19019ournal ofNeurology, Neurosurgery, and Psychiatry 1994;57:190-197 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.57.2.190 on 1 February 1994. Downloaded from Myogenic potentials generated by a click-evoked vestibulocollic reflex

J G Colebatch, G M Halmagyi, N F Skuse

Abstract fall depends on otolith activation, possibly via Electromyograms (EMGs) were recorded connections to the reticular formation and from surface electrodes over the sterno- thereby to the ." Detailed studies mastoid muscles and averaged in on a single patient who had an otolithic response to brief (0.1 ms) clicks played Tullio phenomenon (sound-evoked activation through headphones. In normal subjects, of the vestibular apparatus) showed short- clicks 85 to 100 dB above our reference latency activation of leg muscles, probably via (45 dB SPL: close to perceptual thresh- vestibulospinal pathways.7 The limitations of old for normal subjects for such clicks) our knowledge of vestibular influences on the evoked reproducible changes in the aver- muscles of the trunk and limbs led us to aged EMG beginning at a mean latency reinvestigate earlier reports of activation of of 8-2 ms. The earliest potential change, the vestibular apparatus in normal subjects a biphasic positive-negativity (p13-n23), by loud clicks. occurred in all subjects and the response Bickford et al 8 described the characteristics recorded from over the muscle on each of averaged responses to clicks with record- side was predominantly generated by ings with an active electrode just below the afferents originating from the ipsilateral inion (the "inion response"). They concluded ear. Later potentials (n34, p44), present that the short latency potentials that they in most but not all subjects, were gener- recorded were not, as they had first supposed, ated bilaterally after unilateral ear stim- indicative of an auditory projection to the ulation. The amplitude of the averaged cerebellar vermis, but rather were generated responses increased in direct proportion by reflex changes in the level of EMG of to the mean level of tonic muscle activa- posterior neck muscles, and thus were tion during the recording period. The "myogenic" in origin. They also reported that p13-n23 response was abolished in the evoked response was present in patients patients who had undergone selective with sensorineural deafness, leading them to section of the but was propose that it arose from activation of the preserved in subjects with severe sen- vestibular apparatus and not from activation sorineural loss. It is proposed of the cochlea. Subsequent publications by that the p13-n23 response is generated these workers described the inion response in

by activation of vestibular afferents, patients with different acoustic and vestibular http://jnnp.bmj.com/ possibly those arising from the , lesions and provided further evidence sug- and transmitted via a rapidly conduct- gesting that it depended on activation of the ing oligosynaptic pathway to anterior otoliths, specifically, the saccule.910 The role neck muscles. Conversely, the n34 and of the vestibular apparatus has been disputed p44 potentials do not depend on the by others. Meier-Ewert et al II argued that the integrity of the vestibular nerve and inion response was a part of a generalised probably originate from cochlear sonomotor response that originated from

