Effects of unilateral deafening on the cochlear nucleus of the guinea pig at different ages.

Developmental changes in spherical cell sizes were measured in the ventral cochlear nucleus (VCN) in normal guinea pigs aged 2 days and 2, 7 and 12 weeks to establish the time course of postnatal neuronal growth, as a baseline for our experimental work. A continued growth of spherical cell size was observed in the VCN up to 7 weeks postnatally. Animals were unilaterally deafened by cochlear perfusion with kanamycin sulphate at ages 1 and 6 weeks. After 6 weeks survival the spherical cells were measured in the VCNs of both sides. Unilateral deafferentation at both ages caused an ipsilateral reduction in spherical cell size, neurons of the younger group being smaller than in the older. On the contralateral side these cells in the older group were larger than age-matched controls while in the younger group there was no difference compared with age-matched controls. These findings suggest that the results of deafferentation are age-dependent, and may indicate an ability of the neural circuitry to adapt to the loss of sensory input on the other side.

Structural effects of short term and chronic extracochlear electrical stimulation on the guinea pig spiral organ.

To assess the effects of extracochlear electrical stimulation on cochlear structure, guinea pigs were implanted and stimulated with single middle ear electrodes either at round window or promontory sites, and their cochleae examined by transmission electron microscopy. Implanted but unstimulated, or unimplanted control animals were examined in the same way. Alternating current stimulation at the promontory for 2 h at 150 Hz, 500 microA, caused outer hair cell efferent endings to become dense and vacuolated, but no hair cells were damaged. With direct current stimulation at 500 microA for 2 h the basal regions of the stimulated cochlea were badly damaged and many outer hair cells lysed. Long term (up to 1200 h) round window stimulation at 100 or 141 Hz, 15-91 microA rms, did not cause cell death or inner hair cell damage, but basal outer hair cells and their efferent endings were badly affected in both ipsilateral and contralateral cochleae. The compound action potential of the auditory evoked response to broad band click stimuli was not altered by chronic electrical stimulation. It is concluded that chronic stimulation with the parameters used does not threaten cochlear survival, and it is proposed that the bilateral structural changes induced by chronic stimulation are caused by excessive activation of the cochlear efferent pathways.

Further studies of the effects of continuous white noise of moderate intensity (70--80 dB SPL) on the cochlea in young guinea pigs. Time course and distribution of hair cell degeneration.

Guinea pigs aged one week were exposed to white noise at a maximum of 76 dB SPL for 7 days and were then killed 3, 8 and 16 weeks later for histological examination of the cochlea by the surface preparation method. Appreciable increases in outer hair cell losses were observed in the apical turn 3/3 1/2, chiefly in the outer two rows, between the 3rd and 8th week, but not between the 8th and 16th week. No significant losses were seen in control groups corresponding to 3- and 8-week periods, although in the control group of 16 weeks' survival, small deficits, attributable to natural ageing, were seen in the apical half-turn, 3 1/2.

Extra-tympanic electrocochleography.

A non-invasive technique for recording the cochlear action potential in adults without recourse to sedation or local anaesthesia is presented. This technique has been assessed in two ways: (1) A group of normal subjects was tested to obtain distributions of response amplitude and latency as functions of stimulus intensity. (2) A group of patients with Meniere's disease was tested with trans- and extra-tympanic electrocochleography to compare the intensity amplitude functions and wave-forms obtained from the two methods. On the basis of this study the use of extra-tympanic electrocochleography as a replacement for the trans-tympanic method is discussed.

The effects of combined gentamicin and white noise on the spiral organ of young guinea pigs. A structural study.

The present work describes the effects on the spiral organ of very young guinea pigs, of continuous white noise (76 dB SPL, 7 days) combined with gentamicin, using surface preparations and both transmission and scanning electron microscopy to analyse structural changes. Gentamicin only, at 80 mg/kg/day for 5 days did not cause any perceptible loss of hair cells, and only minimal structural changes. When combined with 7 days of white noise, there was a widespread effect on outer hair cells throughout the cochlea, some changes being similar to those induced by sound alone, others being seen only in the combined experiments. Outer hair cell losses with sound and gentamicin treatment were highly variable, but in addition to apical damage, also seen in sound-treated animals, a more basal area of cell loss appeared in the spiral organ.

Scintigraphic evaluation of glomus tumours.

