Spatial hemineglect in humans - Cisi

Progress in Neurobiology 63 (2001) 1±27
www.elsevier.com/locate/pneurobio
Spatial hemineglect in humans
Georg Kerkho€*
EKN-Clinical Neuropsychology Research Group, Department of Neuropsychology, Hospital Bogenhausen, Dachauerstr. 164,
D-80992 Munich, Germany
Received 6 March 2000
Abstract
The paper reviews the main ®ndings of studies of hemispatial neglect after acquired brain lesions in people. The behavioral
consequences of experimentally induced lesions in animals and electrophysiological studies, which shed light on the nature of the
disorder, are brie¯y considered. Neglect is behaviorally de®ned as a de®cit in processing or responding to sensory stimuli in the
contralateral hemispace, a part of the own body, the part of an imagined scene, or may include the failure to act with the
contralesional limbs despite intact motor functions. Neglect in humans is frequently encountered after right parieto-temporal
lesions and leads to a multicomponent syndrome of sensory, motor and representational de®cits. Relevant ®ndings relating to
neglect, extinction and unawareness are reviewed and include the following topics: etiological and anatomical basis, recovery;
allocentric, egocentric, object-centered and representational neglect; motor neglect and directional hypokinesia; elementary
sensorimotor and associated disorders; subdivisions of space and frames of reference; extinction versus neglect; covert processing
of information; unawareness of de®cits; human and animal models; e€ects of sensory stimulation and rehabilitation
techniques. 7 2000 Elsevier Science Ltd. All rights reserved.
Contents
1. Introduction ............................................................ 2
2. Anatomy and recovery. .................................................... 2
2.1. Etiology and lesion localization ......................................... 2
2.2. Mechanisms of recovery. .............................................. 3
3. Allocentric spatial de®cits .................................................. 4
4. Egocentric spatial de®cits ................................................... 5
5. Object-centered neglect .................................................... 6
6. Representational neglect ................................................... 7
7. Motor neglect and directional hypokinesia ...................................... 7
Abbreviations: MCA, middle cerebral artery; BA, Brodman area; SSA, subjective straight ahead; CT, computerized cranial tomography;
(f)MRI, (functional) magnetic resonance imaging of the brain; 2DG, 2-desoxyglycose; rCBF, regional cerebral blood ¯ow; PET, positron emission
tomography of the brain; SC, superior colliculus; PmS, posterior middle-suprasylvian cortex (in cats).
* Tel.: +49-89-154057; fax: +49-89-156781.
E-mail address: georg.kerkho€@extern.lrz-muenchen.de (G. Kerkho€).
0301-0082/00/$ - see front matter 7 2000 Elsevier Science Ltd. All rights reserved.
PII: S0301-0082(00)00028-9

2
G. Kerkho€ / Progress in Neurobiology 63 (2001) 1±27
8. Elementary sensory, motor and associated disorders. ............................... 9
9. Subdivisions of space and di€erent frames of reference. ............................ 10
9.1. Behavioral dissociations in di€erent sectors of space in neglect .................. 10
9.2. Neurophysiologic and functional imaging evidence for di€erent types of space coding in
the brain. ........................................................ 10
10. Extinction versus neglect .................................................. 11
11. Covert processing of information ............................................ 13
12. Unawareness of de®cits ................................................... 13
13. Models ............................................................... 14
13.1. Early sensory theories ............................................... 14
13.2. Attentional theories ................................................. 15
13.3. Representational theories ............................................. 17
13.4. Transformational theories ............................................ 17
13.5. Cerebral balance theories ............................................. 18
13.6. One model or a synthesis of models?. .................................... 19
14. Modulation of neglect, extinction and unawareness by sensory stimulation .............. 19
15. Rehabilitation approaches ................................................. 20
16. Outstanding questions .................................................... 22
Acknowledgements. .......................................................... 22
References ................................................................. 22
1. Introduction
Neglect (synonymous with: hemispatial neglect, hemiinattention,
hemisensory neglect, hemineglect ) denotes
the impaired or lost ability to react to or process sensory
stimuli (visual, auditory, tactile, olfactory) presented
in the hemispace contralateral to a lesion of the
human right or left cerebral hemisphere. Besides the
aforementioned aspects of sensory neglect, motor
neglect may occur and manifest itself as the reduced
use or nonuse of a contralateral extremity (arm, leg)
during walking or bimanual activities. Finally, neglect
may occur in the imagination of spatial scenes (representational
neglect). By de®nition, neglect is not
merely the result of elementary sensory (i.e. hemianopia,
hemisensory loss), motor (i.e. hemiparesis) or cognitive/emotional
disorders (i.e. reduced intelligence,
depression). Table 1 summarizes the most frequent
neglect phenomena in these di€erent categories.
2. Anatomy and recovery
2.1. Etiology and lesion localization
The most frequent etiological cause of neglect in
humans is (often large) infarctions in the territory of
the right, less often the left middle cerebral artery
(MCA; Vallar, 1993), causing lesions which center on
the inferior parietal cortex (Brodman areas, BA 40, 7).
Accompanying damage to adjacent structures such as
the optic radiation, the insula, dorsolateral frontal cortex
(BA 4,6,44,45, 46) and superior temporal cortex
(BA 22, 37) is frequently apparent (Smania et al.,
1998). Furthermore, neglect occurs after posterior thalamic
(Cambier et al., 1980) or basal ganglia lesions
(Damasio et al., 1980), as a result of intracerebral
bleedings, but has never been described following pure
occipital lesions (Smania et al., 1998; Vallar, 1993).
Occasionally, neglect after lateral frontal lesions has
been reported (Husain and Kennard, 1996) where similar
lesions in animals regularly lead to contralesional
neglect (Rizzolatti et al., 1983; Deuel and Collins,
1984). Neglect may also result from tumors or traumatic
injuries of the aforementioned areas (Vallar,
1993). In general, severe and multimodal neglect is
caused by very large rightsided lesions which encroach
on parietal, temporal, and regions of occipital or frontal
cortex as well as subcortical structures (Vallar and
Perani, 1986).
Contralesional neglect occurs in some 33% of lefthemisphere
and more than 50% of right-hemisphere

G. Kerkho€ / Progress in Neurobiology 63 (2001) 1±27 3
Table 1
Summary of sensory, motor and representational neglect phenomena occurring after unilateral lesions in humans
Type of neglect
Visual
Auditory
Somatosensory
Olfactory
Motor
Representational
De®nition and typical behaviour
Patient searches for stimuli with eye- and head-movements preferentially in the ipsilesional hemispace. Omission of
contralesional stimuli during reading, writing, drawing of geometric stimuli, bisecting horizontal lines, or eating
from a plate. Ipsilesional deviation of the perceived subjective straight ahead.
Patient does not react to sound/speech stimuli from the contralateral hemispace. He/she may turn to the
ipsilesional side when addressed from the contralesional. When several speakers are present the patient responds
preferentially to the most ipsilesional one, irrespective of who has spoken. Ipsilesional deviation of the perceived
auditory midline position in front space.
Ignoring of tactile stimulation (i.e. touch) or painful stimuli (cold/hot stimuli, jammed ®ngers in wheel or spokes of
the wheelchair) on the contralesional body half. Mislocalization of tactile stimuli in this part. Subjective shift of
own body-midline (i.e. position of the spine) to the ipsilesional side.
Ignoring smells delivered to one nostril. Rarely observed in daily life since stimuli are easily detected with the other
nostril.
Reduced use of contralesional arm/leg which is not completely attributable to a sensorimotor loss. Reduced arm
sway during walking; reduced use of contralesional arm during bimanual activities (i.e. eating, carrying loads);
dragging behind the contralesional leg/foot during walking.
Patient describes few items located in the contralesional part of an imagined scene (i.e. a famous city place, the
own living room or house), but describes much more items when describing the same scene from a di€erent
perspective (1808 rotated).
lesioned patients 1 (Stone et al., 1991) when tested immediately
(within 7 days) after lesion onset. The absolute
percentage of neglect depends critically on the
criterion or test used but the asymmetry in the occurrence
of contralesional neglect has been found across
di€erent samples and methods (Schenkenberg et al.,
1980). Recovery is considerably quicker and more
complete in neglect after left-hemisphere lesions as
opposed to right-hemisphere lesions (Stone et al.,
1991). Thus, there is a clear hemispheric asymmetry
showing that neglect is more frequent, more severe and
more permanent following right-hemispheric lesions.
However, transient rightsided neglect after left unilateral
lesions occurs in some cases (Welman, 1969; Peru
and Pinna, 1997; Kerkho€ and Zoelch, 1998). More
long-lasting rightsided neglect occurs in patients with
bilateral cerebral lesions (Weintraub et al., 1996).
2.2. Mechanisms of recovery
1 Since leftsided neglect after right cerebral lesions is the most frequent
type of neglect the term ``neglect'' in this review refers always
to leftsided neglect in humans if not indicated otherwise. Of course,
this does not exclude the fact that rightsided neglect after uni- or bilateral
lesions may occur (more rarely) as well.
Recovery from the most obvious signs of neglect
(i.e. the tendency to orient to the ipsilesional side and
the lack of visual exploration in the contralesional
hemispace) has been noted in the majority of patients
within the ®rst 6 months (Lawson, 1962; Hier et al.,
1983). In the remaining 25% neglect may persist for
up to 12 years (Zarit and Kahn, 1974) and performance
in tasks which are sensitive to neglect may decline
again after cessation of apparently successful rehabilitation
treatment in the clinic (Paolucci et al., 1998;
Hier et al., 1983). Recovery from neglect is more prominent
after left compared with right-sided cerebral
lesions (Stone et al., 1991). Furthermore, recovery
from ``frontal'' neglect is more rapid and more complete
in humans than from the classical ``parietal''
neglect syndrome (Mattingley et al., 1994a). Substantial
recovery is less likely after large lesions and in
those patients with di€use brain atrophy in addition to
the focal right hemispheric lesion (Levine et al., 1986)
Little is known about the mechanisms guiding spontaneous
recovery and/or those enabling treatmentguided
improvements during rehabilitation. Pantano et
al. (1992) reported a concomitant increase in regional
cerebral blood ¯ow (rCBF) in the posterior areas of
the damaged right hemisphere and the anterior areas
of the intact, left hemisphere probably including the
frontal eye ®elds after a speci®c neglect treatment in
their patients. Only the left frontal activation, in the
region of the frontal eye ®elds, covaried with improved
visual scanning behavior after treatment. The authors
concluded that the left (intact) frontal eye ®elds are
crucial for recovery of visual scanning in neglect. In a
later PET study with three neglect patients, this ®nding
was not uniformly replicated (Pizzamiglio et al., 1998).
In this study, behavioral recovery seemed to covary
with improved blood ¯ow in surviving areas of the
lesioned hemisphere.
Similar results have been obtained in primate studies
where neglect was induced by lesioning the frontal
polysensory association cortex. Metabolic mapping for
local glucose utilization (2-DG) showed a widespread
reduction of glucose in ipsilesional striatal and partially
thalamic nuclei connected with the frontal lobe
whereas no reductions were found in cortical areas

4
G. Kerkho€ / Progress in Neurobiology 63 (2001) 1±27
connected to the frontal lobe (Deuel and Collins, 1983,
1984). Behavioral recovery of visual somatosensory
and motor neglect was paralleled by a normalization
of glucose metabolism in these subcortical circuits of
the lesioned hemisphere (Deuel and Collins, 1983,
1984). To summarize, as in the few human imaging
studies neglect after focal rightsided lesions of the
frontal or parietal cortex is associated with widespread
depressions of metabolic activity in the same hemisphere;
behavioral recovery is paralleled (or enabled)
by a normalization of activity in this neural network
for spatial attention that includes cortical and subcortical
areas. This widespread depression of activity
helps to explain why neglect occurs after cortical and
subcortical lesions of di€erent anatomical structures
(see Section 13).
judgments in hemianopic patients without neglect
(Axenfeld, 1894; Lohmann, 1911). These patients
bisect a horizontal line in most cases too far to their
blind hemi®eld (Kerkho€, 1993; Barton et al., 1998)
whereas neglect patients without hemianopia place
their bisection mark too far to their ipsilesional side
thus reproducing a too large line segment in their contralesional
hemispace (Halligan et al., 1990; Halligan
and Marshall, 1991b; Barton et al., 1998; cf. Fig. 1A).
In a variant of this task termed line extension (Fig. 1B)
the subject views only the part of the line displayed in
the ipsilesional hemispace and subsequently estimates
how long a bar has to be extended to the contralesional
hemispace until both parts appear as equally
long. In this task neglect patients typically oversize the
line segment in their neglected hemispace Ð just as
they do in line bisection (Fig. 1B).
3. Allocentric spatial de®cits
Because damage is invariably widespread and compromises
multiple neural systems, principally located
in the parieto-temporal cortex (in human neglect) as a
result of large lesions a variety of de®cits are encountered
in neglect. These may be analyzed with respect to
di€erent aspects of spatial cognition. A distinction
may be drawn between allocentric, egocentric and
object-centered de®cits. Allocentric space is de®ned in
this context as concerning the spatial relationship
between two stimuli separated in space, i.e. the length
of two lines or the two halves of a bisected line. In a
broader sense, allocentric relationships de®ne spatial
relations between two or more stimuli in three-dimensional
space, including those entailed in spatial navigation.
In contrast, egocentric de®cits relate to spatial
impairments in relation to the patient's own body or
speci®c body parts, i.e. the subjective estimate of her/
his tactile body midline, the auditory or visual sense of
straight ahead in relation to the sagittal midline of the
body or head. Object-centered (or environment-centered)
de®cits indicate hemispatial de®cits or omissions
in the contralesional half of one object, i.e. a face or a
clock face (see below). In contrast to the allocentric
and egocentric de®cits which ®t relatively easy into a
left-right or contralesional/ipsilesional dichotomy of
space (impairments in left/contralesional hemispace,
normal or nearly normal performance in right/ipsilesional
hemispace) object-centered neglect means that a
patient ignores the left/contralesional part of one
object (i.e. a word, a drawing, or a face), regardless of
the object's location in space (Walker, 1995; Olson and
Gettner, 1996).
One of the most frequent allocentric de®cits investigated
in patients with visual neglect is horizontal line
bisection (Schenkenberg et al., 1980; Burnett-Stuart et
al., 1991), a task originally devised to measure spatial
Fig. 1. Survey of de®cits in allocentric visuospatial tasks in patients
with leftsided visual neglect. The vertical stippled line represents the
putative border of the contralesional and ipsilesional hemispace
aligned to the objective median plane of the patient. (A) In horizontal
line bisection the neglect patient transects the bar too far to the
ipsilesional, right side, indicating a deviated subjective midline (cf
Halligan et al., 1990). (B) Oversized left line segment in a line extension
task (Bisiach et al., 1996). In this task, the subject ®rst views
only the black, rightsided bar. He/she is then instructed to estimate
how long the leftsided (dotted) bar has to be drawn until it appears
to have the same length as the rightsided black bar. (C) The subject
views a horizontal distance in the ipsilesional hemispace which has
to be reproduced with the two black markers in the contralesional,
left hemispace. Note the signi®cant overestimation of the leftsided
distance (``space distortion'', indicated by the shaded area; redrawn
after (Kerkho€, 2000). (D) Typical overestimation of horizontal bar
length in the contralesional hemispace (``size distortion''; indicated by
the shaded area; redrawn after (Milner and Harvey, 1995). (E,F)
Normal, veridical coding of vertical size and of symmetric shapes in
neglect (redrawn after Milner and Harvey, 1995).

