BJMB
Brazilian Journal of Motor Behavior
Research Article
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Négyesi et al.
2020
VOL.14
N.3
110 of 120
Navigated transcranial magnetic stimulation of the primary somatosensory cortex evokes
motor potentials in healthy humans’ flexor carpi radialis muscle - A pilot study
JÁNOS NÉGYESI
1
| TAKAYUKI MORI
2
| KOUTA ATAKA
2
| SHINICHI IZUMI
2
| TIBOR HORTOBÁGYI
3
| RYOICHI
NAGATOMI
1,4
1
Division of Biomedical Engineering for Health & Welfare, Tohoku University Graduate School of Biomedical Engineering, Sendai, Japan.
2
Department of Physical Medicine and Rehabilitation, Tohoku University Graduate School of Medicine, Sendai, Japan.
3
Center for Human Movement Sciences, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
4
Department of Medicine and Science in Sports and Exercise, Tohoku University Graduate School of Medicine, Sendai, Japan.
Correspondence to:!János Négyesi. 2-1, Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. Tel/Fax: 8122-717-8588.
email: negyesi@tohoku.ac.jp
https://doi.org/10.20338/bjmb.v14i3.173
HIGHLIGHTS
• No interhemispheric differences, but larger
peak-to-peak amplitudes and variability of
MEPs occurred after M1 as compared to S1
stimulation.
• On the other hand, latency and waveforms of
MEPs did not differ between S1 vs. M1
stimulation.
• Our results indicate that TMS over S1 using a
90 mm outer diameter figure-of-eight coil is not
selective enough and can excite M1
interneurons thus producing MEPs on the
contralateral FCR.
• Future studies should carefully consider these
results when targeting S1 with TMS even if
using a neuronavigation system.
ABBREVIATIONS
CSE corticospinal excitability
ECR extensor carpi radialis muscle
EMG electromyography
FCR flexor carpi radialis muscle
FDI first dorsal interosseous muscle
M1 primary motor cortex
MEP motor evoked potential
MRI magnetic resonance imaging
rANOVA repeated measures analysis of
variance
rMT resting motor threshold
rMTS repetitive transcranial magnetic
stimulation
S1 primary somatosensory cortex
S2 secondary somatosensory cortex
TMS transcranial magnetic stimulation
PUBLICATION DATA
Received 26 04 2020
Accepted 23 07 2020
Published 01 09 2020
BACKGROUND: Background: Although previous studies targeted S1 by TMS to investigate its effect on the
corticospinal pathway, there is no evidence if such stimuli produced by TMS would distinctly be restricted to it
and not reach M1 interneurons adjacent to S1.
AIM: The aim of the present pilot study was to determine the effects of stimulation location, i.e., S1 vs. M1, on
MEP waveform-related parameters, including amplitude, latency, and variability in the contralateral FCR muscle.
METHOD: Healthy volunteers (n = 8, 2 females, age: 29.9 ± 5.49y) received single-pulse TMS over each
hemisphere at each intensity of 90, 100, 110, and 120% of rMT in a randomized order. MEPs from the
contralateral FCR were recorded.
RESULTS: We found no interhemispheric differences, but larger peak-to-peak amplitudes and variability of MEPs
after M1 as compared to S1 stimulation. However, latency and waveforms of MEPs did not differ between S1 vs.
M1 stimulation supporting the idea that TMS over S1 is not selective enough and can excite M1 interneurons
thus producing MEPs on the contralateral FCR.
CONCLUSION: Future studies should carefully consider these results when targeting S1 with TMS even if using a
neuronavigation system.
KEYWORDS: Brain Stimulation | FCR | Motor Cortex | Neuronavigation | Somatosensory Cortex
INTRODUCTION
Transcranial magnetic stimulation (TMS) is a neurophysiological technique that
makes it possible to non-invasively probe the functional integrity of the corticospinal tract
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and the function of the motor cortex, M1.
1
When TMS is delivered to the scalp over M1, it
may induce short-latency motor evoked potentials (MEPs) in contralateral limb muscles
through activating the pyramidal cells indirectly via excitatory interneurons.
