by bl day, cd marsden*, ja obesot and jc rothwell from

J. Physiol. (1984), 349, pp. 519-534 519With 7 text-figures

Printed in Great Britain

RECIPROCAL INHIBITION BETWEEN THE MUSCLES OF THE HUMANFOREARM

BY B. L. DAY, C. D. MARSDEN*, J. A. OBESOt AND J. C. ROTHWELLFrom the University Department of Neurology, Institute of Psychiatry and King's

College Hospital Medical School, Denmark Hill, London SE5 8AF

(Received 5 September 1983)

SUMMARY

1. Peripheral and central mechanisms of reciprocal inhibition between antagonistmuscles in the forearm have been studied in ten human subjects.

2. H reflexes were evoked in flexor muscles by stimulating the median nerve withsingle shocks at around motor threshold intensity. Peripheral inhibition of the flexorH reflex was produced by motor threshold stimulation with a single shock ofthe radialnerve supplying the extensor muscles. The conditioning radial nerve stimulusproduced inhibition of the flexor H reflex consisting of three phases.

3. In some individuals, an H reflex could be evoked in extensor muscles of theforearm. Stimulation ofthe median nerve produced inhibition of the extensor H reflexwith a similar time course to that from extensors to flexors.

4. The first phase of inhibition was apparent when the test median nerve shockwas given from 1 ms before to 3 ms after the conditioning radial nerve shock. It wasabrupt in onset and short in duration and could be evoked with a conditioningstimulus intensity as low as 0 75 x motor threshold. The second and third phases ofinhibition were evident when the conditioning radial nerve stimulus preceded themedian nerve test shock by 5 to 50, and 50 to 500 ms respectively. The characteristicsof these later phases of inhibition are to be the subject of a separate report.

5. The difference in timing of the peak initial short-latency inhibition fromextensor to flexor and from flexor to extensor muscles enabled an estimate to be madeof the central synaptic delay of the inhibitory process. This method yielded a centraldelay of 0 95 ms in excess of that of the H reflex. We conclude that the first phaseof inhibition is mediated via large group I afferents acting through a single inhibitoryinterneurone.

6. Central inhibition of the flexor H reflex was demonstrated with the radial nerveanaesthetized by injection of local anaesthetic at the elbow. Subjects were asked totry to contract the paralysed extensor muscles. Under this condition, attemptedvoluntary wrist extension inhibited the flexor H reflex even though no movementoccurred.

7. A shock was delivered to the radial nerve at a site proximal to the anaesthetic

* To whom correspondence should be addressed.t Present address: Movement Disorders Unit, Department of Neurology, Clinica Universitania,

University of Navarra, Medical School, Pamplona, Spain.

B. L. DAY AND OTHERS

block. When the shock was applied in conjunction with an attempted voluntarycontraction of the paralysed extensor muscles, the depth of inhibition was greaterthan that predicted from the effect of either a shock or a willed contraction actingindependently. The result was consistent with spatial facilitation from descendingand peripheral sources acting at the level of a spinal interneurone.

8. The depth of flexor H-reflex inhibition from a radial nerve shock was studiedas a function of flexor torque in the intact subject. Over the range of torques used(0-15 N m) the depth of inhibition diminished as an approximate linear function offlexor torque.

INTRODUCTION

The essence of Sherrington's principle of reciprocal innervation is that duringcontraction of agonist muscles, the antagonists do not behave passively, but areactively inhibited by central nervous mechanisms.Experiments on animals (see Baldissera, Hultborn & Illert, 1981) have shown that

part, or all, of this reciprocal behaviour arises from excitation of Ia inhibitoryinterneurones in the spinal cord. Activity in these interneurones is modulated largelyfrom two different sources: by central descending commands from the brain and byperipheral input from agonist muscle spindle Ia afferents. A descending commandto excite agonist muscles to move a limb also inhibits antagonist muscles centrallyvia the Ia inhibitory interneurone. When the agonist muscle is activated, its spindleI a afferent discharge, through action of the gamma loop (Vallbo, Hagbarth,Torebjork & Wallin, 1979), may increase and feed back to the spinal cord to inhibitantagonist muscles peripherally via the Ia inhibitory interneurone.

In man, these mechanisms of reciprocal inhibition have been studied only in themuscles of the leg. A reflex muscle discharge (H reflex) was evoked by monosynapticexcitation of motoneurones after electrical stimulation of homonymous Ia afferentfibres. Mizuno, Tanaka & Yanagisawa (1971) attempted to activate the Ia inhibitoryinterneurone by stimulating the large Ia afferent fibres from ankle dorsiflexors toinhibit the H reflex elicited in ankle plantarflexors. In these muscles, it turned outthat such action of the Ia interneurone could only be revealed when the peripheraland central components summated. Thus the soleus H reflex was inhibited only whenshort trains of stimuli were given to antagonist Ia fibres at the same time as thesubject contracted tibialis anterior to dorsiflex the foot. It was not possible toinvestigate either mechanism in isolation. Similarly, the alternative approach ofmeasuring changes in firing patterns of single motor units following an antagonistIa volley (Ashby & LaBelle, 1977; Kudina, 1980) suffered in the same way since itrequired that the subject voluntarily activated the motor unit. This act, in itself, maymodulate transmission in the Ia inhibitory interneurone (see Baldissera et al. 1981).In this paper we investigate the peripheral and central components of reciprocalinhibition between extensor and flexor muscles in the human forearm. We show thatthe arm is different to the leg in that the peripheral component of reciprocal inhibitioncan be revealed by a single shock to the antagonist muscle nerve with the subjectat rest. Also, the central component of inhibition is demonstrated in the absence ofperipheral feed-back. The time course of peripheral inhibition in the flexors and

