REVIEW

published: 25 November 2020

doi: 10.3389/fneur.2020.593919

Effects of Noise Exposure on the

Vestibular System: A Systematic
Review
Courtney Elaine Stewart 1,2*, Avril Genene Holt 3,4 , Richard A. Altschuler 1,2 ,
Anthony Thomas Cacace 5 , Courtney D. Hall 6,7 , Owen D. Murnane 8,9 , W. Michael King 1 and
Faith W. Akin 8,9
1
University of Michigan Department of Otolaryngology/Head-Neck Surgery, Kresge Hearing Research Institute, Ann Arbor,
MI, United States, 2 VA Ann Arbor Healthcare System, Research Service, Ann Arbor, MI, United States, 3 Department of
Ophthalmology Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI, United States,
4
John D. Dingell VA Medical Center, Molecular Anatomy of Central Sensory Systems Laboratory, Research Service, Detroit,
MI, United States, 5 Department of Communication Sciences and Disorders, Wayne State University, Detroit, MI,
United States, 6 Department of Rehabilitative Sciences, Doctor of Physical Therapy Program, East Tennessee State
University, Johnson City, TN, United States, 7 Gait and Balance Research Laboratory, James H. Quillen VA Medical Center,
Mountain Home, TN, United States, 8 Department of Audiology and Speech-Language Pathology, East Tennessee State
University, Johnson City, TN, United States, 9 Vestibular Research Laboratory, James H. Quillen VA Medical Center, Mountain
Home, TN, United States

Despite our understanding of the impact of noise-induced damage to the auditory

system, much less is known about the impact of noise exposure on the vestibular
system. In this article, we review the anatomical, physiological, and functional evidence
for noise-induced damage to peripheral and central vestibular structures. Morphological
studies in several animal models have demonstrated cellular damage throughout the
Edited by:
Michael Strupp,
peripheral vestibular system and particularly in the otolith organs; however, there
Ludwig Maximilian University of is a paucity of data on the effect of noise exposure on human vestibular end
Munich, Germany
organs. Physiological studies have corroborated morphological studies by demonstrating
Reviewed by:
disruption across vestibular pathways with otolith-mediated pathways impacted more
Leonardo Manzari,
MSA ENT Academy Center, Italy than semicircular canal-mediated pathways. Similar to the temporary threshold shifts
Ian S. Curthoys, observed in the auditory system, physiological studies in animals have suggested a
The University of Sydney, Australia
capacity for recovery following noise-induced vestibular damage. Human studies have
*Correspondence:
Courtney Elaine Stewart
demonstrated that diminished sacculo-collic responses are related to the severity of
[email protected] noise-induced hearing loss, and dose-dependent vestibular deficits following noise
exposure have been corroborated in animal models. Further work is needed to better
Specialty section:
This article was submitted to
understand the physiological and functional consequences of noise-induced vestibular
Neuro-Otology, impairment in animals and humans.
a section of the journal
Frontiers in Neurology Keywords: vestibular system, noise-induced vestibular loss, saccule and utricle, semicircular canals, impulse
noise, continuous noise, vestibular nuclear complex
Received: 11 August 2020
Accepted: 28 September 2020
Published: 25 November 2020
INTRODUCTION
Citation:
Stewart CE, Holt AG, Altschuler RA, It is well-established that noise overstimulation has the potential to cause temporary or permanent
Cacace AT, Hall CD, Murnane OD,
damage to sensory cells in the cochlea and the afferent neurons innervating them, resulting in
King WM and Akin FW (2020) Effects
of Noise Exposure on the Vestibular
temporary or permanent loss of hearing [for review see: (1, 2)]. Less known and considerably less
System: A Systematic Review. understood are the effects of noise on vestibular and balance function. Similar to the cochlea, the
Front. Neurol. 11:593919. vestibular sensory end organs are housed within the temporal bone and membranous labyrinth
doi: 10.3389/fneur.2020.593919 of the inner ear. Hair cells, the sensory cells of the inner ear, share similar morphology in

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Stewart et al. Noise-Induced Vestibular Loss

