Jean K. Moore

The human auditory system: A timeline of development

This review traces the structural maturation of the human auditory system, and compares the timeline of anatomical development with cotemporaneous physiological and behavioral events. During the embryonic period, there is formation of basic structure at all levels of the system, i.e. the inner ear, the brainstem pathway, and the cortex. The second trimester is a time of rapid growth and development, and by the end of this period, the cochlea has acquired a very adult-like configuration. During the perinatal period, the brainstem reaches a mature state, and brainstem activity is reflected in behavioral responses to sound, including phonetic discrimination, and in evoked brainstem and early middle latency responses. The perinatal period is also the time of peak development of brainstem input to the cortex through the marginal layer, and of the long latency cortical potentials, the N2 and mismatch negativity. In early childhood, from the sixth post-natal month to age five, there is progressive maturation of the thalamic projections to the cortex and of the longer latency Pa and P1 evoked potentials. Later childhood, from six to twelve years, is the time of maturation of the superficial cortical layers and their intracortical connections, accompanied by appearance of the N1 potential and improved linguistic discriminative abilities. Some consideration is given to the potential negative effects of deafness-induced sound deprivation during the perinatal period and childhood.

Cytoarchitectural and Axonal Maturation in Human Auditory Cortex

This study followed the maturation of human auditory cortex from the beginning of the second trimester of gestation to young adulthood. Histological and immunohistochemical techniques were used to trace the development of a laminar cytoarchitecture and an adult pattern of axonal neurofilament expression. From the 16th fetal week to the 4th postnatal month, the cortex progresses from a marginal layer and an undifferentiated cortical plate to incipient lamination. Between the 22nd fetal week and the 4th postnatal month, a two-tiered band of neurofilament-immunoreactive axons develops in layer I, but subsequent to the 4th month, the number of immunopositive axons in this layer is greatly reduced. Between the middle of the first year of life and age 3 years, the laminar pattern of cytoarchitecture becomes fully mature and a network of immunostained axons develops in layers VI, V, IV, and IIIc. This axonal plexus in the deep cortical layers continues to increase in density until age 5. Beginning at 5 years of age, a network of neurofilament-positive axons develops in the superficial layers IIIb, IIIa, and II, and by 11-12 years of age, overall axonal density is equivalent to that seen in young adulthood. This extended time span of axonal maturation has implications for the emergence of auditory cortical function.

Auditory Brainstem Implant: I. Issues in Surgical Implantation:

Most patients with neurofibromatosis type 2 (NF2) are totally deaf after removal of their bilateral acoustic neuromas. Twenty-five patients with neurofibromatosis type 2 have been implanted with a brainstem electrode during surgery to remove an acoustic neuroma. The electrode is positioned in the lateral recess of the fourth ventricle, adjacent to the cochlear nuclei. The present electrode consists of three platinum plates mounted on a Dacron mesh backing, a design that has been demonstrated to be biocompatible and positionally stable in an animal model. Correct electrode placement depends on accurate identification of anatomic landmarks from the translabyrinthine surgical approach and also on Intrasurglcal electrophysiologic monitoring. Some tumors and their removal can result in significant distortion of the brainstem and surrounding structures. Even in the absence of Identifiable anatomic landmarks, electrode location can be adjusted during surgical placement to find the location that maximizes the auditory evoked response and minimizes activation of other monitored cranial nerves. Stimulation of the electrodes produces auditory sensations in most patients, with results similar to those of single-channel cochlear Implants. A coordinated multldlscipllnary team is essential for successful application of an auditory brainstem implant.

Time course of axonal myelination in the human brainstem auditory pathway

Structures in the human brainstem auditory pathway, from the proximal end of the cochlear nerve to the inferior colliculus, undergo myelination between the 26th and 29th fetal weeks. By the 26th week of gestation, axons in the cochlear nerve and brainstem pathways have acquired linear arrays of oligodendrocytes, and faint myelin sheaths can be distinguished. By the 29th week, definitive myelination is present in all auditory pathways, including the proximal end of the cochlear nerve, trapezoid body, lateral lemniscus, dorsal commissure of the lemniscus, commissure of the inferior colliculus and brachium of the inferior colliculus. Subsequent to the 29th gestational week, density of myelination increases in all pathways until at least 1 year postnatal age. The time of onset of myelination coincides with the onset of acousticomotor reflexes and brainstem auditory evoked responses, processes which depend on rapid, synchronized conduction of auditory impulses in the cochlear nerve and brainstem. The cotemporality in appearance of myelin, reflex responses, and evoked responses supports the idea that the 26th to 28th gestational weeks are a critical period in the onset of human central auditory function. The subsequent increase in myelin density is likely to be a factor in the steady decrease in ABR wave III-V latencies observed during the perinatal period.

