Journal ofPhysiology (1993), 466, pp. 521-534 521
With 5 figures
Printed in Great Britain
SILENT PERIOD EVOKED BY TRANSCRANIAL STIMULATION OF
THE HUMAN CORTEX AND CERVICOMEDULLARY JUNCTION
By M. INGHILLERJ, A. BERARDELLI, G. CRUCCU AND M. MANFREDI
From the Department ofNeurological Sciences, University ofRome 'La Sapienza',
Viale Universita' 30, Rome, Italy
(Received 3 February 1992)
1. The silent period evoked in the first dorsal interosseous (FDI) muscle after
electrical and magnetic transcranial stimulation (TCS), electrical stimulation of the
cervicomedullary junction and ulnar nerve stimulation was studied in ten healthy
2. With maximum-intensity shocks, the average duration of the silent period
was 200 ms after electrical TCS, 300 ms after magnetic TCS, 43 ms after
stimulation at the cervicomedullary junction and 100 ms after peripheral nerve
3. The duration of the silent period, the amplitude of the motor-evoked
potential, and the twitch force produced in the muscle were compared at increasing
intensities of magnetic TCS. When the stimulus strength was increased from 30 to
70 % of the stimulator output, the duration of the silent period lengthened as the
amplitude of the motor potential and force of the muscle twitch increased. At 70 to
100 % of the output, the amplitude of the motor potential and force of the muscle
twitch saturated, whereas the duration ofthe silent period continued to increase.
4. Proximal arm muscle twitches induced by direct electrical stimulation of the
biceps and extensor wrist muscles produced no inhibition of voluntary activity in
the contracting FDI muscle.
5. The level of background activation had no effect on the duration of the silent
period recorded in the FDI muscle after magnetic TCS.
6. Corticomotoneurone excitability after TCS was studied by means of a single
magnetic conditioning shock and a test stimulus consisting either of one single
magnetic shock or single and double electrical shocks (interstimulus interval 1P8 ms)
in the relaxed muscle. A conditioning magnetic shock completely suppressed the
response evoked by a second magnetic shock, reduced the size of the response
evoked by a single electrical shock but did not affect the response evoked by double
electrical shocks. Inhibition of the test magnetic shock was also present during
7. Our findings indicate that the first 50 ms of the silent period after TCS are
produced mainly by spinal mechanisms such as after-hyperpolarization and
recurrent inhibition of the spinal motoneurones. If descending inhibitory fibres
M. INGHILLERI AND OTHERS
contribute, their contribution is small. Changes in proprioceptive input probably
have a minor influence. From 50 ms onwards the silent period is produced mainly
by cortical inhibitory mechanisms.
Marsden, Merton & Morton (1983) first demonstrated that electrical stimulation
of the motor cortex in man produces a muscle twitch followed by a silence of EMG
activity. They suggested that this silent period after cortical stimulation was
different from the silent period evoked by stimulation of a peripheral nerve
(Merton, 1951). Since then, other authors have recorded a silent period in the hand
muscles after transcranial stimulation (TCS) and have investigated the underlying
physiological mechanisms. Using surface EMG and needle recordings of single
motor units from the forearm muscle, Calancie, Nordin, Wallin & Hagbarth (1987)
studied the silent period after electrical TCS and suggested that the inhibitory
period was determined mainly by changes in proprioceptive input induced by the
muscle twitch and partly by activation of descending inhibitory influences. In a
study of the silent period and H reflex conditioning in wrist flexors after magnetic
TCS, Fuhr, Agostino & Hallett (1991) concluded that the silent period depended
initially on spinal mechanisms and subsequently on the interruption of voluntary
In this study we investigated the physiological mechanisms of the silent period
occurring after transcranial cortical stimulation. To examine the possible role of
proprioceptive inflow and spinal mechanisms, we measured the duration of the
silent period, the amplitude of the motor-evoked potential (MEP) and the muscle
twitch force, at various intensities of the magnetic shock and at different levels of
background force. In addition, we compared the silent period evoked by electrical
and magnetic TCS with that produced by electrical stimulation of the motor tracts
at the cervicomedullary junction (Ugawa, Rothwell, Day, Thompson & Marsden,
1991; Berardelli, Inghilleri, Rothwell, Cruccu & Manfredi, 1991 b) and studied the
excitability of muscle responses evoked by transcranial stimulation with paired
Ten normal subjects aged between 25 and 41 years participated in the study. Experiments
were repeated in a smaller group of five subjects including the authors. Informed consent was
obtained and the study was approved by the local ethical committee.
