Perceptual phenomena and cortical reorganization Neuroscience Vol. 102, No. 2, pp.

263±272, 2001263
q 2001 IBRO. Published by Elsevier Science Ltd
Pergamon Printed in Great Britain. All rights reserved
PII: S0306-4522(00)00491-7 0306-4522/01 $20.00+0.00
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THE RELATIONSHIP OF PERCEPTUAL PHENOMENA AND CORTICAL

REORGANIZATION IN UPPER EXTREMITY AMPUTEES

È SSER, b* C. WINTER, b W. MU
S. M. GRU È HLNICKEL, b C. DENKE, b A. KARL, c K. VILLRINGER d and
H. FLOR a*
a
Department of Neuropsychology, Central Institute of Mental Health, Mannheim, Germany
b
Department of Psychology, Clinical Psychology and Behavioral Neuroscience Unit, Humboldt-University, Berlin, Germany
c
Department of Biopsychology, University of Technology, Dresden, Germany
d
Department of Radiology, University Clinical Center Benjamin Franklin, Free University, Berlin, Germany

AbstractÐIn this study 16 unilateral upper extremity amputees participated in a comprehensive psychophysiological
examination that included the assessment of painful and non-painful phantom and stump sensations, thermal and electric
perception as well as two-point discrimination thresholds, the detailed analysis of referred sensation and the measurement of
reorganizational changes in primary somatosensory cortex using neuroelectric source imaging. Reorganization of the
primary somatosensory cortex was associated with increased habitual phantom limb pain, telescoping, non-painful stump
sensations and painful referred sensation induced by painful stimulation. It was unrelated to non-painful phantom sensations,
non-painful referred sensation elicited by painful or non-painful stimulation, painful referred sensation elicited by non-
painful stimulation, perception thresholds and stump pain.
These data substantiate the hypothesis that painful and non-painful phantom phenomena are mediated by different neural
substrates. q 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.

Key words: cortical plasticity, phantom limb pain, phantom phenomena, referred sensations, neuroelectric source imaging, traumatic
amputation.

