Modeling the vestibular evoked myogenic potential

Measuring the vestibular evoked myogenic potential (VEMP) promises to become a routine method for assessing vestibular function, although the technique is not yet standardized. To overcome the problem that the VEMP amplitude depends not only on the inhibition triggered by the acoustic stimulation of the vestibular end organs in the inner ear, but also on the tone of the muscle from which the potential is recorded, the VEMP is often normalized by dividing through a measure of the electromyogram (EMG) activity. The underlying idea is that VEMP amplitude and EMG activity are proportional. But this would imply that the muscle tone is irrelevant for a successful VEMP recording, contradicting experimental evidence. Here, an analytical model is presented that allows to resolve the contradiction. The EMG is modeled as the sum of motor unit action potentials (MUAPs). A brief inhibition can be characterized by its equivalent rectangular duration (ERD), irrespective of the actual time course of the inhibition. The VEMP resembles a polarity-inverted MUAP under such circumstances. Its amplitude is proportional to both the ERD and the MUAP rate. The EMG activity, by contrast, is proportional to the square root of the MUAP rate. Thus, the normalized VEMP still depends on the muscle tone. To avoid confounding effects of the muscle tone, the standard deviation of the EMG could be considered. But the inhibition effect on the standard deviation is small so that the measuring time would have to be much longer than usual today.     

An analytical model of the vestibular evoked myogenic potential

The vestibular evoked myogenic potential (VEMP) can be modeled (scaling factors aside) as a convolution of the motor unit action potential (MUAP) of a representative motor unit, h(t), with the temporal modulation of the MUAP rate of all contributing motor units, r(t). Accordingly, the variance modulation associated with the VEMP can be modeled as a convolution of r(t) with the square of h(t). To get a deeper theoretical understanding of the VEMP phenomenon, a specific realization of this general model is investigated here. Both r(t) and h(t) were derived from a Gaussian probability density function (in the latter case taking the first derivative). The resulting model turned out to be simple enough to be evaluated analytically in the time and in the frequency domain, while still being realistic enough to account for the basic aspects of the VEMP generation. Perhaps the most significant conclusion of this study is that, in the case of noisy data, it may be difficult to falsify the hypothesis of a rate modulation of infinitesimal duration. Thus, certain aspects of the data (particularly the peak amplitudes) can be interpreted using a short-modulation approximation rather than the general model. The importance of this realization arises from the fact that the approximation offers an exceptionally simple and convenient way for a model-based interpretation of experimental data, whereas any attempt to use the general model for that purpose would result in an ill-posed inverse problem that is far from easy to solve.     

Vestibular evoked myogenic potentials: optimal stimulation and clinical application

Summary By easily stimulating the ear with loud sound and recording on tonically contracted neck muscles, vestibular evoked myogenic potential (VEMP) test can reflect inner ear function other than the cochlea and semicircular canal. This expands the test battery for clinicians to explore saccular disease, adding a potential usefulness to the sacculo-collic reflex. The ideal stimulation mode for VEMPs is as follows: 95 dB tone bursts, frequency 500 Hz, stimulation repetition rate 5 Hz, rise/fall time 1 ms, plateau 2 ms, binaural stimulation with bilateral recordings. Animal model using guinea pigs has been established, which sets the stage for useful future studies investigating VEMPs in guinea pigs that would appear to resemble human VEMP responses. Clinically, VEMP test has been widely used in central and peripheral vestibular disorders.Grant no. NSC 94-2314-B002-239 from National Science Council, Taipei, Taiwan. Presented at the 8th Japan-Taiwan Joint Conference in Otolaryngology, Taipei, December 17, 2005.     

Galvanic vestibular stimulation improves the results of vestibular rehabilitation

Here, we present findings from a three-step investigation of the effect of galvanic vestibular stimulation (GVS) in normal subjects and in subjects undergoing vestibular rehabilitation (VR). In an initial study, we examined the body sway of 10 normal subjects after one minute of 2 mA GVS. The effect of the stimulation lasted for at least 20 minutes in all subjects and up to two hours in 70% of the subjects. We then compared a group of patients who received conventional VR (40 patients) with a group that received a combination of VR and GVS. Results suggest a significant improvement in the second group. Finally, we attempted to establish the optimal number of GVS sessions and to rule out a placebo effect. Fifteen patients received "systematic" GVS: five sessions, once a week. Five patients received "nonsystematic" galvanic stimulation in a sham protocol, which included two stimulations of the clavicle. These data were analyzed with Fisher's exact test and indicated that the best results were obtained after three sessions of GVS and no placebo effect was observed.     