Department of on September 24, 2021 by guest. Protected copyright. Neurology, Institute of afferents. cochlear afferents. Additionally, averaged Neurological Sciences, responses at the inion were not unique to Prince ofWales Hospital, Randwick, (7 Neurol Neurosurg Psychiatry 1994;57:190-197) click stimuli: Cody and Bickford'2 were able Sydney 2031, Australia to record a similar-looking response to both J E Colebatch light flashes and electric shocks, albeit at N F Skuse The have powerful projec- longer latency than the response to sound. Department of tions to the ocular motor nuclei, the cerebel- These uncertainties have led to the view that Neurology, Royal Prince Alfred lum, the reticular formation, and the spinal the inion response is non-specific and it has Hospital, cord.' In humans, the most accessible and not been accepted as a useful measure of Camperdown, Sydney best studied vestibular pathway is that vestibular reflex fumction."I 2050, Australia G M Halmagyi between the and the ocu- We have used different recording sites from those of Bickford and to Correspondence to: lar motor nuclei: the standard test of vestibu- co-workers, Dr J G Colebatch, lar function, caloric induced , demonstrate the presence of short latency Department ofNeurology, neck muscles after Institute ofNeurological measures the effect of horizontal canal activa- EMG changes in anterior Sciences, Prince ofWales tion on eye movements.2 The reflex effects clicks. Also, the response can be separated Hospital, High Street, two the earlier Randwick, Sydney 2031, resulting from activation of the otoliths and into distinct components: only Australia the function of the direct vestibular projec- of these depends specifically on the integrity Received 18 December tions to the spinal cord in humans are diffi- of vestibular afferents. The findings from one 1992 and in revised form of a brief 31 March 1993. cult to study and poorly understood.3 The patient have been the subject Accepted 8 April 1993 initial muscle excitation after an unexpected report. 14 Myogenic potenttals generated by a click-evoked vestibulocollic reflex 191 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.57.2.190 on 1 February 1994. Downloaded from Methods 50-60 ,V. In most trials the subjects were Recordings were made from 10 normal vol- told to press their foreheads against the bar in unteers (seven men, three women; ages 29 to front of them to achieve the necessary bilat- 63 years) and from eight patients with well eral muscle activation but recordings were defined lesions affecting the . For also made while the subjects held their heads most of the recordings, the subjects were turned to one side (predominantly unilateral seated with a padded bar adjusted to be just muscle activation) and during bilateral mus- in front of their foreheads. The subjects cle activation due to voluntarily holding the pressed against the bar to activate their neck head slightly raised when lying supine. flexors to the degree required throughout the The clicks were rarefactive square waves averaging runs (see later). 0-1 ms long, generated by an ST10 evoked Surface EMG activity was recorded from potential stimulator (Medelec Ltd, Surrey, symmetrical sites over the upper half of each UK) and delivered by calibrated headphones. sternomastoid muscle by means of surface Click intensities were adjustable in 5 dB electrodes with a reference over the upper increments. Although the subjects' threshold sternum. These sites were chosen in prefer- for detecting the clicks was always measured, ence to the inion both to allow greater cer- the click intensity actually used was not tainty as to the specific muscles likely to be related to their subjective thresholds and the generating any response seen, and also to same stimulus intensity was always used for avoid the uncertainties inevitably associated both ears. With the duration used here with the use of a midline recording site when (0- 1 ms), most subjects cannot hear clicks investigating the effects of unilateral stimuli. softer than 45 dB SPL, and this level was The EMG from each side was amplified, therefore used as a reference (the same refer- bandpass filtered (8 Hz-1i6 kHz), and aver- ence as used during clinical recordings of aged using a sampling rate for each channel evoked brainstem potentials in our labora- of 2-5 kHz. Initial experiments were per- tory). The click intensities routinely used in formed with a Medelec Sensor evoked poten- these experiments were either 95 dB or 100 tial averager (Medelec Ltd, Surrey, UK); dB above the reference (140 and 145 dB later experiments used a laboratory interface SPL). These clicks are within the range used (1401, CED Electronics Ltd, Cambridge, clinically to record brainstem evoked UK) and an IBM compatible personal com- responses. puter. Simultaneous averages of unrectified Peaks on the averaged EMG record will be and rectified EMG were collected from 20 ms described with the mean latency preceded by before the clicks to 80 ms afterwards. The lower case letters (p13, n23 etc), as proposed clicks were presented at 3/s (preliminary find- ings indicated little change in the responses with repetition rates up to 5/s) and the 75 dB response to 512 stimuli averaged for each condition. Also, EMG activity was rectified and low pass filtered for display on an oscillo- scope screen in front of the subject. A target 85 dB level of EMG activity was set and the subjects instructed to keep the levels of smoothed, http://jnnp.bmj.com/ rectified EMG just above the target level for the duration of each average (about three minutes). The usual target corresponded to a mean rectified EMG activity of about Subject Subject 2 I1n23 on September 24, 2021 by guest. Protected copyright. R St-mr I L St-mr 100 lv]