the vestibular end organs and in the organ of Corti; they 2–4 min, respectively), and utricular collapse did not appear
both transduce displacement of hair-bundles into neural activity to occur at a specific frequency. Interestingly, rupture of the
through the shared vestibulocochlear nerve (CN VIII). Five saccule was not changed with post-noise exposure recovery time,
peripheral vestibular end organs (three semicircular canal cristae but rupture of the utricle became less common as post-noise
and two otolith organs) provide sensory input to vestibular nuclei exposure recovery time increased. Conversely, utricular collapse
as well as the vestibular cerebellum and contribute to vestibulo- was not impacted by post-noise exposure recovery time, but
ocular and vestibulo-spinal reflexes (VOR and VSR; Figure 1). saccular collapse was more common as post-noise exposure
Although a primary role of the mammalian vestibular system is to recovery time increased. This study laid the groundwork for
maintain gaze and postural stability, neurophysiological studies more recent work and provided early evidence of noise-induced
demonstrate that, like the cochlea, the vestibular end organs, and damage to the vestibular periphery.
the saccule and utricle (otolith organs) in particular, are sensitive Hsu et al. (16) demonstrated the impact of duration of noise
to sound [e.g., (3–5) for reviews see (6, 7)]. Large diameter exposure on tissue damage by delivering a broadband noise
afferents with calyceal terminations are characterized by phase- of identical intensity (115 dB SPL) to guinea pigs for either
locking and an irregularly discharging firing rate (8–10), high 30 min or 40 h. Assessment of general morphology using light
sensitivity to linear forces (11), and increased firing in response to and electron microscopy showed no signs of saccular disruption
air-conducted sound or bone-conducted vibration (3, 4, 12). The 1 week after noise exposure with the short term 30-min exposure.
properties of irregular vestibular afferents have been described The long-term 40-h exposure resulted in otolithic membrane
in detail [(13); for reviews see (6, 14)]. Their physiological disruption, as well as atrophy and vacuolization in type I saccular
properties and sound-sensitivity put these afferents at greater risk hair cells. There was little damage to type II hair cells or
for noise-induced damage. Specifically, since irregular vestibular supporting cells and the vestibular nerve was intact 1 month after
afferents can be activated by sound, it follows that this population noise exposure (16).
may be over-stimulated by sound, and therefore susceptible to The time course of noise exposure also influences the potential
noise-induced damage. Noise exposures can be grouped into for peripheral vestibular damage. Akdogan et al. (17) compared
one of two types—impulse or continuous noise. Continuous vestibular changes in guinea pigs exposed to an intense (120
noise occurs over an extended period of time, whereas impulse dB SPL) 6-h 4 kHz octave band (continuous) noise vs. a group
noise occurs rapidly, and generally at a considerably higher exposed to intermittent noise (1-h exposure followed by a 1-
sound pressure level (SPL). Both types of noise exposures will h break, alternating for 12 h). Damage was identified in the
be explored in this review with a description of the anatomical, continuous, but not the intermittent noise exposure group. This
neurophysiological, and functional evidence for noise-induced damage included large vacuoles and enlarged mitochondria with
damage to the vestibular system. crystolysis in epithelial cells from saccular maculae and apoptosis
of non-sensory cells (stromal cells and osteocytes). This study
suggests that intermittent noise exposure is less damaging to
ANATOMICAL EVIDENCE FOR the vestibular system than continuous noise exposure. In a
NOISE-INDUCED DAMAGE TO THE similar study, rats were exposed to a continuous 6-h intense
(120 dB SPL) 1.5 kHz 3-octave band noise. Figure 2 shows
VESTIBULAR PERIPHERY
significant decrease in calretinin immunolabeled calyceal endings
Continuous Noise Exposure observed in rat saccular maculae following a 28-day recovery
Similar to the auditory system, animal models of continuous period; however, hair cell loss was not observed in this study
noise exposure have revealed that damage to the vestibular (18). Following a 3-h 116 dB SPL broadband noise exposure,
periphery is dependent on characteristics of the noise, including: damage to stereocilia bundles without qualitative observation
duration, frequency, level, and time course. The duration of of hair cell loss (absence of scarring where hair-bundles were
noise exposure varies across experiments ranging from <1 h to missing in sensory epithelia) was significant through most of the
more than 1 day and likely contributes to the level of tissue vestibular labyrinth (saccule, utricle, and anterior and horizontal
damage observed across studies. In an early study, Mangabeira- semicircular canals), with the greatest effect observed in the
Albernaz et al. (15) used a wide range of frequencies (170– otolith organs in tissue collected 7 days after noise exposure
50,000 Hz) and durations (5–160 min) at high SPLs (118–133 [(19); Figure 3].
dB), and then allowed 0–133 days of recovery before tissue The sound levels used to study the effects of continuous
collection. Across all of the tissue analyzed, saccular collapse noise on the vestibular periphery have ranged from 70 to 150
was observed in approximately one third of the samples and dB SPL with even higher levels used in impulse noise exposure
utricular rupture was observed in approximately one third of paradigms. Exposure to lower sound levels over a long time
the samples. Saccular rupture was identified in ∼25% of the period can produce signs of peripheral vestibular injury (20),
samples, and utricular collapse was least commonly observed, whereas higher sound levels can produce damaging effects
in ∼15% of samples. When this damage is categorized by within minutes (21). Tamura et al. (20) observed a reduction
frequency, saccular rupture was most prevalent with 0.5–2 kHz in the number of vestibular hair cells and increased oxidative
noise exposure (142–150 dB SPL, 1–4 min), and saccular collapse stress in mice exposed to a relatively low sound level (70 dB
was most prevalent with 4 kHz noise exposure (150–163 dB SPL, SPL) for 1 month. In contrast, a 20-min exposure to a much
1–2 min). Utricular rupture was most prevalent with 1–4 kHz, higher sound level (136 to 150 dB SPL) band-limited noise
and 40–50 kHz (142–163 dB SPL, 1–4 min and 140–144.5 dB, produced saccular collapse, destruction of otolithic membrane,

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Stewart et al. Noise-Induced Vestibular Loss

FIGURE 1 | Schematic drawing showing peripheral vestibular sensory organs and central pathways. (A) The vestibular labyrinth contains three semicircular canal
cristae (anterior, horizontal, and posterior; blue) and two otolith organs (saccule, red; utricle, green). (B) The semicircular canal cristae, utricle, and saccule are
innervated by the vestibulocochlear nerve (CN VIII). Afferent fibers terminate in the vestibular nuclear complex, containing the superior, lateral, medial, and inferior
vestibular nuclei. The medial longitudinal fasciculus, lateral vestibulospinal tract, and medial vestibulospinal tract are critical central components of vestibular reflex
pathways.

and detached macular sensory cells (21). It should be noted, ischemia and free-radical production also contribute to noise-
however, that in this study the non-saccular vestibular end organs induced damage observed in the vestibular periphery. Using
were not affected by the noise exposure. quench-assisted magnetic resonance imaging (QUEST MRI) to
Evidence for frequency-dependent noise-induced damage has measure excessive free radical production in vivo, Kühl et al.
also been described. Tamura et al. (20) examined otolith organs (22) identified noise-induced free radical production not only
collected from mice that were chronically exposed to low- in the cochlea, but also in the vestibular aspect of the inner
intensity (70 dB SPL), low-frequency (0.1 kHz) noise. They ear of rats exposed to 118 dB SPL, 10 kHz-centered 1/3 octave
identified fewer vestibular hair cells and elevated markers of band noise for 4 h. When compared to normal hearing controls
oxidative stress including D-beta-aspartic acid and oxidized and ears protected from noise exposure by silicone elastomer,
phospholipids compared to control animals. Interestingly, the unprotected cochlea of noise exposed rats exhibited elevated
damage was not observed in animals exposed to the same MRI R1 values. These increased MRI R1 values were “quenched”
duration and level of high-frequency (16 kHz) noise. These by anti-oxidant treatment, indicating the presence of noise
results are consistent with the finding that vestibular afferents are induced free radicals. Measurement of MRI R1 values in vivo
most sensitive to low-frequency sound stimulation [e.g., (3)]. within vestibular related regions of the inner ear in these same
The studies reviewed in this section have outlined the animals suggest increased free radical levels after noise exposure
consequences of continuous noise exposure and mechanisms (Figure 4). Other studies have used post-life measures of noise-
underlying damage to the vestibular periphery. Although induced free radical production. Fetoni et al. (23) exposed guinea
noise-induced vestibular damage is attributed to excitotoxicity pigs to a 6 kHz pure tone at 120 dB SPL for 1 h and identified
(especially when type I hair cells and calyceal afferents are hair cell loss, a large, progressive increase in vascular endothelial
preferentially impacted) and to direct mechanical trauma, growth factor (VEGF), and a small increase in 4-hydroxynonenal

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Stewart et al. Noise-Induced Vestibular Loss

FIGURE 2 | Upper left, 40× magnification image of a non-noise exposed sacculus labeled with calretinin, a marker of calyx-only afferent terminals. Upper right,
zoomed image of the bend of the sacculus showing numerous well-labeled calyces in non-noise-exposed tissue. Lower left, 40× magnification image of a
noise-exposed sacculus. Lower right, zoomed image of the bend of the sacculus showing a reduction in the number of calretinin-labeled calyces 28 days after noise
exposure (18).