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FOREARM RECIPROCAL INHIBITION

extensors allows accurate measurements to be made which suggest that the inhibitoryprocess is disynaptic. The technique provides a powerful system for determiningchanges in the Ia inhibitory pathway accompanying movement (Day, Rothwell &Marsden, 1983), or in neurological diseases (Rothwell, Obeso, Day & Marsden, 1983)in man. Some of this work has appeared previously in abstract form (Day, Marsden,Obeso & Rothwell, 1981, 1982; Day & Rothwell, 1983).

METHODS

Subjects were ten normal volunteers from the departmental staff aged 21-32 years, and includedthree of the authors (B.L.D., J.A.0 and J.C.R.). In all experiments, the surface electromyogram(e.m.g.) was recorded from 1 cm diameter silver-silver chloride disc electrodes placed 3 cm apartat mid-forearm level over the bellies of flexor carpi radialis and flexor digitorum sublimis, and overextensor digitorum communis and extensor carpi radialis. Because of the wide pick-up area of theelectrodes, we shall refer to the muscles recorded from by the general terms wrist and finger flexorsand wrist and finger extensors. E.m.g.s were amplified (Devices 3160 pre-amplifier and Devices 3120amplifier), filtered (bandpass filter 80 Hz to 2-5 kHz) and converted into digital format (samplingfrequency of 5 kHz). Data was collected by a PDP12 computer using programs written by MrH. B. Morton.

Inhibition from wrist and finger extensors to wrist and finger flexor muscles was elicited by givingsingle, low-intensity, electrical shocks from a Disa constant-current stimulator, to the radial nervein the spiral groove. Stimulus intensity was set to be just below motor threshold by monitoringthe surface e.m.g. response from the extensor muscles.Monosynaptic H-reflex testing of relaxed subjects was used to follow the time course of reciprocal

inhibition of wrist and finger flexor motoneurones from the radial nerve afferents. Low-intensitystimuli (1 ms; 5-6 mA) were given to the median nerve in the cubital fossa in order to elicitapproximately half-maximal H reflexes in wrist and finger flexor muscles (with a minimum directM response) at various times before and after the conditioning shock to the radial nerve. At eachtime interval, ten control and ten test trials, in which the median nerve stimulus was paired withthe radial nerve shock, were given alternately every 4-5-5 s. The size of the test H reflex was thenexpressed as a percentage of the size of the control (unconditioned) H reflex at each point. Byconvention, the timing of the test (median nerve) shock was referred to that of the conditioning(radial nerve) shock. If the test shock came first, then the conditioning-test interval was said tobe negative.

In some subjects, an H reflex also could be elicited at rest in the extensor muscles. In thoseindividuals, the time course of reciprocal inhibition from flexor to extensor muscle also was testedin the same way. In this case, the radial nerve stimulation became the test shock, and that to themedian nerve the conditioning shock.

Method of estimating the central inhibitory delayWe define the central inhibitory delay as the extra time required for afferent impulses to inhibit

antagonist motoneurones, over and above that required to excite homonymous motoneurones toproduce an H reflex. An estimate of this value may be obtained if the following assumptions aremade: (1) the same afferent fibres are responsible both for the H reflex and the short-latencyinhibition of the antagonist H reflex; (2) maximum inhibition of the H reflex occurs when theexcitatory signal, from homonymous afferents, and the inhibitory signal, from antagonist afferents,arrive simultaneously at the motoneurone. Let the time taken for an afferent volley to reach thehomonymous motoneurone pool be Te for the radial nerve and Tr for the median nerve. Let theextra time taken for impulses to reach antagonist motoneurones, in excess of that required to reachhomonymous motoneurones, be the same for both nerves and equal Ti. It follows that maximalinhibition of the H reflex evoked in flexor muscles will occur if the median nerve stimulus is givenat an interval If after a conditioning radial nerve stimulus, where

If = Te +Ti-Tr- (1)

Similarly, if the stimulating electrodes remain in the same positions then an H reflex evoked in

521

B. L. DAY AND OTHERS

the extensor muscles will be maximally inhibited if the radial nerve shock is applied at an intervalIe after a conditioning median nerve shock, where

e= T +i-Te. (2)

Adding eqns. (1) and (2) givesT1 = (Ie+I)/2.

