Sensory Systems · Unit 6: Hearing and balance

The Cochlear Amplifier and Otoacoustic Emissions

The core course showed that outer hair cells need prestin to amplify sound. This lesson asks how the motor works, whether the hair bundle is a second engine, why a healthy ear sends sound back out, and where inside the living cochlea the gain is built. Afterwards you can read a nonlinear-capacitance curve, say what a structure of a ligand-bound protein can and cannot show, and interpret in vivo motion measurements and an otoacoustic emission test.

Watch first What the returning sound leaves out · 2:58

A microphone sealed in a healthy ear canal can record sound that the cochlea made. What does that returning sound tell us about the amplifier, and what does it leave out?

The core lesson hearing and balance established that outer hair cells shorten and lengthen with voltage, that the protein prestin is the motor, and that a knock-in mouse supports a requirement for its motility. This lesson starts after that point. It asks how the motor works, whether the hair bundle is a second engine, what sound the ear emits, and where inside the living cochlea the gain is built. Each answer comes from a different preparation, and none of them is complete.

What a motor must do, and what the structures show

A tone at 20 kHz, near the top of the human range, completes a cycle every 50 microseconds. An amplifier that adds energy on every cycle cannot wait for a chemical step each time, so the outer hair cell uses a protein that responds to voltage directly. Prestin belongs to the SLC26 family of anion transporters (membrane transport), yet in the outer hair cell it works as a motor.

Three structural papers appeared within about a year, each on a different species and with a different emphasis:

  • Ge and colleagues (Cell, 2021) solved full-length human prestin, expressed in HEK293 GnTI-minus cells and purified into detergent micelles or lipid nanodiscs. It is a domain-swapped homodimer. The dimers solved in chloride and in salicylate differ by about 200 square angstroms (2 square nanometres) in mean transmembrane cross-sectional area, and an ordered ring of lipid surrounds the protein. The authors proposed that a shape change of the protein is coupled to a change in membrane area.
  • Bavi and colleagues (Nature, 2021) resolved recombinant dolphin prestin in six distinct states. They suggested that the voltage sensor is a composite of a bound anion, coordinating charged residues and a helix dipole, and interpreted salicylate inhibition as the protein being held in one conformation.
  • Butan and colleagues (Nature Communications, 2022) solved gerbil prestin at 3.6 angstroms. Each protomer has 14 transmembrane helices, and the cytoplasmic STAS domains are swapped. The anion-site mutant S398E kept its nonlinear capacitance in 20 millimolar salicylate, which the authors argued is hard to reconcile with a chloride-only extrinsic voltage sensor.

A later study combined molecular dynamics of human prestin with fluorescence and functional tests on rat prestin constructs (in cultured CHO cells and Xenopus oocytes) and supported an elevator-like movement of a transport domain, while stating that chloride’s role was still unclear (Kuwabara and colleagues, Nature Communications, 2023).

Read these as complementary views, not one settled movie. Every structure is of purified protein held in a state by a ligand. Butan and colleagues cautioned that salicylate- or sulfate-stabilized structures could differ from the shapes of a voltage-driven protein. The 200 square angstrom figure compares two structures. It is not a stroke measured in a hair cell, and it is not mechanical work.

Reading a nonlinear-capacitance curve

How do you connect a structure to an electrical response? One answer is nonlinear capacitance (NLC). In whole-cell voltage clamp a cell expressing prestin shows a bell-shaped capacitance that peaks at one voltage. The usual reading is that NLC reports voltage-dependent displacement of charge in the protein. Depolarization shifts prestin toward a contracted state, the state associated with outer hair cell shortening.

A minimal model has two states. With occupancy f of the contracted state, an effective valence z and a half-activation voltage Vh:

f(V) = 1 / (1 + exp(-z (V - Vh) / (kT/e))), normalized NLC = 4 f (1 - f)

Worked problem. Butan and colleagues fitted gerbil prestin in an induced HEK cell line with Vh = -112 mV and z = 0.70 (an effective charge, not a count of transported chloride ions). Assume 295 K, a two-state equilibrium, no linear capacitance and no kinetics, so kT/e = 25.42 mV. What are the occupancy and normalized NLC at Vh and at -62 mV?

Step 1: at Vh. The exponent is zero, so f = 0.5 and normalized NLC = 4 x 0.5 x 0.5 = 1, the peak.

