~ R N A L OF ~ E

NEUROLOGICAL
SCIENCES

ELSEVIER

Journal of the Neurological Sciences 125 (1994) 29-38

Cerebral network underlying unilateral motor neglect:
evidence from positron emission tomography
Hans-Jiirgen von Giesen, Gottfried Schlaug, Helmuth Steinmetz, Reiner Benecke,
Hans-Joachim Freund, Riidiger J. Seitz *
Department of Neurology, Heinrich Heine University Diisseldo~ MoorenstraJ3e 5, D-40225 Diisseldo~ Germany
Received 29 October 1993; revised 24 February 1994; accepted 2 March 1994

Abstract
In 4 male patients (age range 50-73 years) with unilateral motor hemineglect as a sequelae of circumscribed cerebral
infarction, depressions of the regional cerebral glucose metabolism (rCMRGlu) were mapped to identify the metabolically
affected cerebral structures. Motor neglect was defined according to Castaigne by lack of spontaneous and pain-induced motor
activity on one side of the body in the absence of paresis, pyramidal signs, and sensory loss. The depressions of the rCMRGlu as
determined by positron emission tomography (PET) were found to exceed the areas of structural damage but to be restricted to
the affected cerebral hemisphere. Significant mean rCMRGIu depressions followed a focal pattern involving the premotor,
prefrontal, parietal and cingulate cortex, as well as the thalamus. In correspondence to the lack of significant mean rCMRGIu
depressions in primary sensorimotor cortex, basal ganglia, and cerebellum the cortico-spinai pathway was spared as indicated by
preserved magnetic evoked motor potentials. Our data provide evidence suggesting that motor hemineglect is a disturbance in a
cerebral network of higher order cortical areas subserving motor activity in the presence of an intact motor cortical output
system.

Key words: Motor neglect; Cerebral glucose metabolism; Positron emission tomography; Evoked potentials; Motor network
1. Introduction
The neglect syndrome (Heilman 1985) is defined as
a behavioral failure to report, respond, or orient to
novel or meaningful stimuli presented to the body side
contralateral to a brain lesion. This failure cannot be
attributed to either sensory or motor defects. The
neglect syndrome may affect different modalities appearing either as hemi-inattention, sensory extinction
or motor neglect (akinesia, intentional neglect). Although often accompanied by multimodal neglect, pure
motor neglect can be defined as a clinical entity
(Castaigne et al. 1970, 1972). Neglect may be caused by
lesions of the parietal (Critchley 1953; Castaigne et al.
1970) or frontal cortex (Castaigne et al. 1972) or by
subcortical lesions that damage or functionally suppress a presumed subcortico-cortical network (Mesulam 1981). Recent S P E C T studies (Bogousslavsky et al.

* Corresponding author• Tel.: ( + 49-211) 311-8977; Fax: ( + 49-211)
311-8469.
0022-510X/94/$07.00 © 1994 Elsevier Science B.V. All rights reserved

SSDI 0 0 2 2 - 5 1 0 X ( 9 4 ) 0 0 0 5 5 - S

1988) or P E T on hemineglect (Fiorelli et al. 1991)
revealed a widespread depression of perfusion or
metabolism involving the entire cerebral cortex ipsilateral to the lesion. The present P E T study describes
patients with motor neglect showing specific patterns
of significant metabolic disturbances in the affected
cerebral hemisphere. Thus, we were able to examine
the hypothesis that interference with cortical higher
order control areas may underlie motor hemineglect.
Further, we ascertained by means of magnetic motor
evoked potentials that the primary motor cortical output system was electrophysiologically intact in our patients. Our results substantiate the hypothesis of a
distributed cerebral network outside the cortical motor
strip subserving voluntary motor activity.
2. Patients and methods
Four patients were examined neurologically by three
independent observers. The clinical findings are summarized in Table 1. Neurological examination was in
particular directed to establish the degree of motor

31)

H.-J. t,on Giesen et al. / Journal of the Neurological Sciences 125 (1994) 29-38

impairment. Paresis was graded according to the quantitative scale by Demeurisse et al. (1980). Motor neglect was assessed by eight clinical criteria as established by Castaigne et al. (1970, 1972). These criteria
were: (1) absence of paresis, (2) absence of muscle tone
changes, (3) absence of pyramidal signs, (4) absence of
spontaneous limb movements of the affected side, (5)
limb movement of the affected side in response to
tough encouragement, (6) absence of withdrawal of
affected limbs out of uncomfortable positions, (7) normal sensation, (8) normal rapid alternating movements.
Sensory neglect was excluded by simultaneous cutaneous stimulation of homologous sites of both sides of
the body (cancellation test), visual neglect by line bisection test (Albert 1973; Halsband et al. 1985).
Case reports
Case 1. J.Sc., a right-handed, 50-year-old clerk suffered two
infarctions in the territory of the left medial cerebral artery following
an angiographically proven occlusion of the left internal carotid
artery. The first stroke led to an infarct of the left mid-frontal gyrus