Therefore, an estimate of the central inhibitory delay may be obtained by measuring the optimumconditioning-test intervals for maximum inhibition of flexor and extensor H reflexes.

Central reciprocal inhibition after radial nerve anaesthe8iaIn five subjects, informed consent was obtained to anaesthetize the radial nerve. 5-8 ml plain

1 % lignocaine was injected around the nerve at the level of the elbow according to the techniquedescribed by Eriksson (1979). When the block was complete, motor power was lost and no e.m.g.activity could be recorded from surface electrodes when the subject attempted to extend the wristand fingers. Such complete nerve block usually lasted 5-10 min. During this period, H reflexes wereelicited in the flexor muscles, and in alternate trials, the subject was instructed to attempt to extendhis paralysed wrist during the test. Twenty trials, with and without attempted voluntaryactivation, were averaged. In three subjects it was possible to examine the combined effect ofcentraland peripheral reciprocal inhibition by giving low-intensity shocks to the radial nerve, proximalto the block, at the same time as the subject attempted to move. Four sets of trials were intermixed:(1) control trials, subject relaxed, unconditioned H reflex; (2) peripheral reciprocal inhibition,subject relaxed, H reflex conditioned by radial nerve shock; (3) central inhibition, subjectattempting wrist extension, unconditioned H reflex; (4) combined inhibition, attempted wristextension plus conditioned H reflex. It was not possible to monitor whether the degree of attemptedvoluntary wrist extension was the same from trial to trial but, by randomizing the stimuluspresentation, we presumed that this variable would be excluded from the average results.

Reciprocal inhibition accompanying voluntary activityTo study the effect of flexor activation on peripheral reciprocal inhibition the subject was asked

to hold his wrist in a constant position against a constant torque, which acted to extend the wrist.The subjects were seated comfortably, with the upper arm abducted and the elbow flexed to 900.The forearm was semipronated and supported on a horizontal board. Torque was applied by a torquemotor (Printed Motor, type G12M4) mounted coaxial to the wrist with the forearm and hand firmlyclamped. The position of the wrist was transduced by a Bournes 2 in. diameter thin-filmpotentiometer and displayed to the subject on an oscilloscope screen. H reflexes were evoked inthe flexor muscles. On alternate trials the H reflex was conditioned by a radial nerve volley. Tenpaired responses were evoked in each subject at different torque levels of 0 to 1-5 N m. Torquesabove 1.5 N m were not studied because of suspected contamination from distant postural muscles,which, even with firm clamping of the arm, were used to stabilize the arm at high force levels. Eachsize of torque was presented in random order.

RESULTS

H reflexes8 in wri8t and finger flexor musclesH reflexes, recorded electromyographically from wrist and finger flexor muscles

were identified using three criteria: latency, effect of stimulus strength on reflex sizeand response to muscle vibration (Deschuytere, Rosselle & deKeyser, 1976). Valuesof H-reflex onset latency ranged from 17 to 21 ms which, from measurements ofdistance from both recording and stimulating electrodes to the spinal cord (at theC7 spinous process), were found to be compatible with a fast-conducting (60-80 m/s),monosynaptic pathway. The size of the reflex was measured by its peak-to-peakvoltage, which was found to vary with the strength ofthe electrical stimulus deliveredto the median nerve. The stimulus intensity characteristics ofthe H reflex in the wrist

522

FOREARM RECIPROCAL INHIBITION 523

and finger flexors were similar to those reported for the soleus muscle. An examplefrom one subject is illustrated in Fig. 1 A and B. The H reflex appeared at sub-motorthreshold current, increased in amplitude as the current was increased, until amaximum value was attained at an intensity above motor threshold for directstimulation ofmotor axons (M wave). Further increases in stimulus intensity resulted

A B ^Am

200 a

55mA 0 a

'100

I | 2MmA Stimulus intensity (mA)

l if7-1mA Con~otrol

60mA 0IV

¢ _ ~~+Vibration50 ms

Fig. 1. A and B, relationship between the strength of stimulus to the median nerve in thecubital fossa, and size of direct M wave (- -)and H reflex (I *0) in the wrist andfinger flexor muscles of one subject. Size of responses measured peak to peak. Averageof ten trials at each intensity. Panel to left (A) shows examples of raw data used toconstruct the graph (B). Each trace is an average of ten responses made at graduallyincreasing stimulation strengths (from top to bottom). Stimulation applied at start ofsweep. TheH reflex appears first at a latency ofabout 20 ms; theM wave appears at higherintensities immediately after the stimulus artifact. The highest stimulus intensity used(7 mA) was much less than that required to produce a maximal M wave, which normallyhas an amplitude of some 510 mV. C, effect of vibration at 50 Hz applied to the flexortendons at the wrist on the H reflex recorded from wrist flexor muscles. Upper panel showsa single response without vibration, lower panel with vibration. Vibration was applied 0-5 s

before the start of the lower sweep and lasted for Is. The H reflex is almost abolishedwhilst the earlier, small, M wave remains of constant size.

in a decrease in H-reflex size with a progressive increase in M-wave amplitude. Theeffect of vibrating muscles in the forearm, whilst a test shock was given to the mediannerve, was to diminish the H-reflex amplitude without affecting the size ofthe M wave(Fig. 1 C), as also occurs with the coleusH reflex (e.g. Ashby, Verrier &mCarleton, 1980).

