Elsevier

Neurobiology of Aging

Volume 23, Issue 4, July–August 2002, Pages 565-578
Neurobiology of Aging

Behavioral and neural measures of auditory temporal acuity in aging humans and mice

https://doi.org/10.1016/S0197-4580(02)00008-8Get rights and content

Abstract

Three experiments compared auditory temporal acuity in humans and in the behavior and single cells in the inferior colliculus (IC) of mice, to establish the comparability of aging effects on temporal acuity across species, and to suggest a neural foundation. The thresholds for silent gaps placed in white noise (MGTs) were similar in young mice and young humans, and increased in some but not all old humans and old mice. Neural MGT in the most sensitive cells of both young and old mice was comparable to behavioral MGT in the young of both species, but older mice had more cells with very high MGT. Human listeners were selected to have minimal absolute hearing loss. Older mice had significant hearing loss that was correlated with MGT in behavioral, but not in neural, measures. Some old mice and some old IC cells, however, had low MGTs coupled with elevated absolute hearing thresholds. Age-related changes in temporal acuity appear comparable in humans and mice. The data suggest a common deficit in neural mechanisms.

Introduction

As people age they often experience more difficulty with speech perception than would be predicted by their increased audibility thresholds for speech sounds, especially when listening in a noisy environment [1]. Correlations between self-assessed hearing handicap scores and absolute audibility thresholds for various frequencies are moderate (0.5–0.6) in older listeners, indicating that individual differences in absolute thresholds account for no more than about 30% of the variance in perceived hearing ability [6]. Changes in absolute thresholds typically result from peripheral degeneration of sensory receptors in the ear, but the speech data suggest that age-related changes in processing that occurs in the central auditory system must also be examined in order to explain the effects of aging in complex listening tasks (presbycusis). Such central effects may result from damage accumulated over a lifetime from drug-, chemical-, and noise-exposure occurring throughout the auditory system, from genetic predisposition, or from physiological effects intrinsic to the aging process. These varied contributors to presbycusis are difficult to parcel out in human listeners, but may be studied more readily in animal models. In the present series of hearing experiments we compare age-related changes in human listeners with especially good hearing for their age to age-related changes in the behavior and neural activity of mice that are known to be free of environmental insults and genetic predispositions for age-related hearing loss. The common auditory task across experiments was to measure temporal acuity, a sensory task that in humans captures our ability to detect rapid temporal changes that characterize everyday speech signals. In these studies we show that some old human listeners and some old mice are deficient in threshold measures of temporal acuity, and that individual differences in temporal acuity unrelated to changes in absolute thresholds are present in humans, and to a lesser extent, in the behavior of mice. We show also that some onset neurons in the inferior colliculus (IC) of these old mice show large decrements in sensitivity to gaps while other old cells maintain normal thresholds, again unrelated to their varying sensitivity to detecting noise bursts.

Temporal acuity for acoustic transients is commonly measured in humans by determining the threshold for detecting brief silent gaps in an otherwise continuous sound (the minimum gap threshold or MGT). Increased speech recognition thresholds in background noise have been correlated with increased MGTs [16], [37], [39], and it has been found that older listeners have longer MGTs than young listeners [17], [33], [34], [36], [37], though it has also been reported that not all old listeners have longer MGTs even among those with diminished sensitivity for sounds, as demonstrated by absolute threshold measures [29], [30]. Correlations with MGT also account for no more than 30 to 40% of the variance in speech perception abilities, and so while this ability is important, it must be considered as only one among several factors that separately or jointly contribute to speech perception. Gap thresholds are influenced by moderate-to-severe hearing losses in absolute sensitivity in both younger [9] and older [13] listeners, and the interactive effect of age and absolute sensitivity has been controlled in studies of age-related temporal acuity deficits in several ways. One study [34] measured listeners’ absolute thresholds and presented gap stimuli (tones) at 40 and 60 dB SL. The older listeners (most of whom had less than 25 dB hearing loss) had longer MGTs than the younger listeners, but MGTs were unaffected by the sensation level of the gap stimulus and were independent of the listener’s absolute thresholds. In other studies [36], [37] each younger listener was closely matched with an older listener using audiometric thresholds. MGTs were measured using gaps in noise bursts that were amplitude modulated to sound more speech-like. Again, an age-related MGT difference was found, and MGTs were uncorrelated to audiometric thresholds for both age groups. These results indicate that auditory temporal acuity may deteriorate with age even when the sound is transduced normally (in the sense of audiometric sensitivity) by the peripheral auditory system.

A physiological correlate of this age-related temporal deficit has been reported in the human central nervous system (CNS) [42]. The Wave V latency of the auditory brainstem response (ABR) of younger and older listeners was measured in a forward-masking paradigm. The stimuli were same-frequency tone pairs separated by an interval that varied between 2 and 64 ms, durations that span the range of gap detection. Wave V (commonly attributed to neural activity at the level of the auditory midbrain) was delayed more in old compared to young listeners when the interval between the tone bursts was very short, suggesting that the processing of rapid temporal events by the auditory midbrain is impaired with age. Furthermore, listeners in the two age groups had similar audiograms, again showing that temporal processing decrements need not be accompanied by peripheral hearing loss.