The amputation of a limb is usually accompanied by the
development of non-painful phantom sensations in the
now absent limb. In up to 85% of the cases there are
also painful sensations in the phantom. 14,37 So far it is
not known which mechanisms contribute to the occur-
rence of these phantom phenomena. Both central and
peripheral factors have been implicated. For example,
Melzack 24 postulated the existence of a neuromatrix
involving several brain areas which are thought to under-
lie phantoms. Sherman 35 and others have pointed out that
peripheral processes involving local psychophysiological
changes at the stump may signi®cantly contribute to both
non-painful phantom sensations and phantom limb pain.
Decades ago it had already been suggested that plastic
alterations at the spinal, thalamic or cortical level might
be related to phantom phenomena. 3 In recent years,
animal experiments have shown that deafferentation of
a nerve is followed by reorganization of the primary
somatosensory area of the cortex. 15,25,31 For example,
*Corresponding authors. Tel.: 149-621-1703918; fax: 149-621-
1703932.
E-mail address: gruesser@rz.hu-berlin.de (S. M. GruÈsser),
¯or@as200.zi-mannheim.de (H. Flor).
Abbreviations: D1, digit one; D5, digit ®ve; EEG, electroencephalo-
graphy; MPI, Multidimensional Pain Inventory; MRI, magnetic
resonance image; RFS, referred sensation; SI, primary somatosen-
sory cortex; SVD, singular value decomposition; VAS, visual
analogue scale.
263
Merzenich and colleagues 25 showed that the amputation
of a ®nger in an adult owl monkey led to an invasion of
1±2 mm of adjacent areas into the cortical representation
of the deafferented ®nger in primary somatosensory
cortex (SI; area 3b). An even more extensive reorganiza-
tion of about 1±2 cm was reported by Pons et al. 31 who
studied adult macaques who had undergone deafferenta-
tion of an upper extremity 12 years earlier. The area
below the mouth and the cheek now activated neurons
in the former arm and hand area. The magnitude of this
reorganization suggested that the mechanism involved
might be more than just sprouting at the dendritic
trees. 10,11 Ramachandran, Rogers-Ramachandran and
Stewart 33 found that stimulation of the face area of
upper limb amputees led to referred sensations in the
phantom hand with a one-to-one relationship of indivi-
dual stimulation sites and areas of phantom sensations in
the hand (see also Refs. 3, 12, 20). Based on the Pons et
al. 31 data, they proposed that this phenomenon might be a
perceptual correlate of cortical reorganization.
Katz 17 postulated that cortical reorganization might be
an adaptive and potentially phantom pain-relieving
mechanism and assumed that telescoping was a per-
ceptual correlate of this reorganization which he believed
to be negatively correlated with phantom limb pain. In
humans, electroencephalographic and magnetoence-
phalographic methods combined with magnetic reson-
ance imaging have revealed reorganizational changes
264 S. M. GruÈsser et al.
Table 1. Clinical characteristics of the study sample
Mean
Phantom limb pain
MPI (range 0±6) 2.06
VAS (range 0±100) 43.44
Non-painful phantom sensations
Index of frequency £ intensity (range 0±24) 5.04
Stump pain
MPI (range 0-6) 0.96
Non-painful stump sensations
Index of frequency £ intensity (range 0±24) 0.47
Percentage of telescoping 31.38
Cortical reorganization (mm) 14.96
MPI, Multidimensional Pain Inventory; VAS, Visual Analogue Scale
following amputation that are comparable to those
observed in animals. 1,4±6,40 However, Elbert and collea-
gues 4 were unable to ®nd a positive relationship between
referred sensations and cortical reorganization in ®ve
upper extremity amputees. Flor et al. 5 showed that corti-
cal reorganization in SI was signi®cantly related to the
magnitude of phantom limb pain, and Knecht et al. 20
reported a close association between cortical reorganiza-
tion and the number of sites from which phantom sensa-
tions could be elicited by painful stimulation. The
purpose of this study was to determine the relationship
between cortical reorganization and the various percep-
tual sequelae of amputation using comprehensive, reli-
able and valid assessment instruments in order to better
understand the neural substrates of various phantom
phenomena.
EXPERIMENTAL PROCEDURES
Participants
Sixteen unilateral upper extremity amputees, 14 male and two
female, were studied. Their mean age was 57.5 years
