344

l:lectroencephalography and clinical Neurophysiology, 81 (199t ) 344-352 ~ 1991 Elsevier Scientific Publishers Ireland, Ltd. 0924-980X/91/$03.50 ADONIS 0924980X9100094A

E L M O C O 90170

Silent period induced by cu~neous stimu~tion A . U n c i n i , T. K u j i r a i , B. G l u c k a n d S. P u l l m a n Clinical Motor Physiology Labora tory, Department of Neurology, College of Physicians and Surgeons of Columbia University, New York, NY ( U.S,A. ) (Accepted for publication: 15 January 1991)

Summary An electrical stimulus applied to a cutaneous nerve during isometric muscle contraction causes a suppression of E M G activity (silent period) followed by a rebound. The extent of inhibition is related to the stimulus intensity as the silent period is more evident when stimulation is perceived as painful. T h e silent period is present in different limb and cranial muscles after stimulation of the same cutaneous nerve and in the same muscle after stimulation of distant cutaneous nerves. It also occurs synchronously in antagonist muscles. Within the silent period induced after cutaneous stimulation the maximal inhibition on the opponens pollicis motor neuron pool, as tested by the motor response evoked after transcranial cortical stimulation, occurs between 50 and 70 msec. Using the double stimulus technique to study the recovery cycle, the silent period is present at interstimulus intervals as low as t00 msec, and does not habituate with trains of stimuli at frequencies up to 5 Hz. Our results suggest that motor neuron inhibition from nociceptive stimulation may be mediated by Renshaw cells directly activated by high threshold cutaneous afferents. Key words: Silent period; Cutaneous afferents; Transcranial cortical stimulation

The electromyographic silent period (SP), first described by Hoffmann in 1922, may be defined as "a transitory, relative or absolute decrease of E M G activity, evoked in the midst of an otherwise sustained contraction" (Shahani and Young 1973a). The SP induced by supramaximal electrical stimulation of the mixed nerve (Merton 1951) has a complex multifactorial origin due to traveling of antidromic impulses in motor axons, non-selective stimulation of muscular and cutaneous afferents and unloading of the spindle because of the evoked twitch (Shahani and Young 1973a, Struppler et al. 1973). Thus, it is difficult to determine the origin of the silent period from mixed nerve stimulation. A silent period can be induced by a single strong electrical stimulation restricted to cutaneous fibers (Shahani and Young 1973a) but its basic neurophysiology is still not completely understood. An even more complex modulation of the tonic E M G activity, consisting of up to 4 alternating phases of facilitation and inhibition, has been averaged after low intensity cutaneous stimulation (Gassel and Ott 1970; Caccia et al. 1973; Jenner and Stephens 1982). In order to more fully elucidate the underlying neural substrates and physiological mechanisms of the cutaneously induced SP, in this study we (1) quantified the SP by rectifica-

Correspondence to: Dr. Seth L. Pullman, The Neurological Institute, 710 W 168th Street, New York, NY 10032 (U.S.A.).

tion and integration of the E M G signal, (2) investigated the effect of altering various stimulus and acquisition parameters, (3) studied the topography of the SP by changing stimulus and recording sites, and (4) recorded the effect of concurrently evoked motor responses by transcranial cortical stimulation (Merton and Morton 1980) within the SP.

Materials and methods

The SP was evoked by electrical stimulation applied to cutaneous nerves in 8 normal healthy volunteers (5 men, 3 women, age range, 18-36 years, average age 30.8 ~ 4.4 years, average height: 170 + 3 cm) instructed to isometrically contract specific muscles at approximately 50% effort. Constant current square wave stimuli of 0.5 msec duration up to 32 mA intensity, at least 10 times the subjective sensory threshold (ST) and always above the subjective pain threshold were delivered pseudo-randomly at 30-60 sec intervals while the subjects rested comfortably in a chair. Ring electrodes were used to stimulate digit 2 (D2) and digit 5 (D5) at the interphalangeal joints. A bar electrode (30 mm inter-electrode distance) was used for cathodal stimulation of the superficial radial nerve (RAD) at the wrist, musculocutaneous (MUSC) at the elbow, supraorbital (SO) at its foramen and the sural nerve at the ankle. E M G activity was recorded with surface electrodes (10 mm diameter), in a belly-tendon arrangement and

