tw
au
se 5
nd
article info
Article history:
Accepted 5 December 2008
Available online 10 January 2009
Keywords:
Short afferent inhibition
Transcranial magnetic stimulation
Sensorimotor integration
abstract
et al., 1992). Such sensorimotor interaction can be tested in paired
pulse paradigms, where conditioning electrical stimuli given to the
median nerve at the wrist or digital nerves are followed by trans-
cranial magnetic stimulation (TMS) pulses to the contralateral pri-
mary motor cortex (M1) hand area at short latencies (starting at
19 ms) (Classen et al., 2000; Tokimura et al., 2000) or longer laten-
tens de Noordhout et al., 1992; Tokimura et al., 2000).
There is some debate as to the somatotopic specificity of senso-
rimotor integration. On the one hand, functional MRI studies dem-
onstrated that receptive fields of non-adjacent fingers do not
overlap in Brodmann area 3b, where afferent stimuli are perceived
(Kurth et al., 2000; Krause et al., 2001; Ruben et al., 2001; van Wes-
ten et al., 2004) suggesting strict somatotopic organization. On the
other hand, in Brodmann areas 1 and 2 that are densely connected
with M1, receptive fields of the fingers are not segregated (Kurth
et al., 2000; Krause et al., 2001). Also, movements rather than
* Corresponding author. Tel.: +49 40 42803 9367; fax: +49 40 42803 5086.
E-mail address: Baeumer@uke.uni-hamburg.de (T. Bäumer).
Clinical Neurophysiology 120 (2009) 610–618
Contents lists availab
Clinical Neuro
.el1
Both the authors contributed equally to this work.1. Introduction
Motor output is influenced by sensory input (Tokimura et al.,
2000). The integration of sensory input with motor output is
thought to have an important role in fine manual control and mo-
tor learning in healthy humans (Asanuma and Pavlides, 1997)as
well as in patients with motor disorders (Maertens de Noordhout
cies (150–600 ms) (Chen et al., 1999; Classen et al., 2000). Typi-
cally, motor evoked potentials (MEPs) are suppressed when the
TMS pulse given to M1 is preceded by electrical stimuli at inter-
stimulus intervals (ISIs) between 20 ms, i.e. at the arrival of the
afferent volley to the motor cortex corresponding to the first corti-
cal component of sensory evoked potential, and 50 ms. This has
been referred to as short-latency afferent inhibition (SAI) (Maer-1388-2457/$36.00  2008 International Federation o
doi:10.1016/j.clinph.2008.12.003Objective: To examine the distribution and inter-limb interaction of short-latency afferent inhibition
(SAI) in the arm and leg.
Methods: Motor evoked potentials (MEPs) in distal and proximal arm, shoulder and leg muscles induced
with ranscranial magnetic stimulation (TMS) were conditioned by painless electrical stimuli applied to
the index finger (D2) and great toe (T1) at interstimulus intervals (ISIs) of 15, 25–35, 80 ms (D2) and
35, 45, 55, 65 and 100 ms (T1) in 27 healthy human subjects. TMS was delivered over primary motor cor-
tex (M1) arm and leg areas. Electrical stimulus intensities were varied between 1 and 3 times the sensory
perception thresholds. We also tested effects of posterior cutaneous brachial nerve (PCBN) stimulation on
MEPs in arm muscles at ISIs of 18 and 28 ms.
Results: D2 but not PCBN electrical conditioning reduced MEP amplitudes in upper limb muscles at ISIs of
25 and 35 ms. SAI was more pronounced in distal as compared to proximal arm muscles. Also, SAI follow-
ing D2 stimulation increased with higher conditioning intensities. D2 stimulation did not change lower
limb muscles MEPs. In ontrast, T1 stimulation did not induce SAI in any muscles but caused MEP facili-
tation in a foot muscle at an ISI of 55 ms and in upper limb muscles at ISIs of 35 and 55 ms. Short interval
intracortical inhibition (SICI) and intracortical facilitation (ICF) were not affected by electrical T1 condi-
tioning.
