ax-motoneurone axons and recording the changes in firing probability of single tibialis

Transcription

1 Journal of Physiology (1989), 414, pp With 5 text-figures Printed in Great Britain RECIPROCAL INHIBITION FOLLOWING LESIONS OF THE SPINAL CORD IN MAN BY P. ASHBY AND M. WIENS From the Playfair Neuroscience Unit, University of Toronto and Lyndhurst Hospital, Toronto, Canada (Received 20 September 1988) SUMMARY 1. Reciprocal inhibition was studied in normal subjects and patients with spinal cord lesions by stimulating the posterior tibial nerve below the threshold of the soleus ax-motoneurone axons and recording the changes in firing probability of single tibialis anterior motor units activated by voluntary contraction. A short-latency (about 35 ms) period of decreased firing probability was assumed to represent reciprocal inhibition. 2. For a given stimulus intensity this inhibition was greater in patients with spinal lesions than in normal subjects. 3. The stimulus intensities at which soleus motoneurones and the Ia inhibitory interneurones were brought to threshold provided an estimate of the relative excitability of these two neural populations. In the patients with spinal lesions the I a inhibitory interneurones were more excitable than soleus motoneurones, whereas in normal subjects the excitabilities were approximately equal. 4. Stimulation of the posterior tibial nerve below the threshold of a-motoneurone axons also resulted in a second period of inhibition with a latency of approximately 50 ms. This was less prominent in the patients with spinal cord lesions. 5. It is concluded that transmission through the pathways mediating reciprocal inhibition of flexor muscles during their voluntary contraction is enhanced following a spinal cord lesion in man but that a later inhibitory process is depressed. INTRODUCTION Injury to the spinal cord in animals or man is followed by a disorder of motor function known as spasticity. Characteristically there is a loss of the ability to activate muscles precisely (or at all) and exaggeration of spinal reflexes such as those in response to cutaneous stimuli or displacement of the limb. The latter is emphasized in Lance's (1980) definition of spasticity as 'a motor disorder characterized by a velocity dependent increase in tonic stretch reflexes ('muscle tone') with exaggerated tendon jerks resulting from hyperexcitability of the stretch reflex'. The various neurophysiological abnormalities which may underly this disorder have been reviewed by Pierrot-Deseilligny & Mazieres (1985) and by Ashby & McCrea (1987).

2 146 P. ASHBY AND M. WIENS Voluntary movements in subjects with spasticity may be accompanied by inappropriate activation of both agonist and antagonist muscles (McLennan, 1977; Knutsson & Martensson, 1980; Benecke, Conrad, Meinck & Hohne, 1983; McLellan, Hassan & Hodgson, 1985; Corcos, Gottlieb, Penn, Myklebust & Agarwal, 1986) and it has been postulated that one of the important abnormalities in spasticity may be decreased reciprocal inhibition (e.g. Pierrot-Deseilligny & Mazieres, 1985). Studies of reciprocal inhibition in spasticity using H reflexes conditioned by antagonist muscle afferent volleys (Yanagisawa, Tanaka & Ito, 1976; Yanagisawa & Tsukagoshi, 1977; Yanagisawa, 1980; Gottlieb, Mykelebust, Penn & Agarwal, 1982) have been inconclusive (see Discussion). For this reason we have re-examined this question using a more direct method and find no evidence for a decrease in reciprocal inhibition of flexor motoneurones in patients with spinal lesions. A later inhibition also apparently arising from group I afferents, however, is decreased. METHODS Studies were performed, with informed consent, on normal subjects and patients with welldefined, traumatic spinal cord lesions who had brisk tendon jerks and increased, velocitydependent stretch reflexes. The methods were approved by the Human Experimentation Committee of the University of Toronto. A clinical neurological examination was completed on each subject and a scoring system was used to document lower limb function. Muscle strength was recorded using the Medical Research Council scale (0-5) for four muscle groups in each leg (normal total score = 40). Stretch reflexes were graded using a 0-4 scale for four muscle groups in each leg (normal total score = 0, highest possible total score = 32). The quadriceps, hamstrings and triceps surae tendon reflexes were scored from 0-4 (normal total score = 12, highest possible total score = 24). Surface electrodes 3 cm apart were placed over the tibialis anterior, soleus and medial gastrocnemius muscles. A concentric needle electrode was inserted into the tibialis anterior and positioned close to a motor unit activated by a gentle voluntary contraction. The action potentials of the motor unit were extracted using a window discriminator and were displayed on an oscilloscope using a delay line. The subject was provided with visual and auditory feedback of the motor unit's activity and instructed to keep the unit firing at a constant rate. Stimuli, 0-5 ms duration, were delivered to the posterior tibial nerve in the popliteal fossa using a bipolar stimulating electrode. The stimulus strength which just excited thea-motoneurone axons of soleus was called the motor threshold (MT) and all subsequent stimulus strengths were expressed as a proportion of this value. Stimuli below MT were delivered at 303 ms intervals and peristimulus time histograms (PSTH), with bin widths of 200,ts and 400Us, of the discharges of single tibialis anterior motor units were generated using a laboratory computer. The presence or absence of a soleus H reflex was noted for each run. The mean background firing probability in the PSTH was obtained from the 30 ms pre-stimulus period. Periods of reduced firing probability were detected by comparing the mean firing probability of the 30 ms pre-stimulus period with the mean of running five-bin segments in the post-stimulus period using a series of t tests. The duration of a period of reduced firing probability was calculated from the number of contiguous bins forming the centre of the five-bin segment in which the averaged bin count was significantly reduced. The number of displaced counts in a period of reduced firing probability was normalized to 1000 stimuli. In order to obtain an exact value for the number of displaced counts it was decided, arbitrarily, that the run should be continued until two or less (usually zero) of the 200 Bus bins in the period of inhibition remained empty (e.g. Fig. 1, bottom right or top left; Fig. 2, square symbols). This sometimes required up to 7000 stimuli. The inhibition was often so profound that it was clear that some bins in the period of inhibition would never become filled even with prolonged recording. In these cases an exact value for the number of displaced counts could not be obtained (e.g. Fig. 1, top right; Fig. 2,