(S.D. ˆ 10.68, range 39±74). Thirteen participants were right-
handed, three had no clear hand preference, and none was left-
handed. Mean age at the time of the amputation was 21.83 years
(S.D. ˆ 10.95, range 2±47). The average time since amputation
was 50.33 years (S.D. ˆ 15.14, range 15±65). The mean stump
length was 33.38 cm (S.D. ˆ 18.67, range 0±54). Forty-four per
cent of the sample had been amputated on the right and 56% on
the left side of the body. In one case, the amputation was due to an
osteosarcoma; in all other 15 cases, it was caused by traumatic
injury (mostly combat-related injuries). Fourteen of the 16 parti-
cipants experienced non-painful phantom sensations, and 11
reported phantom limb pain (see Table 1). Only two subjects,
both with amputations performed during childhood, experienced
no phantom limb whatsoever. Written informed consent of the
subjects was obtained and the study was approved by the local
Human Subjects Committee.
Methods
Subsequent to a comprehensive neurological assessment, the
subjects participated in a psychometric evaluation including an
interview about the amputation and its consequences such as
preamputation pain, phantom pain, non-painful phantom
phenomena, telescoping, stump pain and stump sensations. 6,20
The interview included Visual Analogue Scales (VAS, 0±
100 mm: ªnoneº to ªvery strongº) and, for the painful phantom
and stump phenomena, adjective lists (0 ˆ ªnot at all trueº to
4 ˆ ªexactly trueº) based on the McGill Pain Questionnaire. 23
S.D. Range No. of subjects reporting
the phenomenon
11
1.81 0±5.33
34.15 0±100
13
5.00 0±16.07
6
1.64 0±5.67
5
.90 0±2.74
44.36 0±100 5
9.23 0.20±27.50 16
For the non-painful phantom and stump phenomena, the interview
included a list of sensations taken from the relevant literature 14,36
that were rated with respect to intensity (0 ˆ ªnoneº to 3 ˆ ªvery
strongº) and frequency of occurrence (0 ˆ ªneverº to 8 ˆ
ªconstantº). The instrument also included an assessment of the
telescoping phenomenon. The interviewer marked in a template
the location, position and size of the phantom limb as experienced
by the patient. The percentage of telescoping was determined by
measuring the distance from the phantom ®ngertips to the stump,
subtracting it from the length of the intact arm and relating this
difference to the maximum phantom length possible (length of the
intact arm subtracted by length of the stump). This yielded a
percentage score with 100% telescoping signifying a complete
shrinkage, i.e. a phantom not exceeding the stump length.
In addition, phantom and stump pain were assessed with the
Pain Intensity Scale of the West Haven±Yale Multidimensional
Pain Inventory (MPI), 18 a reliable and valid measure of the
amount of pain which was modi®ed to separately assess phantom
and stump pain. Handedness was determined by the Edinburgh
Handedness Inventory. 30
Sensations referred to the phantom limb were assessed by
applying painful and non-painful stimuli. Stimulation was
performed in randomized order in the four modalities pain,
touch, vibration and heat on 234 sites that were more closely
spaced in areas near the amputation site and had wider spacing
in more distant areas. Touch stimuli were delivered with a cotton
applicator as described by Ramachandran and colleagues, 33 pain-
ful stimuli were applied with a safety needle. 20 Vibratory stimuli
were tested by a battery-operated vibrator and heat stimuli by a
thermode of 408C (thermal stimulator Medoc 2001). The duration
of each stimulus was 1 s in all four modalities. The duration of the
entire assessment was about 120 min. The participants localized
and evaluated the quality and intensity of stimulation they felt at
the site of stimulation and reported and evaluated sensations else-
where (e.g. in the phantom). Instructions to the subjects were
neutral with respect to the potential sites of mislocalization.
The localization of sensations perceived at the site of stimulation
as well as on the phantom was marked on the subject's body,
drawn in a body template, videotaped and recorded on polaroid
photographs. The intensity of the sensations was evaluated on a
seven-point rating scale ranging from no sensation to very strong
sensation, the quality was described by the subjects using the
same adjective lists that were employed in the interview. Referred
sensations (RFS) were measured in two ways: (i) the number of
sites from which (painful or non-painful) RFS could be elicited in
