Brain (1991), 114, 1891-1902
NEW OBSERVATIONS ON THE NORMAL AUDITORY STARTLE REFLEX IN MAN by P. BROWN, J. C. ROTHWELL, P. D. THOMPSON, T. C. BRITTON, B. L. DAY and C. D. MARSDEN (From the MRC Human Movement and Balance Unit, and University Department of Clinical Neurology, Institute of Neurology, London) SUMMARY
INTRODUCTION
Previous studies on the normal startle response in man have considered the first event in the auditory startle reflex to be the blink (Landis and Hunt, 1939; Suhren et al., 1966; Gogan, 1970; Fox, 1978; Wilkins et al., 1986). We present evidence that the initial activity in orbicularis oculi is an auditory blink reflex, and not part of the subsequent true startle response. Previous investigations also have given insufficient information on the distribution and latency of the true startle response in different muscles to deduce its site of origin and the characteristics of its efferent pathways (Jones and Kennedy, 1951; Suhren etai, 1966; Rossignol, 1975; Wilkins et al., 1986). We define the EMG pattern of the normal auditory startle response in man; it has a quite distinct timing and distribution in different muscles. The activity responsible for the startle response originates in the caudal brainstem and is conducted up the brainstem and down the spinal cord by a relatively slowly conducting efferent pathway. METHODS The startle reaction was recorded in 12 healthy subjects (mean age 37.1 yrs, range 18 — 80 yrs) following their informed consent. Auditory stimuli were presented randomly about once every 20 min, while the subject sat relaxed in a chair. The stimulus was a standardized auditory tone burst of 1000 Hz frequency, Correspondence to: Professor C. D. Marsden, University Department of Clinical Neurology, Institute of Neurology, Queen Square, London, WC1N 3BG, UK. © Oxford University Press 1991
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The latency and pattern of muscle recruitment in the startle response elicited by unexpected auditory stimulation was determined in 12 healthy subjects. Reflex EMG activity was recorded first in orbicularis oculi. This was of similar latency to the normal auditory blink reflex and, unlike the generalized startle response, persisted despite the frequent presentation of the test stimulus. It is argued that this early latency activity in orbicularis oculi represents a normal auditory blink reflex and is not part of the generalized auditory startle reflex. With the exception of this early latency activity in orbicularis oculi, the relative latencies of both cranial and distal muscles in the auditory startle response increased with the distance of their respective segmental innervations from the caudal brainstem. Thus the earliest EMG activity was recorded in sternocleidomastoid. The recruitment of caudal muscles was relatively slow and the latencies of the intrinsic hand muscles were disproportionately long. The pattern of recruitment of cranial muscles suggests a brainstem origin for the normal startle response. Studies on the auditory startle reflex in animals are reviewed in the light of this finding.
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50 ms duration and 124 dB presented binaurally through earphones. (The intensity of the stimulus used exceeded safety standards for continuous acoustic stimulation, and the authors would recommend caution in the use of similar stimulus intensities in future experimentation.) Electromyographic (EMG) recordings were made using bipolar silver/silver chloride electrodes placed 2 cm apart longitudinally over the muscle bellies. Records were collected as single sweeps triggered at the start of the auditory stimulus. The sampling rate was 1500 Hz per channel. The latency to onset of reflex EMG activity was measured by visual inspection of single trials on a computer display. The latency of the initial voltage sustained above the background level of EMG activity was taken to be the start of reflex EMG activity. The latency and duration of the auditory blink reflex to the same stimulus was also investigated. For this, auditory stimuli were presented randomly about every minute, and the responses to the first 5 stimuli were discarded to avoid recording a startle response. Medians and ranges were recorded. Statistical analysis was performed using the Mann-Whitney U test for unpaired data and Wilcoxon signed-ranks test for paired data. RESULTS
TABLE I. THE LATENCY TO ONSET OF EMG ACTIVITY IN THE NORMAL STARTLE RESPONSE TO SOUND* Range (ms) Muscle R orbicularis oculi R R R L R R R R R R R R
masseter stemoclcidomastoid C4 paraspinal muscles biceps biceps triceps forearm extensors forearm flexors APB FD1 ADM rectus abdominis
Median 36.7
Lowest 25.0
Highest 69.0
n 70
59.0 58.3 60.2 68.9 76.2 71.0 73.2 81.9 98.6 98.8 95.9 82.3
39.4 40.4 47.9 59.8 67.0 53.2 61.9 60.1 74.5 71.7 76.3 76.6
122.2 136.0 120.0 91.7 146.5 147.8 172.8 199.9 178.9 175.5 104.0 98.8
29 53 23 10 21 12 24 27 26 26 6 11
* The startle responses were elicited in 12 healthy sitting subjects by a 1000 Hz 124 dB tone of 50 ms duration delivered to both ears randomly, up to 3 times an hour. Muscle activity was approximately synchronous bilaterally. EMG activity was recorded in masseter significantly later (P < 0.001, Wilcoxon signed-ranks test) than in stemocleidomastoid. The latencies of the intrinsic hand muscles were disproportionately long. Activity in tibialis anterior (110.7 ms, range 103.5— 122.0 ms, n = 6) and in soleus (120.8 ms range 105.5— 122.0 ms, n = 5) was only present in 1 subject. Abbreviations: right (R) and left (L) abductor pollicis brevis (APB), first dorsal interosseous (FDI) and abductor digiti minimi (ADM).
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The most generalized startle response to the standard sound stimulus employed consisted of eye closure, grimacing, neck flexion, trunk flexion, slight abduction of the arms, flexion of the elbows and pronation of the forearms. There was considerable variation in the degree to which this response was expressed, and in some subjects only eye closure and flexion of the neck was apparent. There was also considerable variation in the latency to onset of the EMG activity in individual muscles during the startle response (Table 1). However, although the range of latencies was wide, most responses occurred with early latencies. The variation in
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the latency of EMG activity in sternocleidomastoid is shown in fig. 1. The latencies of other muscles showed similar skewed distributions. Despite the variation in latency, the overall pattern of the response to sound was distinctive. A blink reflex was always seen, regardless of the presence of a more generalized startle response. The latency to onset of this blink reflex (median 36.7 ms, range 25—69 ms) was much shorter than that of the startle response in sternocleidomastoid (58.3 ms, range 40.4-136 ms). The blink reflex persisted despite the repetition of the auditory stimulus every minute. In contrast, the startle response habituated within 2 to 6 trials, despite the random presentation of the stimulus about every 20 min. 35 30 25 20 15 10 5 0
50
100
150
200
Latency to onset of sternocleidomastoid EMG response (ms) FIG. 1. The latencies to onset of EMG activity in the sternoclerdomastoid muscle in individual auditory startle responses (n = 53) in normal subjects (n = 12).