3 RECIPROCAL INHIBITION IN MAN upward-pointing triangles). Runs with more than 2000 stimuli in which no inhibition was detected or in which the number of displaced counts (normalized to 1000 stimuli) was 7 or less were classified as negative (Fig. 2, downward-pointing triangles). The 'threshold for detection' of an effect such as inhibition was obtained in the following way: if the effect was observed with a stimulus strength of 0-8 MT but not with a stimulus strength of 0 7 MT (the separation had to be 0-1 MT or less), the 'threshold for detection' was recorded as 0 75 MT. Periods of increased firing probability were accepted if the contents of three consecutive bins was greater than the mean of the pre-stimulus period plus two standard deviations. Statistical evaluations were made using x2, Student's t test and Mann-Whitney U test. For further details of the method see Mao, Ashby, Wang & McCrea (1984), and for the interpretation of the PSTH see Ashby & Zilm (1982) and Midroni & Ashby (1989). ~li-i IS I 0-75 MT 0-73 MT JhLlaIiIh.IIbhIhILII.1 I.,iA. N.i...i. L 1 LL.L UAL dwlallailll"m ilium-mald -A c 0.75 MT 0-6 MT Time (ms) Fig. 1. Examples of peristimulus time histograms (PSTH) of single tibialis anterior motoneurones following stimulation of the posterior tibial nerve below the threshold of the a-motoneurone axons (MT). The apparent reduction in firing probability immediately after time zero in the top left histogram results from stimulus artifact. On the right are examples from two patients with spinal cord lesions. Short-latency (approximately 35 ms) inhibition could be obtained with stimuli of low intensity (e.g. 0-6 MT, bottom right). With stronger stimuli (e.g MT, top right) the inhibition became more prominent without later responses being present. On the left are examples from two normal subjects. The short-latency inhibition required stronger stimulation (e.g MT, top left). Longer latency inhibition (40-70 ms) and longer latency facilitation ( ms) were observed in normal subjects even when the short-latency inhibition was not (e.g. bottom left). RESULTS Data were obtained from forty-two observations on normal subjects (n = 11, age 26-56) and twenty-four observations on patients with spinal cord lesions (n = 4, age 27-58). The patients had incomplete, traumatic spinal cord lesions between C6 and T9 which had occurred 7 months to 3 years prior to the examination. All had increased tone (stretch reflex scores 5-19, mean = 11P5) and extensor plantar responses, and all but one had increased tendon jerks (tendon reflex scores 11-22, mean = 18-5). None had loss of vibration, but two had partial loss of pain and temperature in the legs. Short-latency inhibition Stimulation of the posterior tibial nerve below the threshold of the soleus cc-motoneurone axons resulted in a short-latency (approximately 35 ms, range ms) inhibition of tibialis anterior motor units in all normal subjects (e.g. Fig. 1, top

