Akinesia in Parkinson's disease. I.

Shortening of simple reaction time with

focal, single-pulse transcranial magnetic stimulation
A. Pascual-Leone, J. Valls-Sol, J. P. Brasil-Neto, L. G. Cohen and M. Hallett
Neurology 1994;44;884

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Akinesia in Parkinsons disease.

I. Shortening of simple reaction time with
focal, single-pulse transcranial magnetic stimulation
A. Pascual-Leone, MD, PhD; J. Valls-Sol& MD, PhD; J.P. Brasil-Neto, MD;
L.G. Cohen, MD; and M. Hallett, MD

Article a b s t r a c G W e studied the effects of transcranial magnetic stimulation (TMS) of the motor cortex on simple reaction time (RT) in 10 patients with Parkinsons disease compared with 10 age-matched normal controls. The subjects
flexed their right elbow rapidly in response to a visual go-signal. In random trials, TMS was applied to the left motor
cortex at varying delays after the go-signal. In trials without TMS, RT was longer in the patients. However, in the trials with subthreshold TMS, RT in the patients became as fast as RT in trials without TMS in the controls. This shortening was associated with normalization of the voluntary triphasic EMG pattern and the pre-movement cortical excitability increase.
NEUROLOGY 1994;44:884-891

Delayed motor initiation (akinesia) and slowness of

ongoing movements (bradykinesia) are probably
the most debilitating manifestations of Parkinsons
disease (PD).1,2Akinesia is marked by a prolonged
reaction time (RT),while bradykinesia leads to prolonged movement time. The pathophysiologic
mechanisms responsible for these disturbances remain unclear. Content, selection, and assembly of
motor programs are essentially n ~ r m a l , l ,while
~-~
there is marked impairment in their execution.1,2,9-13
This may be related to the fact that in PD it takes
abnormally long to activate the motor cortex suffciently to initiate the execution of the motor program.2 If so, externally increasing the excitability
of the motor cortex may help improve RT.
In normal volunteers, transcranial magnetic
stimulation (TMS) delivered over the motor cortex
at intensities below motor threshold speeds up simple RT to acoustic, visual, and somatosensory go~igna1s.l~
The effects of TMS on RT are thought to be
due to modulation of intracortical connection^.^^-^^ In
the present study, we investigated the effects of
TMS on simple RT in patients with PD.
Methods. Subjects. We studied six men and four women
with PD, aged 48 to 73 years (mean, 62 years), whose
characteristics are summarized in the table. All patients
were evaluated by the Cognitive Neuroscience Section at
NINDS with a battery of neuropsychologic tests, and
none of the patients entered in this study showed any evidence of cognitive impairment. All patients were taking
carbidopailevodopa and deprenyl; patients 2, 4,5, and 7
were also on anticholinergic medications. The medication

regimen had been stable in all patients for a t least 4

months prior to the study. The experiments were conducted at the time of peak levodopa effect in all patients.
The peak levodopa effect was defined based on the patients subjective reports of their motor capabilities in relation to the time of the last levodopa dose and on serial
neurologic examinations between doses. In addition, patients l, 3, and 6 were also studied after withholding
their medications for 3 days in order to evaluate the effects of levodopa on the results.
We also studied 10 normal volunteers, six men and
four women, aged 52 to 71 years (mean, 60 years). All
these control subjects were naive to the RT task used in
the study, but all had participated in previous studies in
our laboratory and had experienced TMS. All subjects
gave written informed consent for participation in the
study, which had been approved by the institutional review board.
Experimental design. The subject was seated comfortably on a chair with the right arm slightly abducted a t
t h e shoulder and flexed 90 at the elbow so t h a t the
pronated arm rested on a horizontal platform. An auditory warning signal was followed at a random interval (1
to 5 seconds) by a visual go-signal. In response to the gosignal, the subject flexed the right elbow as rapidly as
possible to touch the right shoulder with the hand. The
visual go-signal was a flash generated by a Grass PS22
photic stimulator and delivered at 100% of the stimulators output intensity by a lamp positioned at eye level 30
cm in front of the subject.
The subjects were allowed some time to practice before
the experiments began in order to familiarize them with
t h e task. During 30 practice trials, the subjects were
given feedback about their RTs and encouraged to move
as fast as possible in order to minimize RT variability.