the phantom, calculated for painful and non-painful stimulation,
and (ii) the percentage of sites at which the subjects experienced
painful or non-painful RFS related to painful or non-painful
stimulation.
In a psychophysical examination, thermal and electric percep-
tion thresholds were assessed at the thenar eminence of the intact
hand, the stump 6 cm proximal to the amputation line and a
homologous site on the intact arm, and the lower corners of the
mouth. Three ascending series of stimuli were used. In addition,
two-point discrimination thresholds were assessed at the same
 Perceptual phenomena and cortical reorganization
sites, excluding the thenar eminence and instead including the
®rst and the ®fth digit of the intact hand. A caliper-probe which
started at 0.5 mm was opened progressively wider in three ascend-
ing series. Electric stimuli were applied by a Toennies electric
stimulator which delivered unipolar impulses of 100 ms duration.
For determination of thermal thresholds, a Medoc thermal stimu-
lator with a stimulation range from 0 to 508C was used.
Neuroelectric source imaging (64-channel EEG) was used to
assess cortical reorganization. The recordings were performed
with a 61-channel electrode matrix. The AgAgCl electrodes
were mounted in an electrocap where the corners of the 10 £ 6
matrix were F7, T5, F8 and T6 according to the 10±20 EEG-
system. The reference electrode was placed at Cz. The electrodes
had a distance of 1.5 cm from center to center. The individual
matrix distribution was digitized with an infrared camera system
(Optotrak) including reference landmarks on the nasion, the left
and right preauricular points and Cz. In addition, horizontal and
vertical electro-oculograms were recorded. One-thousand pneu-
matic stimuli were delivered to the left and right corner of the
lower lip and the ®rst and ®fth digits of the intact hand, respec-
tively. Two Synamps ampli®ers with Scan software (Neuroscan)
were used for data acquisition. The signals were continuously
sampled with a 1 kHz sampling rate and ®lter settings from d.c.
to 200 Hz. The data were then digitally ®ltered from 2 to 20 Hz.
Magnetic resonance images (MRI) were recorded to obtain the
anatomic structure of the subjects' cortices (Siemens Vision MR
1.5 T scanner, T1-weighted, TR ˆ 22 ms, TE ˆ 10 ms, alpha ˆ
30 degrees, slice thickness ˆ 1 mm).
The data were analysed with the MUSIC algorithm, which ®ts
probe dipoles to potential dipole locations in the region of inter-
est. 28 The region of interest here was a grid covering the indivi-
dual surface of the cortex of the patients. The time range was 0±
100 ms with respect to trigger onset. The signal subspace con-
tained the largest four components of the data singular value
decomposition (SVD). The generator in SI was determined by
selecting those dipole locations with maximum probability within
the somatosensory cortex. 29 The source localizations were super-
imposed onto the individual MR images.
The measure of cortical reorganization was determined in the
following manner: The Euclidean distance between the ®ngers
(mean of d1 and d5) and the mouth representation on the intact
side was computed for the anterior±posterior, medial±lateral and
superior±inferior coordinates. This yielded a mouth±digit distance
measure in millimetres. Based on the symmetry assumption of the
two hemispheres, 9 the locations of the ®ngers of the intact side were
transposed along the midsagittal plane to the hemisphere that repre-
sents the amputation side and mirror locations of the digits were
determined. The same distance measure was now calculated for the
amputated side, and the difference between the Euclidean distances
on the intact and the amputation side was then used as an indicator
of the amount of cortical reorganization. 4 This procedure yielded a
measure of the shift of the cortical representation of the mouth into
the representation of the deafferented area in millimetres.
Data analysis
Depending on scale characteristics, Spearman rank correlations
and Pearson correlation coef®cients were calculated to determine
the relationship between the amount of cortical reorganization and
phantom and stump sensations, thresholds, and referred sensations.
In addition, group differences between subjects with and without
phantom pain and non-painful phantom phenomena were tested
employing t-tests for unrelated samples. Since a priori hypotheses