Human nonspecific response to sound stimulation

Basic physiological responses were studied in healthy adult men exposed to various types of sound stimulation (white noise, pure tones, infrasound). The reaction of the cardio-vascular system to noise turned out to be nonuniform. Changes were observed in the patterns of standard electrocardiograms as well as spatial ballistocardiograms and dynamocardiograms. The magnitude of heart rate responses in the initial stage of stimulation showed a clearcut dependence on the level of noise load. In the first phase of adaptation distinct examinee-to-examinee variations were observed in the time to heart rate normalization, depending on the pattern of personality characteristics. Similar variations were also manifested in biochemical responses as well as in the patterns of EEG.     

Eye movements and brainstem neuronal responses evoked by cerebellar and vestibular stimulation in chicks

Summary The vestibulo-ocular reflex undergoes adaptive changes that require inputs from the cerebellar flocculus onto brainstem vestibular neurons. As a step toward developing an in vitro preparation in chicks for studying the synaptic basis of those changes, we have elucidated the organization of the pathways through which the flocculus influences vestibulo-ocular movements. Electrical stimulation of the vestibular ampulla evoked brief, contralaterally directed movements in both eyes. Although single current pulses to the flocculus elicited no response, conjunctive stimulation of the flocculus and the vestibular apparatus significantly reduced the vestibularly-evoked movement. Trains of current pulses applied to the flocculus and ampulla evoked eye movements directed toward and away from the side of stimulation, respectively. Recordings from the brainstem revealed neurons that were activated by ipsilateral vestibular stimulation and inhibited by ipsilateral floccular stimulation. Our sample included neurons in the lateral vestibular nucleus, the ventrolateral portion of the medial vestibular nucleus, and the superior vestibular nucleus. Similarities between these findings and those of similar studies in mammals indicate that the chick will provide a good model system for cellular studies of adaptive changes in the vestibulo-ocular reflex.Abbreviations FTN flocculus target neuron - VOR vestibuloocular reflex     

Effects of adequate vestibular stimulation on evoked rhythmic activity in the forelimb nerves of immobilized guinea pigs

The effects of adequate vestibular stimulation, achieved by turning the animal around its longitudinal axis, on intensity of rhythmic activity in forelimb muscle nerves were investigated during experiments on immobilized decerebrate guinea pigs. This activity was produced by electrical stimulation of the mesencephalic locomotor region, following the action of DOPA administered i.v. Rhythmic activity arises mainly in the flexor muscle nerve under these circumstances. The intensity of such activity alters as the body was tilted, diminishing and increasing as the body is tilted to the ipsi- and contralateral side, respectively. Alterations in activity are characterized by an acceleration-related phase lag of –110 to –150° during cyclic tilting at the rate of 0.02–0.4 Hz.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 22, No. 2, pp. 223–227, March–April, 1990.     

Simulation of the power transmission of bone-conducted sound in a finite-element model of the human head

Bone conduction (BC) sound is the perception of sound transmitted in the skull bones and surrounding tissues. To better understand BC sound perception and the interaction with surrounding tissues, the power transmission of BC sound is investigated in a three-dimensional finite-element model of a whole human head. BC sound transmission was simulated in the FE model and the power dissipation as well as the power flow following a mechanical vibration at the mastoid process behind the ear was analyzed. The results of the simulations show that the skull bone (comprises the cortical bone and diploë) has the highest BC power flow and thereby provide most power transmission for BC sound. The soft tissues was the second most important media for BC sound power transmission, while the least BC power transmission is through the brain and the surrounding cerebrospinal fluid (CSF) inside the cranial vault. The vibrations transmitted in the skull are mainly concentrated at the skull base when the stimulation is at the mastoid. Other vibration transmission pathways of importance are located at the occipital bone at the posterior side of the head while the transmission of sound power through the face, forehead and vertex is minor. The power flow between the skull bone and skull interior indicate that some BC power is transmitted to and from the skull interior but the transmission of sound power through the brain seem to be minimal and only local to the brain–bone interface.     