Cortical stimuli were delivered by a magnetic stimulator (modified version of Novametrix
Magstim 200) with a flat coil, having an outer diameter of 14 cm. The coil was centred over the
vertex, with the current flowing anticlockwise when viewed from above. The cortex was also
stimulated electrically with a prototype electrical stimulator that delivered single or paired
shocks at short time intervals (700 V maximum output, 100 Us time constant). The anode was
placed on the scalp overlying the motor areas (7 cm from the mid-line on a line joining the vertex
to the external auditory meatus) and the cathode on the vertex. Stimulation varied in intensity
from 50 to 100 % ofthe output ofthe stimulator.
Electrical stimulation of the descending motor tracts at the level of the cervicomedullary
junction was performed using the method of Ugawa et al. (1991). Briefly, surface electrodes were
placed on the posterior edge of each mastoid process on both sides of the inion, with the anode on
the right and the cathode on the left. Electrical stimuli were delivered with a Digitimer D180
SILENT PERIOD AFTER TRANSCRANIAL STIMULATION
stimulator. Stimulus intensity varied in different subjects from 40 to 60 % of the output. Higher
intensities produced spread of current to the cervical roots; this was recognized by a shortening of
response latency (latencies to root stimulation were shorter than those evoked by stimulation of
the descending motor tracts) and the presence ofresponses at rest (Ugawa et al. 1991).
The ulnar nerve was stimulated at the wrist with supramaximal electrical stimuli (250 V,
0-2 ms duration).
The biceps and wrist extensor muscles were activated directly with electrical stimuli (150 V,
0'5 ms) delivered through surface electrodes placed over the belly ofthe muscle.
The rate of TCS, descending motor tracts, peripheral nerve and muscle stimulation was always
longer than 0 1 Hz.
The subjects were seated comfortably on a chair with their forearm resting on a table. They
were instructed to exert a 30-40 % of maximum voluntary contraction of the first dorsal
interosseous (FDI) muscle and the silent period was recorded after: (1) transcranial magnetic; (2)
transcranial electrical; (3) electrical stimulation of the cervicomedullary junction; (4) ulnar nerve;
and (5) biceps and wrist extensor muscles stimulation.
The subjects maintained the isometric contraction of the FDI muscle by abducting the index
finger against a strain gauge. A strap attached to the table immobilized the fingers and wrist so as
to prevent finger and hand movement assisting the first dorsal interosseous muscle. A strain
gauge attached to the proximal interphalangeal joint of the index finger measured the twitch
force produced by cortical and brainstem stimulation in the FDI muscle.
The silent period was also studied during three levels of muscle contraction (30, 60 and 100 %
of the maximum effort measured using a strain gauge).
EMG activity from the FDI muscle was recorded with surface electrodes and sampled with an
OTE Basis device (bandwidth 2-5000 Hz) or a Cambridge Electronic Design 1401 programmable
interface. The EMG was also full-wave rectified and ten trials were averaged. From the rectified
EMG activity, a screen cursor measured the duration of the silent period, from the end of the
muscle potential evoked by cortical stimulation to the return of EMG activity. The latency ofthe
MEPs was measured at the onset and the amplitude was measured peak to peak. The amplitude
of the twitch force was measured from the onset to the peak.