0 20 40 60 ms 0 20 40 ms 0 20 40 ms Figure 2 Effect ofdiffering intensities ofstimulation in a Figure 1 Averaged unrectified EMG responses recordedfrom surface electrodes over the single subject. A constant targetfor muscle activation was right (R St-m) and left (L St-m) sternomastoid muscles in two different normal subjects. usedfor all the trials, resulting in similar levels ofmean, In this and subsequent illustrations, the unrectified averages are shown such that negative prestimulus, rectified EMG (67 0-74-3 p V. averages of voltage changes at the active electrode cause an upward deflection. Both sets ofaverages rectified EMG not shown). Bilateral dicks were used and (each of512 trials) were obtained with the same click duration and intensity (95 dB averages of 512 presentations madefrom recording above the reference intensity, see methods) and during tonic activation ofthe neck muscles. electrodes over the right sternomastoid. All components of The clicks were applied 20 ms after the beginning ofthe sweeps, at the time shown by the the averaged response become progressively larger as the arrows. In each subject the responses on the right and left sides were similar. The earliest intensity ofthe clicks is increased. The p44 potential is potential, a diphasic positive-negativity (pl3-n23), was present in both the subjects as well evident at the lowest intensity used (75 dB) but the as all the other nor7nal volunteers. In most subjects this wasfollowed by additional p13-n23 response only appears at the next highest intensity potentials (n34, p44), as shown for subject 1. (85 dB). 192 Colebatch, Halmagyi, Skuse J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.57.2.190 on 1 February 1994. Downloaded from Figure 3 Simultaneous averages ofrectified and Unrecttified 10 this early response was present in every sub- unrectified EMGfrom over ject. Additional potentials often followed the right sternomastoid ofa (n34, p44) and for any given subject, the normal volunteer evoked response recorded on the right and (n=512). Clicks were presented bilaterally 20 ms left sides to bilateral clicks had similar wave- after the onset ofthe traces. forms. The p1 3-n23 response was present As shown here, the evoked only with high intensity clicks and the thresh- responses were more clearly seen on the unrectified than .old varied from 75-85 dB between subjects the rectified average. The ied V (fig 2). The threshold for the later responses mean level ofrectified was below that for the p13-n23 response; as EMG was calculatedfrom low as 50 dB in one subject. the 20 ms before 100 presentation ofthe stimuli and in this example was Peak latencies 65 7 V (arrow). The Latencies on the right and left sides were not calibration bar applies to both traces. significantly different for any of the waveform 0 -.______, _,peaks, but, as noted earlier, only the p13 and 0 20 40 60 ms n23 potentials were present on both sides in all subjects. For the 10 subjects (20 sides) the mean latency of the first positivity (p13) was 13-3 (1-5) ms and that for the first negativity (n23) was 22-6 (2 4) ms. Six of the 10 sub- Figure 4 (A) Three jects had waveforms similar to that illustrated separate averages made A for subject 1 (fig 1), whereas in the remainder over the right Weak one or more of the later peaks was absent sternomastoid in one subject with bilateral clicks unilaterally or bilaterally. A second negativity of 95 dB intensity during (n34, present in 15 of the 20 sides) occurred weak, moderate, and Moderate at 33-8 (2.4) ms and was separated from the strong contractions ofthe neck flexors. The clicks were presented 20 ms after A0 ;Lv the average began, at the Clicks left ear position indicated by the R St-m stimulus artifact. The Strong l.Vjo mean level ofrectified EMG preceding the three trials was 41*3, 59-2 and 147 5 u Vrespectively. L St-m Size ofthe averaged 0 20 40 60 ms potentials was clearly related to the level oftonic ~~~~~~~~~~~~I muscle contraction during the collection period. (B) Clicks right ear (Same subject) peak to peak amplitude of the p13-n23 response to 95 dB clicks is plotted against the mean level ofprestimulus, c4 rectified EMGfor a total http://jnnp.bmj.com/ of 19 observations made at cv different levels oftonic 0.) muscle activation. In this and the other volunteers, Clicks right and left the relation between the amplitude of the evoked muscle potential and the 40 60 80 100 120 140 160 180 200 level oftonic EMG activity was linear. The points Mean EMG activity (RV) include the three on September 24, 2021 by guest. Protected copyright. observations shown in (A) (arrows, the leftmost by Yoshie and Okudaira"5 to distinguish them 0 representing the weakest from conventional, neurally generated evoked o- mean contraction level), Mean values are with SDs. averages made during potentials. given I I I maintained head rotation Amplitudes were measured either peak to 0 20 40 60 to either the left or right peak or, for a single peak, with reference to ms side and also during the mean level of activity in the 20 ms pre- Figure 5 Averaged responses to clicks of 95 dB intensity unilateral stimulation of ceding the clicks. applied to each ear in turn. Stimuli applied 20 ms after the ipsilateral (right) ear. each trace starts in aUl cases. Responsesfrom over the left sternomastoid (L St-m) are shown below thosefrom the right (R St-m) in each case. With stimulation ofthe left Results ear (top pair oftraces) the early response occurs only in the recording made over the ipsilateral muscle (L St-m). FINDINGS IN NORMAL VOLUNTEERS Similarly, stimulation of the right ear (middle pair) causes All the normal volunteers showed short an early positive-negative response only in the recording latency responses to 95 dB clicks given during made over the right sternomastoid (R St-m). All subjects tonic neck flexor activation 8-2 showed an ipsilateral dominancefor the origin ofpl3-n23, (onset latency indicating that this response is mediated by an ipsilaterally (0-6) ms (right), 8-2 (0 7) ms (left)). projecting pathway. Unilateral stimulation ofeach ear Presented bilaterally, these clicks evoked does, however, generate longer-latency responses on both averaged EMG changes on both the and sides, indicating that the afferents responsiblefor these later right potentials have bilateral reflex effects. Stimulation ofboth left sides, which always began with an initial ears simultaneously (bottom pair) results in p13-n23 positive-negative wave (pI3-n23: fig 1). Only responses on both sides, as well as laterpotentials. Myogenic potentials generated by a click-evoked vestibulocollic reflex 193 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.57.2.190 on 1 February 1994. Downloaded from n23 potential by a n inconstant positive going to press their forehead against the bar or by inflexion (present in 13 of the 20 sides) at a holding their head rotated to either the left or mean latency of 28B-6 (2 3) ms. A second pos- right side. As reported for the inion response, itivity (p44, preseint in 17 of the 20 sides) the amplitude of the averaged potentials after occurred at 43-7 (35-6) ms. clicks of a fixed intensity was dependent on the level of tonic muscle activation. In all Effect oftonic EMG activity subjects there was a linear relation between Bickford et al 8 rep orted that the amplitude of the amplitudes of the p13-n23 (and the p44) the potentials evolked by clicks at the inion peak of the evoked response and the mean was influenced by loading the neck muscles level of rectified EMG before the stimulus and thereby alterinig their tonic activation. In presentation (fig 4). In one subject only the the present study, averages of rectified EMG p13-n23 response seemed to saturate at the were collected prirnarily to quantify the level highest level of EMG: p13-n23 = 374 ,V, of tonic muscle acd tivation based on the mean mean rectified EMG = 224,uV, obtained with rectified value priu Dr to the stimulus (fig 3). a near maximal contraction. Values of the Changes in the avrerage rectified EMG after squared correlation coefficient for the linear the stimulus were always less pronounced fit between p1 3-n23 amplitude and mean rec- than for the simulttaneously acquired unrecti- tified EMG ranged from 0-81 to 0-99. fied average and gamplitudes for the evoked Two values define each linear regression: responses were me;asured from. the unrectified the intercept on the abscissa (the EMG averages. threshold for a response) and the gradient The level of toniic neck muscle EMG was (the gain of the evoked response). The EMG altered between trials by asking the subjects thresholds derived from the regression of p13-n23 amplitude against rectified EMG were 11 3,uV (right) and 11 6 uV (left) and R St-m did not differ significantly between the two

sides (t = -0.12). The gain of the response to

95 dB clicks varied from 0-38 to 3-26, was usually similar for both the right and left sides, and was greater than in all but 1S00rV unity one subject. The regression equation, once defined, can be used to predict the size of the L St-m_ 1 p13-n23 response for any given level of recti- fied EMG activity-that is, to generate a nor- malised response. For a mean rectified EMG activity of 60,uV, the normalised p1 3-n23 responses to 95 dB clicks varied between sub- jects from 18-3 to 137-1 pV (mean 88-8 0 20 40 60 ms 0 20 40 60 ms (right) and 81-8,uV (left)). -10 -10 , ...... 0 0 ......