with the full clinical picture of motor neglect as described in Table 1.
All signs were completely reversible. The second stroke 6 weeks
later led to a complete right-sided hemiplegia with only partial
recovery for the right leg in spite of continuous therapy with heparin.
PET scanning was performed shortly before the occurrence of the
second stroke.
Case 2. J.Si., a right-handed, 73-year-old retired tram driver
suffered a circumscribed hypertensive hemorrhage in the left anterior thalamus. He was on warfarin therapy since left-side femoro-crural bypass surgery 3 years before. On admission the patient was
drowsy and markedly disoriented. Neurological examination disclosed a right-sided loss of motor activity and amnestic aphasia. In
addition, there was a severe motor neglect as specified in Table 1. In
parallel with resorption of the hemorrhage the patient's state improved remarkably with complete recovery of motor function within
8 weeks. In contrast, a slight residual amnestic aphasic speech
disturbance was still present at that time. PET scanning was performed 2 months after hemorrhage. There was additional evidence
of mild sensory polyneuropathy due to diabetes mellitus.
Case 3. W.K., a right-handed, 66-year-old chemistry worker presented with a hypertensive and initially space-occupying hemorrhage
involving the right thalamus and the posterior part of the internal
capsule. Clinically, he showed left-sided homonymous hemianopia,
hemihypesthesia and motor neglect (Table 1). In addition, there was

Table 1
Clinical presentation and electrophysiology of 4 male patients with motor neglect
Case

1.

2.

3.

Criteria of motor neglect
(Castaigne et al. 1970;
1972)

Motricity
Index
(Demeurisse
et al. 1980)

MEP
(CMCT; amplitude)
(msec)

SSEP
(latency; amplitude)

no paresis
no muscle tone changes
no pyramidal signs
no spontaneous activity
no activity without
enforcement
no withdrawal of limbs
no sensory disorders
no disturbance of rapid
alternating movements
no muscle tone changes
no spontaneous activity
no activity without
enforcement
no withdrawal of limbs
no sensory disorders
no paresis
no muscle tone changes
no pyramidal signs
no spontaneous activity
no activity without
enforcement

upper limb
100
lower limb
100
total
100

left FDI
right FDI
left TA
right TA
left deltoid
right deltoid

6
4.4
7
7.1
16
6.3
17
4.2
6
1.7
no answer

not done

upper limb
75
lower limb
54
total
65
upper limb
100
lower limb
100
total
100

left FDI
right FDI
left TA
right TA

5
5
19
19

3.8
5,0
2.8
4.8

left M
right M
left T
right T

21.2
21.6
47.6
47.6

9.2
7.0
2.7
2.9
1.8
3.5
1.8
6.5
8.1
8.2
3.5
6.1
7.3
3.8
1.1
5.0

21.6
0.5
20.4
2.5
no answer
43.6
0.5

upper limb
100
lower limb
100
total
100

8
8
17
17
7
7
13
11
7
7
18
18
13
13
7
5

left M
right M
left T
right T

no paresis
no muscle tone changes
no pyramidal signs
no spontaneous activitiy
no activity without
enforcement
no withdrawal of limbs
no distubance of rapid
alternating movements

left FDI
right FDI
left TA
right TA
left biceps
right biceps
left rectus
right rectus
left FDI
right FDI
left TA
right TA
left rectus
right rectus
left deltoid
right deltoid

left M
right M
left T
right T

21.2
20.4
45.6
43.6

(mV)

(msec)

EEG

(/zV)
10/sec alpha activity (50/~V)
4 / s e c theta focus in FP1, F3, F7,
T3 and T5

FDI: first dorsal interosseus muscle; TA: tibial anterior muscle; M: median nerve; T: tibial nerve.

5.7
5.7
0.7
0.7

5.3
10.4
1.4
5.8

8 - 9 / s e c alpha activity (20/~V)
diffuse bihemispheric presence
of theta waves,
delta waves are seen in FP1, F3,
C3, P3, O1 and accentuated in
F7 T3 and T5
generalized slowing with predominant 6 - 7 / s e c theta activity
(50 ~V)
2 / s e c delta focus in F8, T4, T6

9 / s e c alpha activity (70 ~V) in O1
alpha reduction (30/zV) in 0 2
diffuse presence of theta waves
over the entire right hemisphere
2 / s e c delta focus in F8, T4, T6