Velocity of body lean evoked by leg muscle vibration potentiate the effects of vestibular stimulation on posture

To investigate the vestibular and somatosensory interaction in human postural control, a galvanic vestibular stimulation of cosine bell shape resulting in a small forward or backward body lean was paired with three vibrations of both soleus muscles. The induced body lean was registered by the position of the center of foot pressure (CoP). During a quiet stance with eyes closed the vibration of both soleus muscles with frequency (of) 40 Hz, 60 Hz and 80 Hz resulted in the body lean backward with velocities related to the vibration frequencies. The vestibular galvanic stimulation with the head turned to the right caused forward or backward modification of CoP backward response to the soleus muscles vibration and peaked at 1.5-2 s following the onset of the vibration. The effect of the paired stimulation was larger than the summation of the vestibular stimulation during the quiet stance and a leg muscle vibration alone. The enhancement of the galvanic stimulation was related to the velocity of body lean induced by the leg muscle vibration. The galvanic vestibular stimulation during a faster body movement had larger effects than during a slow body lean or the quiet stance. The results suggest that velocity of a body postural movement or incoming proprioceptive signal from postural muscles potentiate the effects of simultaneous vestibular stimulations on posture.     

Changes in receptive field of tectal neurons evoked by vestibular and acoustic stimulation in pigeons

Responses to visual, acoustic, and vestibular stimuli were studied in neurons of the middle and deep layers of the tectum in the pigeon. Changes in the receptive field (RF) were assessed from comparison of unit responses to isolated movement of a shaped visual stimulus with responses to movement of a stimulus during simultaneous action of a vestibular or acoustic stimulus. Changes in RF of the neuron could be observed during the action of both a vestibular and an acoustic stimulus. These changes affected the identification of the predominant direction of movement of the stimulus, the position of the maximum in the response histogram, and the duration and number of spikes in the response. The direction of change in RF of the neuron was found not necessarily to coincide with the sign of the response to the same neuron to isolated presentation of a vestibular or acoustic stimulus. It is postulated on the basis of the results and data in the literature that the tectum transforms the flow of impulses arriving from the retina depending on the nature of the information received by it from other sensory systems.     

Findings of somatosensory evoked potential to stimulation of the sciatic nerve in two different rat strains.

No comparative study about somatosensory evoked potentials (SEP) on different rat strains has been done yet. It is evident that comparative SEP studies are important since different rat strains have different physiological properties. We aimed to compare early latency SEP values from stimulation of sciatic nerve in Wistar (Wr) and Sprague-Dawley (SDr) rats which are frequently used rat strains in experimental studies. In Wr group, the mean of first far field potential (Ff1) latency was shorter and the mean Ff1 amplitude was lower than that of Sprague-Dawley rat group. Mean cortical potential latency in Wr group was longer than that of SDr group while amplitude was not different. Central conduction time (CCT) in Wistar rat group was found to be longer than that of SDr group. Shorter Ff1 latency in Wr group implies that afferent volley reaches cervical posterior fasciculus from sciatic nerve earlier than SDr group while longer CP latency implies that afferent volley reaches cortex later than SDr group. Similarity between the latencies of lumbar potentials implies that peripheral conduction velocity has no effect on the difference of Ff1 latencies.     

Harnessing the potential of myogenic satellite cells

Adult skeletal muscle has remarkable regenerative potential, which is mainly attributable to a small population of undifferentiated skeletal muscle precursors called satellite cells. These cells reside underneath the basal lamina of skeletal myofibers and can be activated to proliferate, differentiate and fuse to form new muscle tissue. Satellite cells have long been considered promising mediators of therapeutic muscle regeneration. However, in practice, the regenerative function of such cells, which in many cases have been derived or expanded by ex vivo cultures, can be surprisingly low. A recent study from Montarras and colleagues has provided new insights into the requirements for efficient muscle engraftment from purified muscle satellite cells, suggesting possible strategies to enhance their therapeutic potential.     

Auditory evoked responses to rhythmic sound pulses in dolphins

The ability of auditory evoked potentials to follow sound pulse (click or pip) rate was studied in bottlenosed dolphins. Sound pulses were presented in 20-ms rhythmic trains separated by 80-ms pauses. Rhythmic click or pip trains evoked a quasi-sustained response consisting of a sequence of auditory brainstem responses. This was designated as the rate-following response. Rate following response peak-to-peak amplitude dependence on sound pulse rate was almost flat up to 200 s⁻¹, then displayed a few peaks and valleys superimposed on a low-pass filtering function with a cut-off frequency of 1700 s⁻¹ at a 0.1-amplitude level. Peaks and valleys of the function corresponded to the pattern of the single auditory brain stem response spectrum; the low-pass cut-off frequency was below the auditory brain stem response spectrum bandwidth. Rate-following response frequency composition (magnitudes of the fundamental and harmonics) corresponded to the auditory brain stem response frequency spectrum except for lower fundamental magnitudes at frequencies above 1700 Hz. These regularities were similar for both click and pip trains. The rate-following response to steady-state rhythmic stimulation was similar to the rate-following response evoked by short trains except for a slight amplitude decrease with the rate increase above 10 s⁻¹. The latter effect is attributed to a long-term rate-dependent adaptation in conditions of the steady-state pulse stimulation. Accepted: 18 June 1998     