SILENT PERIOD FROM CUTANEOUS STIMULATION

amplified using a Pathfinder signal analyzer (Nicolet Corporation, Madison, WI) set at 500-1000 /zV/div sensitivity and 30-3000 Hz bandpass with a sampling rate of 2000 Hz. The SP was obtained from the following muscles during sustained isometric voluntary contraction: opponens pollicis (OP), abductor digiti minimi (ADM), flexor carpi ulnaris (FCU), extensor carpi radialis (ECR), biceps brachialis (BB), tibialis anterior (TA), gastrocnemius lateralis (GL), orbicularis oculi (O OC) and masseter (MA). Contraction level of finger and hand muscles was kept at about 50% of maximum strength using a strain gauge device which provided constant visual feedback on an oscilloscope 1 m in front of the subject. Subjects were instructed to maintain the cue midway across the display which had been calibrated such that the entire screen width was set to 100% effort. In muscles not suitable for strain gauge measurement in this set-up, isometric force at 50% effort was estimated by opposing resistance (BB, TA and GL) or subjectively (O OC and MA). EMG was recorded in 500 msec trials divided into 2 equal analysis epochs: 250 msec before cutaneous stimulation (baseline 'EMG activity), and 250 msec after the stimulus (EMG activity which included the induced SP). EMG responses were full wave rectified and averaged over 8-12 trials. To obtain the SP from the averaged trials, an off-line analysis program calculated integrated EMG activity during 4 periods of time in the EMG tracing. The first period consisted of 100 msec of baseline activity (PRE) from the pre stimulus epoch. The other 3 periods, taken from the post-stimulus epoch, consisted of the silent period (SP), 50 msec before (PI) the SP and 50 msec after (PIII) the silent period itself (Fig. 1). The SP was determined by visual inspection of the rectified averaged EMG as that portion of the tracing clearly lower in amplitude than any other part of the tracing beforehand or afterwards. When the stimulus intensity was 10 times ST or more, the beginning of the SP was evident as at least a 50% decrease in EMG activity. The end of the SP was also determined by visual inspection of the rectified averaged EMG tracings, and was clearly evident as an abrupt resumption in EMG activity. The average amplitude for each period was calculated by dividing integrated EMG value by its duration. In addition, in order to compare different periods in the same subject, the following average amplitude ratios were calculated: the ratio of baseline EMG to EMG activity just prior to the onset of the silent period ( P R E / P I ) , the ratio of the silent period to the preceding EMG activity (SP/PI), and the ratio of EMG activity just before and just after the silent period (PIII/PI). The use of these ratios also allowed the comparison of data obtained from different subjects without regard to the variability in absolute amplitude values.

