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A Sound-Evoked Vestibulomasseteric Reflex in Healthy Humans

¹Department of Biomedical Sciences, Section of Human Physiology and Bioengineering, University of Sassari, Sassari, Italy; and ²Sobell Research Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, London, United Kingdom

Submitted 23 November 2004; accepted in final form 8 December 2004

	ABSTRACT

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Averaged responses to loud clicks were recorded in the unrectified and rectified masseter electromyogram (EMG) of 18 healthy subjects. Unilateral clicks (0.1 ms, 3 Hz, 70–100 dB NHL), delivered during a steady masseter contraction, evoked bilateral responses that appeared to consist of 2 components on the basis of threshold, latency, and their appearance in rectified EMG. The lowest threshold response appeared as a p16 wave (onset 11–13 ms) in the unrectified EMG and corresponded with a 10- to 12-ms period of inhibition in the rectified EMG. Higher-intensity clicks recruited an earlier p11 response in the unrectified EMG (onset 7.0–9.2 ms) that sometimes appeared as an initial increase in the rectified EMG before suppression. The amplitude of the p11 wave scaled with background EMG level and was asymmetrically modulated by 30° tilt of the whole body. The threshold of the early p11/n15 wave in masseter was the same as the threshold for click-induced vestibulocollic reflexes. Single motor unit recordings demonstrated that responses in masseters corresponded to a silent period in unit firing that began earlier and lasted longer at 100 dB than at 80 dB. We propose that loud clicks induce 2 partially overlapping short-latency reflexes in masseter muscle EMG: a p11/n15 response, which we suggest is of vestibular origin, and a p16/n21 response, which we suggest is equivalent to the previously described jaw–acoustic reflex.

	INTRODUCTION

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Although sound is not a natural physiological vestibular stimulus, it is well known that at high intensities it can have effects on the vestibular system. Indeed in humans intense sound is well known to produce vestibular symptoms and illusions of movement (Parker et al. 1975). Experiments in animals have suggested that the saccule is the most sensitive part of the vestibular system to sound. Acoustic energy enters the labyrinth through the middle ear, by air conduction, and activates saccular hair cells (Cazals et al. 1983; Mc Cue and Guinan 1994; Murofushi et al. 1995; Young et al. 1977), which project monosynaptically to neurons in the isplateral lateral vestibular nucleus (Murofushi and Curthoys 1997; Murofushi et al. 1996a). Saccular hair cells are activated by sound in a way that resembles natural linear acceleration, i.e., it excites hair cells on one side of the striola and inhibits hair cells on the other side, and consequently secondary vestibular neurons receive different inputs from hair cells on each side of the striola (Ogawa et al. 2000; Uchino et al. 1997b).

Assessment of vestibular function in man has traditionally relied on measuring reflex eye movements induced by stimulation of the semicircular canals, whereas measurement of otolith function has remained problematical. Acoustic stimulation is a noninvasive, safe, and simple method to activate the otoliths and it has the advantage of more natural stimuli in that it can be delivered to each labyrinth separately. However, a limitation in using sound activation of the otoliths is that the duration of the acoustic stimulus must be short to prevent damage to the cochlea by the high intensities needed to activate the saccule. Conventional methods of monitoring the effects of vestibular input involve observing evoked eye movements and, unfortunately, these are not very sensitive to such short-duration inputs. In fact, although sound-evoked vestibuloocular reflexes have been recently described in trained monkeys (Zhou et al. 2004), sound-induced eye movements have not yet been demonstrated in healthy subjects (Halmagyi et al. 2003).

A second method that can be used to monitor the effects of saccular stimulation is by recording the reflexes evoked in neck and cranial muscles by loud sounds. Bickford and colleagues originally described the characteristics of short-latency potentials recorded from posterior neck muscles, with an active electrode placed just below the inion, after click stimulation. They concluded that these responses were myogenic in origin and that they arose from activation of the vestibular apparatus and not from activation of the cochlea (Bickford et al. 1964; Cody et al. 1964). Subsequent publications by these authors provided evidence that the inion response depended on activation of the otoliths, specifically the saccule (Cody and Bickford 1969; Townsend and Cody 1971) but this was disputed by others (Meier-Ewert et al. 1974). For many years the inion response was thought to be nonspecific and it was not accepted as a useful test of vestibular reflex function (Douek 1981) until Colebatch and colleagues reinvestigated the phenomenon 10 yr ago.

Colebatch et al. 1994 noted that high-intensity clicks (95–100 dB NHL) evoked a reflex response in active sternocleidomastoid muscles. This consisted of a short-latency, high-threshold p13/n23 response that occurred ispilateral to the side of stimulation, and a late lower-threshold and bilateral n34/p44 response. The earlier response was shown to depend on the integrity of vestibular afferents, whereas cochlear activation was thought to be responsible for the late response (Colebatch and Halmagyi 1992; Colebatch et al. 1994). The neurophysiological substrate for the short latency p13/n23 potential (i.e., the sacculocollic reflex arc), was later described in animals by Uchino and colleagues (Kushiro et al. 1999; Uchino et al. 1997a). The findings of Colebatch et al. (1994) have been confirmed by a number of other groups (Ferber-Viart et al. 1999; Todd and Cody 2000) and additional methods of evoking vestibular-dependent reflexes in the same pathway have since been published (Halmagyi et al. 1995; Watson and Colebatch 1998b). Thus the vestibular-evoked myogenic potentials (VEMPs, i.e, the click-induced p13/n23 wave), recorded from sternocleidomastoid muscles, are currently used in clinical practice as an indicator of unilateral saccular function (Clarke 2001; Colebatch 2002; Colebatch et al. 1998; de Waele et al. 1999; Matsuzaki et al. 1999; Murofushi et al. 1996b, 1998; Patko et al. 2003; Tsutsumi et al. 2001).