524 B. L. DA Y AND OTHERS

Peripheral inhibition offlexor H reflexH reflexes were evoked in wrist and finger flexor muscles at rest by median nerve

stimulation at different times relative to a motor threshold conditioning stimulus tothe radial nerve supplying the extensor muscles in the forearm. The results from asingle subject are shown in Fig. 2A. In this subject, when the median nerve shockwas given 1 ms before (-1Ims) or 2 ms after (+ 2 ms) the conditioning radial nerveshock, there was no effect on the size of the H reflex in the flexor muscles. However,when the radial nerve shock was given simultaneously with the test median nerve

A 8Percentage of Percentage ofcontrol H-reflex size control H-reflex size

100 100

50 5

Median first Radial first§ ~ ~ ~~~~~II.

-1 0 1 2 -1 0 1 2Conditioning-test interval (ms) Conditioning-test interval (ms)

Fig. 2. Time course of H-reflex inhibition in the wrist flexors following single motorthreshold conditioning shocks given to the radial nerve in the spiral groove. A shows theresults from a single subject. Each point is the mean of ten trials + 1 S.E. of the mean. Bshows the results from six different individuals. The abscissa plots the timing of the mediannerve test shock relative to that of the radial nerve conditioning shock which was givenat t = 0 ms. Negative timings indicate that the median nerve shock occurred first. At eachtime interval, the size of the conditioned H reflex was expressed as a percentage of thesize of ten control (unconditioned) reflexes (100% is shown as the dotted horizontal lines)elicited in alternate trials.

shock, there was maximum (75 %) inhibition of the flexor response. The excitabilitychanges were similar in six other subjects (Fig. 2B), although the exact timing anddepth of maximum inhibition varied. This probably was because of differences inelectrode placing and peripheral nerve length in each individual.As the conditioning-test interval was extended into more positive timings, later

phases of inhibition became apparent in the flexor H reflex. There were no furtherinhibitory effects at more negative timings. The over-all time course of inhibition isshown in the average data of Fig. 3, on a much extended time scale. There was asecond phase of inhibition which started at an interval of 5 ms and reached a peakof approximately 75% inhibition at an interval of 20 ms. This inhibitory phase wasfollowed by a return to about 80% of control values at an interval of 50 ms. This


partial recovery was followed by a further depression of the H reflex which lasteduntil 05-1 s after the conditioning shock to the radial nerve. In this paper we shalldescribe only the characteristics of the first, short-latency phase of inhibition, whichwe believe is mediated by the disynaptic Ia inhibitory pathway of the spinal cord.The two later phases of inhibition, which are similar to those seen in the leg (Mizunoet al. 1971; El-Tohamy & Sedgwick, 1983), will be analysed in a subsequent paper.The radial nerve stimulus intensity required to activate the short-latency inhibition

of the flexor H reflex was investigated in five subjects. The flexor H reflex was foundto be inhibited at stimulus strengths as low as 075 x motor threshold suggesting the

__---------------------------- -------------------------------_____-_--_-__-_

100

0x075

0

05o 25

O 5~~0 10;0 150 200 1000Conditioning-test interval (ms)

Fig. 3. Extended time course of H-reflex inhibition in the wrist flexors following a singleconditioning shock to the radial nerve at t = 0 ms. Data is the average from eightsubjects+ I s.E. of the mean. The abscissa plots the timing of the median nerve test shockrelative to the conditioning shock. On this time scale, the early phase of inhibition shownin Fig. 2 has been compressed to one data point. It is followed by two much longer-lastingphases of inhibition.

involvement of large group I afferents. The time course and duration of theshort-latency inhibition remained virtually constant at all stimulation intensities.Fig. 4 shows how the average depth of maximum inhibition varied with stimulationintensity in five subjects. The depth of inhibition increased with increasing stimulusstrength.The change in H-reflex excitability resulting from a percutaneous shock to the

radial nerve was unlikely to have been due to excitation of rapidly conductingcutaneous afferents under the stimulating electrodes. This was demonstrated bymoving the electrodes a small distance from the optimum position for stimulatingthe radial nerve, so that the nerve was no longer stimulated by the shock, althoughlocal cutaneous afferents were excited as before. This manoeuvre failed to produce

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any of the early changes in H-reflex excitability that were observed upon radial nervestimulation. Also, stimulation of the superficial radial nerve (pure sensory nerve) didnot inhibit the flexor H reflex at such short latency.

Peripheral inhibition of wrist and finger extensor H reflexOn rare occasions, H reflexes could be elicited in the relaxed extensor muscles

following sub-motor threshold stimulation of the radial nerve. Extensor H reflexes

100m

X I

N

x

ai)

50

cL.