345

The effect of varying stimulus intensity and level of voluntary contraction on the SP was investigated. Stimuli, 1-16 times the sensory threshold (ST), were applied at D2 and averaged sensory action potentials (SAP) were recorded from surface electrodes over the median nerve at wrist. The effect of different levels of voluntary contraction (from 25 to 100% effort) on SP was studied while stimulus intensity was held constant. The excitability state of the neuronal substrate of SP was studied by testing habituation and the recovery cycle. Habituation was investigated using trains of 8 stimuli from 0.5 to 5 Hz, and recording real time EMG activity on a Teca TE42 (Teca Corporation, Pleasantville, N J). The recovery cycle was investigated by delivering paired stimuli of the same intensity at different interstimulus intervals (ISI) from 500 msec down to 100 msec. The onset latency, duration, and S P / P I amplitude ratios obtained after the test stimulus were compared with these same values after the conditioning stimulus using factorial analysis of variance. To study the time course of the inhibition produced by cutaneous stimulation on the motor neuron pool, electrical transcranial cortical stimulation (TCCS) (Merton and Morton 1980) with a duration of 50/~sec, and voltage output set at 40% of the maximum was employed using a Digitimer D180 stimulator (Digitimer Ltd, England). TCCS was delivered through 2 saline soaked felt pads (12.7 mm in diameter) positioned 60 mm apart with the anode over the hand area and the cathode positioned anteriorly. D2 stimulation was coupled to TCCS a t different interstimulus intervals (20100 msec) and the EMG was recorded from the opponens pollicis. To determine whether the SP in the opponens pollicis after D2 stimulation could be due to a voluntary relaxation or results from inhibition due to antagonist muscle activation, we recorded EMG activity from OP and abductor pollicis longus (APL) in a reaction time paradigm. Voluntary relaxation of the OP could not be directly studied with the same experimental set-up as the stimulus would always induce an SP (and interfere with relaxation). Two subjects were instructed to maintain constant force by thumb opposition (contracting OP) on an electrical microswitch and to release the switch (contracting APL) as fast as possible after D2 stimulation. The SP onset in OP and the EMG reaction time latencies in APL were recorded over 20 trials. In order to better~understand the role of large myelinated sensory fibers in the origin of SP and EMG rebound, we studied 2 patients (age 26 and 32 years) with Friedreich's ataxia and 1 patient (age 54) with chronic idiopathic ataxic neuropathy (Dalakas 1986). All patients had absent deep tendon reflexes, loss of proprioceptive and vibratory but preserved pain sensations. Motor conduction velocities and amplitude of

A. UNCINI ET AL.

346 PRE

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opponens potticis muscle (OP) during isometric contraction at 50% of maximal strength 250 msec before (left) and 250 ms after digit 2 (D2) stimulation (right). The silent period (SP) begins 66 msec after the stimulus and lasts for 38 msec. SP is followed by a rebound of EMG activity. Upper tracing: EMG integration over 4 designated periods. PRE is the integration of 100 msec of activity in the pre-stimulus epoch; SP is the integration of the silent period for its duration; PI is the integration of 50 msec before the SP; PIII is the integration of 50 msec after SP. The calibration of the integrated EMG is 25 msec-mV.

evoked responses a n d n e e d l e E M G studies were normal. Surface SAPs a n d H reflexes were n o t r e c o r d a b l e in these patients.

Results D2 s t i m u l a t i o n d u r i n g s u s t a i n e d isometric contraction of O P p r o d u c e d the SP, the i n h i b i t i o n of the E M G activity (Fig. 1). T a b l e i s u m m a r i z e s the m e a n values of SP onset latency, d u r a t i o n , a n d the average a m p l i t u d e ratios b e t w e e n different periods r e c o r d e d from O P a n d GL, respectively after D2 a n d sural stimulation. T h e m e a n P R E / P I ratio value was f o u n d to be close to 1.0 in both O P a n d GL, i n d i c a t i n g that average E M G a c t M t y was not c h a n g e d i m m e d i a t e l y after the stimulus. T h e S P / P I ratio is a m e a s u r e of the decrease in E M G activity d u r i n g the SP c o m p a r e d to the preceding 50 msec period. As a c o n f i r m a t i o n to the d e t e r m i n a t i o n of the SP by visual i n s p e c t i o n of the rectified averaged E M G tracings, a silent period was c o n s i d e r e d to be definitely p r e s e n t w h e n the S P / P I ratio was less

-~

Fig. 2. Reaction time experiment. EMG activity is recorded from abductor pollicis Iongus (APL) and opponens pollicis (OP) while pressing a microswitch with the thumb and releasing it as fast as possible after D2 cutaneous stimulation. EMG onset in APL is at 149.8 msec (open arrow) which followed the onset of SP in the OP 0eft filled arrow) by 84.5 msec. The release of the switch at 220 msec is indicated by the vertical displacement in the bottom tracing.