Auditory Brainstem Implant: II. Postsurgical Issues and Performance

The auditory brainstem Implant (ABI) restores some hearing sensations to patients deafened by bilateral acoustic tumors. Electrodes are stable for more than 10 years. In most cases nonaudltory side effects can be avoided by judicious selection of the stimulating waveform and electrode configuration. Most perceptual measurements demonstrate that the ABI produces psychophysical and speech performance similar to that of single-channel cochlear implants. ABI patients receive suprasegmental Information in speech and significant enhancement of speech understanding when the sound from the ABI is combined with Ilpreading.

THE CASE FOR EARLY IDENTIFICATION OF HEARING LOSS IN CHILDREN Auditory System Development, Experimental Auditory Deprivation, and Development of Speech Perception and Hearing

Human infants spend the first year of life learning about their environment through experience. Although it is not visible to observers, infants with hearing are learning to process speech and understand language and are quite linguistically sophisticated by 1 year of age. At this same time, the neurons in the auditory brain stem are maturing, and billions of major neural connections are being formed. During this time, the auditory brain stem and thalamus are just beginning to connect to the auditory cortex. When sensory input to the auditory nervous system is interrupted, especially during early development, the morphology and functional properties of neurons in the central auditory system can break down. In some instances, these deleterious effects of lack of sound input can be ameliorated by reintroduction of stimulation, but critical periods may exist for intervention. Hearing loss in newborn infants can go undetected until as late as 2 years of age without specialized testing. When hearing loss is detected in the newborn period, infants can benefit from amplification (hearing aids) and intervention to facilitate speech and language development. All evidence regarding neural development supports such early intervention for maximum development of communication ability and hearing in infants.

Accessing the tonotopic organization of the ventral cochlear nucleus by intranuclear microstimulation

This study is part of a program to develop an auditory prosthesis for the profoundly deaf, based on multichannel microstimulation in the cochlear nucleus. The functionality of such a device is dependent on its ability to access the tonotopic axis of the human ventral cochlear nucleus in an orderly fashion. In these studies, we utilized the homologies between the human and feline ventral cochlear nuclei and the known tonotopic organization of the central nucleus of the inferior colliculus (IC). In anesthetized cats, stimuli were delivered to three or four locations along the dorsal-to-ventral axis of the posteroventral cochlear nucleus (PVCN), and for each stimulus location, we recorded the multiunit neuronal activity and the field potentials at 20 or more locations along the dorsolateral-ventromedial (tonotopic) axis of the IC. The current source-sink density (CSD), which delimits regions of neuronal activity, was computed from the sequence of field potentials recorded along this axis. The multiunit activity and the CSD analysis both showed that the tonotopic organization of the PVCN can be accessed in an orderly manner by intranuclear microstimulation in several regions of the PVCN, using the range of stimulus pulse amplitudes that have been shown in previous studies to be noninjurious during prolonged intranuclear microstimulation via chronically implanted microelectrodes. We discuss the applicability of these findings to the design of clinical auditory prostheses for implantation into the human cochlear nucleus.