The auditory blink reflex could be studied in isolation, in the absence of a startle response, by delivering the standard sound stimulus every minute (fig. 2A). Under these conditions the latency of the reflex response in orbicularis oculi (median 32.3 ms, range 19.3-68.6 ms, n = 60) was similar to that seen in the auditory startle response, but the duration of the auditory blink reflex was brief (range 63.3-149.2 ms, n = 72). In the presence of a startle response, the duration of the EMG activity in orbicularis oculi was much longer and more variable (range 108 to over 400 ms, n = 70). In 36% of such trials two distinct components were visible in the response of orbicularis oculi (fig. 2B). The earliest EMG activity recorded after the normal auditory blink reflex was in sternocleidomastoid (Table 1). This was the most consistently recorded feature of the startle response and was usually the last component to habituate. In 4 out of the 12 subjects it was the only feature of the startle response, other than a blink, to be recorded under the experimental conditions used. When a more generalized startle response was recorded (Table 1) the EMG activity in masseter started later than in sternocleidomastoid. The difference between the median latencies to onset of EMG activity in sternocleidomastoid and masseter was 0.7 ms (P < 0.001, Wilcoxon signed-ranks test), when all trials were averaged. However, the median difference in latency to onset of EMG activity between sternocleidomastoid
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0
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Orbicularis oculi
Orbicularis oculi
FIG. 2. A, average of 5 auditory blink reflexes (marked by dotted line) recorded in the same normal subject to a 124 dB tone of 50 ms duration, delivered randomly about every 60 s. B, average of 5 startle responses recorded in the same normal subject to an unexpected 124 dB tone of 50 ms duration, delivered randomly about every 20 min. Two components may be distinguished in orbicularis oculi. The first is a normal latency auditory blink reflex (marked by dotted line). The second component consists of EMG activity attributable to the true startle response and can be seen to follow EMG activity in sternocleidomastoid. Rectified EMG records are shown. The horizontal and vertical calibration lines represent 50 ms and 0.1 mV, respectively.
and masseter measured in those single trials in which EMG activity was evident in both muscles, was 3.6 ms (range —4.0—15.2 ms, n = 30). In the startle responses of 1 subject, the latency of EMG activity in mentalis (51.0 ms, range 48 — 53.5 ms) was compared with that in masseter (56.9 ms, range 51.5—62.4 ms), and sternocleidomastoid (43.6 ms, range 38.6—45 ms, n = 7 for each muscle). The EMG activity in mentalis followed that in sternocleidomastoid significantly later (P = 0.01, paired Wilcoxon signed-ranks test), but preceded that in masseter {P = 0.01). Thus the latency of EMG activity in the cranial muscles (with the exception of orbicularis oculi, where an auditory blink reflex was recorded at 29.7 ms, range 22.8 — 32.7 ms, n = 7) increased with the distance of their segmental innervations from the lower brainstem (fig. 3). The latencies of trunk and limb muscles in the auditory startle response also increased with the distance of their respective segmental innervations from the caudal brainstem
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Sternocleidomastoid
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Masseter
Orbicularis oculi
Mentalis
FIG. 3. Unrectified EMG record of a single startle response recorded in a normal individual. A 124 dB tone of 50 ms duration was delivered to both ears at the start of the trace. Excluding the auditory blink reflex, the first EMG activity is recorded in stemocleidomastoid and is followed later by mentalis then masseter. The horizontal and vertical calibration lines represent 50 ms and 0.5 mV, respectively.
(fig. 4, Table 1). Proximal arm muscles were activated before those of the hand. The cervical paraspinal muscles were activated before the abdominal recti. Responses in the legs were seen in only 1 of 12 subjects, and were at longer latency than those of the arms. No EMG activity was recorded in the intrinsic foot muscles of this or any other subject. The difference in latency to onset of EMG activity between stemocleidomastoid and rectus abdominis was relatively long (24.0 ms). A distinctive feature of the pattern of muscle activation in the normal startle response to sound was the disproportionately long latencies of the intrinsic hand muscles (fig. 4, Table 2). The EMG activity in abductor pollicis brevis and first dorsal interosseous occurred 25.4 ms (P < 0.001) and 25.6 ms (P < 0.001) after that in the forearm extensors. DISCUSSION
The normal startle response to a standardized auditory stimulus was determined in 12 healthy subjects. The general pattern of the response was consistent with previous
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Stemocleidomastoid
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Masseter Orbicularis oculi
Stemocleidomastoid
Forearm extensors
Forearm flexors ~_-
Abductor pollicis brevis
Rectus abdominis
FIG. 4. Rectified EMG record of a single startle response recorded in a healthy individual. A 124 dB tone of 50 ms duration was delivered to both ears at the start of the trace. Excluding the auditory blink reflex, the first EMG activity is recorded in stemocleidomastoid and followed later by masseter. There is a disproportionately long latency to abductor pollicis brevis and the first dorsal interosseous. The horizontal and vertical calibration lines represent 50 ms and 0.5 mV, respectively.
reports. Thus the startle reflex consisted of a generalized flexion response (Landis and Hunt, 1939; Wilkins et al., 1986), although EMG activity was recorded in both flexor and extensor muscles. The startle reaction was most prominent around the face, neck and shoulders, and less marked in the lower half of the body (Strauss, 1929). The minimum response, beyond a blink of the eyes, was activity in stemocleidomastoid (Jones and Kennedy, 1951). The latter was often the last component of the generalized startle reflex to disappear with repeated presentation of the stimulus (Jones and Kennedy, 1951). This habituation of the response was rapid, usually occurring within 2 to 6 trials, although the blink reflex persisted (Landis and Hunt, 1939; Wilkins et al., 1986). Previous reports have stressed that the latency of the normal startle response is relatively long and very variable (Landis and Hunt, 1939; Wilkins et al., 1986). Most authors, however, report either the range (Wilkins et al., 1986), or the mean of reflex latencies (Landis and Hunt, 1939; Suhren et al, 1966; Rossignol, 1975). We found that the latencies to onset of any given muscle in the startle reflex were not normally distributed.