than 0.6 ( m e a n value of S P / P I + 3 S.D.). T h e P I l I / P I ratio was f o u n d to be g r e a t e r t h a n 1.0 showing that the E M G activity i m m e d i a t e l y after the SP was markedly increased in c o m p a r i s o n to the P R E a n d PI periods indicating the p r e s e n c e of r e b o u n d E M G activity. This r e b o u n d had a m e a n onset latency of 107.1 msec a n d a m e a n d u r a t i o n of 60.8 msec in the OP. In the e x p e r i m e n t designed to evaluate the possibility that SP was a v o l u n t a r y response indirectly due to a n t a g o n i s t inhibition (of the OP), the average reaction time to the onset of E M G activity in the A P L was 149.8 + 23 msec. R e a c t i o n time due to the actual release of the switch occurred at 220 msec + 28.7 msec. T h e average SP onset in O P was 65.3 msec. p r e c e d i n g E M G activity in A P L by 84.5 + 21.3 ms (Fig. 2). T h e t o p o g r a p h i c d i s t r i b u t i o n of SP was studied by s t i m u l a t i n g D2 and recording from several different muscles (Fig. 3). T h e i n h i b i t i o n o n the E M G activity t e n d e d to be g r e a t e r in distal limb muscles: however, the SP was also p r e s e n t in a cranial muscle (MA) a n d in the c o n t r a l a t e r a l OP. O n s e t latencies of the SP t e n d e d to be shorter in m o r e proximal limb a n d cranial muscles (Fig. 3). SP d i s t r i b u t i o n was also investigated s t i m u l a t i n g different sensory nerves a n d r e c o r d i n g from o n e muscle: the o p p o n e n s pollicis (Fig. 4). SP was clearly p r e s e n t after s t i m u l a t i o n of m e d i a n (D2), u l n a r (D5), R A D a n d M U S C nerves. SP was always p r e s e n t after c o n t r a l a t e r a l s t i m u l a t i o n with a n onset latency

TABLE l Summary of the mean values of silent period latency onset, duration and average amplitude ratios between different periods recorded from opponens pollicis and gastrocnemius lateralis after D2 (cutaneous) and sural nerve stimulation, respectively. The PRE/PI compares baseline EMG activity to activity immediately after the stimulus, the SP/PI measures the relative amount of EMG inhibition during the silent period, and the PIII/PI measures the relative rebound in EMG activity immediately after the silent period. Ranges are given in parentheses. Onset (msec)

Duration (msec)

PRE/PI

SP/PI

PIII/PI

Opponens pollicis

69.8 ± 4.9 (62.0-76.0)

37.3 _+ 9.1 (30.0-50.0)

1,08 ± 0A6 (0.90-1.20)

0.29_-4-0.10 (0.16-0.50)

1.88 ± 0.45 (1.40-2.80)

Gastrocnemius lateralis

93.7 _+10.8 (82.0 ± 115)

47.0 ± 11.4 (30-66)

0.93 ± 0.08 (0.80-1.04)

0.37 _+0.07 (0.24-0.47)

1.68 + 0.37 ( 1.30-2.39)

SILENT PERIOD FROM CUTANEOUS STIMULATION

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(69.1 + 8.1 msec) which was similar to SP o n s e t from ipsilateral s t i m u l a t i o n , a l t h o u g h the s u p p r e s s i o n of E M G activity was less p r o n o u n c e d . SP was p r e s e n t after SO (in 4 / 8 subjects) or sural (in 2 / 8 subjects) s t i m u l a t i o n . T h e o n s e t latency of the SP in the oppon e n s pollicis after SO s t i m u l a t i o n was 50.8 + 3.4 msec which is significantly different from the o n s e t latency after D 2 s t i m u l a t i o n ( T a b l e I, P < 0.001). SP o n s e t latencies in O P t e n d e d to be l o n g e r after sural stimulation (Fig. 4). SP after D2 s t i m u l a t i o n was r e c o r d a b l e in a n t a g o n i s t muscles (such as F C U a n d E C R ) w h e n separately activated (Fig. 3). I n a n o t h e r e x p e r i m e n t we f o u n d the SP in c o - c o n t r a c t i n g a n t a g o n i s t s such as T A a n d G L after sural s t i m u l a t i o n . H e r e the SP a n d the E M G r e b o u n d were s y n c h r o n o u s in b o t h muscles (Fig. 5). T h e SP was distinctly elicited in all subjects w h e n s t i m u l a t i o n was perceived as p a i n f u l ( 8 - 1 0 times ST), a n d the a m o u n t of E M G s u p p r e s s i o n c o r r e l a t e d to the i n t e n s i t y of s t i m u l a t i o n as i n d i c a t e d by the d e c r e a s e in the S P / P I ratio (Fig. 6). However, SP was d e t e c t a b l e