G. Kerkho€ / Progress in Neurobiology 63 (2001) 1±27 5
Similarly, neglect patients overreproduce a horizontal
distance displayed in their contralesional hemispace
when the ``reference'' distance is displayed in their ipsilesional
space (Fig. 1C). The same phenomenon is
observed when a horizontal bar has to be reproduced
in the left hemispace (Fig. 1D). Here patients reproduce
the bar in the contralesional hemispace too long,
which has been termed ``size distortion'' (Harvey et al.,
1995; Milner and Harvey, 1995; Milner et al., 1998).
In contrast, neglect patients show veridical coding of
vertical bars (Fig. 1E) and of symmetrical, global
shapes like circles (Fig. 1F). This disturbed size coding
may remain a purely perceptual phenomenon since it
does not necessarily imply disturbed adjustment of ®nger
grip aperture when scaling the size of an object in
grasping (Pritchard et al., 1997). Together, these
results indicate a non-veridical coding of within-object
(length of an object) and between-object (distance
between objects) spatial extension in the horizontal
plane which is not found when vertical size cues are
apparent. The advanced interpretation for these allocentric
spatial disorders is that the contralesional hemispace
appears ``constricted'' or ``distorted'' in relation
to the ipsilesional hemispace (Milner et al., 1998). As a
consequence, elongated objects presented in this hemispace
have to be larger in order to match the length of
an object in ipsilesional hemispace. This has been
found for horizontal object-size, and as well for the
horizontal distance between objects (Kerkho€, 2000;
see also Karnath and Ferber, 1999 for di€erent results
and interpretations). Measures of perceptual distortions
in patients with neglect may be quite sensitive
since they may reveal size distortions even after apparent
recovery of other signs (line bisection; Harvey and
Milner, 1999).
4. Egocentric spatial de®cits
Fig. 2. Representative egocentric de®cits in neglect. (A) Deviated
visual judgments of neglect patients (without visual ®eld defects)
when indicating the position of a diode in total darkness in relation
to their bodily subjective straight ahead position. The judgments
were similarly shifted to the ipsilesional, right side in two distances
(1.2 and 3 m), indicating a rotation of the visual subjective straight
ahead (SSA) in front space (redrawn after Ferber and Karnath,
1999). (B) Ipsilesionally shifted visual search area in total darkness
(solid line) and similarly shifted tactile search area (with the ipsilesional
hand, not drawn) with blindfolded neglect patients (cf. Karnath
and Perenin, 1998). Search areas are drawn schematically and
not to scale. (C) Judgments of the subjective visual and tactile vertical,
horizontal and oblique orientation matches in a patient with leftsided
neglect (upper two polar plots) and a matched normal subject
(lower two plots). Each thin black lines represents the result of one
trial. Visual tests were taken with stimuli displayed on a PC-screen
via software (Kerkho€ and Marquardt, 1995), tactile tests employed
the judgment of a metal bar mounted on a vertical board in front of
the patient (Kerkho€, 1999a). Note the counterclockwise tilt of perceptual
judgments in both modalities in the neglect patient. Together,
these results indicate a subjective rotation of sensory space in the
frontal plane going beyond the shift of the SSA in the sagittal plane
(A) in neglect patients.
It is a relatively new idea that neglect is not only
found in relation to the left half of space but more
precisely in relation to what is left of the patient's
trunk midline, head sagittale or even the position of
the patient's hand in space. In one of the early studies
on that topic (Heilman et al., 1983) neglect patients
were required to point towards their subjective straight
ahead (SSA) in relation to their trunk midline. The
patients' responses were ipsilesionally deviated to the
right side while non-neglecting patients with left hemispheric
lesions showed quite accurate pointing results.
Similar results are obtained when neglect patients have
to indicate their visual SSA without pointing (Fig. 2A).
If egocentric de®cits are related to the body midline
or certain body parts modi®cations of their position in
space might in¯uence neglect. In an early study examining
this question (Bisiach et al., 1985), neglect
patients had to tactually explore a honeycomb-shaped
board with their ipsilesional hand to ®nd a marble.
The authors found that neglect covaried with the position
of the trunk-vertical axis and with the head/eyeaxis.
Shifting either the trunk or the head to the left in
relation to the stationary honeycomb-board reduced
the number of omissions in the tactile neglect task.
Karnath (summarized in Karnath, 1997) has investigated
the in¯uence of body-and-head position in more
detail. In a saccadic reaction-time study, it was found
that leftward trunk-rotation but not head-rotation
improved the delayed reactions to visual targets
appearing in contralesional hemispace (Karnath et al.,

6
G. Kerkho€ / Progress in Neurobiology 63 (2001) 1±27
1991). This role of the trunk-sagittale as one major
anchor for determining left versus right in space in relation
to the observer has been replicated in several
subsequent studies using line bisection and reading
tasks (Chokron and Imbert, 1995; Schindler and Kerkho€,
1997; Vuilleumier et al., 1999). However, the
trunk midline is not the only axis that might be important
for spatial orientation: the head sagittale plays
a similar important role as suggested by behavioral
and neurophysiological studies (behavioral: Bisiach et
al., 1985; Kerkho€ and Schindler, 1997; Vuilleumier et
al., 1999; neurophysiological: Andersen et al., 1989,
1990, 1997; Duhamel et al., 1997). Other types of egocentric
or body-centered de®cits in neglect are summarized
in Fig. 2. Patients with pure neglect (without
®eld defects) often show an ipsilesionally deviated subjective
estimate of straight ahead (Fig. 2A) which
seems to be anchored to the trunk midline, although
not every neglect patient shows this de®cit (Bartolomeo
and Chokron, 1999). The visual and tactile ®elds
of search in neglect patients (as measured by optoelectronic
devices) are shifted to the ipsilesional, right side
(Fig. 2B), even when no external stimulus is present.
Fig. 3. (A) Examples of object-centered neglect in drawing a clock or
¯owers. The arrows indicate the omission of relevant details. Note
that the neglect patient drew two ¯owers laterally beneath each
other, but neglected the leftsided details of each ¯ower. (B) Objector
word-centered neglect during reading an indented reading text.
The crossed-out words indicate complete omissions of whole words
(space-based reading errors) while the bold, shadowed, leftsided
parts of words (see arrows) indicate word-based omissions. Note
that in most cases the patient read some words correctly which were
located to the left of the word-centered errors, similar to the fact
that both ¯owers were drawn (see A), but with leftsided, object-centered
omissions of details in their Gestalt (B based on results from
Kerkho€ et al., 1999b).
However, the deviations of spatial orientation in the
horizontal plane are not the only ones encountered in
neglect. These patients can also show a tilt of their
subjective vertical or horizontal or judgments of
whether two obliquely oriented stimuli are parallel, in
their frontal plane (Fig. 2C). Hence, a 908-oriented,
vertical bar has to be oriented to 1008 (tilted counterclockwise)
to be perceived as vertical by a neglect
patient. This de®cit occurs both in the visual (Kerkho€
and Zoelch, 1998) and tactile (Kerkho€, 1999a) modality
and indicates that the spatial anchoring of subjective,
egocentric space is disturbed in neglect patients
in at least two spatial planes: the horizontal plane,
leading to the pathological, ipsilesionally oriented
body orientation (cf. Fig. 2A,B), and the frontal plane,
leading probably to abnormal posture of the head,
trunk and legs during sitting and stance, as found in
neglect patients (Rode et al., 1997, 1998; Perennou et
al., 1998, 1999).
5. Object-centered neglect
When we look at or imagine an object we are aware
of its structure. Consider the face of a friend of yours,
your watch or the letter `d'. We know that in order to
transform the letter `p' from `d', we have to rotate the
letter `d' in the plane of the page. Likewise, you know
if and on which side your friend has a birth mark on
his face, or on which side of your watch the date is
indicated. This kind of structural awareness very likely
depends on a neural system with two features: neurons
selective for locations as de®ned relative to a reference
frame around an object, and an arrangement of several
of such neurons so that their spatial ®elds form a map
of object-centered space (Olson and Gettner, 1995,
1996). Patients with spatial neglect may copy or mark
every feature in an array, yet they may fail to reproduce
the left part of an object (leftsided numbers on a
clock face, a ¯ower, or the left part of a word, cf.
Fig. 3).
Hillis and Caramazza (1991) described a patient
with rightsided neglect dyslexia who made reading
errors chie¯y at the end of a word Ð irrespective in
which visual ®eld the word appeared, or if it were
printed from left to right, right to left or vertically
from top to bottom. In all these experimental modi®cations,
the errors occurred at the end of the word.
These results support the idea that meaningful words
form a kind of ``perceptual unit'' (Baylis et al., 1994)
and have an object-centered representation. Likewise,
faces may be coded in a similar way which ®ts neatly
the observation of leftsided neglect for the contralesional
half of objects or faces (Walker, 1995).
Which factors do determine that a patient neglects
the left half of an object? Is the gravitational vertical

G. Kerkho€ / Progress in Neurobiology 63 (2001) 1±27 7
or the intrinsic vertical of an object the relevant variable?
To decide between these two possibilities, rotated
®gures with critical elements on the left or right side of
the intrinsic ®gure axis have been utilized. Some
patients persist in showing neglect of the contralesional
part of the rotated object (Driver et al., 1994). This
type of axis-based neglect demonstrates neatly that
neglect might be attached to the object's intrinsic axis
and not necessarily to the physical, left side of an
object (but see Farah and Buxbaum, 1997, for an
alternative interpretation).
6. Representational neglect
Neglect is not restricted to perception or action in
the contralesional part of external space. It may occur
as well when subjects have to scan their inner spatial
representation of a scene. Bisiach and Luzzatti (1978)
reported in their famous experiment two patients who
were unable to recall speci®c locations on the left side
of the Piazza de Duomo in Milano when they imagined
facing it from a particular vantage. When they
had to describe the square from a 1808-rotated perspective
they recalled the omitted details on their left
from the previous condition but neglected now particular
items on their left side which were on the right side
in the prior test condition. The authors concluded that
their patients had an unilateral representational de®cit
for one hemispace. In later studies, these results were
con®rmed experimentally using an elegant technique
(Bisiach et al., 1981). Similar de®cits are found when
patients are required to recall cities from their country
(Bartolomeo et al., 1994; Rode and Perenin, 1994 cf.
Fig. 4).
Fig. 4. Example of representational (imaginal) neglect in a patient
asked to visualize mentally the map of France and to name as many
towns as possible during a limited period of time (2 min). The number
at the bottom indicates the number of recalled cities in the two
conditions. Temporary remission through caloric (vestibular) stimulation
is seen on the right side of the ®gure. Reproduced from Perenin
(1997), with permission from Springer-Verlag.
Representational neglect seems to be less frequent
than frank visual neglect: only some 25% of the latter
patients show representational neglect when they are
required to recall cities located on the left or right side
of a map of their own country (Beschin et al., 1997;
Bartolomeo et al., 1994). Typically, the patients recall
easily cities located on the right side of the map and
fail to report those located on the contralesional, left
side Ð just as in the Piazza de Duomo example
described above. Clinically, similar de®cits can be suspected
when patients have to remember where on the
ward their bedroom is or when they have to recall
details from their home, i.e. the living room.
7. Motor neglect and directional hypokinesia
Two types of de®cient motor behavior in neglect
have to be distinguished clearly: the reduced spontaneous
use or complete nonuse of the contralesional
hand, arm or leg during motor activities (termed motor
neglect; cf. Laplane and Degos, 1983; von Giesen et
al., 1994) and the slower execution of arm movements
with the ipsilesional hand or arm towards the contralesional
hemispace (termed directional hypokinesia, Heilman
et al., 1985; Bisiach et al., 1990; Mattingley et al.,
1994c; Bisiach et al., 1995). The latter is associated
with a delayed movement initiation and a reduced
movement velocity and is probably a rare form of
neglect (Milner et al., 1993). Akin to the directional
hypokinesia for leftward arm movements, neglect
patients show delayed (Sundquist, 1979) and hypometric
(Girotti et al., 1983) saccadic eye movements to
left hemispace and their pattern of visual search is
shifted to the ipsilesional hemispace (Che dru et al.,
1973; Ishiai et al., 1987; Hornak, 1992; Karnath et al.,
1996; as depicted in Fig. 2B).
In contrast, motor neglect a€ects only the contralesional
extremity; the use of the neglected hand/arm
often can be prompted by the allocation of attention
to it (Ghika et al., 1998), similar to the cueing e€ects
in sensory neglect (see Section 14). This motor neglect
is not a result of a paresis which can be excluded by
the examination of magnetic evoked potentials (Von
Giesen et al., 1994). Patients with motor neglect have
often lesions involving the thalamus, basal ganglia or
the frontal cortex but spare the primary sensorimotor
cortex (Laplane and Degos, 1983). Motor neglect is
also found as a transient phenomenon after unilateral
ventrolateral thalamotomy for the treatment of hemiparkinsonism
(Vilkki, 1984). Similar to the results of
the 2-DG mapping studies in primate neglect (Deuel
and Collins, 1984) imaging investigations in humans
(PET, Von Giesen et al., 1994) indicate a more widespread
metabolic dysfunction in the premotor, prefrontal,
cingulate and partially parietal cortex of the