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First dorsal interosseous
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TABLE 2. A COMPARISON OF THE EFFERENT PATHWAYS SUBSERVING THE NORMAL AUDITORY STARTLE REFLEX WITH CORTICOBULBAR AND PYRAMIDAL PATHWAYS IN MAN*
Excess latency of masseter over SCM
Auditory startle reflex 0.7 ms
Magnetic stimulation of motor cortex - 2 . 9 ms (masseter precedes SCM)
Excess latency of RA over SCM
24.0 ms
8.0 ms
Excess latency of APB over biceps
22.4 ms
10.5 ms
* The differences in the latencies to onset of EMG activity between individual muscles in the normal auditory startle reflex are calculated from the median latencies given in Table 1. The differences in the latency to onset of EMG activity between masseter and sternocleidomastoid (SCM), sternocleidomastoid and rectus abdominis (RA), and between biceps and abductor pollicis brevis (APB), following magnetic stimulation of the motor cortex, are calculated from the mean latencies reported by Cruccu el al. (1989) and Thompson (1991) in normal subjects. The pattern of recruitment of cranial nerves seen following magnetic stimulation of the motor cortex is reversed in the normal auditory startle reflex. The differences in latency to onset of EMG activity between sternocleidomastoid and rectus abdominis, and between biceps and abductor pollicis brevis, is longer in the auditory startle reflex than following magnetic stimulation of the motor cortex.
The distinction between the auditory blink reflex and the startle response in orbicularis oculi The presence of a short latency blink reflex of brief duration to auditory stimulation in normal subjects has been established (Rushworth, 1962). Lesioning experiments suggest that a central circuit involving the inferior colliculus and the midbrain reticular formation underlies this auditory blink reflex (Hori et al., 1986). Projections between the midbrain reticular formation and the facial nucleus exist (Hinrichsen and Watson, 1983). This mesencephalic circuit for the auditory blink reflex is in contrast to the bulbopontine origin proposed for the auditory startle response (Szabo" and Hazafi, 1965; Davis et al., 1982). The auditory blink reflex has been considered to be an integral part of the normal startle response (Landis and Hunt, 1939; Suhren etal., 1966; Gogan, 1970; Fox, 1978; Wilkins et al., 1986). However, the auditory blink reflex may be seen without any other manifestation of the startle response and, unlike the normal startle response, it does not readily habituate. Reflex EMG activity in muscles other than orbicularis oculi was no longer recorded after 2 to 6 repetitions of the auditory stimulus every 20 min. In contrast, reflex EMG activity was recorded in orbicularis oculi with repetition of the same auditory stimulus every minute. The amplitude of the auditory blink reflex does habituate with briefer interstimulus intervals (Fox, 1978).
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Although the range of latencies was large, most responses were of short latency. Calculation of the mean latency of an individual muscle is therefore inappropriate and misleading (calculation of the mean latency to onset of EMG activity in sternocleidomastoid from the present results gives a value 5.1 ms in excess of the median).
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When seen in the context of a startle response the latency of the blink reflex is much shorter than the latency of onset of EMG activity in other cranial muscles. In 1 subject, the latency of mentalis in the startle response was determined. This muscle has a similar innervation and peripheral efferent conduction time to orbicularis oculi (M0ller and Jannetta, 1986; Benecke et al., 1988). The EMG startle activity in mentalis was recorded about 21 ms after the blink reflex in orbicularis oculi in the auditory startle response. When a true startle response is elicited by unexpected auditory stimulation, the duration of the EMG activity in orbicularis oculi is much longer, and it is sometimes possible to distinguish two separate components in the EMG response in orbicularis oculi. It is therefore suggested that the early latency auditory blink reflex is physiologically separate from the generalized startle response. In contrast, the true startle response in orbicularis oculi is of longer latency and is often seen grafted on to the end of the normal auditory blink reflex. The EMG response in orbicularis oculi may also show two components in the pathological auditory startle response (Colebatch et al., 1990; Brown et al., 1991).
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Efferent pathways of the normal auditory startle reflex in man The earliest recorded EMG activity in the true generalized startle response was in sternocleidomastoid (innervated by the eleventh cranial nerve). EMG activity in masseter (innervated by the fifth cranial nerve) occurred significantly later {see Table 2). This is the reverse of the rostrocaudal pattern of activation of cranial nerve innervated muscles seen in cortical reflex myoclonus (Hallett et al., 1979). Similarly, with magnetic stimulation of the motor cortex, activity in masseter occurs about 2.9 ms before that in sternocleidomastoid (Cruccu etal., 1989; Thompson, 1991). The latency of the true startle response in orbicularis oculi (innervated by the seventh cranial nerve) was difficult to define exactly as its onset was usually obscured by EMG activity attributable to the normal auditory blink reflex. EMG activity in mentalis, however, (also innervated by the seventh cranial nerve) occurred significantly later than that in sternocleidomastoid and before that in masseter. Given the approximately similar peripheral efferent conduction delays to masseter, orbicularis oculi, mentalis and sternocleidomastoid (M0ller and Jannetta, 1986; Benecke et al., 1988), the overall pattern of muscle recruitment in the physiological startle response to auditory stimulation suggests that in man, as in animals, the auditory startle response originates in the caudal brainstem, with propagation rostrally to the seventh then fifth cranial nerve nuclei. A similar pattern of activation of cranial nerve innervated muscles is seen in reticular reflex myoclonus, where myoclonic activity is propagated rostrally from a myoclonic generator in the caudal brainstem (Hallett et al., 1977). The latencies of the startle response in trunk and limb muscles also increase with the distance of their segmental innervation from the caudal brainstem. The proximal arm muscles were activated before those of the hand, and the cervical paraspinal muscles were activated before the abdominal recti. Responses in the legs were seen in only 1 of 12 subjects (when sitting relaxed) and were at longer latency than those of the arms. The difference in latency of onset of EMG activity between sternocleidomastoid and rectus abdominis (24.0 ms) is about 16 ms longer than the difference in latency between these muscles when they are activated by magnetic stimulation of the motor cortex (Table 2). This suggests that the conduction velocity in the spinal efferent pathways utilized by the normal startle response is relatively slow. The latency to onset of EMG
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activity in the intrinsic hand muscles is disproportionately long (Table 2), even when allowance is made for the slowness of conduction in spinal efferent pathways. The slowness of the spinal efferent pathways and the disproportionate latencies of the intrinsic hand muscles distinguishes the normal auditory startle reflex from cortical and brainstem reflex myoclonus (Hallett et al., 1977, 1979). In summary, the electrophysiological evidence suggests that the physiological auditory startle reflex in man is mediated by an efferent system with its origin in the caudal brainstem. The spinal projections of this system are relatively slowly conducting and distributed predominantly to axial muscles. The pattern of muscle recruitment in the normal auditory startle is then determined by the distance of each segmental level from the caudal brainstem, with two exceptions. First, an auditory blink reflex precedes the auditory startle reflex in orbicularis oculi. Secondly, the latencies of the intrinsic hand muscles are disproportionately delayed (Table 2), suggesting that the pathways responsible for activation of these muscles differ, at least in part, from those underlying the rest of the startle reflex. An alternative hypothesis is that the relative latencies of the many muscles involved in the startle reflex represent activity in multiple central circuits with differing central processing times.