H.-J. yon Giesen et al. /Journal of the Neurological Sciences 125 (1994) 29-38
visuomotor ataxia as described by Rondot et al. (1977), impaired
memory with disorientation in time and space, and depressed mood.
Within two m o n t h s a good recovery of his general condition occurred. A two-year follow-up revealed a persistent hemihypesthesia
on the left side of the body with deafferentation of the left arm and
concomitant sensory hemineglect of the left leg, face and trunk. Also
the left-sided h o m o n y m o u s hemianopia and visuomotor ataxia had
persisted. At this stage P E T scanning was performed.
Case 4. K.B., a right-handed, 57-year-old biological technical
assistant developed an acute ischemic stroke of the right basal
ganglia on the basis of an occlusive cerebral artery disease including
a 90% stenosis of the right internal carotid artery and a 7 0 - 8 0 %
stenosis of the left internal carotid artery. Four weeks prior to
admission, he had suffered a few right hemisphere transient ischemic
attacks. As evident from M R I there was a further brain lesion in the
right angular and superior parietal gyrus. There was a history of
coronary and peripheral arterial disease, nicotin abuse and hypercholesterinemia. Neurological examination disclosed a severe leftsided loss of motor activity involving the face, arm and leg fulfilling
seven criteria of motor neglect (Table 1). In addition, there was a
slight reduction of pinprick sensation on the side of his body. P E T
scanning was performed three weeks after infarction of the basal
ganglia when there was still a motor neglect for the left hand but no
changes of muscle tone and no pyramidal signs. The further clinical
course during the following weeks revealed a slight residual left-sided
central hemiparesis including presence of pyramidal signs.

Electrophysiology
Motor evoked potentials (MEP) as indicators for the
fastest conducting nerve fibers in the cortico-spinal
tract (Hess et al. 1987) were elicited by transcranial
magnetic stimulation of the brain with a Novametrix
200 HP ® (maximum output of 2.0 tesla). Capacitors
were rapidly discharged through a standard fiat circular coil (outer diameter 12 cm). Technical and methodological details have been given repeatedly (Barker et

31

al. 1985; Boyd et al. 1986; Benecke et al. 1988a,b;
Maccabee et al. 1991). To obtain MEP of the upper
extremities, the coil was positioned with its center over
the vertex, to obtain MEP of the lower extremities, it
was positioned 4 cm anteriorly (Meyer et al. 1991).
Clockwise and anticlockwise coil currents were used to
stimulate the right or left hemisphere, respectively.
Stimulation strength was individually determined for
every limb at 1.5 threshold level. Threshold level was
defined as the stimulation strength which induced a
visible MEP in at least 3 of 5 trials with the muscle
examined at rest. During stimulation all patients were
encouraged to perform a voluntary contraction of the
examined muscle. Surface EMG recordings were taken
from various muscles in all patients including the first
dorsal interosseus (FDI) and tibial anterior (TA) muscles representing distal muscles of the upper and lower
extremities and the deltoid (patients 1 and 4), rectus
femoris muscle (patients 3 and 4) and the biceps brachii
muscle (patient 3) all representing proximally located
muscles. EMG signals were amplified using a Toennies
Myograph II ® with bandpass filtering between 20 and
3000 Hz. Data were collected and evaluated on an
IBM-compatible PC using Autolab ® data collecting
programs. Maximum peak-to-peak amplitudes of compound muscle action potentials and minimum onset
latencies were determined, five trials for each muscle
were analyzed. Furthermore, the amplitudes were expressed as a percentage of the compound muscle action potential obtained after supramaximal electrical
stimulation of the supplying nerve (maximal M wave)
and compared to normal values (Benecke et al. 1988a).

Fig. 1. Localization of structural defects in the 4 patients with motor neglect. Lesions were plotted on templates derived from the atlas of Matsui
and Hirano (1978). Shown are the slices with the largest lesion extent. Left in the templates corresponds to right in the patients. The coordinates
of the lesion centers in the stereotactic space of Talairach and Tournoux (1988) are x = - 3 6 , y = 20, z = 24 (case 1), x = - 14, y = 13, z = - 7
(case 2), x = 18, y = - 20, z = - 6 (case 3), x = 24, y = - 5, z = - 8 and x = 45, y = - 36, z = 44 (case 4).

32

H, -J. ~ron Giesen et aL /Journal of the Neurological Sciences 125 (1994) 29-38

Central motor conduction time was calculated by subtracting the peripheral conduction time after nerve
root stimulation from the onset latency of the fastest
cortically evoked potential (Claus 1990; Hess et al.
1987).
Somatosensory evoked potentials (SSEP) were registered with a Medilec MS 92 ® registration unit after
serial electrical stimulation of the median and tibial
nerves (3 sweeps/sec just below motor threshold) in
patients 1, 2 and 4. 200 responses were averaged for
each registration, electrodes were positioned at Cz' for
the tibial and at C3'/C4' for the median nerve, respectively. As detailed by St6hr et al. (1983) base-to-peak
amplitudes were calculated.
Electroencephalography (EEG) was registered routinely with a Mingograf ® E E G 21 (Siemens) with an
input impedance of 200 Mf~, 500 pF, symmetrical, and
C M R R of 100 dB with AC suppressor. Scalp electrodes were placed following the international "10-20
system" (Jasper 1958).