Step 2: at -62 mV. The shift is -62 - (-112) = +50 mV. The exponent is -0.70 x 50 / 25.42 = -1.377, so f = 1 / (1 + 0.2523) = 0.798. Occupancy rose by 0.298.

Step 3: capacitance. Normalized NLC = 4 x 0.798 x 0.202 = 0.644, about 64 percent of the peak.

Step 4: check. At -162 mV, 50 mV hyperpolarized from Vh, f = 0.202 and NLC is again 0.644.

This is charge movement in a cell line at room temperature, under stated assumptions. It says how the protein’s charge responds to voltage. It does not say how much force or power a hair cell produces. The Butan result also shows why controls matter: before reading drug insensitivity of NLC, you need expression, localization and baseline NLC for each mutant.

Prestin charge bell — occupancy and nonlinear capacitance⚙ original · interactive
(available up to +26 mV)

Hollow orange circles mark the mirror voltage, the same distance on the other side of Vh.

V − Vh
+50 mV
Exponent −z(V − Vh)/(kT/e)
−1.377
Occupancy f (contracted)
0.798
Change in f from Vh (0.5)
+0.298
NLC as a fraction of peak
0.644

In this sketch: two-state equilibrium, no linear capacitance, no kinetics, kT/e = 25.42 mV (295 K). Vh = −112 mV and z = 0.70 are the values fitted to gerbil prestin in an induced HEK cell line at room temperature (Butan and colleagues, 2022). The curves are computed from the lesson’s equation, not recorded.

Keep this rule: the bell reports how the protein’s charge responds to voltage in a cell line. It does not say how much force or power a hair cell produces.

A second engine, measured in a frog

Outer hair cell bodies are not the only candidate. Martin and Hudspeth (PNAS, 1999) used adult bullfrog saccular epithelium in vitro, with the otolithic membrane removed. A two-compartment chamber let the apical side bathe in artificial endolymph. A flexible probe moved single bundles while photometry tracked them. Some bundles oscillated spontaneously, up to 50 nanometres, at 5 to 40 Hz.

AI-generated illustration: cutaway of a two-compartment chamber with a thin sheet of bullfrog saccular epithelium across the middle, endolymph-like fluid above and a different solution below, a flexible probe touching one hair bundle and a light path tracking it. An inset compares the small energy the probe supplies with the larger energy lost to drag.
Martin and Hudspeth held an excised bullfrog saccule with its apical side in artificial endolymph and moved single hair bundles with a flexible probe while photometry tracked them. A bundle lost more energy to drag than the probe supplied, so the bundle itself added energy. This is one frog organ in a dish; the split between bundle and cell body in mammals is not established.

Why does a work balance matter more than a large movement? A passive bundle pushed by a probe can move far, because the probe supplies the energy. The authors found that the bundle dissipated more energy through viscous drag than the probe supplied, so the bundle itself added energy.

Mammals are different cells in a different organ. In his review (Nature Reviews Neuroscience, 2014), Hudspeth states that in mammals bundle motility operates in conjunction with prestin-based somatic motility, and that both bundles and the whole cochlea operate near a dynamical instability, the Hopf bifurcation. The frog experiment gives no mammalian number for how the work is split between the two, and no split has been established. The current that drives both engines is the subject of the hair-cell transduction channel.

Sound coming back out

Kemp (J. Acoust. Soc. Am., 1978) studied human ears in vivo. Brief acoustic impulses were delivered to the closed ear canal and the canal response was signal-averaged. Beyond 5 milliseconds after the stimulus, a slowly decaying component remained, with a decay constant over 12 ms. In the ears with cochlear deafness that were tested, it was absent. That supports a cochlear source. It does not identify a motor.

A second kind of emission uses two tones. If f1 and f2 are played together, a nonlinear cochlea also produces energy at 2f1 - f2; Boero and colleagues recorded this distortion product in mice. Suppose f1 = 2,000 Hz and f2 = 2,400 Hz in an invented example: 2 x 2,000 - 2,400 = 1,600 Hz, a frequency the stimulus did not contain.

Emission tests are used in newborn hearing screening. A pass shows that outer hair cell activity can produce an emission through the middle ear. It does not show intact hearing, because auditory neuropathy can present with a normal emission and an absent or very abnormal auditory brainstem response (NIDCD). Emission and brainstem tests probe different stages.

