ec
cor
uptm
aging
2 Au
e 26
tran
number of studies (Grandori and Rossini, 1988; Nathan
et al., 1987, 1990; Cracco et al., 1990; Day et al., 1989;
Mills et al., 1987, 1992; Rossini et al., 1985; Rossini,
Clinical Neurophysiology 1E-mail address: stephan.brandt@charite.de (S.A. Brandt).stimulation (TMS) can activate similar neuronal structures of the human motor cortex, as indicated by electromyographic recordings.
Methods: Focal TMS was performed on three subjects inducing a postero-anterior directed current (p-a), TES with postero-anteriorly (p-a)
and latero-medially (l-m) oriented electrodes. We analyzed the onset latencies and amplitudes (single-pulse) and intracortical inhibition and
excitation (paired-pulse).
Results: TMS p-a and TES p-a produced muscle responses with the same onset latency, while TES l-m led to 1.4–1.9 ms shorter latencies.
Paired-pulse TMS p-a and TES p-a induced inhibition at short inter-stimulus intervals (ISI) (maximum: 2–3 ms) and facilitation at longer
ISIs (maximum: 10 ms). No inhibition but a strong facilitation was obtained from paired-pulse TES l-m (ISIs 1–5 ms).
Conclusions: Our findings support the hypothesis, that current direction is the most relevant factor in determining the mode of activation for
both TMS and TES: TMS p-a and TES p-a are likely to activate the corticospinal neurons indirectly. In contrast, TES l-m may preferentially
activate the corticospinal fibres directly, distant of the neuronal body.
Significance: TES is a suitable tool to induce intracortical inhibition and excitation.
q 2005 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
Keywords: Transcranial electrical stimulation; Human motor cortex; Transcranial magnetic stimulation; Intracortical inhibition; Intracortical facilitation
1. Introduction
Since the pioneering studies of Merton and Morton
(1980) several different forms of transcranial electrical
(TES, e.g. anodal and cathodal unifocal or bifocal) and
magnetic cortex stimulation (TMS, e.g. focal or round coil)
have been developed.
As the induced electric field must have a component
that is parallel to the neuronal fibre in order to stimulate
the neuron (Rushton, 1927), the site of excitation is likely
to be dependent on the direction of the induced electric
field. The electric fields produced in the brain by TES and
TMS have been theoretically modelled and compared by a
et al., 1993; Saypol et al., 1991). While TMS induced
electrical fields are highly localised and parallel to the
skull, near the head surface, electric stimulation produced
electrical fields with a similar parallel component but also
an additional component perpendicular to the surface
(Saypol et al., 1991). As these induced electric field
components depend on electrode arrangements, distances,
polarity (anodal or cathodal) or coil orientation, previous
studies have compared a variety of kinds of cortex
stimulation. They demonstrated a strong relationship
between coil orientation (TMS) or electrode arrangement
(TES) and the induced stimulation effects (e.g. AmassianTranscranial magnetic and el
Does TES activate intra
J. Brocke, K. Irlbacher, B. Ha
Department of Neurology, Berlin NeuroIm
Accepted 1
Available onlin
Abstract
Objective: To determine whether, and under which conditions,trical stimulation compared:
tical neuronal circuits?
ann, M. Voss, S.A. Brandt
*
Center, Charite´, 10117 Berlin, Germany
gust 2005
October 2005
scranial electrical stimulation (TES) and transcranial magnetic
16 (2005) 2748–2756
www.elsevier.com/locate/clinphWe directly compared bifocal TES and TMS on the
motor hand area with the same postero-anterior orientation
(p-a), following the hypothesis that the site of excitation of
1388-2457/$30.00 q 2005 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.clinph.2005.08.015
*
Corresponding author. Tel.: C49 30 450560111; fax: C49 30
450560942.1988; Werhahn et al., 1994; Zarola et al., 1989).

electrode arrangement (l-m, anodal TES) and TMS with an
ophysinduced postero-anterior directed current (TMS p-a) revealed
that TES induces motor responses with latencies of 1–2 ms
shorter than that of TMS (Day et al., 1989; Werhahn et al.,
1994). This difference in response latencies is thought to result
from the activation at different sites in motor cortex,
corresponding to the ‘D- and I-wave’ hypothesis. While
transcranial electrical stimulation is supposed to activate
cortico-spinal fibres directly inducing D-waves, TMS acti-
vates the pyramidal cells indirectly via excitatory interneurons
inducing I-waves and leading to longer latencies (Day et al.,
1989;forareviewZiemann and Rothwell, 2000). Several
studieswith direct recording of descending spinal cord volleys
in anaesthetised humans (Berardelli et al., 1990; Thompson
et al., 1991) and in patients with chronically implanted spinal
electrodes (Kaneko et al., 1996; Nakamura et al., 1996)
confirm this hypothesis.