2
These MEPs
can be recorded by electromyography (EMG). Although the induced field reaches the
target region of stimulation, it may involve adjacent brain regions. A commonly used
double-cone magnetic coil may produce a magnetic field in the brain tissue of up to
140mm radial from the center of the target region with smaller peripheral peaks of
approximately 50% the amplitude of the central peak on either side of the winding coil,
3
making it difficult to target a particular brain region with high selectivity.
The primary somatosensory cortex (S1), Brodmann areas 3,1 and 2, is known to
receive abundant projections from spinal and brain stem neurons that receive input from
myelinated afferents. These inputs from peripheral tactile, joint, tendon and muscle
receptors provide sensory information about limb position, movement sense, muscle
tension and force to the central nervous system and this information is used in turn to
control voluntary movements.
4
Somatosensory and motor interactions have a fundamental
role in motor control
5
and motor performance
6
, as afferent inputs are key determinants of
motor output. Therefore, the ascending somatosensory system plays a key role in
movement control and in the acquisition of new motor skills. In animal models, besides
these ascending pathways to the somatosensory cortex however, descending efferent
fibers from the sensory cortex have been confirmed, which show similar organization in the
brains of domestic dogs and cats, raccoons, and in a few species of monkeys and apes.
7
Brodmann area 3a, contains some of the largest corticospinal neurons outside the motor
cortex, area 4 and projections from both areas appear to overlap within the spinal cord,
8
and it appears to project slightly more dorsally within the spinal grey matter than does
Brodmann area 4.
9
Furthermore, areas 3b, 1, 2, and also the secondary somatosensory
area (S2) have projection, albeit sparse, from small diameter pyramids,
10
and they
terminate chiefly in the dorsal horn9. They may be the potential tracts to convey
descending signals to the muscles. Although electrophysiological studies
7-9
describing
descending pathways from S1 in animal models suggest that such S1 cells can be excited
by induced current, it remains unknown whether such descending pathways exist in
human.
In human, there is clear evidence that stimulation of the somatosensory area may
result in recordable and reproducible muscle twitches. A somatosensory evoked potential
is the electrical activity of the brain generated by the activation of sensory pathways at
peripheral, spinal, subcortical and cortical levels of the nervous system, elicited by
electrical, tactile, mechanical, or thermal stimuli.
11
Using optimal intensity peripheral
sensory stimuli may induce skeletal muscle response. Sensory signals from S1 may reach
pyramidal tract cells in layer V through monosynaptic connections or via oligosynaptic
connections, with interneurons relaying the signals in layers II and III,
12
resulting in a
descending volley to the muscle resulting in an MEP. Reasonably, latency of these MEPs
are longer compared with M1 TMS-evoked MEPs.
13
Previous studies have reported a high degree of variability in TMS-evoked
MEPs.
14,15
This variability can affect the interpretation of the results of studies investigating
changes in corticospinal excitability (CSE) after TMS. It can pose limitations and can also
make it difficult to determine whether reported changes in MEP amplitude are true
changes in CSE or whether they are merely a reflection of the inherent variability in TMS-
evoked MEPs
16
even if coil placement and stimulation intensity are constant.
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TMS over S1 has been extensively used to determine its effect on kinesthetic
perception
17
or in motor learning.
18
These studies, however, used coils with different size
that may pose variable range of influence on the adjacent area of the cortex. Moreover,
previous studies have targeted the extensor carpi radialis (ECR)
18
or the first dorsal
interosseous (FDI) muscles
19
but never the flexor carpi radialis (FCR) muscle. Because we
are interested in the contribution of S1 to motor learning, and one of our future targets is
the skill acquisition of wrist movement, we focused on the FCR related corticospinal
excitability in this study.
Taken together, the aim of the present pilot study was to determine the effects of
stimulation location, i.e., S1 vs. M1, on MEP waveform-related parameters, including
amplitude, latency, and variability in the contralateral FCR muscle. We hypothesized that
stimulating S1 vs. M1 would produce smaller MEP size, greater MEP variability but no
difference in MEP latency. These expectations are based on the poor focality of the
magnetic pulse: even if TMS is guided by neuronavigation the pulse is wide enough to
excite M1 interneurons when S1 is targeted. In addition, sensorimotor performance is
known to have a hemispheric asymmetry that underlies dynamic coordination
20
and may
also predict hand selection.