4 148 P. ASHB Y AND M. WIENS left) and all patients with spinal cord injury (Fig. 1, right) which probably represents reciprocal inhibition (see Discussion). The mean threshold for detection (see Methods) of this inhibition was 0-85 MT in normal subjects and 0-65 MT in the patients (t = 4-13; P < 0005). Overall, the inhibition was greater in the patient group than in the normal subjects 50 A._0 A AA A 0 A 0~~~~~ o 0~~~~~~~~ 0~~~~0 0 A A A A Stimulus motor threshold Fig. 2. Strength of reciprocal inhibition (in terms of the number of displaced counts per 1000 stimuli) in normal subjects (open symbols) and patients with spinal cord lesions (filled symbols). The square symbols indicate the exact number of displaced counts. The upward-pointing triangles indicate that the number of displaced counts was equal to or greater than this value. The downward-pointing triangles indicate where no inhibition was detected. (Some of the baseline triangles represent several data points.) (Mann-Whitney U test; z = 3-8, P < 0-01) (Fig. 2) in spite of the fact that slightly higher stimulus intensities had been used in normal subjects (mean = 0-80 MT for normal subjects, 0-72 MT for patients, t = 2-96; P < 0 005) as a consequence of the higher threshold in the normal subjects. To avoid any possible distortion produced by differences in stimulus intensity the data between 0-71 and 0-85 MT were analysed separately. For the data in this zone there were no significant differences in stimulus intensity (mean = 0 79 MT in normal subjects, 0-78 MT in patients; t = 1P02, 0-4 < P < 0 3), but the inhibition was still greater in the patient group (Mann-Whitney U test; z = 3 3, P < 0-01). The duration of the inhibition was also longer in the patients with spinal lesions both for all studies (normal mean = 3-2 ms, patient mean = 5-5 ms) and for those in which the stimuli were between 0-71 and 0-85 MT (t = 5.44, P < 0-001). As the duration of the inhibition was correlated with the number of displaced counts this probably simply reflects the greater magnitude of the inhibition. The excitability of soleus motoneurones and the presumed I a inhibitory

5 RECIPROCAL INHIBITION IN MAN interneurones could be compared by noting whether an H reflex occurred in soleus (indicating that the soleus a-motoneurones had been brought to threshold) at the same stimulus intensity at which inhibition of tibialis anterior motoneurones was detected (indicating that the Ia inhibitory interneurones had been brought to threshold). As can be seen from Fig. 3 reciprocal inhibition of tibialis anterior motor 149 Spinal patients I-m M asd&j A 0 Normal subjects 0 A U04 1 Stimulus motor threshold Fig. 3. Number of trials at a given stimulus strength (expressed in terms of the threshold of the soleus a-motoneurone axons) in which reciprocal inhibition of tibialis anterior motor units was observed without an H reflex in soleus (O), in which both reciprocal inhibition of tibialis anterior motor units and an H reflex in soleus were observed (0) and in which an H reflex was observed without reciprocal inhibition of tibialis anterior motor units (L). units was frequently seen without a soleus H reflex in the patient group whereas in the normal subjects the inhibition rarely occurred without an H reflex (X2 = 6X24, 0-05 > P > 0-01), and sometimes the H reflex occurred alone. These findings indicate that the Ia inhibitory interneurones were more readily brought to threshold than soleus motoneurones in the patients with spinal cord lesions. Long-latency inhibition A later inhibition (Fig. 1, left) was observed with a latency between 40 and 70 ms (mean 51 ms) in both groups. This occurred without the presence of an H reflex. More detailed studies of the afferents responsible for this later inhibition were carried out in three normal subjects. The inhibition could be obtained with stimulus intensities similar to or lower than the threshold for reciprocal inhibition (e.g. Fig. 1, bottom left) but only by stimulation over the posterior tibial nerve in the popliteal fossa. When the stimulating electrode was moved to other sites in the popliteal fossa within a 10 cm radius no inhibition occurred even when stronger stimuli and/or double