07 08 0.9 1.0Stimulation intensity (x motor threshold)

Fig. 4. The effect of stimulation intensity on the maximum depth of flexor H-reflexinhibition evoked by single conditioning shocks to the radial nerve. The strength of theconditioning shock to the radial nerve (abscissa) is expressed as a percentage of motorthreshold intensity (monitored by e.m.g. leads over the extensor muscles). Size of theconditioned H reflex expressed as a percentage of the size of control H reflexes ( = I100% )elicited in alternate trials. Average data from five subjects± I sagc. of the mean.

were recorded at rest in two of the ten subjects in whom they were looked for. Theywere not present in these individuals on every occasion. These reflexes had a latencyof 17-20 ms and were abolished by muscle vibration. Low-intensity stimulation oflarge afferents in the median nerve also produced inhibition of the extensor muscleH reflexes. The time course of the short-latency phase of this effect was similar tothat from extensor to flexor muscles (Fig. 5A).

Estimation of central delay of inhibitory pathwayOn the basis of distances of stimulation sites from the spinal cord, and nerve

conduction velocities, the first inhibitory phase appeared to be a short-latency, spinalevent. It was not possible, however, to measure nerve conduction velocities anddistances with sufficient accuracy for a precise determination ofthe central conductiontime needed for this inhibitory process. Accordingly a technique was devised formeasuring this value without the need to determine detailed peripheral conductiontimes (see Methods). The essence of the technique was to measure the optimum

526


0 1 2Conditioning-test interval (ms)

B

-1

Interval /e (Ms)

2 .

4 I

0Interval /I (Ms)

Fig. 5. A, time course for short-latency reciprocal inhibition from wrist extensors to flexors(@-*, to left) and from flexors to extensors (O-0, to right) in one subject. Test Hreflexes were elicited either in the flexor muscles and conditioned by a motor thresholdconditioning shock to the radial nerve (t = 0 ms) or, using the same electrode positions,were elicited in the extensor muscles conditioned by a shock to the median nerve (t = 0 ms).Each point is the average of ten trials. The H-reflex size at each time interval is expressedas a percentage of the control H-reflex size elicited in alternate trials (= 100 %). If andIe mark the conditioning-test interval for maximum inhibition of the flexor or extensorH reflexes respectively. In this subject it was possible to elicit an H reflex with a sub-motorthreshold electric shock to the radial nerve when the subject was at rest. B, plot of therelationship between If (abscissa) and Ie (ordinate) in five different subjects. A least-squareslinear regression line has been fitted through the points. The intercept on the ordinate(1-9 ms) is equal to 21j where T1 is the central synaptic delay of the reciprocal inhibitorypathway over and above that of the H reflex.

527

1

l

B. L. DA Y AND OTHERS

interval (I,) between conditioning and test stimuli for maximum inhibition of theflexorH reflex from an extensor afferent volley. Then, without moving the stimulatingelectrodes their status was reversed and the optimum interval was measured formaximum inhibition of the extensor H reflex from a flexor afferent volley (Ie) Theintensity used at each site of stimulation was approximately the same for both halvesof the experiment. Because of interposed interneurones in the inhibitory pathway,the path length from agonist afferents to antagonist motoneurones is longer than thatto agonist motoneurones. The calculation in Methods shows that if we assume thatthis excess delay (Ti) is the same for both flexor and extensor afferents, thenX = (Ie+hf)/2.

This procedure was performed on five subjects. In this experiment an extensor Hreflex could be evoked at rest in one subject only. In the remaining four subjects anextensor H reflex could be elicited only when the extensor muscle was slightlyactivated. This manoeuvre did not change the time course of inhibition from thatseen in the relaxed state.An example from one subject is shown in Fig. 5A. In this example the optimum

conditioning-test interval for maximum inhibition was -0O6 ms for the flexor Hreflex (Tf) and 2-4 ms for the extensor H reflex (Te), giving an excess central conduc-tion time of (2-4- 0-6)/2 = 09 ms. These intervals were measured in each subject andplotted against each other as shown in Fig. 5B. Linear-regression analysis enabledthe best straight line to be fitted to the data. The intersection of the line with theaxis divided by two is then the best estimate for the excess central conductiontime. This was calculated to be 095 ms.

Central inhibition of antagonist musclesThe preceding experiments were concerned with the peripheral mechanisms of

reciprocal inhibition from large afferents in the antagonist nerve onto the agonistmotoneurone pool. However, other pathways are known to converge on the Iainhibitory interneurones in cats and primates (see Baldissera et al. 1981). Thefollowing experiments were devised to investigate the influence ofvoluntary descend-ing commands on these neurones.