Conditioning experiments with paired transcranial shocks
Cortical excitability was tested in five subjects at rest. A single magnetic shock was given as a
conditioning stimulus. This was then followed by a test stimulus consisting of either a single
magnetic shock or single or double electrical shocks given at short intervals (1P8 ms) (Inghilleri,
Berardelli, Cruccu, Priori & Manfredi, 1989, 1990). The intensity of the conditioning magnetic
stimulus was set to 80 % of the output of the stimulator. When the test stimulus was a magnetic
shock, two Novametrix Magstim 200 stimulators were used (one for conditioning and the other
for test shocks) and the two coils were positioned one above the other on the scalp. The
conditioning and test shock were given at a similar intensity (80 %). Because the coil delivering
the test shock was farther from the scalp, the amplitude of the unconditioned test MEP (control)
was slightly smaller than the amplitude of the MEP evoked by the conditioning stimulus. The
magnetic field generated by the conditioning shock had no effect on the current induced by the
test shock and measured by a probe placed near the test coil.
When a single electrical shock was used as the test stimulus the intensity of stimulation was
set at 60-70 % of the stimulator output to evoke a response with an amplitude similar to that
evoked by the magnetic test shock.
The use of double instead of single electrical shocks allowed us to evoke MEPs of an amplitude
similar to that yielded by the magnetic shocks, despite keeping the electrical stimulator at a low
intensity (45 % output).
The intervals between the conditioning and test stimuli (single magnetic and single or double
electrical shocks) were 100, 150 and 200 ms. For each interval five trials were averaged and the
various conditions were randomized and then averaged.
The experiments using double magnetic shocks were also performed during maximum
voluntary contraction. The intervals between the conditioning and test stimulus were 100 and
Statistical significance was evaluated using Student's t test. All results are given as means
+ S.D. unless otherwise stated.
M. INGHILLERI AND OTHERS
Silent period after cortical (magnetic and electrical), cervicomedullary and peripheral
Magnetic stimulation produced an MEP followed by a total inhibition of the on-
going EMG activity. With maximum output of the stimulator, the average
duration of the silent period in ten subjects was 300 + 54 ms (range 190-400 ms).
The mean latency of the MEPs was 20X6 + 1 ms and the amplitude was 7X4 + 2 mV.
Fig 1. Silent periods after transcranial magnetic (A), electrical (B), and nerve (C)
stimulation. Recordings from the FDI muscle during maximum voluntary contraction
in one normal subject. Superimposition oftwo single trials. Stimulation rate 0 1 Hz.
Electrical cortical stimulation evoked an MEP followed by total inhibition of the
on-going EMG activity. At maximum stimulus intensities the average duration of
the silent period was 205 + 80 ms (range 130-320 ms). The mean latency of the
MEP was 20-0 + 1P1 ms and the amplitude was 7-1 + 2-2 mV.
In five subjects electrical stimulation of the cervicomedullary junction evoked
MEPs at a latency of 18-3 + 1 ms and an amplitude of 6-6 + 1-6 mV. The MEP was
followed by a silent period of 43'1 + 4-6 ms (range 38-50 ms). Supramaximal ulnar
nerve stimulation also inhibited on-going EMG activity in the FDI muscle (mean
duration of the silent period in ten subjects was 97 7 + 13 1 ms; Fig. 1). The M wave
amplitude was 11-7 + 1-9 mV.
Comparison between the silent period evoked by transcranial and cervicomedullary
Since the amplitude of MEPs evoked by cervicomedullary junction stimulation
were lower than those produced by transcranial stimulation we compared the
duration of the silent period following MEPs of the same size. The intensity of
cervicomedullary junction stimulation, and magnetic and electrical TCS were
SILENT PERIOD AFTER TRANSCRANIAL STIMULATION
adjusted to produce MEPs of similar amplitude for each of the three stimuli
(6-6 + 1P9 mV magnetic MEP; 6-5 + 1P4 mV electric MEP; 66 + 16 mV
cervicomedullary MEP). The magnetic and electrical TCS intensities were 65 + 5
and 70 + 5 % of the maximum output respectively.
