Clinical Neurophysiology 114 (2003) 1477–1488

www.elsevier.com/locate/clinph

Changes in median nerve somatosensory transmission and motor output

following transient deafferentation of the radial nerve in humans
B.A. Murphya,*, H. Haavik Taylora, S.A. Wilsonb, J.A. Knighta, K.M. Mathersa, S. Schugc
a
Department of Sport and Exercise Science, Tamaki Campus, University of Auckland, Private Bag 92019, Auckland, New Zealand
b
School of Science, Mathematics & Medical Imaging, Christchurch Polytechnic, Christchurch, New Zealand
c
Anaesthesia & Pain Medicine Institution, University of Western Australia, Perth, Western Australia

Accepted 17 April 2003

Abstract
Objective: To determine if transient anaesthetic deafferentation of the radial nerve would lead to alterations in processing of early
somatosensory evoked potentials (SEPs) from the median nerve or alter cortico-motor output to the median nerve innervated abductor
pollicis brevis (APB) muscle.
Methods: Spinal, brainstem, and cortical SEPs to median nerve stimulation were recorded before, during and after ipsilateral radial nerve
block with local anaesthesia. Motor evoked potentials (MEPs) and motor cortex output maps were recorded from the APB muscle.
Results: There were no significant changes to most early SEP peaks. The N30 peak, however, showed a significant increase in amplitude,
which remained elevated throughout the anaesthetic period, returning to baseline once the anaesthetic had completely worn off. MEP amplitude of
the median nerve innervated APB muscle was significantly decreased during the radial nerve blockade. There was also a significant alteration in
the APB optimal site location, and a small but significant decrease in the silent period during the radial nerve blockade.
Conclusions: Transient anaesthetic deafferentation of the radial nerve at the elbow leads to a rapid modulation of cortical processing of
median nerve input and output. These changes suggest an overall decrease in motor cortex output to a median nerve innervated muscle not
affected by the radial nerve block, occurring concomitantly with an increased amplitude of the median nerve generated N30 SEP peak,
thought to represent processing in the supplementary motor area (SMA). Independent subcortical connections to the SMA are thought to
contribute to the N30 response observed in this study. Unmasking of pre-existing but latent cortico-cortical and/or thalamo-cortical
connections may be the mechanism underlying the cortical SEP increases observed following radial nerve deafferentation.
Significance: Transient deafferentation of the radial nerve, which supplies wrist and hand extensor muscles, has been shown to alter
sensory processing from and motor output to the median nerve innervated thenar muscles.
q 2003 International Federation of Clinical Neurophysiology. Published by Elsevier Science Ireland Ltd. All rights reserved.
Keywords: Somatosensory evoked potentials; Brain plasticity; Radial nerve; Deafferentation; Transcranial magnetic stimulation; Motor evoked potentials