From the Human Cortical Physiology Unit, Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and
Stroke, National Institutes of Health, Bethesda, MD.
Received December 27, 1991. Accepted for publication in final form October 26, 1993.
Address correspondence and reprint requests to Dr. Mark Hallett, Building 10, Room 5N226, NINDS, NIH, Bethesda, MD 20892.
884 NEUROLOGY 44 May 1994

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Table. Clinical characteristics of the patients with Parkinsons disease

I
1
2
3
4
5
6
7
8
9
10

Age*

Sex

H & Yt

S & ES

Freezing

56
62
59
67
73
70
65
48
54
69

M
M

I1
11

F
M
F
F
M
M
F
M

111

80%
70%
80%
70%
60%
60%
70%
70%
70%
80%

0
1
0
1
3
2
2
1
3
2

I1
IV
111
111
111

I11
I11

URSPO
Tremor Rigidity
0
0
1
1
1

2
1

0
0
2

1
2
2
2
3
3
3
1
2
2

Bradykinesia#

Duration*

2
3
3
2
4
3
4
4
3
3

9
12
9
7
14
6
9
2
3
4

* Expressed in years.
t Hoehn and Yahr classification.
$ Schwab and England Activities of Daily Living Scale.
0 Unified Rating Scale for Parkinsonism.
Mean score for the following URSP categories: tremor, tremor a t rest, and action or postural tremor.
# Mean score for the following URSP categories: finger taps, hand movements, rapid alternating movements of hands, leg agility, and body
bradykinesia.

Experiment 1: reaction time. The experiment was performed in sets of 10 trials presented in random order. In
each set, five of the trials were control trials (go-signal
only), three were test trials (go-signal plus TMS), and
two were catch trials (TMS only) (figure 1A). In the test
trials, TMS was delivered before (negative) or after (positive) the go-signal; delay ranged from -50 msec to +60
msec and was randomly varied in the different trials. We
also studied the effects of varying intensities of TMS delivered concurrently with the go-signal (delay = 0). The
catch trials served t o ensure that the subjects were responding to the go-signal and not to the magnetic stimulus.l4JSTwenty sets of trials (200 trials) were completed
by each subject. If the subject responded to any of the
catch trials in a given set, the entire set of 10 trials was
discarded from further analysis. We found no difference
in the frequency of responses t o catch trials between PD
patients and controls. The main reason for omitting an
entire set of trials when the subject responded to a single
catch trial was t o allow comparison of the results with
those obtained in our previous studies on normal volunt e e r ~ . In
~ ~addition,
J~
errors in catch trials indicate a
lapse of attention, and we wanted to make sure that the
attention level and the performance of each subject
across sets of trials was as constant as possible.
Experiment 2: pre-movement excitability buildup. We
recorded 100 t o 200 trials per subject. In one-half of the
trials we used the visual go-signal (control trials). In the
other half, the go-signal was the same visual stimulus
coupled with a subthreshold transcranial magnetic stimulus delivered t o the ideal position for inducing motor
evoked potentials in the contralateral biceps (test trials)
(figure 1B). In both control and test trials, a subthreshold transcranial magnetic stimulus (probing stimulus)
was delivered at varying times after the go-signal to assess the probability of inducing motor evoked potentials
in the biceps as a function of the proximity of voluntary
EMG onset.14J9In test trials, the probing stimulus was
identical in intensity and localization to the magnetic
stimulus coupled with the visual stimulus as part of the
go-signal. The amplitude of the motor evoked potential
was expressed a s a percentage of the maximal M-response following peripheral electrical nerve stimulation.
Electromyographic recording. Pairs of surface elec-