Lesion topography
Lesions were localized initially by computed tomography (CT) with a Siemens Somatom Plus and subsequently by magnetic resonance imaging (MRI) with a
1.5 T Siemens Magnetom. Structural defects as visualized in Tl-weighted MR images in the chronic stage
were outlined and plotted on the corresponding templates from the anatomical atlas of Matsui and Hirano
(1977). Lesions are depicted with their largest extent in
Fig. 1. In addition, the spatial coordinates of the lesions were localized in the stereotactic space of Talairach and Tournoux (1988).

Positron emission tomography
For this P E T study, 12 healthy volunteers (mean age
48 + 14 yrs (SD)) served as controls. All controls denied any neurological, psychiatric or medical disorder
and were normal on neurological and neuropsychological examination. All patients and controls were informed that the purpose of the study was to investigate
the rCMRGIu pattern during resting wakefulness. None
had undergone previous P E T scanning. Written informed consent was obtained in accordance with guidelines approved by the Ethics Committee of the Heinrich Heine University Diisseldorf and the Declaration
of Human Rights, Helsinki 1975.
P E T scanning was performed with a Scanditronix
PC 4096/7WB P E T camera as described in detail
previously (Seitz et al. 1994). In short, the subjects'
were placed comfortably on the scanner bed and the
gantry of the P E T camera was aligned with the orbitomeatal line. There was no noise in the scanner room,
speech was prohibited and the lights were dimmed.
The subjects were asked not to move or speak, their
eyes were open to prevent sleep. Prior to P E T scanning, the subjects' left hand was warmed up to about

40°C for 45 min to ensure arterialization of blood in
the dorsal hand veins with an oxygen saturation of
more than 90%. After bolus injection of 200 MBq
2-[lSF]fluoro-2-deoxy-D-glucose (FDG), 23 arterialized
venous blood samples with an initial frequency of 6 per
min were drawn to determine the arterial F D G input
function. Calculation of the rCMRGIu was performed
according to Phelps et al. (1979). The kinetic constants
and the lumped constant of 0.52 were taken from
Reivich et al. (1985). Image reconstruction was carried
out with a Hanning filter of 5 mm (full width half
maximum, FWHM) which provided an image resolution (FWHM) of 7.1 mm and an axial resolution
(FWHM) of 6.5 mm (Rota Kops et al. 1990).
Image evaluation was done by use of the CBA on a
SPX 3100/M76 VAX station. As described in detail
earlier (Seitz et al. 1990) the brain atlas structures were
adapted by translations, angulations, and linear and
nonlinear scaling to fit the brain shape of each subject
as presented in the P E T and MR images. Thereafter,
using these deformation parameters the individual
parametric P E T images were reformatted to the spatial
orientation and standard shape of the atlas brain.
Thus, a set of 14 spatially standardized parametric
images was obtained for each of the different subjects.
By this procedure, all stroke lesions were transposed
into the left hemisphere. From these spatially standardized parametric P E T images, mean images and corresponding images of the mean standard error (SEM)
could be calculated pixel-by-pixel for our patients and
control subjects. The differences of the mean rCMRGlu between the patients and controls were calculated
pixel-by-pixel and their significance assessed from tmaps. Only mean rCMRGIu differences with a t > 3.182
(3 degrees of freedom, corresponding to p < 0.05; Sachs
1984) that occurred in clusters of at least 12 pixels were
considered as reliable signals (Seitz et al. 1994). The
mean rCMRGlu differences were localized to anatomical structures by interactive overlay of the anatomical
structures retrieved from the data base of the computerized brain atlas (Greitz et al. 1991). Finally, the
centers of gravity of the cortical and cerebellar ROIs as
defined in the t-images were localized in the stereotactic space of Talairach and Tournoux (1988), as the
spatial dimension and orientation of the computerized
brain atlas were known (Seitz et al. 1990; Gulyas and
Roland 1992).

3. Results

Table 1 shows that five to eight criteria of motor
neglect as defined by Castaigne (1970, 1972) were
present in our patients. Only one patient had a slight
hemiparesis resulting in a mean motricity index of
91.3 +_ 17.6 (SD) according to Demeurisse et al. (1980)

H.-J. t~on Giesen et aL /Journal of the Neurological Sciences 125 (1994) 29-38

Electrophysiological data

for all subjects. These data clearly support the diagnosis of motor neglect. Still, in case 3 there was an
additional mild sensory neglect and a homonymous
hemianopia to the right side. One patient presented
with a slight amnestic aphasia (case 2).
Fig. 1 demonstrates the localization of the structural
brain lesions in the 4 patients. It is evident that the
lesions were confined to one hemisphere and circumscribed in all patients. One lesion was located in the
left midfrontal gyrus, one in the anterior part of the
left thalamus, one in the right thalamus extending into
the posterior limb of the internal capsule, and one in
the right lentiform nucleus. In the latter patient a
further brain lesion was present in the right angular
and superior parietal gyri. All lesions resulted from
vascular events and were located at various sites known
to possibly result in motor neglect (Heilman et al.
1983). However, patient 1 who fulfilled all criteria of
motor neglect had a lesion in the left premotor cortex
(Fig. 1).