10 10 . :...... Effect ofstimulus intensity ...... o 20 ...... 20 were (A All the normal subjects studied at three

. http://jnnp.bmj.com/ 30 '. 30 ...... to five different stimulus intensities above m 40 ., ., 40 . - . .5 50 ...... ~~...... so ...... threshold for their p1 3-n23 response, includ- 60 60 ing 100 dB clicks in five subjects. Each of the w 70 .> > > > > 70 runs was performed with a constant EMG 80 D 1...... 80 (

= 90 90 target to minimise changes in tonic activity. 100 100 The p13-n23 amplitude increased with 110 110 increasing stimulus intensity and on average 125 250 500 1000 2000 4000 8000 125 250 500 1000 2000 4000 8000 the p13-n23 response to 100 dB clicks was on September 24, 2021 by guest. Protected copyright. Frequecy, Hz Prequcy Hz 36% larger than that to 95 dB clicks (fig 2). The effect of suprathreshold click intensity seemed to be linear (intensity measured in 300C dB) with squared correlation coefficients 0-78 or greater in all but the right side of one sub- ject. Thresholds for the p13-n23 response 440C deduced from the intercept of this relation varied from 64 to 80 dB. p4NYVf~~~~~~~~~~~P~...... Laterality of responses Figure 6 Click-evoked vestibular potentials in response to 1OOdB monaural stimulation A clear difference between the origin of the in a 14-year-old boy with severe bilateral hearing loss and no vestibular symptoms. The left and right panels relate to the left and right ears. Top: there was an ipsilateral pl3-n23 early (p13-n23) response and of the later response to stimulating the left ear and the right ear individually (thick lines). Theefine potentials was seen after unilateral ear stimu- lines show the effect of bilateral clicks. Note that the patient was unable to hear the lation. With clicks applied to only one ear, stimulus when presented tO the right ear. Middle: audiograms show a greater than 100 dB the was on (ISO) sensorineural hearing loss in both ears. There was no response ('n-r') from the p13-n23 potential always larger patient to either (< and >) or air conduction (x and o) at maximal the ipsilateral side (fig 5). In several subjects outputfrom the stimulator. Bottom: caloric testing showed slightly reduced vestibular this ipsilateral predominance was complete responses from the left ear (53% left canal paresis) and normal responses from the right ear and there was no detectable crossed p13-n23 after stimulation with water at 30° and 44°C. Upward deflections indicate rightward eye movement, downward deflections indicate leftward eye movements. Calibration bars are response. On average, the ipsilateral p13-n23 10' and I s. response evoked by unilateral stimulation was 194 Colebatch, Halmagyi, Skuse J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.57.2.190 on 1 February 1994. Downloaded from 98% (91% for responses recorded on the Additionalfindings in normal subjects right side, 104% for responses recorded from In two subjects, control studies showed that the left) of that evoked by bilateral stimula- there was no response to unilateral clicks pre- tion, whereas the crossed response to unilat- sented when the external ear canal was eral ear stimulation was on average only 12% plugged and that the response returned com- of that evoked by bilateral ear stimulation pletely when a small hole was made in the (10% recorded right; 14% left). By contrast plug. The responses of one subject were pro- with this finding, the later potentials always foundly attenuated when tested during an occurred bilaterally even with unilateral stim- upper respiratory tract infection with sinusitis ulation, and the effects of bilateral stimula- but returned to normal on recovery. In tion were additive: thus the amplitude of the another subject a Valsalva manouevre per- p44 response evoked with unilateral ear stim- formed against an occluded nose also attenu- ulation was on average about half the size of ated the response (not illustrated). that recorded at the same site with bilateral stimuli (mean 55% of the bilateral response RECORDINGS FROM PATIENTS WITH LESIONS OF amplitude). THE INNER EAR Occasionally, the absence of a p13-n23 Selective sensorineural deafness response on the contralateral side with unilat- Three patients who were found to have pro- eral stimulation revealed the presence of a nounced sensorineural deafness in one or short latency negativity, starting slightly later both ears were studied. They had no symp- than the usual p13 potential. This seemed to toms or signs of vestibular disease and caloric habituate between trials and was not studied testing was normal. Pure tone audiograms in detail. showed perceptual thresholds higher than 80 dB (ISO) at all frequencies for each patient's most severely affected ear. All three patients had p13-n23 responses after stimulation of their affected ear (fig 6). R St-m Selective vestibular nerve section Five patients who had each undergone selec- tive surgical section of the vestibular nerve as treatment for intractable vertigo'6 were stud- 50 uV ied. One man was studied before and three L St-m months after selective nerve section (also reported by Colebatch and Halmagyi'4) and the four women had undergone the operation from one to seven years previously. None of 0 20 40 6( ms 0 20 40 60 ms the five had severe hearing loss in either ear. -10 -10 _ The findings in four of the patients were the 0 0O ...... same: the p13-n23 response was obtained 10 10 . .... L- from the ear innervated the intact 20 20 - ...... only by 30 30 - vestibular nerve (fig 7) although longer ...... e 40 40 - ...... latency potentials were still obtainable from http://jnnp.bmj.com/ .1 50 50 . a .~ ~ \.. the operated ear. The ipsilateral p1 3-n23 60 60 ...... 70 . 70 - response previously present was selectively 80 80 ...... abolished postoperatively in the man (the 90 90 . remaining woman, known to have otosclero- 100 100 ...... 110 110 sis, had no detectable p13-n23 after stimula- tion of either ear at 100 dB intensity). 125 250 500 1000 2000 4000 8000 12!5 250 500 1000 2000 4000 8000