8
G. Kerkho€ / Progress in Neurobiology 63 (2001) 1±27
Table 2
Frequently associated de®cits in neglect. Percentages are based on studies with neglect patients after right hemisphere lesions, or on right-hemisphere lesioned patients in general and may di€er
between studies. In patients with small, circumscribed parietal lesions, other percentages are obtained (indicated by , see Ghika et al., 1998). In the rightmost column diagnostic procedures are
suggested to di€erentiate between elementary sensory or motor de®cits and neglect-related impairments. If the peripheral sensorimotor pathways are intact VEP, SEP and transcranial magnetic
stimulation should reveal largely normal results
De®cit Frequency
(%)
Source Procedures for di€erential diagnosis
Visual ®eld defects (hemianopia, quadrantanopia) 70±90 Vallar and Perani, 1986; Kerkho€, 1999a Visually evoked potentials (VEP), Vallar et al., 1991;
Spinelli et al., 1994; De Keyser et al., 1990; Special
perimetry, Walker et al., 1991
Hemianaesthesia (impaired position and pain sense in contralesional limbs)
63 Vallar et al., 1995b; Vallar et al., 1997; Sterzi et al., 1993; Ghika et al., 1998
Somatosensory evoked potentials (SEP); Cueing of
patient's attention to the neglected limb; Ghika et al., 1998
Hemiplegia/-paresis 100 Sterzi et al., 1993 Transcranial magnetic stimulation of motor cortex; Von
Giesen et al., 1994
Pseudoparesis of the hand 90 Ghika et al., 1998 Transcranial magnetic stimulation (TMS) of motor cortex
Von Giesen et al., 1994
Abnormal ®nger and hand postures 67 Ghika et al., 1998 ±
Ipsilesional deviation of body posture in stance 70 Rode et al., 1997; Hesse et al., 1994 Posturography; Rode et al., 1997
Increased pain, avoidance of contralesional limb use 34 Ghika et al., 1998 Measurement of prolonged ``silent periods'' in the EMG
after TMS; Classen et al., 1997
Contralateral gaze palsy (tonic ipsilesional eye deviation) 30±50 De Renzi et al., 1982; Tijssen and Gisbergen, 1993 ±
Visuospatial and tactilespatial disorders, impaired time 90 Kerkho€, 1999a; Basso et al., 1996 Evaluation of spatial perception; Kerkho€ and
perception
Marquardt, 1995
Fatigue, reduced sustained attention ± Robertson et al., 1997 ±

G. Kerkho€ / Progress in Neurobiology 63 (2001) 1±27 9
Fig. 5. Highly schematic demonstration of the typical di€erence
between leftsided, visual hemineglect and leftsided, homonymous
hemianopia without neglect. In neglect, elementary visual perception
up to the striate cortex may be largely intact in the contra- and ipsilesional
visual hemi®eld. In contrast, this is the principal de®cit in
homonymous, leftsided hemianopia. The opposite is found on a
higher, more abstract level of spatial representation of the environment
and the own body. Here, the left hemispace is less well represented
in neglect, but seems intact in hemianopia without neglect.
Note, however, that hemianopia or other ®eld defects may be present
due to damage of adjacent cortical structures in some 70% of neglect
patients, especially in those with large parieto-temporal lesions compromising
the optic radiation. The ®gure is intended to clarify the
crucial di€erence between a low-level visual disorder for one side of
space (hemianopia) and a high-level hemispatial disorder (neglect).
Note further, that in hemianopia a clear-cut, often stable border
between seeing and blind ®eld regions is normally obtained in perimetric
testing. In contrast, the border between neglected and nonneglected
hemispace is more variable and subject to many modulations,
illustrated below in Fig. 10.
injured hemisphere in motor neglect than the lesion
shown by the structural CT/MRI scans. Classen et al.
(1997) studied the neurophysiological basis of motor
neglect and found an exaggerated ``silent period'' in
the electromyogram of small hand muscles after transcranial
magnetic stimulation. According to their
results, this ``silent period'' might considerably delay
the initiation of directed motor activities of the contralateral
extremities, and thus lead to the symptoms
of hypokinesia, underutilization of the contralateral
extremities as well as delayed movement initiation
(Classen et al., 1997).
8. Elementary sensory, motor and associated disorders
Most patients with neglect have low-level sensory
2 It has been proposed recently that primary visual cortex is also
involved in high resolution visual imagery (Kosslyn et al., 1999).
Consequently, striate cortex lesions might cause not only hemianopia
but also a unilateral imagery de®cit similar to that of neglect
patients. However, clinical experience with purely hemianopic
patients does not support such a hemi-imagery de®cit, at least not
on a coarse level. Possibly, such hemi-imagery de®cits require lesions
upstream area 17 (Goldenberg, 1993).
and motor impairments as well as other associated deficits
(see Table 2). This often creates a diagnostic
dilemma in the clinical examination of these patients
since it may be dicult to decide whether a patient has
for instance hemianopia or neglect or both. Examinations
with evoked potentials and magnetic stimulation
of the motor cortex may be used to test the integrity
of the peripheral sensorimotor pathways up to their
primary cortical representation (Table 2).
The frequent co-occurrence of associated disorders is
explained by the characteristically large lesions of
neglect patients which cause damage to many adjacent
structures such as the optic radiation, the pyramidal
tract, temporal, occipital, frontal and other cortical or
subcortical areas. Nevertheless, well-examined single
cases demonstrate that neglect is not caused by such
associated de®cits, although it is almost certainly
aggravated by their presence. Despite the phenomenological
similarity of both types of de®cit (i.e. in the
sense of a hemivisual de®cit) there is a fundamental
di€erence between the two disorders, illustrated in
Fig. 5.
To summarize, the hemianopic patient without
neglect has a largely intact, abstract spatial representation
of both hemispaces (left, right) 2 including his
Fig. 6. Schematic demonstration of subdivisions in subjective space.
Body-space, ultranear space, reaching (or peripersonal) space, far (or
extrapersonal) space and imagined (or representational) space are
distinguished. While these di€erent space sectors Ð with the exception
of imagined space Ð are folded like layers around the subject
imagined space is represented in a more abstract fashion and is
therefore drawn apart from the subject. These subdivisions of space
do not relate only to (frequently investigated) sensory events or
actions in the front of a subject (Front space) but also to auditory
and tactile stimuli occurring from behind the subject (Back space),
which have only rarely been investigated in neglect patients so far.
In imagined (or representational) space a neglect patient may omit
the church on the left when recalling the scene depicted in the left
lower part of the ®gure when viewed from perspective B. However,
when describing the same scene from perspective A (1808 rotated,
looking towards B) the patient may now omit the long building situated
now on his/her left side, which was previously on his/her right
side. Approximate distance in meter (m).

10
G. Kerkho€ / Progress in Neurobiology 63 (2001) 1±27
own body, while the neglect patient without hemianopia
may have an intact peripheral visual system apparently
sucient to perceive his environment and own
body Ð but fails because this sensory information is
compromised at a higher level of space representation.
The same reasoning holds true for the somatosensory,
auditory or olfactory modality.
9. Subdivisions of space and di€erent frames of
reference
9.1. Behavioral dissociations in di€erent sectors of space
in neglect
We subjectively experience our surrounding space as
well as our body in space as a single and coherent multisensory
unit, including imagined space and back
space as well. Far extrapersonal space, peripersonal or
reaching space, near and ultranear space (personal
space), as well as imagined (or representational) spaces
are usually distinguished (see Fig. 6).
Why are these distinctions? First, there is a behavioral
evidence from neglect patients and those with
other spatial disorders that these di€erent space systems
may partially dissociate. Second, there is an
increasing physiological evidence indicating that di€erent
brain areas code di€erent aspects of space (see Section
9.2). The behavioral dissocations in-patients have
been interpreted in terms of this distributed coding of
space in our brain.
Neglect may occur selectively in near space (Halligan
and Marshall, 1991a; Mennemeier et al., 1992) or
be more severe in far space (Cowey et al., 1994). Such
dissociations are rare (Guariglia and Antonucci, 1992)
and often task-dependent (Keller et al., 1999), and in
most patients neglect occurs in near and far space (Pizzamiglio
et al., 1989). Nevertheless, such dissociations
show that there is probably not one single all-purpose
space map in our brain Ð as suggested by introspection.
Furthermore, these space maps are probably
dynamically calibrated, for instance by tool use (Berti
and Frassinetti, 2000), so that far space may be
remapped into near space when we reach targets with
a stick in far space. Similarly, it is very likely that
di€erent sensory space maps interact with each other
in creating a uni®ed space map (Knudsen and Brainard,
1995). In a recent study concerning the in¯uence
of vision on auditory space, we found a rapid recalibration
of auditory space in neglect patients by a few
minutes of visual motion stimulation (Kerkho€ et al.,
2000). This suggests plasticity and continuous reorganization
of space maps by sensory or motor experience,
particularly in neglect patients. Apart from the
dissociations in external space, neglect may occur
solely in the representation of space (Guariglia et al.,
1993; Beschin et al., 1997) while sparing external
space.
9.2. Neurophysiologic and functional imaging evidence
for di€erent types of space coding in the brain
There are several distinct space maps coding di€erent
sectors of space (Graziano and Gross, 1995; Olson
and Gettner, 1995; Rizzolatti et al., 1997; Colby,
1998). Many areas participating in space representation
are motor areas (Rizzolatti et al., 1997) located
in frontoparietal cortex. One important area is located
in the ventral premotor cortex; neurons in this area
discharge when the arm or head of the animal moves.
Many cells are bimodal, thus responding to visual
and/or tactile stimulation within a particular body or
space sector around the animal. Although these cells
are chie¯y activated through moving stimuli it has
recently been shown (Graziano et al., 1997) that such
neurons can also tonically signal the presence of an
object in darkness following its silent removal so as to
deceive the monkey that it is still present. This indicates
that a spatial representation can be generated or
held in memory by the monkey on the basis of previous
experience Ð just as when we recall where we
positioned the alarm clock beneath our bed.
Another type of oculocentric space representation
has been shown in another cortical area, the monkey's
ventral intraparietal cortex (VIP; Colby, 1998). The
bimodal cells in this area seem to code ``ultranear''
space since they react to cutaneous and/or visual stimuli
in a particular sector of the animal's body, principally
around the mouth and extending up to 30 cm
into surrounding space (Colby and Duhamel, 1996).
Two types of neurons were found in this area. First,
bimodal neurons, that signaled the presence of stimuli
very close (ultranear) to the animal. The second type
were trajectory neurons, which responded to movements
of stimuli Ð apparently coding the point where
a stimulus might contact the animal's body (Colby,
1998). Trimodal cells coding near space have been
found in the ventral premotor cortex reacting to tactile,
visual and auditory stimuli in front space, and in
part also to auditory and tactile stimuli presented
behind the monkey's head (Graziano et al., 1999). This
study shows that there is a physiological correlate of
sensory space behind the head for cutaneous or acoustic
stimuli. Cells in the monkey's supplementary eye
®eld seem to code space in yet another, more abstract
spatial manner (Olson and Gettner, 1995). These cells
react to stimuli around an object irrespective of the
position of that object in space Ð exactly as in the
case of object-centered neglect of a word-part (Hillis
and Caramazza, 1991).
Imaging investigations support the physiological
results summarized above. Fink et al. (1997) investi-

G. Kerkho€ / Progress in Neurobiology 63 (2001) 1±27 11
gated object-based and space-based perceptual judgments
in normal subjects with PET. They found partially
overlapping, in addition to diverging neural
activations in the medial parieto-occipital cortex indicating
separable representations of objects versus the
space between objects. These results were largely replicated
in another study (Honda et al., 1999) showing
that object-based spatial judgments activates ventral
stream areas bilaterally. In addition, they found that
the coupling of object-centered coding with a motor
response by the subject resulted in rightsided posterior
parietal and bilateral frontal activations (ventral premotor,
dorsolateral prefrontal and anterior supplementary
motor areas, Honda et al., 1999). In yet another
imaging study (Galati et al., 2000), it was showed that
egocentric and allocentric coding of space in humans is
represented in partially overlapping, but also diverging
anatomical regions. While egocentric space coding activated
a large fronto-parietal network with greater activations
in the right hemisphere, a small fronto-parietal
subset of the activated areas was activated during an
allocentric space task. This ®nding explains why egoand
allo-centric signs of neglect often coexist (due to
overlapping neural circuits), and secondly, why egocentric
signs of neglect are more frequently entailed
than object-centered signs (due to the larger network
for egocentric space coding).
In summary, there is a growing evidence that there
are numerous representations of space and objects in
space in our brain. How exactly these di€erent space
maps are integrated and coordinated remains to be
established. However, some details concerning the merging
of sensory space are already known. Bimodal and
trimodal neurons are likely to participate in ``binding''
di€erent sensory space maps together. Furthermore,
subcortical structures (superior colliculus, SC; Meredith
and Stein, 1985, 1986a, 1986b; Stein et al., 1988;
Knudsen and Brainard, 1995), the pulvinar nuclei
(Grieve et al., 2000) and cortical areas (anterior ectosylvian
cortex of the cat; Stein et al., 1988; Wallace et
al., 1992; Wilkinson et al., 1996, the likely homologue
of the temporo-parietal cortex in humans), are
involved in intersensory integration. Furthermore, parietal
cortex (Lateral intraparietal cortex, cf. Batista et
al., 1999) serves as a sensorimotor interface for visually
guided reaching movements. Thus, various cerebral
structures are involved in creating a uni®ed space map
Ð similar to our introspective feeling of a unitary
sense of space.
10. Extinction versus neglect
In contrast to neglect, extinction is de®ned as the inability
to process or attend to the more contralesionally
located stimulus when two stimuli are
simultaneously presented, or when two actions have to
be performed with both hands simultaneously (see
Table 3). By de®nition, the processing of a single
stimulus or action should be intact or only marginally
impaired because otherwise an elementary sensory or
motor de®cit should be suspected. In that case, sensory
extinction may nevertheless be examined with uni- and
bi-lateral stimulation in the intact visual hemi®eld or
body side (cf. Rapcsak et al., 1987; Ladavas et al.,
1990).
Hence in contrast to extinction, neglect can readily
be observed when only one stimulus (i.e. a laser spot;
Karnath, 1994) or no external stimulus at all is present,
i.e. when describing a scene from memory
(Bisiach and Luzzatti, 1978) or when searching for a
nonexistent visual target in complete darkness (Hornak,
1992). Apart from the inherent di€erences
between neglect and extinction, their distinction is
further strengthened by the di€erential lesion sites associated
with them. Patients with sensory extinction
often have subcortical (basal ganglia) lesions (Vallar et
al., 1994), whereas neglect patients most frequently
have parietal lesions (see Section 2). This distinction
may be less clear in light of the recent report by Smania
and colleagues (Smania et al., 1998) who described
visual extinction in four patients with lesion of the anterior
parietal lobe (BA 1,2,3) which extended posteriorly
(BA 39, 40). De Renzi et al. (1984) reported
patients with auditory extinction whose de®cits were
dissociable from both visual extinction and as well
from severe visual neglect. Their patients with persistent
auditory extinction had neither subcortical nor
Table 3
De®nition and description of extinction phenomena occurring after unilateral brain lesions in humans
General de®nition
Sensory extinction
Crossmodal extinction
Motor extinction
Inability to perceive two sensory stimuli when presented simultaneously at di€erent locations (one
contralesionally, one more ipsilesionally located). By de®nition, single, unilaterally presented stimuli in the
contra- and ipsilesional location should in most trials be perceived correctly in order to rule out an elementary
sensory defect.
When two visual, auditory or tactile stimuli are presented simultaneously the patient frequently does not report
(``extinguishes'') the more contralesional stimulus.
The more contralesional stimulus of two stimuli presented in di€erent modalities is extinguished (i.e. a visual
stimulus on the left and a tactile stimulus on the right side).
When bimanual actions are required the patient frequently ``forgets'' to use the contralesional hand/arm.