The details of the MEP are given in Table 1. In all
patients, threshold levels were symmetrical both for
upper and lower extremities, the absolute stimulation
strength varying between 1.5 and 1.9 tesla for both the
upper and lower extremities. MEP to distal muscles
(FDI, TA) were normal on both sides with regard to
central motor conduction time (CMCT), amplitude,
and configuration of the evoked muscle potentials.
With the exception of patient 1, where no answer to
the contralateral deltoid muscle could be elicited, MEP
to al! other proximal muscles (deltoid, biceps brachii,
rectus femoris muscles) showed normal CMCT in all
patients with no relevant side differences. The evoked
muscle action potential of the contralateral deltoid
muscle was reduced in amplitude (1.1 vs 5.0 mV) and
disperse in patient 4 (see Fig. 2). In patient 3, the
evoked muscle potential of the rectus femoris muscle
was slightly reduced in amplitude (1.8 vs 6.5 mV). MEP
to the more distal muscles under study did not deviate

mV

mV

1.0

./~

L Delta

-1,0 ~

,~

.

4.5

'A

L FDI

3.0]

L._ ,A

5.0 /

L Rectusfemoris

'~J

4.5 ~

A

0

i~,~

45
.

T

2.5

R FDI

,

,~ectus

femoris

25

2.5
I

De,ta

.

.

-5 01

33

L TA

2.5~

'~

~~
msec
100 0

RTA
.,.!

;
~'1

msec
100

Fig. 2. Motor evoked potentials of patient 4 with bilaterally normal responses to distal muscles (first dorsal interosseus, tibialis anterior) and the
proximal rectus femoris muscles with regard to central motor conduction time, amplitude and configuration. In contrast, MEP to the left deltoid
as proximal muscle showed slight abnormalities with amplitude reduction and potential dispersion.

34

H.-J. l~on Giesen et al. /Journal of the Neurological Sciences 125 (1994) 29-38

Table 2
Mean rCMRGIu depressions in 4 patients with motor neglect due to unilateral stroke
Antomical region
(Greitz et al. 1991)

Functional Area
(Roland 1987)

Stereotaxic Coordinates
(Talairach and Tournoux 1988)

Mean rCMRGIu
depression (%)

(crn 3)

Mean rCMRGIu
of Controls ± SD
(tzmol/100 g/min)

G. precentralis
G. postcentralis
G. frontalis medius
G. frontalis medius
G. front, inf. p. triang.
G. pariet, sup. lat.
Precuneus
C. supramarginalis
G. angularis
G. opercularis
G. temporalis sup.
G. frontalis medius
G. front, inf. p. orbit.
G. cinguli
Thalamus
Putamen/PaUidus
Cerebellum

Motor hand area
Sensory hand area
Premotor cortex
Frontal eye field
Broca's area
Sup. parietal Iobule
Sup. parietal medial
Supramarginal
Angular
Sec. somatosensory (SII)
Superior temporal
Midfrontal anterior
Inferior prefrontal
Cingulate gyrus
Thalamus
Basal ganglia
Cerebellar hemisphere

x = - 37, y = - 15, z = 49
x = - 36, y = - 28, z = 48
x = - 40, y = - 7, z = 40
x = - 26, y = 20, z = 48
x = -26, y = 19, z = 4
x = - 26, y = - 48, z = 45
x = - 16, y = - 58, z = 49
x = -43, y = -37, z = 38
x = -51, y = -59, z = 24
x = - 42, y = - 24, z = 18
x = - 59, y = - 15, z = 9
x = - 28, y = 37, z = 6
x = -40, y = 41, z = - 4
x = - 7, y = - 6, z = 28
x = -13, y = -21, z = 14
x = - 22, y = - 1, z = 6
x = 21, y = - 63, z = 22

46
54
50 *
50 *
51 *
49 *
5l *
54 *
51 *
42 *
48 *
56 *
56 *
36
52 *
57
41

4.25
3.96
5.84
3.21
6.56
3.78
8.14
2.51
19.32
3.36
3.59
2.91
2.72
5.67
5.85
6.20
5.79