1. Introduction Florence and Kaas, 1995; Merzenich et al., 1983a). There is

Dramatic reorganization of the primary somatosensory
cortex has been observed, within minutes to hours, follow-
ing deafferentation (Calford and Tweedale, 1991; Dono-
ghue et al., 1990; Merzenich et al., 1983a). The deafferented
cortex does not stay quiescent, but is taken over by body
representations adjacent to the deafferented body part
(Calford and Tweedale, 1991; Donoghue et al., 1990;
* Corresponding author. Tel.: þ61-649-3737599x6856; fax: þ 61-649-
373-7043.
E-mail address: b.murphy@auckland.ac.nz (B.A. Murphy).
1388-2457/03/$30.00 q 2003 International Federation of Clinical Neurophysiology. Published by Elsevier Science Ireland Ltd. All rights reserved.
doi:10.1016/S1388-2457(03)00131-7
good evidence that these rapid reorganizational processes
are mediated by unmasking (disinhibition) of existent but
latent cortico-cortical or thalamo-cortical connections, and
that the mechanisms involved include the removal of local
inhibition and changes in synaptic efficacy (Cohen et al.,
1999b; Florence and Kaas, 1995). A similar large-scale
reorganization has been known to develop progressively
over time (Florence and Kaas, 1995; Merzenich et al.,
1983b; Pons et al., 1991). These long-term changes are
thought to be due to an increase in synaptic efficacy of
previously existent synapses, and the establishment of new
anatomical connections (sprouting) (Merzenich et al.,
1478 B.A. Murphy et al. / Clinical Neurophysiology 114 (2003) 1477–1488
1983b; Pons et al., 1991). Large-scale somatosensory
reorganization has also been shown to occur at subcortical
levels, in the spinal cord (Dostrovsky et al., 1976; Florence
and Kaas, 1995; Pettit and Schwark, 1993), brainstem
(Dostrovsky et al., 1976; Florence and Kaas, 1995), and
thalamus (Nicolelis et al., 1993).
In humans, neural reorganization has been demonstrated
utilizing a number of techniques, such as motor evoked
potentials (MEPs) (Cohen et al., 1999a; Ziemann et al.,
1998), positron emission topography (Sadato et al., 1995),
and magnetoencephalography (Rossini et al., 1994).
Recently, cortical (Tinazzi et al., 1997, 1998), and
subcortical (Tinazzi et al., 1998) reorganization has been
demonstrated in humans utilizing somatosensory evoked
potentials (SEPs). These experiments indicated the levels in
the lemniscal somatosensory pathway in which the plastic
changes were taking place, which had not been previously
demonstrated (Tinazzi et al., 1997, 1998). Transient deaf-
ferentation of the ulnar nerve produced only cortical
changes in response to median nerve stimulation (Tinazzi
et al., 1997), whereas long-term deafferentation of the
median nerve produced subcortical as well as cortical
changes, following ulnar nerve stimulation (Tinazzi et al.,
1998). This difference suggests that transient peripheral
denervation may exert its effects independently of changes
in excitability of spinal and brainstem structures.
Recent psychophysical work (Murphy and Dawson,
2002) has demonstrated a decrease in the ability to
discriminate non-painful intramuscular stimulation deliv-
ered to the forearm extensor muscles following just 15 min
of either repetitive typing or forearm ischaemia. Given this
apparent decrease in afferent input from the radial-
innervated extensor muscles in the typing task, it would
be worthwhile to determine whether specifically decreasing
afferent input from the radial nerve leads to central
processing changes in a similar manner to the changes in
the median and ulnar nerves demonstrated previously
(Tinazzi et al., 1997, 1998).
There is also a growing body of evidence suggesting that
movement disorders such as dystonia are linked to abnormal
central integration of somatosensory input (Abbruzzese
et al., 2001; Bara-Jiminez et al., 1998; Byrnes et al., 1998;
Tinazzi et al., 2000). These studies demonstrate the
importance of investigating the effect of altered sensory
input on motor output. Previous studies, which utilized
TMS, have demonstrated changes in motor output following
both ischaemia deafferentation (Brasil-Neto et al., 1993)
and anaesthetic blocking of the nerve supplying the muscles
under investigation (Ziemann et al., 1998). We therefore
sought to investigate both sensory processing and motor
cortical output when investigating the effects of altered
afferent input on cortical functioning.
The present study investigated the short-term effect of
transient deafferentation, induced by nerve block of the
radial nerve, on SEPs evoked by stimulation of the median
nerve ipsilateral to the nerve block and on motor cortex
output to the abductor pollicis brevis (APB), a median nerve
innervated muscle, on the same side as the radial nerve
block.
2. Methods
2.1. Subjects
Six healthy subjects, one male and 5 females, between
the ages of 22 and 44 years participated in this study.
Exclusion criteria were neurological disease, previous head
injury, implanted metal plates in the head, or a cardiac
pacemaker. The project was approved by the University of
Auckland Human Subjects Ethics Committee. Written
informed consent was obtained from each subject. A
modified Edinburgh Handedness Inventory (Bryden, 1976)
was administered to determine the subject’s preferred hand.
The SEP data from one subject could not be analysed due to
electrical interference in the EEG recordings. The TMS data
from all 6 subjects were analysed.
2.2. SEP stimulation and recording
For SEP recording, the subjects were seated in a reclining
La-Z-boye chair, in a quiet room. All recording electrodes
were placed according to the International Federation of
Clinical Neurophysiologists (IFCN) recommendations
(Nuwer et al., 1994). Disposable adhesive recording
electrodes (7 mm Ag/AgCl Hydrospote from Physiome-
trix) were placed on the ipsilateral Erb’s point, over the C5
spinous process (Cv5), and 2 cm posterior to contralateral
central and frontal scalp sites C3/C4 and F3/F4, which will
be referred to as Cc0 , and Fc0 , respectively. Finally a
recording electrode was also placed 2 cm posterior to the
ipsilateral central scalp site C3/C4. This will be referred to
as Ci0 and is utilized in order to record any possible arousal
effect from the anaesthetisation procedure. The Cc0 and Fc0
recording electrodes were referenced to both Fz and the
contralateral acromion process. The Erb’s and Cv5 record-
ing electrodes were referenced only to the contralateral
acromion process. A ground electrode was attached to the
forehead. The stimulating electrodes were placed over the