The present results suggest that the system subserving the motor limb of the startle reflex in man originates, as in animals, in the caudal brainstem. The observation that the startle reflex exists in anencephalic infants (Edinger and Fisher, 1913) would support this hypothesis. The descending spinal efferent pathways in the normal auditory startle reflex in man are slowly conducting and this might suggest the involvement of pathways
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The physiology of the normal startle response Studies in animals also suggest that the startle response originates in the caudal brainstem. The short latency startle responses to sound persist after decerebration (Forbes and Sherrington, 1914; Szab6 and Hazafi, 1965). Lesioning experiments in the rat have implicated the medial bulbopontine reticular formation (Szabd and Hazafi, 1965), particularly the nucleus reticularis pontis caudalis (Hammond, 1973; Leitner et al., 1980; Davis et al., 1982) as the primary centre subserving the acoustic startle reflex. Electrical stimulation of the nucleus reticularis pontis caudalis (Davis et al., 1982; Yeomans et al., 1989), but not the nucleus reticularis gigantocellularis (Davis etal., 1982), elicits short latency startle-like responses in the rat. In the cat the area of the medial reticular formation involved in the auditory startle reflex may extend more caudally, into the medulla (Wright and Barnes, 1972; Wu et al., 1988). If the medial pontomedullary reticular formation is the primary centre subserving the acoustic startle reflex, then the efferent limb of the reflex may be provided by the bulbobulbar (Scheibel and Scheibel, 1958) and reticulospinal (Torvik and Brodal, 1957) pathways originating in this area. In particular, Shimamura and Livingston (1963) have identified a spinobulbospinal reflex system relayed in the medial medullary reticular formation in cats, the efferent limb of which is formed by moderately slowly conducting descending spinal pathways. This efferent system may also form the basis of the chloralose jerk (Shimamura and Yamauchi, 1967) and the audiospinal reflex responses recorded in decerebrate and chloralose anaesthetized cats (Wright and Barnes, 1972). The spinobulbospinal reflex has also been identified in dogs and monkeys (Shimamura et al., 1964) and, tentatively, in man (Shimamura et al., 1964; Meier-Ewert et al., 1972; Shimamura, 1973).
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ACKNOWLEDGEMENT We thank Mr R. Bedlington for his technical assistance. REFERENCES ANDERSEN RA, ROTH GL, AITKIN LM, MERZENICH MM (1980a) The efferent projections of the central
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similar to the efferent limb of the spinobulbospinal reflex. The study of patients with abnormal startle responses to both somaesthetic and auditory stimuli has provided further evidence linking the startle reflex to the spinobulbospinal reflex (Brown et al., 1991). Both the pattern of muscle recruitment in man and studies in animals therefore suggest that the system subserving the motor limb of the auditory startle reflex originates in the bulbopontine brainstem in man, possibly in the medial reticular formation. This system may be activated by auditory afferent inputs at the subcortical level as suggested by animal experiments, either directly from the lateral lemniscus (Davis et al., 1982) or via the inferior colliculus (Wright and Barnes, 1972). Alternatively, the afferent limb of the startle reflex may involve a cortical relay. Several authors have reported a lack of an overt startle response to unexpected sounds in patients with bitemporal cortical damage (Woods et al, 1984; Ho et al., 1987). In addition, Liegeois-Chauvel et al. (1989) reported that the facilitation of the spinal monosynaptic reflex by auditory stimulation, considered to be related to the startle reaction, is selectively depressed by lesions of the caudal part of the superior temporal gyrus. It is most likely that die auditory cortex acts to facilitate subcortical reflex loops (Ascher et al., 1963). In the chloralose anaesthetized cat strychnization of the primary auditory cortex facilitates the generalized reflex response to sound, but complete bilateral neodecortication does not abolish the reflex response (Ascher et al., 1963). Such cortical facilitation could involve corticopontine tracts (Brodal, 1969) or the projection from the auditory cortex to the inferior colliculus (Andersen et al., 1980a, b). In conclusion, it is suggested that the motor response in the normal auditory startle response in man is organized in the caudal brainstem, probably in the medial reticular formation. This site may be activated by subcortically or cortically relayed afferent inputs, or by a combination of these influences.