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Fig. 3. Topographic distribution of the SP recorded from different muscles after D2 stimulation. Each trace is the averaging of 10 rectified responses. OP = opponens pollicis, onset latency 62.2 msec; ADM = abductor digiti minimi, onset latency 71.0 msec; FCU= flexor carpi ulnaris, onset latency 60.4 msec; ECR = extensor carpi radialis, onset latency 61.8 msec; BB = biceps brachialis, onset latency 53.2 msec; MA ~ masseter, onset latency 41.6 msec, O PC = orbicularis oculi; CONTRA OP = contralateral opponens pollicis, onset latency 61.0 msec. Note that the EMG suppression, although more evident in hand and forearm muscles, is also present in a cranial muscle (MA). The EMG suppression did not reach significance in the O PC (SP/PI = 0.75). SP is present in antagonist muscles such as FCU and ECR.

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Fig. 4. Topographic organization of SP recorded from right opponens pollicis after stimulation of different sensory nerves. Each trace is the average of 10 rectified responses. D2 = digit 2; D5 = digit 5; RAD = radial nerve, MLISC = musculocutaneous; SO = supraorbital. Rt = right; Lt = left. Note that the EMG suppression, although more evident after stimulation of digital and cutaneous nerves of the ipsilateral hand and forearm, is detectable after contralateral D2, ipsi- and contralateral SO and (in this case) also after sural stimulation. SP onset latencies are 65 msec after right D2, 53 msec after right SO, 57 msec after left SO, and 83.2 msec after right sural stimulations.

in 1 subject at the subjective sensory t h r e s h o l d w h e n n o S A P was r e c o r d a b l e from the m e d i a n n e r v e at wrist with surface electrodes. W e also f o u n d that the E M G s u p p r e s s i o n was inversely r e l a t e d to the s t r e n g t h of c o n t r a c t i o n (Fig. 6). SP from c u t a n e o u s s t i m u l a t i o n did n o t show h a b i t u a t i o n even at stimulus f r e q u e n c i e s u p to 5 H z (Fig. 7).

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348

A. U N C I N I

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neuropathy. However in these patients the E M G rebound following the SP recorded in the opponens pollicis was diminished as the patients' P I I I / P I value (1.05 _+ 0.09) was significantly different ( P < 0.02) compared to normal controls (1.88 ___0.45).

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Furthermore, study of the recovery cycle showed no significant difference in SP onset, duration or S P / P I amplitude ratio after the test stimulus compared with the same parameters after the conditioning stimulus even with ISI as low as 120 msec (Fig. 8). With smaller interstimulus intervals (100 ms), the stimulus artifact of the test shock entered into the SP of the conditioning response, precluding accurate measurement. Nevertheless, the test SP was still present (Fig. 8). TCCS applied at set intervals after D2 stimulation inducing an SP in the opponens pollicis, resulted in a gradual decrease of the amplitude and duration of the evoked M response, reaching the lowest values at an ISI between 50 and 70 msec (Fig. 9). The M response r e t u r n e d to its original amplitude and duration at an ISI of 100 msec. SP was recordable in the 2 patients with Friedreich's ataxia and the patient with chronic idiopathic ataxic