median nerve at the wrist of the dominant arm. Stimuli were
delivered at 103% of the motor threshold using a constant
current stimulation at a rate of 2 Hz, a rate that does not lead
to SEP attenuation (Fujii et al., 1994).
The SEP electrodes were in place before and during the
anaesthetic block. Prior to the transcranial magnetic
stimulation, a permanent marking pen was used to draw
around the Fc0 and Cc0 electrodes which were removed.
Following the ‘during’ and post-anaesthetic TMS record-
ings, the Fc0 and Cc0 electrodes were repositioned and the
post-anaesthetic SEP data were collected.
Experiments were conducted prior to the anaesthetic
block experiments where SEP traces were shown to be
 B.A. Murphy et al. / Clinical Neurophysiology 114 (2003) 1477–1488
reproducible after electrode repositioning at the Fc0 and Cc0
sites.
2.3. Transcranial magnetic stimulation
There were two recording sessions for this experimental
protocol. These sessions were separated by an average of
4 days (range 2– 10 days). During the first session the
threshold and estimated optimal site for the APB muscle
were ascertained. The motor representation area of APB
was then mapped for the contralateral hemisphere corre-
sponding to the dominant hand, during which MEPs and
silent periods (SPs) at the optimal site were obtained.
The second session involved mapping APB while the radial
nerve was blocked.
Surface electromyography (EMG) was recorded from the
APB muscle, using Grassw gold electrodes (Astro-Med,
Inc.) with the active electrode over the motor point and the
inactive electrode over the metacarpophalangeal joint. The
ground electrode was placed on the lateral epicondyle of the
distal end of the humerus. EMG was digitised at 2 kHz, with
a low pass filter at 1 kHz and a high pass filter at 10 Hz. Data
were amplified by 10,000, and recorded for a period of
500 ms after the stimulus.
A custom designed computer program using AMLABw
data acquisition triggered the TMS stimuli. This occurred
when the root mean square (RMS) level of APB EMG
activity corresponded to a muscle contraction that was
within 10 ^ 3% of the subject’s maximum voluntary
contraction (MVC) for 3 consecutive 500 ms epochs. The
RMS level of EMG activity was shown online to provide
feedback to the subject as to their level of muscle contraction.
The data were stored to disk for off-line analysis.
A Magstim 200w magnetic stimulator with a 50 mm
diameter figure-of-8 coil was used. Stimulus intensity,
described as the percentage of stimulator output, was
threshold adjusted. The precise placement of the stimulating
coil over the pre-marked site was achieved by aligning a
fiducial mark on a fine metal rod with a fiducial mark on a
piece of clear plastic that was glued to the TMS coil. The
coil had been previously X-rayed to determine its exact
centre. The end of the metal rod was placed over the
stimulation site and the mark on the rod was lined up with a
mark on the piece of clear plastic that was attached to the
TMS coil. This ensured that the maximum magnetic field
was applied over the exact pre-marked location on the scalp
or cap (see Fig. 1). The metal rod was withdrawn before
stimulation. The stimulator coil was held tangentially to the
skull with the handle in an antero-posterior orientation
(handle posterior). Current flow at the centre of the coil was
towards the coil handle. Threshold was defined as the
intensity at which at least 6 out of 10 stimuli evoked a MEP
that was readily discernable above the background EMG at
the estimated optimal site of stimulation. Given that the
subjects were maintaining a 10% background contraction
this level was approximately 600 mV.
1479
For stimulus site location, the scalp was modelled as a
hemisphere and stimulation sites positioned using a
latitude/longitude-based coordinate system, with the vertex
as the origin. The stimulation sites were pre-marked onto a
snug fitting, flexible, translucent cap, with spacing of 1 cm
latitude and longitude. Stimuli were delivered approxi-
mately 6 s apart with 4 stimuli delivered at each site. The
first site stimulated was the estimated optimal site for
eliciting an MEP and then the sites surrounding this were
stimulated until MEPs could no longer be identified, and the
borders of the representation area for the muscle were
determined in all directions. There were approximately 35
sites stimulated during each mapping session. The stimulus
intensity used was 10% of the stimulator output above the
threshold for that muscle. The mean MEP peak-to-peak
amplitudes for each site were then calculated off-line. The
SP durations were measured individually and then averaged.
3. Map analysis
A purpose-written mapping program was used to
generate the cortico-motor output maps which calculated
the optimal site location using spline functions. The
protocol has previously been described in detail (Byrnes
et al., 1998; Thickbroom et al., 1999; Wilson et al., 1993).
The program converted the absolute position of the stimu-
lation site in centimetres to an angular position on an
idealized sphere of half-circumference given by the
subject’s inter-aural distance. A complete map was then
generated by spherical spline interpolation between stimu-
lus sites. This resulted in a fit function which enabled the
estimated MEP amplitude to be determined at any given
latitude/longitude value. The centre of each map was deter-
mined from the location of the peak map value, and was
defined by two distances, the distance from vertex (latitude)
and the distance from the inter-aural line along a line of
constant latitude (anterior positive). These distances were
expressed in millimetres based on a standardized inter-aural
distance of 37 cm.
3.1. Radial nerve block
The anaesthetic block was administered on the second
experimental session. A peripheral nerve stimulator was
used by the anaesthetist to locate the optimal site for
anaesthetic administration. This site was located approxi-
mately 1 cm lateral to the biceps tendon in the cubital fossa.
Prilocane (1%) was injected into this region. The anaes-
thetic effectively blocked the radial nerve distal to the
elbow, which supplies the posterior forearm muscles and the
skin over the dorsum of the thumb. The APB innervation,
via the median nerve, was left intact.
For the purposes of this study, the radial nerve block was
considered to be in effect as long as both EMG from
recording electrodes over the radial nerve innervated
1480 B.A. Murphy et al. / Clinical Neurophysiology 114 (2003) 1477–1488