12
G. Kerkho€ / Progress in Neurobiology 63 (2001) 1±27
parietal lesions but had sustained largely superior-temporal
lesions which involved the auditory pathways.
Since extinction may occur with diverse lesion sites
Ð just as neglect Ð the search for di€erential mechanisms
might be more rewarding. Exactly such a criterion
for di€erentiation was recently reported by Smania et
al. (1998) in reaction-time experiments for visual stimuli
delivered in contra- and ip-silesional hemispace (see
Fig. 7).
This study shows that neglect patients when
responding to a single visual stimulus have a gradient
of reaction time increase in the contralesional hemispace
and a paradoxical reaction time decrease in the
ipsilesional hemispace around 108 eccentricity. In contrast,
extinction patients and the normal control subjects
respond more slowly to more eccentric, compared
with more central visual targets. A similar reactiontime
advantage for the more ipsilesional stimulus over
Fig. 7. Contrasting results in a visual reaction-time task in patients
with spatial neglect versus extinction (redrawn after results from
(Smania et al., 1998). Note the progressive speeding up of reaction
times (lower ®gure) and increase of correct detections (upper ®gure)
of a stimulus in ipsilesional hemispace of patients with left neglect
while patients with leftsided extinction do not show this pattern in
their ipsilesional hemi®eld.The arrow in the upper ®gure indicates
the paradoxical speeding of reaction times in the more peripheral
208-position as contrasted to the 108- position in the ipsilesional ®eld
in the neglect group. Note that neither the extinction patients nor
the normal controls subjects show this pattern. Instead their reaction
times are progressively slower for more eccentric visual targets.
the more contralesional one has been reported by
Ladavas et al. (1990).
Visual extinction can be reduced by using stimuli
that are perceptually ``grouped'' (Ward et al., 1994)
into a coherent ``Gestalt'' or when the two stimuli
show the same, (e.g. horizontal) orientation and
appeared in a paracentral area of 2 88 in the visual
®eld (Pavlovskaya et al., 1997). The bene®cial e€ect of
co-oriented stimuli on visual extinction seems to only
hold true for the central visual ®eld (Pavlovskaya et
al., 1997). This may be explained by the known longrange
horizontal interactions in visual cortex which
evidently may remain intact in patients with extinction.
In a unique single-case study, Mattingley et al. (1997a,
1997b) showed that extinction no longer occurred
when two visual stimuli form one perceptual object.
The authors concluded from this that preattentive
mechanisms occurring presumably in ``early'' visual
cortical processing stages are intact in visual extinction.
Tactile extinction is usually tested with light touches
on the back of the patient's left and right hand
(Bender, 1952, 1977), or more quantitatively with same
or di€erent tactual surfaces delivered to either or both
hands (Schwartz et al., 1977) and the patient has to
identify both tactile surfaces beyond the mere detection
of a touch (Schwartz et al., 1977). In some cases, tactile
extinction may be so severe that real objects held
in the contralesional hand are extinguished when
another object is held in the ipsilesional hand simultaneously
(Berti et al., 1999). However, general testing
is accomplished when the hands are placed adjacent to
each other (left hand left of body midline, right hand
right of body midline). Crossing the position of the
hands, so that the left hand is positioned in right hemispace
and vice versa, signi®cantly reduces the tactile
extinction rate on the contralesional left hand signi®cantly
(apparently 30%, cf. Smania and Aglioti, 1995).
This indicates Ð as in egocentric neglect phenomena
Ð a modulating in¯uence of hand position in relation
to the midline of the body or head. Moscovitch and
Behrmann (1994) investigated tactile extinction with
touches on the patients' left and right wrist. They
reported that tactile extinction always occurred for the
more contralesional, leftsided stimulus, independent of
whether the hand was placed palm up or palm down.
This indicates that spatial information in the somatosensory
system is not coded in somatotopic coordinates
but in a more abstract, body-centric frame of
reference. Remy et al. (1999) found in a PET-study
that tactile extinction is associated with reduced activity
in the secondary somatosensory cortex, but not
in the primary somatosensory cortex, suggesting that
processing of bilateral tactile stimuli requires a
``higher'' stage in somotosensory processing.
Apart from unimodal extinction, crossmodal extinc-

G. Kerkho€ / Progress in Neurobiology 63 (2001) 1±27 13
tion may also occur. Mattingley et al. (1997b) showed
in three patients that stimuli in di€erent modalities
(i.e. touch and vision) may extinguish each other. Likewise
crossmodal extinction of visual and tactile stimuli
near the face region was recently shown (LaÁ davas et
al., 1998) indicating an integrated visuo-cutaneous
space map around the subject's head (see Section 9.2).
Finally, motor extinction has been reported when a
patient has to act with both hands simultaneously
(Robertson and North, 1994).
To summarize, extinction phenomena are nearly as
diverse and dissociable as neglect phenomena. They
may occur in any modality, dissociate from each other
and from neglect as well although they may often
occur in conjunction, possibly due to damage of overlapping
neural circuits. They are modulated in part by
similar spatial principles as neglect (i.e. egocentric
manipulations). As neglect, extinction phenomena are
strongly modulated by attentional and expectational
factors, as well as fatigue (Bender and Teuber, 1946;
De Renzi et al., 1984).
11. Covert processing of information
Since the neglect of sensory stimuli in neglect
patients is not per se caused by an elementary de®cit
(see Section 8), it is most likely that the patients have
seen, heard or felt the stimuli but deny their presence.
This leads one to question on which level of processing
the contralesional de®cit arises, or up to which level
the incoming information concerning the neglected
stimulus is still preserved, albeit partially. Volpe et al.
(1979) examined four patients with right parietal
lesions and visual extinction. During unilateral tachistoscopic
presentation of drawings or words, all performed
nearly perfectly in both hemi®elds. However,
during bilateral stimulus presentation two failed to
identify any stimulus in the left contralesional hemi-
®eld, while the other two correctly identi®ed 23% and
46% of items. In contrast to their inability to identify
the leftsided stimulus explicitly, all four patients were
able to decide if both stimuli presented in bilateral
stimulation were identical or not. Though two patients
claimed that they did not perceive anything in the contralesional
hemi®eld, and that the task was senseless
for them they performed correctly (88%, 100%) when
forced to guess if both stimuli were identical or not. In
a subsequent investigation (Berti and Rizzolatti, 1992),
this ®nding was replicated and extended showing that
extinction patients were also able to decide if both
stimuli belonged to the same category of objects (i.e.
fruits, animals).
In another type of experiment Marshall and Halligan
(1988) showed drawings of two houses to a neglect
patient. The houses were arranged vertically over each
other and were identical except that ®re emerged from
the left side of one house. Their patient indicated that
both houses were identical, thus ignoring the ®re on
the left, but when asked in which house she preferred
to live she always chose the house without ¯ames.
Bisiach and Rusconi (1990) replicated these results
only partially in four neglect patients; two preferred
the house with the ¯ames on the left side, thus indicating
no covert processing.
Residual, but unconscious processing of somatosensory
information in tactile extinction has also been
reported as well (Maravita, 1997). In another study
(Peru et al., 1997) covert processing was investigated
with chimeric stimuli. Chimerics are ®gures constructed
of two halves that normally do not belong
together (i.e. left half of a cow combined with the right
half of a horse). The two halves were either semantically
(same category) or perceptually (similar form) related
to each other or were completely incompatible to
each other. Interestingly, the number of leftsided
extinction errors was minimal when the perceptual discrepancy
between the chimerics was maximal. Thus,
perceptual con¯icts (based on object shape) were more
e€ective in reducing the extinction errors than semantic
con¯icts (Peru et al., 1997). Electrophysiological
evidence shows that nonextinguished visual stimuli in
the contralateral visual ®eld (during bilateral stimulation)
are associated with activations of the P1 and
N1 components which were absent during extinguished
trials (Marzi et al., 2000).
Together, these results indicate that visual and tactile
information may be well represented at a preattentive
level (Peru et al., 1997) and sometimes even up to
a categorical (Berti and Rizzolatti, 1992) or semantic
(McGlinchey-Berroth et al., 1993) level of stimulus
processing in neglect and extinction. Nevertheless, it
seems unlikely that every patient shows this type of
intact, covert processing. Feinberg and colleagues
(Feinberg et al., 1994) also found confabulations
regarding the identity of stimuli ¯ashed in their contralesional
hemi®eld which were in no way related to
the shown target. These interesting studies show that
covert or unconscious processing of visual information
is not only found in hemianopic patients with hindsight
following occipital lesions (Stoerig and Cowey,
1997) but also to an even higher level of processing in
parietal neglect and extinction (see Driver and Mattingley,
1998 for review).
12. Unawareness of de®cits
Unawareness of disease (also termed anosognosia) is
frequent in cerebral diseases (McGlynn and Schacter,
1997) but in no way exclusively coupled with neglect,
since it occurs also with Wernicke's aphasia (Lebrun,

14
G. Kerkho€ / Progress in Neurobiology 63 (2001) 1±27
1987), severe amnesia, dysexecutive (problem-solving)
de®cits after frontal lobe lesions (McGlynn and Schacter,
1990), or psychiatric disease (McGlynn and Schacter,
1997). Historically, unawareness for hemiplegia
(Babinski, 1914) and cerebral blindness (Redlich and
Dorsey, 1945) was described several decades ago. Since
both types of unawareness are frequent in neglect
(Bisiach et al., 1986) unawareness of hemiplegia and/or
hemianopia is viewed as a frequently associated, but
dissociable disorder (Feinberg et al., 1994) in neglect.
In the acute phase of neglect, the patient is mostly
unaware of his de®cits and their cause, and can not
imagine further consequences. This is in contrast to
patients with elementary hemisensory de®cits, i.e. leftsided,
homonymous hemianopia without neglect, who
often show awareness of their impairments and can
therefore describe them in detail (see Table 4 for two
contrasting case examples).
Table 4
Case examples of a patient with leftsided, homonymous hemianopia
(HH ), without neglect, and a patient with leftsided neglect (N ), without
hemianopia. E: Examiner. Both patients had objective de®cits in
reading (omissions on the left side of the text; slowness of reading,
omissions of single lines) as well as in visual exploration of the environment
(causing bumping into objects on their left side, or failing
to perceive them in time). Based on Kerkho€ (1999c)
Anamnesis with a left hemianopic patient without neglect
E: Did you experience any signi®cant changes in vision since your
illness (brain infarction)?
HH: Yes, I have problems perceiving things on my left; and reading
is a problem.
E: Why is reading a problem?
HH: It is slower than before my illness and more exhausting.
Sometimes I omit words on my very left.... or I omit a whole line. I
only realize it at the end of a sentence when it doesn't make sense...
E: Do you have any other visual impairments?
HH: Yes, sometimes I bump into things or persons on my left, or
detect them rather late... E: What about your orientation outside the
clinic, can you ®nd your way?
HH: It's dicult, especially when many people are around, on
places... or when I have to ®nd one particular thing, i.e. in a
supermarket,... when it is on the left..
Anamnesis with a left hemineglect patient without hemianopia
E: Did you experience any signi®cant changes since your illness
(brain infarction)?
N: No, I haven't realized any changes. Except... the spectacles don't
®t.
E: Do you have problems with reading?
N: No, not really.
E: Do you omit words or syllables on your left side?
N: No, I don't think so.
E: Have you noticed that your vision is impaired on your left side?
N: The left eye is ®ne, no problem.
E: Do you bump sometimes into things or persons walking on your
left side?
N: Rarely! Well, sometimes it occurs, but that is because there are so
many people in this hospital, and they don't care...
E: Can you ®nd your way inside the clinic, and outside?
N: I ®nd everything that I want to ®nd.
As in neglect, multiple dissociations can also occur
in (un)awareness for certain de®cits. Hence, a patient
may deny the paresis of her left arm but acknowledge
reading problems or cognitive problems. Likewise,
unawareness for hemiplegia is dissociable from neglect
for the left side of the body (personal neglect, cf.
Adair et al., 1995).
Recent analyses of the behavior and lesions in
patients with unawareness of hemiplegia (Ellis and
Small, 1997) revealed that it is dissociable from visuospatial
neglect, and that most patients (87%) show deep
white matter or basal ganglia lesions. Although transient
unawareness for hemianopia is found in the ®rst
week after various lesion sites in pure hemianopia
(Celesia et al., 1997) more chronic unawareness of ®eld
defects is most often found after right parietal lesions
(Koehler et al., 1986). In contrast to many neglect
patients, hemianopic patients with temporal or occipital
lesions (and thus probably without neglect) rapidly
gain insight into their visual problems in daily life and
learn from their daily experience (i.e. omissions in
reading, bumping into objects, Kerkho€, 1999b).
To summarize, unawareness of the disorder is frequently
associated with, but not causally linked to,
neglect and extinction, and is caused by separable
white matter lesions (for hemiplegia) and parietal
lesions (for hemianopia). It is likely that other types of
unawareness (i.e. for visuospatial disorders like the
tilted visual vertical and horizontal in Fig. 2C) are associated
with slightly di€erent lesion sites. This would
suggest a distributed, patchwork-like cerebral network
for awareness and consciousness of de®cits in sensory,
motor, cognitive or emotional areas (see McGlynn and
Schacter, 1997). Focal lesions to this distributed network
would then lead to a variety of distinct and dissociable
phenomena of unawareness. Milner (1995) has
suggested that elaborate awareness may require the
ventral stream and its connections to memory structures
while the dorsal visual stream is more engaged in
unconscious, rapid visuomotor behavior.
13. Models
13.1. Early sensory theories
Early models of neglect and extinction have stressed
the importance of low-level sensory impairments as
well as a generalized deterioration of cognitive and
intellectual functions (Bender, 1952; Battersby et al.,
1956). Although such disorders certainly have an
aggravating e€ect they cannot be the core de®cit since
both neglect and extinction occur without elementary
sensorimotor impairments (cf. Section 8). Current
models can be grouped in four main categories: atten-

