44

Electroencephalography and clinical Neurophysiology, 1990, 75:44-55 Elsevier Scientific Publishers Ireland, Ltd.

EEG 02381

Responses of monkey precentral neurones to passive movements and phasic stretch: relevance to man J.G. Colebatch 1, R.J. Sayer, R. Porter 2 and O.B. W h i t e Experimental Neurology Unit, John Curtin School of Medical Research, P.O. Box 334, Canberra, A.C. 7". 2601 (Australia) (Accepted for publication: 18 June 1989)

Summary Single cell recordings were made from movement-related neurones from the precentral cortex of two monkeys, trained to perform a simple lever-pulling task. They were also trained to remain relaxed while the arm was explored with passive movements at different joints, cutaneous stimuli and during the application of two types of phasic muscle stretch: percutaneous vibration and percussion of muscle tendons. Recordings were made of the responses of cortical neurones both to the ' natural' stimuli and to vibration of specific muscle tendons or percussion of the triceps tendon. Both tendon percussion and vibration excited neurones within area 4 with an average latency for tendon percussion of 21.0 msec. There was a high degree of consistency in the effects on single neurones of tendon percussion and vibration at the same site. Although long-term facilitation was not seen, vibration-induced discharge in the motor cortex should be considered as a potential mechanism of its effects in intact man. In contrast to the similarity of the effect of the two forms of phasic stretch, the relationship between a single nenrone's response to either tendon percussion or vibration and to passive movement was complex. The dissociation seen between the effects of phasic muscle stretch and that of passive movement may underlie the failure, in man, to find uniformly increased long-latency stretch reflexes in clinical states of extrapyramidal rigidity. Key words: Motor cortex; Stretch reflexes; Rigidity; Parkinson's disease; Primate; Vibration

Rigidity, a resistance to imposed movements of characteristic quality, is a cardinal feature of akir~etic-rigid syndromes, of which the most common is Parkinson's disease (Marsden 1986). Despite the increased resistance to muscle stretch felt during passive movements, phasic stretch reflexes, such as the tendon jerk, are usually normal (Berardelli et al. 1983; Rothwell et al. 1983; Adams and Victor 1986). A better correlation exists between clinical measures of rigidity and 'long-latency' re-

i Current address: Institute of Neurology, National Hospital, Queen Square, London W C I N 3BG, U.K. z Present address: Dean, Faculty of Medicine, Monash University, Clayton, Victoria 3168, Australia.

Correspondence to: Dr. J.G. Colebatch, National Hospital, Institute of Neurology, Queen Square, London WC1N 3BG

(O.K.).

flexes to sudden stretch (Tatton and Lee 1975; Berardelli et al. 1983; Rothwell et al. 1983). The long-latency stretch reflex appears to depend, at least in part, on a transcortical pathway through the motor cortex (for review see Wiesendanger and Miles 1982; Marsden et al. 1983) and this has led to the proposal that disease of the basal ganglia causing rigidity can alter the gain of this reflex as a secondary phenomenon (Lee and Tatton 1978; Marsden 1984). Despite the plausibility of these arguments, the relationship between clinical assessment of rigidity and measures of the size of the long-latency reflex remains an overall one only: individual exceptions are common (1/~othwell et al. 1983) and the results overlap with normal values (Cody et al. 1986). Experiments on subhuman primates have shown that both passive movements of the limbs (Fetz and Baker 1969; Ros6n and Asanuma 1972;

0013-4649/90/$03.50 © 1990 Elsevier Scientific Publishers Ireland, Ltd.

MOTOR CORTEX RESPONSESTO MUSCLE STRETCH Lemon and Porter 1976; Wong et al. 1978) and sudden perturbations during movement (Evarts 1973; Evarts and Tanji 1976; Tatton et al. 1978; Wolpaw 1980) alter motor cortical discharge. More recently Cheney and Fetz (1984) provided direct evidence for the existence of a transcortical loop via the motor cortex which contributed to the long-latency stretch reflex at the wrist. These authors also reported, however, that for nearly half their sample of corticomotoneuronal cells, the responses to passive movements did not agree in all respects with their responses to torque perturbations during movement. Such differences in the response to sudden stretch and passive' movement, if a general property of motor cortical neurones, might explain the failure to find a strictly parallel relationship between rigidity and increased long-latency stretch reflexes in man. The present study was designed to compare directly the responses of neurones in motor cortex to imposed passive movement with their responses to phasic muscle stretch under conditions similar to those used in studies of human subjects. The crucial observation in this study to explain the apparent inconsistencies between the clinical measures and the tests of reflex function will be the differences shown, for individual motor cortical neurones, in the response to passive movements compared to the response to phasic muscle stretch. By avoiding anaesthesia and dissection, we have been able in addition to compare the relative effectiveness of tendon percussion and vibration under conditions in which the neurones were not artificially deprived of normal amounts of background facilitation.