In five subjects, the radial nerve was completely blocked by injection of localanaesthetic at the elbow, and the subjects were instructed to attempt to extend theirwrist and fingers voluntarily. Since the muscles were paralysed, no movementoccurred, and the effect of the voluntary command could be analysed in the absenceof any change in peripheral afferent feed-back. H reflexes were evoked in the flexormuscles during this period and compared with those obtained at rest. In all subjects,there was a decrease in the size of the flexor H reflexes. The results in three subjectsare shown in Fig. 6.We cannot say from this result whether the descending inhibition of the flexor

muscles was produced via the Ia inhibitory interneurones or by other inhibitorypathways. However, in three of the subjects we investigated the peripheral reciprocalinhibition from extensor to flexor muscles during attempted voluntary wrist extension.Low-intensity stimuli were given to the radial nerve proximal to the anaesthetic block,and the depth of inhibition of the flexor H reflex was examined with and withouta superimposed voluntary command to move. The results are shown from all three

528


subjects in Fig. 6. Either attempted voluntary wrist extension or the radial nerveshock inhibited the flexor H reflex when given alone. However, when both were giventogether, the effect on the H reflex was much greater than that predicted from thesum ofthe two separate effects. Thus for subject B.L.D. in Fig. 6, a radial nerve shockalone reduced the flexor H reflex size to 33 % of its unconditioned value and anattempted voluntary extension produced 50% inhibition. If these two effects wereindependent we would predict that when both occurred together there would be a

Subject B.L.D. Subject J.A.O. Subject J.C.R.

A Control

B + Radial nerveshock

C + Attemptedwrist extension

D + Radial nerve

200 pV ~~~~shock and[ 200 MV attempted wrist

r , ~~~~~~~~~~~~extension

50 ms

Fig. 6. The effect ofa single radial nerve conditioning shock and attempted voluntary wristextension on the size of wrist flexor H reflexes in three different subjects during totalanaesthetic block of the radial nerve at the elbow. Each column shows the average (often) H reflexes under four different conditions: A, control reflex; B, reflex inhibited bya radial nerve conditioning shock applied simultaneously with the median nerve testshock; C, reflex elicited whilst subject was attempting to extend the wrist voluntarily;D, reflex inhibited by a conditioning shock during attempted wrist extension.

reduction of the H reflex to 17% (0 33 x 0-5) of its basal level. In fact, the H reflexwas inhibited to 5% of its control value. Corresponding figures for the other twosubjects were: predicted values 15 %, 50%; observed values 9%, 27% respectively.These effects, therefore, cannot be considered independent. The results are consistentwith spatial facilitation from descending and peripheral sources acting at the levelof a spinal interneurone (see Discussion).

Reciprocal inhibition accompanying voluntary activityIn seven subjects we examined the effect of a constant level of voluntary flexor

activity on the depth and time course of reciprocal inhibition evoked by radial nervestimulation. The subject held his wrist flexed at 1600 against each of six levels of


torque supplied by an electric motor. The intensity of nerve stimulation remainedconstant.The size of both the unconditioned and the conditioned H reflex increased with

the force exerted (Fig. 7A), but the time course of inhibition remained unchanged.However, the amount of inhibition, calculated from the unconditioned/conditionedH reflex ratio, was found to decrease with increasing flexor force (Fig. 7B). Fromprevious studies in relaxed muscle, it was established that a change in the H reflexsize per se was not accompanied by a change in the percentage inhibition produced

A 75 B

N

300 x

a, |-c 50 -X~0

0~~~~~~~~~~~~~~~~~' 200

4-

O ^bS W .25cM 1 00 K0 aJ i 2

o

0 0o-. . 1 0 0.2 0. 07 1.0 1.

t S S as X ~~~~~~~~~~~, 25XCL~~~~Feo toqu1N Flxotoru (Nm

a,~~~~~~~O~ I -I--- -- ~- . | f 5 _0 05 1 0 ~~~~1*5 0 0-2505 075 10 1-5

F lexor torque (N m> F lexor torque (N m)

Fig. 7. A, change in size of the control (@-@) and conditioned (by a radial nerve shock;*----E) flexor H reflex with different levels of background flexor force. Opposingextensor torque supplied by a motor mounted coaxial with the wrist joint. Conditioningradial nerve shock given simultaneously with the median nerve test shock. The size of theH reflex expressed as a percentage of the control size when the subject was at rest(torque = 0 N m). Ten trials each of alternate control and conditioned reflexes were madefor each subject at every torque level. Points are the average data from sevensubjects+1 s.E. of mean. B, average (±1 s.E. of the mean) size of inhibited H reflexexpressed as a percentage of the size of the control H reflex at each torque studied. Samesubjects and data as in A.

by a constant radial nerve afferent volley, even when the H-reflex size was variedover a three- to fourfold range by varying the median nerve stimulus intensity (Dayet al. 1983). In the present case, therefore, voluntary flexor activity appeared todepress transmission in the inhibitory pathway from the extensor muscle group Iafferents.