LIa 50 ms
Fig 2. Silent period after brainstem (A and B), electrical (C and D) and magnetic (E and F)
transcranial stimulation. Traces are averages of 10 single trials in one subject. In A, C and
Ethe EMG is unrectified and in B, D and Fit is rectified. Vertical calibration is 3 mV in A,
Cand Eand 400,uV in B, D and F
The duration of the silent period was 234 + 68-7 ms after magnetic stimulation,
102 + 42 ms after electrical stimulation and 43 1 + 4X6 ms after cervicomedullary
junction stimulation. Differences between the silent periods were statistically
significant (P < 0 001).
Because the twitch force produced by cervicomedullary junction stimulation was
always smaller than that produced by transcranial stimulation, the silent period
after transcranial and after cervicomedullary junction stimulation could not be
compared at twitch forces ofsimilar amplitude.
Effect of increasing intensities of magnetic cortical stimulation on the silent period,
MEP amplitude and twitch force
In six subjects, the behaviour of the silent period was studied with increasing
intensities of cortical stimulation. The silent period progressively increased with
the strength of magnetic stimulation. Figures 3 and 4 show the behaviour of the
silent period in relation to the peak size of the MEPs and in relation to the size of
the twitch force produced by the MEP. When the intensity ofmagnetic stimulation
M. INGHILLERI AND OTHERS
was increased from 30 to 100 % of the output of the stimulator the duration of the
silent period progressively increased, unlike the peak-to-peak size of the MEP and
the twitch force, which at first increased and then plateaued at 60-70 % of the
output ofthe stimulator.
1880BGj> _ % ~~~~80%
Fig 3. Effect of increasing stimulation intensity (80 and 100 %) on the silent period after
transcranial magnetic stimulation in one normal subject. Increasing the stimulation
intensity from 80 to 100% of maximum caused the duration of the silent period to
increase, whereas the amplitude of the MEPs (A and D) and of the twitch force (C and F)
saturated. Traces are averages of 10 single trials. The EMG is unrectified in A and D, and is
rectified in B and E. Vertical calibration is 3 mV in A and D; 200 ,uV in B and E; and 5 N
in Cand F Horizontal calibration is 50 ms. Stimulation rate 0 1 Hz.
Although the size of the MEP and the twitch force usually reached a plateau at
approximately the same intensity of stimulation, in some subjects the size of the
MEP saturated first. This phenomenon has been already described by Day et al.
Effect of twitches of other muscles on the FDI voluntary activity
High intensity transcranial stimulation also produces twitches in proximal
muscles. Afferent feedback from these muscles might, therefore, contribute to the
silent period in the FDI muscle. To verify whether afferent activity from proximal
arm muscles contributed to the silent period, electrical stimuli were delivered
directly to the biceps and wrist extensor muscles, thus evoking a strong twitch in
these muscles, while the subjects voluntarily contracted the FDI muscles. In the
five subjects tested twitches in the proximal muscles failed to inhibit EMG activity
in the FDI muscle.
SILENT PERIOD AFTER TRANSCRANIAL STIMULATION 527
Effect of voluntary contraction on the silent period after magnetic stimulation
Five subjects were studied at 80 % maximum stimulation strength, while
exerting increasing levels of background contraction. With a 30 % maximum
muscle contraction, the duration of the silent period was 191P4 + 40 ms. With a
60 % contraction, the duration of the silent period was 182 + 51 ms and with a
100 % contraction, the duration ofthe silent period was 183 + 60 ms.
