Age-related changes of auditory brainstem responses in nonhuman primates.

Nonhuman primates, compared with humans and rodents, have historically been far less used for studies of age-related hearing loss, primarily because of their long life span and high cost of maintenance. Strong similarities in genetics, anatomy, and neurophysiology of the auditory nervous system between humans and monkeys, however, could provide fruitful opportunities to enhance our understanding of hearing loss. The present study used a common, noninvasive technique for testing hearing sensitivity in humans, the auditory brainstem response (ABR), to assess the hearing of 48 rhesus macaques from 6 to 35 yr of age to clicks and tone stimuli between 0.5 and 16.0 kHz. Old monkeys, particularly those above 21.5 yr of age, had missing ABR waveforms at high frequencies. Regression analyses revealed that ABR threshold increased as a function of age at peaks II and IV simultaneously. In the suprathreshold hearing condition (70 dB peak sound pressure level), ABR-based audiograms similarly varied as a function of age such that old monkeys had smaller peak amplitudes and delayed latencies at low, middle, and high frequencies. Peripheral hearing differences remained a major influence associated with age-related changes in audiometric functions of old monkeys at a comparable sensation level across animals. The present findings suggest that hearing loss occurs in old monkeys across a wide range of frequencies and that these deficits increase in severity with age. Parallel to prior studies in monkeys, we found weak effects of sex on hearing, and future investigations are necessary to clarify its role in age-related hearing loss.

Age-related neurochemical changes in the rhesus macaque superior olivary complex.

Positive immunoreactivity to the calcium-binding protein parvalbumin (PV) and nitric oxide synthase NADPH diaphorase (NADPHd) is well documented within neurons of the central auditory system of both rodents and primates. These proteins are thought to play roles in the regulation of auditory processing. Studies examining the age-related changes in expression of these proteins have been conducted primarily in rodents but are sparse in primate models. In the brainstem, the superior olivary complex (SOC) is crucial for the computation of sound source localization in azimuth, and one hallmark of age-related hearing deficits is a reduced ability to localize sounds. To investigate how these histochemical markers change as a function of age and hearing loss, we studied eight rhesus macaques ranging in age from 12 to 35 years. Auditory brainstem responses (ABRs) were obtained in anesthetized animals for click and tone stimuli. The brainstems of the sesame animals were then stained for PV and NADPHd reactivity. Reactive neurons in the three nuclei of the SOC were counted, and the densities of each cell type were calculated. We found that PV and NADPHd expression increased with both age and ABR thresholds in the medial superior olive but not in either the medial nucleus of the trapezoid body or the lateral superior olive. Together these results suggest that the changes in protein expression employed by the SOC may compensate for the loss of efficacy of auditory sensitivity in the aged primate.

Perception of auditory signals.

Auditory signals are decomposed into discrete frequency elements early in the transduction process, yet somehow these signals are recombined into the rich acoustic percepts that we readily identify and are familiar with. The cerebral cortex is necessary for the perception of these signals, and studies from several laboratories over the past decade have made significant advances in our understanding of the neuronal mechanisms underlying auditory perception. This review will concentrate on recent studies in the macaque monkey that indicate that the activity of populations of neurons better accounts for the perceptual abilities compared to the activity of single neurons. The best examples address whether the acoustic space is represented along the "where" pathway in the caudal regions of auditory cortex. Our current understanding of how such population activity could also underlie the perception of the nonspatial features of acoustic stimuli is reviewed, as is how multisensory interactions can influence our auditory perception.

Populations of auditory cortical neurons can accurately encode acoustic space across stimulus intensity.