Methods

Two male monkeys (M. fascicularis sp.) weighing 2.0 and 3.1 kg were studied. They were trained, using food rewards, to pull a spring-loaded lever into a target zone and also to remain relaxed and permit the experimenter to explore the limb by touch and with passive joint movements at rates similar to those used clinically (Lemon and Porter 1976; H o m e and Porter 1980). Two forms of

45 phasic muscle stretch were used, tendon percussion and percutaneous vibration, both applied with the monkey relaxed to avoid potential effects of central 'set' (Tsumoto et al. 1975). Prolonged training with food rewards was necessary to adapt the animals to accept these stimuli without withdrawing their limbs. For tendon percussion we used a small clinical tendon hammer (Martin Instruments 17-190-20), modified to generate a timing pulse on skin contact. In practice, this technique was essentially limited to the tendon of triceps brachii. A Pifco physiotherapy vibrator (Model 1556, 100 Hz, 10 W) was used for percutaneous vibration and proved suitable for application over a variety of muscle tendons: the usual sites used were over the biceps, triceps and forearm flexor and extensor tendons. Once well trained, the monkeys were anaesthetized with a combination of ketamine (Ketalar, Parke-Davis, 10 m g / k g ) and xylazine (Rompun, Bayer, 1 m g / k g ) and a headpiece (modified from Porter et al. 1971) attached to the skull centred over the left precentral gyrus. Supplementary doses of anaesthetic were given during the operation as required. Electromyographic (EMG) activity was recorded from 3 muscle groups of the right arm using stainless steel wires inserted directly into the muscle bellies and led subcutaneously to a multipin connector on the headpiece. In the first animal the muscles recorded were flexor carpi radialis,

extensor digitorum communis, and biceps brachii; in the second these were biceps brachii, triceps brachii and deltoid. Recordings were made with a bandwidth of 100 H z - 1 0 kHz with later filtering above 1.0 or 2.5 kHz to avoid aliasing. Control observations of unrestrained activity indicated that electrical pickup between different muscles was not significant and nor was there significant interference from the vibrator. Once the monkeys had recovered from the acute operation single unit recordings were begun. A microelectrode (glass-coated tungsten, exposed tips 20-30/~m, tapering to diameters of 2 - 3 / t m ) was held in a hydraulic microdrive (Trent Wells) and advanced through the underlying cortex while the monkey pulled the lever repeatedly. Different locations within the headpiece were explored by

46 adjusting a pair of eccentric rings on which the microdrive was mounted and the positions recorded. Discharges of single neurones were separated by amplitude using a Schmitt trigger. Once isolated, a histogram was collected of the neurone's spontaneous discharge while the monkey pulled the lever to confirm that it showed clear modulation during movement ('movement-related neurones'). We did not specifically identify neurones as belonging to the pyramidal tract because previous studies have shown that the projections from the arm to pyramidal and non-pyramidal tract neurones have only minor differences (Evarts 1973; Lucier et al. 1975; Lemon and Porter 1976). Once the histogram of the cortical cell's discharge during lever pulling had been collected, the monkey's arm was tested by the experimenter to define the types of peripheral stimuli which could excite the neurone and the areas from which these were effective. The stimuli consisted of passive movements of joints from the fingers to the shoulder and tapping, brushing and gently squeezing the arm and hand. Neurones were classified as either responsive to passive movements only (' movement-responsive'), to cutaneous stimuli only ('cutaneous-responsive') or to both ('mixed-responsive'). Histograms of the cell's discharge to repeated presentations of effective natural stimuli were made, with the stimulus presentation being indicated (semi-quantitatively) by closure of a footswitch by the experimenter (see also Lemon and Porter 1976). Once the pattern of response to peripheral stimuli was established, further histograms were collected for vibration over specific tendons (those of muscles passively lengthened by the effective movement and thus most likely to hold the receptors responsible for the excitation) a n d / o r percussion of the triceps tendon. Neurones responsive only to cutaneous stimuli were tested with vibration over the excitatory zone. Sometimes, application of the inactive vibrator to the skin was itself sufficient to alter neuronal discharge. To avoid this effect, all histograms using vibration were recorded with the vibrator held continuously on the skin and activated intermittently using a zero-crossing switch (International Rectifier $228). The combined electrical and mechanical delays