E 9-6 J 320X
7*2 -// 240 C-0
E 4-8 -
- 160 ,
w 24 - -80 lo
0 20 40 60 80 100 120
9 J 320 E
Z - 240 r-
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0 20 40 60 80 100 120
Intensity (% output)
Fig. 4. Effect of increasing stimulation intensity (20 to 100 %) on the silent period after
transcranial magnetic stimulation in six normal subjects. The upper panel shows the
relationship between the amplitude of muscle evoked responses (MEP, continuous line),
the duration of the silent period (SP, dashed line) and the intensity of magnetic
stimulation. The lower panel shows the relationship between the size of the twitch force
(Force, continuous line), duration of the silent period (SP, dashed line) and intensity of
magnetic stimulation. Increasing the stimulation intensity from 60 to 100 % of maximum
output caused the MEP and the twitch force to increase progressively in size and then
saturate at 60 and 70 % respectively, whereas the silent period became longer. The
continuous and dashed lines represent the mean values + S.E.M.
Conditioning experiments with paired cortical stimuli
In five subjects, cortical excitability was tested with a magnetic shock as
conditioning stimulus and either a single magnetic shock or electrical shocks (single
and double) as test stimuli. The experiments were performed with the subjects at
rest: (1) to minimize the variability due to changes in spinal cord excitability, and
(2) to see whether interrupting the voluntary cortical drive played a role in
producing the silent period.
At time intervals of 100, 150 and 200 ms the conditioning magnetic shock
completely abolished the test response to the single magnetic shock and markedly
reduced the amplitude of the test response evoked by a single electrical shock (the
M. INGHILLERI AND OTHERS
test response was 10 + 4 % of the control response at 100 ms; 9 + 4 % at 150 ms and
57 + 18 % at 200 ms intervals). The conditioning magnetic shock did not suppress
the test response evoked by the double electrical shocks (Fig. 5): the test response
was 107 + 10 % at 100 ms, 100 + 9 % at 150 ms and 115 + 20 % at 200 ms
f. ,.PA Magnetic
Fig 5. Effect ofmagnetic conditioning stimulation on magnetic and electrical test stimuli
given at a time interval of 100 ms. The magnetic conditioning shock completely
suppressed the test magnetic response (A), reduced the size of the response evoked by a
single electrical shock (B), but did not inhibit the response evoked by double electrical
shocks (C). Traces are averages of 10 single trials in one subject. Dashed traces represent
the unconditioned responses.
Figure 5 shows these responses in a normal subject after conditioning and test
stimuli given at an interval of 100 ms. The conditioning magnetic shock completely
suppressed the test response to magnetic shocks; the test response to a single
electrical shock was inhibited but the test response to double electrical shocks was
To see whether the inhibition present in relaxed muscle was also evident in
active muscle, the recovery curve of the response to a second magnetic stimulus
delivered at intervals of 100 and 200 ms after a conditioning magnetic shock was
studied during maximum voluntary contraction. The test response was completely
suppressed at 100 ms and strongly inhibited at 200 ms (29-8 + 25 % of the control
As observed by Marsden et al. (1983), transcranial stimulation of the motor
cortex produces a long-lasting silent period. We found silent periods lasting 200 ms
after electrical and 300 ms after magnetic stimulation, decidedly longer than the
silent periods evoked by electrical stimulation of the peripheral nerve. With
SILENT PERIOD AFTER TRANSCRANIAL STIMULATION
magnetic stimulation, silent periods lasting up to 350-400 ms could be obtained by
setting the stimulator to maximum output and placing a large coil over the vertex.
The silent period following electrical stimulation of a peripheral nerve in a
contracting muscle is generally agreed to be the result of a sequence of events
(Merton, 1951; Shahani & Young, 1973). Initially, a partial collision of orthodromic
and antidromic impulses occurs in the motor fibres. Motoneurone inhibition due to
after-hyperpolarization (AHP) and the activation of the recurrent inhibition by
antidromic impulses then follows. The last part ofthe inhibition is multifactorial in
origin. The mechanisms responsible include muscle spindle unloading, Golgi tendon
organ activation, and excitation ofcutaneous fibres.
