ranscranial magnetic stimulation and functional imaging in
cognitive brain research: possibilities and limitations
a,b ,
a,c
*
Alexander T. Sack
, David E.J. Linden
a
�
Laboratory for Neurophysiology and Neuroimaging
, Department of Psychiatry, Johann Wolfgang Goethe-Universitat, Heinrich-Hoffmann-Str. 10,
60528 Frankfurt am Main, Germany
b
Department of Neurocognition
, Faculty of Psychology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands
c
�
Max-Planck-Institut f ur Hirnforschung
, Deutschordenstrasse 46, 60528 Frankfurt am Main, Germany
Accepted 17 April 2003
Abstract
Transcranial magnetic stimulation (TMS) is a widely used tool for the non-invasive study of basic neurophysiological processes and the
relationship between brain and behavior. We review the physical and physiological background of TMS and discuss the large body of
perceptual and cognitive studies, mainly in the visual domain, that have been performed with TMS in the past 15 years. We compare TMS
with other neurophysiological and neuropsychological research tools and propose that TMS, compared with the classical neuropsychologi-
cal lesion studies, can make its own unique contribution. As the main focus of this review, we describe the different approaches of
combining TMS with functional neuroimaging techniques. We also discuss important shortcomings of TMS, especially the limited
knowledge concerning its physiological effects, which often make the interpretation of TMS results ambiguous. We conclude with a
critical analysis of the resulting conceptual and methodological limitations that the investigation of functional brainbehavior
relationships still has to face. We argue that while some of the methodological limitations of TMS applied alone can be overcome by
combination with functional neuroimaging, others will persist until its physical and physiological effects can be controlled. 2003 Elsevier B.V. All rights reserved.
Theme
: Neural basis of behaviour
Topic
: Cognition
Keywords
: Transcranial magnetic stimulation; Cognition; Vision; Functional imaging; Brainbehavior relationship; Methods in neuroscience
Contents
1
. Introduction ............................................................................................................................................................................................
42
1
.1. Basic principles of transcranial magnetic stimulation .........................................................................................................................
42
1
.2. Stimulation characteristics and parameters ........................................................................................................................................
42
1
.3. Safety and persistence of TMS .........................................................................................................................................................
43
2
. Cognitive studies with TMS .....................................................................................................................................................................
44
2
.1. The frequency dependence of TMS-induced effects ...........................................................................................................................
44
2
.2. Studies on the timing of sensorimotor processing with spTMS ...........................................................................................................
44
2
.3. Studies on the timing of perceptual processing with spTMS ...............................................................................................................
45
2
.4. rTMS in the study of cognitive paradigms .........................................................................................................................................
46
2
.5. Enhancing cognitive functions..........................................................................................................................................................
47
3
. The unique contribution of TMS in comparison to other techniques in cognitive neuroscience ......................................................................
47
4
. Combining TMS and functional imaging ...................................................................................................................................................
48
*Corresponding author. Department of Neurocognition, Faculty of Psychology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The
Netherlands. Tel.: 131-43-388-4267; fax: 131-43-388-4125.
E</i>-<i>mail address
:
a.sack@psychology.unimaas.nl
(A.T. Sack).
0165-0173 / 03 / $ see front matter 2003 Elsevier B.V. All rights reserved.
doi:10.1016 / S0165-0173(03)00191-7 42
A
.T. Sack, D</i>.<i>E</i>.<i>J</i>. Linden / Brain Research Reviews 43 (2003) 4156
4
.1. Synchronized and experimental combinations of TMS and functional imaging ....................................................................................
48
4
.2. The technical feasibility of synchronized TMS and functional imaging ...............................................................................................
49
4
.3. fMRI artifacts produced by TMS coils ..............................................................................................................................................
49
4
.4. Combining TMS and functional imaging to evaluate its neurophysiological effects ..............................................................................
49
4
.5. Experimental designs for combining TMS and functional imaging ......................................................................................................
50
4
.6. Co-registration of TMS and functional imaging .................................................................................................................................
50
5
. How the experimental combination of TMS and fMRI can reveal new constraints for models of hemispheric specialization............................
51
6
. Limitations to the interpretation of TMS studies ........................................................................................................................................
52
7
. Conclusion and perspective ......................................................................................................................................................................
52
Acknowledgements ......................................................................................................................................................................................
53
References...................................................................................................................................................................................................
53
1
. Introduction
opposite directions. The magnetic elds of these two coil
loops are summed at the intersection of the coils, resulting
1
.1. Basic principles of transcranial magnetic
in a more focused magnetic eld distribution than in the
stimulation
case of a circular coil.
Transcranial magnetic stimulation (TMS) is based on
the principles of electromagnetic induction (
Fig. 1
). A
1
.2. Stimulation characteristics and parameters
brief, high-amplitude pulse of current, lasting for approxi-
mately 100 to 200 ms, is discharged into an electro-
In TMS, it is important to distinguish stimulation
magnetic coil held over the cranium. This current produces
characteristics from stimulation parameters. While the
a magnetic eld perpendicular to the current. In tissue, this
stimulation parameters describe the physical properties of
magnetic eld induces an electric eld perpendicular to
the applied magnetic stimulation, the stimulation charac-
itself. The strength of the induced electric eld mainly
teristics refer to the induced physiological effect of TMS.
depends on the rate of change of the magnetic eld, which,
The main stimulation characteristics are the strength and
in turn, depends on the rate of change of the electrical
distribution of the induced electric eld, the depth of
current in the coil. Due to the electrical conductivity of
penetration and the accuracy of stimulation. These effects
living tissue, the electric eld leads to an electrical current
are determined by many physical and physiological fac-
in the cortex parallel, but opposite in direction to, the
tors, including coil geometry, coil size, scalp shape, scalp-
current in the coil (Lenzs law) and subsequently to
cortex distance, anatomical properties orientation
depolarization of the underlying neurons
[30].
extent and conductivity of the stimulated tissue, and, of
The TMS apparatus itself consists of two major devices:
course, the stimulation parameters: pulse intensity, pulse
a main power pulse generation unit that charges a bank of
amplitude, pulse frequency, duration, rise time, magnetic
capacitors capable of producing high discharge currents,
eld distribution, pulse wave form, and peak magnetic
and an electromagnetic stimulating coil to apply magnetic
energy.
pulses of up to several Tesla. The capacitors are rapidly
Changes in the stimulation parameters can affect differ-
discharged through the coil, which is connected to the
ent stimulation characteristics in very different ways. For
stimulator by a strong copper cable carrying the high and
instance, smaller coils produce stronger and more focal
rapidly changing currents (
�2000 V, 10,000 A), in order to
elds than larger coils with the same current because the
create very short magnetic eld pulses (
�200 ms). The two
magnetic ux is more concentrated. However, the eld
types of coils most widely used are the circular coil and
strength produced by smaller coils decreases more rapidly
the gure-of-eight coil, both co