The silent period produced in a contracting muscle by supramaximal stimulation of its mixed nerve (Merton 1951) is thought to be the result of the complex interaction among several physiologic mechanisms which include: collision in the motor axons between antidromic impulses generated by the stimulus and orthodromic voluntary activation, inhibition of alpha motor neurons due to antidromic activation of Renshaw cells. Ib inhibition due to Golgi tendon organ activation with the increase in tension produced by the muscle twitch and stimulation of cutaneous afferents. Muscle shortening produced by supramaximal stimulation also may be responsible for the withdrawal of reflex excitation on motor neurons through unloading of the spindles with consequent pause in the discharge of Ia afferents (Shahani and Young 1973a; Struppler et al. 1973). In our study we experimentally restricted the multifactorial origin of the SP by limiting the stimulation to cutaneous nerves: digital nerves, the sural and supraorbital nerves. These consist only of type II and III myelinated afferents without type I fibers from muscle spindles or Golgi organs (Buchthal and Rosenfalk 1966. Boyd and Davey 1968. Shahani and Young 1973b). A preliminary issue which needs to be addressed before further discussion of our results is whether the SP after cutaneous stimulation can be produced voluntarily. As the SP represents suppression of E M G , it is important to demonstrate that this suppression is not due to voluntary relaxation or reciprocal inhibition by antagonist activation. We found that in a reaction time experiment where the subject was instructed to extend the thumb as soon as possible after D2 stimulation, the onset of E M G activity of the abductor pollicis longus was considerably more prolonged (149.8 msec) than the cutaneously induced SP onset latency (65.3 msec) in the opponens polticis (Fig. 2). While indirect, the short latency of the SP shows that it cannot be caused by descending central inhibition of the OP during voluntary contraction of its antagonist (Day et al. 1984). If the SP were due to this inhibition, its average onset latency would be more than doubled. Furthermore. the average onset latency of the cutaneously induced SP was too short for any known stimulus-induced voluntary action except set-related automatic activity (Traub et al. 1980). The lack of any set-related paradigm and the pseudo-random passive cutaneous stimulation in

SILENT PERIOD FROM CUTANEOUS STIMULATION 0.51 sec

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Fig. 7. Real time EMG activity recorded in raster mode from OP after trains of 8 stimuli with frequency from 0.5 to 5 Hz applied to the second digit. "lst" and "8th" indicate the first and eighth stimulus in each series. Note that SP did not show habituation.

our experimental design precludes any possibility of obtaining set-related automatic activity. Hence, the suppression of EMG activity in the OP cannot be considered a voluntary response and by inference, cutaneously induced SP in other muscles are likely not voluntary.

ISI 200

ISI 150

ISI 120

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/o.3 v 25ms Fig. 8. Rectified and averaged (10 responses) EMG recorded at the opponens pollicis after paired shocks applied to the second digit with different interstimulus intervals (ISI) from 200 to 100 msec. The silent period latency, duration, and the SP/PI ratios after the test stimulus are not significantly different with those after the conditioning stimulus.

The underlying pathways and neural substrates of the SP and the subsequent EMG rebound after cutaneous stimulation may be hypothesized on the basis of our results. Because the SP was detectable in 1 subject at threshold stimulation and because some inhibition of tonic EMG activity can be elicited also by finger tip tapping (Caccia et al. 1973), the SP could be, at least in part, due to type II fibers. However, the suppressive effect on EMG of cutaneous stimulation increased with the stimulus intensity (Fig. 6) and SP was most easily obtainable in all subjects when the stimulus was perceived as painful. Moreover, SP was present in patients with Friedreich's ataxia and chronic idiopathic ataxic neuropathy with no recordable SAPs, indicating that, at least in these conditions, the inhibitory response was due only to nociceptive stimulation involving type III and IV afferents. EMG suppression decreased with increasing strength of contraction (Fig. 6). This was probably due to the greater number of motor neurons recruited a n d / o r the increase in discharge frequency of single units. At maximal contraction, the expression (1-SP/PI) approximates that fraction of the total motor neuron pool inhibited by cutaneous stimulation. SP onset and duration vary from trial to trial (Fig. 7). The origin of this variability is not fully understood, but depends on the timing of the induced inhibition within the excitation cycle of the motor neurons firing during contraction. Using a single discharging motoz neuron as a model for the SP, if the inhibitory cuta-