The question we ask here is whether sound-evoked vestibular activation can lead to reflex responses in cranial muscles. There is a long history of reflex responses to sound in cranial muscles (postauricular, frontalis, orbicular oris, orbicular oculi, mylohyoideus, temporalis, and masseter muscles) but these were always attributed to activation of cochlear rather than vestibular afferents (Kiang 1963; Meyer-Ewert et al. 1974). In particular, a jaw–acoustic reflex was originally described by Meier-Ewert et al. (1974) in normal subjects, as a long-lasting dual inhibitory response elicited in active masseter muscles by acoustic stimulation. These authors provided evidence that the response was of cochlear rather than vestibular origin. However, because we (Deriu et al. 2003) have recently shown that electrical activation of vestibular inputs may evoke short-latency, short-duration reflexes in masseter muscles, the question is whether sound may also be able to evoke vestibular reflexes in these muscles. To this end we investigated the effects induced by loud-click stimulation in unrectified and rectified mean EMG as well as single motor units in the masseter muscles. Responses to click stimulation were then compared with the EVS-induced vestibulomasseteric reflex that we had described previously (Deriu et al. 2003) and to the click-induced vestibulocollic reflex (Colebatch et al. 1994).

	METHODS

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Eighteen healthy volunteers of both sexes (aged 22–51 yr) participated in the study after informed consent was given by each of them. The study was conducted in accordance with the ethical standards established in the 1964 Helsinki Declaration and was approved by the local ethics committee. Experiments were carried out with the subjects seated on a comfortable chair, with the head straight, the trunk upright, and the lower limbs in a semiflexed position.

EMG recordings

Surface EMG recordings from both masseter muscles (MM) were carried out using standard techniques with the reference electrode placed at the level of the lower border of the mandible and the active electrode about 2 cm above this. This electrode configuration was previously found (Deriu et al. 2003) to be the one where the largest responses could be detected, in agreement with previous reports (Godaux and Desmedt 1975; Widmer and Lund 1989) that the masseter motor point is located in the lower third of the muscle. The ground electrode was placed over the forehead. Both unrectified and rectified masseter EMG activities were recorded simultaneously (Digitimer D360 client Beta Version, Digitimer, Hertfordshire, UK), amplified (x5,000) and filtered (bandwidth 0.3–2,000 Hz). EMG was sampled (5 kHz) from 50 ms before to 100 ms after stimulus delivery, using a 1401 plus A/D converter (Cambridge Electronic Design, Cambridge, UK) and Signal 2.10 software on a PC. The subjects were given a target level of muscle activity [50% of maximal voluntary contraction (MVC)] to be maintained steadily during the data collection. To assist subjects, they were given visual feedback of filtered and rectified masseter EMG on an oscilloscope screen.

In 7 subjects recordings from 18 single motor units (SMUs) were performed using disposable concentric needle electrodes (Medelec model NDF C25, Oxford Instruments, Surrey, UK) inserted into either the right or left masseter muscle, very close to where the surface electrodes were placed. The subjects were asked to make a gentle contraction of the masseter muscles so that only a single or few motor units were active and they received audio-visual feedback of the firing of the SMU, enabling them to maintain a regular discharge rate. The response of all SMUs (n = 18) to bilateral click stimulation at 100 dB was studied; 3 of them were tested with unilateral stimulation applied to the ear ipsi- and contralateral to the unit. The response of 9 SMUs to bilateral click stimulation at 80 dB was compared with that induced in the same unit by 100-dB bilateral clicks. In 2 units, a comparison was also made between the response of the same unit to contralateral click stimulation at 100 dB and to cathodal electric mastoid stimulation at 5 mA applied to the contralateral mastoid process.

Click stimulation

Click stimuli of 0.1 ms duration were generated using a custom-built click generator and delivered randomly through TDH-49P earphones (Telephonics, Huntington, NY) either to the right or left or to both ears at a frequency of 3 Hz. All click intensities are expressed with respect to the normal hearing threshold for such clicks [0 dB NHL, normal hearing level, equal to 45 dB SPL (sound pressure level)]. Click intensities were adjustable in 10-dB increments. The click intensity routinely used in these experiments ranged from 70 to 100 dB NHL and was always the same in each ear.

EFFECTS OF BACKGROUND MUSCLE ACTIVATION. In 11 subjects click parameters were kept constant while the level of tonic muscle activation was varied between 25 and 75% of MVC. Click intensity was 100 dB in 8 subjects and 90 dB in 3 subjects. Frequent pauses in data collection were made for strong contractions to prevent fatigue.

