PhD student, University of Sydney
Dynamic response and sensitivity of the vestibular system, in vivo, to clinical stimuli.
The vestibular apparatus in our inner ear, has two distinct systems for sensing motion. The otoliths (utricle and saccule), which sense linear acceleration, tilts and gravity, and the semicircular canals (anterior, horizontal, and posterior canals), which detect rotations or angular accelerations. Pathologies of the vestibular system result in a decreased standard of living, whereby sufferers experience symptoms such as hearing loss, imbalance, spatial disorientation, vertigo and vomiting. In the aging population, it is the main cause of falls resulting in serious injury and even death.
Current vestibular testing called the Vestibular Evoked Myogenic Potential (VEMP) use both bone-conducted vibration (BCV) and air-conducted sound (ACS) to stimulate the vestibular system and measure its function. A complete understanding of how both stimulation methods activate the vestibular system and at what frequencies is currently unknown. Therefore, further research is required to better understand the physiology and health and disease of the vestibular system.
A large portion of vestibular research involves in vitro preparations, which although study the ‘isolated’ inner ear at the smallest scale, do so in vastly different conditions to living physiology. A more precise method for studying both the function and disease of the vestibular system is through in vivo experimentation in the anesthetized animal. My research uses this in vivo approach in the guinea pig, to measure the function of the vestibular neurons and hair cells in response to BCV and ACS, used in the clinic.
We have also used laser doppler vibrometry to measure micrometer displacements of the vestibular system in response to BCV and ACS. This allows us to characterise how and at what frequencies the vestibular system is activated by standard clinical stimulation methods, and at what frequencies the vestibular hair cells and neurons are most sensitive.
Abstract: The main objective of this study was to determine whether bone-conducted vibration (BCV) is equally effective in activating both semicircular canal and otolith afferents in the guinea pig or whether there is preferential activation of one of these classes of vestibular afferents. To answer this question a large number (346) of single primary vestibular neurons were recorded extracellularly in anesthetized guinea pigs and were identified by their location in the vestibular nerve and classed as regular or irregular on the basis of the variability of their spontaneous discharge. If a neuron responded to angular acceleration it was classed as a semicircular canal neuron, if it responded to maintained roll or pitch tilts it was classified as an otolith neuron. Each neuron was then tested by BCV stimuli-either clicks, continuous pure tones (200-1,500 Hz) or short tone bursts (500 Hz lasting 7 ms)-delivered by a B-71 clinical bone-conduction oscillator cemented to the guinea pig's skull. All stimulus intensities were referred to that animal's own auditory brainstem response (ABR) threshold to BCV clicks, and the maximum intensity used was within the animal's physiological range and was usually around 70 dB above BCV threshold. In addition two sensitive single axis linear accelerometers cemented to the skull gave absolute values of the stimulus acceleration in the rostro-caudal direction. The criterion for a neuron being classed as activated was an audible, stimulus-locked increase in firing rate (a 10% change was easily detectable) in response to the BCV stimulus. At the stimulus levels used in this study, semicircular canal neurons, both regular and irregular, were insensitive to BCV stimuli and very few responded: only nine of 189 semicircular canal neurons tested (4.7%) showed a detectable increase in firing in response to BCV stimuli up to the maximum 2 V peak-to-peak level we delivered to the B-71 oscillator (which produced a peak-to-peak skull acceleration of around 6-8 g and was usually around 60-70 dB above the animal's own ABR threshold for BCV clicks). Regular otolithic afferents likewise had a poor response; only 14 of 99 tested (14.1%) showed any increase in firing rate up to the maximum BCV stimulus level. However, most irregular otolithic afferents (82.8%) showed a clear increase in firing rate in response to BCV stimuli: of the 58 irregular otolith neurons tested, 48 were activated, with some being activated at very low intensities (only about 10 dB above the animal's ABR threshold to BCV clicks). Most of the activated otolith afferents were in the superior division of the vestibular nerve and were probably utricular afferents. That was confirmed by evidence using juxtacellular injection of neurobiotin near BCV activated neurons to trace their site of origin to the utricular macula. We conclude there is a very clear preference for irregular otolith afferents to be activated selectively by BCV stimuli at low stimulus levels and that BCV stimuli activate some utricular irregular afferent neurons. The BCV generates compressional and shear waves, which travel through the skull and constitute head accelerations, which are sufficient to stimulate the most sensitive otolithic receptor cells.