trodes (DISA 13K60) were placed 4 cm apart on the skin

overlying the belly of the right biceps and triceps brachii,
and a Grass accelerometer was taped to the subjects
forearm. EMG and accelerometer signals were amplified
and filtered (100 to 2,000 Hz) by Grass amplifiers, digitized with a sampling rate of 5,000 Hz per channel, rectified, and collected using an AST personal computer. Alternatively, EMG activity was recorded by a Dantec
Counterpoint electromyograph with a bandpass of 30 Hz
to 2 kHz and sensitivity ranging from 50 to 1,000 pV per
division.
Transcranial magnetic stimulation. We used a Cadwell MES 10 magnetic stimulator (experiment 1) or a
Cadwell Rapid-Rate magnetic stimulator (experiment 2)
and a n 8-shaped coil in which each wing measured 4.5
cm in diameter. The Cadwell Rapid-Rate magnetic stimulator is capable of delivering twin pulses at intervals as
short as 30 msec without changes in the amplitude of the
p u l ~ e .The
~ ~coil
, ~ was
~ held flat on the scalp with the intersection of the two wings centered over the position at
which TMS induced motor evoked potentials of maximal
amplitude in the contralateral biceps. This position was
determined, with the patient a t rest, by stimulating several times at the stimulators maximal output intensity
(approximately 2.5 T) over different scalp positions.21
The handle of the coil was held parallel t o the sagittal
axis of the subjects head, pointing occipitally. This technique allows relatively focal stimulation, mostly limited
to cortical layers of the brain.22,23Stimulation intensity
was expressed in relationship to the stimulators lowest
output intensity capable of inducing five motor evoked
potentials in the contralateral biceps of at least 50 pV in
a series of 10 stimuli (threshold intensity).
Data analysis. RT was measured from the go-signal to
the onset of biceps EMG activity. Movement onset was
measured to the first deflection of the accelerometers
trace. In experiment 1,mean f SD RT was calculated for
all control trials and for each delay tested in the test trials. Results across subjects were compared with one-way
analysis of variance (ANOVA). Comparison of RTs in
control and test trials and between normal volunteers
and patients was performed using one-way ANOVAs, collapsing across subjects. Significance level, tested with
Scheffgs test, was set at p < 0.05. To analyze the probaMay 1094 NEUROLOGY 44 885

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CONTROL TRIALS

CONTROL TRIALS

Warning
signal

Reaction
(Arm flexion)

Go-Signal

Warning
Signal

Go-Signal Probing
(Flash) Stimulus

React ion
(Arm flexion)

TEST TRIALS
Magnetic
Stimulus

TEST TRIALS
Go-Signal
(Flash t
Magnetic
Stimulus)

+lv

Reaction t h e

CATCH TRIALS
'

Reaction time

Figure 1. Experimental designs for experiments 1 (A)

and 2 (BI. See text for details.
bility of the probing stimulus inducing a motor evoked
potential in experiment 2, we aligned the trials a t EMG
onset (response) and expressed the probability as a function of the interval between probing stimulus and EMG
onset. We compared the probability curves in the control
trials with those in the test trials to assess the effect of
TMS in the go-signal (test trials) on the buildup of motor
cortex excitability during the RT. We compared the probability curves in normal volunteers and patients to assess the effect of PD on the results.