The outer hair cell also receives input from the brain. Medial olivocochlear efferents release acetylcholine, which acts through nicotinic receptors containing the alpha-9 and alpha-10 subunits. Calcium entry activates nearby calcium-dependent potassium channels, and acetylcholine suppresses outer hair cell electromotility by shunting and hyperpolarization (reviewed by Fuchs and Lauer, 2019). In mice, Boero and colleagues (2018) exposed animals at postnatal day 21 to 1 to 16 kHz noise at 100 dB SPL for one hour. Wild-type mice recovered thresholds but lost ribbon synapses. Mice lacking Chrna9 kept permanent threshold elevations, and mice with a gain-of-function receptor (L9’T) resisted the same protocol. That is conditional protection in constitutive mouse genotypes at one age and one exposure, not a treatment and not evidence about people.

Inside the living cochlea: where gain accumulates

Older measurements of the basilar membrane gave one number at one place. Newer optical methods look at several depths in the living organ of Corti. Three mouse studies are worth comparing.

  • Ren, He and Kemp (PNAS, 2016) used anaesthetized CBA/CaJ mice aged 3 to 5 weeks, at a basal site about 0.85 mm from the base. Reticular-lamina motion exceeded basilar-membrane motion at lower frequencies and near the best frequency at 20 to 50 dB SPL, but not significantly at 60 to 80 dB SPL. The magnitude and phase differences disappeared postmortem.
  • Lee and colleagues (J. Neurosci., 2016) imaged the apex through the intact otic capsule in mice aged P28 to P42, with tones from 2 to 13 kHz. Radial tuning persisted postmortem, which they took to suggest a passive contribution within the organ of Corti.
  • Dewey, Applegate and Oghalai (J. Neurosci., 2019) used 4 to 6 week old CBA/CaJ mice and a site whose best frequency was about 9 to 9.5 kHz, with two-tone suppression. They concluded that forces from outer hair cells accumulate mainly near the peak of the travelling wave.

These studies used different sites, different questions and different readouts, so they do not simply contradict or confirm one another. The unsettled point is how far along the cochlea gain is built, and how much is local.

AI-generated illustration: a block cross-section of the organ of Corti with a basilar membrane at the bottom, three outer hair cells standing on it and a reticular lamina across their tops, with a light beam read at both layers. Two insets compare a living mouse, where the reticular lamina moves more, with after death, where the two move equally.
Optical measurements read motion at the reticular lamina and the basilar membrane together. In living mice Ren and colleagues found larger reticular-lamina motion at lower frequencies and near the best frequency at lower sound levels, and the difference disappeared after death. Motion is not work done, and one basal site is not a map of the cochlea.

Design problem

Two groups measure motion inside the living cochlea. One favours gain that accumulates along the cochlea; the other favours gain made locally. Design an experiment to separate them, then interpret this result: in a living mouse, reticular-lamina motion exceeds basilar-membrane motion at and below the best frequency, and the difference disappears postmortem.

One way to do it

Measure motion at matched sites with depth and direction resolved, so the reticular lamina and the basilar membrane are read in the same radial segment. Probe near the best frequency, then add a second suppressing tone with its frequency place basal to the measurement site. If gain accumulates from distant regions, suppressors there should reduce the local response. If gain is made locally, only suppressors near the site should matter. Repeat each condition postmortem in the same animal as a control.

Dewey and colleagues made the suppression measurements in living mice at an apical site with a 60 dB SPL probe near the best frequency; they did not repeat them after death, so the postmortem control is an extension proposed here. They estimated buildup distances of 0.95 +/- 0.024 mm (mean +/- SEM, n = 8) for the basilar membrane and 0.71 +/- 0.042 mm (n = 10) for the reticular lamina. That points to a limited stretch of cochlea contributing, not the whole base.

For the stated result: a difference that vanishes after death depends on the living state, and larger reticular-lamina motion shows the organ of Corti is not moving as one block. The result does not show where the energy comes from or how it is split between bundles and cell bodies. Motion is not work done. One apical site in one strain at one level is not a map of the cochlea, and the basal site of Ren and the apical site of Dewey cannot be assumed to behave alike.

How we measure it

Single-particle cryo-EM

Purified protein is frozen in a thin film and imaged, and many particle images are averaged into a three-dimensional map. It shows the architecture and ligand-associated states of the protein, but it does not measure force, work or voltage-driven movement.

Whole-cell voltage clamp with nonlinear-capacitance analysis

The voltage of a cell is stepped or ramped while capacitance is measured. A bell-shaped capacitance peak reports voltage-dependent displacement of charge, and a two-state Boltzmann fit gives a half-activation voltage and an effective charge.