(4-HNE). 4-HNE is a product of lipid peroxidation and used phospholipids and D-beta-aspartic acid. Both studies suggest that
as a marker of oxidative stress. VEGF is primarily viewed noise exposure can lead to production of free-radicals; however,
as an angiogenic factor; it has been suggested that it is also differences in the identification of free-radicals by Tamura et al.
protective against apoptosis (24, 25) and is upregulated in (20) and Fetoni et al. (23) are likely due to differences in the
noise-induced hearing loss (26–28). It is possible that VEGF animal model, the selection of antibody targets, and the duration
is induced by ischemia (24) and related to the production of of post-noise recovery prior to tissue analyses. It is also possible
reactive oxygen species (29). Tamura et al. (20) exposed mice to a that a long duration or a low frequency noise exposure produces
continuous 0.1 kHz noise at 70 dB SPL for 1 month. After noise the greatest damage, a finding that is relevant to environmental
exposure, the inner ears were paraffin-embedded and sectioned. health and workplace safety.
In sections of the vestibule that contained the otolith organs, hair In summary, these studies suggest that both brief exposure
cell loss and elevated levels of oxidative stress were observed. to an elevated sound level and sustained exposure to low-
Oxidative stress was determined as elevated presence of oxidized frequency continuous sound at more moderate levels can have

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Stewart et al. Noise-Induced Vestibular Loss

FIGURE 3 | (A,B) Representative images of the saccular macula and the utricular macula stained with phalloidin from control (left panels) and noise-exposed rats
(right panels). Arrows indicate intact cuticular plates with missing stereocilia bundles. Scale bar is 50 µm. Noise exposure decreases stereocilia bundle density in both
the striolar and extra-striolar regions of the saccules and the utricles (**P < 0.01; ***P < 0.0005). (C–E) Representative images of the anterior (AC), horizontal (HC),
and posterior (PC) semicircular canal cristae stained with phalloidin from control (left panels) and noise-exposed rats (right panels). Arrows indicate missing stereocilia
bundles. Scale bar is 50 µm. Noise exposure decreases stereocilia bundle density in the AC and HC, but not the PC (*P < 0.05; ***P < 0.0005). Adapted from (19).

a damaging impact on the vestibular periphery. Comparisons models; however, it is clear that vestibular damage is measurable
across studies are difficult due to differences in frequency following noise exposure. Animal models have revealed cellular
range, duration, sound level, time course, and even animal and anatomical changes to the vestibular periphery associated

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Stewart et al. Noise-Induced Vestibular Loss

FIGURE 4 | Noise-evoked inner ear oxidative stress measured in vivo with QUEST MRI. R1 (1/T1) maps were generated and used to compare protected (plugged
ear) and unprotected vestibular end organs and cochleae. Scale bar is a graded colorimetric representation of R1 values. High values are represented as a gradient
from red to yellow and low values are represented from blue to purple. Vestibular regions–area within ovals with dashed lines. The R1 values were collected in vivo
from 400 µm MRI scans. Scans through the cochlear and vestibular ducts were sampled and analyzed from caudal to rostral. Therefore, the coronal image in
Figure 4, provides views of the regions of interest from caudal to rostral (e.g., the right cochlea is viewed on the right side of the image). Adapted from (22).

with noise overstimulation. Continuous noise-induced damage Kumagami (34) reported that moderate to extensive
has been identified with markers of oxidative stress and ischemia; endolymphatic hydrops occurred 1 year after exposure to
fewer calyceal terminals, loss of stereocilia bundles, hair cell firecracker explosion in Albino guinea pigs. According to the
loss, and, with sufficient sound pressure, a complete collapse of author, from 6 months to 1-year post-exposure, the vestibule and
the saccule, and destruction of the otoconial matrix overlaying semicircular canals showed slight to moderate endolymphatic
this structure. Most of the research on the effects of continuous hydrops without overt damage to the sensory maculae contained
noise on the vestibular periphery has examined the impact on within these structures. In this temporal trajectory, three
the otolith organs, and the saccule is likely the most susceptible prominent post-traumatic events occurred: (1) after 4 months,
to noise-induced damage due to the anatomical proximity of degeneration of the endolymphatic sac was observed, (2)
the saccule to the stapes footplate (30) [e.g., (17, 19, 21)]. In endolymphatic hydrops developed after disappearance of the
contrast, fewer studies have examined noise-induced damage to Preyer reflex in ∼50% of the animals studied, and (3) damage
the semicircular canals (19). to cochlear hair cells preceded degeneration of epithelial cells in
the endolymphatic sac. In summary, these studies suggest that
Impulse Noise Exposure impulse noise may have a broad impact, damaging the ampullary
To our knowledge, there is no report that has examined the cristae, otolith organ maculae, and endolymphatic sac; however,
vestibular aspect of the human temporal bone after continuous or literature on the impact of impulse noise on tissue damage in the
impulse noise exposure. Kerr and Byrne (31), however, examined vestibular periphery is limited.
temporal bones of two victims killed in a Northern Ireland
restaurant bombing and their histological examination revealed
rupture of the saccule, utricle and basilar membranes following a ANATOMICAL EVIDENCE FOR
close-proximity blast. NOISE-INDUCED DAMAGE TO CENTRAL
In guinea pigs exposed to impulse noise from 90 to 300 VESTIBULAR PATHWAYS
rifle shots with a peak level of 158 dB SPL at 1.1 kHz, Ylikoski
(32) found that the most severe damage occurred in ampullary There is some anatomical evidence for central vestibular
cristae and the cochlea. This damage was characterized as a pathway damage following exposure to continuous and impulse
separation of sensory epithelium from underlying connective noises. A gas chromatography mass spectrometry (GC/MS)-
tissue and damage to sensory cells. With this noise exposure based metabolomics platform has been used to show changes
condition, epithelial separation occurred less frequently and was in neurotransmitter-related metabolites after exposing rats
less severe in utricular and saccular maculae than in cristae (32). unilaterally for 1 h to a 16 kHz 110 dB SPL tone (35). After
In contrast, Lien and Dickman (33) exposed mice to 63 kPa peak 6 months, increases in glutamic acid were found in both
blast waves and observed stereocilia bundle loss in the utricular the vestibular nuclear complex (VNC) and the cerebellum.
maculae and horizontal semicircular canal cristae (the sacculus There were also significant increases in the relative abundance
and vertical semicircular canals were not measured), suggesting of cysteine, urea, and inosine in the VNC while glycine, 3-
a broader effect of blast exposure than is seen in other noise hydroxybutyrate, and myo-inositol concentrations were elevated
exposure paradigms. in the cerebellum. These chronic changes in metabolites are