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SUHREN O, BRUYN GW, TUYNMAN JA (1966) Hyperekplexia: a hereditary startle syndrome. Journal of the Neurological Sciences, 3, 577—605. SZABO I, HAZAFI K (1965) Elicitability of the acoustic startle reaction after brain stem lesions. Acta Physiologica Academiae Scientiarum Hungaricae, 27, 155—165. THOMPSON PD (1991) Motor Cortex Stimulation in Man. PhD thesis, University of London. TORVIK A, BRODAL A (1957) The origin of reticulospinal fibers in the cat: an experimental study. Anatomical Record, 128, 113-137. WILKINS DE, HALLETT M, WESS MM (1986) Audiogenic startle reflex of man and its relationship to startle syndromes: a review. Brain, 109, 561—573. WOODS DL, KNIGHT RT, NEVILLE HJ (1984) BitemporaJ lesions dissociate auditory evoked potentials and perception. Electroencephalography and Clinical Neurophysiology, 57, 208—220. WRIGHT CG, BARNES CD (1972) Audio-spinal reflex responses in decerebrate and chloralose anesthetized cats. Brain Research, Amsterdam, 36, 307—331. Wu M-F, SUZUKI SS, SIEGEL JM (1988) Anatomical distribution and response patterns of reticular neurons active in relation to acoustic startle. Brain Research, Amsterdam, 457, 399—406. YEOMANS JS, ROSEN JB, BARBEAU J, DAVIS M (1989) Double-pulse stimulation of startle-like responses
in rats: refractory periods and temporal summation. Brain Research, Amsterdam, 486, 147-158. (Received May 11, 1990. Revised July 26, 1990. Accepted December 18, 1990)
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NEW OBSERVATIONS ON THE NORMAL AUDITORY STARTLE REFLEX IN MAN by P. BROWN, J. C. ROTHWELL, P. D. THOMPSON, T. C. BRITTON, B. L. DAY and C. D. MARSDEN (From the MRC Human Movement and Balance Unit, and University Department of Clinical Neurology, Institute of Neurology, London) SUMMARY
INTRODUCTION
Previous studies on the normal startle response in man have considered the first event in the auditory startle reflex to be the blink (Landis and Hunt, 1939; Suhren et al., 1966; Gogan, 1970; Fox, 1978; Wilkins et al., 1986). We present evidence that the initial activity in orbicularis oculi is an auditory blink reflex, and not part of the subsequent true startle response. Previous investigations also have given insufficient information on the distribution and latency of the true startle response in different muscles to deduce its site of origin and the characteristics of its efferent pathways (Jones and Kennedy, 1951; Suhren etai, 1966; Rossignol, 1975; Wilkins et al., 1986). We define the EMG pattern of the normal auditory startle response in man; it has a quite distinct timing and distribution in different muscles. The activity responsible for the startle response originates in the caudal brainstem and is conducted up the brainstem and down the spinal cord by a relatively slowly conducting efferent pathway. METHODS The startle reaction was recorded in 12 healthy subjects (mean age 37.1 yrs, range 18 — 80 yrs) following their informed consent. Auditory stimuli were presented randomly about once every 20 min, while the subject sat relaxed in a chair. The stimulus was a standardized auditory tone burst of 1000 Hz frequency, Correspondence to: Professor C. D. Marsden, University Department of Clinical Neurology, Institute of Neurology, Queen Square, London, WC1N 3BG, UK. © Oxford University Press 1991
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The latency and pattern of muscle recruitment in the startle response elicited by unexpected auditory stimulation was determined in 12 healthy subjects. Reflex EMG activity was recorded first in orbicularis oculi. This was of similar latency to the normal auditory blink reflex and, unlike the generalized startle response, persisted despite the frequent presentation of the test stimulus. It is argued that this early latency activity in orbicularis oculi represents a normal auditory blink reflex and is not part of the generalized auditory startle reflex. With the exception of this early latency activity in orbicularis oculi, the relative latencies of both cranial and distal muscles in the auditory startle response increased with the distance of their respective segmental innervations from the caudal brainstem. Thus the earliest EMG activity was recorded in sternocleidomastoid. The recruitment of caudal muscles was relatively slow and the latencies of the intrinsic hand muscles were disproportionately long. The pattern of recruitment of cranial muscles suggests a brainstem origin for the normal startle response. Studies on the auditory startle reflex in animals are reviewed in the light of this finding.
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50 ms duration and 124 dB presented binaurally through earphones. (The intensity of the stimulus used exceeded safety standards for continuous acoustic stimulation, and the authors would recommend caution in the use of similar stimulus intensities in future experimentation.) Electromyographic (EMG) recordings were made using bipolar silver/silver chloride electrodes placed 2 cm apart longitudinally over the muscle bellies. Records were collected as single sweeps triggered at the start of the auditory stimulus. The sampling rate was 1500 Hz per channel. The latency to onset of reflex EMG activity was measured by visual inspection of single trials on a computer display. The latency of the initial voltage sustained above the background level of EMG activity was taken to be the start of reflex EMG activity. The latency and duration of the auditory blink reflex to the same stimulus was also investigated. For this, auditory stimuli were presented randomly about every minute, and the responses to the first 5 stimuli were discarded to avoid recording a startle response. Medians and ranges were recorded. Statistical analysis was performed using the Mann-Whitney U test for unpaired data and Wilcoxon signed-ranks test for paired data. RESULTS
TABLE I. THE LATENCY TO ONSET OF EMG ACTIVITY IN THE NORMAL STARTLE RESPONSE TO SOUND* Range (ms) Muscle R orbicularis oculi R R R L R R R R R R R R
masseter stemoclcidomastoid C4 paraspinal muscles biceps biceps triceps forearm extensors forearm flexors APB FD1 ADM rectus abdominis
Median 36.7
Lowest 25.0
Highest 69.0
n 70
59.0 58.3 60.2 68.9 76.2 71.0 73.2 81.9 98.6 98.8 95.9 82.3
39.4 40.4 47.9 59.8 67.0 53.2 61.9 60.1 74.5 71.7 76.3 76.6
122.2 136.0 120.0 91.7 146.5 147.8 172.8 199.9 178.9 175.5 104.0 98.8
29 53 23 10 21 12 24 27 26 26 6 11
* The startle responses were elicited in 12 healthy sitting subjects by a 1000 Hz 124 dB tone of 50 ms duration delivered to both ears randomly, up to 3 times an hour. Muscle activity was approximately synchronous bilaterally. EMG activity was recorded in masseter significantly later (P < 0.001, Wilcoxon signed-ranks test) than in stemocleidomastoid. The latencies of the intrinsic hand muscles were disproportionately long. Activity in tibialis anterior (110.7 ms, range 103.5— 122.0 ms, n = 6) and in soleus (120.8 ms range 105.5— 122.0 ms, n = 5) was only present in 1 subject. Abbreviations: right (R) and left (L) abductor pollicis brevis (APB), first dorsal interosseous (FDI) and abductor digiti minimi (ADM).
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The most generalized startle response to the standard sound stimulus employed consisted of eye closure, grimacing, neck flexion, trunk flexion, slight abduction of the arms, flexion of the elbows and pronation of the forearms. There was considerable variation in the degree to which this response was expressed, and in some subjects only eye closure and flexion of the neck was apparent. There was also considerable variation in the latency to onset of the EMG activity in individual muscles during the startle response (Table 1). However, although the range of latencies was wide, most responses occurred with early latencies. The variation in
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the latency of EMG activity in sternocleidomastoid is shown in fig. 1. The latencies of other muscles showed similar skewed distributions. Despite the variation in latency, the overall pattern of the response to sound was distinctive. A blink reflex was always seen, regardless of the presence of a more generalized startle response. The latency to onset of this blink reflex (median 36.7 ms, range 25—69 ms) was much shorter than that of the startle response in sternocleidomastoid (58.3 ms, range 40.4-136 ms). The blink reflex persisted despite the repetition of the auditory stimulus every minute. In contrast, the startle response habituated within 2 to 6 trials, despite the random presentation of the stimulus about every 20 min. 35 30 25 20 15 10 5 0
50
100
150
200
Latency to onset of sternocleidomastoid EMG response (ms) FIG. 1. The latencies to onset of EMG activity in the sternoclerdomastoid muscle in individual auditory startle responses (n = 53) in normal subjects (n = 12).