Fig. 1. Diagram depicting how the TMS stimulating coil was precisely aligned with the specific stimulating site on the subject’s scalp, with the use of a pre-
marked metal rod. The end of the metal rod was placed over the stimulation site and the mark on the rod was lined up with a mark on the piece of clear plastic
that was glued to the TMS coil once the coil was moved over the rod. Once the coil was in place, the rod was withdrawn before stimulation.

forearm muscles and sensation over the dorsum of the
thumb were absent. The nerve blocks were in place for
2 –4 h which allowed enough time for both the motor maps
and SEP blocks to be completed.
3.2. Experimental sequence
With electrophysiological evidence of a complete nerve
block, 3 blocks of SEP data were collected at intervals of
10 min. The sites of the SEP electrodes were then clearly
marked so that they could be reapplied on completion of the
motor cortex mapping. The electrodes were removed and
the mapping cap was then fitted. The motor map of APB was
then performed. In addition, EMG testing of extensor indicis
proprius (EIP) and extensor carpi radialis (ECR) was
performed before each SEP trial and at the completion of
the muscle mapping session to confirm whether the block
had been in place for the full mapping session.
Once there was EMG evidence that EIP and ECR had
returned to 80% of MVC, the final SEP data were collected.
The SEP electrodes were reapplied in the pre-marked sites,
impedances were checked and 3 post-anaesthetic SEP trials
were collected.
4. Data analysis
administration of the local anaesthetic (pre-anaesthetic
period; mean value trial 1). Another 3 blocks were recorded
during complete anaesthesia (anaesthetic period; trials
2 – 4). Finally 3 blocks of SEPs were recorded after the
local anaesthetic had worn off (post-anaesthetic period;
trials 5 –7).
Amplitudes were measured both from the peak of interest
to the baseline (peak-to-baseline), and where possible, from
the peak of interest to the preceding and/or succeeding peak of
opposite deflection (peak-to-peak). Latencies were measured
to the maximum deflection of each peak. This is in accordance
with the IFCN recommendations (Nuwer et al., 1994).
The amplitude and latency data for all subjects were
analysed for normal distribution and homogeneity of
variance. The data were then examined using a repeated
measures analysis of variance (ANOVA) to test for
significant differences between the pre-anaesthetic blocks.
No significant differences were found so the pre-anaesthetic
blocks were collapsed into pre-anaesthetic mean values. All
peaks were then analysed using repeated measures
ANOVA, with a priori contrasts established between the
pre-anaesthetic mean and subsequent anaesthetic and post-
anaesthetic blocks. The latencies and amplitudes of Erb’s
point N9, spinal N11 and N13 (recorded by the Cv5 electrode),
far-field potentials P14, and N18 (recorded with scalp
electrodes), parietal N20, and frontal N30 were analysed.

4.1. Somatosensory evoked potentials 4.2. Mapping and motor evoked potentials

SEPs were analysed in blocks of 500 averaged artifact- The pre-intervention measures were compared to post-
free trials. Three blocks of SEPs were recorded before intervention measures in two-tailed t tests. Three t tests, for
 B.A. Murphy et al. / Clinical Neurophysiology 114 (2003) 1477–1488 1481

MEP amplitude, SP and optimal site location were Table 1

performed. To adjust for the use of 3 comparisons, the APB MEP amplitude (mV) values for control and nerve block conditions,
and the percentage change from these conditions, for all subjects
p-value was set at p , 0:016 for MEP and SP measures at
the estimated optimal site as well as at the optimal site Subject Control Nerve block MEP decrease (%)
calculated using the mapping program.
1 20.6 17.0 17.4
2 20.6 12.0 41.6
3 22.7 15.8 30.5
5. Results 4 21.9 20.1 8.5
5 22.5 18.7 16.9
6 11.9 8.9 25.8
5.1. Somatosensory evoked potentials

There were no latency changes for any of the peaks under
investigation. Representative data from the pre-intervention
SEP data (Fig. 2) show the reproducibility of the SEP data
prior to the nerve block.
None of the early SEP peaks including the N9 peripheral
volley showed any amplitude alterations. The N30 –P40
complex showed a significant increase in amplitude in the
first block during the anaesthetic period (see Fig. 3),
increasing to 149% above baseline. This increase persisted
throughout the anaesthetic period and gradually returned to
baseline in the 3 blocks of SEPs collected once the
anaesthetic had worn off. Representative traces from a
single subject depict the N30 increase during the anaesthetic
and its return to baseline afterwards (Fig. 4).
5.2. Transcranial magnetic stimulation
5.2.1. MEP amplitude
The results for the APB MEP amplitude at the estimated
optimal site are shown in Table 1. The MEP amplitude was
significantly decreased during the nerve block ðp ¼ 0:006Þ.
The average decrease was 23.4% (range: 8.4– 41.6%). The
averaged MEP decrease at the estimated optimal site for a
representative subject is shown in Fig. 5.

5.2.2. Silent period duration

The results for the SP duration at the estimated optimal
site are shown in Table 2. The average change in SP
duration was 8.9% (range: 2 1.0 to 30.6%). One subject had
a much larger increase than the others.