DISCUSSION

In the cat, the key component involved in active inhibition of antagonist musclesis the Ia inhibitory interneurone in the spinal cord. Group Ia spindle afferent fibresfrom agonist muscles project monosynaptically onto these interneurones to mediatedisynaptic inhibition of antagonist motoneurones (Jankowska & Roberts, 1972). The


I a inhibitory interneurone also receives a number of additional inputs including, inthe cat forelimb and in primate, a monosynaptic excitation from the corticospinaltract (Illert & Tanaka, 1976; Jankowska, Padel & Tanaka, 1976). In man, previousexperiments have suggested a comparable spinal mechanism controlling musclesaround the ankle, although the relative contribution from Ia spindle afferent fibresand descending motor fibres could not be separated in normal subjects (Mizuno etal. 1971). The present experiments demonstrate that this spinal mechanism ofreciprocal inhibition also plays a role in controlling muscles of the human forearm.Furthermore, for these forearm muscles, the peripheral components of reciprocalinhibition can be analysed in the relaxed subject, and the central inhibition also canbe demonstrated.The method we have used relies upon H-reflex testing. Although the H reflex

generally is assumed to be due to monosynaptic excitation of ez-motoneurones by theIa afferent fibres, recently it has been observed (Burke, Gandevia & McKeon, 1983)that other pathways also may be involved. The reasoning is that if, for example, theI a conduction velocity in the arm ranges from 60-80 m/s, then over the distance fromthe cubital fossa to the cervical cord, there would be a 2 ms or so difference in latencybetween the time of arrival of impulses in the fastest and slowest Ia afferent fibres.This allows the possibility of di- or even (for the very fastest fibres) trisynapticlinkages to participate in the H reflex. At the present time, it is generally assumedthat the contribution of polysynaptic pathways to the H reflex is small. We havetaken this standpoint in this discussion. However, it is possible that some of the effectswe have observed may partially be due to actions on interneurones in this polysynapticpathway rather than on the spinal a-motoneurone pool.

Peripheral reciprocal inhibitionA single stimulation of the radial nerve produced a series of changes in the

excitability of the flexor monosynaptic reflex which lasted for up to 1 s. The first,short-latency inhibitory component has been analysed in this paper. We suggest thatthis inhibitory pathway in man is analogous to the I a disynaptic pathway reportedin animal studies, for the following reasons: (1) the inhibition was evoked withstimulus intensities as low as 0-75 x motor threshold suggesting the involvement oflarge group I afferent fibres; (2) the time course of the initial phase of inhibition wasabrupt in onset and short-lasting and very similar to that expected from the shapeof an inhibitory post-synaptic potential (Araki, Eccles & Ito, 1960); (3) peakinhibition from extensors to flexors occurred approximately when the radial nerveconditioning shock was given at the same time as the median nerve test shock. Wehave no direct measure of the exact peripheral nerve lengths involved in conductionto the cord. However, it seems likely that with the stimulating electrodes in the spiralgroove and cubital fossa, the impulses arrive within 0-2 ms of each other, indicatingthat the inhibition is evoked by short-latency pathways. In addition, by assumingthat the inhibitory process from flexor group I afferents to extensor muscles wasmediated by a similar mechanism to that from extensors to flexors, and that thecentral latencies of these pathways were the same, we could calculate the centralinhibitory delay of this first phase of inhibition. On average, this was 0-95 ms longerthan the central delay in the H reflex which is compatible with the presence of an

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additional synapse within the inhibitory pathway (Araki et al. 1960). These findingsare in agreement with the belief that the disynaptic Ia inhibitory pathway also isused to control forearm muscles in man.

Central reciprocal inhibitionBy studying the effect of attempted voluntary contraction of the paralysed wrist

and finger extensor muscles on short-latency reciprocal inhibition, we have shownthat (1) the voluntary extensor command inhibited the flexor monosynaptic reflexin the absence of any peripheral feed-back from the agonist muscles and (2) thisdescending command facilitated the inhibitory pathway produced by stimulation ofthe peripheral nerve.

In the absence of detailed knowledge of time relationships, it is not possible tospecify exactly the mechanism whereby the voluntary extensor command inhibitedthe flexor H reflex. The simplest explanation would be a direct descending inhibitionacting either post-synaptically on the flexor motoneurones or presynaptically on theI a afferent terminals. However, there is little evidence from animal experiments tosupport this concept. Renshaw cells of the extensor pool must be considered as asource of inhibition in these circumstances since they also would be activated by thismanoeuvre. However, they do not project from extensor to flexor motoneurones inthe cat (see Baldissera et al. 1981). In addition, although the extensor Renshaw cellsmonosynaptically inhibit the I a inhibitory interneurones to flexor motoneurones, theover-all effect would be to produce excitation of the flexor pool rather than inhibition.We would favour a mechanism whereby the descending command to activateextensor motoneurones also acts to excite the I a interneurones from extensor to flexormuscles. This idea is strengthened by the fact that a voluntary extensor commandcould facilitate the Ia inhibition produced by peripheral nerve stimulation. Theincrease in percentage inhibition produced during attempted wrist extension couldtherefore be explained by a spatial facilitation at the level of the I a inhibitoryinterneurone as described for the monkey (Jankowska et al. 1976) and in previousexperiments on the leg in man (Tanaka, 1974).