The auditory blink reflex could be studied in isolation, in the absence of a startle response, by delivering the standard sound stimulus every minute (fig. 2A). Under these conditions the latency of the reflex response in orbicularis oculi (median 32.3 ms, range 19.3-68.6 ms, n = 60) was similar to that seen in the auditory startle response, but the duration of the auditory blink reflex was brief (range 63.3-149.2 ms, n = 72). In the presence of a startle response, the duration of the EMG activity in orbicularis oculi was much longer and more variable (range 108 to over 400 ms, n = 70). In 36% of such trials two distinct components were visible in the response of orbicularis oculi (fig. 2B). The earliest EMG activity recorded after the normal auditory blink reflex was in sternocleidomastoid (Table 1). This was the most consistently recorded feature of the startle response and was usually the last component to habituate. In 4 out of the 12 subjects it was the only feature of the startle response, other than a blink, to be recorded under the experimental conditions used. When a more generalized startle response was recorded (Table 1) the EMG activity in masseter started later than in sternocleidomastoid. The difference between the median latencies to onset of EMG activity in sternocleidomastoid and masseter was 0.7 ms (P < 0.001, Wilcoxon signed-ranks test), when all trials were averaged. However, the median difference in latency to onset of EMG activity between sternocleidomastoid
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0
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Orbicularis oculi
Orbicularis oculi
FIG. 2. A, average of 5 auditory blink reflexes (marked by dotted line) recorded in the same normal subject to a 124 dB tone of 50 ms duration, delivered randomly about every 60 s. B, average of 5 startle responses recorded in the same normal subject to an unexpected 124 dB tone of 50 ms duration, delivered randomly about every 20 min. Two components may be distinguished in orbicularis oculi. The first is a normal latency auditory blink reflex (marked by dotted line). The second component consists of EMG activity attributable to the true startle response and can be seen to follow EMG activity in sternocleidomastoid. Rectified EMG records are shown. The horizontal and vertical calibration lines represent 50 ms and 0.1 mV, respectively.
and masseter measured in those single trials in which EMG activity was evident in both muscles, was 3.6 ms (range —4.0—15.2 ms, n = 30). In the startle responses of 1 subject, the latency of EMG activity in mentalis (51.0 ms, range 48 — 53.5 ms) was compared with that in masseter (56.9 ms, range 51.5—62.4 ms), and sternocleidomastoid (43.6 ms, range 38.6—45 ms, n = 7 for each muscle). The EMG activity in mentalis followed that in sternocleidomastoid significantly later (P = 0.01, paired Wilcoxon signed-ranks test), but preceded that in masseter {P = 0.01). Thus the latency of EMG activity in the cranial muscles (with the exception of orbicularis oculi, where an auditory blink reflex was recorded at 29.7 ms, range 22.8 — 32.7 ms, n = 7) increased with the distance of their segmental innervations from the lower brainstem (fig. 3). The latencies of trunk and limb muscles in the auditory startle response also increased with the distance of their respective segmental innervations from the caudal brainstem
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Sternocleidomastoid
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Masseter
Orbicularis oculi
Mentalis
FIG. 3. Unrectified EMG record of a single startle response recorded in a normal individual. A 124 dB tone of 50 ms duration was delivered to both ears at the start of the trace. Excluding the auditory blink reflex, the first EMG activity is recorded in stemocleidomastoid and is followed later by mentalis then masseter. The horizontal and vertical calibration lines represent 50 ms and 0.5 mV, respectively.
(fig. 4, Table 1). Proximal arm muscles were activated before those of the hand. The cervical paraspinal muscles were activated before the abdominal recti. Responses in the legs were seen in only 1 of 12 subjects, and were at longer latency than those of the arms. No EMG activity was recorded in the intrinsic foot muscles of this or any other subject. The difference in latency to onset of EMG activity between stemocleidomastoid and rectus abdominis was relatively long (24.0 ms). A distinctive feature of the pattern of muscle activation in the normal startle response to sound was the disproportionately long latencies of the intrinsic hand muscles (fig. 4, Table 2). The EMG activity in abductor pollicis brevis and first dorsal interosseous occurred 25.4 ms (P < 0.001) and 25.6 ms (P < 0.001) after that in the forearm extensors. DISCUSSION
The normal startle response to a standardized auditory stimulus was determined in 12 healthy subjects. The general pattern of the response was consistent with previous
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Stemocleidomastoid
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Masseter Orbicularis oculi
Stemocleidomastoid
Forearm extensors
Forearm flexors ~_-
Abductor pollicis brevis
Rectus abdominis
FIG. 4. Rectified EMG record of a single startle response recorded in a healthy individual. A 124 dB tone of 50 ms duration was delivered to both ears at the start of the trace. Excluding the auditory blink reflex, the first EMG activity is recorded in stemocleidomastoid and followed later by masseter. There is a disproportionately long latency to abductor pollicis brevis and the first dorsal interosseous. The horizontal and vertical calibration lines represent 50 ms and 0.5 mV, respectively.
reports. Thus the startle reflex consisted of a generalized flexion response (Landis and Hunt, 1939; Wilkins et al., 1986), although EMG activity was recorded in both flexor and extensor muscles. The startle reaction was most prominent around the face, neck and shoulders, and less marked in the lower half of the body (Strauss, 1929). The minimum response, beyond a blink of the eyes, was activity in stemocleidomastoid (Jones and Kennedy, 1951). The latter was often the last component of the generalized startle reflex to disappear with repeated presentation of the stimulus (Jones and Kennedy, 1951). This habituation of the response was rapid, usually occurring within 2 to 6 trials, although the blink reflex persisted (Landis and Hunt, 1939; Wilkins et al., 1986). Previous reports have stressed that the latency of the normal startle response is relatively long and very variable (Landis and Hunt, 1939; Wilkins et al., 1986). Most authors, however, report either the range (Wilkins et al., 1986), or the mean of reflex latencies (Landis and Hunt, 1939; Suhren et al, 1966; Rossignol, 1975). We found that the latencies to onset of any given muscle in the startle reflex were not normally distributed.
