Invited reviewA critical review of the neurophysiological evidence underlying clinical vestibular testing using sound, vibration and galvanic stimuli
Introduction
Evoked potentials are widely used to evaluate the functional status of the visual and auditory systems, and in the last 15 years they have started to be used for vestibular evaluation (Rosengren et al., submitted for publication, for a companion review). In order to generate evoked potentials it is necessary to use stimuli with abrupt onsets which can be presented repeatedly, however typical vestibular stimuli (e.g. calorics, angular accelerations) do not meet these requirements. The stimuli which have been used for vestibular-evoked myogenic potentials – air conducted sound (ACS) and bone conducted vibration (BCV) and galvanic pulses – do have abrupt onsets and can be presented repeatedly, but do these “auditory” and galvanic stimuli actually stimulate vestibular receptors and afferents? Obviously sound and vibration will activate cochlear receptors, but a fundamental question has to be whether ACS and BCV and galvanic stimuli really do stimulate vestibular receptors. The strongest evidence that they do has come from recordings of single primary vestibular neurons in animals to these stimuli. Given such physiological evidence, it is mainly animal studies which clarify the neural pathways which result in the observed evoked potentials. However the physiological results which are frequently used to interpret clinical results have problems and issues which are rarely highlighted in research reports. It is necessary to be aware of these problems in order to evaluate the physiological data appropriately in interpretation of results of clinical tests. These are the matters which are the focus of this review.
Considering the BCV stimulus is an informative start. Moderate BCV stimuli applied to the head cause the bones of the skull to move by small amounts (von Békésy, 1960, Stenfelt and Goode, 2005, Stenfelt et al., 2000), and measurements by small, lightweight, sensitive triaxial linear accelerometers on the skin overlying the mastoids are necessary to show the full complexity of the linear acceleration stimuli generated by the BCV which stimulate the linear acceleration detectors in the inner ear – the otolithic receptors. The exact pattern of mastoid displacement (and so the pattern of otolithic receptor stimulation) depends on many parameters, including the stimulus frequency and the location of the BCV stimulator. For example during a light tap at Fz (the midline of the forehead at the hairline) by a tendon hammer, triaxial linear accelerometers on the mastoids show that there is a rapidly changing linear acceleration of about 0.4 g peak measured at the skin over the mastoid (Iwasaki et al., 2008a) (Fig. 1). Similarly a 500 Hz BCV at Fz causes rapid changes in linear acceleration at the mastoids, and a changing linear acceleration is a potent stimulus for one class of vestibular neurons – otolithic irregular neurons (Goldberg, 2000, for a review) and, as we show below, recordings from identified vestibular neurons in guinea pigs show that primary irregular otolithic neurons do respond vigorously to BCV even at very low stimulus intensities, close to or even below ABR threshold.
The situation with ACS is not as clear – it has been suggested that sound causes the stapes to generate a shock wave in the fluid-filled inner ear which causes vestibular hair-cell receptors to be deflected (Murofushi and Curthoys, 1997). However the exact mechanism by which stapes movement by an air conducted sound causes vestibular hair-cell deflection is not known.
Recordings from single primary vestibular neurons in response to ACS and BCV have been used to show that ACS and BCV stimuli really do activate vestibular receptors. However some major criteria need to be met in order to substantiate that conclusion:
- •
there has to be physiological evidence from experiments on appropriate animal models showing that anatomically and physiologically identified primary vestibular neurons are activated by ACS or BCV or both;
- •
the stimulus levels needed for activation of these neurons must be at intensities comparable to those used for evoking responses in human subjects and patients. Stimuli at intensities above the normal physiological range may be expected to activate any receptor;
- •
ideally the stimuli of the same frequency and comparable intensity as used for human clinical testing should cause a similar behavioural response in the animal model as it does in humans;
- •
retrograde staining from the recording sites should verify that the neurons activated by ACS and BCS are vestibular neurons and provide exact information about their sense organ of origin. Identifying the origin and projections of these neurons is vital in understanding the cause of the behavioural response.
The following reviews results meeting these criteria, showing that there is now excellent evidence that ACS, BCV and galvanic stimulation activate primary vestibular afferent neurons and that projections via vestibulo-spinal pathways to the neck muscles underlie the cervical vestibular-evoked myogenic potential (cVEMP) and projections via the vestibulo-ocular pathways to the eye muscles underlie the ocular vestibular-evoked myogenic potential (oVEMP), and there is growing animal behavioural data confirming the effect of these stimuli.
Section snippets
Background
The major thrust of my physiological work in this area has been to provide the physiological evidence for clinical vestibular testing. Rather than undertaking parametric studies of the response of individual vestibular neurons to all aspects of a stimulus, I have sought evidence from population studies of many neurons using the same stimuli which have been used for clinical testing and asking the questions: do these stimuli activate vestibular receptors? are receptors for all vestibular sensory
Mechanism
What could be the mechanism by which BCV and ACS activate otolithic receptors? In a number of species it has been shown that some otolithic afferents are extremely sensitive to vibration (Narins and Lewis, 1984). In the frog for example some saccular afferents have thresholds as low as 5 μg, possibly to facilitate frog communication, courtship and mating (Koyama et al., 1982). It seems that the molecular mechanisms at the hair-cell receptor allowing this great sensitivity have been preserved in
ACS vs BCV
One of the most difficult questions to answer is whether the population of primary vestibular afferents activated by ACS and BCV is the same. On the basis of testing many hundreds of neurons to these stimuli I do not think that it is the same population. I have yet to find a neuron which can be activated by ACS but which cannot be activated by BCV so it is highly likely that every neuron activated by ACS is also activated by BCV of the appropriate direction. However some neurons which respond
Projections
In understanding how vestibular receptor activation by ACS and BCV can cause behavioural responses measured in humans (cVEMP and oVEMP) we need to consider the evidence about the neural projections in the vestibulo-spinal and vestibulo-ocular systems.