33.6 + 7.1
32.7 + 6.9
35.7 ± 7.3
34.9 ± 6.9
34.1 ± 8.0
35.7 ± 6.9
35.1 ± 7.6
32.0±6.9
34.2±8.1
36.9 ± 8.0
35.9 ± 7.6
31.3 ± 6.6
31.1 ±6.6
28.2 ± 6.7
33.4±7.3
36.2 ± 7.9
31.6 ± 6.6

* Significant mean rCMRGIu depressions ( p < 0.001, corrected for effective image resolution) were on the side of the stroke lesion. Mean
rCMRGIu depressions were calculated as (rCMRGlucontroI - rCMRGIu ycgl~ct)x 100/rCMRGlucomrot.
f r o m n o r m a l s i n t h e i r a m p l i t u d e s e x p r e s s e d as a p e r c e n t a g e o f t h e m a x i m a l M - w a v e s ( B e n e c k e e t al. 1988a).
F o r c o m p a r i s o n , in a p r e v i o u s s t u d y , in m o r e t h a n 3 0 %
of healthy subjects responses to the deltoid or vastus
m e d i a l i s m u s c l e s f a i l e d t o a p p e a r ( B e n e c k e e t al.
1988a). T h u s , w h i l e M E P s t o d i s t a l m u s c l e s w e r e n o r mal, MEPs to proximal muscles were only mildly but
not significantly altered in our patients.
Somatosensory
evoked
potentials
(SSEP) were
r e c o r d e d i n 3 p a t i e n t s ( T a b l e 1). I n c a s e 1 n o S S E P
were recorded, since he did not show any impairment
of sensation. Patient 2 showed symmetrical SSEP suggesting that the thalamic hemorrhage did not affect the
ventral posterolateral nucleus. Bilateral latency prolongation from the tibial nerves was due to slight concomitant polyneuropathy. Patients 3 and 4 had prolonged
latencies and diminished amplitudes from the affected
leg o r a r m a n d l e g c o r r e s p o n d i n g t o t h e i r c l i n i c a l
d e f i c i t s ( T a b l e 1).
Electroencephalography
(EEG) recordings revealed
slow w a v e s o f t h e t h e t a - b a n d o v e r b o t h h e m i s p h e r e s
( p a t i e n t s 2 a n d 3) a n d c o n c o m i t a n t f o c a l s l o w i n g p r e d o m i n a n t l y o v e r t h e f r o n t a l a n d t e m p o r a l e l e c t r o d e s in
all p a t i e n t s .
Metabolic data
I n all p a t i e n t s P E T r e v e a l e d a w i d e s p r e a d d e p r e s s i o n o f r C M R G I u c l e a r l y e x c e e d i n g t h e s t r u c t u r a l les i o n s . T h e m e a n C M R G I u f o r t h e w h o l e b r a i n (17.8
~ t m o l / 1 0 0 g / m i n ; p < 0.02) w a s s i g n i f i c a n t l y r e d u c e d
c o m p a r e d t o t h e a g e d - m a t c h e d c o n t r o l s d u e t o a severe reduction
in t h e a f f e c t e d h e m i s p h e r e
(14.0
/ z m o l / 1 0 0 g / m i n ; p < 0.02) a n d a s l i g h t r e d u c t i o n in
t h e c o n t r a l a t e r a l h e m i s p h e r e (20.7 ~ z m o l / 1 0 0 g / m i n ;

p < 0.05). R e g i o n a l a n a l y s i s s h o w e d t h a t t h e d e p r e s sions of the mean rCMRGIu were restricted to the
cerebral hemisphere ipsilateral to the stroke lesions
i n c l u d i n g t h e p r e - a n d p o s t c e n t r a l gyrus, t h e l e n t ± f o r m
n u c l e u s a n d t h e c o n t r a l a t e r a l c e r e b e l l u m ( T a b l e 2).
While common areas were identified by t-map analysis
( F i g . 3); t h e i n d i v i d u a l d a t a s h o w e d a 3 5 % r e d u c t i o n
compared to the left side in the right primary visual
a n d v i s u a l a s s o c i a t i o n c o r t e x r e l a t e d t o t h e left
h o m o n y m o u s h e m i a n o p i a a n d v i s u a l a t a x i a in c a s e 3.
Similarly, there was a 15% reduction of the rCMRGIu
compared to the right side in the left parietal opercular
r e g i o n in c a s e 2 w h o s u f f e r e d f r o m a m n e s t i c a p h a s i a .
The degree of the significant mean rCMRGIu depress i o n s w a s in t h e r a n g e o f 41 t o 5 6 % c o m p a r e d t o t h e
v a l u e s in t h e h e a l t h y c o n t r o l s u b j e c t s ( T a b l e 2). T h e
structures involved included the medial and inferior
frontal gyrus, the precuneus, the superior lateral parie t a l gyrus, t h e s u p r a m a r g i n a l a n d a n g u l a r g y r u s , t h e
superior temporal gyrus, and the thalamus. The two
largest areas of significant rCMRGlu depression were
l o c a l i z e d in t h e a n g u l a r g y r u s a n d t h e m e d i a l s u p e r i o r
parietal cortex (precuneus). However, there were also
l a r g e a r e a s o f r C M R G I u d e p r e s s i o n s in t h e p r e m o t o r
cortex and Broca's areas. There was also a pronounced
mean rCMRGlu depression in the midportion of the
c i n g u l a t e gyrus, t h i s , h o w e v e r , d i d n o t r e a c h signific a n c e ( F i g . 3).

