Cortical laminar thickness and column spacing in human temporal and inferior parietal lobes: intra-individual anatomical relations.

Harasty, Seldon, Chan, Halliday, and Harding (2003) and Seldon (2005) have proposed a "balloon model" which suggests that myelin growth stretches the cerebral cortex, causing the cortical thickness to decrease and the columnar spacing to increase, in turn affecting the cortical capacity to differentiate afferent signals. This has been tested using temporal lobe (area TA) and inferior parietal lobule (areas PG, PF) histological specimens from human donors. The temporal and inferior parietal regions differ in ways that have never been described. Correlations between the thickness of laminae II-III and columnar spacing in lamina III within individual cytoarchitectonic areas in both hemispheres of each donor were calculated. Those in areas PG/PF are predominantly negative in both hemispheres, as predicted by the model. This is also true for the left hemisphere TA, but the right hemisphere TA shows no correlations between thickness and spacing. Comparisons of thickness and spacing between left and right hemispheres in PG/PF of each donor show no consistent direction, whereas those in TA fairly consistently show thinner laminae and wider column intervals on the left. In the left area TA, females have thinner laminae than males. Thus, intra-area predictions of the balloon model are supported in most areas, whereas the hemispheric asymmetry predictions appear to hold for TA, but not for the inferior parietal lobe.

The left human speech-processing cortex is thinner but longer than the right.

We present histological data from 21 post-mortem, adult human cases that indicate the neocortex on the left planum temporale (secondary auditory cortex) is thinner but longer than that on the right side. The volumes of the left and right regions are approximately equal. Thus, the left planum temporale cortex is long and thin and the right short and thick. The present data fit excellently with previous studies of the volume, surface area, cytoarchitectonics, and neuronal structures of these areas. From these studies we suggest that the hemispheric differences arise from a so-called "balloon model" of cortical development. In this the cortex is extended and stretched by white matter growth. The stretching is greater on the left side, leaving greater distances between neuronal columns and more tangentially (to the pial surface) oriented dendrites on that side. This difference in fine structure can result in more independent activity of individual columns on the left, and could be an anatomical factor in the usual dominance of the left hemisphere for speech perception (Seldon, 1982, 1985).

Effects of intracochlear factors on spiral ganglion cells and auditory brain stem response after long-term electrical stimulation in deafened kittens.

Using an animal model, we have studied the response of the auditory brain stem to cochlear implantation and the effect of intracochlear factors on this response. Neonatally, pharmacologically deafened cats (100 to more than 180 days old) were implanted with a 4-electrode array in both cochleas. Then, the left cochlea of each cat was electrically stimulated for total periods of up to 1000 hours. After a terminal (14)C-2-deoxyglucose (2DG) experiment, the fraction of the right inferior colliculus with a significant accumulation of 2DG label was calculated. Using 3-dimensional computer-aided reconstruction, we examined the cochleas of these animals for spiral ganglion cell (SGC) survival and intracochlear factors such as electrode positions, degeneration of the organ of Corti, and the degree of fibrosis of the scala tympani. The distribution of each parameter was calculated along the organ of Corti from the basal end. There was a positive correlation between SGC survival and the level of fibrosis in the scala tympani, and a negative correlation between SGC survival and the degree of organ of Corti degeneration. Finally, there was a negative correlation between the 2DG-labeled inferior colliculus volume fraction and the degree of fibrosis, particularly in the 1-mm region nearest the pair of electrodes, and presumably in the basal turn.

Chronic study on the neuronal excitability of the cochlear nuclei of the cat following electrical stimulation.

To examine the safety of auditory brainstem prosthesis, the cat cochlear nuclei were implanted and stimulated chronically with bipolar surface electrodes using charge-balanced biphasic current pulses at rates of 250 pulses/s. The stimulation was continuous 16 h/day for up to 12 weeks. The electrically-evoked auditory brainstem response (EABR) was used to monitor neuronal excitability of the cochlear nuclei following the chronic electrical stimulation. The body weight, respiration, and body temperature of the cats were monitored throughout the experiment. The amplitudes and latencies of the EABR waves were measured fortnightly and compared before, during and after the electrical stimulation. The results showed that the respiration, body weight and body temperature of the cats remained within normal limits during the chronic stimulation. During the stimulation, no change was found in the EABR waveform, but a decreased threshold and wider dynamic range were observed after the stimulation. There was no significant change in the amplitudes and latencies of the EABR waves after stimulation. The present findings suggest that chronic bipolar electrical stimulation with surface electrodes at rates of 250 pulses/s is safe for neuronal excitability of the cochlear nuclei in the cat.

Intracochlear factors contributing to psychophysical percepts following cochlear implantation.