Optical coherence vibrometry with two-tone suppression

Light reflected from several depths of the living cochlea gives motion of the basilar membrane and the reticular lamina at once. A second, suppressing tone then tests which regions of the cochlea set the gain at the measured site.

Ear-canal acoustic recording with signal averaging

A microphone in the sealed ear canal records the response to clicks or to two pure tones, and averaging separates the faint cochlear emission from noise. It tests outer hair cell function without entering the ear.

Finish line

Test yourself

8 questions

Practice and MCAT-style, with explained answers.

Next · Lesson 24

Hidden Hearing Loss, Gene Therapy and Regeneration

A mouse can pass its hearing test after loud noise and still have lost about half the ribbon synapses at one place in the cochlea. What does a normal threshold actually tell you?

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← Lesson 22 · The Hair Cell's Transduction Channel

Pascal Martin and A. James Hudspeth

Pascal Martin and A. James Hudspeth

Showed in the excised bullfrog sacculus that hair bundles can oscillate spontaneously and that bundle motion dissipated more energy through drag than the stimulus probe supplied.

Cochlear amplification was usually attributed to the outer hair cell body. Martin and Hudspeth asked whether the hair bundle itself could add energy. They used adult bullfrogs (Rana catesbeiana), taking the saccular epithelium out of the animal and removing the otolithic membrane. A two-compartment chamber let the top of the cells sit in an artificial endolymph while the base sat in a different solution, as in the intact organ. They deflected individual bundles with a flexible probe and tracked bundle motion by photometry. Some bundles oscillated spontaneously, with amplitudes as great as 50 nanometres at 5 to 40 hertz. When the probe drove a bundle at a frequency near its own oscillation, the energy lost to viscous drag exceeded the work the probe supplied. The authors took this to show that the bundle supplied energy. The result was measured in one frog organ in a dish. It gave later workers a clear question about mammals, where the share of bundle and cell body is still debated.

✓ verbatim Martin & Hudspeth, Proc. Natl. Acad. Sci. USA (1999), doi:10.1073/pnas.96.25.14306; Hudspeth, Nat. Rev. Neurosci. (2014), doi:10.1038/nrn3786.
David Kemp

David Kemp

Recorded in human ear canals a late acoustic response to brief impulses that was absent in ears with cochlear deafness, which pointed to a cochlear source for sound returning from the ear.

An ear canal is normally treated as a place where sound goes in. Kemp asked whether anything came back. In a study of human ears published in the Journal of the Acoustical Society of America in 1978, he delivered brief acoustic impulses to the external ear and used signal averaging to pull faint responses out of the noise in the canal. He examined the response more than 5 milliseconds after the stimulus. In the normal ears a slowly decaying component remained, with a decay constant over 12 milliseconds. In the ears tested that had cochlear deafness it was absent. That pairing supported a cochlear origin for the returning sound. It did not name a molecule or a motor. It did give clinicians and physiologists a way to listen to outer hair cell function without placing anything inside the ear.

✓ verbatim Kemp, J. Acoust. Soc. Am. (1978), doi:10.1121/1.382104.
Jingpeng Ge, Johannes Elferich and Eric Gouaux

Jingpeng Ge, Johannes Elferich and Eric Gouaux

With colleagues, solved cryo-EM structures of human prestin in two anion conditions and proposed that its conformational change alters the area of the membrane.

By 2021 prestin was known to be necessary for outer hair cell amplification, but nobody had seen what the full-length protein looked like. Ge, Elferich and colleagues, with Eric Gouaux, expressed full-length human prestin in HEK293 GnTI-minus cells, purified it into detergent micelles or lipid nanodiscs, and used cryo-EM. They found a homodimer in which the two halves exchange domains. They solved the protein in the presence of chloride and in the presence of salicylate, a drug that inhibits prestin function. Comparing the two structures, they found a mean difference of about 200 square angstroms in the cross-sectional area of the part of the dimer inside the membrane, and they resolved an ordered ring of lipid around the protein. They proposed that prestin couples a change of protein shape to a change in membrane area. The structures are of purified protein held by ligands, so they are a map of candidate end states, not a recording of a working motor.