J.G. COLEBATCH ET AL. resulted in the initial movement of the vibrator (outwards) occurring on average 7 _+ 3 msec after the switch was activated. Histograms for tendon percussion had binwidths of 6 msec (50 bins) and those for vibration either 25 or 30 msec (50 bins). These records were used to determine whether there was a significant alteration in the cell's discharge to the stimulus during either the first 50 msec after tendon-tapping or the first 125-130 msec after the onset of vibration. These intervals ensured that the relaxation phase of the tendon jerk was avoided as was the monkeys' voluntary response to the stimulus. Histogram bin counts were assumed to fit a Poisson distribution with the mean determined from the control discharge. A significant alteration of neuronal discharge was taken to be present if the contents of a bin in the time limits after the stimulus presentation differed from the control distribution at the 1% level (2-tailed). Sometimes the low level of control discharge meant that inhibition, even if it had silenced the neurone. would not have been recognised. Once a significant response had been detected, the latency was determined by replaying the original recordings and using a cusum technique (Ellaway 1977) for histograms with 2 msec binwidths. Peak discharge was calculated after subtracting the mean control discharge. Interspike interval histograms of cellular discharge during vibration were made using a computer program written by one of the authors with a sampling rate of 1 kHz. After recording from each monkey for over 50 days, both animals were killed with an overdose of pentobarbitone and perfused with saline and formalin. On the previous day, marker tracks had been made at specific sites in both monkeys and. in the second monkey. 4 DC electrolytic lesions had also been made during the course of the experiments. Histological sections were cut at 80 /~m intervals through the pericentral cortex. parasagittally in one monkey and coronally in the other and stained with thionin. The marker tracks and DC lesions were all identified and used to determine the position of other tracks. Only data from neurones shown to be precentral (area 4 or the part of area 3a anterior to the central sulcus) were considered further. The criteria of Jones and

MOTOR CORTEX RESPONSES TO MUSCLE STRETCH Porter (1980) were used in setting the rostral b o r d e r of area 3a.

Results

Behavioural and E M G responses Both t e n d o n percussion a n d p e r c u t a n e o u s vibration caused p o t e n t excitation of muscles (Fig. 1). Although, i n general, these stimuli were tolerated well b y the monkeys, p r o x i m a l l y applied stimuli at times caused startle responses i n one

47 ( C o l e b a t c h a n d Porter 1987). Results reported here were o b t a i n e d i n the a b s e n c e of startle. A l t h o u g h the r e s u l t a n t m o v e m e n t i n d i c a t e d a n e t c o n t r a c t i o n of the u n d e r l y i n g muscle, the excit a t i o n p r o d u c e d b y t e n d o n percussion a n d vibration was n o t c o n f i n e d to the muscles directly stimulated. This was clear at the elbow where c o n t r a c t i o n of a n t a g o n i s t s was also visible with percussion or v i b r a t i o n applied to either the flexor or extensor tendons. V i b r a t i o n at the wrist produced less o b v i o u s muscle excitation t h a n at the elbow but, usually, w h e n the ventral surface was

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Fig. 1. Triceps EMG in response to tendon percussion (upper half) and vibration (lower). The left half of the figure shows representative single trials and the right rectified and averaged responses from 30 trials. The single trial of tendon percussion is shown above a marker pulse indicating the time at which the tendon hammer made contact with the skin. This stimulus evoked a large EMG response with a latency of 5 msec. Occasionally there was a second burst of activity (latency 56 msec). The single trial of vibration is shown above the gating pulse fed to the electronic switch. Vibration over the triceps tendon also caused a powerful EMG discharge, beginning at 15 rnsec and followed by 2 or 3 further peaks of activity before falling to a sustained level. Cessation of vibration was followed by a prompt reduction in EMG. The bars indicate the duration of vibration in the averaged records.

