The Relative and Combined Effects of Noise Exposure and Aging on Auditory Peripheral Neural Deafferentation: A Narrative Review

Abstract

Animal studies have shown that noise exposure and aging cause a reduction in the number of synapses between low and medium spontaneous rate auditory nerve fibers and inner hair cells before outer hair cell deterioration. This noise-induced and age-related cochlear synaptopathy (CS) is hypothesized to compromise speech recognition at moderate-to-high suprathreshold levels in humans. This paper evaluates the evidence on the relative and combined effects of noise exposure and aging on CS, in both animals and humans, using histopathological and proxy measures. In animal studies, noise exposure seems to result in a higher proportion of CS (up to 70% synapse loss) compared to aging (up to 48% synapse loss). Following noise exposure, older animals, depending on their species, seem to either exhibit significant or little further synapse loss compared to their younger counterparts. In humans, temporal bone studies suggest a possible age- and noise-related auditory nerve fiber loss. Based on the animal data obtained from different species, we predict that noise exposure may accelerate age-related CS to at least some extent in humans. In animals, noise-induced and age-related CS in separation have been consistently associated with a decreased amplitude of wave 1 of the auditory brainstem response, reduced middle ear muscle reflex strength, and degraded temporal processing as demonstrated by lower amplitudes of the envelope following response. In humans, the individual effects of noise exposure and aging do not seem to translate clearly into deficits in electrophysiological, middle ear muscle reflex, and behavioral measures of CS. Moreover, the evidence on the combined effects of noise exposure and aging on peripheral neural deafferentation in humans using electrophysiological and behavioral measures is even more sparse and inconclusive. Further research is necessary to establish the individual and combined effects of CS in humans using temporal bone, objective, and behavioral measures.

Keywords: age-related hearing loss (ARHL); auditory brainstem response (ABR); cochlear synaptopathy (CS); envelope-following response (EFR); middle ear muscle reflex (MEMR); noise exposure; speech-perception-in-noise (SPiN); summating potential to action potential ratio (SP:AP).

Figure 1

The left panel represents the proportion of remaining synapses as a function of the maximum average noise exposure of the studies summarized in Table 1. All studies exposed their subjects to octave-band noise, except for studies numbered 7, 10, and 13 employed broadband noise (study 13 only used blast noise). Studies number 2 and 12 involved multiple noise-exposure session, while all other studies exposed their subjects during one session only. The right panel shows the proportion of remaining synapses as a function of the age of the oldest animals in percent lifespan for the studies summarized in Table 2. The reference lifespan for the animals is 25 months for the Wistar rat, 36 months for the Mongolian gerbil and 30 months for both CBA and UMHET4 mouse.

Figure 2

The proportion of remaining IHC-ANF synapses at basal cochlear regions as a function of age in humans given two models of synapse/ANF vulnerability: All synapses vulnerable (A,C) and only low- and medium-SR ANFs vulnerable (B,D). The two models are based on two assumptions: regular constant lifetime acoustic over-exposure (A,B) and one single event of intense noise exposure occurring at age 20 or 60 (C,D). In (B,D), the dashed line is an asymptotic line defining the percentage of synapse loss beyond which no further CS occurs.

Figure 3

(A) Shows the relation between age-related decline in wave 1 amplitude and remaining IHC-ANF synapses as estimated in the 5.6, 11.2, and 32 kHz cochlear regions in CBA/CaJ mice. Redrawn from the data reported in panel D of Figure 5 in Sergeyenko et al. (2013) using the online tool of WebPlotDigitizer version 4.5 (Rohatgi, 2021). (B) Illustrates ABR wave I amplitude as a function of age across five different human studies. Redrawn from the data reported in Figure 4 in Bramhall (2021) using the online tool of WebPlotDigitizer version 4.5 (Rohatgi, 2021).

Figure 4

MEMR thresholds and growth functions (expressed as the difference in-ear canal SPL as a function of contralateral noise level) in noise-exposed and control mice measured at stimulus onset and offset. A wideband chirp covering a range of 4–64 kHz was presented contralaterally. This figure is redrawn from the data reported in panels A, B, and C of Figure 7 in Valero et al. (2016) using the online tool of WebPlotDigitizer version 4.5 (Rohatgi, 2021).