EFFECTS OF BODY TILT. In 7 subjects masseter responses evoked by bilateral clicks in control conditions, i.e., with the subject keeping the trunk upright and the head straight (vertical position), were compared with those recorded during a 30° tilt of the body to either the left or right side. The subjects were seated on a tilting chair with full lateral support of the head, trunk, hips, and legs. After changing the tilt angle, a 2-min rest was given before we began to collect data to allow a steady state to develop and to avoid possible interference from fast adapting receptors.

Control experiments

ELECTRIC STIMULATION OF THE VESTIBULAR SYSTEM. In the masseter muscles of 10 subjects we compared unrectified and rectified EMG responses elicited by sound to those elicited by electric vestibular stimulation (EVS), which has been shown to activate vestibular afferents through an action exerted on the most distal part of the vestibular nerve (Courjon et al. 1987; Goldberg et al. 1984). Responses of single motor units to the 2 different stimuli were also compared in 2 subjects (n = 2 units). EVS was achieved using square-wave current pulses (2-ms duration, 3-Hz frequency, 5-mA intensity) delivered by a constant-current–isolated stimulator (model DS3, Digitimer) through large electrodes placed over the mastoid processes.

CLICK-INDUCED MYOGENIC POTENTIALS IN STERNOCLEIDOMASTOID MUSCLES. In 7 subjects the threshold of responses elicited by loud clicks in masseter muscles was compared with the threshold of vestibular myogenic potentials (VEMPs) elicited by the same stimuli in sternocleidomastoid muscles (SCMs). VEMPs were recorded from symmetrical sites over the upper half of each SCM belly by means of surface electrodes with a reference over the medial clavicle and ground electrode over the upper sternum. Click stimuli (0.1-ms duration, 3-Hz frequency, 70- to 100-dB NHL intensity) were delivered bilaterally while the subjects voluntarily activated their SCMs by holding their head slightly raised when lying supine.

The magnitude of masseter and SCM responses to sound were compared in 5 subjects using the corrected amplitudes (i.e., the ratio between peak amplitude and background muscle activity) of the masseteric p11 and sternocleidomastoid p13 responses to ipsilateral click stimulation.

CONDUCIVE HEARING LOSS. To exclude a possible role played by receptors other than those located in the inner ear (particularly the trigeminal receptors of external auditory canal and tympanic membrane), masseter responses to click stimulation at 100 dB were studied in a patient affected by right conductive hearing loss resulting from an alteration within the right middle ear.

EMG and data analysis

CLICK EXPERIMENTS. The reflex responses were measured from both the unrectified and rectified averages (n = 300–500). The latter was also used to quantify the level of muscle tonic activation. Peaks in averaged unrectified EMG were described using the same notation used by Colebatch et al. (1994) to describe the click-induced vestibulocollic reflex in SCMs, i.e., the mean latency preceded by the lower case letters "p" for positive peaks (downward deflections) and "n" for negative peaks (upward deflections). Response amplitudes in unrectified EMG were measured either for a single peak or peak to peak, with reference to the mean level of activity in the 50 ms preceding the clicks. These amplitude values were then divided by the mean of the rectified EMG for the 50 ms preceding the stimulus onset. This gives a value for response amplitude relative to the level of background muscle activation.

EVS EXPERIMENTS. In all EVS experiments, we recorded averaged unrectified and rectified masseter responses to 800 stimuli delivered at 3 Hz, both during tonic muscle activation ("active trace") and during relaxation ("relaxed trace"). To reduce or remove the large stimulus artifact induced by EVS, we applied the methodology suggested by Watson and Colebatch (1998b), i.e., subtraction of the "relaxed trace" from the "active trace". Responses in unrectified EMG were measured as above reported for click-induced responses (for more details see Deriu et al. 2003).

SMU EXPERIMENTS. Two different techniques were used to analyze SMU data. The former was the classical technique that involved calculation of peristimulus time histograms (PSTHs) of single-unit discharges. PSTHs were generated using a personal computer attached to a laboratory interface (1401 plus, CED Electronics, Cambridge, UK) and associated software. Previous studies (Colebatch and Rothwell 1993, 2004) indicated that a large number of trials would be required to detect reliably any excitability changes and to give a stable prestimulus baseline discharge frequency. A total of 800 to 1,600 presentations of each stimulus was used for each histogram, which was composed of 150–250 bins, each 1 ms wide, with a prestimulus period of 50–100 ms. The criteria for significant inhibition or excitation were chosen empirically, to be the presence of 2 adjacent bins each containing less than half or over 50% more discharges than the prestimulus mean (Colebatch and Rothwell 1993, 2004; Deriu et al. 2003). The latter technique was the peristimulus frequencygram (PSF), obtained by plotting the instantaneous discharge frequencies of one SMU against time of the stimulus as described in detail in the work of Türker and Cheng (1994). To this aim long runs of SMU recordings were acquired (Spike2 5.06 program), whereas 1,000 presentations of the stimulus were given at 1-Hz frequency. The mean background firing rate ± 3SD was calculated from the prestimulus discharge rate and those limits were placed on the mean firing rate to evaluate reliably stimulus-induced changes in the postsynaptic potentials underlying SMU responses.

All values are given as means ± SD. Statistical comparisons were made using Student's t-test and linear correlation analysis.

	RESULTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION GRANTS ACKNOWLEDGMENTS REFERENCES

 
Unilateral or bilateral click stimuli (70–100 dB NHL) were delivered during tonic activation of masseter muscles in all subjects. They evoked 2 different short latency responses that were distinguished by their threshold, latency, and appearance in the averaged rectified EMG. These short-latency responses were often followed by later responses (n28, p34, n44) that varied considerably in amplitude and latency between subjects; they were more often seen at high stimulation intensities and more frequently after bilateral stimulation.

We focused our attention on the 2 short-latency responses.

Responses evoked by click stimulation in the averaged unrectified EMG of masseter muscle

The clearest responses were evoked by stimulation at 100 dB during a 50% MVC of the masseter muscles. As illustrated in the 2 subjects shown in Fig. 1, unilateral or bilateral click stimuli evoked responses in both masseters that began with a clear p11 wave with onset latency ranging from 7.0 to 9.2 ms. This initial p11 wave was followed, in most subjects (12/18), by a less clear n15 wave and by a later variable n21 wave (Fig. 1A, first 3 traces from top to bottom, for left and right masseter). Sometimes the n15 wave was just a deflection in a simple biphasic p11/n21 wave (Fig. 1B, top traces).

View larger version (22K): [in this window] [in a new window]   FIG. 1. Responses induced by unilateral and bilateral click stimulation in averaged electromyogram (EMG) recorded from surface electrodes over the left and right masseter muscles (MM), in 2 different normal subjects. Both sets of averages (each of 300 trials) were obtained with the same click duration (0.1 ms), frequency (3 Hz), and intensity (100 dB NHL) and during a tonic activation of MM at 50% of maximal voluntary contraction. Click stimulation induced, in different subjects, 2 different patterns of responses in the averaged unrectified EMG. A: example of the former pattern of MM response is reported, consisting of a p11 wave followed by a less-defined n15 wave and by an n21 wave. From top to bottom: the first 3 traces are the unrectified EMG averages, the 4th traces are the rectified averages of responses to bilateral click stimulation, recorded simultaneously to the 3rd traces. B: second pattern of MM response to bilateral click stimulation is shown, consisting of a simple biphasic p11/n21 wave. Simultaneous averages of unrectified and rectified EMGs are reported (top and bottom traces, respectively). In all traces arrows indicate the time of stimulus application.

View larger version (19K): [in this window] [in a new window]   FIG. 2. Effects of varying the intensity of click stimulation on masseter muscle EMG responses to loud clicks. Both sets of unrectified averages (each of 500 trials) were obtained while subjects were activating masseters (MM) at a constant tonic level (50% of maximal voluntary contraction) and click stimuli of fixed duration (0.1 ms) and frequency (3 Hz) were delivered at decreasing intensity values (reported on the left). A: selection of averaged EMG traces recorded from a subject is reported: at 90 dB a clear p11 wave is evident; at 70 dB the p11 wave is no longer visible, whereas a p16 wave is clearly detectable. At 80 dB an intermediate condition is appraisable in which the p11 and p16 waves overlap. B: selection of averaged EMG traces recorded from another subject is reported. In this case the threshold for the p11 wave is >90 dB: at this intensity the p11 wave is already missing and a clear p16 wave, which was not visible at 100 dB, becomes evident.

View larger version (18K): [in this window] [in a new window]   FIG. 3. Amplitude of masseter EMG responses to click stimulation at a fixed intensity scaled with the mean level of EMG activity. A: selection of couples of unrectified and rectified (top and bottom traces of each pair of traces, respectively) EMG averages (n = 500), simultaneously recorded from a single subject performing decreasing levels of masseter contractions, is reported. Responses of both masseter muscles (MM) to bilateral clicks at fixed stimulation parameters (100 dB, 0.1 ms, 3 Hz) are shown. For both muscles: peak size of p11/n21 waves is indicated by vertical calibration on the left of unrectified EMG averages; level of prestimulus mean EMG and degree of click-induced EMG decrease are indicated by vertical calibrations on the left of rectified EMG traces. Horizontal calibration at the bottom of A refers to all traces. In all traces arrows indicate the time of stimulus onset. B: relationship between the amplitude of the click-induced p11 wave and level of background muscle activation in all tested subjects is shown. Graph reports response amplitude (peak-to-peak amplitude, uncorrected for different levels of muscle activation) vs. mean rectified EMG level. Circles correspond to single subjects (n = 8 subjects, 16 sides), each one performing 3 different levels of muscle activation during bilateral click stimulation at 100 dB. Line is the fitted linear regression line.

View larger version (11K): [in this window] [in a new window]   FIG. 4. Static tilt of the body on both sides, with respect to the vertical position, induced asymmetrical changes in the magnitude of the p11 wave induced in averaged unrectified masseter muscle EMG by loud-click stimulation. The amplitude of the p11 wave (expressed as peak amplitude corrected for the prestimulus EMG level) induced by bilateral clicks in subjects with the trunk upright and with head straight is taken as 100% (indicated by the horizontal dashed line). Histograms represent the percentage amplitude (mean ± SD, n = 7 subjects, 14 sides) of the masseter p11 wave recorded from subjects tilted 30° ipsilaterally and contralaterally to the side of recording (ipsilateral tilt and contralateral tilt, respectively).