5.2.3. Optimal site location

The results for the APB optimal site location are shown
in Tables 3 and 4; Fig. 6. Table 3 summarizes the APB
optimal site location recorded in two separate control
sessions. Analysis of the optimal sites for the two control
sessions demonstrated that there were no significant
differences between these sessions ðp ¼ 0:84Þ. The average
difference was 2.1 mm with a range of 1.7 – 2.7 mm.
Table 4 summarizes the changes in optimal site location
during the radial nerve block. The average change was
3 mm with a range of 1.6 –5 mm. The change in optimal site
location during the radial nerve block was significantly
different from the control optimal site ðp ¼ 0:003Þ. The
shifts in optimal site location in the mediolateral location
during the nerve block are shown in Fig. 2.

6. Discussion

The major findings of this present study are that transient

Fig. 2. Erb’s point (Erb), cervical (Cv5), post-central (Cc0 ) and pre-central peripheral denervation of radial nerve produces rapid
(Fc0 ) SEP traces from one representative subject prior to radial nerve block.
Traces are superimposed to show reproducibility of the measured peaks.
reversible changes to:
Cc0 and Fc0 were recorded with a cephalic reference. Erb’s and Cv5 had
non-cephalic references. 1. the pre-central N30 median nerve SEP peak,
1482 B.A. Murphy et al. / Clinical Neurophysiology 114 (2003) 1477–1488

Fig. 3. Averaged group SEP data. The dotted lines define the anaesthetic period. Block 1 represents the mean pre-anaesthetic SEP values; blocks 2, 3 and 4 are
during anaesthetic; blocks 5, 6 and 7 are post-anaesthetic. The N9, N20 and N30 complexes (panel a, b and c) showed no changes in amplitude during the
anaesthetic. The N30–P40 complex (d) showed a significant increase (*) in amplitude during the first 10 min of anaesthetic, which then remained elevated
while the anaesthetic was in place, gradually returning to baseline once the anaesthetic had worn off.

2. the motor cortex output (MEPs), and
3. motor cortex maps to the median nerve innervated APB
muscle.
6.1. Somatosensory evoked potentials
The increased cortical SEPs are consistent with previous
human transient denervation studies (Tinazzi et al., 1997),
as well as previous animal studies (Calford and Tweedale,
1991; Merzenich et al., 1983a). These short-term changes
could reflect an immediate unmasking of pre-existing, but
latent cortico-cortical connections and removal of local
inhibition (Cohen et al., 1999a), and/or unmasking of
existent but latent thalamo-cortical connections (Florence
and Kaas, 1995).
It has been hypothesized that rapid reorganization is
 B.A. Murphy et al. / Clinical Neurophysiology 114 (2003) 1477–1488 1483

Fig. 4. Pre-rolandic median nerve SEP waves in one representative subject before, during, and after radial nerve block showing the increase in N30 during the
block which then returns to an even lower than baseline value once the block has worn off. The SEP waves were recorded at Fc0 with a cephalic reference.

mediated through N-methyl-D -aspartate (NMDA)-recep-
tors. This usually requires the down-regulation of local
inhibitory circuits with a removal of g-aminobutyric acid
(GABA) related cortical inhibition, since intracortical
administration of NMDA-receptor blockers has demon-
strated a lack of rapid cortical reorganization (Cohen et al.,
1999a). A lack of rapid cortical reorganization has also been
reported in studies with enhancement of GABA action
(Tegenthoff et al., 1999).
Therefore, the short-term amplitude enhancement of
median nerve cortical SEPs shown in the present study
could reflect disinhibition of latent cortico-cortical and
thalamo-cortical projections arising from median nerve
territories adjacent to the radial nerve deafferented zone.
The shift in the optimal site for eliciting APB MEPs during
the radial nerve block provides further evidence of
unmasking of latent cortico-cortical connections, as a result
of the radial nerve block.
6.2. Cortical somatosensory evoked potentials
The N30 – P40 complex was the only SEP peak that
significantly increased during the radial nerve block. Some
authors suggest that the N30 originates in the post-central

Fig. 5. Averaged MEPs measured at the estimated optimal site before and during (heavier trace) radial nerve block in one representative subject.
1484 B.A. Murphy et al. / Clinical Neurophysiology 114 (2003) 1477–1488

Table 2 Table 4
The APB SP duration (ms) for the control and nerve block conditions, and Optimal site locations (cm) of APB for control and nerve block conditions,
the percentage change following the nerve block, for all subjects and the difference (cm) between the two conditions, for all subjects

Subject Control Nerve block SP change (%) Subject Control Nerve block Difference (mm)