In the silent period after transcranial stimulation, some of the effects of
peripheral nerve stimulation, namely collision and direct activation of sensory
fibres, do not take place. Other spinal mechanisms, including AHP, recurrent
inhibition and changes in proprioceptive input produced by the muscle twitch,
may follow both transcranial and peripheral stimulation. Activation of descending
inhibitory fibres, interruption of the voluntary cortical drive, and activation of
cortical inhibitory systems may also play a role.
Role of 'spinal' mechanisms
In comparison to the silent period after cortical stimulation, the silent period
that we observed after stimulation of the motor tracts at the cervicomedullary junction
was remarkably short, 43 ms. Stimulation across the base of the skull activates the
motor tracts at a latency that is approximately 1X5-2 ms shorter than the latency
of the responses evoked by cortical stimulation (Ugawa et al. 1991; Berardelli et al.
1991 b). On the basis of collision experiments between cortical and medullary
volleys, Ugawa et al. (1991) suggested activation of the large-diameter axons of
the corticospinal tract. The authors also commented that the short-onset latency
and stability of the EMG responses suggest that axons with rapid conduction
velocity and monosynaptic connections are activated. Although other ascending
and descending fibres are probably excited by the cervicomedullary junction
stimulation, it is unlikely that activation of other fibres could modify cortical and
spinal excitability to shorten the silent period. Single electrical shocks delivered to
the descending tracts produce only short-lasting changes in spinal cord excitability
(Lemon & Mantel, 1989; Inghilleri et al. 1990). Excitation of ascending systems
may alter cortical excitability; for example, cutaneous afferent input can enhance
cortical excitability to magnetic stimulation (Day et al. 1988; Deuschl, Michels,
Berardelli, Schenck, Inghilleri & Lucking, 1991) but these changes are relatively
small. Furthermore, the silent period to cervicomedullary stimulation cannot be
affected by post-twitch proprioceptive input until 50 ms after the onset of the MEP
(approximately 20 ms for muscle shortening and receptor activation, and 30 ms for
afferent and efferent conduction times; Shahani & Young, 1973).
Overall, it seems unlikely that excitation of other systems is responsible for the
short silent period to cervical junction stimulation. In addition, because
cervicomedullary stimulation bypasses the cortex, the silent period to this form of
stimulation is not influenced by the level of cortical excitability.
Having excluded these influences as contributing to the short-lasting silent
period after cervicomedullary stimulation, we must now consider the influence of
M. INGHILLERI AND OTHERS
spinal inhibitory mechanisms (AHP and recurrent inhibition) and the activation of
descending inhibitory fibres on the silent period.
After-hyperpolarization and recurrent inhibition start immediately after
antidromic invasion, quickly reach maximum, decline after 20-25 ms and
disappear within 200 ms (Bussel & Pierrot-Deseilligny, 1977; Kernell, 1983;
Morales, Boxer, Fung & Chase, 1987). These mechanisms have also been proposed
to explain the refractoriness of motoneurones observed in studies using paired
cortical stimuli (Inghilleri et al. 1990). Activation of descending inhibitory fibres
probably has little bearing upon the production of the silent period. In animal
experiments, stimulation of corticofugal inhibitory fibres (Cheney, Fetz & Palmer,
1985; Lemon, Muir & Mantel, 1987) produces a short-lasting suppression of the on-
going EMG activity; inhibition starts a few milliseconds after excitation. Using
transcranial stimulation and the H reflex technique in man, Cowan, Day, Marsden
& Rothwell (1986) demonstrated in the upper limbs a short period of facilitation
followed by an inhibition lasting 1-2 ms.
The silent period produced by cervicomedullary stimulation thus appears to
depend mostly on the spinal inhibitory mechanisms that follow motoneuronal
excitation: AHP and recurrent inhibition. The same spinal mechanisms probably
operate in the first 40-50 ms ofthe silent period after cortical stimulation.