Pub.: 09 Jun '06, Pinned: 31 Aug '17
Abstract: This study tested whether air-conducted sound and bone-conducted vibration activated primary vestibular afferent neurons and whether, at low levels, such stimuli are specific to particular vestibular sense organs. In response to 500 Hz bone-conducted vibration or 500 Hz air-conducted sound, primary vestibular afferent neurons in the guinea pig fall into one of two categories--some neurons show no measurable change in firing up to 2 g peak-to-peak or 140 dB SPL. These are semicircular canal neurons (regular or irregular) and regular otolith neurons. In sharp contrast, otolith irregular neurons show high sensitivity: a steep increase in firing as stimulus intensity is increased. These sensitive neurons typically, but not invariably, were activated by both bone-conducted vibration and air-conducted sound, they originate from both the utricular and saccular maculae, and their sensitivity underpins new clinical tests of otolith function.
Pub.: 30 Nov '10, Pinned: 31 Aug '17
Abstract: Previous studies have shown that the vestibular short-latency-evoked potential (VsEP) in response to the brief head acceleration stimulus is a compound action potential of neurons innervating the otolith organs. However, due to the lack of direct evidence, it is currently unclear whether the VsEP is primarily generated by the activity of utricular or saccular afferent neurons, or some mixture of the two. Here, we investigated the origin of the VsEP evoked by brief bone-conducted vibration pulses in guinea pigs, using selective destruction of the cochlea, semicircular canals (SCCs), saccule, or utricle, along with neural blockade with tetrodotoxin (TTX) application, and mechanical displacements of the surgically exposed utricular macula. To access each end organ, either a dorsal or a ventral surgical approach was used. TTX application abolished the VsEP, supporting the neurogenic origin of the response. Selective cochlear, SCCs, or saccular destruction had no significant effect on VsEP amplitude, whereas utricular destruction abolished the VsEP completely. Displacement of the utricular membrane changed the VsEP amplitude in a non-monotonic fashion. These results suggest that the VsEP evoked by BCV in guinea pigs represents almost entirely a utricular response. Furthermore, it suggests that displacements of the utricular macula may alter its response to bone-conduction stimuli.
Pub.: 20 Jun '13, Pinned: 31 Aug '17
Abstract: Various theories suggest endolymphatic hydrops may cause a rupture of the membranous labyrinth or may force open the utriculo-saccular duct, resulting in a sudden change in inner ear function. Here, we have used slow injections of artificial endolymph into either scala media or the utricle of anaesthetised guinea pigs to investigate the effects of hydrops. Vestibular function was continuously monitored in addition to the measurements of cochlear function developed in our laboratory (Brown et al. Hear Res, 2013). Scala media injection induced consistent functional changes, which occurred in two stages. Initial changes involved were associated with an increased hydrostatic pressure in scala media that only affected cochlear function. After 3-4 μl of endolymph had been injected, cochlear function spontaneously recovered, and was often shortly followed by a transient increase or decrease in utricular sensitivity, with the effects varying between animals. Endolymph injection directly into the utricle produced variable effects across animals, although in 2 experiments it produced similar changes as those observed for scala media injections, suggesting that the fluid pathway between scala media and the utricle was continuous in these animals. The mechanism underlying the sudden, spontaneous functional changes is not yet clear, but we tentatively suggest that in some cases it may be caused by the utriculo-saccular duct suddenly opening to alleviate an elevated hydrostatic pressure in the pars inferior, resulting in a change in utricular function due to an increase in its volume. These changes are comparable to the sudden or fluctuating functional changes in Ménière's sufferers, and support the hypothesis that endolymphatic hydrops can directly cause some symptoms of this syndrome.
Pub.: 26 Jun '13, Pinned: 31 Aug '17
Abstract: The mechanism by which vestibular neural phase locking occurs and how it relates to classical otolith mechanics is unclear. Here, we put forward the hypothesis that sound and vibration both cause fluid pressure waves in the inner ear and that it is these pressure waves which displace the hair bundles on vestibular receptor hair cells and result in activation of type I receptor hair cells and phase locking of the action potentials in the irregular vestibular afferents, which synapse on type I receptors. This idea has been suggested since the early neural recordings and recent results give it greater credibility.