The performance of cochlear implant patients may be related to intracochlear, histopathological factors. We have performed detailed post-mortem examinations of five human, implanted cochleas and for each electrode correlated the psychophysical threshold, comfortable level and dynamic range with spiral ganglion cell survival, presence of fibrous tissue and/or new bone, and distance between the centers of the electrode bands and Rosenthal's canal. The psychophysical parameters were strongly interrelated. Threshold and comfort levels correlated with the distance between the electrodes and Rosenthal's canal. Threshold levels also correlated with the presence of intracochlear fibrous tissue and new bone, especially with the former. The dynamic range showed a negative correlation with intracochlear pathology, especially with new bone. Comfort levels and dynamic range were related to spiral ganglion cell survival. The distance between the electrodes and the modiolus increased with increasing levels of fibrous tissue and new bone. Spiral ganglion cell survival was decreased with increasing levels of fibrous tissue and new bone.

Acute study on the efficacy and safety of an auditory brainstem prosthesis.

Patients with profound binaural sensorineural hearing loss can be treated with cochlear implantation. In recent years, patients who have lost the integrity of the auditory nerve between the spiral ganglion and the cochlear nucleus in the brainstem, and cannot benefit from a cochlear implant, have reported auditory sensations following direct stimulation of the cochlear nucleus with an auditory brainstem prosthesis. To examine the safety and efficacy of such a prosthesis, the cochlear nuclei of guinea-pigs were acutely implanted and stimulated unilaterally with bipolar surface electrodes using the parameters of human implants. The activation of the central auditory pathway by the prosthesis was demonstrated using the 2-deoxyglucose technique. There was broad 2-deoxyglucose labelling in the ipsilateral cochlear nucleus and bilaterally in the inferior colliculi, indicating unusual stimulation of the ipsilateral ascending pathway. Histological examination was performed on all cochlear nuclei. The volumes of cochlear nuclei and the neuron sizes and density in the cochlear nuclei were analysed with three-dimensional reconstruction techniques, and comparisons were made between the stimulated and unstimulated sides. No histological difference, either by direct visual observation or by statistical comparisons, was observed between the stimulated cochlear nuclei and the control sides. These results suggest that in the acute case the auditory brainstem prostheses can safely and effectively activate the auditory pathway in guinea-pigs.

Acute study on the neuronal excitability of the cochlear nuclei of the guinea pig following electrical stimulation.

To help deaf patients who cannot benefit from the cochlear implant due to interruption of the auditory nerve, a central auditory prosthesis has been developed to directly stimulate the cochlear nucleus in the brainstem. The electrode array lies on the surface of the cochlear nucleus and is designed to stimulate at 250 pulses/sec. To examine the safety of this prosthesis, guinea pig cochlear nuclei were stimulated acutely with bipolar surface electrodes using charge-balanced biphasic current pulses at rates of 250, 500 or 1,000 pulses/s and charge intensities of 1.8, 2.8, 3.5 or 7.1 microC/phase cm(-2). The electrically evoked auditory brainstem response (EABR) was used to monitor neuronal excitability of the cochlear nuclei following this acute electrical stimulation. Respiration rate and body temperature were also monitored during the experiment. The amplitudes and latencies of the EABR waves were measured and compared among the before, during and after stimulation periods. The results showed that respiration rate and body temperature remained within normal limits for the duration of the acute stimulation. During and after electrical stimulation, no change was found in the EABR waveform, dynamic ranges and threshold with up to 6 h direct continuous stimulation of the cochlear nucleus. There was no significant change in the amplitudes and latencies of the EABR waves after stimulation. However, a slight temporary reduction in the amplitude of the EABR waves was observed at 30-60 min during the course of acute stimulation using the highest charge density (7.1 microC/phase cm(-2)). This reduction showed a stronger correlation with the stimulus current, charge/phase and charge density than threshold. The present findings suggest that acute bipolar electrical stimulation with surface electrodes at rates up to 1,000 pulses/s and charge density up to 7.1 microC/phase cm(-2) is safe for neuronal excitability of the cochlear nucleus in guinea pig.

Histological and physiological effects of the central auditory prosthesis: surface versus penetrating electrodes.

To rehabilitate profoundly deaf patients who are not suitable for cochlear implants, central auditory prostheses have been implanted. To compare two possible electrode configurations - penetrating and surface ones - electrical stimulation of the cochlear nucleus with both types of arrays was tested on guinea pigs and cats. Electrophysiological, autoradiographic and histological measures were used to study effects of the central auditory prostheses on the auditory pathway. The results showed that a successful electrically evoked auditory brainstem response could be recorded with both surface and penetrating electrodes in cats and guinea pigs. In guinea pigs the penetrating electrodes had advantages over surface arrays in the sense of lower thresholds and wider dynamic ranges. In cats penetrating electrodes showed lower thresholds than surface ones. In cats and guinea pigs stimulated with either surface or penetrating electrodes, evoked 2-deoxyglucose (2-DG) label was found in the auditory pathway from the cochlear nucleus to the inferior colliculus. No non-auditory tissues were found with evoked 2-DG label. Histological results showed that in subdivisions of the guinea pig cochlear nucleus stimulated with penetrating electrodes the neurone density was decreased, and the mean soma area was increased compared with the control side. In the cat, penetrating electrodes were associated only with increased mean soma area in parts of the stimulated cochlear nucleus. These results suggest that the physiological advantages of penetrating electrodes over surface ones were achieved with some trade-off in safety, especially in the guinea pig.