Questions for future research
- •
More evidence is needed on the tuning of otolithic afferents for frequency of BCV stimulation. This requires equating the magnitude of the linear acceleration at the mastoid for different frequencies. At low frequencies, semicircular canal neurons may be activated, so testing a response with frequencies less than 500 Hz may be confounding otolithic and canal responses.
- •
What is the directional selectivity of BCV stimulation? Different locations and directions of BCV stimulation generate different
Summary
Sound and vibration stimulate vestibular as well as cochlear receptors. One small group of primary vestibular afferents – otolith irregular afferents – is selectively activated at low intensities by 500 Hz BCV and many are also excited by ACS. On the other hand semicircular canal neurons are insensitive to these 500 Hz stimuli. The choice of 500 Hz as a stimulus frequency appears to ensure that otolithic neurons are selectively activated. ACS and BCV activate receptors and afferents from both the
Acknowledgements
I am grateful for the support of NH&MRC of Australia and the Garnett Passe and Rodney Williams Memorial Foundation. Many people have contributed to the work reported here and I thank them.
References (65)
- et al.
Vestibular-evoked extraocular potentials by air-conducted sound: another clinical test for vestibular function
Clin Neurophysiol
(2007) Nystagmus evoked by utricular stimulation
Exp Neurol
(1970)- et al.
Responses of vestibular-nerve afferents in the squirrel monkey to externally applied galvanic currents
Brain Res
(1982) - et al.
Eye movements evoked by the selective stimulation of the utricular nerve in cats
Auris Nasus Larynx
(2003) - et al.
Eye movements evoked by selective saccular nerve stimulation in cats
Auris Nasus Larynx
(2004) - et al.
Ocular vestibular evoked myogenic potentials to bone conducted vibration of the midline forehead at Fz in healthy subjects
Clin Neurophysiol
(2008) - et al.
The role of the superior vestibular nerve in generating ocular vestibular-evoked myogenic potentials to bone conducted vibration at Fz
Clin Neurophysiol
(2009) - et al.
Responses of primary vestibular neurons to galvanic vestibular stimulation (GVS) in the anaesthetised guinea pig
Brain Res Bull
(2004) - et al.
Acute seismic sensitivity in the bullfrog ear
Brain Res
(1982) - et al.
Effects of vestibular nerve section on sound-evoked myogenic potentials in the sternocleidomastoid muscle of monkeys
Clin Neurophysiol
(2007)
Attachment of the utricular and saccular maculae to the temporal bone
Hear Res
Click-evoked myogenic potentials recorded on alert guinea pigs
Hear Res
The vestibular nerve of the chinchilla: II. Relation between afferent response properties and peripheral innervation patterns in the semicircular canals
J Neurophysiol
Hair cell bundles: flexoelectric motors of the inner ear
PLoS ONE
Vestibular evoked potentials in human neck muscles before and after unilateral vestibular deafferentation
Neurology
Myogenic potentials generated by a click-evoked vestibulocollic reflex
J Neurol Neurosurg Psychiatry
Vertical and horizontal eye movement responses to unilateral and bilateral bone conducted vibration to the mastoid
J Vestib Res
Scarpa’s ganglion in the rat and guinea pig
Acta Otolaryngol
The response of primary horizontal semicircular canal neurons in the rat and guinea pig to angular acceleration
Exp Brain Res
Eye movements produced by utricular and saccular stimulation
Aviat Space Environ Med
Bone conducted vibration selectively activates irregular primary otolithic vestibular neurons in the guinea pig
Exp Brain Res
Zur Innervation der Macula sacculi bei Säugetieren
Anat Anzeiger
Zur vergleichenden Anatomie der Labyrinthinnervation
J Comp Neurol
Effect of intratympanic application of aminoglycoside on click-evoked myogenic potentials in guinea pigs
Ear Hearing
Acoustic responses recorded from the saccular bundle on the eighth nerve of the guinea pig
Hear Res
Physiology of peripheral neurons innervating otolith organs of the squirrel monkey: III. Response dynamics
J Neurophysiol
The vestibular nerve of the chinchilla: III. Peripheral innervation patterns in the utricular macula
J Neurophysiol
Utricular stimulation and oculomotor reactions
Laryngoscope
Saccular stimulation and oculomotor reactions
Laryngoscope
The vestibular nerve of the chinchilla: IV. Discharge properties of utricular afferents
J Neurophysiol
Cited by (310)
Pattern analysis of peripheral-vestibular deficits with machine learning using hierarchical clustering
2022, Journal of the Neurological SciencesModernising vestibular assessment
2024, Journal of Laryngology and OtologyDynamic change of vestibular function and the long-term prognosis of vestibular neuritis
2024, Journal of Vestibular Research: Equilibrium and OrientationGuiding Human Navigation with Noninvasive Vestibular Stimulation and Evoked Mediolateral Sway
2024, Journal of Cognitive EnhancementVestibular Testing—New Physiological Results for the Optimization of Clinical VEMP Stimuli
2023, Audiology Research