Effects of Infrasound Exposure on Measures of Endolymphatic Hydrops

Infrasound is generated within the human body by processes such as respiration and myocardial
contraction. External sources include those produced naturally, such as wind and earthquakes,
and those that are human-made, such as automobile engines and heavy machinery. Wind turbines
are known to emit infrasound with a fundamental frequency of 1 Hz with intensities
approaching 100 decibels (dB), depending on wind speed. Over 75,000 wind turbines have been
deployed between 2003 and 2015 in the U.S. alone. As environmental infrasound exposure has
increased in prevalence and intensity with the advent of technologies such as large-scale
wind turbines, renewed attention has been directed to the effects of infrasound on exposed
individuals.

As it falls below audible thresholds, conventional wisdom would dictate that infrasound does
not affect humans. However, some individuals living in proximity to wind turbines experience
increased levels of annoyance and sleep disturbance in a dose-response fashion. Other
reported symptoms from infrasound exposure include aural fullness, tinnitus, dizziness, and
vertigo. Some researchers hypothesize that these otologic symptoms are related to the
infrasonic component of wind turbine noise affecting inner ear function. However, since the
mechanism or causal role have yet to be established, others attribute such symptoms to a
psychosomatic or "nocebo" effect (i.e. worsening symptoms produced by negative expectations).
As wind farms and other infrasound-generating sources become widespread, there is now a
critical need to determine the effects of infrasound on inner ear function.

Studies conducted in humans have confirmed that infrasound has measurable effects within the
cochlea. Hensel et al presented infrasound tones of 6 and 12 Hz at 130 dB sound pressure
level (SPL) while simultaneously measuring distortion product otoacoustic emissions (DPOAEs).
They observed considerable increases in DPOAE amplitudes in the presence of infrasound
compared to when these tones were absent. The authors attributed this effect to the
displacement of the cochlear partition during infrasound exposure. Further, Dommes et al
demonstrated activity in the primary auditory cortex on functional magnetic resonance imaging
during infrasound exposure, providing evidence that perception of infrasound occurs through
known auditory pathways.

Reversible hydropic changes of the endolymphatic space have been observed during short-term
exposure to infrasound and low frequency sound in several guinea pig models. Flock and Flock
utilized an explanted guinea pig temporal bone model to visualize expansion of the
endolymphatic space on confocal microscopy while applying tone bursts of 140 Hz between
88-112 dB. Shortly after this work, Salt detected changes indicative of endolymphatic hydrops
in vivo using volume and flow markers iontophoresed into the endolymphatic space of guinea
pigs during 3 minutes of exposure to 200 Hz tone bursts at 115 dB SPL. The observed changes
in flow and volume in the endolymphatic space were reversible. The recovery half time in this
study was 3.2 minutes. Subsequent work by Salt et al demonstrated that infrasound at 5 Hz
generated larger endolymphatic potentials in the third cochlear turn than did frequencies in
the audible range from 50-500 Hz. This was despite a presentation level expected to be below
the hearing threshold of the guinea pigs. These studies demonstrate that infrasound and
low-frequency tones have measurable effects on inner ear physiology, even at sub-threshold
hearing levels.

While there is evidence that the human cochlea is stimulated by infrasound, it is not known
if infrasound induces endolymphatic hydrops in humans. The proposed work will test the
central hypothesis that short-term infrasound exposure induces reversible endolymphatic
hydrops in the human inner ear. This hypothesis is based on the observations in the presented
animal studies and the observed combination of auditory and vestibular symptoms reported to
be associated with infrasound exposure.

In order to test the hypothesis in living humans, the proposed study will utilize
electrophysiologic tests that are currently employed as clinical tests for endolymphatic
hydrops. By using a combination of tests, evidence of hydrops will be sought in both the
cochlea and the vestibular system.

1. Electrocochleography (ECoG). ECoG is an electrophysiologic test of cochlear function.
Conditions such as Ménière's disease, which are characterized by endolymphatic hydrops,
demonstrate an elevated summating potential to action potential (SP/AP) ratio on
electrocochleography (ECoG). An increase in the SP relative to the AP is thought to be
due to a deflection of the basilar membrane position toward the scala tympani.
Accordingly, abnormal ECoG has been correlated with the finding of cochlear hydrops (in
the basal turn) on gadolinium-enhanced MRI.

2. Vestibular evoked myogenic potentials (VEMPs). VEMPs arise from sound-induced activation
of otolith organs and their associated vestibular neurons. The cervical VEMP (cVEMP) and
ocular VEMP (oVEMP) are theorized to originate from the saccule and utricle,
respectively. Thresholds, defined as the lowest stimulus intensity at which a response
is seen, can be obtained at multiple test stimulus frequencies (250, 500, 750, 1000 Hz)
and threshold response curves can be constructed. The lowest threshold for eliciting a
response is typically seen at 500 Hz for both oVEMP and cVEMP. In hydropic conditions
such as Ménière's disease, VEMP thresholds can be elevated or absent at all tested
frequencies. Additionally, VEMP tuning curves can be shifted such that the lowest
threshold is observed at a different tested frequency (e.g. 750 or 1000 Hz). A shift in
resonance frequency of the otolithic organs due to pressure changes in the endolymphatic
space is hypothesized to cause these changes.

Successful completion of the aims of this study will afford better understanding of the
potential effects of infrasound on inner ear function. The findings of this work will fuel
additional investigation of risks of infrasound exposure and may spur efforts to reduce
individual and environmental exposure. A newly described mechanism would provide researchers,
regulators and advocacy groups with a previously absent and crucial understanding of the
effects of infrasound on inner ear function when crafting policy, designing new technologies,
and ensuring the safety of exposed individuals

Inclusion Criteria:

1. Age of 18 to 60 years

2. Absence of otologic symptoms based on screening questionnaire

3. Normal otoscopic examination

4. Audiometric thresholds less than 25 dB at 250, 500, 750, 1000 Hz.

Exclusion Criteria:

1. Age less than 18 or greater than 60 years. Age greater than 60 is considered an
exclusion criterion as prior studies have demonstrated elevated VEMP thresholds
attributed to age

2. Presence of any positive symptom on the questionnaire

3. Thresholds greater than 25 dB at the tested frequencies

4. Abnormal otoscopic examination (e.g., ear canal occlusion, tympanic membrane
perforation, tympanic membrane retraction)

5. History of prior ear surgery.