Present results explain the origin of Tullio phenomena, where a dehiscence or fistula in the bony labyrinth results in pathological and debilitating vestibular responses to sound. Introducing a flexible window in the bony labyrinth alters pressure gradients in the inner ear, which causes hearing loss and introduces abnormal vestibular sensitivity to sound. Conductive hearing loss and vestibular sensitivity to low-frequency stimuli are relatively straightforward to explain on the basis of pressure-driven displacement of inner ear fluids6,8,9,19, but sustained responses of SCC afferent neurons to auditory frequency stimuli are more difficult to explain. Here, we present experimental and theoretical evidence that sustained SCC responses to auditory frequency stimuli are due to traveling waves arising at the site of the dehiscenc and propagate in both directions to pump endolymph around the afflicted SCC. Two consequences of these waves combine to generate vestibular sensitivity to sound. First, the waves vibrate the membranous labyrinth, leading to cycle-by-cycle displacement of sensory hair bundles, modulation of mechano-electrical transduction currents, and phase-locked action potentials. Second, traveling waves pump endolymph around the SCC loop21, mimicking angular head acceleration, leading to tonic hair bundle displacements, and evoking sustained changes in action potential firing rate. Notably, sound-evoked vibration and endolymph pumping caused by waves are also present in the intact labyrinth, however are decreased by two orders of magnitude or more.

The fact that waves originate at the dehiscence and travel in both directions toward the sound source might seem counterintuitive, but the phenomenon arises directly from the mechanics. Compressibility of the inner ear fluids is negligible at physiologically relevant pressures, so any net inward movement of fluid driven by sound pressure at the oval window must be balanced by an outward movement at the dehiscence and the round window. If the dehiscence size is small compared to the vestibule, the fluid displacement at the dehiscence will be relatively large. Hence, the largest pressure modulation acting across the vestibular membranous labyrinth is at the dehiscence, giving rise to traveling waves propagating away from the dehiscence (e.g. Fig. 1Ai). Because of this, the condition can be modeled experimentally by mechanical stimulation at the site of the dehiscence. Notably, in many cases of canal dehiscence, there is sufficient bone loss to allow dura to herniate into the canal, which defects the membranous labyrinth and induces pulsatile oscillopsia synchronous with heartbeat31,32,33. Frequency-dependent endolymph pumping occurs due to asymmetric traveling wave reflection. Multiple reflections lead to a combination of standing waves and traveling waves in the both limbs of the dehisced canal (e.g. Fig. 2). As a result, pumping occurs ampullofugal or ampullopetal depending on which limb of the canal admits the dominant traveling wave. The direction of wave pumping can switch with frequency (e.g. Figs 4E and 5), because the extent of reflection in the two directions is dependent on tissue morphology and stimulus frequency. Accounting for bi-directional propagation is essential to capture frequency dependence of the direction and magnitude of pumping – features of Tullio phenomena that cannot be explained by unidirectional wave propagation21.

The fundamental mechanisms responsible for waves in the vestibular labyrinth are identical to those responsible for traveling waves in the cochlea. In both cases, the system consists of two fluid compartments separated by a flexible partition. The fluids provide the kinetic energy (mass) and the partition provides the potential energy (stiffness), which combine with viscosity to give rise to dispersive traveling waves. In the cochlea, the oval and round windows are positioned in such a way to preferentially excite traveling waves on the flexible cochlear partition, while avoiding excitation of traveling waves on the flexible “vestibular partition”. Introduction of a SCC dehiscence or fistula adds a third flexible window that allows vibration of the oval window to excite traveling waves along the vestibular partition. Since the vestibular system lacks the specialized morphology of the cochlea, there is no equivalent “place principle” or traveling wave frequency decomposition. Nevertheless, there is sound-evoked wave propagation very similar to the cochlea. Waves originate at the dehiscence, propagate in both directions, decay with distance, reflect due to changes in geometry, and combine to generate frequency-dependent patterns of standing and traveling waves. Like the cochlea, cycle-by-cycle vibration of hair bundles leads to afferent nerve responses phase-locked to auditory frequency stimuli. In addition, nonlinear wave pumping evokes slow responses that build up during the acoustic stimulus and decay upon cessation of the stimulus. The same wave pump phenomenon is present in the cochlea, but its effect on cochlear mechanics and potential impact on the sensation of sound has not yet been examined. Avoiding responses to low-frequency wave pumping might be one reason why auditory hair cells evolved to selectively encode to high-frequency signals through the high-pass filter characteristics of their mechano-electrical transduction channels34,35. Many SCC hair cells, in contrast, do not have this high-pass characteristic29, thus making the canals sensitive to low-frequency physiological stimuli as well as pathological nonlinear wave pumping in dehisced canals.