The principal feature of the rectified EMG responses was a period of inhibition beginning at 11–14 ms and lasting 10–12 ms; peak inhibition usually occurred at 16–20 ms from click onset. This inhibition was visible at all stimulation intensities (70–100 dB NHL) and appeared to correspond to the p16 wave in the unrectified averages. The high-threshold p11 wave was rarely seen in the averaged rectified EMG except on occasion during high-intensity clicks as a small increase above baseline before the inhibition. The latency of this peak corresponded to the p11 peak in the unrectified EMG (Fig. 1A, bottom traces). As with the unrectified responses, responses in the rectified EMG were always bilateral, even after unilateral stimulation, although the latter were always smaller in amplitude. The depth of inhibition scaled with the level of muscle contraction (Fig. 3A) and was greatest at the highest stimulation intensities.

Control experiments

COMPARISON OF MASSETER EMG RESPONSES TO CLICK AND ELECTRICAL VESTIBULAR STIMULATION. In 10 subjects, we compared masseter EMG responses elicited by click stimuli to the vestibulomasseteric reflex evoked by electrical vestibular stimulation over the mastoid (Deriu et al. 2003). Data from a typical subject are shown in Fig. 5. In all subjects, the response to 100-dB clicks and to 5-mA EVS began, in the unrectified EMG, with a p11 wave of similar magnitude and latency. By contrast, the following n15 wave was clearly present after EVS, whereas it was unclear or just a deflection in a biphasic p11/n21 wave after clicks. Later potentials were variable both between subjects and between stimulation types.

View larger version (14K): [in this window] [in a new window]   FIG. 5. Masseter responses elicited by click and electrical vestibular stimulation (EVS) in a representative subject. A selection of averaged unrectified and rectified EMGs recorded simultaneously from the left masseter muscle is reported. Masseter response to bilateral EVS (5 mA, 2 ms, 3 Hz, cathode on the left mastoid) in the unrectified EMG consisted of a p11/n15 wave that was not detectable in the rectified EMG. Responses to 100-dB clicks differed from those induced by EVS as for the absence of the n15 wave in the unrectified EMG and for a clear decrease in mean rectified EMG level. This silent period in the rectified EMG exhibited a time course different from that of p11/n15 potentials but similar to the p16 response visible in the unrectified EMG when clicks of a subthreshold intensity (80 dB) for the p11 wave were delivered.

COMPARISON OF THE THRESHOLD OF CLICK-INDUCED EMG RESPONSES IN MASSETER WITH THOSE EVOKED IN STERNOCLEIDOMASTOID MUSCLES. In 7 subjects we compared the threshold intensity needed for bilateral clicks (0.1 ms, 3 Hz, 70–100 dB NHL) to evoke the masseter p11 wave with the threshold for the p13/n23 wave elicited in the sternocleidomastoid muscles. Because 10-dB increments in intensity were used in the present study, a precise determination of the threshold of the 2 reflexes could not be achieved. However, the threshold intensity for the 2 responses was the same in both muscles of each subject and the mean threshold was 84 dB (n = 7 subjects).

To evaluate the relative strength of the vestibular projection to sternocleidomastoid and to masseter muscles, the corrected amplitudes of the p13 and p11 waves elicited by 100-dB ispilateral click stimulation were compared in 5 subjects. Results showed that sternocleidomastoid response to clicks was 30% larger than the masseteric response.

CLICK-INDUCED RESPONSES IN A PATIENT WITH CONDUCTIVE HEARING LOSS. Masseter EMG responses to 100-dB clicks applied to the right, left, and both ears were studied in a patient affected by a pathology of the right middle ear responsible for a right conductive hearing loss. This patient had previously shown a lack of VEMPs in the right SCM after right ear stimulation, but a normal response in the left SCM after left ear stimulation. Results showed no response in both masseters after unilateral right stimulation but a clear bilateral p11/n21 response after unilateral left stimulation. Bilateral click stimulation induced a bilateral response of amplitude similar to that induced by unilateral left stimulation, i.e., reduced in size with respect to responses induced by bilateral stimulation in normal subjects (data not shown).

Single motor unit responses to click stimulation

Loud clicks inhibited ongoing activity in all 18 single motor units (SMUs) that we studied. PSTHs showed that bilateral click stimulation (100 dB NHL) produced a clear inhibition of unit firing lasting 5–12 ms (mean onset latency across all 18 units, 11.6 ± 1.3 ms; mean duration 8.0 ± 2.4 ms), which was sometimes followed by late variable facilitation. It is difficult to interpret an apparent facilitation in a PSTH when it follows a period of inhibition (Türker and Cheng 1994). Because of this we also analyzed the same data using the PSF method. An example from one motor unit is shown in Fig. 6. In the PSTH, bilateral click stimulation at 100 dB induced a short-latency brief silent period followed by a late excitation; in the PSF there was a slight decrease in mean frequency corresponding to the inhibition of firing in the PSTH but no sign of late facilitation, suggesting that the late facilitation in the PSTH was attributed to "rebound" firing of motor units after a pause and not to a true excitatory event. It is noteworthy that the inhibition in SMU firing, so clear and deep in the PSTH, led to only a slight decrease in frequency in the PSF. This may be attributed to the fact that the duration of the inhibitory effect is so short that any change in frequency occurring in this brief period is small in comparison to the baseline variability in unit firing rate.