1 93 121 30 1 5.04 5.20 1.6

2 112 111 21 2 5.27 5.59 3.2
3 179 190 6 3 5.63 6.10 4.7
4 139 144 4 4 4.67 4.49 1.8
5 159 167 5 5 4.52 4.38 1.4
6 131 143 9 6 6.42 6.92 5.0

cortical regions (i.e. S1) (Allison et al., 1989, 1991), while increased exclusively in the SMA during mental program-
others suggest that this SEP component is related to a more ming of fast finger movements (without execution),
complex cortical and subcortical loop linking the basal suggesting that the gating of N30 during simulated move-
ganglia, thalamus, pre-motor areas (especially the sup- ment is further evidence for SMA being its neural generator.
plementary motor area, SMA), and primary motor cortex The increase of the N30 – P40 complex observed in our
(Cheron and Borenstein, 1991, 1992; Desmedt et al., 1983; study suggests that there may be an increase in SMA activity
Mauguiere et al., 1983; Rossini et al., 1987; Rossini and following median nerve stimulation during radial nerve
Babiloni, 1989; Waberski et al., 1999). deafferentation. It is interesting to note that there was no
Several groups have presented findings suggesting that significant increase in the N20 – P27 complex, which is
the N30 waveform is generated in the SMA (Cheron and known to be generated in S1 (Desmedt and Cheron, 1980;
Borenstein, 1991; Cheron and Borenstein, 1992; Mauguiere Mauguiere, 1999; Nuwer et al., 1994). Given that some
et al., 1983; Rossini et al., 1987; Rossini and Babiloni, authors have suggested a post-central origin for the N30
1989). Two groups have shown that it reaches maximal peak (Allison et al., 1989, 1991), our results suggest that this
amplitude overlying the SMA (Desmedt and Cheron, 1981; contributor to the N30 peak was not affected by the
Rossini et al., 1987) whereas Valeriani et al. (2000) provide deafferentation of the radial nerve.
data to suggest that a central electrode site provides a clearer
N30 SEP peak, less contaminated by the N24. Rossini and 6.3. Evidence suggesting separate thalamo-cortical
Babiloni (1989) demonstrated that the N30 component was connections to supplementary motor area
absent in a subject who suffered from unilateral SMA
compression, due to a meningioma of the falx. The frontal
This suggests that the supplementary motor cortical
N30 was clearly absent on the side of compression. Waberski
reorganization is not merely a flow on effect from the
et al. (1999) used dipole source localization and current
density reconstruction with realistically shaped head models,
and demonstrated that the N30 generator was tangentially
oriented and located in the pre-central gyrus. The N30
component is also the most vulnerable SEP component to
the gating effect that occurs during voluntary muscle
contraction (Cheron and Borenstein, 1991). Interestingly,
this gating of N30 does not require the actual movement of
voluntary muscles, but occurs even when the subjects only
mentally simulate a series of finger movements (Cheron and
Borenstein, 1992). Roland et al. (1980) have previously
demonstrated that regional cerebral blood flow (rCBF) is
Table 3
The APB optimal site locations (cm) for the two control sessions, and the
differences between the two (mm)

Session 1 Session 2 Difference (mm)