6 150 P. ASHBY AND M. WIENS stimuli (5 ms separation) including those producing pain were used (Fig. 4, bottom). Branches of the sural nerve may be stimulated by an electrode over the posterior tibial nerve. Informed subjects can readily recognize when this occurs. By moving the stimulating electrode to different sites in the popliteal fossa it was possible to excite the main trunk of the posterior tibial nerve alone (recognized by eliciting an -LS~~~~~ Time (ms) +170 Fig. 4. Three PSTHs from the same tibialis anterior motor unit in a normal subject. Top: stimulation of the posterior tibial nerve below the threshold of the soleus H reflex and the soleus ac-motoneurone axons (12 V, 0-92 MT) results in an early inhibition with onset of 44 ms (reciprocal inhibition) and a later inhibition with onset 68 ms and a later facilitation with onset 103 ms. Middle: stimulation (12-5 V) over the sural nerve 10 cm below the popliteal fossa results in a similar late facilitation but no periods of inhibition. Bottom: stimulation of the popliteal fossa away from the tibial nerve using double stimulation at time zero and 5 ms (15 V) did not produce any significant changes in firing probability. H reflex at low threshold), the sural nerve alone (recognized by the presence of tingling in the distribution of the sural nerve) or both together. The inhibition was never seen with stimulation of the sural nerve alone although a later facilitation did occur (Fig. 4, middle). This late inhibition was more prominent in the normal subjects (Fig. 5), (Mann-Whitney U test; z = 3 35, P < 0 01) but, as the stimulation intensity was also greater in normal subjects (mean = 0-82 MT in normal subjects, 0 70 MT in patients, t = 3 07, P < 0-005), the analysis was repeated with data between 0-71 and 0-85 MT, a zone where there was no significant difference in stimulus strength (mean = 0-79 MT in normal subjects and 0-79 MT in patients; t = 0417). The inhibition remained greater in the normal subjects (Mann-Whitney U test; z = 2-56, P < 0-01). The duration of this late inhibition was slightly, but not significantly, longer in the normal group (t = 1P3, 0-3 < P < 0 2).

7 RECIPROCAL INHIBITION IN MAN E._~~~~~~~ _ o 0 0 O_J 0 0 0)~~~~~~ U * * On ra _ wewv Stimulus motor threshold 1 Fig. 5. Strength (in terms of the number of displaced counts per 1000 stimuli) of the longer latency inhibition (occurring between 40 and 70 ms) in normal subjects (open symbols) and patients with spinal lesions (filled symbols). The downward-pointing triangles indicate where no inhibition was obtained. (Some of the baseline triangles represent several data points.) An even later facilitation (Fig. 1, top left) occurred between 70 and 120 ms (mean 97-4 ms) in both groups. This also appeared to be greater in normal subjects although this could not be demonstrated statistically. 0 DISCUSSION Short-latency inhibition The short-latency inhibition of tibialis anterior motor units from afferents of the posterior tibial nerve has been described previously (Mao et al. 1984) and is attributed to reciprocal inhibition for the following reasons: it arises from lowthreshold afferents in muscle nerves, it is only seen in the motor units of antagonist muscles, it is of short latency, and the duration of the inhibition in normal subjects is brief (3-2 ms), similar to that obtained by conditioning the tibialis anterior H reflex (Pierrot-Deseilligny, Morin, Bergego & Tankov, 1981; Crone, Hultborn, Jesperson & Nielsen, 1987). In patients with spinal spasticity we found that: (1) this inhibition was greater than in normal subjects for a given range of stimulus intensities; (2) the inhibition of tibialis anterior motoneurones could be detected at a lower stimulus intensity than that required to elicit the soleus H reflex whereas in the normal subjects both events occurred at about the same stimulus intensity. Evidently, in the patients with spinal lesions, the Ia interneurones projecting to tibialis anterior motoneurones can be brought to threshold more readily than soleus motoneurones by a given group I volley whereas in normal subjects the thresholds of the two neurone populations are similar. It is unlikely that the increased inhibition in patients was due to a different