48

J.G. C O L E B A T C H ET AL.

stimulated, the wrist slowly flexed while vibration over the extensor surface caused finger extension. Percussion of the triceps tendon caused a brisk jerk with the evoked E M G activity beginning at a latency of 5 msec. Recordings from biceps confirmed that it too was activated by percussion of the triceps tendon although the response was only

one quarter of the size evoked by percussion of its own tendon (although this value appears reasonable in view of the visible contraction, we cannot completely exclude some electrical cross-talk under these conditions of highly synchronised activity). Vibration over tendons evoked E M G activity at greater latency than tendon percussion in all

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Fig. 2. An area 4 neurone excited by passive elbow flexion. On the upper left is shown the discharge evoked by passively flexing the elbow twice. This is shown as a histogram for 20 trials on the fight (here zero is the time of closure of the footswiteh by the experimenter, indicating the approximate start of the imposed movement). Percussion of the triceps tendon excited this neurone at a latency of 30 msec, and this is shown in the lowest part of the figure. On the left are 3 consecutive single trials and on the right is a histogram of 30 repetitions of the stimulus (note shorter timebase than above). The middle panel shows that vibration over the triceps tendon also excited this neurone, at a latency of 36 msec. Two single trials are shown on the left and a histogram of 20 repetitions on the right in which the duration of vibration is shown as a bar. H E = n u m b e r of trials, TC = total spike count.

MOTOR CORTEX RESPONSES TO MUSCLE STRETCH muscles. In triceps, the first E M G activity with vibration began at 15 msec and similar latencies were found for the other muscles. The size of the first peak of activity was similar to that obtained with t e n d o n percussion. The delay between the trigger pulse and the onset of vibration, together with the initial m o v e m e n t (away from the skin), is sufficient to account for the greater latency with vibration than with tendon percussion. All the muscles studied were excited by vibration. The E M G activity was maximal initially and then fell to a lower, tonically sustained level (Fig. 1). In biceps and triceps, there was initial segmentation with multiple peaks, whereas the other muscles showed only a single initial peak. Cessation of vibration was followed b y a rapid reduction in the E M G beginning 15 msec after the gating voltage was removed. Single cell recordings f r o m neurones in area 4: responses to triceps tendon percussion The effects of percussion of the triceps t e n d o n were studied in 47 movement-related neurones from area 4, all of which responded to natural stimulation of the limb. Based o n their responses to passive movements or cutaneous stimulation (see Methods), 26 neurones were mixed-responsive, 20 movement-responsive and 1 cutaneous-responsive. Thirty neurones responded at short latency following t e n d o n percussion: 29 were excited (Fig. 2) and 1 was inhibited. The excitatory effects had a m e a n latency of 21.0 + 8.2 msec, peaked an average of 8 msec later and lasted on average 37 + 22 msec (Fig. 3). The 46 neurones whose discharge could be modulated by passive m o v e m e n t were further analysed to c o m p a r e the effects of triceps t e n d o n tap with the type and direction of the effective passive movements defined using natural stimulation (Table I). T h e latency of excitation was the same for all groups. Seven neurones were excited b y b o t h passive flexion and passive extension of the elbow and all these neurones were excited by triceps tendon percussion. Twenty-eight neurones were excited by passive elbow m o v e m e n t in only one direction and these were less frequently excited b y triceps tendon percussion (18 of 28). Surprisingly, for this group, the direction of the effective

49 6O9 .J .J LU

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Fig. 3. Excitatory latency for 29 neurones in area 4 following percussion of the triceps tendon. The mean latency was 21.0 msec. Filled columns: movement-responsive neurones; open columns: cutaneous-responsive neurones; hatched: mixed-responsive neurones. passive m o v e m e n t seemed to have little influence on the result so that percussing the triceps t e n d o n excited a similar fraction of neurones responding to either passive flexion or passive extension of the elbow (10 of 17 and 8 of 11). N e u r o n e s which were not excited by passive elbow m o v e m e n t (i.e., either inhibited b y elbow m o v e m e n t or excited b y passive m o v e m e n t of other joints) were least likely to show an excitatory response to triceps t e n d o n percussion (3 of 11) and this difference in the TABLE I Effects of triceps tendon percussion on 46 neurones in area 4, all of which responded to passive movement of the limb (20 movement-t'esponsive and 26 mixed-responsive). All 7 neurones excited by both directions of passive elbow movement were excited by percussion of the triceps tendon (top row). Excitatory responses were also frequently recorded from neutones which were excited by either passive elbow flexion or extension (middle rows). Percussing the triceps tendon caused excitation least often in neurones excited by passive movements at other joints and the proportion of responses was significantly less (P < 0.01) than for the other 3 groups. Passive movement causing excitation Elbow flexion and extension Elbow flexion only Elbow extension only No excitation with elbow movement

No.