The preferential axonal activation induced by TES l-m
can be used as a control tool in TMS studies on human
motor cortex physiology: To confirm the hypothesis of an
intracortical origin of paired-pulse induced inhibition and
facilitation (ICI and ICF) by TMS p-a, Kujirai et al. (1993)
used an anodal electrical test stimulus (latero-medial
oriented electrodes, l-m) as a control condition. They
demonstrated that the magnetic conditioning stimuli failed
to suppress the electrically induced test responses. This
finding was interpreted as evidence for a direct activation of
corticospinal fibres by TES, probably distal to the neuronal
cell body where inhibitory and excitatory effects on a
cortical level have little or no influence.
Until now TMS and bifocal TES on the motor hand area
were usually compared using TMS in a p-a direction but l-m
oriented TES. It is still unknown whether TES with an
electric field component in the p-a direction (TES p-a) could
activate similar neuronal structures as TMS p-a, inducing
comparable stimulation effects. We, therefore, specifically
asked whether current direction induced by TES on the
motor hand area determines the mode of corticospinal
activation.
To further clarify this question, we compared the
stimulation effects of TMS and TES with two different
electrode arrangements (p-a and l-m; Fig. 3) in three
subjects. First, single pulse TES and TMS were used to
compare latency and amplitude of the compound muscle
potential. Then intracortical inhibitory and excitatory
mechanisms were investigated by applying pairs of either
electrical or magnetic pulses.
2. Methods
Three healthy volunteers (male, 28, 30 and 35 years ofpyramidal neurons is predominantly dependent on current
direction and not on stimulation methods.
Previous comparisons of bifocal TES with a latero-medial
J. Brocke et al. / Clinical Neurage) participated in the experiment. The local EthicsCommittee approved the protocol, and subjects gave their
written informed consent.
Subjects were seated in a comfortable reclining chair
during the procedures. Surface electromyographic record-
ings (EMG) were made from the first dorsal interosseous
muscle (FDI) with the active electrode placed over the
muscle belly and the reference electrode on the metacarpo-
phalangeal point. With a sampling rate of 5 kHz, responses
were continuously recorded, amplified and band-pass
filtered (20 Hz–3 kHz) by CED 1902 amplifiers (Cambridge
Electronic Design, Cambridge, UK), recorded through a
CED 1401 power laboratory interface (Cambridge Elec-
tronic Design, Cambridge, UK) and stored on a personal
computer using Spike 2 (version 4.12, Cambridge Elec-
tronic Design, Cambridge, UK).
TMS and TES were applied over the hand area of the
motor cortex of the dominant hemisphere. Resting motor
threshold (RMT) was defined as the intensity needed to
evoke a muscle response in relaxed muscle ofO50 mVin5
of 10 consecutive trials.
2.1. Transcranial magnetic stimulation (TMS)
TMS was performed using a Magstim 200 magnetic
stimulator (Magstim Co., Whiteland, Dyfed, UK) and a
focal eight-shaped coil (70 mm outer wing diameter). Paired
pulse stimulation was applied using two Magstim 200
stimulators connected via a BiStim module (Magstim).
During all TMS conditions, the coil was held in a way that it
induced a posterior to anterior directed current (p-a) in the
brain, approximately perpendicular to the central sulcus.
Optimal scalp position was determined as the stimulation
position, at which stimuli of slightly suprathreshold
intensity consistently produced the largest muscle responses
in the FDI.
2.2. Transcranial electrical stimulation (TES)
TES of the right motor hand area was performed using a
Digitimer D 185 stimulator (Welwyn, Great Britain) with a
50 ms time constant and two non-magnetic gold electrodes
(diameter of 1 cm). In order to change the current potential
between two stimuli within milliseconds for paired pulse
stimulation, the Digitimer 185 stimulator was modified with
four independent potentiometers. These potentiometers
were triggered separately by an external trigger signal.
The optimal scalp position for stimulation of the hand
motor area was pre-defined using focal TMS. Single and
paired pulse TES was then performed in two conditions with
different electrode arrangements: In both conditions, the
anode was fixed over the motor hand area, approximately
5 cm lateral to the intersection line from the vertex to the
external auditory meatus. The cathode was placed either (i)
5 cm anterior of the anode on a line parallel to the midline in
the postero-anterior arrangement (TES p-a), or (ii) medial of
iology 116 (2005) 2748–2756 2749the anode over the vertex in the latero-medial arrangement