about the direction of the association were present, one-tailed levels
of signi®cance were used, with the exception of stump phenomena
and stump pain where no previous reports on the association with
cortical reorganization existed.
RESULTS
Painful and non-painful phantom phenomena and corti-
cal reorganization
Eleven of the 16 amputees in the study suffered from
265
phantom limb pain. They showed a signi®cantly larger
amount of reorganization of primary somatosensory
cortex as assessed with the Euclidean distance measure
(M ˆ 20.25 mm, S.D. ˆ 5.15) than the remaining ®ve
amputees without phantom limb pain [M ˆ 3.36 mm,
S.D. ˆ 2.87; t(14) ˆ 6.79, P , 0.001]. Phantom limb
pain as assessed by the MPI Pain Intensity Scale was
highly correlated with cortical reorganization (r16 ˆ
0.91, P , 0.001).
Non-painful phantom sensations such as tickling or
movements of the phantom limb were reported by 14
of 16 subjects. These phenomena, as assessed by the
index of intensity and frequency of sensations, were posi-
tively but not signi®cantly related to cortical reorganiza-
tion (r16 ˆ 0.38, n.s.). Group differences of the Euclidean
distance measure between amputees with (M ˆ 15.92 mm,
S.D. ˆ 8.14) and without non-painful phantom phenom-
ena (M ˆ 10.90 mm, S.D. ˆ 14.53) were not signi®cant
[t(14) ˆ 20.84, n.s.]. To closer evaluate the relation
between painful and non-painful phantom phenomena
and cortical reorganization, partial correlation coef®-
cients were computed. The correlation between non-
painful phantom sensations and cortical reorganization
dropped to r13 ˆ 0.35 (n.s.) when phantom limb pain
(MPI) was controlled for, and to r13 ˆ 20.04 when
VAS measures were used for both perceptual phenom-
ena. However, the association between phantom limb
pain (MPI) and cortical reorganization remained stable
with r13 ˆ 0.90 (P , 0.001) when non-painful phantom
sensations (index) were controlled for.
Six of the 16 subjects reported telescoping, that is, a
progressive regression of the phantom limb towards the
stump. Three subjects had a complete telescope, i.e. the
phantom arm had shrunk to stump length. Three addi-
tional subjects showed a partial telescope with a shrink-
age between 34 and 85%. All subjects with telescoping
also suffered from phantom limb pain, and both phenom-
ena were positively correlated (r16 ˆ 0.43, P ˆ 0.05).
Furthermore, telescoping was signi®cantly positively
associated with the amount of cortical reorganization
(r16 ˆ 0.65, P ˆ 0.003). There was a signi®cant group
difference in the amount of cortical reorganization
between amputees with (M ˆ 22.50 mm, S.D. ˆ 2.74)
and without telescoping [M ˆ 10.46 mm, S.D. ˆ 8.80;
t(12) ˆ 24.01, P ˆ 0.002]. When only subjects with
phantom limb pain were considered, the difference
between those with and without telescoping failed to
reach signi®cance [M ˆ 22.50, S.D. ˆ 2.74 vs M ˆ
17.56, S.D. ˆ 6.34; t(9) ˆ ±1.74, n.s.] and the correlation
between telescoping and cortical reorganization was
lower (r11 ˆ 0.49, n.s.).
Referred sensations and cortical reorganization
Six of the 16 subjects reported a referral of sensation
into the phantom limb when they were stimulated at
various body sites (see Table 2). All six patients also
suffered from phantom limb pain. RFSs were elicited
mainly from the stump (n ˆ 5), but also bilaterally from
the shoulder (n ˆ 5), the face (n ˆ 3), the back and neck
areas (n ˆ 4), from the intact arm (n ˆ 4) and from the leg
266
Table 2. Number and percentage of sites from which referred sensations could be elicited
Painful n of sites
Referred % 63.89*
Sensation Non-painful n 1.17
%*
*Percentage related to the number of sites where RFS were elicited in the respective stimulation modality.
(n ˆ 1). None of the subjects reported a topographic one-
to-one relationship of individual stimulation sites and
areas of phantom sensations in the hand.
In four of the 16 subjects, painful stimulation elicited
painful RFSs in the phantom. There was a signi®cant
group difference in the amount of cortical reorganization
between these subjects (M ˆ 23.3 mm, S.D. ˆ 3.93) and
the remaining subjects who did not report this phenom-
enon [M ˆ 12.2 mm, S.D. ˆ 8.86; t(14) ˆ 2.39, P ˆ 0.03;
see Fig. 1]. No signi®cant differences emerged when
subjects with and without non-painful RFSs induced by
painful stimulation [M ˆ 21.77, S.D. ˆ 7.64 vs M ˆ
13.41, S.D. ˆ 9.09; t(14) ˆ 1.47, n.s.], painful RFSs
elicited by non-painful stimulation [M ˆ 21.90,
S.D. ˆ 3.37 vs M ˆ 13.38, S.D. ˆ 9.48; t(14) ˆ 1.50,