5.04 5.23 1.9

6.16 6.42 2.6
6.30 6.03 2.7 Fig. 6. Changes in the APB optimal site location during the radial nerve
5.27 5.09 1.8 block for all subjects. Locations prior to and during the nerve block are
6.04 6.26 2.2 calculated by the mapping program in centimetres of latitude (mediolateral
5.94 6.11 1.7 direction). Note: the open circles indicate the pre-intervention value and the
closed circles indicate the post-intervention value.
 B.A. Murphy et al. / Clinical Neurophysiology 114 (2003) 1477–1488
primary somatosensory cortex, but that separate thalamo-
cortical connections may contribute to the observed N30
changes. A growing body of research (Insola et al., 1999;
Mauguiere et al., 1983; Mauguiere and Desmedt, 1991;
Pierantozzi et al., 1999; Rossini et al., 1987; Rossini and
Babiloni, 1989) provides strong evidence that sensory
inputs reach motor and pre-motor areas via parallel direct
pathways from thalamic relays. Insola et al. (1999)
demonstrated an abolishment of the P14 –N20 – N25 post-
central complex in the days immediately following a
thalamic implant while the N18 far-field and pre-rolandic
P22 –N30 complex remained unaffected. Both Insola et al.
(1999) and Pierantozzi et al. (1999) demonstrated enhance-
ment of the N30 complex following deep brain stimulation
without any corresponding change in the post-central SEP
waveforms.
Previous work has also shown that the frontal N30
component is dramatically affected by increasing the
stimulation rate, compared to other SEP components that
remain much more stable (Garcı́a-Larrea and Mauguiére,
1990). Fujii et al. (1994) have suggested that increasing
stimulus rates leads to muscle contraction and secondary
excitation of spindle and tendon afferents. It is also known
that the N30 peak is the most vulnerable SEP component to
vibration interference (Hoshiyama and Kakigi, 2000).
Vibration of relaxed muscles, as used in Hoshiyama and
Kakigi’s study (2000), predominantly stimulates the group
Ia fibers from muscles spindles (Roll et al., 1989) while
group Ib and II fibers are not sensitive to this type of
stimulation (Roll et al., 1989). This indicates that the N30
SEP is particularly sensitive to altered input from muscle
afferents. The afferent component of the radial nerve at the
elbow, which was anaesthetised in our study, contains
mainly muscle afferents, as the bulk of the cutaneous
innervation to the forearm is supplied from the superficial
radial nerve branch that exits superior to the elbow
(Romanes, 1976). This may partially account for the fact
that we only saw a change in the N30 component, whereas
Tinazzi et al. (1997) found that all early cortical SEP peaks
were significantly increased. The difference between our
results and those of Tinazzi et al. (1997) may be that the
ulnar and median nerves which they investigated, innervate
functionally synergistic muscles, whereas the radial nerve,
investigated in our study, innervates forearm extensor
muscles that are antagonists to the median nerve innervated
flexor muscles. This functional difference may be reflected
in a physiological difference in the way in which the
individual nerves of the forearm respond to deafferentation.
Previous animal studies have shown that the pattern of
reorganization in the primary somatosensory cortex follow-
ing median, ulnar or radial nerve section is not the same
(Schroeder et al., 1995). Somatosensory afferent input from
the dorsum of the hand, carried by the radial nerve, has been
shown to have preferential access to the cortical territories
normally expressing glabrous inputs carried by the median
and ulnar nerves. This is believed to be due to pre-existing
1485
but latent radial nerve inputs to the glabrous regions of
cortex (Schroeder et al., 1995).
6.4. Subcortical somatosensory evoked potentials
No change was observed for the N9 SEP component (see
Fig. 3a), indicating there was no change to the peripheral
afferent volley in the brachial plexus from median nerve
stimulation, following ipsilateral radial nerve blockade.
This is what was expected, as the median nerve was not
blocked, and is consistent with previous transient denerva-
tion SEP studies (Tinazzi et al., 1997, 1998).
There was no significant alteration in the subcortical
peaks (see Fig. 3b for the P14 –N18 complex). The P14 is
thought to originate in the medial lemniscus (Noel et al.,
1996), and the N18 is thought to originate in the brain stem,
rostral to the pontine level yet below the mid-brain (Noel
et al., 1996; Sonoo et al., 1991; Urasaki et al., 1990, 1992).
The lack of change in subcortical SEPs is consistent with the
work of Tinazzi et al. (1997). They found no changes to any
subcortical structures following median nerve stimulation
during anaesthetic block to the ulnar nerve (Tinazzi et al.,
1997).
6.5. Motor evoked potential changes
The MEP amplitudes to the median nerve innervated
APB muscle were decreased during the radial nerve block,
suggesting decreased cortico-motor output, while the N30
SEP peak, which may partially reflect afferent processing in
the SMA, was increased. Previous studies using ischaemic
nerve block have demonstrated an increase in MEP ampli-
tude for unaffected muscles that were proximal to the site of
ischaemic block (Brasil-Neto et al., 1992, 1993; Ziemann
et al., 1998). It is possible that the decrease found in this
study is linked with the anatomical position of the APB,
being distal to the site of the blocked muscles rather than
proximal.
Recent work by Tokimura et al. (2000) has demonstrated
a short latency inhibition of the APB muscle by somato-
sensory input from the hand. This suggests that the func-
tional complexity of many hand tasks requires a more
complex pattern of cortical inhibition, than the reciprocal
inhibition that has been demonstrated in the motor cortex
between forearm flexors and extensors (Bertolasi et al.,
1998). Another factor that may contribute to the differences
between the results for the anaesthetic and the ischaemic
experiments, is that the posterior forearm muscles are
functionally related to APB activity. During the perform-
ance of many everyday tasks, the posterior forearm muscles,
the intrinsic thumb muscles and the intrinsic finger flexors
must work together to produce actions. For example when
performing a typing task, the muscles are rhythmically
contracted to hit the keyboard, and their functional links are
1486 B.A. Murphy et al. / Clinical Neurophysiology 114 (2003) 1477–1488
obvious. Recent work on the first dorsal interosseous,
confirms that there are task-dependent excitability
differences in cortico-motor output to TMS stimulation,
including different contributions from synergistic muscles