G. Kerkho€ / Progress in Neurobiology 63 (2001) 1±27 15
tional, representational, transformational, and cerebral
balance theories (cf. Table 5).
13.2. Attentional theories
According to the orienting vector model, proposed
by Kinsbourne (Kinsbourne, 1987, 1993), both hemispheres
contain a kind of orienting vector that directs
attention to the contralateral hemispace. These orienting
tendencies are not only active in the exploration of
external space but also of internal spatial representations
(Kinsbourne, 1993). Lesion to this putative vector
in the right hemisphere therefore leads to a
hypoexploration of the left hemispace and a hyperattention
for stimuli located in the ipsilesional, right
hemispace due to the intact attentional vector in the
healthy left hemisphere which operates in right hemispace.
According to this theory, every unilateral hemispheric
lesion should produce contralateral neglect Ð
which obviously is not the case (see Section 2).
Another critical point of the theory is that it fails to
explain why there is this striking hemispheric asymmetry
in the frequency and severity of spatial hemineglect.
This would require the assumption of a stronger
right-hemispheric attentional vector and a weaker lefthemisphere
vector.
This is exactly what two other theories of neglect by
Heilman and coworkers (1995) and Mesulam (1998)
have proposed. Heilman and Van Den Abell (1980)
proposed some 20 years ago that the right hemisphere
might be dominant for attention in both hemispaces
while the left is only specialized for the right hemispace.
Mesulam later restated this idea in anatomical
terms. His theory states that the right hemisphere contains
a neural network for directed visuo- or tactilespatial
attention which is specialized for both the left
and right hemispace, while the comparable system in
the left hemisphere subserves only the right hemispace.
The neural network includes the lateral premotor cortex
(frontal eye ®elds), posterior parietal cortex, cingulate
cortex and subcortically the basal ganglia and
thalamus (Mesulam, 1998). While the more anterior
areas in each hemisphere are relevant for shifting the
focus and guiding exploration posterior areas in the
parietal cortex deal with visual salience of stimuli in
external space (see Fig. 8A). Lesions to the right hemisphere
would produce left neglect while left hemisphere
lesions lead only rarely to contralesional neglect since
the stronger right-hemispheric attentional system may
compensate for the de®cit as a result of its bilateral
attentional focus. This model is supported by imaging
studies for tactile-spatial (Gitelman et al., 1996) and
visuospatial attention (Nobre et al., 1997; Gitelman et
al., 1999) in healthy subjects. In both studies, a stronger
right parietal activation was found in most but not
all subjects that would neatly explain how right neglect
may occur sometimes after leftsided lesions, but is
nevertheless rare. Furthermore, the di€erent stations of
Table 5
Summary of current neglect theories (see text for further details)
Attentional theories: Neglect is viewed as
An exaggeration of the orienting of attention towards the ipsilesional side (ipsilesional hyperattention, Kinsbourne (1987).
A de®cit in disengaging attention from an ipsilesional focus towards a new stimulus on the contralesional side (Posner and Driver, 1992).
As a result of damage to a neuronal network preferentially elaborated in the right hemisphere for the directing of attention towards the ipsiand
contralesional hemispace (Heilman and Van Den Abell 1980; Nobre et al., 1997).
The result of damage to a visual salience map located predominantly in the human right hemisphere (Anderson, 1996).
Representational theories
Perception of sensory events requires their mental representation. Neglect results from an impairment in the representation of the contralesional
space and body (Bisiach and Luzzatti 1978; Bisiach et al., 1981).
Each hemisphere contains a topographically organized memory map of the contralateral visual world (Ga€an and Hornak, 1997), which is
disrupted in neglect.
Di€erent parts of extrapersonal and body space are motorically coded or represented by di€erent neural structures. A lesion of these
structures causes contralesional neglect (Rizzolatti et al., 1997).
Transformational theories
Acting in space requires a transformation of the various sensory input informations from sensory (visual, auditory, tactile, olfactory) into
motor coordinates which operate in body-part-centered coordinates (eye-,hand-, arm-, head-centered, Vallar, 1997; Karnath, 1997; Colby,
1998). This coordinate transformation is thought to be impaired in neglect.
Cerebral balance theories
Neglect studies in cats indicate that is not the absolute level of neural activity within each cerebral hemisphere that determines neglect but the
relative (in)balance between cortical and subcortical structures in the lesioned and intact hemisphere (Lomber and Payne, 1996; Payne et al.,
1996). Complex, excitatory and inbibitory interactions occur on a cortical and subcortial level between the lesioned and the nonlesioned
hemisphere, probably via callosal ®bres (Payne et al., 1991).
Dorsal versus ventral contributions to neglect
Without intending to o€er a complete model of neglect it is suggested (Milner, 1995, 1998) that neglect results from a dysfunction of the
ventral stream while visuomotor functions are thought to be largely spared because of the integrity of the visuomotor functions in the dorsal
stream.

16
G. Kerkho€ / Progress in Neurobiology 63 (2001) 1±27
the neural network would explain why neglect occurs
after lesions to structures as divergent as the thalamus,
basal ganglia, the dorsolateral frontal lobe and posterior
parietal cortex.
Posner and Driver (1992) have argued that the disengagement
of attention from a current ipsilesional
focus to a contralesional stimulus is the core de®cit in
neglect patients. In support of their ``spotlight-ofattention''
theory, it was found that patients with superior
parietal lesions show such disengagement de®cits
and that valid cueing of their attention towards a
target appearing later in the contralesional hemispace
reduced this de®cit signi®cantly (Posner et al., 1984).
Similarly, Baynes et al. (1986) found that both left and
right hemisphere lesions cause a slowing of reaction
several times but only right parietal lesions cause a
selective de®cit in the orienting of attention towards
the contralesional left hemispace. In support of this
theory, Steinmetz and colleagues (1994; Steinmetz,
1998) found that parietal neurons of macaques are
engaged in covert attentional shifts towards the contralateral
hemispace.
While Posner's theory could explain why neglect
patients have diculties in directing their attention
to left hemispace, it would probably not explain
why they search preferentially in their ipsilesional
hemispace in total darkness and in the absence of
sensory stimuli (cf. Hornak, 1992; Karnath et al.,
1996), or why the visual or auditory SSA is ipsilesionally
deviated in neglect.
Recently, an elaborated mathematical model of
neglect has been proposed by Anderson (1996) which
makes rather explicit assumptions about the strength
and spatial distribution of the left- and right-hemispheric
hypothesized attentional vectors (see Fig. 8B).
The model assumes a weaker and more contralaterally
(around 10±208 eccentricity towards the right side)
shifted salience function of the healthy left hemisphere
and a stronger salience function operating in both
hemi®elds Ð similar to the model of Heilman and
Watson (1995), and Mesulam (1998). Furthermore,
Anderson's model assumes that the salience functions
of the two hemispheres add (cf. Fig. 8B, lower plot).
Disruption of the stronger right hemisphere salience
function would lead to left neglect while damage to
the left hemisphere salience system would be compensated
by the bilaterally operating right hemisphere system.
Simulations of this model can e€ectively explain
the typical line bisection e€ects (Burnett-Stuart et al.,
Fig. 8. Schematic illustration of the neglect model by Mesulam (A) and the salience model by (Anderson (B). (A) The circles represent visual targets
in the left and right hemispace, the arrows attached to the circles represent the attentional vectors (short arrows: left-hemisphere vectors;
large arrows: right hemisphere attentional vectors). Below the ®gure, the two hemispheres of a brain are drawn schematically. Anterior areas are
thought to be responsible for active exploration and shifting of the attentional focus, while posterior areas contain a salience map for visual targets
in the two hemispaces. (B) The salience functions of the two cerebral hemispheres are drawn in the top ®gure (small curve: left hemisphere
salience function; large curve: right hemisphere salience function). The lower ®gure shows the combined function.

G. Kerkho€ / Progress in Neurobiology 63 (2001) 1±27 17
1991; Harvey et al., 1995; Barton et al., 1998) in leftsided
visual neglect.
13.3. Representational theories
Bisiach and colleagues formulated a model of topological
space representation (Bisiach and Luzzatti,
1978; Bisiach et al., 1981). This model assumes that
every sensory event has a representation. This mental
representation can be activated either through sensory
a€erences or by memory engrams. More particularly,
the model assumes that this topological space is not
coded veridically in neglect patients. Their left side of
representational space is enlarged whereas the right
side is constricted compared with normal subjects
(Bisiach et al., 1996). In contrast to the premotor theory
by Rizzolatti (see below), this model does not
detail where and how this topological space representation
is created. This model is compatible with the
recent evidence in patients with a unilateral temporal
lobe removal (Hornak et al., 1997) and experimentally
induced neglect in monkeys (Ga€an and Hornak,
1997; see review in Ga€an and Hornak, 1999). According
to these ®ndings, widespread cortical areas in each
cerebral hemisphere interact with each other in memory
retrieval to produce a retinotopically organized
representation of the contralateral visual world.
Lesioning of the temporal cortex Ð which is often but
probably not always included in neglect patients Ð
would then produce a hemi-amnesia for things occurring
in the contralateral hemispace. This is compatible
with Bisiach's theory. One possible problem with this
theory is the explanation of the hemispheric asymmetry
in neglect.
A more physiologically oriented theory of neglect
states that space representation is enabled by the activity
of premotor cortical structures (Rizzolatti et al.,
1997) which are linked closely to attention (Sheliga et
al., 1995). According to this view, space is motorically
coded by actions towards positions in certain space
sectors (cf. Section 9.2). A lesion to these specialized
premotor structures would then cause a neural representational
de®cit leading to neglect in a certain
space sector. Since attention and movement towards
targets in contralateral space are intricately connected,
this theory would encompass attentional and motor
neglect phenomena as well. Moreover, it is not incompatible
with the more cognitive representational
account of Bisiach, although it di€ers from the latter
in that it does not hypothesize one topological spatial
map but rather a number of decentrally organized
(Rizzolatti et al., 1983) space maps, which relate to the
di€erent motor e€ectors (Rizzolatti et al., 1997).
13.4. Transformational theories
These theories assume that the transformation of
sensory (input) information into motor (output)
action, which is necessary due to the di€erent reference
frames or `format' in which sensory and motor informations
are coded in the brain is impaired in spatial
neglect (Jeannerod and Biguer, 1987, 1989). Since such
coordinate transformations are likely to be computed
in parietal cortex (Andersen, 1995; Andersen et al.,
1997) a parietal lesion causing neglect might impair
such transformations. In a variant of this original
account both Vallar (1997) and Karnath (1997) have
proposed that this coordinate transformation seems to
work with a consistent error, i.e. the straight ahead
direction is not coded as 08 but as +158 to +208 ipsilesionally,
thus causing the observed shift in the subjective
straight ahead and the deviated visual and
tactile exploratory patterns (Fig. 2A, B). The two theories
di€er in their assumptions regarding the type of
spatial error. Vallar postulates a translation of the egocentric
midsagittal representation in relation to the
trunk midline while Karnath assumes a rotation
around the subject's body midline (see Fig. 9).
While the assumptions of both models (at least in
front space) would ®t the observed data on egocentric
de®cits in neglect, it remains unclear exactly how this
``error term'' in the coordinate transformation models
is created and on which physiological grounds it is
based. The transformational theories do not deal with
allocentric and object-centered neglect and do not
attempt to explain these phenomena in their framework.
Fig. 9. Schematic demonstration of translation of the auditory subjective
straight ahead (SSA, left ®gure) and rotation of the auditory
SSA (right ®gure) in leftsided neglect. The translational results
(redrawn based on data by Vallar et al., 1995a) indicate a similar
shift of the SSA in front and back space towards the right, ipsilesional
side by 15±208. In contrast, the rotational hypothesis is based
on a rightsided shift of the SSA in front space and a corresponding
leftward shift of the SSA in back space. Note that these results are
not due to peripheral hearing de®cits since pure tone audiometry
reveals normal peripheral hearing functions in these patients.