n.s.] or non-painful RFSs induced by non-painful stimu-
lation [M ˆ 18.67, S.D. ˆ 5.81 vs M ˆ 14.12, S.D. ˆ 9.84;
t(14) ˆ 0.76, n.s.] were compared. Likewise, only the
percentage of sites where painful stimulation induced
painful RFS was signi®cantly associated with the amount
of cortical reorganization (r16 ˆ 0.57, P ˆ 0.01), whereas
the remaining associations between cortical reorganiza-
tion and RFSs remained insigni®cant.
Subjects with painful RFSs elicited by painful stimu-
lation also showed signi®cantly more phantom limb pain
as measured by the MPI (M ˆ 3.58, S.D. ˆ 1.20) than
subjects without this type of RFS [M ˆ 1.56, S.D. ˆ 1.73;
t(14) ˆ 2.16, P , 0.05]. No signi®cant differences in
phantom limb pain intensity emerged when patients
with and without non-painful RFSs induced by painful
stimulation [M ˆ 3.33, S.D. ˆ 1.86 vs M ˆ 1.77, S.D. ˆ
1.75; t(14) ˆ 1.39, n.s.], painful RFSs induced by non-
painful stimulation [M ˆ 3.0, S.D. ˆ 0.33 vs M ˆ 1.85,
S.D. ˆ 1.96; t(13.89) ˆ 2.0, P ˆ 0.07] or non-painful
RFSs induced by non-painful stimulation [M ˆ 2.67,
S.D. ˆ 0.88 vs M ˆ 1.92, S.D. ˆ 1.97; t(14) ˆ 0.63, n.s.]
were compared.
Perception thresholds and cortical reorganization
Means and standard deviations for thermal, electric
and two-point discrimination thresholds at the stump,
the homologous site at the intact arm and the lower
corners of the mouth are shown in Table 3. There were
no signi®cant correlations between perception thresholds
and the amount of cortical reorganization (see Table 4).
S. M. GruÈsser et al.
Stimulation modality
Painful Non-painful
M (S.D.) M (S.D.)
3.83 (4.07) 5.17 (8.06)
(49.91) 53.85* (50.73)
(1.60) 2.67 (3.27)
36.11* (49.91) 46.15* (50.73)
Other amputation-related variables and cortical
reorganization
Other amputation-related variables such as time since
amputation, age at the time of amputation or stump
length were not signi®cantly correlated with cortical
reorganization (see Fig. 2).
Stump phenomena and cortical reorganization
Six subjects suffered from stump pain. The correlation
between cortical reorganization and stump pain tended to
be signi®cant for stump pain measured by the MPI Pain
Intensity Scale (r16 ˆ 0.50, P ˆ 0.05), but became
nonsigni®cant when phantom limb pain was controlled
for (r13 ˆ 0.18, n.s.). There was a signi®cant positive
correlation between the amount of phantom limb pain
and the amount of stump pain, both measured by the
MPI Pain Intensity Scale (r16 ˆ 0.48, P ˆ 0.03). When
subjects with and without stump pain were compared,
no signi®cant differences in the amount of cortical
reorganization [with stump pain: M ˆ 17.38, S.D. ˆ
9.69; without stump pain: M ˆ 13.53, S.D. ˆ 9.153;
t(14) ˆ 0.80, n.s.] or phantom limb pain [with stump
pain: M ˆ 2.56, S.D. ˆ 1.80; without stump pain: M ˆ
1.7667, S.D. ˆ 1.853; t(14) ˆ 0.83, n.s.] emerged.
Five of the 16 subjects reported spontaneous non-
painful stump sensations. A signi®cant correlation with
cortical reorganization was found when the adjective lists
(index of intensity and frequency) were used as stump
sensation measure (r16 ˆ 0.62, P ˆ 0.01). After control-
ling for phantom limb pain (MPI), this correlation
dropped to r16 ˆ 0.53 (P ˆ 0.04), and even further to
r16 ˆ 0.12 (n.s.) when the VAS was used as measure of
phantom pain intensity. There were no signi®cant group
differences in the magnitude of cortical reorganization
[M ˆ 19.36, S.D. ˆ 7.546 vs M ˆ 12.98, S.D. ˆ 9.55;
t(14) ˆ 1.31, n.s.] or the amount of phantom limb pain
[M ˆ 2.80, S.D. ˆ 1.80 vs M ˆ 1.73, S.D. ˆ 1.80;
t(14) ˆ 1.10, n.s.] between subjects with and without
non-painful stump sensations.
DISCUSSION
Correlates of cortical reorganization and mechanisms of
phantom limbs
Painful and non-painful phantom sensations. Cortical
reorganization in primary somatosensory cortex was
Fig. 1. (a) Averaged somatotopic source localizations. The coronal view shows the averaged localizations for amputees with painful
sensations referred from painful stimulation (n ˆ 4). In this group, the localization of the corner of the mouth in the hemisphere
contralateral to the amputation side has shifted far into the former hand region. (b) The coronal view shows the averaged localiza-
tions for amputees without painful sensations referred from painful stimulation (n ˆ 12). Compared to (a), there is a smaller shift of
the mouth localization contralateral to the amputation side into the former hand region.
268 S. M. GruÈsser et al.