8 152 P. ASHBY AND M. TWIE1SM strategy of movement (for example a co-contraction of soleus during dorsiflexion which would enhance the excitability of the Ia interneurones being considered). There was no visible difference in the way that the tonic dorsiflexion was performed and no evidence for greater co-contraction in the patients with spinal lesions from the surface EMG recordings from the flexors and extensors of the ankle during tonic dorsiflexion or plantar flexion. Reciprocal inhibition may be easier to demonstrate in subjects who are habitually physically active (Crone, Hultborn & Jespersen, 1985) but the normal subjects used in this study were all physically active individuals (likely to be more active than the patients rather than less). There is nothing to suggest that the population of motor units sampled was different. For both normal subjects and patients the units studied were among the first to be recruited. In any case there are no major differences in the facilitatory projections of muscle and cutaneous afferents to tibialis anterior motor units recruited at various force levels (Ashby, Hilton-Brown & Stalberg, 1987) to suggest that subpopulations of motor units in this muscle receive different afferent projections. The mean firing rate of the motor units was less in the patients with spinal lesions (4-5 Hz) than in normal subjects (6-4 Hz) but this should not influence the total number of displaced counts in PSTHs (Ashby & Zilm, 1982; Midroni & Ashby, 1989). The present findings could certainly be explained by loss of descending facilitation of flexor motoneurones and their associated I a inhibitory interneurones as propose(1 by Yanagisawa et al. (1976) for hemiplegic spasticity. Corticospinal pathways in primates facilitate tibialis anterior motoneurones and (initially at least) inhibit soletus motoneurones (Preston, Shende & Uemura, 1967). This is also the case in manl (Cowan, Day, Marsden & Rothwell, 1986) and may explain why a lesion of these pathways in man produces greater weakness of dorsiflexion than of plantar flexion of the foot. Corticospinal pathways in primates also excite I a inhibitory interneurones (Jankowska, Padel & Tanaka, 1976) and there is evidence that these interneurones are also activated by voluntary contraction in man (Day, Marsden, Obeso & Rothwell, 1984). If these descending projections in man conform to the rule of a-y linked reciprocal inhibition (Baldissera, Hultborn & Illert, 1981) and if mutual inhibition exists between Ia inhibitory interneurones in man as it appears to do (Baldissera, Cavallari, Fournier, Pierrot-Deseilligny & Shindo, 1987) then the selective loss of descending facilitation of flexor motoneurones and their associated la interneurones would disinhibit extensor motoneurones and I a inhibition of flexors. The differential changes in the excitability of soleus motoneurones and l a interneurones inhibiting tibialis anterior motoneurones may indicate that this linkage is not immutable, as Crone et al. (1987) have already shown, or that the spinal lesion has changed the biophysical properties of the interneurones or has in) some way altered the balance of the many segmental inputs which synaps;e til)oml them. Our findings can be compared to those of Hultborn & Malmsteri (1983) who examined spinal reflexes in cats with chronic spinal hemisection. Reciprocal inhibition (from deep peroneal nerve to gastrocnemius-soleus motoneurones and Xvice versa) was found to be increased on the side below the hemisection. This was attributed either to altered transmission in spinal reflex pathways or to the