Fequency. Hz Frquewc. Hz on September 24, 2021 by guest. Protected copyright. Discussion NATURE AND ORIGIN OF THE RESPONSE 300C These experiments have demonstrated that brief, intense clicks cause reproducible, short- latency alterations in EMG activity in the 440C ° anterior neck muscles of normal subjects. Faithful transmission of the clicks to the inner 00c ear was required: conductive hearing loss either from occlusion of the external ear or Figure 7 Click-evoked potentials in response to 100 dB monaural stimulation in a 35- due to alterations within the middle ear, year-old woman with a history ofintractable vertigo, who had undergone selective lekft attenuated or abolished the evoked responses. vestibular neurectomy two years previously. The lekft and right panels relate the left and right ears. Top: stimulation ofthe left ear evoked only late potentials whereas stimulation In normal volunteers the evoked response of the intact right ear evoked a pl3(*)-n23 response largest in the ipsilateral recording site comprised two distinct components. The (R St-m). The light tracing shows the effect of bilateral click stimuli recordedfrom the right first, a biphasic positive-negative wave (p13- side. Middle: audiograms show essentially normal hearing bilaterally, albeit with some trivial lowfrequency conductive loss and some loss at 8 kHz on the right (symbols as forfig n23), was generated predominantly by affer- 6). Bottom: caloric testing confirmed absent responses from the left ear after stimulation ents originating ipsilaterally and depended on with water at 300, 440, and 0°C. The 2°/s right beating nystagmus present during left ear the integrity of the labyrinth and the vestibu- stimulation is the usual permanent sequel oftotal unilateral vestibular deafferentiation.42 The caloric responses on the right are normal. Upward deflections indicate rightward eye lar division of the eighth nerve. This initial movements; calibration bars asforfig 6. response always had a high stimulus thresh- Myogenic potentials generated by a click-evoked vestibulocollic reflex 195 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.57.2.190 on 1 February 1994. Downloaded from old. The later components of the averaged CENTRAL PATHWAY OF THE VESTIBULAR response, not always present in normal sub- DEPENDENT RESPONSE jects, usually began with a negativity and The latency of the earliest responses recorded were generated by afferents originating from here implies a rapidly conducting, disynaptic both ears. These potentials were present pathway. The observed latency represents the when the cochlea and cochlear component of sum of the delays due to activation of recep- the eighth nerve alone were intact. This evi- tors, conduction to the brainstem, central dence indicates that the p1 3-n23 response conduction from the to the motor originates from afferents travelling within the nucleus of the sternomastoid muscle, and vestibular nerve whereas the later potentials peripheral conduction from the motor probably arise from cochlear afferents. Both nucleus to the muscle itself. In guinea pigs, a Ruhm et al 17 and Yoshie and Okudaira 5 pro- click-evoked volley in the inferior vestibular posed that both cochlear generated and nerve appears at a latency of less than 0 5 ms vestibular generated myogenic reflexes might (fig 2 of Didier and Cazals23) and electrical exist but implicitly assumed that at each spe- stimulation of the vestibular nerve in cats cific recording site, one or other mechanism evokes spike potentials in the axons entering was responsible. Our findings that both the brainstem at a mean latency of 0-66 ms.24 vestibular and cochlear generated effects The spectrum of vestibular nerve fibre diame- underlie the evoked response, if also true of ters is similar in monkeys and guinea pig,25 the effects of clicks on posterior neck mus- and, allowing for the greater conduction dis- cles, would largely resolve the apparent con- tance in humans, a peripheral conduction tradictory reports as to the origin of the inion delay to the brainstem of at least 1 ms seems response. appropriate. The fibres innervating the ster- Sound-evoked myogenic responses in cra- nomastoid muscle originate from the second nial muscles-the postauricular response'8 to the fifth cervical spinal segments and and the acoustic jaw reflex"-are well ascend through the foramen magnum and described. Both these reflexes seem to then leave the cranium through the jugular depend on cochlear afferents and are evoked foramen.' Brown et al 26 used magnetic stim- bilaterally after stimulation of one ear. ulation over the spinal roots, and estimated Indeed, this may be a general feature of all peripheral conduction delay to the sternomas- reflexes generated by cochlear afferents, as toid muscle to be 5-2 ms. Several subjects in auditory pathways in the brainstem are char- the present series had latencies to the onset of acterised by well developed commissural con- the p13 potential of 8 ms or less. With this nections at multiple levels.' The second part figure, only 1 8 ms remains for central con- of the averaged response described here was duction time. As nearly all primary vestibular distributed bilaterally and seems attributable afferents terminate in the vestibular nuclei,' to cochlear activation. This cochlear depen- central conduction time must include at least dent response might be thought to be related two synaptic delays-the second being at the to the startle reflex, a normal response to any level of the stemomastoid motor nucleus. If unexpected, intense stimulus. Physiological 0-6 ms is allowed for each synapse, the cen- startle to sound is characterised by rapid tral pathway cannot include more than these habituation, a prolonged refractory period, two synapses and the conduction delay of the and a much longer latency than the averaged vestibulocollic projection fibres must be of http://jnnp.bmj.com/ responses documented here'9 and thus is best the order of 0 5 ms. Taking the distance from regarded as a separate phenomenon. mid-pons to mid-C2 as 5 cm,27 a 0 5 ms con- The p13-n23 potential had characteristics duction delay implies that the second order that distinguish it from the later potentials neurons have a conduction velocity of about and seems to originate from activation of the 100 m/s. These features are consistent with ipsilateral labyrinth. In certain disorders previously reported characteristics of