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Stewart et al. Noise-Induced Vestibular Loss

suggestive of changes in neuronal activity and the balance neuronal activity that is sometimes observed following loud noise
between excitation and inhibition (i.e., increased endocytosis). exposure and could be associated with the perception of tinnitus
Kaur et al. (36) evaluated the cerebellar cortex of rats in and/or hyperacusis.
response to blast exposure. When examined 4 to 7 days after the
blast exposure, ultrastructural analysis using electron microscopy
revealed neurons with darkened dendrites (dark appearance ELECTROPHYSIOLOGICAL EVIDENCE
of cytoplasm within dendritic processes). Darkened dendrites FOR NOISE-INDUCED DAMAGE TO THE
can indicate that neurons are in an atrophic state due to VESTIBULAR SYSTEM
trauma and have been reported following axotomy and exposure
to neurotoxins (37, 38). Additionally, microglia at this same Neurophysiological studies have focused primarily on otolith
time point exhibited morphological changes and proliferation, organ pathways in examination of the impact of noise exposure
suggesting a massive inflammatory response mediated by on vestibular function. The majority of animal studies have
microglia. Microglia were observed near and sometimes even used the vestibular short latency evoked potential (VsEP) to
wrapping around some of the darkened dendritic processes. At study changes in central and peripheral activity after noise
21–28 days after the blast, however, no darkened dendrites were exposure [(18, 42–45) for review of VsEPs see: (46)]. VsEPs
observed, and the morphological characteristics and numbers of have predominantly been recorded from experimental animals in
microglia had returned to pre-blast levels. The data suggest that response to brief linear acceleration impulses applied to the skull
these proliferating microglia removed, at least a portion of, the using an electrodynamic shaker that is bolted or clamped to the
affected dendrites. The authors postulated that acute changes in animal’s skull [Figure 5; e.g., (47)]. VsEPs remain intact following
affected neurons and activation of microglia may have resulted cochlear extirpation whereas the response is abolished following
in a prolonged atrophic state and/or release of factors that damage to the vestibule or eighth nerve or the administration
caused other chronic effects (e.g., changes in neuronal activity, of neural blocking agents [e.g., (48)]. Further, the use of air
increased endocytosis). conduction masking does not eliminate the VsEP response (48,
Although some morphological changes were acute as reported 49). For a review of the vestibular specificity of the VsEP, see
by Kaur et al. (36), studies in other animal models showed Brown et al. (50). The VsEP reflects the synchronous compound
persistent effects. The impact of mild repetitive blast (3 blasts field potential of peripheral and/or central vestibular neurons in
20–30 min apart ranging from 15–19 psi = 107–133 kPa) response to the onset of head/body motion (jerk). The VsEP is
on brain microstructure and volume was examined using well-validated and used to evaluate the effects of noise exposure
magnetic resonance imaging (MRI) in Sprague Dawley rats, on irregular otolithic afferents. It is known that irregular afferents
at two time points (7 and 90 days) after exposure (39). At that contribute to central vestibular reflex pathways are sound
90 days post-trauma, localized reductions in volume were sensitive [e.g., (3); for review see (6)]. Furthermore, it has
observed in the cerebellum and the VNC. Microstructural been demonstrated that damage to this population of afferents
changes in the cerebellum were observed at 7 days and (Figure 2; calretinin-positive calyx-only afferent terminals) is
persisted through the 90-day time point. The specific details associated with loss or reduction of the VsEP response (18, 45).
surrounding the morphological changes were not reported. In summary, the VsEP is an appealing metric to evaluate the
Although ipsilateral vs. contralateral damage was discussed, vestibular consequences of noise exposure in animal models;
neither damage of specific subnuclei nor localization within however, due to challenges in recording VsEPs in humans,
subnuclei were described (i.e., rostro-caudal, dorso-ventral, or the impact of noise exposure on the human VsEP has not
medio-lateral). Another question is whether particular neuronal been examined.
phenotypes were disproportionately affected (e.g., excitatory To examine the impact of noise on the human vestibular
vs. inhibitory). Other studies have addressed the differential system, most laboratories have used vestibular evoked myogenic
impact of continuous noise on neurons within vestibular nuclei. potentials (VEMPs; Figure 6). VEMPs are short-latency
Specifically, in Barker et al. (40), neurons in the lateral vestibular myogenic potentials arising from vestibular afferents that
nucleus (LVN) of the rat project to the dorsal cochlear nucleus are responsive to air-conducted sound or bone-conducted
(DCN). Combining tract tracing and immunohistochemistry 5 vibration (51). Cervical VEMPs (cVEMPs; Figure 6A), a
days after a noise trauma (15 kHz, 110 dB SPL for 6 h), synaptic measure of the sacculo-collic pathway, are recorded from surface
terminals originating from LVN neurons were shown to be more electrodes over the sternocleidomastoid muscle. Ocular VEMPs
numerous in the DCN when compared to sham noise-exposed (oVEMPs; Figure 6B), a measure of utricular/superior vestibular
control animals. They further determined that the synaptic nerve function, are recorded from surface electrodes over the
terminals were glutamatergic, immunolabeling for vGLUT2 inferior oblique extraocular muscle. cVEMPs are mediated
(vesicular glutamate transporter 2), a protein responsible for by an ipsilateral reflex pathway originating in the saccule and
loading glutamate into synaptic vesicles. Others have postulated projecting to motoneurons of the sternocleidomastoid muscle
that neuropathic pain and inflammatory processes induced by via the inferior vestibular nerve, vestibular nuclei and descending
noise may underlie the increased excitatory vGLUT2 neurite medial vestibulospinal tract [for review, see (6)]. oVEMPs are
outgrowth from the LVN into the cochlear nucleus [e.g., (41)]. mediated by a contralateral reflex pathway originating in the
These new synaptic terminals could be evidence of cross- utricle and projecting to motoneurons of the inferior oblique
modal plasticity and contribute to an increase in spontaneous muscle via the superior vestibular nerve, vestibular nuclei, medial