Table 3. Perception thresholds

Two-point discrimination Electric thresholds Thermal thresholds

Mean (mm) S.D. Mean (mA) S.D. Mean (8C) S.D.

Stump 23.74 19.84 1.44 0.52 34.86 1.84

Intact arm (homologous site) 22.58 14.48 1.26 0.42 34.80 1.97
Corner of the mouth (amputation side) 7.47 3.74 1.33 0.37 33.34 0.50
Corner of the mouth (intact side) 6.88 3.22 1.32 0.20 33.64 2.16

Table 4. Perception thresholds and cortical reorganization

Two-point discrimination Electric thresholds Thermal thresholds

r P r p r p

Stump 20.002 0.497 20.040 0.888 0.302 0.274

Intact arm (homologous site) 20.044 0.436 0.289 0.296 20.054 0.855
Corner of mouth (amputation side) 0.299 0.130 0.160 0.569 0.414 0.125
Corner of mouth (intact side) 0.145 0.296 0.234 0.402 0.275 0.322

Statistical analyses (Pearson, one-tailed) and signi®cance levels.

positively associated with phantom limb pain, and this
phenomenon seems to be very stable. 1,5,6,22,27 Non-painful
phantom sensations were not consistently related to these
plastic cortical changes. When a signi®cant correlation
was found, it was entirely mediated by phantom limb
pain. We assume that other cortical areas, for example,
the posterior parietal cortex and SII, may be involved in
the subjective awareness of a still existent, non-painful
limb. 7,19
Painful and non-painful stump sensations. There was a
signi®cant positive relationship between both painful and
non-painful stump phenomena and cortical reorganiza-
tion. In the case of stump pain, the association dis-
appeared after phantom limb pain was controlled for
while for non-painful stump sensations the relationship
was stable. Peripheral mechanisms such as neuroma,
vascular or muscular changes 32 may contribute to both
phantom limb and stump pain. Several studies, including
our study (r16 ˆ 0.48, P , 0.05) reported a positive asso-
ciation between stump and phantom limb pain 26,34 and it
has been suggested that there are common underlying
peripheral mechanisms triggering both phantom limb
and stump pain. 26,35 Random input from the periphery
may, moreover, contribute to reorganizational changes. 38
For example, the elimination of peripheral input by
brachial plexus anesthesia led to concurrent reductions
in both phantom limb pain and cortical reorganization in
about half of the upper limb amputees studied. In the
other half, both variables were unaffected. 1 In line with
these ®ndings, non-painful stump sensations were also
positively correlated with cortical reorganization. The
peripheral factors that contribute to phantom limb pain,
stump pain and cortical reorganization need to be further
investigated.
Telescoping. The development of telescoping and
its relationship to phantom limb pain and cortical
reorganization has been a matter of controversy. In
contrast to Katz, 17 who assumed a negative relationship
between phantom pain and telescoping and postulated
that this might be due to a bene®cial adaption through
cortical reorganizational processes, we found a positive
relationship between cortical reorganization and phan-
tom limb pain as well as telescoping. Since all patients
with telescoping also suffered from phantom limb pain,
the two variables could not be evaluated separately in
this study. However, when the relationship of cortical
reorganization and telescoping was examined only in
the phantom limb pain group, telescoping was no longer
positively related to SI reorganization suggesting that it
is not primarily mediated by SI. It is possible that tele-
scoping is more related to changes in brain regions
underlying non-painful phantom limb phenomena, such
as posterior parietal cortex. Based on our data, the
putative bene®cial nature of telescoping with respect to
phantom limb pain must be questioned.
Referred sensations. In contrast to the assumption of
Ramachandran and colleagues 33 that touch-induced
referred sensations are a perceptual correlate of cortical
reorganization, we could not ®nd a signi®cant correlation
between non-painful referred sensations induced by pain-
ful or non-painful stimulation and cortical reorganiza-
tion. Analogous to Knecht et al. 20,21 who demonstrated
a strong relationship between the amount of cortical
reorganization and the number of stimulated body sites
which elicited referred sensations based on painful (but
not non-painful) stimulation, we found a positive rela-
tionship between the number of sites from which painful
referred sensations could be elicited by painful stimula-
tion and the degree of cortical reorganization. This rela-
tionship re¯ects the close association of phantom limb
pain and SI reorganization. In the Knecht et al. 20,21 study
the type of referred sensation had not been evaluated. No
signi®cant differences in cortical reorganization were
 5 10

n of nonpainful RFS by nonpainful stimulation

4 8
n of nonpainful RFS by painful stimulation
7

3 6

2 4

1 2

1
r = .36 (ns) r = .14 (ns)
0 0
0 10 20 30 0 10 20 30
cortical reorganization in mm cortical reorganization in mm

30 10

9
25
8
n of painful RFS by nonpainful stimulation

n of painful RFS by painful stimulation

7
20
6

15 5

4
10
3

2
5
1
r = .35 (ns) r = .51*
0 0
0 10 20 30 0 10 20 30
cortical reorganization in mm cortical reorganization in mm
3
10

8
nonpainful phantom sensations (index)
nonpainful stump sensations (index)

4
1

r = .62 r = .38 (ns)

0 0
0 10 20 30 0 10 20 30
cortical reorganization in mm cortical reorganization in mm
r(part) = .53 controlling for phantom pain r(part) = .35 (ns) controlling for phantom limb pain
6 6

5 5

4 4

3 3
phantom limb pain (MPI)

2 2
stump pain (MPI)