4. Discussion
Since the early work by Hartmann (1907) and Liepm a n n ( 1 9 0 8 ) a n d l a t e r b y C r i t c h l e y ( 1 9 5 3 ) it is w e l l

H.-J. yon Giesen et al. /Journal of the Neurological Sciences 125 (1994) 29-38

established that abnormal motor behavior in the absence of hemiparesis may be caused by circumscribed
lesions of the cerebral cortex outside the primary sensorimotor cortex. Lesions in the parietal lobe have
been related to apraxia, while lesions in the frontal
lobe were related to disturbance of preparation, initiation and skillful execution of movement (reviewed by
Freund 1987). Castaigne described a further clinical
entity of abnormal motor behavior that he established
as motor neglect (Castaigne et al. 1970, 1972). In
strictly clinical terms he described motor neglect as "a
motor disorder localized to the right or the left hemibody, consisting of paucity of movement without paralysis or hypertension, without sensory changes, asomatognosia or anosognosia" and defined eight criteria

35

including absence of pyramidal signs. According to our
experience spontaneous withdrawal of affected limbs
out of uncomfortable positions is lacking in motor
neglect. However withdrawal to painful stimuli or
movement in response to vigorous encouragement is
usually preserved.
Although defined as clinical entity, underlying structural lesions were reported in various locations including the temporal, parietal, frontal and cingulate cortex
as well as subcortically in thalamus and mesencephalic
reticular formation (Castaigne et al. 1972; Watson et
al. 1973, 1974, 1979, 1981; Damasio et al. 1980; Heilman et al. 1983; Laplane et al. 1986). Unlike our
patients motor neglect is most often one aspect of a
more generalized multimodal neglect or hemi-inatten-

a

d

Fig. 3. Areas of significant mean rCMRGIu depression in the 4 patients with motor neglect compared to healthy controls. Only the depression in
the cingulate gyrus did not reach significance. Over the t-maps the structures of the computerized brain atlas (Greitz et al. 1991) were
superimposed. Besides the cerebral surface the cerebral structures shown are putamen, inferior frontal gyrus pars triangularis and lateral
ventricles (a), putamen, thalamus, lateral ventricles, lateral sulcus (b), precentral, central, postcentral (c,d) and intraparietal (c) sulcus. Left in the
images corresponds to the affected side.

3~

ff.-J, t'on Giesen et al. /Journal of the Neurological Sciences 125 (1994) 29-38

tion in severe cerebral stroke (Coslett et al. 1993;
Mesulam 1990).
The neurobehavioral discussion swings between
views stating that neglect may result from a defect of
intention (Watson et al. 1978) from an arousal-attention mechanism (Heilman and Valenstein 1972; Watson et al. 1973, 1977b; Halsband et al. 1985) or from a
neural representation deficit inducing attentional disturbances as secondary phenomena with predominant
damage to the right cerebral hemisphere (Bisiach and
Vallar 1988; Laplane 1990; Rizzolatti and Berti 1990).
In a more general conception, Mesulam (1990) proposed a disruption of a cortical network in hemineglect
that is normally sustained in conscious awareness. This
network is composed of local components including the
parietal association cortex, a limbic component in the
cingulate gyrus, a frontal component (premotor cortices including the frontal eye field) and a subcortical
component attributed to the mesencephalic reticular
formation, the ventrolateral thalamus and the intralaminar thalamic nuclei (Mesulam 1981, 1990; Laplane and
Degos 1983). Lesions in only one component of this
network yield partial unilateral neglect syndromes.
Thus, the multiplicity of neglect-causing lesions does
not result from a diffuse cerebral localization but,
instead, reflects the existence of a highly organized and
interconnected network subserving directed attention
(Mesulam 1990). While the individual components allow for behavioral specialization such as sensory representional and motor exploratory function mediated primarily in the parietal lobe (Pause et al. 1989; Bisiach et
al. 1990; Daffner et al. 1990; Liu et al. 1992), a separate role has been attributed to the anterior and posterior cingulate cortex, possibly reflecting a segregation
between attentional and intentional neural mechanisms (Paillard et al. 1990).
Therefore, we wished to map anatomically the cerebral structures that were metabolically affected secondary to a circumscribed vascular lesion in patients
who had suffered from motor neglect. The aim of this
study was to examine, if this approach provides a
means to identify those areas in the brain that subserve
normal motor activity but are functionally impaired in
motor neglect. It would, of course, be more elegant to
demonstrate the functional impaired brain regions in a
PET activation study. By definition however, voluntary
movements of the affected limbs are not performed by
patients suffering from motor neglect. Thus, our intention was to identify the brain areas with remote
metabolic depressions. For the purpose of this study,
the PET images of different subjects were spatially
standardized and a statistical comparison to a group of
healthy subjects was performed pixel-by-pixel. We provided evidence that the rCMRGIu was severely depressed in our patients throughout the cerebral hemisphere ipsilateral to the stroke lesion. This widespread