The auditory cortex is critical for perceiving a sound's location. However, there is no topographic representation of acoustic space, and individual auditory cortical neurons are often broadly tuned to stimulus location. It thus remains unclear how acoustic space is represented in the mammalian cerebral cortex and how it could contribute to sound localization. This report tests whether the firing rates of populations of neurons in different auditory cortical fields in the macaque monkey carry sufficient information to account for horizontal sound localization ability. We applied an optimal neural decoding technique, based on maximum likelihood estimation, to populations of neurons from 6 different cortical fields encompassing core and belt areas. We found that the firing rate of neurons in the caudolateral area contain enough information to account for sound localization ability, but neurons in other tested core and belt cortical areas do not. These results provide a detailed and plausible population model of how acoustic space could be represented in the primate cerebral cortex and support a dual stream processing model of auditory cortical processing.

Representation of con-specific vocalizations in the core and belt areas of the auditory cortex in the alert macaque monkey.

Auditory cortical processing in primates has been proposed to be divided into two parallel processing streams, a caudal spatial stream and a rostral nonspatial stream. Previous single neuron studies have indicated that neurons in the rostral lateral belt respond selectively to vocalization stimuli, whereas imaging studies have indicated that selective vocalization processing first occurs in higher order cortical areas. To test the dual stream hypothesis and to find evidence to account for the difference between the electrophysiological and imaging results, we recorded the responses of single neurons in core and belt auditory cortical fields to both forward and reversed vocalizations. We found that there was little difference in the overall firing rate of neurons across different cortical areas or between forward and reversed vocalizations. However, more information was carried in the overall firing rate for forward vocalizations compared with reversed vocalizations in all areas except the rostral field of the core (area R). These results are consistent with the imaging results and are inconsistent with early rostral cortical areas being involved in selectively processing vocalization stimuli based on a firing rate code. They further suggest that a more complex processing scheme is in play in these early auditory cortical areas.

Effects of stimulus azimuth and intensity on the single-neuron activity in the auditory cortex of the alert macaque monkey.

It has been hypothesized that the primate auditory cortex is composed of at least two processing streams, one of which is believed to selectively process spatial information. To test whether spatial information is differentially encoded in different auditory cortical fields, we recorded the responses of single neurons in the auditory cortex of alert macaque monkeys to broadband noise stimuli presented from 360 degrees in azimuth at four different absolute intensities. Cortical areas tested were core areas A1 and rostral (R), caudal belt fields caudomedial and caudolateral, and more rostral belt fields middle lateral and middle medial (MM). We found that almost all neurons encountered showed some spatial tuning. However, spatial selectivity measures showed that the caudal belt fields had the sharpest spatial tuning, A1 had intermediate spatial tuning, and areas R and MM had the least spatial tuning. Although most neurons showed their best responses to contralateral space, best azimuths were observed across the entire 360 degrees of tested space. We also noted that although the responses of many neurons were significantly influenced by eye position, eye position did not systematically influence any of the spatially dependent responses that we measured. These data are consistent with the hypothesis that caudal auditory cortical fields in the primate process spatial features more accurately than the core and more rostral belt fields.

Auditory influences on visual temporal rate perception.

Visual stimuli are known to influence the perception of auditory stimuli in spatial tasks, giving rise to the ventriloquism effect. These influences can persist in the absence of visual input following a period of exposure to spatially disparate auditory and visual stimuli, a phenomenon termed the ventriloquism aftereffect. It has been speculated that the visual dominance over audition in spatial tasks is due to the superior spatial acuity of vision compared with audition. If that is the case, then the auditory system should dominate visual perception in a manner analogous to the ventriloquism effect and aftereffect if one uses a task in which the auditory system has superior acuity. To test this prediction, the interactions of visual and auditory stimuli were measured in a temporally based task in normal human subjects. The results show that the auditory system has a pronounced influence on visual temporal rate perception. This influence was independent of the spatial location, spectral bandwidth, and intensity of the auditory stimulus. The influence was, however, strongly dependent on the disparity in temporal rate between the two stimulus modalities. Further, aftereffects were observed following approximately 20 min of exposure to temporally disparate auditory and visual stimuli. These results show that the auditory system can strongly influence visual perception and are consistent with the idea that bimodal sensory conflicts are dominated by the sensory system with the greater acuity for the stimulus parameter being discriminated.