9 RECIPROCAL INHIBITION IN MAN formation of new connections. We did not examine reciprocal inhibition from flexors to extensors and cannot distinguish between disinhibition of one or both populations of these interneurones. Reciprocal inhibition from extensors to flexors has not previously been directly compared in normal subjects and patients with adult onset spasticity. Yanagisawa et al. (1976) examined three patients with hemiplegia in whom H reflexes were obtained in the tibialis anterior. Low-intensity stimulation of the posterior tibial nerve resulted in 'marked' short-latency, presumed reciprocal, inhibition of the tibialis anterior H reflex. Similar studies on four patients with spinal lesions showed little or no inhibition (Yanagisawa, 1980). There were no normal controls in these studies but the findings in hemiplegia are not necessarily different from those in normal subjects. Pronounced inhibition of the tibialis anterior H reflex can also be obtained in normal subjects (Tanaka, 1974; Pierrot-Deseilligny et al. 1981; Crone et al. 1987). In fact reciprocal inhibition in normal man is generally greater from extensors to flexors than the reverse (Mao et al. 1984; Crone et al. 1987; Bayoumi & Ashby, 1989). Gottlieb et al. (1982) recorded short-latency EMG (electromyogram) activity with surface electrodes placed over the tibialis anterior muscle in twelve patients with cerebral palsy in response to a tap to the Achilles tendon. This EMG activity, which they termed 'reciprocal excitation' was also found in 'some' patients in response to electrical stimulation of the posterior tibial nerve. They concluded that facilitatory reciprocal connections were present in patients with spasticity from perinatal lesions. It is important to exclude spread of the vibration wave from the tendon tap, spread of the electrical stimulus to the peroneal nerve and volume conduction of muscle action potentials (Hutton, Roy & Edgerton, 1988) in such studies as the authors point out. Corcos et al. (1986) noticed that when subjects with spasticity attempted to dorsiflex the foot rapidly a stretch reflex was generated in the soleus. When this occurred there was a clear short-latency inhibition of tibialis anterior activity suggesting that reciprocal inhibition was preserved. Thus from these studies there is no unequivocal evidence that reciprocal inhibition from extensors to flexors is decreased in spasticity. Neither has reciprocal inhibition from flexors to extensors been directly compared in normal subjects and patients with spasticity. Yanagisawa et al. (1976), in a study of eleven hemiplegic patients, found that stimulation of the peroneal nerve produced inhibition of the soleus H reflex in two, no effect in six, and facilitation in three. Yanagisawa & Tsukagoshi (1977) examined reciprocal inhibition in nineteen patients with spinal cord lesions. Low-intensity stimulation of the peroneal nerve produced inhibition of the soleus H reflex in six and facilitation in eight. There were no normal controls in either of these studies but their findings may not differ from those in normal subjects. Reciprocal inhibition of the soleus H reflex at rest shows considerable variability occurring in 0/7 (Mizuno, Tanaka & Yanagisawa, 1971), 1/6 (Tanaka, 1974), 2/9 (Pierrot-Deseilligny et al. 1981), 4/5 (Shindo, Harayama, Kondo, Yanigisawa & Tanaka, 1984), 27/27 (Crone et al. 1985), 6/7 (Iles, 1986) and 53/60 (Crone et al. 1987) of tested normal subjects. Mao et al. (1984) examined reciprocal effects from low-threshold afferents in the common peroneal nerve to soleus motoneurones by recording changes in their firing probability. Short-latency 153

10 154 P. ASHBY AND M. WIENS facilitation occurred in forty-two and inhibition in six studies. Thus it cannot be concluded from the studies of Yanagisawa et al. (1976) or Yanagisawa & Tsukagoshi (1977) that reciprocal inhibition from flexors to extensors is altered in spasticity. Long-latency inhibition A second, later period of inhibition was seen in the PSTH of normal subjects in the present studies. This inhibition was longer and more profound than reciprocal inhibition (in terms of displaced counts) and is thus, potentially, of greater functional importance. The inhibition began about 17 ms after the short-latency inhibition (i.e. at about 50 ms after the stimulus) and had a duration of up to 37 ms. It arose from large, low-threshold afferents in the tibial nerve and not from local cutaneous afferents in the popliteal fossa or from the sural nerve. As such low-threshold afferents must have fast conduction velocities, the additional 17 ms delay must be occurring within the central nervous system. We considered three possible explanations for this late inhibition. (1) It represents presynaptic inhibition of the on-going flexor la or lb activity which accompanies a steady contraction (and which would presumably be detected on PSTH). It is true that the effects of presynaptic inhibition are generally of longer duration, i.e. up to 500 ms (Hultborn, Meunier, Morin & Pierrot-Deseilligny, 1987; Ashby, Stalberg, Winkler & Hunter, 1987), although they may appear to be curtailed at ms by a superimposed facilitation from cutaneous afferents (Uultborn et al. 1987). (2) It represents postsynaptic inhibition of tibialis anterior motoneurones through spinal polysynaptic pathways. In the cat group I affererits project to interneurones in laminae V and VI including those which mediate oligosynaptic facilitation (Jankowska, McCrea & Mackel, 1981 a) and 'non reciprocal inhibition' of many species of motoneurones including those of tibialis8 anterior (Jankowksa, McCrea & Mackel, 1981 b). Group I afferents also project to more rostral interneurones with monosynaptic projections from group II aff/rents (Edgley & Jankowska, 1987; Cavallari, Edgley & Jankowska, 1987). These polysynaptic projections from group I afferents may also be present in man. Facilitation of quadriceps motoneurones from quadriceps group I afferents has been demonstrated beginning 5-12 ms after presumed monosynaptic events (Fournier, Meunier, Pierrot-Deseilligny & Shindo, 1986). The late inhibition that we observe, however, has a rather longer latency than can be explained by these presumed di- or trisynaptic pathways although the latency that we measured could be distorted by the earlier changes in firing probability. (3) It represents transmission involving supraspinal relays. The latency is too short for a reflex pathway involving the cortex which would have a latency of about 60 ms (Burke, Skuse & Lethlean, 1981; Robinson, Jantra & Maclean, 1988) but would be sufficient for a relay to the brain stem. A similar late inhibition following reciprocal inhibition has been reported by others (at least from flexors to extensors in the lower limb). Mizuno et al. (1971) described late inhibition, which they called DI, of the soleus H reflex in normal subjects resulting from stimulation of the peroneal nerve. The inhibition started about 7 ms, was maximum at about 20 ms and ended about 40 ms after reciprocal inhibition. This late effect could be obtained with stimulation at 0-96 MT and did not appear to arise from local cutaneous afferents near the stimulating electrode. The authors attributed this inhibition to presynaptic inhibition of I a afferents. Crone et al. (1987),