(Hasegawa et al., 2001).
It is a possibility, that the optimal site shift during the
intervention period meant that the MEP amplitude was no
longer measured at the same place relative to the optimal
site. To confirm this we looked back at the averaged MEP
amplitudes for the sites around the original manually
determined optimal site. The averaged MEP amplitudes
were still the largest at the original optimal site. The
‘optimal site’ as described by the mapping program is
calculated using spline functions. The shift in the optimal
site for the APB muscle as calculated by the mapping
program demonstrates that the transient radial nerve deaf-
ferentation altered cortical output to the median nerve. The
lack of alteration in the P14– N18 median SEP complex
during the radial nerve block, suggests that the most likely
mechanism for the map alterations is unmasking of pre-
existing cortico-cortical connections, rather than an altera-
tion at the thalamic level.
The inhibitory action of forearm flexor muscle afferents,
from median nerve stimulation, on cortico-spinal output to
radial nerve innervated forearm extensor muscles, has been
previously demonstrated (Bertolasi et al., 1998). A number
of lines of evidence suggest that the mechanism of this
reciprocal inhibition is intracortical. The latency of the
inhibition and the fact that it was sensitive to the TMS-
induced anterio-posterior current flow (which preferentially
activates cortical interneurones), favour an intracortical
mechanism for the inhibition. The authors found a similar
pattern of inhibition when they stimulated the radial nerve
and measured MEPs in the forearm flexors (Bertolasi et al.,
1998). Interestingly, the mechanism of the MEP amplitude
decrease observed in our study may be due to an increase in
cortical inhibition. However, the MEP amplitude decrease
we observed may not be entirely accounted for by an
increase in inhibition, as our SP duration increased by only
8.9%, in the face of a 23.4% decrease in MEP amplitude.
The underlying physiological mechanisms of the SP are not
yet fully understood. Studies have shown that the first part
of the SP (about 50 ms) after TMS is produced mainly by
spinal mechanisms such as after-hyperpolarization and
Renshaw recurrent inhibition of the spinal motoneurons
(Chen et al., 1999; Inghilleri et al., 1993). Reciprocal
inhibitory effects on the target muscle may also contribute,
since the magnetic stimulation often causes simultaneous
activation of antagonists. The rest of the SP (after about
50 ms) is produced mainly by cortical inhibition (Chen et al.,
1999; Cantello et al., 1992; Inghilleri et al., 1993; Kukowski
and Haug, 1992). The exact mechanisms of this cortical
inhibition are, however, more difficult to establish. Most
evidence suggests that this inhibition is presynaptic to the
cortico-spinal neurons, rather than due to a decreased
excitability of these cortico-spinal neurons (which would be
reflected by a decreased MEP) (Cantello et al., 1992;
Inghilleri et al., 1993; Tergau et al., 1999). Some argue that
it results from activation of inhibitory neurons projecting
onto the pyramidal cells of the motor cortex (Inghilleri et al.,
1993). The increased SP we observed may therefore reflect
an increase in cortical inhibition which may be partly
responsible for the decreased APB MEP amplitudes during
the radial nerve block.
In the SEP study previously described (Tinazzi et al.,
1997), initial SEP changes occurred in the N20 cortical, as
opposed to subcortical peaks, suggesting that sensory
modulation occurs first at cortical levels. In addition,
motor experiments have also provided strong evidence
that the level of motor modulation occurs at the cortical
level (Brasil-Neto et al., 1993). Using H-reflexes and spinal
cord excitation, Brasil-Neto et al. (1993) demonstrated that
there were no changes in spinal cord excitability during
ischaemic nerve block. The MEP response to transcranial
electrical stimulation (TES) was much less than that to
TMS during ischaemic block. This further confirmed the
fact that the changes originated at motor cortical level, as
TMS preferentially activates pyramidal tract neurons
transynaptically, while TES activates their axons (Day
et al., 1989).
As the anaesthetic radial nerve block in the current
investigation results in a similar type of deafferentation to
the ischaemic nerve block experiments, there is a strong
probability that the modulation seen with the radial nerve
block is also cortical in origin. The decrease in motor output
suggests that competing mechanisms control the ultimate
motor output during altered sensory input. This study is of
potential relevance to the development of overuse injuries,
especially those related to keyboard use. Both typing and
forearm ischaemia have been shown to impair the ability to
discriminate non-noxious intramuscular stimuli delivered to
the forearm extensor muscles (Murphy and Dawson, 2002).
The suggested mechanism for this decreased discrimination
following the typing task was a decrease in Ia input due to
partial ischaemia resulting from the fact that the wrist
extensor muscles are statically contracting throughout the
typing task. There is evidence that performing a repetitive
task at as little as 5% of a MVC can indeed impair blood
flow to the forearm musculature (Byström and Kilbom,
1990). Static muscular contractions of 16% of MVC also
impede intramuscular blood flow (Järvholm et al., 1988).
The design of this study, using median nerve SEPs and
TMS output to a median nerve muscle during an
anaesthetic block of the radial nerve, provided a unique
opportunity to investigate the consequences of decreas-
ing radial nerve afferent input on median nerve
processing. The increase in median nerve N30 – P40
and the decrease in motor output to the APB muscle
during radial nerve deafferentation indicated that partial
ischaemic deafferentation could indeed be a mechanism
which initiates the neuroplastic changes that lead to overuse
injuries becoming chronic.
 B.A. Murphy et al. / Clinical Neurophysiology 114 (2003) 1477–1488
7. Summary
The effect of transient denervation of the radial nerve at
the elbow showed rapid modulation of sensory processing
of median nerve input in the SMA, and in motor cortex
output to the APB, a median nerve innervated muscle. The
N30 SEP increased while the motor output to the APB
muscle decreased during the radial nerve block. These
findings are of potential relevance to the development of the
overuse injuries that develop with prolonged keyboard use.
Acknowledgements
We would like to thank Dr Gary Thickbroom for
allowing us to use his mapping program.
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