18
G. Kerkho€ / Progress in Neurobiology 63 (2001) 1±27
13.5. Cerebral balance theories
Although some of the attentional theories in a way
imply an imbalance of psychological attentional mechanisms
in the two hemispheres in neglect, there are
more direct experiments and theories favoring this
account on a physiological level. Sprague (1966)
showed, in a pioneering experiment in cats, that hemianopia
caused by a cortical lesion can be improved by
ablating the SC on the opposite side to the cortical
damage or by cutting the intertectal commissure. In an
extension of this experimental philosophy, Payne,
Lomber and coworkers (Lomber and Payne, 1996;
Payne et al., 1996) by reversible deactivation studies
through local cooling of the posterior middle-suprasylvian
cortex (PmS) or SC postulated that there are
dynamic interactions in spatial attention based on the
level of neural activity in these structures of both
hemispheres. As reported earlier with unilateral SC
lesions (Sprague, 1966) and small unilateral perisylvian
lesions in cats (Hardy and Stein, 1988), cooling of
these same structures causes a profound visual hemineglect
of the contracooled hemispace (Payne et al.,
1996). Subsequent cooling of the homologue area in
the other hemisphere completely abolished the neglect
behavior, or created now a neglect contralateral to the
second cooled hemisphere if the cooling temperature
was slightly lower than that in the originally cooled
hemisphere (Geraerts and Vandenbussche, 1999).
Together these results indicate that the PmS in cats
Ð like the SC Ð is engaged in directing visuospatial
attention to the contralesional hemispace. More importantly
for human neglect models, it is not the absolute
level of activity within a cortico-subcortical spatialattentional
network but the ratio of neural activity in
these structures within cerebral structures of one hemisphere
and between the two hemispheres. This cerebral
(in)balance theory has implications for our thinking of
neglect and for the development of treatment techniques.
Although cooling of the healthy hemisphere in
a patient with left neglect from a right parietal lesion
is of course impossible for ethical reasons alternative
methods might be developed to either strengthen the
lesioned hemisphere or weaken the healthy hemisphere
by speci®c sensory stimulation maneuvers. For
instance, stimulating the right hemisphere via leftsided
somatosensory magnetic stimulation might increase
neural activity in the lesioned hemisphere. Transcranial
magnetic stimulation of the parietal cortex in the
healthy hemisphere would lead to a transient decrease
of activity in this hemisphere and might consequently
reduce leftsided neglect by changing the cerebral
(in)balance. Moreover, optokinetic stimulation of one
visual hemi®eld might speci®cally activate cortical and/
or subcortical structures in the contralateral hemisphere
(Pizzamiglio et al., 1990; Brandt et al., 1998;
Fig. 10. E€ects of sensory stimulation on di€erent neglect phenomena.
(A) Line cancellation performance before (baseline), immediately
after caloric (ice-water) stimulation of the contralesional
horizontal ear canal, and 5 min after stimulation. Note the signi®cant
reduction of omissions (uncrossed lines) in the left part of the
display during stimulation (after Rubens, 1985). (B) E€ect of linear
visual background motion during a horizontal, visual size judgment
test in neglect. When the background stimuli are stationary (no
motion) the left bar is reproduced too large as compared to the right
bar on the screen. Left motion alleviates this size distortion while
rightsided background motion (velocity: 7.58/s) produces similar
e€ects as no motion (based on Kerkho€, 2000; Kerkho€ et al.,
1999c). (C) Cueing of attention to the left, contralesional side. Having
the patient identify the letter on the left of the bisection line (z)
prior to bisection reduces the ipsilesional deviation in line bisection
(cf. Riddoch and Humphreys, 1983). Display of apparent movement
of a light at the contralesional end of the line (squares with arrows)
has a similar bene®cial e€ect on line bisection, even if this phi-movement
is not consciously perceived due to an additional leftsided ®eld
defect (cf. Butter et al., 1990). (D) E€ect of head orientation (circle,
black triangle indicating nose, and thus head direction) and trunk rotation
to the left (L, 208 rotation) on line bisection judgments. Leftward
head orientation (with the trunk straight ahead) and leftward
trunk orientation (with the head straight ahead) both lead to a normalization
of the line bisection error (cf. Schindler and Kerkho€,
1997; Fujii et al., 1996). E€ect of vibrating the left posterior neck
muscles in leftsided visual neglect leads to an ocular exploration pattern
in total darkness that is organized more symmetrically around
the body midline (very right plot). Note, in contrast, the ipsilesionally
(to the right) deviated exploration pattern in the condition without
vibration (cf. Karnath et al., 1996). (E) E€ects of head-on-trunkrotation
(circles, black arrows indicating head orientation) and visual
background motion displayed on a computer screen while neglect
patients read a text displayed on the same screen. The shaded area
indicates approximately the omitted words (= neglect dyslexia).
Note that leftsided head rotation (208, without visual background
motion) as well as left visual background motion (with the head and
trunk remaining straight) both reduce neglect dyslexia; the strongest
reduction of omissions is seen when both conditions are combined,
indicating a summation of both e€ects (cf. Kerkho€ et al., 1999b).

G. Kerkho€ / Progress in Neurobiology 63 (2001) 1±27 19
Dieterich et al., 1998) thus modulating neural activity
in a way that reduces neglect (see Section 14).
13.6. One model or a synthesis of models?
Given the multiple and dissociable phenomena of
spatial neglect and the characteristically large lesions
in neglect patients, it seems unlikely that any one
model can explain all features of neglect. Rather, every
model is able to explain some features but not other,
and vice versa. Furthermore, some theories are compatible
with each other although this point is rarely
admitted by their proponents. For instance, the shift
of the SSA and visual exploration towards the ipsilesional
hemispace by about 15±208 in left neglect is
equally well explained by the transformational theory
as well as the salience model. Likewise, the reactiontime
data by Smania et al. (1998), with the pathological
reaction-time decrease in the neglect patients
around 15±208 ipsilesionally is consistent with both
accounts. Finally, it would be possible to test the hypothesis
whether the de®cit in the disengagement of
attention (Posner et al., 1984) is modulated by egocentric
parameters, i.e. the position of the head, hand
or trunk in space, thus combining attentional and
transformational approaches. Finally, many of the sensory
stimulation experiments described below are compatible
with the idea of a cerebral (in)balance between
various neural relay stations of a network distributed
within and across both hemispheres.
To conclude, mutual in¯uences between the theories
and research paradigms in the study of neglect in particular,
and space coding in general, might be more
fruitful than strict demarcations between the various
`claims'. Finally, the recent animal work on neglect
(Lomber and Payne, 1996; Payne et al., 1996) deserves
more attention.
14. Modulation of neglect, extinction and unawareness
by sensory stimulation
A variety of di€erent techniques (see Vallar et al.,
1997, for a detailed review) has been used to in¯uence
neglect behavior (Fig. 10). Caloric (ice±water) stimulation
of the contralesional ear (usually the left) or
warm water stimulation of the ipsilesional ear (the
right in patients with left neglect) stimulates the horizontal
ear canal of the vestibular system and leads to a
tonic deviation of the eyes towards the contralesional
hemispace thereby reducing sensory neglect for some
10±15 min. This procedure also improves neglect-related
disturbances of the body scheme on the contralesional
side of the body as well (Rode et al., 1998) and
in some cases transiently relieves the patient from his/
her anosognosia for the left hemiplegia (10±15 min;
Rode et al., 1992). An easier and more tolerable stimulation
procedure is optokinetic or slow visual motion
stimulation with large-®eld visual displays containing
stimuli all moving to the left or right. Leftward motion
(in case of left neglect) temporarily reduces the linebisection
error (Pizzamiglio et al., 1990; Mattingley et
al., 1994b). Similarly slow motion stimulation towards
the neglected hemispace reduces the ``size'' and
``space'' distortions transiently (cf. Fig. 10B, Kerkho€,
2000) and temporarily reduces tactile extinction (Nico,
1999). However, negative e€ects have also been
observed with this procedure in a line-extension task
with leftward optokinetic stimulation (Bisiach et al.,
1996). It is likely that fast optokinetic stimulation
leads to constant changes in eye-position which may
render the perceptual task more dicult for a patient.
We have found that slow motion stimulation (velocity:
7.58/s) is completely sucient to observe full normalization
in perceptual neglect tasks (Kerkho€, 2000).
This further indicates that the motor component of the
optokinetic nystagmus obtained with high-speed stimulation
is not crucial for the modulatory e€ect on
neglect (Mattingley et al., 1994b).
Another simple stimulation is `cueing' the patient to
attend to stimuli in the contralesional hemispace
(Fig. 10C). Cueing may simply be the verbal command
to look further to the left or to require the patient to
read a letter located on the left side of a line before he
is allowed to attempt bisection (Riddoch and Humphreys,
1983) or to display ¯ickering stimuli in the
contralesional hemispace (Butter et al., 1990). Lin et
al. (1996) have recently elaborated this cueing paradigm.
They showed that circling of a digit at the left
end of a line and the tracing of the complete line with
the right index ®nger was the most e€ective cueing
procedure: it led to a complete normalization of the
line bisection error in left neglect.
Vibration of the contralesional neck muscles leads to
a temporary shift of the SSA towards the contralesional
hemispace (Karnath et al., 1993) and reduces
neglect-related omissions of visual stimuli in this hemispace.
A similar transient e€ect can be achieved
through selective rotation of the head (Schindler and
Kerkho€, 1997; Kerkho€ et al., 1999b) or trunk (Karnath
et al., 1991; Schindler and Kerkho€, 1997; Spinelli
and Di Russo, 1996) towards the left hemispace
while ®xation remains straight ahead (Fig. 10D, E).
Similar e€ects have been reported with di€erent body
positions (upright versus supine). The activity of the
otoliths of the vestibular system is reduced in a supine
body position. Positioning neglect patients in a supine
position reduces neglect (i.e. in line bisection; Mennemeier
et al., 1994; Pizzamiglio et al., 1997).
Apart from passive arm positioning active movements
of the contralesional, left arm in left hemispace
further leads to a temporary reduction of sensory

20
G. Kerkho€ / Progress in Neurobiology 63 (2001) 1±27
neglect phenomena (Robertson and North, 1993).
Another in¯uential factor is cueing with alerting stimuli,
i.e. a sudden beep. This leads to an immediate
alertness reaction and temporarily improves visual
neglect (Robertson, 1999). Transcutaneous electroneural
stimulation (TENS) is widely used in physiotherapy,
i.e. to treat stays or to stimulate muscles.
TENS of the left hand has a small e€ect on perceptual
neglect (Vallar et al., 1995c) but this e€ect is much
weeker than vibration of the left neck (Karnath, 1995).
Scherder et al. (1995) obtained similar bene®cial e€ects
in Alzheimer's disease suggesting that TENS probably
increases the arousal level. In contrast, Guariglia et al.
(1998) reported small, but signi®cant improvements in
representational neglect and drawing after leftsided
and deteriorations after rightsided stimulation of the
neck with TENS, thus suggesting a more speci®c
e€ect.
All these di€erent methods show that neglect is considerably
in¯uenced by sensory, attentional or gravitational
factors. This elucidates mechanisms crucial to
the genesis of neglect and might in the future help to
®nd e€ective, systematic rehabilitation techniques.
15. Rehabilitation approaches
Despite recovery of the most obvious signs of hemineglect
a considerable portion of neglect patients Ð
especially with large right-hemispheric lesions Ð is
severely impaired in functional activities of daily living
(ADL), i.e. dressing, eating, transfer from bed to the
wheelchair, wheelchair navigation or reading. Neglect
patients have a delayed recovery from hemiplegia
(Paolucci et al., 1996), postural problems (Rode et al.,
1997) and require further ambulant treatment after discharge
from the hospital (Paolucci et al., 1998). Few
neglect patients recover in a way that allows them to
live independently or even return to their premorbid
job. Neglect is therefore a major negative predictor of
recovery from brain lesions (Denes et al., 1982; Paolucci
et al. 1996; Katz et al., 1999).
Early treatment approaches for neglect, which began
in the 1970s (Diller and Weinberg, 1977), were mainly
based on clinical experience and were less theory-driven
than more recent approaches to the syndrome
(Robertson, 1999). Since disturbed visual exploration
of space is one of the most obvious de®cits in neglect
patients, this was one that received most attention in
Table 6
Summary of treatment techniques with permanent improvements (unshaded part of table) and experimental procedures yielding transient
improvements (lightly shaded part of table) in patients with hemispatial neglect
Treatment Basic therapeutic/modulating principle Practicability/outcome/transfer/source
Visual
exploration
Limb activation
Sustained
attention
Neck muscle
vibration
Spatial
perception
TENS
Prisms
Optokinetics
Vestibular
stimulation
Cueing
Improvement of search strategy and speed using paper-pencil
and wide-®eld projection devices. Reduction of critical
omissions by systematic strategy
Improvement of visual neglect by acting with the
contralesional arm (usually the left) in the contra-lesional
hemispace. Such activities are believed to activate attentional
circuits in the lesioned hemisphere
Amelioration of neglect phenomena by activating sustained,
nonlateralized attentional capacities by stimuli which have an
alerting quality (i.e. brisk tone)
Vibration of left dorsal neck muscles leads to a shift of
subjective space towards the contralesional hemispace
Easy to realize in a rehabilitation setting; Limited transfer to
daily activities; Needs numerous training sessions (i.e. 40)
(Antonucci et al., 1995; Kerkho€, 1998)
Easy to use in clinic and at home; Demonstrated transfer to
daily activities; Often not applicable due to severe
contralesional sensorimotor de®cits (arm/hand) (Robertson and
North, 1993; Robertson, 1999)
Easy to use in clinic and at home; Transfer to non-trained
activities Ð Stability of improvements questionable (Robertson
et al., 1995)
Easy to use in di€erent daily situations (i.e. self-care)); Transfer
to non-trained activities and to the tactile modality (Schindler
et al., 1999)
Feedback-related training of visuospatial de®cits in neglect;
reduction of uncertainty in space perception
Transfer to daily activities; Requires relatively few training
sessions (