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First dorsal interosseous
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TABLE 2. A COMPARISON OF THE EFFERENT PATHWAYS SUBSERVING THE NORMAL AUDITORY STARTLE REFLEX WITH CORTICOBULBAR AND PYRAMIDAL PATHWAYS IN MAN*
Excess latency of masseter over SCM
Auditory startle reflex 0.7 ms
Magnetic stimulation of motor cortex - 2 . 9 ms (masseter precedes SCM)
Excess latency of RA over SCM
24.0 ms
8.0 ms
Excess latency of APB over biceps
22.4 ms
10.5 ms
* The differences in the latencies to onset of EMG activity between individual muscles in the normal auditory startle reflex are calculated from the median latencies given in Table 1. The differences in the latency to onset of EMG activity between masseter and sternocleidomastoid (SCM), sternocleidomastoid and rectus abdominis (RA), and between biceps and abductor pollicis brevis (APB), following magnetic stimulation of the motor cortex, are calculated from the mean latencies reported by Cruccu el al. (1989) and Thompson (1991) in normal subjects. The pattern of recruitment of cranial nerves seen following magnetic stimulation of the motor cortex is reversed in the normal auditory startle reflex. The differences in latency to onset of EMG activity between sternocleidomastoid and rectus abdominis, and between biceps and abductor pollicis brevis, is longer in the auditory startle reflex than following magnetic stimulation of the motor cortex.
The distinction between the auditory blink reflex and the startle response in orbicularis oculi The presence of a short latency blink reflex of brief duration to auditory stimulation in normal subjects has been established (Rushworth, 1962). Lesioning experiments suggest that a central circuit involving the inferior colliculus and the midbrain reticular formation underlies this auditory blink reflex (Hori et al., 1986). Projections between the midbrain reticular formation and the facial nucleus exist (Hinrichsen and Watson, 1983). This mesencephalic circuit for the auditory blink reflex is in contrast to the bulbopontine origin proposed for the auditory startle response (Szabo" and Hazafi, 1965; Davis et al., 1982). The auditory blink reflex has been considered to be an integral part of the normal startle response (Landis and Hunt, 1939; Suhren etal., 1966; Gogan, 1970; Fox, 1978; Wilkins et al., 1986). However, the auditory blink reflex may be seen without any other manifestation of the startle response and, unlike the normal startle response, it does not readily habituate. Reflex EMG activity in muscles other than orbicularis oculi was no longer recorded after 2 to 6 repetitions of the auditory stimulus every 20 min. In contrast, reflex EMG activity was recorded in orbicularis oculi with repetition of the same auditory stimulus every minute. The amplitude of the auditory blink reflex does habituate with briefer interstimulus intervals (Fox, 1978).
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Although the range of latencies was large, most responses were of short latency. Calculation of the mean latency of an individual muscle is therefore inappropriate and misleading (calculation of the mean latency to onset of EMG activity in sternocleidomastoid from the present results gives a value 5.1 ms in excess of the median).
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When seen in the context of a startle response the latency of the blink reflex is much shorter than the latency of onset of EMG activity in other cranial muscles. In 1 subject, the latency of mentalis in the startle response was determined. This muscle has a similar innervation and peripheral efferent conduction time to orbicularis oculi (M0ller and Jannetta, 1986; Benecke et al., 1988). The EMG startle activity in mentalis was recorded about 21 ms after the blink reflex in orbicularis oculi in the auditory startle response. When a true startle response is elicited by unexpected auditory stimulation, the duration of the EMG activity in orbicularis oculi is much longer, and it is sometimes possible to distinguish two separate components in the EMG response in orbicularis oculi. It is therefore suggested that the early latency auditory blink reflex is physiologically separate from the generalized startle response. In contrast, the true startle response in orbicularis oculi is of longer latency and is often seen grafted on to the end of the normal auditory blink reflex. The EMG response in orbicularis oculi may also show two components in the pathological auditory startle response (Colebatch et al., 1990; Brown et al., 1991).
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Efferent pathways of the normal auditory startle reflex in man The earliest recorded EMG activity in the true generalized startle response was in sternocleidomastoid (innervated by the eleventh cranial nerve). EMG activity in masseter (innervated by the fifth cranial nerve) occurred significantly later {see Table 2). This is the reverse of the rostrocaudal pattern of activation of cranial nerve innervated muscles seen in cortical reflex myoclonus (Hallett et al., 1979). Similarly, with magnetic stimulation of the motor cortex, activity in masseter occurs about 2.9 ms before that in sternocleidomastoid (Cruccu etal., 1989; Thompson, 1991). The latency of the true startle response in orbicularis oculi (innervated by the seventh cranial nerve) was difficult to define exactly as its onset was usually obscured by EMG activity attributable to the normal auditory blink reflex. EMG activity in mentalis, however, (also innervated by the seventh cranial nerve) occurred significantly later than that in sternocleidomastoid and before that in masseter. Given the approximately similar peripheral efferent conduction delays to masseter, orbicularis oculi, mentalis and sternocleidomastoid (M0ller and Jannetta, 1986; Benecke et al., 1988), the overall pattern of muscle recruitment in the physiological startle response to auditory stimulation suggests that in man, as in animals, the auditory startle response originates in the caudal brainstem, with propagation rostrally to the seventh then fifth cranial nerve nuclei. A similar pattern of activation of cranial nerve innervated muscles is seen in reticular reflex myoclonus, where myoclonic activity is propagated rostrally from a myoclonic generator in the caudal brainstem (Hallett et al., 1977). The latencies of the startle response in trunk and limb muscles also increase with the distance of their segmental innervation from the caudal brainstem. The proximal arm muscles were activated before those of the hand, and the cervical paraspinal muscles were activated before the abdominal recti. Responses in the legs were seen in only 1 of 12 subjects (when sitting relaxed) and were at longer latency than those of the arms. The difference in latency of onset of EMG activity between sternocleidomastoid and rectus abdominis (24.0 ms) is about 16 ms longer than the difference in latency between these muscles when they are activated by magnetic stimulation of the motor cortex (Table 2). This suggests that the conduction velocity in the spinal efferent pathways utilized by the normal startle response is relatively slow. The latency to onset of EMG
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activity in the intrinsic hand muscles is disproportionately long (Table 2), even when allowance is made for the slowness of conduction in spinal efferent pathways. The slowness of the spinal efferent pathways and the disproportionate latencies of the intrinsic hand muscles distinguishes the normal auditory startle reflex from cortical and brainstem reflex myoclonus (Hallett et al., 1977, 1979). In summary, the electrophysiological evidence suggests that the physiological auditory startle reflex in man is mediated by an efferent system with its origin in the caudal brainstem. The spinal projections of this system are relatively slowly conducting and distributed predominantly to axial muscles. The pattern of muscle recruitment in the normal auditory startle is then determined by the distance of each segmental level from the caudal brainstem, with two exceptions. First, an auditory blink reflex precedes the auditory startle reflex in orbicularis oculi. Secondly, the latencies of the intrinsic hand muscles are disproportionately delayed (Table 2), suggesting that the pathways responsible for activation of these muscles differ, at least in part, from those underlying the rest of the startle reflex. An alternative hypothesis is that the relative latencies of the many muscles involved in the startle reflex represent activity in multiple central circuits with differing central processing times.