Results. E x p e r i m e n t 1: reaction t i m e . In control

trials, RT in the patients with PD was slower than
in the normal volunteers (173.6 f 22.8 msec versus
151.6 * 17.9 msec, p < 0.001). In test trials, RT was
shortened in patients and normal subjects. The
amount of RT shortening by TMS depended on
stimulation intensity and delay between go-signal
and TMS (figure 2). At delay of 0 msec and 90%
motor threshold intensity, the mean shortening of
RT by TMS was significantly larger in the patients
than in the normal volunteers (41.9 msec versus 28
msec,p < 0.001).
In normal volunteers, the shortening of RT by
subthreshold TMS was significant ( p < 0.01 to

40

-xi-40.30-20

-10 o 10 20

40

so 60

Delay (ms)

so

70

110

no

tso

TMS intensity
(% of motor threshold)

Figure 2. Difference in RT i n trials with and without

TMS according to delay and TMS intensity in normal
volunteers (open circles) and patients with PD (filled
circles). Negative RT difference implies shortening of RT
by TMS;positive values imply prolongation of RT b.y
TMS.Asterrsks mark significant differences between
normal Subjects arid patients (p < 0.0011.

886 NEUKOI,O(:Y 44 May 1994

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BICEPS

WITHOUT
MAGNETIC
STIMULATION

I
I
TRICEPS ,
I

BICEPS

Figure 3. RT (mean S D ) i n the parkinsonian patients

i n trials without T M S (control, open circle) and i n trials
with T M S at various intensities. The gray band marks
the range of R T s i n trials without T M S i n the normal
volunteers.

0.005) at delays of -10 msec to +20 msec. At 2 +50

msec delay, RT w a s significantly prolonged
( p < 0.05) by subthreshold TMS in normal volunteers. In the patients, RT was significantly shortened ( p < 0.01 to 0.005)by subthreshold TMS at delays of -10 msec to +50 msec. Prolongation of RT
by subthreshold TMS in the patients was never observed a t the delays tested. Comparison of the effects of subthreshold TMS on RT according t o the
delay in normal volunteers and patients revealed
significant differences (figure 2).
The effects of TMS on RT according to TMS intensity were also significantly different between
normal volunteers and patients (figure 2). In the
normal subjects, TMS significantly shortened RT ( p
< 0.01 to 0.005) at 70% to 90% motor threshold intensity, whereas it significantly prolonged RT
( p c 0.01 to 0.005) at 120% to 150% motor threshold intensity. In the patients, TMS significantly
shortened RT ( p < 0.01 to 0.005) at 70% to 130%
motor threshold intensity. Prolongation of RT by
TMS in patients was seen only in occasional trials
at 150% motor threshold intensity.
In the patients, RT in trials with TMS at 70% to
130%)motor threshold intensity and 0 msec delay
became as short as RT in the normal volunteers in
trials without TMS (figure 3). This normalization
of RT by TMS was associated with a change in the
agonist-antagonist EMG pattern (figure 4). In trials without TMS, patients frequently displayed an
EMG pattern characterized by multiple agonist
and antagonist bursts. In trials with TMS, the first
agonist burst was frequently of larger amplitude,
and was part of a triphasic (agonist-antagonist-agonist) pattern characteristic of ballistic movements
in normal subject^.^^^'" The duration of the agonist
and antagonist bursts did not change in trials with
or without TMS.
The possibility that the effects of TMS on RT
were a function of RT itself was evaluated with a
correlation analysis between t h e RT a n d t h e

TRICEPS

1.

WITH
MAGNETIC
STIMULATION

I
I

Go-Signal

200 p v

100 rns

Figure 4. Representative examples of rectified EMG

traces i n a patient with PD i n trials without and with
T M S . I n the trial with T M S , the shortened RT is
associated with higher amplitude bursts and the absence
of both a second antagonist and a third agonist burst.