G. Kerkho€ / Progress in Neurobiology 63 (2001) 1±27 21
treatment studies (Diller and Weinberg, 1977; Weinberg
et al., 1979). Later studies have implemented a
similar approach and compared the training of ecient
scanning in neglect patients with nonspeci®c cognitive
training (Antonucci et al., 1995) or combined it with
speci®c visuospatial training (Weinberg et al., 1979)
patients. Cognitive training has only minor e€ects on
neglect, while speci®c visuospatial training ameliorates
the associated spatial problems, but does not in¯uence
visual scanning. Table 6 summarizes evaluated treatment
approaches as well as stimulation techniques
with transient e€ects that might eventually become
e€ective techniques of treatment.
As in other areas of neurorehabilitation, pharmacological
treatments have been suggested for di€erent
types of disorders (Feeney and Hovda, 1985; Kertzman
et al., 1990; McDowell, 1991; MuÈ ller and von
Cramon, 1994; Huber et al., 1997). Treatment of
neglect with dopaminagonists was prompted by the
observation that experimental reduction of dopamine
unilaterally in monkeys (Apicella et al., 1991) and rats
(Carli et al., 1985) causes neglect-like de®cits in these
animals. Fleet et al. (1987) reported improved scanning
in two neglect patients following application of a
dopamine agonist. However, the opposite e€ect was
reported in a recent study (Grujic et al., 1998) Evidently
no ®rm conclusion is at present possible concerning
pharmacological stimulation in the
rehabilitation of neglect.
In contrast to the variety of stimulation and rehabilitation
procedures that are being proposed for neglect,
very little is known about how extinction can be treated.
Since it persists even when the most overt neglect
signs have recovered (Karnath, 1988) treatments of
extinction clearly would be of practical importance.
Goldman (1966) described impressive and stable
improvements in 20 brain damaged patients with tactile
extinction following a teaching strategy with the
aim to direct the patient's attention to the extinguished
side and improve his/her awareness for the contralateral
stimulus. This shows that the allocation of attention
(cueing) is also helpful in extinction. Another,
more physiologically oriented promising treatment
approach is somatosensory magnetic stimulation of the
contralesional hand. This procedure led to an increase
in the identi®cation rate in bilateral tactile stimulation
by some 40%, in one patient (Heldmann et al., 2000).
Since the testing took place some 30 min after the end
of the magnetic stimulation, this indicates that the
e€ect is not merely a short-lived ``on/o€'' stimulation
e€ect but obviously has enduring e€ects overlasting
the stimulation period. Possibly, repetitive stimulation
of this type might help to rehabilitate tactile extinction
more permanently than the short-lived sensory stimulation
maneuvers reported above.
Despite the improvements that have been made in
the last decade in the development of theory-based
treatment techniques for neglect and extinction, the
patients often remain impaired at the end of clinical
rehabilitation. This shows that the e€orts so far are
only partially e€ective. Therefore, the scienti®c development
of e€ective treatment techniques in this ®eld is
urgently required. The increasing physiological, anatomical,
neuropsychological and cognitive knowledge
concerning sensory, motor and representational aspects
of space coding in health and pathology will hopefully
help to develop such treatments for the severely disabled
patients with neglect. In exchange, the results
obtained with such new methods will in¯uence our
current thinking of normal spatial processing in the
human brain.
Table 7
Outstanding questions and topics for further research
. Neglect is often multimodal. What is the exact interplay between these di€erent modalities and which principles guide this type of multisensory
interaction and integration?
. Models of human neglect have payed little attention to recent contributions of animal experimentation in the domain of neglect. Integrating
these ®ndings will probably lead to another, novel view of the mechanisms and possible modulations of neglect.
. Auditory and somatosensory neglect are not well understood. The more sophisticated technical examination of space in these two modalities
might improve our understanding of the cortical organisation of auditory and somesthetic space.
. Are representational neglect and unilateral, scene-based memory de®cits related to each other? The study of this relationship might help to
understand how short- and long-term memory feed into spatial imagery in neglect.
. How do extinction and neglect relate to each other? Is extinction a completely di€erent disorder from neglect, or does it simply re¯ect a less
severe, residual form of it?
. Which treatment methods for the rehabilitation of neglect are e€ective? How can di€erent treatment approaches be combined e€ectively to
reach a maximal outcome for the patient?
. Which mechanisms guide spontaneous recovery and enable improvements during systematic rehabilitation? Functional imaging may be useful
to evaluate which cortical and subcortical regions in the damaged and healthy hemisphere contribute to these two processes. Such studies
could compliment the physiological basis for current behavioral rehabilitation studies.

22
G. Kerkho€ / Progress in Neurobiology 63 (2001) 1±27
16. Outstanding questions
It has become obvious that hemineglect is a multicomponent
syndrome resulting from damage to a
number of cerebral structures, and hence neural circuits
relevant for sensory, motor and cognitive functioning
in the brain. Although much progress has been
made in the last two decades, many issues are presently
still unresolved or controversial (summarized in
Table 7).
Most of the open questions center around the issue
of how our subjective, introspective feeling of one perceptual,
motor and cognitive space (including our own
body) is accomplished although so many di€erent egocentric,
allocentric and object-centered neural representations
of di€erent spatial aspects exist in our brain.
How these are interwoven (Driver and Spence, 1998)
and how they relate to awareness is a fascinating
research task for the next years to come.
Acknowledgements
I am grateful to Professor Charles Heywood, Durham,
and Igor Schindler, Ph.D., Lyon, for helpful suggestions
on a previous version of the manuscript.
References
Adair, J.C., Na, D.L., Schwartz, R.L., Fennell, E.M., Gilmore, R.L.,
Heilman, K.M., 1995. Anosognosia for hemiplegia: test of the
personal neglect hypothesis. Neurology 45, 2195±2199.
Anderson, B., 1996. A mathematical model of line bisection behaviour
in neglect. Brain 119, 841±850.
Andersen, R.A., 1995. Encoding of intention and spatial location in
the posterior parietal cortex. Cerebral Cortex 5, 457±469.
Andersen, R.A., Bracewell, R.M., Barash, S., Gnadt, J.W., Fogassi,
L., 1990. Eye position e€ects on visual, memory, and saccade-related
activity in areas LIP and 7a of macaque. J. Neuroscience
10, 1176±1196.
Andersen, R.A., Snyder, L.H., Bradley, D.C., Xing, J., 1997.
Multimodal representation of space in the posterior parietal cortex
and its use in planning movements. Ann. Rev. Neurosci. 20,
303±330.
Antonucci, G., Guariglia, C., Judica, A., Magnotti, L., Paolucci, S.,
Pizzamiglio, L., Zoccolotti, P., 1995. E€ectiveness of neglect rehabilitation
in a randomized group study. J. Clin. and Exp.
Neuropsych. 17, 383±389.
Apicella, P., Legallet, E., Nieoullon, A., Trouche, E., 1991. Neglect
of contralateral visual stimuli in monkeys with unilateral striatal
dopamine depletion. Behav. Brain Res. 46, 187±195.
Axenfeld, D., 1894. Eine einfache methode hemianopsie zu constatiren.
Neurol. Centralbl. 13, 437±438.
Babinski, M.J., 1914. Contribution l'tude des troubles mentaux dans
l'he miple gie organique ce re brale (Anosognosie). Rev. Neurol. 22,
845±848.
Bartolomeo, P., Chokron, S., 1999. Egocentric frame of reference: its
role in spatial bias after right hemisphere lesions.
Neuropsychologia 37, 881±894.
Bartolomeo, P., D'Erme, P., Gainotti, G., 1994. Relationship
between visuospatial and representational neglect. Neurology 44,
1710±1714.
Barton, J.S., Behrmann, M., Black, S., 1998. Ocular search during
line bisection. The e€ects of hemi-neglect and hemianopia. Brain
121, 1117±1131.
Basso, G., Nichelli, P., Frassinetti, F., Dipellegrino, G., 1996. Time
perception in a neglected space. NeuroReport 7, 2111±2114.
Batista, A.P., Buneo, C.A., Snyder, L.H., Andersen, R.A., 1999.
Reach plans in eye-centered coordinates. Science 285, 257±260.
Battersby, W.S., Bender, M.B., Pollack, M., Kahn, R.L., 1956.
Unilateral ``spatial agnosia'' (``inattention'') in patients with cerebral
lesions. Brain 79, 68±93.
Baylis, G.C., Driver, J., Baylis, L.L., Rafal, R.D., 1994. Reading of
letters and words in a patient with Balint's syndrome.
Neuropsychologia 32, 1273±1286.
Baynes, K., Holtzman, J.D., Volpe, B.T., 1986. Components of
visual attention. Alterations in response pattern to visual stimuli
following parietal lobe infarction. Brain 109, 99±114.
Bender, M.B., 1952. Disorders in Perception. Academic Press,
Spring®eld, Illinois, pp. 1±109.
Bender, M.B., 1977. Extinction and other patterns of sensory interaction.
In: Weinstein, E.A., Friedland, R.P. (Eds.), Advances in
Neurology. Raven Press, New York, pp. 107±110.
Bender, M.B., Teuber, H.L., 1946. Phenomena of ¯uctuation, extinction
and completion in visual perception. Arch. Neurol.
Psychiatr. 55, 627±658.
Berti, A., Oxbury, S., Oxbury, J., A€anni, P., Umilt, C., Orlandi, L.,
1999. Somatosensory extinction for meaningful objects in a
patient with right hemisphere stroke. Neuropsychologia 37, 333±
343.
Berti A., Frassinetti F., 2000. When far becomes near: re-mapping of
space by tool use. J. Cogn. Neurosci. in press.
Berti, A., Rizzolatti, G., 1992. Visual processing without awareness:
evidence from unilateral neglect. J. Cogn. Neurosci. 4, 345±351.
Beschin, N., Cocchini, G., Dellasala, S., Logie, R.H., 1997. What the
eyes perceive, the brain ignores Ð a case of pure unilateral representational
neglect. Cortex 33, 3±26.
Bisiach, E., Rusconi, M.L., 1990. Breakdown of perceptual awareness
in neglect. Cortex 26, 643±649.
Bisiach, E., Vallar, G., Perani, D., Papagno, C., Berti, A., 1986.
Unawareness of disease following lesions of the right hemisphere:
anosognosia for hemiplegia and anosognosia for hemianopia.
Neuropsychologia 24, 471±482.
Bisiach, E., Capitani, E., Luzzatti, C., Perani, D., 1981. Brain and
conscious representation of outside reality. Neuropsychologia 19,
543±551.
Bisiach, E., Capitani, E., Porta, E., 1985. Two basic properties of
space representation in the brain: evidence from unilateral
neglect. JNNP 48, 141±144.
Bisiach, E., Gemianiani, G., Berti, A., Rusconi, M.L., 1990.
Perceptual and premotor factors of unilateral neglect. Neurology
40, 1278±1281.
Bisiach, E., Luzzatti, C., 1978. Unilateral neglect of representational
space. Cortex 14, 129±133.
Bisiach, E., Pizzamiglio, L., Nico, D., Antonucci, G., 1996. Beyond
unilateral neglect. Brain 119, 851±857.
Bisiach, E., Tgner, R., Ladavas, E., Rusconi, M.L., Mijovic, D.,
Hjaltason, H., 1995. Dissocation of ophthalmokinetic and melokinetic
attention in unilateral neglect. Cerebral Cortex 5, 439±447.
Brandt, Th., Bucher, S.F., Seelos, K.C., Dieterich, M., 1998.
Bilateral functional MRI activations of the basal ganglia and
middle temporal/medial superior temporal motion-sensitive areas
Ð optokinetic stimulation in homonymous hemianopia. Arch.
Neurol. 55, 1126±1131.
Burnett-Stuart, G., Halligan, P., Marshall, J.C., 1991. A newtonion
model of perceptual distortion in visuo-spatial neglect.
NeuroReport 2, 255±257.