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Stewart et al. Noise-Induced Vestibular Loss

FIGURE 5 | VsEP recording set-up. The skull of an anesthetized rat is fixed to the arm of an electrodynamic transducer (ET-132-203, Labworks, Inc.) and linear
head-jerks (left) are delivered in the naso-occipital plane to elicit responses (right) with characterisitic P1N1 and P2N2 waveforms that can be measured before and
after noise exposure to track vestibular loss and recovery over time.

longitudinal fasciculus, and the oculomotor nucleus [for review, exposures (42). Although this result is surprising, the relatively
see (52)]. moderate level combined with the broadband frequency content
of the noise exposures might explain the lack of vestibular loss
Otolith Organ Pathways observed in the Sohmer et al. (42) and Biron et al. (43) studies,
Vestibular Short-Latency Evoked Potentials (VsEPs) compared to the high-level impulse noise used by Perez et al.
Animal studies using VsEPs have demonstrated changes in (44), and the low-frequency high-level noise used by Stewart
VsEP characteristics following noise exposure. Perez et al. (44) et al. (18, 45). Neurophysiological studies are consistent with
observed a reduction in VsEP amplitude elicited by a ∼3 anatomical studies that suggest the site, degree, and duration
g/ms head-jerk in rats following exposure to impulse noise (10 of damage observed in the vestibular periphery (temporary vs.
gunshots at ∼160 dB SPL). Six weeks after noise exposure, the permanent) is impacted by the level, frequency, and duration of
VsEP amplitude recovered but the latency did not, suggesting noise exposure.
an incomplete recovery. Similarly, Stewart et al. (45) reported a
reduction in VsEP amplitude in rats exposed to high-intensity Cervical Vestibular Evoked Myogenic Potentials
(120 dB SPL) low-frequency (0.5–4 kHz) continuous noise for (cVEMPs)
6 h. Unlike the Perez et al. (44) study, the initial reduction in The approach to determining noise-related damage to the
VsEP amplitude using head-jerk stimuli up to 1.2 g/ms did not human vestibular system has primarily focused on recording
recover 3 weeks post-noise exposure (Figure 7). In a follow-up air-conducted sound cVEMPs in individuals with noise-induced
study that used the same noise exposure paradigm, larger head hearing loss (NIHL). NIHL is characterized by an audiometric
jerk stimuli were used to elicit VsEP responses and track recovery notch or “noise-notch” (decrease in hearing sensitivity at or
for 28 days post-noise exposure (18). Even with larger head- near 4 kHz) and serves as a biomarker for noise-related damage
jerk stimuli, the post-noise exposure response amplitudes were to the cochlea. cVEMPs are absent in individuals with NIHL
severely attenuated and exhibited longer latencies than those with an incidence ranging from 20 to 58% (53–60). Akin
obtained from the non-noise exposed animals. In fact, these et al. (53) examined cVEMPs in 43 military veterans (mean
deficits showed minimal recovery 28 days after noise exposure age = 52 years) with a history of noise exposure greater in
[(18); Figure 8]. It is likely that differences between the results one ear than the other and asymmetric NIHL (defined as a
of Perez et al. (44) and Stewart et al. (18, 45) were related, noise notch at 4 kHz of ≥35 dB HL in the poorer hearing ear
at least in part, to differences in the level and duration of the with a minimum interaural asymmetry of 20 dB HL at the
noise exposure paradigms. In the Perez et al. (44) study, the affected frequencies). cVEMPs were absent in 24% of the poorer-
impulses delivered to the rats were 40 dB SPL greater than in hearing ears (Figure 9). In contrast, cVEMPs were present in
the continuous noise paradigm used by Stewart et al. (18, 45). most (97.5%) of the better-hearing ears of the noise-exposed
However, the effect of continuous noise delivered over 6 h was group and present and symmetrical in the age-matched controls.
considerably more severe and more persistent. In contrast to Other studies have reported a decrease in cVEMP amplitudes
the work of Stewart et al. (18, 45) and Perez et al. (44), two and longer latencies in individuals with NIHL compared to
studies reported that continuous 113 dB SPL white noise did not individuals without noise exposure (54, 56, 59). Similarly,
induce a deficit in VsEP responses in intact animals (42, 43). cVEMP thresholds were higher (poorer) in military veterans
No significant changes were observed in VsEP amplitude or with NIHL than in age-matched controls (53). There is evidence
latency after a 1-h exposure or after 3 weeks of daily 12-h noise that a diminished vestibular response is associated with the

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Stewart et al. Noise-Induced Vestibular Loss

FIGURE 6 | Cervical (A) and ocular (B) vestibular-evoked myogenic potential (VEMP) pathways and waveforms. (A) Cervical VEMPs (cVEMPs) are mediated by an
ipsilateral reflex pathway originating in the saccule and projecting to motoneurons of the sternocleidomastoid muscle (SCM m.) via the inferior vestibular nerve,
vestibular nuclei and descending medial vestibulospinal tract. The cVEMP waveform was obtained using air conduction 500-Hz tone bursts (95 dB nHL) during
activation of the SCM m. with a lateral head turn. (B) Ocular VEMPs (oVEMPs) are mediated by a contralateral reflex pathway originating in the utricle and projecting to
motoneurons of the inferior oblique muscle via the superior vestibular nerve, vestibular nuclei, medial longitudinal fasciculus, and the oculomotor nucleus. The oVEMP
waveform was obtained using bone conduction 500-Hz tone bursts (Brüel & Kjær Model 4,810 mini-shaker applied to the midline forehead; 145 dB peak force level)
during upward gaze. For each waveform, the dashed vertical line at 0 ms indicates stimulus onset. Medial Vestibulospinal Tract, MVST; Accessory Nerve, CNXI;
Sternocleidomastoid, SCM; Oculomotor Nerve, CNIII; Medial Longitudinal Fasciculus, MLF.