amount of RT shortening by TMS. We found no correlation between RT and TMS effects on RT among
the normal volunteers, among the PD patients, or
among all subjects studied. Therefore, the difference in RT reduction by TMS between PD patients
and normal volunteers has to be considered a function of PD itself.
In the three subjects studied off medications, the
RT in the control trials was significantly longer
t h a n on medications (191.4 f 27.4 msec versus
166.2 k 18.6 msec, p < 0.01). However, the effects of
TMS on RT were essentially unchanged, with significant shortening of RT by subthreshold TMS at
delays of -10 msec to +50 msec ( p < 0.01 to 0.005)
a n d a t TMS intensities of 70% t o 130% motor
threshold intensity ( p < 0.01).
Patients 5 to 10 occasionally reported that the
movement in response to trials with high TMS intensity was triggered entirely by TMS rather than
being voluntary. The analysis of the EMG pattern
in such trials revealed that the motor evoked potentials in agonist and antagonist were followed by
a n antagonist burst and then a n agonist burst,
with absence of an initial agonist burst (figure 5).
We do not feel that in such trials a first agonist
b u r s t could have been obscured by t h e motor
evoked potential since the configuration of the
motor evoked potential, its latency, and its duration always matched those of trials with a clearly
present first agonist burst. In addition, if the motor
evoked potential in such trials had coincided with a
first agonist burst, it should have been greatly facilitated by the ongoing contraction of the target
May 1994 NEUROLOGY 44 887

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ME?
GO-SIGNAL+

- 1.0

/I

- 0,s
h

*
-=
s

.
I

-0.6

-0.4

TRICEPS

d2

- 0.2
-nn
-150-140-130-120-110-100 -90 -80 -70 -60 -50 -40 -30 -20

Time to EMG onset (ms)

Figure 6. Probahility of inducing a motor evoked

potential with the probing stimulus according to the
interval between probing stimulus and EMG onset i n
normal volunteers (circles) and parkinsonian patients
(squares). Open symhols indicate trials without T M S i n
the go-signal; filled symbols indicate trials with T M S .

Figure 5. Representative examples of trials with highintensity T M S i n a patient with PD. I n quotations are the
patients perception of the movement. I n the top example,
the motor evoked potentials (MEPs) i n agonist and
antagonist are followed after a pause by a n initial
agonist burst. I n this case the patient felt he had executed
the movement voluntarily. I n the bottom example, the
MEPs are followed by a burst i n the triceps (antagonist)
i n the absence of a n initial agonist burst. The patient felt
that the movement had been normalbut that T M S ,
rather than he, had generated it entirely.

muscle, and this was never the case. Analysis of

the movement pattern clinically and on forearm accelerometer recordings in such trials did not reveal
any substantial differences. Such trials were not
included in the analysis of RT described above.
Experiment 2: pre-movement excitability buildup.
The pre-movement motor cortex excitability increase in control trials was slower in patients than
in normal subjects (figure 6). In relationship to
EMG onset, it began approximately 40 msec earlier
in the patients. Considering a mean difference of
approximately 35 msec in RT in trials without
TMS, the pre-movement facilitation began a t approximately the same time in relation to the go-signal in patients and normal volunteers. Eventually,
20 msec before voluntary EMG onset, the probability of evoking a motor potential with the probing
stimulus was 1.0 in both patients and normal volunteers. Concurrently with the probability of inducing motor evoked potentials with the probing
stimulus, the amplitude of the evoked potentials
increased with shorter times to EMG onset and
reached approximately 40% of the maximal M-response in both patients and normal subjects.
Comparing control a n d t e s t trials, t h e time
course of pre-movement facilitation did not change
in the normal volunteers. However, in the patients,

the excitability increased faster and started closer

to EMG onset in t h e test trials, resembling the
course of the pre-movement facilitation in normal
subjects (figure 6).
The duration of the pre-movement excitability
buildup might have been related to the RT. However, we found no correlation between RT and duration of the excitability buildup in either normal
subjects or PD patients. In addition, comparison of
results of the two PD patients with the fastest RTs
in control trials (155.7 13.9 msec and 159.8 14.9
msec) with those of the two normal subjects with
the slowest RTs in control trials (155.1 17.2 msec
and 162.6 16.1 msec) still showed a mean difference in duration of the excitability buildup of 22
msec. Therefore, the differences in the duration of
the excitability buildup must be interpreted as a
function of PD.