View larger version (30K): [in this window] [in a new window]   FIG. 6. Masseter single motor unit (SMU) recordings clearly showed that the click-induced response is a mere inhibitory response. A: peristimulus time histogram (PSTH; bin duration = 1 ms) of the response of one motor unit recorded from the right masseter muscle to 1,000 consecutive bilateral clicks (100 dB, 0.1 ms, 1 Hz). This histogram shows that after the stimulus (indicated by the arrow at time 0) an early deep inhibition followed by a later excitation of unit firing occurs. B: peristimulus frequencygram (PSF, in 2-ms bins) representing the superimposed firing frequency of the same unit with respect to the stimulus. A total of 1,000 trials were superimposed in this graph. C: averaged frequency rate of the unit reported on the same timescale. Prestimulus mean discharge rate ± 3SD are superimposed to the graph (broken lines). PSF analysis (B and C) shows an early slight decrease in mean frequency but not late facilitation. Position of the stimuli is shown by the vertical line at time 0 (arrows).

View larger version (23K): [in this window] [in a new window]   FIG. 7. Inhibition of masseter SMU firing induced by bilateral click stimulation lasted longer than that induced by unilateral clicks. PSTHs of the response of the same SMU recorded from the left masseter muscle to 800 consecutive click stimuli (100 dB, 0.1 ms, 3 Hz) applied to both ears and to the ear ispilateral and contralateral to the recorded unit are shown. Stimuli were given at time 0, indicated by arrows. Bin duration = 1 ms.

View larger version (24K): [in this window] [in a new window]   FIG. 8. Same masseter single motor unit showed an inhibitory period of different latency and duration depending on click intensity and on type of stimuli (sound or electrical) used to activate the vestibular system. A: effects induced on the same SMU by clicks of different intensity are shown. PSTHs report the response of a SMU recorded from the right masseter muscle to 800 consecutive bilateral click stimuli of 100 dB (top histogram) and of 80 dB (bottom histogram). Silent period in SMU firing induced by 100-dB clicks, occurred at a latency shorter and lasted longer than that induced by click stimulation at 80 dB. B: effects induced on SMU firing by click stimulation and by EVS are shown. PSTHs report the response of SMU recorded from the left masseter to 800 consecutive cathodal stimuli (5 mA, 2 ms, 3 Hz) applied to the contralateral mastoid process (top histogram) and to 800 consecutive click stimuli (100 dB, 0.1 ms, 3 Hz) applied to the contralateral ear (bottom histogram) are reported. SMU inhibition, induced by click stimulation, occurred at the same latency but lasted longer than that induced by cathodal EVS. Stimuli were given at time 0, indicated by arrows. Bin duration = 1 ms.

	DISCUSSION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION GRANTS ACKNOWLEDGMENTS REFERENCES

 
The present results have shown that unilateral acoustic stimulation with a loud click evokes bilateral and symmetrical short-latency responses in active masseter muscles of healthy subjects. Bilateral stimulation evoked similar, but larger-amplitude responses. The responses appeared to consist of 2 components distinguished by their threshold, latency, and their appearance in the rectified EMG. The lower threshold response was a p16 wave in the averaged unrectified EMG, which corresponded with a long-lasting decrease in the mean rectified EMG. The higher threshold response was an earlier p11 wave that appeared in the unrectified EMG, and was sometimes seen in the rectified EMG as an initial short period of excitation before the longer-lasting suppression. The initial p11 wave was followed in most subjects by a small n15 wave and by a later variable n21 wave (sometimes the n15 wave was just a deflection in a simple biphasic p11/n21 wave). Short-latency responses were often followed by later potentials (n28, p34, n44), which were not analyzed in detail.

Recordings from single masseter motor units showed that responses to loud clicks always corresponded to one period of inhibition rather than one or 2 short periods of inhibition followed by excitation. The intensity of the clicks affected the latency, duration, and extent of the inhibition.

Faithful transmission of sound stimuli to the inner ear was required to produce masseter responses. They were absent in a subject with conductive hearing loss attributed to pathology of the middle ear, indicating that they were not dependent on involvement of trigeminal receptors in the external ear or tympanic membrane. We argue below that they are likely to be caused by stimulation of both cochlear and saccular receptors in the inner ear.

Origin of responses induced by sound in masseter muscles

THE P16 WAVE. The p16 wave (onset 11–13 ms) in the unrectified EMG corresponded to a period of suppression in the rectified EMG and to a reduced firing rate in single motor units. It was visible with click intensities lower than those needed to evoke the earlier p11/n15 response. Although we did not test threshold systematically, it was always detectable in masseter EMG at 70 dB, which was the lowest intensity routinely used in these experiments (see Fig. 2A). The p16 component increased linearly with background muscle activation. As the intensity of the clicks was increased, the p16 in the unrectified EMG first became larger, but then became less clear at high intensities after appearance of the p11 wave. Nevertheless, the corresponding period of EMG suppression in the rectified EMG continued to increase.