affecting the middle and inner ear, vestibular vestibulospinal projections. Monosynaptic on September 24, 2021 by guest. Protected copyright. activation can occur with sound-the Tullio effects of vestibulospinal fibres, both excita- phenomenon.720 Vestibular stimulation by tory and inhibitory, are most powerful in neck sound is not confined solely to pathological motoneurons28 and most vestibulocollic neu- states but the intensities needed to excite the rons are monosynaptically excited from the normal vestibular apparatus are louder than ipsilateral labyrinth.29 The lateral vestibulo- normally encountered in everyday life. In spinal tract (LVST) originates predominantly monkeys, single unit recordings from the from the lateral (Deiter's) nucleus and pro- vestibular nerve have shown that saccular jects ipsilaterally. Second order neurons, afferents have the lowest threshold to acoustic monosynaptically excited from the ipsilateral stimulation (typically 106-110 dB SPL for vestibular nerve, are particularly common phase locking to low frequencies) an effect amongst ventral LVST neurons projecting to that is probably the result of direct excitation the neck and the modal conduction velocity of hair cells.2' Bek6sy22 reported that with of the LVST is 90 m/s.30 As saccular afferents continuous sound. in the range of 500-1000 terminate in the LVST,3" at least one poten- dynes/cm' (128-134 dB SPL or 83-89 dB tial pathway has been shown by which the relative to our reference), he could induce effects shown here could reach the sterno- sensations of movement and involuntary head mastoid nucleus. movements in humans. Finally, in guinea pigs, saccular afferents are excited by clicks CHANGES WITH THE LEVEL OF EMG ACTIVITY with the same duration and relative intensity The nature of the click stimulus allowed as those used here.23 study of the effects of tonic neck activation 196 Colebatch, Halmagyi, Skuse J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.57.2.190 on 1 February 1994. Downloaded from on the size of the reflex while keeping suited to modifying or fine tuning voluntary the afferent volley constant. Both the vestibu- motor commands directed to neck muscles. It lar dependent and cochlear dependent is also a simple new method of exploring a components increased linearly with increasing vestibulocollic pathway in intact humans. tonic muscle activation. This relation cannot JGC held a CJ Martin Fellowship from the National Health be due to changes in the discharge of cuta- and Medical Research Council of Australia. This study was neous pressure receptors excited by increas- also supported by a grant from the Clive and Vera Ramaciotti Foundations. We thank Professors JW Lance and D Burke for ing forehead pressure on the head restraint their helpful criticism. because it was also true when the head was free and held rotated (little habituation to the stimulus could have occurred during the course of the experiment, otherwise system- 1 Brodal A. Neurological anatomy. 3rd edn. New York: Oxford University Press, 1981. atic deviations from the linear relation would 2 Baloh RW, Honrubia V. Clinical neurophysiology of the have been apparent). The long-latency . Philadelphia: FA Davis, 1979:132. 3 Brandt T. Man in motion: historical and clinical aspects stretch reflex has the property of scaling in of vestibular function. Brain 1991;114:2159-74. size in proportion to the level of tonic muscle 4 Melvill Jones G, Watt DGD. Muscular control of landing from unexpected falls in man. J Physiol 1971;219: activity, a feature that is of particular impor- 729-37. tance for a reflex, the effectiveness of which 5 Greenwood R, Hopkins A. Muscle responses during sudden falls in man. JPhysiol 1976;254:507-18. must be matched to the voluntary task being 6 Watt DGD. Responses of cats to sudden falls: an otolith- undertaken.32 Although Marsden et al32 ini- originating reflex assisting landing. J Neurophysiol 1976; 39:257-65. tially postulated a supraspinal mechanism for 7 Dieterich M, Brandt Th, Fries W. Otolith function in this scaling, a similar relation has since been man. Brain 1989;112:1377-92. 8 Bickford RG, Jacobson JL, Cody DTR. Nature of shown for the segmental stretch reflex.3 Our averaged evoked potentials to sound and other stimuli finding that both the vestibular-dependent in man. Ann N YAcad Sci 1964;112:204-23. 9 Cody DTR, Bickford RG. Averaged evoked myogenic and cochlear-dependent components of the responses in normal man. Laryngoscope 1969;79:400-16. evoked response scale linearly with the level 10 Townsend GL, Cody DTR. The averaged inion response evoked by acoustic stimulation: its relation to the of tonic EMG suggests that the mechanism saccule. Ann Otol Rhinol Laryngol 197 1;80: 121-31. lies at the level common to both, the ster- 11 Meier-Ewert K, Gleitsmann K, Reiter F. Acoustic jaw reflex in man: its relationship to other brain-stem and nomastoid motor nucleus. Matthews34 has microreflexes. Electroencephalogr Clin Neurophysiol 1974; argued that scaling of both the excitatory and 36:629-37. 12 Cody DTR, Jacobson JL, Walker JC, Bickford RG. inhibitory effects of Ia afferent discharge is Averaged evoked myogenic potentials to sound in man. likely to be an intrinsic feature of the moto- Ann Otol Rhinol Laryngol 1964;80: 121-31. 13 Douek E. Auditory myogenic responses. In: Beagley HA, neuronal pool, given, inter alia, that the reflex ed. and audiological medicine. Oxford: Oxford effects are distributed throughout the University Press, 1981:769-80. 14 Colebatch JG, Halmagyi GM. Vestibular evoked poten- motoneuronal pool and that their nature does tials in human neck muscles before and after unilateral not alter between motoneurons of different vestibular deafferentation. Neurology 1992;42: 1635-6. 15 Yoshie N, Okudaira T. Myogenic evoked potential recruitment thresholds. Clearly, the condi- responses to clicks in man. Acta Otolaryngol (Stockh) tions necessary for such a relation are not 1969;252(suppl):89-103. 16 Silverstein H, Norell H, Rosenberg S. An evolution in unique to proprioceptive reflexes. approach in vestibular neurectomy. Otolaryngol Head Neck Surg 1990;102:374-81. 17 Ruhm H, Walker E, Flanigin H. Acoustically-evoked PHYSIOLOGICAL ROLE OF VESTIBULOCOLLIC potentials in man: mediation of early components. REFLEXES Laryngoscope 1967;77:806-22. 18 Kiang NY. Postauricular electric response to