degree of NIHL. In military veterans with bilateral asymmetric 30 industrial workers with NIHL, cVEMP latency increased and
NIHL, Akin et al. (53) observed that the poorer hearing ear amplitude decreased as a function of a four-frequency pure-tone
of NIHL subjects with absent cVEMPs had a greater degree average (55). Wang et al. (57) examined hearing improvement
of high-frequency hearing loss than the poorer hearing ear of following acoustic trauma in 20 patients and reported that
NIHL subjects with present cVEMPs (Figure 10). Similarly, in absent cVEMP responses or abnormally prolonged cVEMP

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Stewart et al. Noise-Induced Vestibular Loss

FIGURE 7 | Pre- and post-noise exposure VsEP waveforms for 1 animal at 4 stimulus intensities. (Bottom row) stimulus waveforms at 4 intensities (blue, 0.2 g/ms;
green, 0.4 g/ms; red, 0.7 g/ms; magenta, 1.2 g/ms). (Top) Pre-exposure (Cntr) and post-exposure (Day 1–21) VsEP waveforms for each stimulus intensity and the
identified P1N1 and P2N2 components. VsEP is abolished immediately after noise exposure and partially recovers 3–21 days after exposure. Dotted vertical line
marks peak stimulus intensity and was used as the reference (0 ms) to calculate latency. Originally published in (45).

FIGURE 8 | Representative VsEP waveforms in response to a 3.2 g/ms stimulus (left), and a 0.32 g/ms stimulus (right), at baseline (black traces) and 28 days after
noise exposure (red traces) (18).

latency indicated poor prognosis for hearing recovery. Indeed, cVEMP findings in humans are consistent with morphological
absent cVEMP or prolonged cVEMP latency predicted acoustic studies in animals that suggest the sacculus is particularly
trauma hearing outcome with a sensitivity of 44% and specificity susceptible to noise-related damage. Human studies are limited,
of 100%. however, by a lack of histopathological data and difficulty

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Stewart et al. Noise-Induced Vestibular Loss

the motoneurons of muscles at the end of a reflex pathway

that includes central components. These limitations have been
partially addressed by the work of Hsu et al. (16) in which
cVEMPs were measured in guinea pigs following short-term vs.
long-term noise exposure. In this study, a “normal” cVEMP was
defined as the presence of a biphasic waveform at a latency of
6- to 9-ms, with a peak-to-peak amplitude of 5–20 µV. When
a peak was not observed in the latency range of 6- to 9-ms, or
was smaller than 5 µV, the cVEMP response was considered
‘abnormal’. Hsu et al. (16) observed recovery of vestibular
function (return of normal cVEMP responses) following short-
term (30 min) exposure to continuous broadband noise at 114
dB SPL. In contrast, abnormal cVEMP responses persisted for
at least 30 days in most guinea pigs (78%; n = 18) following
exposure to 40 h of continuous broadband noise. These findings
are consistent with anatomical findings described earlier and
FIGURE 9 | Signed interaural amplitude asymmetry ratio for cervical vestibular suggest that permanent physiological damage to the sacculo-
evoked myogenic potentials in 14 age-matched controls (triangles) and 41 collic pathway is more likely following long vs. short-duration
participants with bilateral asymmetric noise-induced hearing loss (circles). For noise exposures.
the noise-exposed group, −100% indicates the cVEMP was absent from the
poorer-hearing ear, whereas 100% indicates the cVEMP was absent from the
better-hearing ear. For the control group, negative values indicate that the
P1-N1 amplitude was greater on the left side and positive values indicate that Semicircular Canal Pathways
the P1-N1 amplitude was greater on the right side. The area between the The studies that have examined the horizontal semicircular
dotted horizontal lines indicates asymmetry ratios within normal limits. Two canal and VOR pathways have yielded inconsistent findings in
noise-exposed participants had cVEMPs absent bilaterally and are not shown. individuals with NIHL. For example, Man et al. (61) observed
Adapted from (53).
a caloric weakness in only one of 176 patients with NIHL,
whereas other studies have revealed a caloric weakness in up
to 25% of individuals with NIHL (56, 57, 62). Using slow
harmonic acceleration, Shupak et al. (63) found that VOR
gain was significantly lower in industrial workers and military
personnel with NIHL compared to a control group with
normal hearing.
Recently, Yilmaz et al. (64) used the video head impulse test to
measure VOR gain for all six semicircular canals in 36 industrial
workers (mean age = 44 years) with high frequency hearing loss
and four or more years working the steel and metal industry.
They reported canal deficits (a decrease in VOR gain in at least
one canal) in 55.5% of noise exposed participants compared
with 6.6% of control participants. Decreased gain was reported
more frequently in the horizontal semicircular canals (47%) than
in the vertical canals (8%), with two noise-exposed participants
demonstrating decreased VOR gain in more than one canal.
Interpretation of these data is limited because NIHL was defined
according to the degree of hearing loss at 4,000 Hz rather than a
characteristic noise notch.
In contrast to cVEMP findings that suggest greater sacculo-
collic pathway damage associated with more severe NIHL, the
relationship between damage to the horizontal semicircular
FIGURE 10 | Mean and SDs for pure-tone thresholds for the poorer-hearing canal/VOR pathways and the degree of NIHL is less clear.
ear of noise-exposed participants (n = 43) with cVEMPs present (n = 29; open
Shupak et al. (63) observed significant correlations between
triangles) and for the poorer-hearing ear of noise-exposed participants with
cVEMPs absent (n = 14; filled triangles). Asterisks indicate significant post-hoc
pure-tone average, VOR gain, and caloric lateralization. Golz
comparisons. Adapted from (53). et al. (62), however, found no correlation between the severity
of hearing loss and abnormal caloric test findings. It is worth
noting, however, that the caloric response is a very low
quantifying noise exposure across a lifespan. Additionally, frequency response and may be independent of central zone
the human cVEMP is somewhat limited as an estimate of hair cells and afferents that might be sensitive to pressure
peripheral vestibular function as the response is recorded from wave disturbances.