Harnessing the therapeutic potential of myogenic stem cells

The potential clinical use of stem cells for cell transplantation therapies to replace defective genes in myopathies is an area of intense investigation. Precursor cells derived from non-muscle tissue with myogenic potential have been identified in many tissues, including bone marrow and dermis, although the status of these putative stem cells requires clarification. The incorporation of circulating bone-marrow derived stem cells into regenerating adult skeletal muscle has been demonstrated in mice but the contribution of donor cells is so minimal that it would appear clinically irrelevant at this stage. The possibility of a true stem cell subpopulation within skeletal muscle that replenishes the satellite cells (conventional muscle precursors on the surface of myofibres) is also very attractive as a superior source of myoblasts for muscle construction. A full understanding of the intrinsic factors (i.e. gene expression within the stem cell) and extrinsic factors (i.e. signals from the external environment) which control the commitment of stem cells to the myogenic lineage, and the conditions which favour stem cell expansion in vivo is required before stem cells can be seriously considered for clinical cell therapy. This revised version was published online in July 2006 with corrections to the Cover Date.     

Somatosensory influence on postural response to galvanic vestibular stimulation

We investigated how postural responses to galvanic vestibular stimulation were affected by standing on a translating support surface and by somatosensory loss due to diabetic neuropathy. We tested the hypothesis that an unstable surface and somatosensory loss can result in an increase of vestibulospinal sensitivity. Bipolar galvanic vestibular stimulation was applied to subjects who were standing on a force platform, either on a hard, stationary surface or during a backward platform translation (9 cm, 4.2 cm/s). The intensity of the galvanic stimulus was varied from 0.25 to 1 mA. The amplitude of the peak body CoP displacement in response to the galvanic stimulus was plotted as a function of stimulus intensity for each individual. A larger increase in CoP displacement to a given increase in galvanic current was interpreted as an increase of vestibulospinal sensitivity. Subjects with somatosensory loss in the feet due to diabetes showed higher vestibulospinal sensitivity than healthy subjects when tested on a stationary support surface. Control subjects and patients with somatosensory loss standing on translating surface also showed increased galvanic response gains compared to stance on a stationary surface. The severity of the somatosensory loss in the feet correlated with the increased postural sensitivity to galvanic vestibular stimulation. These results showed that postural responses to galvanic vestibular stimulus were modified by somatosensory information from the surface. Somatosensory loss due to diabetic neuropathy and alteration of somatosensory input during stance on translating support surface resulted in increased vestibulospinal sensitivity.     

Short and middle latency vestibular evoked responses to acceleration in man

We have succeeded in recording short and middle latency vestibular evoked responses in human subjects. The head was held rigidly in a special, patented head holder, constructed individually for each subject, which gripped the teeth of the upper jaw. The stimulus consisted of 2/sec steps of angular acceleration impulses produced by a special motor with intensities of about 10,000°/sec² and with a rise time of 1–2 msec. The electrical activity was recorded as the potential difference between special forehead and mastoid electrodes having a large, secure contact area with the skin. The activity was digitally filtered and averaged in 2 separate channels by means of a Microshev 2000 evoked response system. The short latency responses, with peaks at about 3.5 msec (forehead positive), 6.0 msec (forehead negative) and 8.4 msec (forehead positive; bandpass: 200–2000 Hz; average of 1024 trials), had amplitudes of about 0.5 μV. The middle latency responses had peaks at about 8.8 msec (forehead positive), 18.8 msec (forehead negative) and 26.8 msec (forehead positive; 30–300 Hz; N = 128 trials), with larger amplitudes (about 15 μV). These responses were consistently recorded in the same subject at different times and were similar in different normal subjects. Strenuous control experiments were conducted in order to ensure that these responses are not artefacts due to the movement of conducting media (head, electrodes and leads) in the electromagnetic field of the motor and are elicited by activation of normal labyrinths. Among other controls, they were not present in a cadaver, in patients with bilateral absence of nystagmus to caloric stimuli and in conducting volumes the size of the human head. They were also not masked by white noise.