acoustic http://jnnp.bmj.com/ Vestibulospinal influences contribute both to stimuli in humans. Q Prog Rep Res Lab Elec M I T 1963; the posture adopted by an organism and to 68:218-25. 19 Brown P, Rothwell JC, Thompson PD, Britton TC, Day maintenance of that posture despite perturba- BL, Marsden CD. New observations on the normal tions. This role is emphasised by the com- auditory startle reflex in man. Brain 1991;114: 1891-902. monly used definition of the (dynamic) 20 Ishizaki H, Pyykko I, Aalto H, Starck J. Tullio phenome- vestibulocollic reflex by its ability to stabilise non and postural stability: experimental study in normal subjects and patients with vertigo. Ann Otol Rhinol the position of the head in absolute space in Latyngol 1991;100:976-83. response to unpredictable displacements. 21 Young ED, Fernandez C, Goldberg JM. Responses of squirrel monkey vestibular neurons to audio-frequency on September 24, 2021 by guest. Protected copyright. Investigations of this property have confirmed sound and head vibration. Acta Otolaryngol (Stockh) a contribution from the vestibular apparatus 1977;84:352-60. 22 von Bekesy G. Uber akustische Reizung des Vestibu- in stabilising head position but one that has larapparates.Pffigers Arch 1935;236:59-76. modest gain and which is dependent on sub- 23 Didier A, Cazals Y. Acoustic responses recorded from the saccular bundle on the eighth nerve of the guinea pig. ject instruction or set.'5-'7 In addition to any Hear Res 1989;37: 123-8. such role, experimental evidence suggests 24 Precht W, Shimazu H. Functional connections of tonic andkinetic vestibular neurons with primary vestibular that vestibular influences may in part deter- afferents. JNeurophysiol 1965;28:1014-28. mine the posture of the head adopted both by 25 Gacek RR, Rasmussen GL. Fiber analysis of the stereo- acoustic nerve of guinea pig, cat, and monkey. Anat Rec animals and humans. Decerebrated animals 1961;139:455-63. tend to maintain their heads vertical indepen- 26 Brown P,Thompson PD, Rothwell JC, Day BL, Marsden CD. Axial myoclonus of propriospinal origin. Brain dent of the position of the rest of the body.'8 1991;114:197-214. Acute unilateral loss of vestibular input in 27 Koritke JG, Sick H. Atlas of sectional human anatomy. 2nd edn.Baltimore: Urban and Schwarzenberg, 1988:24-5. humans is associated with tonic lateral devia- 28 Wilson VJ, Yoshida M. Comparison of effects of stimula- tion of the head and eyes to the same side,'940 tion of Deiters' nucleus and medial longitudinal fascicu- lus on neck, forelimb, and hindlimb motoneurons. usually transient, but occasionally followed by J'Neurophysiol 1969;32:743-58. permanent abnormalities of head posture.4' 29 RapoportS, Susswein A, Uchino Y, Wilson VJ. Properties of vestibular neurones projecting to neck segments of The vestibulocollic reflex demonstrated in the the cat spinal cord. JPhysiol 1977;268:493-510. present experiments occurs at short latency 30 Wilson VJ, Peterson BW (1981) Vestibulospinal and reticulospinal systems. In: Brooks VB, ed. Handbook of and has an amplitude that scales with the physiology, section 1: motor control. Bethesda, MD: mean level of EMG activity. It is thus well American Physiological Society, 1981;2:667-702. Myogenic potentials generated by a click-evoked vestibulocolltic reflex 197 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.57.2.190 on 1 February 1994. Downloaded from 31 Didier A, Cazals Y, Aurousseau C. Brainstem connections 37 Bronstein AM. Evidence for a vestibular input contribut- of the anterior and posterior parts of the saccule of the ing to dynamic head stabilization in man. Acta guinea pig. Acta Otolaryngol (Stockh) 1987;104:385-91. Otolaryngol (Stockh) 1988;105:1-6. 32 Marsden CD, Merton PA, Morton HB. Servo action in 38 Gernandt BE. Vestibular mechanisms. In: Magoun HW, the human thumb. JPhysiol 1976;257:1-44. ed. Handbook of physiology, section 1: neurophysiology. 33 Marsden CD, Rothwell JC, Day BL. Long-latency auto- Washington: American Physiological Society 1959;1: matic responses to muscle stretch in man: origin and 549-64. function. Adv Neurol 1983;39:509-39. 39 Holmes G. Introduction to dinical neurology. Edinburgh: 34 Matthews PBC. Observations on the automatic compen- Livingstone, 1952:139-40. sation of reflex gain on varying the pre-existing level of 40 Halmagyi GM, Curthoys IS, Brandt T, Dieterich M. motor discharge in man. Y Physiol 1986;374:73-90. Ocular tilt reaction: clinical sign of vestibular lesion. 35 Guitton D, Kearney RE, Werely N, Peterson BW. Visual, Acta Otolaryngol (Stockh) 1991;481(suppl):47-50. vestibular and voluntary contributions to human head 41 Bronstein AM, Rudge P. The vestibular system in abnor- stabilization. Exp Brain Res 1986;64:59-69. mal head postures and spasmodic torticollis. Adv Neurol 36 Gresty M (1987) Stability of the head: studies in 1988;50:493-500. normal subjects and in patients with labyrinthine 42 Smith PF, Curthoys IS. Mechanisms of recovery following disease, head tremor, and dystonia. Mov Disord 1987; unilateral labyrinthectomy: a review. Brain Res Rev 2:165-85. 1989;14:155-80.