Discussion. Theoretical model of response preparation and execution. We divide the processes required for response preparation and execution into
a stimulus evaluation system, a task-specific circuitry, a n d a response ~ h a n n e 1 . lThe
~ stimulus
evaluation system has to detect, process, and interpret the go-signal. The task-specific circuitry prepares the motor program for the required response.
The response channel includes all the necessary
structures to execute the response as rapidly as
possible. In a warned, simple RT paradigm, such as
the one used in this study, activation of the taskspecific circuitry may begin even before the warning signal, since the subject is given all the necessary information to plan the appropriate response
in advance. During the foreperiod, the task-specific
circuitry and the stimulus evaluation system are
active in parallel since the prepared motor program
has to be held in memory and the stimulus evaluation system is preparing to detect the go-signal (attentional aspects of set). Identification of a stimulus as the go-signal is completed in the time for

888 NEUROLOGY 44 May 1994

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recognition. The transfer of the motor program

encing the time for initiation without affecting the
from the task-specific circuitry t o the response
time for recognition or the time of development.
channel occurs during the time for initiation. FiTMS could induce an earlier transfer of the motor
nally, the response channel needs a period of time
program from the task-specific circuitry to the re(time of development) to execute the response.
sponse channel or it could speed up the transfer
Therefore, during the RT we can identify a time or
process itself, thus shortening the time for initiarecognition, a time for initiation, and a time of detion.14We think of this transfer process as a switch
ve10pment.l~The identification of these three times
of activity from set-related neurons to movement
before response initiation does not imply that such
onset-related n e u r o n ~ . ~ ~
Subthreshold
-~O
TMS to the
times have to occur in a fixed sequence and cannot
motor cortex may activate corticocortical connecoccur partly in parallel. In fact, there is some evitions, enhancing the information transfer between
dence to suggest that parallel processing does occur
set-related neurons in the premotor and suppleduring response preparati~n.~~+~
mentary motor cortices and movement onset-reSimple RT and PD. In agreement with multiple
lated neurons (corticospinal neurons) in the priprevious studies,s,11,13,2e-31
we found RT in patients
mary motor cortex.
with PD t o be longer than in normal subjects. A
Contrary to the findings in normal subjects,
warning stimulus before the go-signal reduces RT
shortening of RT by TMS in patients with PD was
by the same amount in patients with PD and in
associated with a change in the pre-movement cornormal subjects, and the variation of RT according
tical excitability increase. We hypothesize that
t o the go-signal modality (time for recognition) is
TMS shortens RT in patients with PD by shortenthe same in patients as in normal s ~ b j e c t s .In
~ ~ , ~ing
~ both the time for initiation and the time of deaddition, parkinsonian patients are able to use advelopment. The additional effect on the time of devance information normally to plan a movevelopment may account for the fact t h a t TMS
ment3,jJ1and can hold a motor program in store
shortened RT more in patients than in normal subnormally during a delay RT task.33Therefore, the
jects. As mentioned above, akinesia may be due to
differences in simple RT between parkinsonian padecreased responsiveness of corticospinal neurons
tients and normal subjects cannot be due to differto the inputs involved in movement initiation due
ences in the stimulus evaluation system or in the
to the increased inhibition of thalamocortical neutask-specific circuitry.
r o n ~ In
. ~macaque
~
monkeys with MPTP-induced
Differences in the pre-movement facilitation in
parkinsonism, movement-related neurons in the
patients and normal subjects (experiment 2) have
primary motor cortex demonstrate abnormally low
been preliminarily reported.34 They suggest that
peak discharge frequencies and prolonged latencies
the main abnormality in the slow simple RT in PD
from onset of discharge to motion onset51(time of
development). Subthreshold TMS may raise the
lies in the time of development. We think of time of
development as a n energizing phenomenon
level of corticospinal neurons activation either dimarked by an increase in firing rate of movement
rectly or through activation of excitatory intracortionset-related neurons in the primary motor corcal i n t e r n e u r o n ~ , ~thus
~ - ~ temporarily
j
reversing the
t e ~by~which
~ -the~ motor
~ system excitability is inabnormality underlying akinesia.
creased and response execution occurs when a parNormalization of ballistic EMG pattern by TMS.
ticular threshold level is reached.41 Therefore, the
In normal individuals, ballistic limb movements
a r e characterized electromyographically by a
time of development will depend on the baseline
triphasic (agonist-antagonist-agonist)pattern in
level of cortical activation. In parkinsonism, priwhich the amplitude of the initial agonist burst
mate42and, more recently, human
have
correlates with the movement v e l o ~ i t y .Patients
~~,~~
shown that the motor cortex excitability is lower
with PD display an inability to generate an adea n d inversely correlated with t h e degree of
bradykinesia. In PD, the inhibitory input of the
quate initial agonist burstgJOso that the exerted
force is insufficient to reach the desired target.57
substantia nigra pars compacta on the putamen is
r e d ~ c e d .Therefore,
~ ~ - ~ ~ there is an increased inhibiThe movement is completed by a series of small
tion of the external segment of the globus pallidus
amplitude movements characterized by repeated
and subsequently a disinhibition of the subthalamagonist and antagonist burstsgJOor by a prolonged
ic nucleus. The internal segment of the globus palcontinuous discharge.57D e L ~ n g
has
~ ~suggested
that in PD, due to the high-level tonic discharge of
lidus and the substantia nigra pars reticulata exert
neurons in the internal segment of the globus palexcessive inhibition on thalamocortical neurons belidus, phasic modulation of their activity during
cause of the increased excitatory input from the
subthalamic nucleus. This results in decreased cormovement execution may not be faithfully transmitted to the cortex. Therefore, parkinsonian patical f a ~ i l i t a t i o n ,thereby
~ ~ - ~ ~ prolonging the time
tients are able to scale the first agonist burst ac(time of development) required to build up premovement cortical excitability past the threshold
cording to movement velocity but do so over a rerequired for movement execution.
stricted range.12 In trials with TMS, the first agonist burst was consistently of higher amplitude
Effects of TMS on simple RT, Our present re(figure 4).We suggest that subthreshold TMS actisults on normal volunteers confirm our previous
vates corticospinal neurons, thus transiently norstudies.14Js TMS shortens RT primarily by influMay 1994 NEUROLOGY 44 889