Further exploration of age-related changes is facilitated by animal models, which offer increased control over possible confounding variables and a greater range of research techniques. Temporal processing deficits have been found in old gerbils [4] and CBA mice [20], [41]. The CBA mouse is ideal for this research because its hearing is well understood, it ages quickly compared to larger mammals, and it retains relatively good peripheral sensitivity into old age [27]. In addition, the behavioral response of CBA mice to gaps can be measured using reflex modification audiometry [43], which provides an efficient method for testing large numbers of animal subjects. This method of audiometry is based on the inhibition of the acoustic startle reflex caused by stimuli occurring just before the startle stimulus (ASR inhibition), a phenomenon which reflects neural activity at the level of the inferior colliculus [26], [28]. Thus, with this behavioral test, the mice can provide a link between human psychophysics and animal physiology directed at the inferior colliculus.

Recordings of single unit responses to gaps embedded in noise bursts provide a direct approach to the study of the CNS contribution to temporal processing. In young CBA mice, the response of inferior colliculus (IC) neurons to gaps in noise bursts has been compared with behavioral MGTs obtained using ASR inhibition [40]. It was found that the neural response rate during the gap (for tonic units) or during the noise burst following the gap (for phasic units) changed systematically as the gap was varied in duration. Both the behavioral MGTs and the neural MGTs for phasic onset units were 2–3 ms as they are in human observers under optimal conditions. Importantly, both reached an asymptote for gap durations greater than 3–4 ms, revealing a relationship between neural and behavioral responses to gaps in young CBA mice.

The neurophysiological approach of measuring gap functions in the IC has recently been extended to the study of presbycusis [41]. Age differences were reported in both MGT and the rate of recovery to baseline responding as gap duration increased. When the supra-threshold gap was short, the response rate to the noise burst following the gap (NB2) was generally smaller than the response to the first noise burst (NB1) that was the marker for the onset of the gap. In young mice the NB2 response recovered to 75% of the NB1 rate in almost all units by the 15-ms gap duration, but in many units from old mice such recovery had not occurred by even 50 ms. In addition, old CBA mice were found to have fewer neurons that responded to short gaps. This diminished neural response at the level of the midbrain to gap stimuli represents impaired temporal encoding that may be expected to cause difficulties in perceiving brief, rapid amplitude fluctuations in vocalizations, especially in noisy conditions.

The purpose of the present study was to expand our understanding of age-related changes in temporal processing across species. Age-related changes in MGT between-group averages and within-group variability were measured under similar conditions across experimental paradigms, and relationships between age-related changes in signal audibility and MGT were examined. In addition, the functional significance (or salience) of supra-threshold gaps was examined behaviorally and physiologically. All gaps that are supra-threshold are, by definition, detected, but not all supra-threshold gaps are equally effective in eliciting behavioral and neural responses. We use the term salience to refer to this difference in the effectiveness of supra-threshold gaps. None of these effects has been explored in previous studies. The present study replicated the effects of age on mean MGT and physiological recovery as a function of gap duration. Further, it provides direct comparisons between behavioral and neural gap detection in young and old CBA mice and psychophysical gap detection in younger and older human listeners. Together the results suggest a neural basis for previously reported age-related changes in mean MGT, and affirm the validity of making cross-species comparisons of age-related changes in temporal processing.

Section snippets

Experiment 1: gap detection by human listeners

In this first experiment gap thresholds were measured in older and younger listeners who were very similar with respect to their audiograms up to 4 kHz. In contrast to our previous research, which reported on gap detection in complex noise backgrounds [36], [37], gap detection thresholds were obtained in quiet backgrounds in order to duplicate the backgrounds used in the animal experiments.

Experiment 2: animal behavior

In order to allow a comparison of the human data reported in experiment 1 to MGTs obtained from an animal model of presbycusis, experiment 2 measured absolute thresholds for tones using the auditory brainstem evoked potential (ABR measures) and behavioral MGTs in old and young CBA mice using acoustic startle reflex modification audiometry [43] (ASR inhibition). This strain of mice shows a small hearing loss for high frequencies that very gradually develops over the first 18 months of life, and

Experiment 3: animal physiology

The purpose of the final experiment was to obtain a neural correlate of behavioral gap detection in mice, which could hypothetically serve the same function in human listeners. In order to do this, single cell responses to silent gaps occurring in noise bursts were recorded from IC neurons in young and old CBA mice.

Conclusions

The purpose of this combined multidisciplinary study was to compare sensory measures obtained from humans and CBA mice with each other and with similar measures obtained from CBA mouse IC neurons. Through this comparison the sensory data could be linked to evidence concerning the neural basis of age-related changes in temporal acuity. Table 2 summarizes the results, which are discussed below.

Acknowledgements

A preliminary report of this work was presented at the 23rd Midwinter Research Meeting of the Association for Research in Otolaryngology. This research was supported by the Rochester International Center for Hearing and Speech Research and by an NIH-NIA research grant (AG09524). Ajit Janardan and Neil Rekhi assisted with data collection and Beth Hickman provided programming support.

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