depression of the mean rCMRGlu resulted from the
different locations of the structural brain lesions in the
frontal and parietal cortex as well as in the basal
ganglia and thalamus (Fig. 1). T-map analysis, however,
demonstrated focal areas of significant mean rCMRGlu depression that were common for the examined
cohort as discussed in detail elsewhere (Seitz et al.
1990, 1993). Thus, in spite of the different locations of
the structural lesions in our patients, the areas of
significant mean rCMRGlu depression indicated common abnormalities with small inter-subject variance
among our patients.
We show that the areas of significant mean rCMRGlu depression included on the lesion side the medial
and inferior frontal gyrus, the temporo-parietal region,
the precuneus, the superior lateral parietal gyrus, the
supramarginal and angular gyrus, the superior temporal gyrus, and the thalamus (Table 2). There was also a
pronounced mean rCMRGIu depression in the cingulate gyrus, this was, however, not significant (Fig. 3). In
contrast, no significant mean rCMRGIu depressions
occurred in the primary structures of the motor output
system such as the ipsilateral pre- and postcentral
gyrus, the lentiform nucleus and the contralateral cerebellum. The hypometabolic anatomically defined areas
in our study are thus almost identical to those theoretically discussed in the etiopathogenesis of motor neglect
as outlined above. Since the rCMRGIu has been shown
to be related to synaptic activity (Yarowsky et al. 1983;
Kadekaro et al. 1985) it can be assumed that the
regions with significantly lower mean rCMRGlu represent areas with depressed neuronal activity. We can
thus in vivo reliably demonstrate the existence of the
proposed cortico-subcortical network (Mesulam 1990)
and we can further demonstrate an ubiquitous depression of neuronal activity in all parts of the network
once a damage to one single part occurred. Accordingly and as described earlier (Watson et al. 1977),
electroencephalographic changes in our patients extended over the entire hemisphere with marked E E G
slowing especially over the frontal and temporo-parietal
lobes.
Our findings substantiate and extend earlier results
by Fiorelli and co-workers (1991) who found a
widespread hypometabolism only of the lesioned side
sparing consistently the occipital lobe in predominant
motor neglect. An important difference to our study
are their findings of the inconsistent depression of
metabolism in the thalamus and of the primary motor
and sensory cortical areas at least in some of their
patients. In accordance to measurements of glucose
utilization in monkey with a frontal lobe neglect (Deuel
et al. 1984) that revealed a hypometabolism in various
parts of the thalamus, we interpret our finding as
compatible with the above discussed cortico-subcortical
network, especially as the mesencephalic reticular acti-

14,-J. yon Giesen et al. /Journal of the Neurological Sciences 125 (1994) 29-38

vating system probably projects to the cortex in a
diffuse polysynaptic fashion (Scheibel and Scheibel
1967) and this projection may occur through the thalamus (Steriade and Glenn 1982). Further, in our 4
patients with motor neglect no dysfunction of the cortico-spinal tract could be detected by transcranial magnetic stimulation. Rather, normal CMCT to virtually all
distal and proximal muscles under study proved the
functional integrity of the motor cortical output system.
In conclusion, we interpret the rCMRGlu depressions to represent remote effects that have repeatedly
been demonstrated in patients with focal cerebral lesions (Feeney and Baron 1986), and assumed to underlie the neuropsychological impairment ensuing stroke
(Baron et al. 1986). Evidence from systematic mapping
studies suggests that these remote rCMRGlu depressions are not unstructured or diffuse but circumscribed
in relation to the structural stroke lesion (Heiss et al.
1992). The patterns of the remote rCMRGlu depressions appear to result from deafferentation o r / a n d
retrograde degeneration due to structural nerve fiber
damage thus being detectable for many years after
stroke (Martin and Raichle 1983; Seitz et al. 1994).
Our data indicate that interconnected cortical and
subcortical areas subserving motor activity were affected simultaneously by the underlying stroke lesion.
It is hypothesized that in motor neglect the intact
motor cortical output system is deprived from sensory
information and voluntary drive needed for movement
execution.

Acknowledgement
This study was supported by the Sonderforschungsbereich 194 of the Deutsche Forschungsgemeinschaft.

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