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malizing the scaling of the amplitude of the initial

agonist burst. In any case, the speeding up of RT
and the normalization of the EMG pattern do not
have to be considered to originate from influences
of TMS on different structures. EMG patterns depend on response duration,58and PD patients who
move as rapidly as normal subjects tend to have
normal EMG p a t t e r n ~ . ~ J ~ J ~
Effect of TMS on the perception o f voluntary
movements. Occasionally, some of our patients perceived the response movements in trials with high
TMS intensity as triggered entirely by TMS rather
than being voluntary. In such instances, the motor
evoked potentials were followed by an antagonist
burst with absence of an initial agonist burst separable from the motor evoked potential (figure 5 ) .
An abnormal modulation of the motor cortical output by the basal ganglia46may lead to misinterpretation of the motor evoked potential as the initial
agonist burst, a phenomenon never encountered in
normal subjects. Such an abnormality may also explain why, in parkinsonian patients, slight increases of TMS intensity lead to abnormally large
increases in the amplitude of the induced motor
evoked potential^^^,^^ while facilitation of motor
evoked potentials by isometric contraction of the
target muscle is d e ~ r e a s e d . ~ ~

Acknowledgment
The authors thank Nguyet Dang for technical assistance during
the experiments.

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Akinesia in Parkinson's disease. I. Shortening of simple reaction time with

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