The inhibitory period in the rectified EMG trace that corresponds to the p16 wave in unrectified EMG is very similar in latency and time course to the jaw–acoustic reflex originally described by Meier-Ewert et al. (1974). This reflex was described as a bilateral inhibitory period (approximate latency 14 ms, duration 11 ms) visible in the EMG during voluntary contraction of the masseter muscles after unilateral stimulation with high-intensity clicks or tones. The authors suggested that it might be a local protective reflex and proved that its afferent reflex arc was the acoustic nerve, whereas a vestibular contribution was excluded. They also identified a nonconsistent later silent period at latencies similar to those of the later potentials that we observed in the present study and considered them as a central part of the startle pattern. We suggest that the p16 wave in the unrectified average EMG is equivalent to this jaw–acoustic reflex (Meier-Ewert et al. 1974) and is mediated by activation of cochlear receptors.

THE P11/N15 WAVE. The p11/n15 response (onset 7.0–9.2 ms) was recruited only when high-intensity stimuli (90–100 dB) were used. The n15 component was usually less defined than the p11, but this may be attributable to overlap with the low threshold p16 wave. Although the p11 was clear in the unrectified EMG, it was less obvious in the rectified averages and sometimes appeared as a short period of excitation before suppression. Despite this apparent excitation in the rectified averages, click intensities capable of evoking a p11 wave always suppressed the firing of single motor units. The onset of suppression was some 5 ms earlier than that seen with lower-intensity clicks that evoked only the p16. Our conclusion is that the p11 wave in the unrectified EMG corresponds to an additional earlier period of inhibition in single-unit firing that merges into that seen during the p16 wave. As noted by Widmer and Lund (1989), a sudden onset of motor unit inhibition can sometimes lead to a paradoxical early increase in rectified EMG activity arising from failure of cancellation of the tails of unit action potentials that had begun to discharge before the inhibition began.

Two pieces of evidence suggest that the p11/n15 response to loud clicks is attributed to activation of vestibular receptors. First, we found that it had the same latency and form as the p11/n15 vestibulomasseteric reflex evoked by transmastoid electrical stimulation (Deriu et al. 2003). It scales with background EMG level, is larger at higher stimulus intensity and after bilateral stimuli, is modulated asymmetrically by static tilt of the body, and corresponds to an inhibitory period in single motor unit discharge rate (Deriu et al. 2003). By analogy with experiments in animals (Courjon et al. 1987; Goldberg et al. 1984) transmastoid electrical stimulation is thought to act by polarizing the terminals of the vestibular nerve (Watson and Colebatch 1997, 1998a,b; Watson et al. 1998) and has been used to characterize vestibular-dependent responses in the eye (Kleine et al. 1999; Watson et al. 1998; Zink et al. 1998), jaw (Deriu et al. 2003), neck (Watson and Colebatch 1998b), and limb (Britton et al. 1993; Fitzpatrick et al. 1994; Watson and Colebatch 1997) muscles. It therefore appears likely that the click-evoked p11/n15 response has a similar vestibular origin. Interestingly, single motor unit studies showed that the duration of inhibition evoked by transmastoid electrical stimulation was shorter than that evoked by high-intensity clicks. This may be explained by the fact that clicks cause a later, lower-threshold acoustic reflex that prolongs the single-unit inhibition beyond that seen after transmastoid electrical stimulation.

The p11/n15 response to clicks also is similar to the vestibular-evoked myogenic potential (VEMP) induced in sternocleidomastoid (SCM) muscles by the same stimuli (Colebatch et al. 1994). Both have the same high threshold (90–100 dB NHL), both correspond to a period of inhibition in single-unit activity (Colebatch and Rothwell 1993, 2004), and both scale in amplitude with the background level of tonic EMG activity. The VEMP consists of a p13/n23 wave in the averaged unrectified EMG and, because it disappears after selective vestibular neurectomy and is preserved in patients with a selective sensorineural deafness (Colebatch and Halmagyi 1992; Colebatch et al. 1994), it is usually assumed to be of vestibular origin. We therefore suggest that the p11 potential in masseter may be produced by a similar vestibular mechanism. It should be noted that, although the masseter p11/n15 wave was bilateral and symmetric after unilateral stimulation, the VEMP is predominantly ipsilateral (Colebatch et al. 1994). This is likely to be a result of the different functional role played by these muscles, the 2 SCMs working as antagonists in head rotation, whereas the masseters work together to position the mandible appropriately by its sliding-hinge joint. Another notable difference between effects induced by loud clicks in masseters and SCMs is in the magnitude of responses to the same stimulus. The comparison between corrected amplitudes of the p11 and p13 waves induced by 100-dB ipsilateral clicks in masseters and SCMs, respectively, showed that SCM response was 30% larger than masseter response. This indicates that the strength of vestibular projection to SCMs is more powerful than projection to masseters. This may be a consequence of the predominant role played by neck muscles in postural control compared with that played by jaw-closing muscles.

Nature of the sound-induced masseter responses

We have argued above that the response consists of an early high-threshold vestibular component (p11 in unrectified EMG) followed some 5 ms later by a lower-threshold acoustic response (p16 in the unrectified EMG). Single-unit studies suggest that both are inhibitory. The relation between motor unit inhibition and average surface EMG potentials was explored recently for the vestibulocollic reflex by Colebatch and Rothwell (2004), who showed that periods of motor unit inhibition that are brief in comparison with the duration (as recorded in surface EMG) of the single-unit action potential lead to a positive/negative wave in unrectified surface averages, at least when recorded with a conventional belly-tendon montage. Longer periods of unit suppression are evident only as an initial positive peak in the surface EMG. Our single motor unit data showed that inhibition began some 5 ms earlier when high-threshold clicks were given. This would therefore account for the 5-ms difference in latency of the peak positivities (p11 vs. p16) produced by high- and low-intensity clicks.