11 RECIPROCAL INHIBITION IN MAN also observed late inhibition of the soleus H reflex in normal subjects following stimulation of the peroneal nerve at 0-6 MT. The onset was about 4 ms and the maximum about 20 ms after reciprocal inhibition. El-Tohamy & Sedgwick (1983) observed a similar inhibition of the soleus H reflex following stimulation of the peroneal nerve but provided a different explanation. The inhibition began about 5 ms, was maximum at ms and ended about 30 ms after reciprocal inhibition. The inhibition could not be produced by stimulating cutaneous afferents and, as 4-5 stimuli to the muscle nerve with an intensity of at least 1-2 MT were required, they postulated that it might arise from group II afferents. Late inhibition following reciprocal inhibition has also been observed in the human upper limb (from extensors to flexors). Berardelli, Day, Marsden & Rothwell (1987) observed that stimulation of low-threshold (0 7 MT) afferents in the radial nerve (and not cutaneous afferents) resulted in short-latency inhibition of the H reflex of the wrist and finger flexors. This was followed by a second period of inhibition at condition-test intervals of 5-40 ms. This second period of inhibition was not seen when the excitability of the flexor motoneurones was tested using a corticospinal volley produced by transcranial electrical stimulation leading these authors to conclude that it resulted from presynaptic inhibition of flexor Ia afferents. In our study this late inhibition was more readily obtained in normal subjects than in patients with spinal lesions; a phenomenon noted previously both in spasticity (El-Tohamy & Sedgwick, 1982) and in dystonia (Rothwell, Obeso, Day & Marsden, 1983). The loss of this long-latency inhibition in the patients with spinal cord lesions could represent the reduction of presynaptic inhibition which has been postulated to occur in spasticity (Delwaide, 1973). Alternatively the spinal lesion might interfere with the projections to non-reciprocal inhibitory interneurones (Harrison & Jankowska, 1985) causing them to become less active. Finally, if the long-latency inhibition was transmitted through a supraspinal relay, the responsible fibre systems would be disrupted by a lesion of the spinal cord. We conclude that, following a spinal lesion in man, two abnormalities can be detected: (1) reciprocal inhibition from extensors to flexors is stronger than normal (at least during voluntary activation of the flexor muscles); (2) a longer latency inhibition is decreased. These abnormalities could contribute to the impairment of smoothly co-ordinated movements in spasticity. This work was supported by the Canadian Medical Research Council (grant No. 6727). We thank the patients and physicians of Lyndhurst Hospital for their help and M. Cairoli for preparing the manuscript. 155 REFERENCES ASHBY, P., HILTON-BROWN, P., STILBERG, E. (1987). Afferent projections to tibialis anterior motor units active at various levels of muscle contraction. Acta physiologica scandinavica 127, ASHBY, P. & MCCREA, D. A. (1987). Neurophysiology of spinal spasticity. In Handbook of the Spinal Cord, vol. 4, ed. DAVIDOFF, R. A., pp New York: Marcel Dekker. ASHBY, P., STALBERG, E., WINKLER, T. & HUNTER, J. P. (1987). Further observations on the depression of group Ia facilitation of motoneurons by vibration in man. Experimental Brain Research 69, 1-6. ASHBY, P. & ZILM, D. (1982). Relationship between EPSP shape and cross-correlation profile

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