✓ verbatim Ge et al., Cell (2021), doi:10.1016/j.cell.2021.07.034.
Carmen Butan and Joseph Santos-Sacchi

Carmen Butan and Joseph Santos-Sacchi

With colleagues, solved a 3.6 angstrom gerbil prestin structure and found that a mutant at the anion site kept nonlinear capacitance in salicylate.

About a year after the human structure, another group published on gerbil prestin. Butan, Santos-Sacchi and colleagues made prestin fused to a yellow fluorescent protein in an inducible HEK293 cell line, purified it in detergent and solved its structure at 3.6 angstroms. Each protomer has 14 transmembrane helices, and the cytoplasmic STAS domains of the two protomers are swapped. The group also did what structure alone cannot: they recorded nonlinear capacitance from cultured cells expressing wild-type and mutant prestin. A mutant at the anion site, S398E, kept its nonlinear capacitance in 20 millimolar salicylate. They argued that this undermines the idea that chloride alone is the voltage sensor. The authors also cautioned that structures stabilized by salicylate or sulfate could differ from the shapes the protein takes when driven by voltage. The paper is dated 2022, although 2021 appears in its DOI.

✓ verbatim Butan et al., Nat. Commun. (2022), doi:10.1038/s41467-021-27915-z.
Test yourself
Question 1 of 8 Score 0 / 0

What does a bell-shaped nonlinear capacitance of a prestin-expressing cell report?
Sources & Integrity

Every structure, slide, simulation, and clip on this page is listed below with the source it came from. None of the 3D structures is drawn by hand or by AI: each one loads by accession ID from RCSB PDB or PubChem. This panel is generated from the lesson's own data file, so what it lists is what the page loads.

Simulations

  • Prestin's charge and the capacitance bell · Original interactive — Biochemistrypedia (Deppmann Lab).

Scientist profiles & quotes

  • Pascal Martin and A. James Hudspeth — Martin & Hudspeth, Proc. Natl. Acad. Sci. USA (1999), doi:10.1073/pnas.96.25.14306; Hudspeth, Nat. Rev. Neurosci. (2014), doi:10.1038/nrn3786.
  • David Kemp — Kemp, J. Acoust. Soc. Am. (1978), doi:10.1121/1.382104.
  • Jingpeng Ge, Johannes Elferich and Eric Gouaux — Ge et al., Cell (2021), doi:10.1016/j.cell.2021.07.034.
  • Carmen Butan and Joseph Santos-Sacchi — Butan et al., Nat. Commun. (2022), doi:10.1038/s41467-021-27915-z.

Quotes are verbatim from the cited source. Profile text is original to this site and was checked against the sources cited.

Animated explainer

What the returning sound leaves out · narration: an AI narrator voice (Gemini, Charon) reading narration written from this lesson's text · animation: AI-generated in code (Manim) by Claude, a schematic with no drawn molecular structures, plots computed from their equations · captions from the narration script.

Images & figures

2 illustrations in this lesson are AI-generated: drawn by an image model from a written spec, then checked by a separate AI judge against the spec and the lesson text. None shows a chemical structure or data.

  • cutaway of a two-compartment chamber with a thin sheet of bullfrog saccular epithelium across the middle, endolymph-like fluid above and a different solution below, a flexible probe touching one hair bundle and a light path tracking it. An inset compares the small energy the probe supplies with the larger energy lost to drag.
  • a block cross-section of the organ of Corti with a basilar membrane at the bottom, three outer hair cells standing on it and a reticular lamina across their tops, with a light beam read at both layers. Two insets compare a living mouse, where the reticular lamina moves more, with after death, where the two move equally.

Every 3D structure is rendered live from an accession ID, and every plot is drawn from its equation in the browser.

integrity Machines check the mechanics. The build confirms that every local file exists, that every question's answer key points at a real choice, and that any AI-generated scientific figure names the person who checked it; a weekly job re-resolves every accession ID against its database. Questions are original; MCAT-style items are written for this site and are not real AAMC questions. Banned sources (the Tymoczko textbook, publisher decks, copyrighted figures) are not used.