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Stewart et al. Noise-Induced Vestibular Loss

To examine the impact of noise exposure across multiple Central Vestibular Pathways
vestibular pathways, Tseng and Young (56) performed bithermal Using chronically implanted micro-electrode arrays, Ordek et al.
calorics and cVEMPs and oVEMPs using bone-conducted (65) evaluated cerebellar neuronal activity after mild blast
vibration on 30 individuals with NIHL related to chronic exposure (100–130 kPa). Behavioral testing 24 h and 7 days
occupational noise exposure. Their findings revealed that after blast (ladder climbing, roto-rod, ladder walking) and
cVEMPs were most frequently abnormal (70%) followed by immunohistochemistry for the number of calbindin and caspase-
oVEMPs (57%) and calorics (33%) consistent with other studies 3 (markers of Purkinje cells, oxidative stress, and apoptosis)
that suggest the saccule is more susceptible to acoustic trauma positive cells showed no differences from controls. In contrast,
than other vestibular sensory organs. These findings are also evoked potentials after blast exposure demonstrated sustained
consistent with anatomical findings that show the saccule is most changes beginning 24 h after injury. Potentials related to mossy
susceptible to noise-induced damage, followed by the utricle, and fiber discharges exhibited increased amplitudes and latencies
then the semicircular canals (19). while potentials related to climbing fiber activity exhibited
VsEPs have also been used to assess semicircular canal decreased amplitudes and decreased latencies. They concluded
function by replacing the linear head-jerk stimulus with an that neuronal activity may be more effective than behavioral tests
angular acceleration stimulus [A-VsEP; (42, 44)]. Perez et al. (44) or immunolabeling for neuronal loss in identifying early onset of
delivered a 15,000◦ /s2 (1–3 ms rise time) stimulus to provoke subtle injury after mild blast exposure.
A-VsEPs to assess semicircular canal function in sand rats Other studies have made use of manganese enhanced MRI
(Psammomys obesus) exposed to impulse-noise (160 dB SPL, 10 (MEMRI) to examine noise-induced changes in neuronal activity
impulses). This work found no change in A-VsEP amplitude, and in animal models in vivo (66–68). Manganese is a paramagnetic
only a transient (2–4-h) post-noise increase in A-VsEP latency ion that can be visualized using MRI. Manganese ions act as
that recovered by 1-week post-noise. In another study, the same calcium ion surrogates and enters active neurons via voltage
stimulus was used to assess the effect of a short (1 h) or extended gated calcium channels. Differential uptake of manganese is
and repeated noise exposure (12 h per day for 21 days). There used to identify changes in neuronal activity within vestibular-
was no effect of noise exposure on the A-VsEP with either noise related brain regions at acute (48 h, Figure 11) and chronic
exposure paradigm (42). Furthermore, there was no effect of time points (10 months, not shown) after noise exposure.
noise exposure on the linear VsEP following 113 dB SPL white Increased manganese uptake presumed to reflect increased
noise exposure (42). It should be noted that there was a 7-day neuronal activity, was found in the cerebellar paraflocculus and
rest interval between the last 12-h noise exposure and the post- the primary visual cortex (68, 69). Although vestibular pathways
noise VsEP measurement. It is possible that if measurements had were not a focus, this study provides a basis for future MEMRI
been taken shortly after the last noise exposure, a transient deficit studies that follow the impact of noise on temporal changes in
might have been detected. neuronal activity within vestibular pathways in vivo.
Single unit extracellular recording can be used to assess regular
and irregular vestibular afferent activity arising from all five
vestibular end organs. In a report characterizing changes in FUNCTIONAL EVIDENCE FOR
vestibular nerve activity, 116 dB SPL broadband white noise was NOISE-INDUCED VESTIBULAR DAMAGE
delivered unilaterally to rats for 3 h on a single day. Seven days
later, changes in hearing (ABR) and vestibular nerve activity Loss of vestibular function can result in vertigo (the illusion of
(single unit extracellular recording from the superior vestibular movement), oscillopsia (blurred vision during head movement),
nerve) on the noise exposed side was evaluated (19). Recordings postural instability, and/or motion intolerance. Several studies
from the superior aspect of the vestibular nerve included anterior in humans demonstrate a significant relationship between NIHL
and horizontal semicircular canal afferents as well as otolithic and postural stability. A limitation of these studies is a lack
afferents (utricle and 1/3 of the saccule). Although there was no of vestibular function testing; thus, the mechanism underlying
change in spontaneous firing rate in irregular superior vestibular the association between NIHL and postural stability is not
nerve afferents, spontaneous firing rates were significantly clear. An early study of iron workers (mean age = 53.3 years)
reduced in regular superior vestibular nerve afferents originating with chronic noise exposure (70) demonstrated a significant
from the anterior semicircular canal crista and the otolith organs. relationship between auditory thresholds and postural stability
Furthermore, there were extensive changes in the gain and as measured by sway velocity during static balance testing on
phase of regular horizontal and anterior canal afferents but a a firm surface with eyes open and closed. Service members
minimal effect of the 116 dB SPL broadband noise exposure with NIHL (mean age = 44.6 years) due to chronic impulse
on the irregular canal afferents. As discussed earlier, a post- noise exposure had greater postural sway (i.e., greater instability),
exposure examination of vestibular sensory epithelia reflected especially in the medial-lateral direction, during static balance
broad damage to the hair bundles in all end organs innervated testing with eyes open and closed than controls with normal
by the superior vestibular nerve (utricle, saccule; anterior and hearing and no noise exposure (mean age = 40.7 years) (71,
horizontal semicircular canal cristae). This work identified noise- 72). Guest et al. (73) showed a small reduction in voluntary
induced damage to regular afferents and highlights a limitation of limits of stability as measured by the functional reach test in
VsEP measurements: VsEPs only measure activity arising from military personnel with noise and solvent exposure (n = 601)
irregular afferents. compared to controls (no exposure: n = 391; noise exposure only,

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Stewart et al. Noise-Induced Vestibular Loss

FIGURE 11 | MEMRI (manganese enhanced magnetic resonance imaging) of the vestibular nuclear complex and cochlear nucleus 48 h. After noise exposure (10 kHz,
1/3 octave, 118 dB SPL, 4 h). (A) A schematic of a coronal section through the brainstem taken from a rat atlas showing brain regions of interest. (B) The T1-weighted
image shows brain regions of interest in vivo. Yellow arrows indicate the vestibular nuclear complex while white, green, and blue arrows indicate auditory regions. (C)
When noise-exposed animals are compared to controls 48 h. After the exposure there is increase in manganese uptake in the vestibular and auditory regions.
Colorimetric scale bar–gray indicates lowest Mn2+ uptake while white indicates the highest level of Mn2+ uptake. Adapted from (68).