The current investigations of choice for a suspected glomus tumour are either direct or indirect angiography to include digital subtraction followed by computerized tomography (CT) or magnetic resonance imaging (MRI) or, if available, CT and MRI with gadolinium alone. Although these modalities confirm the diagnosis and give anatomical information to facilitate accurate staging, they do not provide functional data. The use of radionuclide scintigraphy can add an extra physiological dimension to glomus tumour imaging. Iodine-131/123 metaiodobenzylguanidine (MIBG) is a tumour imaging agent which has been used to diagnose head and neck neuroendocrine tumours to include paragangliomata and medullary carcinoma of the thyroid (MCT). However, it is expensive and the new head and neck tumour imaging agent technetium-99 m (Tc99m) (v) dimercaptosuccinic acid (DMSA) has superceded it as the imaging agent of choice to evaluate MCT. We report a patient with a glomus jugulare tumour which was evaluated with I131/I123-MIBG and Tc99m (v) DMSA. The tumour was functional and is the first reported case exhibiting positive accumulation of both I131-MIBG and Tc99m (v) DMSA. The patient was subsequently treated with a therapeutic dose of I131-MIBG. The significance of these results is discussed.

Enhanced horseradish peroxidase uptake in the electrically stimulated cochlea of the guinea pig.

Stimulation with alternating current at the round window causes an accelerated uptake of extracellular HRP by endocytotic vesicles in inner hair cells at the base of the stimulated cochlea, near the site of the electrode, but does not noticeably affect uptake into outer hair cells. After unilateral electrical stimulation, efferent endings on outer hair cells at the cochlear base show increased vesicular and endosomal labelling in both the ipsilateral and contralateral ears. It is concluded that round-window electrical stimulation increases afferent synaptic activity in inner hair cells near the electrode site, and also increases synaptic activity in OHC efferent endings, not only of the ipsilateral cochlea but also of the corresponding region of the contralateral cochlea. Rapid diffuse cytoplasmic labelling of inner and outer hair cells also occurs sporadically in both stimulated and unstimulated cochleae. However, in efferent terminals, diffuse labelling is restricted to stimulated animals, and occurs bilaterally, in corresponding basal regions of the cochlea.

Speech signal presentation to the totally deaf.

We have developed a system for single-channel electrical stimulation of the totally deaf. The patient wears a removeable electrode assembly which stimulates the cochlear promontory and can be inserted and removed like the earmould of a hearing aid. This approach minimises the risk of mechanical or electro-chemical damage to structures within the cochlea. Charge-balanced stimulation is used to present those speech pattern elements that are matched to the patients' lipreading needs and their new sensory abilities. Objective tests show improvements both in patients' perceptive and productive abilities.

Structural alteration of hair cells in the contralateral ear resulting from extracochlear electrical stimulation.

Chronic electrical stimulation of the auditory nerve in patients with profound sensori-neural deafness is becoming increasingly routine. Therefore, it is important to understand more about the long-term consequences of this procedure. Hitherto, structural studies in animals after electrocochlear stimulation have concentrated on the stimulated cochlea. Here we have examined the effects of unilateral extracochlear electrical stimulation on the spiral organ of both the ipsilateral and contralateral ears of the mature guinea pig, and have found alterations in the structure of the outer hair cells and their efferent nerve terminals in the contralateral as well as the ipsilateral cochlea. This is the first evidence for a structural influence of efferent activity on the cochlea. Although the importance of the efferent system, consisting of the crossed and uncrossed olivo-cochlear bundles, is well established in providing central control of the sensory pathways, its exact role in hearing is incompletely understood. However, it is known that the outer hair cells and their efferent innervation are important in their contribution to inner hair cell responses and in modulating the micromechanics of the whole cochlea. These efferent functions now appear to be related to an important part of cochlear morphology, and are also relevant to our understanding of cochlear neurobiology, normal development and the management of hearing disability in both adult and child.

External electrical stimulation of the cochlea: clinical, psychophysical, speech-perceptual and histological findings.

Our progress towards the development of a particular form of cochlear implant for the totally deaf is described. A single channel stimulation at the round window or promontory is used. This involves a minimum of surgical intervention and infective risk, preserves the possibility of remission and allows the application of later developments. The signal used for stimulation is designed to be matched both to the deaf lip-reader's needs and to his new, restricted, auditory ability. This is done by concentrating on the acoustic pattern components of speech which carry intonation and voiced-voiceless information. Surgical electrophysical, psychoacoustic and speech perceptual aspects of our work with twelve patients are described. The tests involve responses, for example, relating to: threshold for sinusoids; frequency difference limens; periodic -aperiodic discrimination; stress placement; and consonant labelling using combined visual and electrical inputs. Relatively extensive measurements were made with six patients. Significant individual differences were found and the sets of responses provide an essential basis for an appraisal of the potential usefulness of our work to the individual patient. Possible reasons for the individual differences are discussed. A brief indication is given of the techniques which we have developed for the future speech training and speech production evaluation of patients with electro-cochlear voice monitoring. The final section of our paper mentions our histological investigation of the effects of this type of stimulation in the guinea pig.