Although the intensity of magnetic cortical stimulation was lowered to produce
MEPs of the same size as those evoked by electrical stimulation at the
cervicomedullary junction, magnetic cortical stimulation still produced a silent
period that lasted far longer (234 versus 43 ms). Assuming that the size of MEPs
gives a relative measure of the number of motoneurones excited, the contribution
of the spinal mechanisms (AHP and recurrent inhibition) appeared similar in the
two conditions. Mechanisms other than AHP and recurrent inhibition must
therefore be responsible for the long silence occurring from 50 to 250 ms.
Role ofproprioceptive mechanisms in the silent period after cortical stimulation
As though the amplitude of MEPs is smaller than the M wave evoked by
peripheral nerve stimulation, cortical stimulation produces a muscle twitch that is
even larger than that produced by peripheral nerve stimulation (Day et al. 1987).
This raises the possibility that there might be greater changes in proprioceptive
inflow after cortical stimulation.
In the experiment testing the effect of magnetic TCS at a range of intensities,
increasing the stimulation intensity from 30 to 70 % of the output of the stimulator
caused the duration of the silent period to increase gradually from 80 to 160 ms.
This was paralleled by a progressive increase in the MEP amplitude and the twitch
force. However, increasing the stimulation intensity from 70 to 100 % did not lead
to a further increase in the MEP amplitude or twitch force, yet the duration of the
silent period continued to increase, reaching 320 ms. If afferent feedback also
reaches a plateau with muscle contraction, it is unlikely to contribute to the
continuing prolongation of the silent period as the intensity of stimulation is
However, at high magnetic stimulation intensities, afferent feedback from other
muscles activated by TCS may contribute to the later parts of the silent period in
SILENT PERIOD AFTER TRANSCRANIAL STIMULATION
the FDJ. This contribution is unlikely to be a major one since electrically induced
twitches in other muscles did not inhibit FDI activity.
The experiments testing the effect of increasing levels of contraction showed that
when the force of contraction increased, the duration of the silent period after
transcranial stimulation remained constant. During maximum contraction Golgi
tendon organs are maximally facilitated and as a consequence the twitch is
expected to generate the maximum proprioceptive input from these receptors.
Whether or not the variations in background force alter the duration of the silent
period evoked by peripheral nerve stimulation is still controversial. According to
some reports the higher the force exerted the shorter the silent period after nerve
stimulation (Merton, 1951). For the silent period evoked by transcranial
stimulation our experiments have ruled out any obvious relationship to
Taken together all the above experiments suggest that changes in the
proprioceptive input induced by muscle twitch play no major role in the silent
period after TCS.
Role of cortical mechanisms in the silent period after cortical stimulation
Several authors suggest that transcranial stimulation may not only excite the
motor cortex but may also interfere with cortical activity. Penfield & Jasper (1954)
first observed that direct stimulation of motor cortex produces slowing and
interruption of movements, and more recently Day et al. (1989 b) and Berardelli,
Inghilleri, Cruccu & Manfredi (1991 a) have shown that electrical and magnetic
transcranial stimulation cause the execution of rapid limb movements to be
delayed or interrupted, an interference they attributed to intracortical
The conditioning experiments with paired cortical stimuli described in this paper
demonstrate that the later part (from 50 ms onward) of the silent period after
magnetic transcranial stimulation is produced by intracortical mechanisms.