Organization of the human superior olivary complex

The distinctive morphology of the human superior olivary complex reflects its primate origins, but functional evidence suggests that it plays a role in auditory spatial mapping which is similar to olivary function in other mammalian species. It seems likely that the well‐developed human medial olivary nucleus is the basis for extraction of interaural time and phase differences. The much smaller human lateral olivary nucleus probably functions in analysis of interaural differences in frequency and intensity, but the absence of a human nucleus of the trapezoid body implies some difference in the mechanisms of this function. A window on human olivary function is provided by the evoked auditory brainstem response (ABR), including its binaural interaction component (BIC). Anatomical, electrophysiological, and histopathological studies suggest that ABR waves IV and V are generated by axonal pathways at the level of the superior olivary complex. Periolivary cell groups are prominent in the human olivary complex. The cell groups located medial, lateral, and dorsal are similar to periolivary nuclei of other mammals, but the periolivary nucleus at the rostral pole of the human olivary complex is very large by mammalian standards. Within the periolivary system, immunostaining for neurotransmitter‐related substances allows us to identify populations of medial and lateral olivocochlear neurons. The human olivocochlear system is unique among mammals in the relatively small size of its lateral efferent component. Some consideration is given to the idea that the integration provided by periolivary cell groups, particularly modulation of the periphery by the olivocochlear system, is an extension of the spatial mapping function of the main olivary nuclei. Microsc. Res. Tech. 51:403–412, 2000.

Audiologic outcomes with the penetrating electrode auditory brainstem implant.

Objective: The penetrating electrode auditory brainstem implant (PABI) is an extension of auditory brainstem implant (ABI) technology originally developed for individuals deafened by neurofibromatosis type 2. Whereas the conventional ABI uses surface electrodes on the cochlear nuclei, the PABI uses 8 or 10 penetrating microelectrodes in conjunction with a separate array of 10 or 12 surface electrodes. The goals of the PABI were to use microstimulation to reduce threshold current levels, increase the range of pitch percepts, and improve electrode selectivity and speech recognition. Patients and Protocol: In a prospective clinical trial, 10 individuals, all with neurofibromatosis type 2, received a PABI after vestibular schwannoma removal via a translabyrinthine approach. All study participants met strict requirements for informed consent as part of a Food and Drug Administration clinical trial. Approximately 8 weeks after implantation, PABI devices were activated and tested at our tertiary clinical and research facility. Mean follow-up time was 33.8 months. Study Design: Using a single-subject design, we measured thresholds and dynamic ranges, electrode-specific pitch percepts, and speech perception performance at regular intervals. Results: Penetrating electrodes produced auditory thresholds at substantially lower charge levels than surface electrodes, a wide range of electrode-specific pitch sensations, and minimal cross-electrode interference and could be used in speech maps either alone or in combination with surface electrodes. However, less than 25% of penetrating electrodes resulted in auditory sensations, whereas more than 60% of surface electrodes were effective. Even after more than 3 years of experience, patients using penetrating electrodes did not achieve improved speech recognition compared with those using surface electrode ABIs. In patients with usable penetrating electrodes, City University of New York Sentence Test scores with sound and visual information were 61.6% in the PABI group and 64.7% in a surface ABI cohort (p = not significant). Conclusion: The PABI met the goals of lower threshold, increased pitch range, and high selectivity, but these properties did not result in improved speech recognition.

The human olivocochlear system : Organization and development

The goals of the present study were to identify olivocochlear neurons in the human brainstem, to establish the time course of their early development and to compare the organization of the human olivocochlear system to that of other mammals. To accomplish these goals, we used immunohistochemistry for choline acetyltransferase (ChAT) and calcitonin gene-related peptide (CGRP) in postmortem brainstems of human subjects ranging in age from 16 fetal weeks to 17 years. By immunostaining, we identified two classes of cells in the superior olivary complex: both classes were seen to be present from the twenty-first fetal week to the seventeenth year. Neurons which are immunostained only for ChAT are located primarily in the dorsomedial, ventral and ventrolateral sectors of the periolivary region. These neurons are predominantly bipolar or multipolar cells, and are probably homologous to medial olivocochlear neurons in other species. A second population of cells is immunoreactive for both ChAT and CGRP. This population includes a cluster of mostly small oval neurons, located on the dorsal edge of the olivary complex, and a variable number of cells found along the margin of the lateral olivary nucleus. These ChAT- and CGRP-immunoreactive cells are likely to be homologous to the lateral olivocochlear system in other mammals. With increasing age, the dorsal cluster of small cells shifts from its original cap-like position over the lateral olivary nucleus to become an extended column of cells lying among the fibers of the olivocochlear bundle.