21
It is therefore possible that MEPs arising from sensorimotor
connections may differ between the two hemispheres. Thus, we also hypothesized inter-
hemispheric differences in MEPs when stimulating dominant left and non-dominant right
S1 or M1.
METHODS
Participants and ethical approval
Healthy volunteers (n = 8, 2 females, age: 29.9 ± 5.49 y), free of neurological
disorders, sensorimotor impairments or contraindications to TMS, participated in the study.
All participants were right-handed, determined by the Edinburgh Handedness Inventory.
22
Each subject gave a written informed consent in accordance with the Tohoku University
Human Ethics Committee (2018-1-792) and the Declaration of Helsinki.
Experimental procedure
In Japan, the Japanese Society of Clinical Neurophysiology (JSCN) has restricted
repetitive TMS (rTMS) administration to medical doctors due to safety concerns. Although
we used single pulse TMS to construct recruitment curves by stimulating S1 and M1 in
each hemisphere in this study, a trained medical doctor (TM) was always present during
the experiments. To increase topical selectivity, we guided TMS by neuronavigation
(BrainSight
TM
, Rogue Research Inc., Montreal, QC), which ensures reliable coil positioning
relative to the cortical target locus and allows us to correct any shift in coil position or
angulation during the measurements.
First, we performed a 3D MR imaging with a 3T scanner (Philips Intera Achieva
3.0-T Quasar Dual; Philips Healthcare Best the Netherlands) using an 8-channel
sensitivity-encoding (SENSE) head coil, operated by an expert MRI technician. Imaging
parameters were as follows: repetition time (TR) = 8.8 ms; echo time (TE) = 5.4 ms; flip
angle = 8°; field of view (FOV) = 256 mm, 1.07 × 1.07 × 1 mm3 voxels, 60 slices. Each
participant’s individual anatomic images were imported into the neuronavigation software
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to allow for stereotaxic registration of the participant’s brain with TMS coil for online control
of coil positioning. Subjects were then co-registered with their structural scans using
readily identifiable points on the head (nasion, tip of the nose, intertragal notches of the
ears).
The TMS measures reported here adhere to a TMS methodological checklist
established by international experts.
23
During TMS, participants were seated in a
comfortable chair with the forearms placed on armrests. Participants were instructed to
remain relaxed throughout the application of TMS. Surface electromyography (EMG)
recordings were monitored to ensure relaxation of each FCR muscle. EMG from each FCR
was continuously monitored using disposable bipolar surface electrodes (Covidien Kendall,
Ag/AgCl, Ref: 31.1245.21, UK). The electrodes were aligned along muscle fibers with a
1cm interelectrode distance and were connected to the MEP element of BrainSight
TM
software. To minimize noise in the EMG signal, the skin over the muscle belly was shaved,
scrubbed with sandpaper, and cleaned with alcohol. A ground electrode was placed on the
upper forearm. MEPs were evoked by delivering monophasic pulses with a 90 mm outer
diameter figure-of-eight coil connected to a Magstim 200 stimulators (Magstim, Whitland,
UK). The TMS coil was oriented tangentially to the scalp with the handle pointing back and
away from midline at 45° during stimulation of both M1s and S1s. The optimal location to
stimulate the left and right FCR, the so-called hotspots, were determined and marked
using the neuronavigation system to minimize variability across trials.
Resting motor thresholds (rMT) in each M1 (mean MNI coordinates: left M1: 44.7,
13.8, 85.7; right M1: -37.9, 14.0, 85.0) was determined as the minimum intensity at the
nearest 1% of maximum stimulator output that evoked MEPs in the FCR of at least 50 µV
in five out of 10 consecutive stimuli (rMT, % of maximum stimulator output, left M1: 60.1 ±
7.8; right M1: 62.6 ± 8.5). S1 areas (mean MNI coordinates: left S1: 55.9, 24.4, 78.3; right
S1: -54.7, 25.9, 74.8) of each hemisphere was targeted by moving the TMS coil one gyrus
backward and approximately 1 cm laterally from the FCR M1 hotspots18. Figure 1 shows a
representative participant demonstrating BrainSight
TM
localization of targets. Recruitment
curves were done over the left dominant and non-dominant right S1 and M1 by delivering 5
single pulses at each intensity of 80, 90, 100, 110, and 120% rMT in a randomized order.