Abstract The effects of repetitive transcranial magnetic
stimulation (rTMS; 20 stimuli at 5 Hz at 120% resting
motor threshold intensity using a biphasic stimulus
pulse) on the excitability of human motor cortex were in-
vestigated in two patients who had an electrode implant-
ed into the cervical epidural space. The corticospinal
D wave increased in amplitude with successive stimuli,
and reached a maximum after three or five pulses. At
this stage, the amplitude of the I waves was unchanged,
but after a further 10 stimuli an additional I wave was re-
cruited. Both effects were still evident 2 min after the
end of the rTMS. The effects are compatible with a
short-term increase in cortical excitability during supra-
threshold rTMS.
Keywords Transcranial magnetic stimulation · Plasticity ·
Motor cortex · rTMS
Introduction
In recent years, repetitive transcranial magnetic stimula-
tion (rTMS) has become a useful tool for investigating
(Cohen et al. 1997, 1998; Pascual-Leone et al. 1998) and
even modulating human brain plasticity (Amassian et al.
1997; Pascual-Leone et al. 1998; Ziemann et al. 1998;
Grafman and Wassermann 1999). Overall, such studies
suggest that low frequency rTMS (stimulus rates of 1 Hz
or less) produces short-term depression of motor cortex
excitability whereas higher frequencies (stimulus rates
of more than 5 Hz), especially at higher intensities
(Modugno et al. 2001) promote a short-term increase in
cortical excitability. Repeated trains of stimuli have been
reported to alleviate symptoms in Parkinson’s disease
(Pascual-Leone et al. 1994a; Siebner et al. 1999a), in
chronic pain syndromes (Amassian et al. 1997; Saitoh et
al. 1999), in dystonia (Siebner et al. 1999b) and primari-
ly in depressed patients (George et al. 1995; Pascual-
Leone et al. 1996), with benefits lasting even weeks after
the end of the treatment. Although there is some debate
over the efficacy of the technique, the demonstration of
some long-lasting modulatory and therapeutic effects of
rTMS implies the induction of one or possibly multiple
forms of synaptic plasticity in the brain by repetitive
stimulation.
Only a small number of studies have examined the
basic physiology underlying the facilitatory effects of
rTMS. Pascual-Leone et al. (1994b) originally reported
that rTMS over motor cortex at 5 Hz and 120% resting
threshold leads to a slow increase in the amplitude of
the motor-evoked potential (MEP) over the course of
20 stimuli. This was confirmed by Berardelli et al.
(1998) who also used H-reflex testing to confirm that the
effect was cortical rather than spinal. Both groups also
showed that higher frequencies and intensities could lead
to eventual recruitment of MEPs in muscles distant from
the target muscle, suggesting a spread of excitation away
from the site of stimulation under the coil. The conclu-
sion was that rTMS with these parameters leads to a
slow increase in cortical excitability that built up over
V. Di Lazzaro (
✉
) · A. Oliviero · F. Pilato · E. Saturno
M. Dileone · P.A. Tonali
Institute of Neurology, Università Cattolica, L.go A. Gemelli 8,
00168 Rome, Italy
e-mail: vdilazzaro@rm.unicatt.it
Tel.: +39-06-30154435, Fax: +39-06-35501909
A. Berardelli
Dipartimento di Scienze Neurologiche,
Istituto Neurologico Neuromed IRCCS,
Università di Roma La Sapienza, Rome, Italy
P. Mazzone
Neurochirurgia CTO, Via S. Nemesio 21, 00145 Rome, Italy
A. Insola
Neurofisiologia CTO, Via S. Nemesio 21, 00145 Rome, Italy
P.A. Tonali
IRCCS “Casa Sollievo della Sofferenza”,
San Giovanni Rotondo, Italy
J.C. Rothwell
Sobell Department of Neurophysiology,
Institute of Neurology and The National Hospital for Neurology
and Neurosurgery, Queen Square, London WC1N 3BG, UK
Exp Brain Res (2002) 144:549–553
DOI 10.1007/s00221-002-1106-9
RESEARCH NOTE
V. Di Lazzaro · A. Oliviero · A. Berardelli
P. Mazzone · A. Insola · F. Pilato · E. Saturno
M. Dileone · P. A. Tonali · J. C. Rothwell
Direct demonstration of the effects of repetitive transcranial
magnetic stimulation on the excitability of the human motor cortex
Received: 29 January 2002 / Accepted: 1 April 2002 / Published online: 30 April 2002
© Springer-Verlag 2002