The present results suggest that the system subserving the motor limb of the startle reflex in man originates, as in animals, in the caudal brainstem. The observation that the startle reflex exists in anencephalic infants (Edinger and Fisher, 1913) would support this hypothesis. The descending spinal efferent pathways in the normal auditory startle reflex in man are slowly conducting and this might suggest the involvement of pathways
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The physiology of the normal startle response Studies in animals also suggest that the startle response originates in the caudal brainstem. The short latency startle responses to sound persist after decerebration (Forbes and Sherrington, 1914; Szab6 and Hazafi, 1965). Lesioning experiments in the rat have implicated the medial bulbopontine reticular formation (Szabd and Hazafi, 1965), particularly the nucleus reticularis pontis caudalis (Hammond, 1973; Leitner et al., 1980; Davis et al., 1982) as the primary centre subserving the acoustic startle reflex. Electrical stimulation of the nucleus reticularis pontis caudalis (Davis et al., 1982; Yeomans et al., 1989), but not the nucleus reticularis gigantocellularis (Davis etal., 1982), elicits short latency startle-like responses in the rat. In the cat the area of the medial reticular formation involved in the auditory startle reflex may extend more caudally, into the medulla (Wright and Barnes, 1972; Wu et al., 1988). If the medial pontomedullary reticular formation is the primary centre subserving the acoustic startle reflex, then the efferent limb of the reflex may be provided by the bulbobulbar (Scheibel and Scheibel, 1958) and reticulospinal (Torvik and Brodal, 1957) pathways originating in this area. In particular, Shimamura and Livingston (1963) have identified a spinobulbospinal reflex system relayed in the medial medullary reticular formation in cats, the efferent limb of which is formed by moderately slowly conducting descending spinal pathways. This efferent system may also form the basis of the chloralose jerk (Shimamura and Yamauchi, 1967) and the audiospinal reflex responses recorded in decerebrate and chloralose anaesthetized cats (Wright and Barnes, 1972). The spinobulbospinal reflex has also been identified in dogs and monkeys (Shimamura et al., 1964) and, tentatively, in man (Shimamura et al., 1964; Meier-Ewert et al., 1972; Shimamura, 1973).
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ACKNOWLEDGEMENT We thank Mr R. Bedlington for his technical assistance. REFERENCES ANDERSEN RA, ROTH GL, AITKIN LM, MERZENICH MM (1980a) The efferent projections of the central
nucleus and the pericentral nucleus of the inferior colliculus in the cat. Journal of Comparative Neurology. 194, 649-662. ANDERSEN RA, KNIGHT PL, MERZENICH MM (198Ofc) The thalamocortical and corticothalamic connections
of Al, AH, and the anterior auditory field (AAF) in the cat: evidence for two largely segregated systems of connections. Journal of Comparative Neurology. 194, 663—701. ASCHER P, JASSIK-GERSCHENFELD D, BUSER P (1963) Participation des aires corticales sensorielles a I'e'laboration de re'ponses motrices extrapyramidales. Electroencephalography and Clinical Neurophysiology, 15, 246—264. BENECKE R, MEYER B-U, SCHSNLE P, CONRAD B (1988) Transcranial magnetic stimulation of the human
brain: responses in muscles supplied by cranial nerves. Experimental Brain Research, 71, 623—632. BRODAL A (1969) Neurological Anatomy in Relation to Clinical Medicine. Second edition. New York and Oxford: Oxford University Press. BROWN P, THOMPSON PD, ROTHWELL JC, BRITTON TC, DAY BL, MARSDEN CD (1991) The hyperekplexias
and their relationship to the normal startle reflex. Brain, 114, 1903-1928. COLEBATCH JG, BARRETT G, LEES AJ (1990) Exaggerated startle reflexes in an elderly woman. Movement Disorders, 5, 167-169.
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similar to the efferent limb of the spinobulbospinal reflex. The study of patients with abnormal startle responses to both somaesthetic and auditory stimuli has provided further evidence linking the startle reflex to the spinobulbospinal reflex (Brown et al., 1991). Both the pattern of muscle recruitment in man and studies in animals therefore suggest that the system subserving the motor limb of the auditory startle reflex originates in the bulbopontine brainstem in man, possibly in the medial reticular formation. This system may be activated by auditory afferent inputs at the subcortical level as suggested by animal experiments, either directly from the lateral lemniscus (Davis et al., 1982) or via the inferior colliculus (Wright and Barnes, 1972). Alternatively, the afferent limb of the startle reflex may involve a cortical relay. Several authors have reported a lack of an overt startle response to unexpected sounds in patients with bitemporal cortical damage (Woods et al, 1984; Ho et al., 1987). In addition, Liegeois-Chauvel et al. (1989) reported that the facilitation of the spinal monosynaptic reflex by auditory stimulation, considered to be related to the startle reaction, is selectively depressed by lesions of the caudal part of the superior temporal gyrus. It is most likely that die auditory cortex acts to facilitate subcortical reflex loops (Ascher et al., 1963). In the chloralose anaesthetized cat strychnization of the primary auditory cortex facilitates the generalized reflex response to sound, but complete bilateral neodecortication does not abolish the reflex response (Ascher et al., 1963). Such cortical facilitation could involve corticopontine tracts (Brodal, 1969) or the projection from the auditory cortex to the inferior colliculus (Andersen et al., 1980a, b). In conclusion, it is suggested that the motor response in the normal auditory startle response in man is organized in the caudal brainstem, probably in the medial reticular formation. This site may be activated by subcortically or cortically relayed afferent inputs, or by a combination of these influences.
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type of human post-hypoxic myoclonus. Journal of Neurology, Neurosurgery and Psychiatry, 40, 253-264. HALLETT M, CHADWICK D, MARSDEN CD (1979) Cortical reflex myoclonus. Neurology, New York, 29, 1107-1125. HAMMOND GR (1973) Lesions of the pontine and medullary reticular formation and prestimulus inhibition of the acoustic startle reaction in rats. Physiology and Behavior, 10, 239-243. HINRICHSEN CFL, WATSON CD (1983) Brain stem projections to the facial nucleus of the rat. Brain, Behavior
and Evolution, 22, 153-163. Ho KJ, KILENY P, PACCIORETTI D, MCLEAN DR (1987) Neurologic, audiologic, and electrophysiologic
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