Von Monakow and Diaschisis dynamic disorders in the whole cortex becomes indis- pensable. For much of the 19th century, clinical localisation The verification of Von Monakow's postulates has rested on the belief that geometric localisation pro- been achieved by oxygen and glucose uptake studies, duced signs dependent on functions derived from that and by disordered blood flow and electrophysiology in focal area. In 1967 Geschwind's "disconnection syn- distant sites. dromes" highlighted the phenomenology of dysfunc- The syndrome of anterior choroidal thrombosis tion at a distance. Geschwind's notions, now causing contralateral hemiplegia, hemianaesthesia, accepted, hark back to the work of Constantin Von and hemianopia is referred to as Von Monakow's syn- Monakow (1853-1930).' He introduced the word drome. He also wrote extensively on the cortex, "diaschisis" to indicate loss of function and signs, microcephaly, anencephaly, and aneurysm of the ver- anatomically removed from the lesion-the equivalent tebral artery. of Geschwind's disconnection. Von Gudden had Bom the son of a Russian nobleman, his family fled shown him atrophy of the superior colliculus in a rab- the Franco-Prussian war, settling in Dresden, then bit after removal of the contralateral eye at birth. In Paris, and Zurich where they were naturalised in 1879 he removed the occipital lobes in two newbom 1869. A huge, bearded figure with a shrill voice, he rabbits and one year later noticed complete degenera- was noted, in youth, for his boisterous, eccentric tion of the lateral geniculate nuclei. behaviour. Later, he eschewed faculty meetings, and Von Monakow described diaschisis cortico-spinalis- was devoted to his family and books. His famous impaired function of spinal motor neurons due to cor- Gehirnpathologie contained over 3000 references that tical motor lesions; diaschisis associativa-cortical he had collected personally. In later life he published dysfunction due to lesions of connected areas within three lectures, entitled: Emotions, morality and the http://jnnp.bmj.com/ one hemisphere, and diaschisis commisuralis-cortical brain. He died of "retention-uraemia" aged 77 while dysfunction due to lesions of the interconnected con- writing on "The value of life". tralateral hemisphere. JMS PEARCE He refuted the purist's notions of localisation: 304 Beverley Road, Anlaby, HuUl The generally accepted theory according to which HUIO 7BG aphasia, agnosia, apraxia etc. are due to destruction of narrowly circumscribed appropriate praxia, gnosia, and phasia centres, must be finally dis- 1 Von Monakow C. Die lokalisation im Grosshirn und der

Abbau der Funktion durch kortikale Herde. Wiesbaden: on September 24, 2021 by guest. Protected copyright. carded on the basis of more recent clinical and Bergmann 1914. Transl. G Harris In: Pribam KH, ed. anatomical studies. It is just in the case of these Brain and Behavior I: Mood States and Mind. focal symptoms that the concept of complicated Baltimore: Penguin 1969:27-36.