350

A. UNCINI ET AI..

neous stimulus occurs within milliseconds after the motor neuron has fired, the onset latency of the consequent SP would be delayed by the time the neuronal impulse takes to travel from the spinal cord to the muscle before that neuron is inhibited. Alternatively, if the cutaneous stimulus occurs a few milliseconds before firing, the motor neuron would be inhibited sooner in the cycle and the SP onset latency of that motor unit would be shorter. As the SP ends at more or less the same time in sequential trials (Fig. 7), the duration of the SP is shortened or lengthened depending on the timing of its onset, tn our experiments, latency and

duration variability were less pronounced than what would be expected recording single motor neurons because surface electrodes recorded several motor units discharging asynchronously and averaging further reduced trial-to-trial timing differences. The onset latency of the SP represents the summation of 3 temporal events: 1) afferent time from the stimulation site to the spine, (2) central time needed to produce the inhibition of alpha motor neurons, and (3) efferent traveling time from spine to muscle of the last potential that fired before the inhibition. The efferent time is the result of impulse conduction in large diame-

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20ma Fig. 9. Two or 3 real time E M G tracings recorded from the opponens pollicis during isometric contraction (at 50% effort) are superimposed. U p p e r panel: single transcranial cortical stimulation (TCCS) at 40% maximum output produces an M response with a latency of 19 msec (stimulus is indicated by the vertical line artifact delivered 30 msec after the start o f t h e trace). Single digit 2 (D2) stimulation p r o d u c e s the normal SP. Lower panel: paired D2 and TCCS at different interstimulus intervals (ISI). Note the gradual decrease in M response amplitude and duration which reach their lowest, values at an ISI of 60 msec. At this interval, the amplitude is approximately 20% and the duration approximately 33% of their baseline values.

SILENT PERIOD FROM CUTANEOUS STIMULATION

ter motor axons, and can be calculated in the upper and lower extremity using the F (or H) and M response latencies recorded from opponens pollicis and gastrocnemius lateralis according to the formula: M + F (or H)/2. In 5 subjects the mean efferent time was found to be 14.7 msec for OP and 15.4 msec for GL. When subtracted from the corresponding SP onset latencies, the resultant values represent the sum of the afferent and central times: 52.3 msec for OP and 71.2 msec for GL. As OP and GL alpha motor neurons and their spinal circuitry are probably similar, it can be assumed that the central times for OP and GL motor neuron pool inhibition are equal; therefore, the mean latency difference between these two values (18.9 msec) divided into the difference of mean distances (246 mm) between the sural nerve at the ankle to L1 vertebra (1076 mm) and D2 to C7 vertebra (830 mm) determines an approximate conduction velocity of the SP afferent fibers: 13.0 m/sec. This velocity is in the range of conduction velocities for group III fibers (Boyd and Davey 1968). The inhibition produced on the OP motor neuron pool by cutaneous stimulation, as studied by pairing D2 stimulation with descending excitatory volleys in the cortico-spinal tracts induced by TCCS, was maximal between 50 and 70 msec (Fig. 9). This time course, when considering the distance between D2 and the spine, is in agreement with conduction along type III afferents. We investigated the central neural network producing alpha motor neuron inhibition by experimenting with habituation and recovery cycles of the SP. Habituation, defined as a reversible decrement in reflex response as the result of repeated stimulation, is considered to be dependent on the number of synapses present in the neuronal pathway (Desmedt and Godaux 1976). Polysynaptic exteroceptive reflexes, such as the R2 component of blink response and late period of the masseter exteroceptive inhibitory reflex, are highly susceptible to habituation and exhibit a slow recovery cycle (Desmedt and Godaux 1976; Kimura and Harada 1976; Cruccu et al. 1984). Considering the above, the lack of habituation (Fig. 7) and the fast recovery cycle (Fig. 8) exhibited by SP found in this study may suggest that the underlying neuronal network of the cutaneous SP is oligosynaptic. An alternative and more likely explanation is that these findings are the consequence of tonic excitatory voluntary activity, used in testing cutaneously induced SP, which results in an increased responsiveness of the interneurons and motor neurons to afferent stimulation (Desmedt and Godaux 1976). The topography of the induced SP does not exhibit a "local sign" (Hagbarth 1952) because EMG suppression was present in muscles distant to the stimulated cutaneous area, there was a convergence of inhibition from different receptive fields (even contralateral to the recording site) and there was non-reciprocity in