Percussion of triceps tendon Excited

Nil

Other

7

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proportion of excitatory responses was statistically significant ( P < 0.01). (The degree to which the discharge rate increased was sensitive to the presence of an excitatory response specifically to passive elbow flexion. For those neurones excited by passive elbow flexion alone or by both passive flexion and extension, percussing the triceps tendon caused a peak increase of 101 i m p / s e c and 73 imp/see, respectively. These values were significantly higher than that for neurones only excited by passive elbow extension (48 imp/see, P < 0.05)). Responses o f cortical neurones to vibration

A total of 146 neurones (52 classified as movement-responsive, 17 cutaneous-responsive, 73 mixed-responsive and 4 not activated by peripheral stimulation) were tested with vibration. Three of the neurones were later shown to have been in the precentral part of area 3a, the rest were from area 4. None of the 4 neurones which could not be activated by peripheral stimuli were affected by vibration. Vibration over triceps tendon. Forty-eight neurones in area 4 were tested for their responses to vibration over the triceps tendon. The relationship of the response to vibration to the effective input closely resembled that seen for tendon percussion: neurones with bidirectional excitation with passive elbow movement showed the greatest frequency of excitatory responses to vibration and those without an excitatory response to passive elbow movement the least (Table II). Of the 30 neurones tested with both tendon percussion and vibration 27 had identical early responses to both stimuli (18 excited and 1 inhibited by both, 8 not affected by either; e.g., Fig. 2). Three were excited by tendon percussion only. The responses to the two stimuli were significantly correlated ( P < 0.01, 2 x 2 contingency table). For the neurones excited by both stimuli, the peak increase in discharge rate for tendon percussion (average 68 imp/see) and for vibration (average 37 imp/see) were also significantly correlated (r = 0.53, P < 0.05). Responses o f cortical neurones to vibration at other sites. Neurones which were excited by pas-

sive movement at either the wrist or the elbow

J.G. COLEBATCH ET A L TABLE I1 Effect of vibration over the triceps tendon for 47 neurones in area 4 all of which responded to some passive limb movement (19 movement-responsive, 28 mixed-responsive). Like tendon percussion, neurones excited by both passive elbow flexion and extension most commonly had excitatory responses to vibration and those without an excitatory response to passive elbow movement were influenced least commonly. Passive movement causing excitation

No.

Both elbow flexion and extension Elbow flexion only Elbow extension only No excitation with elbow movement

Vibration over triceps tendon Excited

Nil

Other

b 23 l0

5 12 6

1 10 4

0 1 0

8

4

4

0

were tested with vibration applied over the tendons of appropriate muscles (Table III and Fig. 4), Excitatory responses to vibration were seen in 58 of the 106 presentations (55%), with similar proportions for all 4 sites. Inhibitory and mixed patterns were uncommon (2 and 3% of occasions, respectively). In the remainder, 40% of the presentations, vibration over the muscle tendon had no significant effect on the cell's discharge even though the neurone had been excited by passive TABLE III Area 4 neurones excited by passive wrist or elbow movement and tested with vibration over the tendons of the muscles lengthened by the effective passive movement. The total number of observations (106) is greater than the number of different neurones (82) as neurones which were excited by more than one passive movement were sometimes tested at more than one site. Excitation was seen in just over half (55%) the presentations, consistent with vibration-sensitive afferents within the muscle having contributed to the excitatory response tO passive movement. The absence of an excitatory effect of vibration in many cases (41%) suggests that these responses to passive movement are mediated by afferents that are not vibration sensitive (see text). Passive movement causing excitation

Wrist flexion Wrist extension Elbow flexion Elbow extension

No.