Using the technique described by Inghilleri et al. (1989, 1990), we delivered a
short-interval doublet of low-intensity electrical shocks, generating two volleys in
the corticospinal axons in order to excite through temporal summation a large
number of spinal motoneurones. The motor potential evoked by this doublet of
electrical shocks was unaffected by a preceding conditioning magnetic shock. This
proves that the spinal motoneurones were not inhibited at the time of arrival ofthe
double descending volleys. As Day, Marsden, Rothwell, Thompson & Ugawa (1990)
also point out, inhibition does occur if the response is evoked by a single electrical
shock. A single electrical shock that activates the corticospinal axons produces a
direct wave, often followed by cortical later waves (Inghilleri et al. 1989; Edgley,
Eyre, Lemon & Miller, 1990; Burke, Hicks & Stephen, 1990). With the muscle at
rest, the size of the response evoked by transcranial electrical stimulation depends
on the arrival of the later cortical waves at the spinal motoneurones (Day et al.
1987). The reduction in size of the response to the test electrical shock, produced by
the conditioning magnetic shock, is probably due to inhibition of the later cortical
waves. When we used a second magnetic shock as a test, and the subject was at rest,
the test motor potential was abolished by the conditioning magnetic shock. In
M. INGHILLERI AND OTHERS
active muscles the test motor response was strongly inhibited, though not
abolished, probably because inhibitory and excitatory inputs summated at the
level of pyramidal cells. The inhibition of the test magnetic response indicates that
the second magnetic shock, which is expected to excite predominantly cortical
elements, is unable to discharge the pyramidal cells (Hess, Mills & Murray, 1987;
Day et al. 1989 a; Berardelli, Inghilleri, Cruccu & Manfredi, 1990).
The reasoning above could also explain the shorter duration of the silent period
after electrical transcranial stimulation (200 ms) compared with that after
magnetic stimulation (300 ms). Inhibition is more powerful after magnetic
stimulation. This is because it predominantly activates cortical elements whereas
electrical stimulation mainly activates corticospinal axons (Rothwell, Thompson,
Day, Boyd & Marsden, 1991).
The exact mechanisms underlying cortical inhibition are more difficult to
establish. Using an H reflex technique to test the excitability of the spinal
motorneurone pool during the silent period produced by cortical stimulation, Fuhr
et al. (1991) propose, as we do, that the beginning of the silent period depends on
spinal inhibitory mechanisms, whereas the later part depends on the interruption
of the voluntary cortical drive. The hypothesis of a simple loss of the cortical drive
onto the spinal motoneurones is ruled out by our experiments demonstrating
inhibition of a test MEP when conditioning and test shocks are delivered in the
fully relaxed subject.
Activation of inhibitory collaterals of the pyramidal cells themselves is also
unlikely since stimulation of the motor tracts at the cervicomedullary junction,
despite producing antidromic invasion of pyramidal cells, only induced a short-
lasting silent period.
We believe that the silent period results from activation of inhibitory neurones
projecting onto the pyramidal cells of the motor cortex. These neurones are widely
disseminated in cortical areas. In animals, Krnjevic, Randic & Straughan (1966a, b)
found that direct and indirect cortical electrical stimuli could produce a long-
lasting inhibition (100-300 ms) of the cortical neurones. Repetitive, surface
stimulation of the motor cortex itself produced the longest-lasting inhibition of the
pyramidal cells. The cells held responsible for the inhibition are the Golgi II cells
with long axons (Krnjevic, Randic & Straughan, 1964).
Finally, the powerful excitation of cortical cells produced by high-intensity
magnetic shocks may give rise to an intense after-hyperpolarization, an effect that
would also contribute to the block ofthe motor cortex.
In conclusion, the silent period after cortical stimulation is generated by several
mechanisms. In the first 50 ms, spinal factors (recurrent inhibition and AHP)
operate, with a possible contribution by descending inhibitory fibres. Although a
contribution by post-twitch proprioceptive changes cannot be definitely excluded,
we believe that the proprioceptive input cannot be responsible for the later part of
the silent period after magnetic stimulation. This part ofthe silent period probably
results from inhibitory effects at the cortical level.
We would like to thank Dr P.D. Thompson for reading the final version and Mrs Diana
Brusoni for typing the manuscript.
SILENT PERIOD AFTER TRANSCRANIAL STIMULATION 533
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