351

antagonistic muscles (Figs. 3-5). This extensive divergence and convergence of different afferent channels on motor neuron pools suggest the utilization of propriospinal pathways. This has been previously shown with reference to reflexes evoked in the leg muscles after brachial nerve stimulation (Meinck and PiesiurStreblow 1981). Cutaneous afferent inputs are considered excitatory in their actions, and the inhibition they exert is mediated through inhibitory interneurons (Eccles 1969). There is experimental evidence that Renshaw cells may be excited, without prior discharge of motor neurons, by stimulation of type II and III fibers via interneurons. The final effect is inhibition on motor neurons (Piercey and Goldfarb 1974). Renshaw cells are known to discharge repetitively for up to 50 msec after a single excitation (Ryall and Piercy 1971), to have a several millimeter rostro-caudal extension of their axons (Ryall et al. 1971) and to show some degree of convergence of excitation from different peripheral afferent segments (Ryall and Piercey 1971). These features resemble some characteristics exhibited by the SP, suggesting that Renshaw cells may have a role in the production of the SP. The increased value of the P I I I / P I ratio (Table I) represents a rebound of EMG activity after the SP. As shown in consecutive EMG tracings, there is a tendency for the resumption of EMG activity to synchronize at the end of the SP, independent of the SP onset (Fig. 7). This synchrony in EMG activity when rectified and averaged produces a higher amplitude signal, the EMG rebound (Fig. 1). The rebound may be due to a brief increase in the discharge frequency of individual motor units or to the recruitment of additional motor units immediately after the inhibition. However, Kranz et al. (1973) using the single fiber recording technique demonstrated that these possibilities are unlikely. The synchronous resumption of firing of the previously inhibited motor units, normally discharging asynchronously during voluntary effort, may have a reflex origin mediated by stretched spindles when the muscle relaxes during the period of inhibition. Circumstantial evidence supporting this hypothesis is the reduced P I I I / P I found in Friedreich's ataxia and chronic idiopathic ataxic neuropathy patients. These patients, representing a model of large diameter fiber deafferentation with spared pain sensitivity (Dyck et al. 1971; Dalakas 1986), exhibit the nociceptively induced SP without a subsequent EMG rebound. This inhibition on motor neurons due to nociceptive stimulation may resemble the withdrawal reflex (Hagbarth 1960) but differs from this for several reasons: the exhibited wide divergence of inhibition on different motor neuron pools, the convergence from distant receptor fields and the non-reciprocity pattern observed in antagonist muscles. It may be that the

352 inhibition of EMG

A. UNCINI ET AL. activity, p r o d u c e d m o r e e f f e c t i v e l y

by n o c i c e p t i v e s t i m u l a t i o n , is a m u l t i s e g m e n t a l r e f l e x w h i c h by b r i e f l y i n h i b i t i n g m o t o r activity, g i v e s h i g h e r c e n t e r s time to p r o c e s s a n d a p p r o p r i a t e l y r e s p o n d to a n u n p r e d i c t a b l e s t i m u l u s . A l t h o u g h t h e b i o l o g i c a l significance o f the c u t a n e o u s l y i n d u c e d SP has yet to be d e t e r m i n e d , a possible application may be the investigation of focal dystonias where a defective central control on interneuronal inhibitory networks has been s u g g e s t e d ( B e r a r d e l l i e t al. 1989a,b).

1985;

Nakashima

e t al.

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