motor with intensities of about 10,000 degrees/sec 2 and with a rise time of 1-2 msec. The electrical activity was recorded as the potential difference between special forehead and mastoid electrodes having a large, secure contact area with the skin. The activity was digitally filtered and averaged in 2 separate channels by means of a Microshev 2000 evoked response system. The short latency responses, with peaks at about 3.5 msec (forehead positive), 6.0 msec (forehead negative) and 8.4 msec (forehead positive; bandpass: 200-2000 Hz; average of 1024 trials), had amplitudes of about 0.5 microV. The middle latency responses had peaks at about 8.8 msec (forehead positive), 18.8 msec (forehead negative) and 26.8 msec (forehead positive; 30-300 Hz; N = 128 trials), with larger amplitudes (about 15 microV). These responses were consistently recorded in the same subject at different times and were similar in different normal subjects. Strenuous control experiments were conducted in order to ensure that these responses are not artefacts due to the movement of conducting media (head, electrodes and leads) in the electromagnetic field of the motor and are elicited by activation of normal labyrinths.(ABSTRACT TRUNCATED AT 250 WORDS)

Semicircular canal fenestration – improvement of bone- but not air-conducted auditory thresholds

Auditory stimulation can, under certain circumstances, activate the vestibular end organs and this is facilitated by fenestration of a semicircular canal (SCC). Several fenestrated profoundly deaf patients reported improvements in their bone- (BC) but not air-conducted (AC) thresholds. Bone conduction auditory thresholds have been reported to be better than normal in several patients with thinning or absence of bone over a SCC (dehiscence). This phenomenon was carefully studied in the fat sand rat (Psammomys obesus) by recording auditory brainstem evoked responses to BC and AC auditory stimulation, before and after SCC fenestration. Fenestration would be expected to decrease the pressure difference across the cochlear partition, causing a reduction in the amplitude of the classical base to apex input traveling wave, and should therefore lead to an elevation in AC and BC thresholds. Instead, BC thresholds decreased (i.e. improved) following fenestration (by 7.0+/-4.2 dB; P<0.005), while AC thresholds did not change. Thus the cochlea becomes more sensitive to BC, but not AC, stimulation in the presence of a SCC fenestration. This may be due to the removal by the fenestration of a factor impeding BC cochlear responses, or by the addition of a facilitating factor. The result that the SCC fenestration did not affect AC threshold provides support for the concept that at low intensities the outer hair cells are directly activated by components of the fluid pressures surrounding them, which alternate at audio-frequencies. These cochlear fluid audio-frequency pressures are induced by stapes footplate movement and not by a base to apex input traveling wave. The audio-frequency pressures would not be affected by SCC fenestration. The outer hair cell motility thus induced somehow excites the inner hair cells and the auditory nerve fibers. At low intensities the outer hair cell motility causes localized displacement at the appropriate position on the basilar membrane.

ABR threshold is a function of blood oxygen level

In order to determine if there is a relation between auditory threshold and oxygen availability, cats were anesthetized, paralyzed and ventilated with room air and with hypoxic gas mixtures. Auditory nerve-brain stem evoked response (ABR) thresholds and arterial blood oxygen levels [partial pressures (PaO2) and percent saturation (SaO2)] were determined. The ABR threshold was unchanged as long as PaO2 was above 30 mm Hg (SaO2 greater than 45%). Below PaO2 20 mmHg (SaO2 less than 25%) the animal was not viable. Between these values, the hypoxia caused ABR threshold elevations which were reversible when the animal was again respirated with room air. ABR threshold was an inverse function of blood O2 level with an approximate 3.05 dB elevation for every mmHg decrease in PaO2 (2.89 dB/% SaO2). These findings are probably due to hypoxia induced depression of the endocochlear potential. Since ABR could be recorded in premature human neonates after at least 28 weeks gestation and since the human fetus in utero is also hypoxic, these results indicate that the fetus (greater than 28 weeks gestational age) has a sensorineural hearing loss in addition to a conductive loss.

Transient evoked otoacoustic emissions can be recorded in the rat

Transient (click) evoked (TEOAE) and distortion product (DPOAE) otoacoustic emissions can be recorded in most normal human ears. Even though DPOAEs have been recorded in many laboratory animals, there has not been much success in recording TEOAEs in non-primate mammals except for guinea pigs. In this study, TEOAEs were unequivocally recorded in every rat (and guinea pig) ear studied by using short pulses (40 microseconds) to generate the clicks and a short (1.1 ms) amplifier gain suppression period. The responses were reproducible in the same rat, above the noise floor and disappeared post-mortem. They were shorter in duration in rats than in guinea pigs and were made up of a broadband frequency spectrum between 2 and 4 kHz. Post-mortem, the TEOAEs to 65 dB SPL clicks disappeared at about the same time as DPOAEs to low stimulus intensities and before the DPOAEs to high stimulus intensities. The ability to record TEOAEs in rats and other animals should permit further experimentation into the basic mechanisms of generation of otoacoustic emissions in general and TEOAEs in particular.

Functional Development of Auditory Sensitivity in the Fetus and Neonate

The human fetus responds to sound stimuli while still in utero. The rat and cat begin to hear only after birth. Therefore neonatal rat and cat are used as models of the development of auditory sensitivity in the human fetus. The inner ear of rat responds to stimuli delivered directly to it (bone conduction) before the middle ear can conduct sounds to the inner ear. During this period, middle ear development involves mesenchyme resorption, ossicular hardening and opening of the external canal. The latter stages of inner ear development involve increased magnitude of the endocochlear potential which augments cochlear transduction and the active cochlear amplifier. These developmental stages are probably controlled by thyroid hormone which activates several genes leading to the synthesis of proteins and enzymes required for the structural and functional maturation of the ear. This likely includes the Na+,K(+)-ATPase of the stria vascularis which generates the endocochlear potential. The magnitude of the endocochlear potential is dependent on oxygen supply so that the human fetus in utero whose blood carries less oxygen than the newborn has a hypoxia-induced sensorineural hearing loss. Upon birth and transition from placental to pulmonary oxygenation, the oxygen content of blood is increased, the magnitude of the endocochlear potential is elevated and auditory sensitivity is enhanced.

Vestibular end-organ impairment in an animal model of type 2 diabetes mellitus.

Objectives/Hypothesis To define and assess the functional impairment of the vestibular part of the inner ear in a diabetic state, using a direct and objective test for evaluating the vestibular end‐organ and an animal model for diet‐induced type 2 diabetes mellitus.