30 30 29 17

Response to vibration over tendon Excited

Nil

Other

17 13 17 11

12 16 11 4

1 1 1 2

51

M O T O R CORTEX RESPONSES TO M U S C L E S T R E T C H

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Fig. 4. Response to vibration of an area 4 neurone activated only by passive movements, including wrist flexion. Single trials are shown on the left and histograms of the neural discharge on the fight. The upper panel shows the discharge evoked by passively flexing the wrist with the timing pulse showing the approximate duration of the imposed movement. The histogram on the right consists of 20 repetitions of the movement, and zero time refers to the onset of the marker pulse. The middle section shows the discharge with vibration over the extensor tendons at the wrist. Here the marker pulse shows the time of the gating pulse fed to the vibrator. Vibration at this site excited the neurone under study at a latency of 16 msec. The lowermost part of the figure shows that vibration applied over the flexor tendons at the wrist had little effect on this neurone. This pattern of response was consistent with an input from vibration-sensitive afferents within the muscle passively stretched by the imposed movement of wrist flexion.

m o v e m e n t . O f 16 c u t a n e o u s - r e s p o n s i v e n e u r o n e s tested with vibration, 8 were excited.

Late effects of vibration There was usually evidence of a brief period of temporal summation in the cortical discharge e v o k e d b y v i b r a t i o n (e.g., Fig. 4). T y p i c a l l y , t h e

n e u r o n a l f i r i n g r a t e i n c r e a s e d s m o o t h l y to a m a x i m u m o c c u r r i n g o n a v e r a g e 70 m s e c a f t e r the o n s e t o f t h e v i b r a t o r g a t i n g v o l t a g e . W h i l e t h e results t h u s far h a v e b e e n c o n f i n e d to t h e earliest e f f e c t s o f v i b r a t i o n , t h e s l o w a u g m e n t a t i o n o f E M G activity c h a r a c t e r i s t i c o f t h e t o n i c v i b r a t i o n r e f l e x - i n m a n ( D e G a i l et al. 1966; H a g b a r t h a n d E k l u n d

52 1966) raises the possibility of longer-term temporal summation of cortical discharge. In an attempt to detect this, the immediate changes in discharge at the end of a 500 msec period of vibration were examined in 68 neurones. A shortlatency fall in discharge at cessation of vibration was interpreted as indicating withdrawal of reflex excitation and an increase as evidence for removal of inhibition. No evidence to support a generalised slow facilitation of the effectiveness of vibration was found. Fifty-two of the 68 neurones had significant responses to either the onset or the cessation of vibration and of these over half responded only at the onset. Seventeen of the 52 showed excitatory responses both at the onset and cessation of vibration but in only one neurone was the later response larger than the initial one. Only one neurone showed excitation at the time of cessation of vibration in the absence of an earlier effect.

Interspike intervals Interspike intervals were calculated for 56 neurones, including two from area 3a, which showed excitatory responses to vibration. Histograms of the interspike intervals for neurones from area 4 showed no evidence of phase-locking to multiples of the vibration period although this was detected for both the neurones from area 3a.

Discussion These experiments have compared, for individual motor cortical neurones, the effect of imposed passive movements at rates similar to those used clinically and that of phasic muscle stretch applied in 2 ways: either once (tendon percussion) or repetitively (vibration). All 3 forms of stimulation used here were found to be effective methods of exciting motor cortical neurones. The 2 forms of phasic stretch, applied to the same tendon, almost always had the same type and similar size of effect on individual cortical neurones. The type of any effective passive movement was defined in order to compare it with specific responses to phasic muscle stretch (thus, for example, excitatory responses to passive elbow flexion, if mediated by