Conclusion: D2 stimulation causes segmental SAI in upper limb muscles with a distal to proximal atten-
uation without affecting leg muscles. In contrast, toe stimulation facilitates motor output both in foot and
upper arm muscles.
Significance: Our data suggest that cutaneo-motor pathways in arms and legs are functionally organized
in a different way with cutaneo-motor interactions induced by toe stimulation probably relayed at a tha-
lamic level. Abnormal cutaneo-motor interactions following electrical toe stimulation may serve as an
electrophysiological marker of thalamic dysfunction, e.g. in neurodegenerative diseases.
 2008 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights
reserved.Sensory afferent inhibition within and be
R. Bikmullina
a,b,1
, T. Bäumer
a,
*
,1
, S. Zittel
a
, A. Münch
a
Department of Neurology, University Medical Centre Hamburg-Eppendorf, Martinistras
b
BioMag Laboratory, HUSLAB, Hospital District of Helsinki and Uusimaa, Helsinki, Finla
journal homepage: wwwf Clinical Neurophysiology. Publisheen limbs in humans
a
2, 20246 Hamburg, Germany
le at ScienceDirect
physiology
sevier.com/locate/clinphed by Elsevier Ireland Ltd. All rights reserved.

uropmuscles seem to be represented in M1 (Rizzolatti et al., 1998;
Beisteiner et al., 2001; Schieber, 2001; Dechent and Frahm,
2003). As regards SAI some studies have suggested finger-specific
somatotopy in the human hand (Classen et al., 2000; Tamburin
et al., 2001), others imply a rather segmental organization (Hel-
mich et al., 2005). One of the main drawbacks of some previous
studies was small sample sizes. To further contribute to the ques-
tion of SAI organization in the arm in humans we examined SAI in
small hand, forearm and upper arm muscles following electrical
digital stimulation and cutaneous stimulation of the upper arm
in a larger group of healthy controls using different stimulation
intensities.
Given that SAI has been taken as a measure of sensorimotor
interaction possibly as a basis of manual control one might expect
it to be an arm-specific phenomenon. To this end, we also tested
SAI in the leg for comparison, i.e. we determined the effects of elec-
trical toe stimulation on motor output in the leg. Stimulation of
cutaneous pain afferents at the ankle causes facilitation of MEPs
in lower limb muscles (Wolfe and Hayes, 1995). However, the ef-
fects of painless stimuli applied to the toe skin to electrical finger
stimulation have to our knowledge not been tested previously.
In addition, to explore inter-limb interactions of sensory inputs
we studied effects of finger stimulation on leg muscles and of toe
stimulation on arm muscles. For instance, electrical nerve stimula-
tion at the hand and foot can result in inter-limb reflexes at inter-
vals of 75–120 ms as shown by Zehr et al. (2001). Also, dorsiflexion
of the ankle causes a shortening of the cortical silent period to a
small hand muscle, which indicates that such inter-limb interac-
tion takes place predominantly at a cortical level (Tazoe et al.,
2007). This notwithstanding, the role of cutaneous afferent input
from upper to lower limb corticospinal excitability and vice versa
is unclear.
We hypothesised that consequences of electrical finger stimula-
tion would differ from those following toe stimulation reflecting
fundamental differences in the organization of sensorimotor inte-
gration in the arm and leg in humans.
2. Methods
2.1. Subjects
Twenty seven healthy subjects (18 females; mean age 27 years
±3 SD) participated in the study. All subjects were consistent
right-handers according to the Edinburgh handedness inventory
(Oldfield, 1971). The protocol was approved by the Medical Ethics
Committee of the University of Hamburg, and all subjects gave
their written informed consent to participate in the study.
2.2. EMG recording
Subjects were seated in a comfortable armchair with both arms
supported by pillows to ensure that arm muscles were completely
relaxed. EMG was recorded by using silver disk surface electrodes
placed according to belly tendon montage over right sided target
muscles (first dorsal interosseous (FDI), abductor digiti minimi
(ADM), extensor digitorum communis (EDC), flexor carpi ulnaris
(FCU), biceps brachii (BB), triceps brachii (TB), deltoid (DEL), exten-
sor digitorum brevis (EDB) and tibialis anterior (TA) muscle).