Experimental evidence reported previously demonstrate that a dehiscence in the superior canal can also increase sound-evoked responses in the horizontal canal and otolith organs8,11,36,37,38. Present results indicate this occurs through the same two mechanisms that affect the dehisced canal – vibration delivered by waves, and wave pumping of endolymph. Waves emanating in both directions from the dehiscence are not restricted to the afflicted canal, but instead are partially transmitted at canal bifurcations to spread throughout the vestibular labyrinth25,39. Multiple waves combine to generate complex patterns of sound-evoked standing and traveling waves that vibrate the sensory hair bundles in the sister canals and otolith organs. This increased vibration would be expected to preferentially activate a class of auditory-frequency sensitive otolith afferents with irregular background discharge statistics at rest, thus explaining the decreased thresholds for eliciting vestibular myogenic potentials in patients with a superior canal dehiscence37,40,41. In addition to vibration, wave pumping in the afflicted canal stagnates endolymph against the cupula, thus giving rise to a pressure gradient around the canal loop (e.g. Fig. 2). The sound-evoked pressure gradient generated by a superior canal dehiscence, for example, would act at canal bifurcations to evoke tonic endolymph displacement in the horizontal canal. These two mechanical facts likely underlie horizontal canal activation as well as the horizontal component of sound-evoked eye movements in patients with superior canal dehiscence8,11.

Results demonstrate why normal physiological function of the semicircular canals and the otolith organs requires the entire vestibular labyrinth to be encased in rigid bone. Any condition that opens an additional mobile window (or windows) in the bony labyrinth would be expected to increase sensitivity of vestibular organs to sound, pressure and vibration because the opening breaks the pressure balance normally present between endolymph and perilymph. Breaking the balance causes pathological responses through deformation/vibration of the membranous labyrinth and nonlinear endolymph pumping. The critical importance of the bony labyrinth likely explains its early appearance as well as uniform presence in early hominids and extant vertebrate species42,43,44,45. Conditions such as an enlarged vestibular aqueduct or surgically introduced windows are clinical examples that would also break the balance46.

It is important to note that the Tullio phenomenon is only one of many symptoms associated with canal dehiscence. For example, patients with a superior canal dehiscence present with an elevated air-bone gap, and increased sensitivity to bone-conducted vibration9,47. Present results support two underlying biomechanical mechanisms. First, a dehiscence diverts acoustic power away from the cochlea when sound enters the inner ear via the ossicular chain19 and second, a dehiscence increases inner ear fluid vibration in response to bone-conducted vibration. In the intact bony labyrinth, linear acceleration or vibration of the temporal bone generates nearly equal pressure gradients in the perilymph and endolymph that cancel each other and minimize pressure driven deformation of the membranous labyrinth. A dehiscence breaks this balance, and introduces pressure driven vibration of inner ear fluids. For vibration stimuli, the transmembrane pressure is proportional to frequency squared and particularly large at the location of the dehiscence. Based on the present work, this vibration induced pressure imbalance would be predicted to trigger traveling waves and fluid pumping. The traveling wave component would be expected to excite the cochlea via cycle-by-cycle pressure modulation at the oval window and increasing sensitivity of the cochlea to bone conducted vibration.

The mechanisms described here also might explain changes in electrocochleography (ECoG) in cases of superior canal dehiscence, where the short-latency stimulus evoked response (SP) increases relative to the long-latency response (AP)48. Sound clicks are known to evoke short latency action potentials in vestibular afferent neurons49, and to generate short latency extracellular field potentials. Results support the hypothesis that the ECoG SP response arises in part from high-frequency responses of vestibular otolith organs (increases with dehiscence), while the AP response arises primarily from the cochlea (decreases with dehiscence). Ménière’s disease and other conditions that differentially alter vestibular vs. cochlear responses to sound could also alter the SP/AP ratio.

Our results support the hypothesis that sound-evoked eye movements observed in patients with a superior canal dehiscence arise from both sustained sound-evoked activation of phase-locking irregularly-discharging SCC afferents combined with slowly developing but sustained excitation/inhibition of regularly discharging SCC afferents11. The phase-locked afferents would be expected to drive the nonlinear high-frequency vestibulo-ocular reflex (VOR) thus leading to rapid onset slow-phase eye movements16. Rapid excitation would almost always be excitatory because vibration-evoked phase-locking is excitatory11,14,30,50. The direction of the rapid eye movement would be expected to map primarily to the dehisced SCC with a secondary component arising from the sister horizontal canal. Superimposed on this rapid excitation is a slower component arising from regularly-discharging afferents with onset following the slow time constant of the semicircular canals (e.g. 10–15 s). Present results demonstrate that slow inhibition vs. excitation of these afferents depends on frequency. Sound-evoked neuronal responses are unilateral, so eye movements are further complicated by the inherent excitatory-inhibitory asymmetry of the unilateral VOR. These effects likely combine to explain the relatively fast onset of slow phase eye movements and the predominantly excitatory direction. Upon cessation of the sound, phase-locked afferent responses immediately cease (e.g. Fig. 3) while sustained responses slowly return to baseline following the slow mechanical time constant of the canal (e.g. Fig. 4, tails). Eye movements recorded during this tail period are therefore a more direct measure of sound-evoked cupula displacement, while eye movements during the onset also include a vibration-induced response.