Colebatch and Rothwell (2004) also showed that the amplitude of the surface potential often scaled with the level of background EMG, as seen in the present experiments for the click-evoked p11 response. They argued that this was attributed to the recruitment properties of motor units in the motoneuron pool and would be likely to occur if the afferent input responsible for inhibition was distributed equally to all motoneurons. Higher levels of contraction might recruit larger motor units, but these would be the first to be derecruited by the inhibitory input leading to "automatic gain compensation" in the reflex (Matthews 1986). The fact that the p11 response scaled with background EMG in the same way as the vestibulomasseteric reflex evoked by transmastoid electrical stimulation is further support that both use the same afferent pathway.

Finally it is important to comment on the apparent latency difference between the responses in surface EMG and those recorded in single units from the same muscle. Two factors tend to make single-unit responses lag those in the surface EMG. First, the needle electrode used to record the unit may be placed some distance from the motor point of the muscle. Given the relatively slow speed to conduction of action potentials along the muscle fiber this can add several milliseconds to the earliest latency of activation seen by a surface electrode at the motor point. The second factor is that single units are usually recorded at low contraction levels, and thus tend to be the earliest recruited units from the population. These may have peripheral motor axons with slower conduction velocities than those that innervate later-recruited units. The latter probably dominate the surface EMG, especially during moderate to high levels of muscle contraction.

Vestibular influences on trigeminal motor system

Trigeminal motoneurons are mainly involved in mastication but they also serve an antigravity function aimed at maintaining the posture of the jaw under dynamic as well as static conditions (Lund and Olsson 1983; Miralles et al. 1987). Like spinal motoneurons innervating neck, trunk, and limb muscles, trigeminal motoneurons innervating jaw muscles receive inputs from the vestibular system. Data obtained from animal experiments show that masseter motoneurons receive tonic, bilateral excitatory inputs from the vestibular system by a polysynaptic pathway (Deriu et al. 1999; Tolu and Pugliatti 1993; Tolu et al. 1996). Vestibular input has also been demonstrated in humans: Hickenbottom et al. (1985) provided evidence that the dynamic input from vestibular ampullar receptors in response to rotation enhances masseteric motoneuron output; Deriu et al. (2000) showed that static tilt induces bilateral asymmetric changes in masseter muscle EMG activity. More recently, we (Deriu et al. 2003) described a new vestibulomasseteric reflex evoked by transmastoid electrical stimulation. Like the earliest high-threshold p11/n15 response to sound described in the present study, the EVS-induced vestibulomasseteric reflex is bilateral, symmetric, inhibitory, has short latency and short duration, and is mediated by no more than 3 synaptic relays. We have suggested that these data in humans are compatible with a dual action of vestibular input on masseter: an excitatory tonic control, which is exerted through indirect pathways, and a short latency inhibitory input that is preferentially activated by phasic inputs. A similar dual organization has been widely described in limb muscles. For example, mastoid EVS evokes 2 sets of responses in leg and arm muscles (Britton et al. 1993; Fitzpatrick et al. 1994; Watson and Colebatch 1997): a short-latency, short-duration response followed by a longer-lasting response of opposite polarity. The latter sustained effect is more powerful and is responsible for the postural sway that EVS evokes in standing subjects.

Vestibular influences may act to stabilize the position of a given part of the body in response to sudden imposed disturbances (phasic reflexes) or may act to define a desired position (set point) with respect to gravity. The receptors capable of mediating responses specifically dependent on gravity are the otoliths, which are characteristically sensitive to tilt (Fernandez et al. 1972) and are activated by sound in a way that resembles natural linear acceleration (Ogawa et al. 2000; Uchino et al. 1997b). In this respect, the natural function of the sound-induced vestibulomasseteric reflex may be to respond to sudden head tilt upward or downward. For instance, if the head is suddenly dropped, it may be of value to inhibit the masseter, and vice versa if the head is suddenly pitched upward. The short-latency, short-duration vestibular influences may be functionally of minor importance in postural control, but they might ensure fine-tuning of voluntary motor output to masseter muscles by allowing vestibular inputs a rapid access to jaw muscle control.

	GRANTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION GRANTS ACKNOWLEDGMENTS REFERENCES

 
This work was supported by grants from the Medical Research Council of the UK, Regione Autonoma della Sardegna, and from the Ministero dell'Istruzione, dell'Università e della Ricerca. Dr. F. Deriu was supported by a grant from Centro Nazionale Ricerche.

	ACKNOWLEDGMENTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION GRANTS ACKNOWLEDGMENTS REFERENCES

 
The authors gratefully acknowledge the technical assistance of P. Asselman.

	FOOTNOTES

 
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Address for reprint requests and other correspondence: F. Deriu, Department of Biomedical Sciences, Section of Human Physiology and Bioengineering, Viale San Pietro 43/b, 07100 Sassari, Italy (E-mail: deriuf{at}uniss.it)

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