1 1

r = .50* r = .91**
0 0
0 10 20 30 0 10 20 30
cortical reorganization in mm cortical reorganization in mm
r(part) = .18 (ns) controlling for phantom limb pain r(part) = .88** controlling for stump pain

Fig. 2. (continued overleaf )

270 S. M. GruÈsser et al.

100 50

80 40

age at the time of amputation (years)

60 30

40 20
telescoping in percent

20 10

r = .65** r = .25 (ns)

0 0
0 10 20 30 0 10 20 30
cortical reorganization in mm cortical reorganization in mm

800 80

700
70

600

age at the time of assessment (in years)

60
500
time since amputation (in months)

400 50

300
40

200
30
100
r = –.03 (ns) r = .22 (ns)
0 20
0 10 20 30 0 10 20 30
cortical reorganization in mm cortical reorganization in mm
60 6

50 5

40 4

30 3
phantom limb pain (MPI)
stump length (in cm)

20 2

10 1

r = –.26 (ns) r = .48*

0 0
0 10 20 30 0 1 2 3 4 5 6
cortical reorganization in mm stump pain (MPI)
r(part) = .06 (ns) controlling for cortical reorganization

Fig. 2. Scatter plots demonstrating the relation between cortical reorganization and various amputation-related variables (n ˆ 16).
*P , 0.05, **P , 0.01; ns, non-signi®cant.

found for subjects with or without non-painful referred Perception thresholds. In contrast to reports by
sensations, especially those sensations that were elicited Haber 13 and Teuber et al., 39 we did not ®nd the stump
by non-painful stimulation. This suggests that other to be more sensitive than the homologous site at the
cortical areas contribute to the experience of these intact arm. This discrepancy could be due to differences
non-painful phantom phenomena. The ®nding that in inclusion criteria of the samples (e.g. we included
referred sensations could be elicited from both the intact patients with vascular disorders) and the exact site
and the amputation side as well as from distal areas such of the sensitivity assessment. In contrast to Haber 13
as the leg 2 suggests an involvement of the thalamus or the who measured thresholds 2.5 cm proximal from the
second somatosensory cortex where the leg and arm stump, we assessed thresholds 6 cm proximal to the
representation are adjacent. stump. Contrary to the hypothesis of Spitzer and
 Perceptual phenomena and cortical reorganization 271

colleagues 38 that reduced stump thresholds are associated
with an expanding cortical representation area, we could
not ®nd a signi®cant relationship between cortical re-
organization and stump perception thresholds. We
also failed to observe this relationship for both two-
point discrimination and perception thresholds at the
mouth although we noted a signi®cant shift of the
cortical representation of the mouth into the region of
the amputated hand. It is unlikely that an insuf®cient
reliability and validity of the threshold assessments
caused this lack of signi®cant associations. Thresholds
can be reliably determined and are stable over time
in healthy controls (Denke C., Karl A., GruÈsser S.,
Birbaumer N. and Flor H., unpublished experiment). In
phantom limb pain patients, the same type of assessment
yielded very heterogeneous results suggesting that these
perceptual phenomena may be variable and may also be
in¯uenced by factors such as concurrent stump pain.
CONCLUSIONS
spontaneously occurring or induced phantom limb pain,
whereas no signi®cant relationship was found with non-
painful phantom phenomena and perception thresholds.
The stable relationship between phantom limb pain and
cortical reorganization 1,5,6,16,22,27 and our present ®ndings
suggest that plastic changes in the primary somato-
sensory cortex may be an important neural correlate of
phantom limb pain. The signi®cant positive relationship
between painful phantom sensations induced by painful
stimulation and cortical reorganization con®rms this
conclusion. Stump pain seems to be mediated by periph-
eral mechanisms which may also trigger phantom pain.
These data suggest that a distributed network involving
various cortical and potentially subcortical areas under-
lies painful and non-painful phantom phenomenaÐsimi-
lar to the concept of a neuromatrix suggested by
Melzack. 24 Peripheral factors involved in stump pain
and stump sensations seem to contribute to both phantom
limb pain and cortical reorganization and need to be
further investigated. 8

The data of this study suggest that reorganizational AcknowledgementÐThis work was supported by the Deutsche
changes in SI appear to be mainly related to Forschungsgemeinschaft (Fl 156/16).

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(Accepted 17 October 2000)