Computer-aided three-dimensional reconstruction in human cochlear maps: measurement of the lengths of organ of Corti, outer wall, inner wall, and Rosenthal's canal.

This paper describes the application of computer-aided three-dimensional reconstruction to measurements of the length of the organ of Corti (mean +/- SD, 35.58 +/- 1.41 mm), scala tympani outer wall (40.81 +/- 1.97 mm), scala tympani inner wall (18.29 +/- 1.47 mm), and Rosenthal's canal center (15.98 +/- 1.33 mm) in eight adult male cochleas. The Rosenthal's canal center ranged between 1 3/4 and 2 turns, did not appear to be linearly related to the organ of Corti, and lay near the basal end of the latter. The length of the organ of Corti measured with three-dimensional reconstruction differed by 7.6% +/- 3.2% ("cutting angle difference") from that derived from traditional two-dimensional reconstruction on the plane perpendicular to the plane of section, and by 2.6% +/- 1.7% ("geometric difference") from that derived from two-dimensional reconstruction on the axial plane at right angles to the modiolar axis.

Does age at cochlear implantation affect the distribution of 2-deoxyglucose label in cat inferior colliculus?

Cochlear implants are one treatment for children who are born deaf or become deaf before acquiring language. The question of optimum age for implantation arises. Using an animal model, we have studied the response of the auditory brainstem to implantation at various ages. Neonatally, pharmacologically deafened cats were implanted with a 4-electrode array in the left cochlea at ages from 100 to over 180 days. Eleven were chronically stimulated (1000 h if possible) with charge-balanced, biphasic current pulses; eight were unstimulated controls. In a terminal experiment, each animal received [14C]2-deoxyglucose i.v. preceding a 45-min stimulation program. The fraction of the right inferior colliculus (IC) with a significant accumulation of label was calculated. If age at implantation were a significant factor in determining the size of the responding region, the fraction would depend on the age; this was not observed. However, there was considerable variation in the IC fraction sizes within both stimulated and unstimulated groups, leading to the conclusion that there are factors other than age which determine the size of the responding region. Thus, for deaf children of corresponding ages, age at implantation may not be of critical importance.

Silastic with polyacrylic acid filler: swelling properties, biocompatibility and potential use in cochlear implants.

We present a new hygroscopic implant material which consists of high-molecular-weight polyacrylic acid (PAA) as a filler in a Silastic matrix. The mixture swells upon immersion in bodily fluids; the degree of swelling depends on the ratio of PAA to Silastic and allows the design of implants that will achieve their final shape and size only after the implantation procedure. In vivo and in vitro biocompatibility tests reveal no adverse cellular or tissue responses. In cochlear implant development the material has been experimentally incorporated into intracochlear electrode arrays which curl after insertion, and in bacteriostatic devices for electrode fixation.

Effect of chronic electrical stimulation on cochlear nucleus neuron size in normal hearing kittens.

Very young cochlear-implant candidates may have undetected islands of residual hearing. Would the maturation of these functioning auditory neurons be affected by chronic cochlear stimulation? This was tested by examining neuron sizes in the cochlear nuclei of young, normal hearing kittens with and without chronic cochlear stimulation. Six animals received bilateral intra- or extracochlear implants and were electrically stimulated unilaterally for periods of 1,000-1,500 hours. After sacrifice, cross-sectional areas of approximately 11,000 neurons somata in the cochlear nuclei were measured with an image-analysis system. There were statistically significant differences between stimulated and unstimulated nuclei, especially the posteroventral cochlear nucleus (PVCN), in individual cats, but the directions of the differences were inconsistent. Overall, there was no significant effect of electrical stimulation on soma size. These results indicate that chronic electrical stimulation of the auditory nerve has no positive or negative trophic effects on otherwise innervated, maturing cochlear nucleus neurons.

Pediatric cochlear implantation. Radiologic observations of skull growth.

We investigated the effects of long-term implantation of auditory prostheses on skull growth in young animals. Four monkeys were implanted with dummy cochlear implants at 6 months of age. To simulate implantation in children, the bed for the receiver-stimulator or interconnecting plug was drilled across a calvarial suture down to the underlying dura. Plain skull roentgenograms were periodically taken to monitor head growth for up to 3 years after implantation. These longitudinal measurements revealed no significant asymmetric skull growth. Postmortem measurements using computed tomographic scans confirmed these results and showed no significant difference in the intracranial volumes between the implanted and control sides of each animal or between experimental and nonimplanted control monkeys. These results suggest that long-term cochlear implantation in very young children will not cause any significant deformity of the skull.