Reciprocal inhibition accompanying voluntary activityWhen the flexor muscles were activated voluntarily, the depth of peripheral

short-latency inhibition from extensors to flexors was reduced. This effect wasapproximately proportional to the flexor force over the range of torques used. Oneexplanation for this effect might be that the descending command to flexor musclesalso directly inhibits activity of the inhibitory pathway from extensors to flexors,either by presynaptic inhibition of the extensor afferent volley, or by inhibition ofthe I a inhibitory interneurone itself. However, there are other more complexpossibilities. For example, in the cat, it has been shown that the population of Iainterneurones from flexors to extensors can themselves inhibit the I a interneuronesfrom extensors to flexors (see Baldissera et al. 1981). In the present experiments, withvoluntary activation of flexor muscles the interneurones from flexor to extensor werelikely to have been facilitated from two sources: (1) by analogy with the previousexperiment, the descending command to flexor muscles would be expected to beassociated with a facilitation of the I a inhibitory interneurones from flexors to

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extensors; (2) likewise, flexor activation might increase spindle afferent discharge viathe gamma loop, which also would activate the I a interneurones from flexors toextensors. Thus, specific populations of I a inhibitory interneurones may be inhibitedor facilitated in a reciprocal manner, according to the nature of the voluntary task(see also Day et al. 1983). However, in the circumstances of the present experiment,flexor activation would also result in Renshaw cell activation. From experiments inthe cat this would be expected to inhibit Ia interneurones from flexors to extensors,in direct contrast to the two effects outlined above. It is impossible to predict theoutcome of these opposing effects in man, since the synaptic weight of eachmechanism is unknown. The present experiments, however, illustrate what actuallyhappens in man. Agonist activity results in a decrease in reciprocal inhibition fromantagonist muscle afferents. Presumably this could be some use to the nervous systemsince it would help prevent agonist inhibition by spindle discharge from the stretchedantagonist muscle, particularly in an isotonic task.

In conclusion, these techniques allow investigation of the disynaptic inhibitorypathway between muscles of the human forearm. The ease with which the peripheralcomponent of reciprocal inhibition can be evoked by a single stimulus to theantagonist muscle nerve makes this a useful experimental preparation in which toinvestigate many other influences which converge onto these spinal I a inhibitoryinterneurones in man.

We should like to thank Mr H. C. Bertoya and Mr R. Miller for their unfailing assistance duringthe course of these experiments. This work was supported by the M.R.C. and the Spastics Societyof Great Britain.

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ARAKI, T., ECCLES, J. C. & ITO, M. (1960). Correlation of inhibitory post-synaptic potential ofmotoneurones with the latency and time course of inhibition ofmonosynaptic reflexes. J. Physiol.154, 354-377.

ASHBY, P. & LABELLE, K. (1977). Effects of extensor and flexor group I afferent volleys on theexcitability ofindividual soleus motoneurones in man. J. Neurol. Neurosurg. Psychiat. 4, 910-919.

ASHBY, P., VERRIER, M. & CARLETON, S. (1980). Vibratory inhibition of the monosynaptic reflex.In Progress in Clinical Neurophysiology, vol. 8, ed. DESMEDT, J. E., pp. 254-262. Basel: Karger.

BALDISSERA, F., HULTBORN, M. & ILLERT, M. (1981). Integration in spinal neuronal systems. InHandbookofPhysiology, section 1 The Nervous System, part 2, vol. 2, ed. BROOKS, V. B., pp. 509-593.Bethesda: American Physiological Society.

BURKE, D., GANDEVIA, S. C. & McKEON, B. (1983). The afferent volleys responsible for spinalproprioceptive reflexes in man. J. Physiol. 339, 535-552.

DAY, B. L., MARSDEN, C. D., OBESO, J. A. & ROTHWELL, J. C. (1981). Peripheral and centralmechanisms of reciprocal inhibition in the human forearm. J. Physiol. 317, 59-60P.

DAY, B. L., MARSDEN, C. D., OBESO, J. A. & ROTHWELL, J. C. (1982). Long-lasting inhibition ofthe flexor monosynaptic reflex from extensor muscles in the human forearm. J. Physiol. 326, 31P.

DAY, B. L. & ROTHWELL, J. C. (1983). Estimation of the central delay in the reciprocal Ia inhibitorypathway of the human forearm. J. Physiol. 336, 32P.

DAY, B. L., ROTHWELL, J. C. & MARSDEN, C. D. (1983). Transmission in the spinal reciprocal Iainhibitory pathway preceding willed movements of the human wrist. Neurosci. Lett. 37, 245-250.

DESCHUYTERE, J., RoSSELLE, N. & DEKEYSER, C. (1976). Monosynaptic reflexes in the superficialforearm flexors in man and their clinical significance. J. Neurol. Neurosurg. Psychiat. 39, 555-565.

EL-TOHAMY, A. & SEDaWICK, E. M. (1983). Spinal inhibition in man: depression of the soleus Hreflex by stimulation of the nerve to the antagonist muscle. J. Physiol. 337, 497-508.

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by bl day, cd marsden*, ja obesot and jc rothwell from

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