Like I'm five

Inside your ear are special cells that push back when a sound comes in, a bit like pushing a swing at the right moment so it goes higher. The pushing part is a tiny protein that changes shape when electricity changes. Scientists have taken pictures of that protein, and they are still working out how it moves. The pushing makes a little sound that leaks back out of your ear, and doctors can listen for it to check the cells are working.
High school

Hearing needs a boost for quiet sounds. Outer hair cells in the cochlea give it by changing length many thousands of times a second, driven by a protein called prestin that responds directly to voltage. Scientists solved the shape of prestin from several species and found that it is a pair of molecules that may change the area it takes up in the cell membrane. Hair bundles on top of the cells may add a second kind of push, shown in frogs. A sensitive microphone in the ear canal can pick up the faint sound the working cells send back out, which is used to screen newborns. A pass does not prove the whole path to the brain works.
College

Prestin (SLC26A5) is a voltage-driven motor whose nonlinear capacitance reports voltage-dependent charge movement. Cryo-EM structures of human, dolphin and gerbil prestin show a domain-swapped dimer; the human Cl- and salicylate structures differ in transmembrane area by about 200 square angstroms, supporting an area-motor model. A gerbil anion-site mutant keeps nonlinear capacitance in salicylate, arguing against a chloride-only sensor. In the bullfrog sacculus, hair bundles oscillate spontaneously and perform work against drag, so bundle motility is a second active process, with its share in mammals unresolved. Otoacoustic emissions are sounds made by the cochlea; a normal emission with an abnormal brainstem response points to the neural side, as in auditory neuropathy. Medial olivocochlear efferents can protect against noise in mice.
Graduate

Nonlinear capacitance in a two-state model is Cnl proportional to f(1 - f), with f given by a Boltzmann function of V - Vh with effective valence z. For gerbil prestin in an induced HEK cell line (Vh = -112 mV, z = 0.70, assuming 295 K), a 50 mV depolarization from Vh gives f = 0.80 and 0.64 of peak capacitance. This reads charge movement, not power. The Ge, Bavi and Butan structures are complementary, ligand-stabilized views, and the Butan authors caution that they may differ from voltage-driven states; later simulation (human prestin) and fluorescence and functional work (rat prestin constructs) supports an elevator-like transport-domain movement, with chloride's role still unclear.

In vivo optical measurements disagree in emphasis. Reticular-lamina motion exceeds basilar-membrane motion at a basal mouse site and the difference vanishes postmortem, radial tuning persists postmortem at the apex, and two-tone suppression suggests gain accumulates mainly over a limited distance near the wave peak. Whether bundle motility sets phase while somatic motility supplies power in mammals has not been measured. What experiment would separate bundle from somatic contributions in the living cochlea is open.
A difference that death erases

Ren, He and Kemp measured motion in the cochleas of living, anaesthetized CBA/CaJ mice aged three to five weeks, at a basal site about 0.85 millimetres from the base. They used a scanning heterodyne low-coherence interferometer to separate the motion of the reticular lamina from that of the basilar membrane. In the living animal the reticular lamina moved more than the basilar membrane at lower frequencies, and near the best frequency at 20 to 50 dB SPL; at the best frequency the difference was not significant at 60 to 80 dB SPL. When they repeated the measurements after death in the same preparation, the differences in magnitude and phase disappeared. The experiment ties the difference to the living state, not to the tissue's anatomy alone.

— Ren, He & Kemp, Proc. Natl. Acad. Sci. USA (2016), doi:10.1073/pnas.1607428113.
Recovered thresholds, lost synapses

Boero and colleagues exposed mice at postnatal day 21 to noise from 1 to 16 kilohertz at 100 dB SPL for one hour, under anaesthesia. Wild-type mice recovered their thresholds, but their ribbon synapses were lost. Mice lacking the gene for one subunit of the efferent receptor, Chrna9, kept permanent threshold elevations. Knock-in mice with a gain-of-function version of the receptor, L9'T, resisted the same exposure protocol. The result shows receptor-dependent protection under one protocol in constitutive mouse genotypes. It is not a treatment, and the authors did not test it in people.

— Boero, Castagna, Di Guilmi, Goutman, Elgoyhen et al., J. Neurosci. (2018), doi:10.1523/JNEUROSCI.0363-18.2018.
A pass that is not a guarantee

An evoked otoacoustic emission test records faint sounds made by outer hair cells in the ear canal after a stimulus. The NIDCD describes auditory neuropathy as a condition in which the emission reading can be normal while the auditory brainstem response is absent or very abnormal. The two tests probe different stages: the emission reflects outer hair cell activity, and the brainstem response depends on the synchronous firing of the auditory nerve. A normal emission therefore excludes some problems but not others, and screening programmes pair it with a follow-up pathway.

— National Institute on Deafness and Other Communication Disorders, health information on auditory neuropathy (accessed 2026).

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