The EMG signals were amplified, filtered (5–1000 Hz; Toenenies
amplifier). The signals were sampled at 5000 Hz, digitized using a
Micro1401 interface (Cambridge Electronics Design, Cambridge,
UK) and stored on a personal computer for display and later offline
data analysis. To capture baseline EMG activity during the mea-
R. Bikmullina et al. / Clinical Nesurements, EMG signals were continuously monitored acoustically
with loudspeakers and visually by an oscilloscope.2.3. Transcranial magnetic stimulation
For TMS stimulation we used a circular coil with an outer diam-
eter of 110 mm which allows simultaneous activation of motor
cortical representation areas of proximal and distal upper limb or
lower limb muscles. In experiment 3 we also used a figure-of-eight
shaped coil for a sub-experiment. The magnetic stimulus had a
nearly monophasic pulse configuration with a rise time of about
100 ls, decaying back to zero over about 0.8 ms. The direction of
the current flow in the brain was clockwise. Magstim 200 (Mag-
stim Ltd., UK) magnetic stimulators were used. For paired TMS
stimulation protocols stimulators were connected to the coil via
a Y-cable.
Resting motor threshold (RMT) was defined as the intensity
needed to elicit MEPs of at least 50 lV in 5 of 10 consecutive trails
in relaxed target muscle. Active motor threshold (AMT) was de-
fined as the intensity to elicit MEPs of at least 150 lV in 5 of 10
consecutive trails in activated (10% of maximum voluntary con-
traction) muscles. Test pulse intensity was defined as the stimula-
tor intensity that elicited MEPs of approximately 0.5–1.5 mV peak-
to-peak amplitude in the recorded muscles.
2.4. Electrical cutaneous nerve stimulation
Conditioning electrical stimuli were applied to the right index
finger (D2), posterior cutaneous brachial nerve (PCBN) or great
toe (T1). For cutaneous afferents stimulation Digitimer Constant
Current Stimulator DS7A (Digitimer Ltd., UK) was used. D2 and
T1 were stimulated through paired ring electrodes with the cath-
ode placed at the proximal part of the right D1 and the anode
2 cm distally in the middle part of D2. The same electrode place-
ment was used for T1 stimulation. The PCBN was stimulated
through bipolar surface electrodes placed above the elbow at the
lateral part of the arm (cathode proximal); the electrode position
was chosen carefully to avoid stimulation of muscle afferents or di-
rect muscle activation. The electrical stimulation consisted of a
brief pulses (1 ms duration, 400 V) using different stimulation
intensities (1–3 times the individual’s sensory perception thresh-
old (SPT)). SPT was defined as the current intensity that was still
detected by the subject in two out of four consecutive electrical
pulses. We applied two series with increasing and two with
decreasing electrical pulse intensities. Thus, starting from a sub-
threshold level, electrical pulses with increasing intensities were
applied until subjects detected these stimuli in the increasing ser-
ies, and supra-threshold electrical pulses were given with decreas-
ing intensities until subjects did not notice these pulses any more.
2.5. Short afferent inhibition
The same conditioning-test protocol design was used to inves-
tigate SAI in the different experiments. In conditioned trials condi-
tioning electrical stimuli delivered to D2, PCBN or T1 were
followed by TMS test pulses applied to the skull. In unconditioned
test trials only TMS pulses were given. For each experiment, 10
unconditioned and 10 conditioned trials were tested for each ISI
in a randomized order.
2.5.1. Experiment 1: influence of conditioning D2 stimulation on
corticospinal excitability of upper limb muscles
D2 was stimulated with an intensity of three times SPT. To ob-
tain MEPs of similar amplitudes simultaneously from all four upper
limb muscles (FDI, EDC, BB and DEL) a round coil was placed over
M1 approximately 2 cm laterally from the vertex. On the basis of
hysiology 120 (2009) 610–618 611previous reports (Helmich et al., 2005; Tamburin et al., 2001)
where SAI was examined the following ISIs were tested: 15, 25,