J.G. COLEBATCH ET AL. muscle afferents, are most likely to arise from receptors within the muscle passively stretched, i.e., triceps; e.g., McCloskey 1978). Despite this, the relation between the effects of phasic stretch and the effects of passive movement was complex although statistically significant. Output connectivities have not been defined in this study which was designed to compare the processing of different kinaesthetic inputs and we assume in what follows that our sample is representative of motor cortical neurones with projections to spinal motoneurones. While vibration was used here primarily as a means of repetitive phasic muscle stretch our observations are also relevant to its effects in man. In human subjects, vibration is known to induce both perceptual (e.g, Goodwin et al. 1972) and motor phenomena (Hagbarth and Eklund 1966; Lance et al. 1966; Matthews 1984) as well as to facilitate the response to transcranial stimulation (Rossini et al. 1987; Claus et al. 1988). Previous studies of the effect of vibration on motor cortical discharge have used anaesthetized, dissected animals (Lucier et al. 1975) and, while demonstrating a projection to motor cortex, did not show a powerful one. This result m a y have been influenced by the anaesthetic ~ or by removal of convergence between different populations of mechanoreceptors on area 4 neurones. In human subjects, the motor phenomena induced by vibration, specifically the tonic vibration reflex, are generally believed to be primarily mediated by subcortical, possibly spinal, pathways (e.g., H o m m a et al. 1973; Hultborn and WigstriSm 1980). Our results have shown that vibration, applied as in man, has potent effects on motor cortical discharge, quantitatively similar to stimuli believed to be capable of evoking transcortical reflexes. Some of the motor effects of vibration in man may thus be mediated through the motor cortex, particularly those occurring at relatively short latencies. Both types of phasic stretch, tendon percussion and vibration, powerfully excite primary spindle afferents in the muscle stimulated (Hagharth and VaUbo 1968; Burke et al. 1976; Roll and Vedel 1982) and their activity probably dominates the evoked discharge even though other afferents are

MOTOR CORTEX RESPONSES TO MUSCLE STRETCH

also excited (Burke et al. 1976, 1983). Both tendon percussion and vibration caused powerful segmental EMG discharge and almost always had the same effect on individual cortical neurones. Primary spindle activity would also be expected to dominate the initial discharge resulting from a sudden external perturbation and, consistent with this view, both the latency and the duration of the cortical excitation induced by tendon percussion overlap previously reported values obtained with external perturbations (Evarts 1973; Evarts and Tanji 1976; Tatton et al. 1978; Wolpaw 1980; Cheney and Fetz 1984). Both tendon percussion and vibration in man (and probably also external torques) set up mechanical waves which can be sufficient to excite primary spindle afferents within antagonistic muscles (Lance and De Gall 1965; Burke et al. 1976, 1983). The same phenomenon, causing excitation of spindles lying within the biceps as well as the triceps muscle when the triceps tendon was suddenly stretched, could explain why excitation was equally common for neurones responding to either direction of passive elbow movement. The highly synchronous input from the two forms of phasic stretch may have also revealed inputs too weak to be detected with passive movements. Passive movements, such as used clinically to assess muscle tone, set up a more continuous afferent input and are known to excite, in addition to primary muscle spindle endings, secondary spindle endings as well as joint and cutaneous receptors. All these afferents are known to project to the motor cortex (Rosrn and Asanuma 1972; Wiesendanger 1973; Lucier et al. 1975). The failure to excite every neurone responding to a particular passive movement by phasic stretch of appropriate muscles is therefore probably a consequence of differences in the composition of the afferent input reaching the cortex. The observation (Table III) that up to 40% of the neurones were not excited by vibration suggests that a similar fraction of the responses to passive movement in precentral neurones do not depend significantly upon inputs from primary spindle receptors. The afferent volley evoked by imposed movement appears to be normal in the parkinsonlan form of akinetic-rigid syndrome (Burke et al. 1977).

53

Thus the reflex component of rigidity appears to be the result of disordered central processing of normal afferent activity. The motor cortex receives a powerful proprioceptive input, forms a part of a 'motor loop' which includes the basal ganglia (DeLong et al. 1984) and is thus a potential site for the abnormality in these patients. Parkinsonian subjects have different degrees of exaggeration of dynamic and static stretch reflexes, with the static stretch reflexes becoming more prominent in severe disease (Andrews et al. 1972). We have shown that the predominant effect on motor cortical neurones of passive movements with speeds and durations similar to those used clinically bears only a loose relationship to the same neurones' response to phasic stretch. Our findings imply that selective facilitation of either the input to, or the responses of, different populations of motor cortical neurones could be responsible for the dissociation sometimes seen between long-latency reflexes to sudden muscle stretch and the clinical measures of rigidity in these patients. J.G.C., R.J.S. and O.B.W. all held Medical Postgraduate Scholarships from the National Health and Medical Research Council of Australia. J.G.C. also held a Johnson and Johnson Australian Training Grant. Professor D. Burke gave helpful criticism. Dr. Colebatch thanks his senior colleagues at the National Hospital for their advice on the revised version.

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