Pub.: 09 Jan '15, Pinned: 31 Aug '17
Abstract: Single-sided deafness patients are now being considered candidates to receive a cochlear implant. With this, many people who have undergone a unilateral vestibular labyrinthectomy for the treatment of chronic vertigo are now being considered for cochlear implantation. There is still some concern regarding the potential efficacy of cochlear implants in these patients, where factors such as cochlear fibrosis or nerve degeneration following unilateral vestibular labyrinthectomy may preclude their use. Here, we have performed a unilateral vestibular labyrinthectomy in normally hearing guinea pigs, and allowed them to recover for either 6 weeks, or 10 months, before assessing morphological and functional changes related to cochlear implantation. Light sheet fluorescence microscopy was used to assess gross morphology throughout the entire ear. Whole nerve responses to acoustic, vibrational, or electrical stimuli were used as functional measures. Mild cellular infiltration was observed at 6 weeks, and to a lesser extent at 10 months after labyrinthectomy. Following labyrinthectomy, cochlear sensitivity to high-frequency acoustic tone-bursts was reduced by 16 ± 4 dB, vestibular sensitivity was almost entirely abolished, and electrical sensitivity was only mildly reduced. These results support recent clinical findings that patients who have received a vestibular labyrinthectomy may still benefit from a cochlear implant.
Pub.: 14 Feb '16, Pinned: 31 Aug '17
Abstract: The classical view of the otoliths-as flat plates of fairly uniform receptors activated by linear acceleration dragging on otoconia and so deflecting the receptor hair bundles-has been replaced by new anatomical and physiological evidence which shows that the maculae are much more complex. There is anatomical spatial differentiation across the macula in terms of receptor types, hair bundle heights, stiffness and attachment to the overlying otolithic membrane. This anatomical spatial differentiation corresponds to the neural spatial differentiation of response dynamics from the receptors and afferents from different regions of the otolithic maculae. Specifically, receptors in a specialized band of cells, the striola, are predominantly type I receptors, with short, stiff hair bundles and looser attachment to the overlying otoconial membrane than extrastriolar receptors. At the striola the hair bundles project into holes in the otolithic membrane, allowing for fluid displacement to deflect the hair bundles and activate the cell. This review shows the anatomical and physiological evidence supporting the hypothesis that fluid displacement, generated by sound or vibration, deflects the short stiff hair bundles of type I receptors at the striola, resulting in neural activation of the irregular afferents innervating them. So these afferents are activated by sound or vibration and show phase-locking to individual cycles of the sound or vibration stimulus up to frequencies above 2000 Hz, underpinning the use of sound and vibration for clinical tests of vestibular function.
Pub.: 29 Jan '17, Pinned: 31 Aug '17
Abstract: Welgampola and Carey have missed evidence that shows how utricular and saccular function can be differentiated, and here the authors note that evidence and report a new result that further substantiates the differentiation.
Pub.: 16 Apr '11, Pinned: 31 Aug '17
Abstract: Short latency linear vestibular sensory evoked potentials (VsEPs) provide a means to objectively and directly assess the function of gravity receptors in mammals and birds. The importance of this functional measure is illustrated by its use in studies of the genetic basis of vestibular function and disease. Head motion is the stimulus for the VsEP. In the bird, it has been established that neurons mediating the linear VsEP respond collectively to the rate of change in linear acceleration during head movement (i.e. jerk) rather than peak acceleration. The kinematic element of motion responsible for triggering mammalian VsEPs has not been characterized in detail. Here we tested the hypothesis that jerk is the kinematic component of head motion responsible for VsEP characteristics. VsEP amplitudes and latencies changed systematically when peak acceleration level was held constant and jerk level was varied from ∼0.9-4.6 g/ms. In contrast, responses remained relatively constant when kinematic jerk was held constant and peak acceleration was varied from ∼0.9 to 5.5 g in mice and ∼0.44 to 2.75 g in rats. Thus the mammalian VsEP depends on jerk levels and not peak acceleration. We conclude that kinematic jerk is the adequate stimulus for the mammalian VsEP. This sheds light on the behavior of neurons generating the response. The results also provide the basis for standardizing the reporting of stimulus levels, which is key to ensuring that response characteristics reported in the literature by many laboratories can be effectively compared and interpreted.
Pub.: 15 Jun '11, Pinned: 31 Aug '17