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Stewart et al. Noise-Induced Vestibular Loss

n = 500). Moreover, there was a significant inverse corelation end organs. Other work has identified evidence of free-
between low-frequency auditory thresholds and functional reach, radical production in the vestibular labyrinth following noise
such that higher (poorer) thresholds were associated with lower exposure, which suggests a mechanism that may contribute
functional reach. to morphological observations. There are limited data on the
Two studies failed to demonstrate a significant relationship effects of noise on the central vestibular system, especially
between NIHL and postural stability (74, 75). Pyykkö et al. found following exposure to continuous noise. Physiological studies
equivalent postural sway velocity between Finnish soldiers (n = have corroborated morphological studies by demonstrating
54) with acute hearing loss due to firearm noise exposure (mean disruption across vestibular pathways with otolith-mediated
age = 27 years) and two control groups (soldiers with no acute pathways (VEMPs and linear VsEPs) impacted more frequently
noise trauma and age-matched civilians). Participants were tested than semicircular canal-mediated pathways. Similar to the
within 5 days of the onset of hearing loss under a variety balance temporary threshold shifts observed in the auditory system,
conditions: eyes open and closed on firm and foam surfaces, physiological studies in animals have suggested a capacity for
with and without calf muscle vibration, and with neck extended recovery following noise-induced vestibular damage. Human
backwards. The lack of a significant relationship between NIHL studies have demonstrated that diminished VEMP responses are
and postural stability may be due to acute noise exposure (vs. related to the severity of noise-induced hearing loss, and dose-
chronic exposure in the previous studies) or the younger age dependent vestibular deficits following noise exposure have been
of the subjects. Prasher et al. (75) examined postural control in corroborated in animal models. In contrast to the anatomical and
four exposure groups: noise only (n = 153; mean age = 53.3 neurophysiologic evidence, less is known about the relationship
years), solvents only (n = 13; mean age = 49.6 years), noise and among noise-induced damage to the inner ear, physiological
solvents (n = 174; mean age = 47.4 years) and controls with no changes associated with this damage, and functional measures
noise or solvent exposure (n = 39; mean age = 47.6 years). As of vestibular impairment (e.g., balance and gait) in animals
expected, the noise exposed group exhibited significantly poorer and humans.
pure-tone thresholds than the other groups, but had normal
postural stability as measured by computerized posturography AUTHOR CONTRIBUTIONS
during static balance with eyes open and closed on firm and
foam surfaces. It is not clear why these findings conflict with the CS reviewed the animal anatomical, physiological, and functional
previous studies. vestibular literature, drafted and revised the review. RA
There is a paucity of data on the effects of noise exposure on reviewed the anatomical literature and provided feedback
agility and motor function in animal models. Tamura et al. (20) on the entire review. AC drafted the blast-related hydrops
observed balance and gait changes in mice subjected to moderate section of the review and provided feedback on the entire
level, low-frequency continuous noise for a one-month time review. CH drafted the human functional section of the
period. Specifically, low-frequency noise-exposed mice exhibited review. AH drafted the central vestibular sections of the
impaired rotarod performance and imbalance, as well as shorter review and provided feedback on the entire review. OM
strides and a winding gait pattern that persisted for 4 weeks post- reviewed physiological and functional literature, and revised
exposure vs. controls or high-frequency noise-exposed mice. the entire review. WK reviewed physiological literature and
These deficits were associated with reduced calbindin labeling revised the entire review. FA reviewed the human anatomical,
of hair cells, and with elevated oxidative stress marker labeling physiological, and functional literature, drafted and revised the
when compared to control and high-frequency noise-exposed review. All authors contributed to the article and approved the
mice (20). submitted version.

CONCLUSIONS FUNDING
This review has examined the current literature on noise- This work was supported by Grant support: VA: 1I01RX001986∗ ,
induced vestibular loss, the differences in characteristics of 1IK2RX003271, E3367R∗ , 1I01RX001095∗ ; NIDCD: DC018003-
noise exposure, and how these differences might contribute to 01, DC015097, DC017063-01, DC000011. This material is based
variability in reported noise-induced vestibular deficits. Early upon work supported (or supported in part) by the Department
studies suggested that the vestibular system was susceptible of Veterans Affairs, Veterans Health Administration, Office of
to noise over-exposure. More recently, morphological studies Research and Development.
have confirmed and extended this early work, showing cellular
damage throughout the peripheral vestibular system, particularly ACKNOWLEDGMENTS
in the otolith organs; however, there is still a paucity of
data on the effect of noise exposure on human vestibular Maverick Dunavan for help with medical illustration.

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Stewart et al. Noise-Induced Vestibular Loss

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57. Wang YP, Hsu WC, Young YH. Vestibular evoked myogenic Conflict of Interest: The authors declare that the research was conducted in the
potentials in acute acoustic trauma. Otol Neurotol. (2006) 27:956–61. absence of any commercial or financial relationships that could be construed as a
doi: 10.1097/01.mao.0000231590.57348.4b potential conflict of interest.
58. Wang YP, Young YH. Vestibular-evoked myogenic potentials in chronic
noise-induced hearing loss. Otolaryngol Head Neck Surg. (2007) 137:607–11. Copyright © 2020 Stewart, Holt, Altschuler, Cacace, Hall, Murnane, King and Akin.
doi: 10.1016/j.otohns.2007.05.005 This is an open-access article distributed under the terms of the Creative Commons
59. Wu CC, Young YH. Ten-year longitudinal study of the effect of impulse noise Attribution License (CC BY). The use, distribution or reproduction in other forums
exposure from gunshot on inner ear function. Int J Audiol. (2009) 48:655–60. is permitted, provided the original author(s) and the copyright owner(s) are credited
doi: 10.1080/14992020903012481 and that the original publication in this journal is cited, in accordance with accepted
60. Zuniga MG, Dinkes RE, Davalos-Bichara M, Carey JP, Schubert academic practice. No use, distribution or reproduction is permitted which does not
MC, King WM, et al. Association between hearing loss and saccular comply with these terms.

Frontiers in Neurology | www.frontiersin.org 16 November 2020 | Volume 11 | Article 593919