G. Kerkho€ / Progress in Neurobiology 63 (2001) 1±27 23
Butter, C.M., Kirsch, N., 1995. E€ect of lateralized kinetic visual
cues on visual search in patients with unilateral spatial neglect. J.
Clin. and Exp. Neuropsychol. 17, 856±867.
Butter, C.M., Kirsch, N.L., Reeves, G., 1990. The e€ect of lateralized
dynamic stimuli on unilateral spatial neglect following right
hemisphere lesions. Rest. Neurol. Neurosci. 2, 39±46.
Cambier, J., Elghozi, D., Strube, E., 1980. Le sions du thalamus droit
avec syndrome de l'he misphe re mineur. Discussion du concept de
ne gligence thalamique. Rev. Neurol. 136, 105±116.
Carli, M., Evenden, J.L., Robbins, T.W., 1985. Depletion of unilateral
striatal dopamine impairs initiation of contralateral actions
and not sensory attention. Nature 313, 679±682.
Celesia, G.G., Brigell, M., Vaphiades, M.S., 1997. Hemianopic anosognosia.
Neurology 49, 88±97.
Che dru, F., Le blanc, M., Lhermitte, F., 1973. Visual searching in
normal and brain damaged subjects: contributions to the study of
unilateral inattention. Cortex 9, 94±111.
Chokron, S., Imbert, M., 1995. Variations of the egocentric reference
among normal subjects and a patient with unilateral neglect.
Neuropsychologia 33, 703±711.
Classen, J., Schnitzler, A., Binkofski, F., Werhahn, K.J., Kim, Y.S.,
Kessler, K.R., Benecke, R., 1997. The motor syndrome associated
with exaggerated inhibition within the primary motor cortex of
patients with hemiparetic stroke. Brain 120, 605±619.
Colby, C.L., 1998. Action-oriented spatial reference frames in cortex.
Neuron 20, 15±24.
Colby, C.L., Duhamel, J.R., 1996. Spatial representations for action
in parietal cortex. Cogn. Brain Res. 5, 105±115.
Cowey, A., Small, M., Ellis, S., 1994. Left visuo-spatial neglect can
be worse in far than in near space. Neuropsychologia 32, 1059±
1066.
Damasio, A.R., Damasio, H., Chang Chui, H., 1980. Neglect following
damage to frontal lobe or basal ganglia. Neuropsychologia
18, 123±132.
De Keyser, M., Neetens, A., Vissenberg, I., 1990. Objective assessment
and detection of hemianopia and hemineglect with visual
evoked potentials. Neuro-Ophthalmology 11, 49±58.
De Renzi, E., Colombo, A., Faglioni, P., Gibertoni, M., 1982.
Conjugate gaze paresis in stroke patients with unilateral damage.
An unexpected instance of hemispheric asymmetry. Archives of
Neurology 39, 482±486.
De Renzi, E., Gentilini, M., Pattacini, F., 1984. Auditory extinction
following hemisphere damage. Neuropsychologia 22, 733±744.
Denes, G., Semenza, C., Stoppa, E., Lis, A., 1982. Unilateral spatial
neglect and recovery from hemiplegia. A follow-up study. Brain
105, 543±552.
Deuel, R.K., Collins, R.C., 1983. Recovery from unilateral neglect.
Exp. Neurol. 81, 733±748.
Deuel, R.K., Collins, R.C., 1984. The functional anatomy of frontal
lobe neglect in the monkey: behavioral and quantitative 2-deoxyglucose
studies. Ann. Neurol. 15, 521±529.
Dieterich, M., Bucher, S.F., Seelos, K., Brandt, T., 1998. Horizontal
or vertical optokinetic stimulation activates visual motion-sensitive,
ocular motor and vestibular cortex areas with right hemispheric
dominance. An fMRI study. Brain 121, 1479±1495.
Diller, L., Weinberg, J., 1977. Hemi-inattention in rehabilitation: the
evolution of a rational remediation program. Adv. Neurol 18,
63±82.
Driver, J., Baylis, G.C., Goodrich, S.J., Rafal, R.D., 1994. Axisbased
neglect of visual shapes. Neuropsychologia 32, 1353±1365.
Driver, J., Mattingley, J.B., 1998. Parietal neglect and visual awareness.
Nature Neuroscience 1, 17±22.
Driver, J., Spence, C., 1998. Attention and the crossmodal construction
of space. Trends Cogn. Sci. 2, 254±262.
Duhamel, J.R., Bremmer, F., Benhamed, S., Graf, W., 1997. Spatial
invariance of visual receptive ®elds in parietal cortex neurons.
Nature 389, 845±848.
Ellis, S., Small, M., 1997. Localization of lesion in denial of hemiplegia
after acute stroke. Stroke 28, 67±71.
Farah, M.J., Buxbaum, L.J., 1997. Object-based attention in visual
neglect: conceptual and empirical distinctions. In: Thier, P.,
Karnath, H.-O. (Eds.), Parietal Lobe Contributions to
Orientation in 3D Space. Springer, Heidelberg, pp. 385±400.
Feeney, D.M., Hovda, D.A., 1985. Reinstatement of binocular depth
perception by amphetamine and visual experience after visual cortex
ablation. Brain Res. 342, 352±356.
Feinberg, T.E., Doane, D.M., Kwan, P.C., Schindler, R.J., Haber,
L.D., 1994. Anosognosia and visuoverbal confabulation. Arch
Neurol. 51, 468±473.
Ferber, S., Karnath, H.-O., 1999. Parietal and occipital lobe contributions
to perception of straight ahead orientation. JNNP 67,
572±578.
Fink, G.R., Dolan, R.J., Halligan, P.W., Marshall, J.C., Frith, C.D.,
1997. Space-based and object-based visual attention: shared and
speci®c neural domains. Brain 120, 2013±2028.
Fleet, W.S., Valenstein, E., Watson, R.T., Heilman, K.M., 1987.
Dopamine agonist therapy for neglect in humans. Neurology 37,
1765±1770.
Fujii, T., Fukatsu, R., Suzuki, K., Yamadori, A., 1996. E€ect of
head-centered and body-centered hemispace in unilateral neglect.
J. Clin. and Exp. Neuropsychol. 18, 777±783.
Ga€an, D., Hornak, J., 1997. Visual neglect in the monkey.
Representation and disconnection. Brain 120, 1647±1657.
Ga€an, D., Hornak, J., 1999. Amnesia and Neglect. In: Burgess, N.,
Je€ery, K.J., O'Keefe, J. (Eds.), Beyond the Delay-Brion System
and the Hebb Synapse. Oxford University Press, Oxford, pp.
345±358.
Galati G., Lobel E., Vallar G., Berthoz A., Pizzamiglio L., Le Bihan
D. 2000. The neural basis of egocentric and allocentric coding of
space in humans: a functional magnetic resonance study. Exp.
Brain. Res. in press.
Geraerts S., Vandenbussche E., 1999. E€ect of cooling on reversible
hemineglect in cats. Rest. Neurol. Neurosci. 14, 237±250.
Ghika, J., Ghika-Schmid, F., Bogousslavsky, J., 1998. Parietal motor
syndrome: a clinical description in 32 patients in the acute phase
of pure parietal strokes studied prospectively. Clin. Neurol.
Neurosurg. 100, 271±282.
Girotti, F., Casazza, M., Musicco, M., Avanzini, G., 1983.
Oculomotors disorders in cortical lesions in man: the role of unilateral
neglect. Neuropsychologia 21, 543±553.
Gitelman, D.R., Alpert, N.M., Kosslyn, S., Da€ner, K., Scinto, L.,
Thompson, W., Mesulam, M.M., 1996. Functional imaging of
human right hemispheric activation for exploratory movements.
Ann. Neurol. 39, 174±179.
Gitelman, D.R., Nobre, A.C., Parrisch, T.B., LaBar, K.S., Kim, Y.-
H., Meyer, J.R., Mesulam, M.-M., 1999. A large-scale distributed
network for covert spatial attention. Brain 122, 1093±1106.
Goldenberg, G., 1993. The neural basis of mental imagery. Baillire's
Clinical Neurology 2, 265±286.
Goldman, H., 1966. Improvement of double simultaneous stimulation
perception in hemiplegic patients. Arch. Phys. Med.
Rehabil. 63, 681±687.
Graziano, M.S.A., Gross, C.G., 1995. The representation of extrapersonal
space: a possible role for bimodal, visual-tactile neurons.
In: Gazzaniga, M.S. (Ed.), The Cognitive Neurosciences. The
MIT Press, Cambridge, Massachusetts, pp. 1021±1034.
Graziano, M.S.A., Reiss, L.A.J., Gross, C.G., 1999. A neuronal representation
of the location of nearby sounds. Nature 397, 428±
430.
Graziano, M.S.A., Tian Hu, X., Gross, C.G., 1997. Coding the locations
of objects in the dark. Science 277, 239±241.
Grieve, K.L., Acua, C., Cudeiro, J., 2000. The primate pulvinar
nuclei: vision and action. TINS 23, 35±39.
Grujic, Z., Mapstone, M., Gitelman, D.R., 1998. Dopamine agonists

24
G. Kerkho€ / Progress in Neurobiology 63 (2001) 1±27
reorient visual exploration away from neglected hemispace.
Neurology 51, 1395±1398.
Guariglia, C., Antonucci, G., 1992. Personal and extrapersonal
space: a case of neglect dissociation. Neuropsychologia 30, 1001±
1009.
Guariglia, C., Lippolis, G., Pizzamiglio, L., 1998. Somatosensory
stimulation improves imagery disorders in neglect. Cortex 34,
233±241.
Guariglia, C., Padovani, A., Pantano, P., Pizzamiglio, L., 1993.
Unilateral neglect restricted to visual imagery. Nature 364, 235±
237.
Halligan, P.W., Manning, L., Marshall, J.C., 1990. Individual variation
in line bisection: a study of four patients with right hemisphere
damage and normal controls. Neuropsychologia 28, 1043±
1051.
Halligan, P.W., Marshall, J.C., 1991a. Left neglect for near but not
far space in man. Nature 350, 498±500.
Halligan, P.W., Marshall, J.C., 1991b. Spatial compression in visual
neglect: a case study. Cortex 27, 623±629.
Hardy, S.C., Stein, B.E., 1988. Small lateral suprasylvian cortex
lesions produce visual neglect and decreased visual activity in the
superior colliculus. J. Comp. Neurol. 273, 527±542.
Harvey, M., Milner, A.D., 1999. Residual perceptual distortion in
`recovered' hemispatial neglect. Neuropsychologia 37, 745±750.
Harvey, M., Milner, A.D., Roberts, R.C., 1995. An investigation of
hemispatial neglect using the landmark task. Brain and Cognition
27, 59±78.
Heilman, K.M., Bowers, D., Coslett, H.B., Whelan, H., Watson,
R.T., 1985. Directional hypokinesia: prolonged reaction times for
leftward movements in patients with right hemisphere lesions and
neglect. Neurology 35, 855±859.
Heilman, K.M., Bowers, D., Watson, R.T., 1983. Performance on
hemispatial pointing task by patients with neglect syndrome.
Neurology 33, 661±664.
Heilman, K.M., Van Den Abell, T., 1980. Right hemisphere dominance
for attention: the mechanism underlying hemispheric asymmetries
of inattention (neglect). Neurology 30, 327±330.
Heilman K.M. and Watson R.T. (1995). The neglect syndrome Ð a
unilateral defect of the orienting response. Handbook of
Neuropsychology (Boller, F., Grafman, eds.); pp. 285±302.
Heldmann B., Kerkho€ G., Struppler A., Jahn Th., 2000. Repetitive
peripheral magnetic stimulation alleviates tactile extinction.
NeuroReport, submitted.
Hesse, S., Schauer, M., Malezic, M., Jahnke, M., Mauritz, K.-H.,
1994. Quantitative analysis of rising from a chair in healthy and
hemiparetic subjects. Scand. J. Rehab. Med. 26, 161±166.
Hier, D.B., Mondlock, J., Caplan, L.R., 1983. Recovery of behavioral
abnormalities after right hemisphere stroke. Neurology 33,
345±350.
Hillis, A.E., Caramazza, A., 1991. De®cit to stimulus-centered, letter
shape representations in a case of ``unilateral neglect''.
Neuropsychologia 29, 1223±1240.
Honda, M., Wise, S.P., Weeks, R.A., Deiber, M.-P., Hallett, M.,
1999. Cortical areas with enhanced activation during objectcentred
spatial information processing. A PET study. Brain 121,
2145±2158.
Hornak, J., 1992. Ocular exploration in the dark by patients with
visual neglect. Neuropsychologia 30, 547±552.
Hornak, J., Oxbury, S., Oxbury, J., Iversen, S.D., Ga€an, D., 1997.
Hemi®eld-speci®c visual recognition memory impairments in
patients with unilateral temporal lobe removals.
Neuropsychologia 35, 1311±1315.
Huber, W., Willmes, K., Poeck, K., Van Vleymen, B., Deberdt, W.,
1997. Piracetam as an adjuvant to language therapy for aphasia:
a randomized double-blind placebo-controlled pilot study.
Archives of Physical Medicine and Rehabilitation 78, 245±250.
Husain, M., Kennard, C., 1996. Visual neglect associated with frontal
lobe infarction. Journal of Neurology 243, 652±657.
Ishiai, S., Furukawa, T., Tsukagoshi, H., 1987. Eye-®xation patterns
in homonymous hemianopia and unilateral neglect.
Neuropsychologia 25, 675±679.
Jeannerod, M., Biguer, B., 1987. The directional coding of reaching
movements. A visuomotor conception of spatial neglect. In:
Jeannerod, M. (Ed.), Neurophysiological and Neuropsychological
Aspects of Spatial Neglect (The Directional). North-Holland,
Amsterdam, pp. 87±113.
Jeannerod, M., Biguer, B., 1989. Re ference e gocentrique et espace
repre sente . Rev. Neurol. 145, 635±639.
Karnath, H.-O., 1988. De®cits of attention in acute and recovered
visual hemi-neglect. Neuropsychologia 26, 27±43.
Karnath, H.-O., 1994. Subjective body orientation in neglect and the
interactive contribution of neck muscle proprioceptive and vestibular
stimulation. Brain 117, 1001±1012.
Karnath, H.-O., 1995. Transcutaneous electrical stimulation and vibration
of neck muscles in neglect. Experimental Brain Research
105, 321±324.
Karnath, H.-O., 1997. Spatial orientation and the representation of
space with parietal lobe lesions. Philosophical Transactions of the
Royal Society, London B, B352.
Karnath, H.-O., Christ, W., Hartje, W., 1993. Decrease of contralateral
neglect by neck muscle vibration and spatial orientation of
trunk midline. Brain 116, 383±396.
Karnath, H.-O., Ferber, S., 1999. Is space representation distorted in
neglect? Neuropsychologia 37, 7±15.
Karnath, H.-O., Fetter, M., Dichgans, J., 1996. Ocular exploration
of space as a function of neck proprioceptive and vestibular input
Ð observations in normal subjects and patients with spatial
neglect after parietal lesions. Experimental Brain Research 109,
333±342.
Karnath, H.O., Perenin, M.-T., 1998. Tactile exploration of peripersonal
space in patients with neglect. NeuroReport 9, 2273±2277.
Karnath, H.O., Schenkel, P., Fischer, B., 1991. Trunk orientation as
the determining factor of the `contralateral' de®cit in the neglect
syndrome and as the physical anchor of the internal representation
of body orientation in space. Brain 114, 1997±2014.
Katz, N., Hartman-Maeir, A., Ring, H., Soroker, N., 1999.
Functional disability and rehabilitation outcome in right hemisphere
damaged patients with and without unilateral spatial
neglect. Arch. Phys. Med. Rehabil. 80, 379±384.
Keller, I., Schindler, I., Golz, D., 1999. The in¯uence of distance and
motor response on visual hemineglect. Neural Plasticity Suppl 1,
156±157.
Kerkho€, G., 1993. Displacement of the egocentric visual midline in
altitudinal postchiasmatic scotomata. Neuropsychologia 31, 261±
265.
Kerkho€, G., 1998. Rehabilitation of visuospatial cognition and
visual exploration in neglect: a cross-over study. Rest. Neurol.
Neurosci. 12, 27±40.
Kerkho€, G., 1999a. Multimodal spatial orientation de®cits in leftsided
visual neglect. Neuropsychologia 37, 1387±1405.
Kerkho€, G., 1999b. Restorative and compensatory therapy
approaches in cerebral blindness Ð a review. Rest. Neurol.
Neurosci. 15, 255±271.
Kerkho€, G., 1999c. Neglect. In: GoÈ tze, R., Hfer, B. (Eds.),
Alltagsorientierte Therapie. Thieme, Stuttgart, pp. 102±110.
Kerkho€ G., 2000. Multiple perceptual distortions and their modulation
in patients with left visual neglect. Neuropsychologia in
press.
Kerkho€, G., Artinger, F., Ziegler, W., 1999a. Contrasting spatial
hearing de®cits in hemianopia and spatial neglect. NeuroReport
10, 3555±3560.
Kerkho€, G., Kriz, G., Keller, I., Marquardt, C., 1999b. Head direc-

G. Kerkho€ / Progress in Neurobiology 63 (2001) 1±27 25
tion and optokinetic stimulation modulate space-based but not
word-based neglect dyslexia. Neural Plasticity Suppl 1, 155±156.
Kerkho€, G., Schindler, I., Keller, I., Marquardt, C., 1999c. Visual
background motion reduces size distortion in spatial neglect.
NeuroReport 10, 319±323.
Kerkho€, G., Marquardt, C., 1995. VS Ð a new computer program
for detailed o‚ine analysis of visual-spatial perception. J.
Neurosci. Meth. 63, 75±84.
Kerkho€ G., Ziegler W., Artinger F., 2000. Coherent visual motion
recalibrates auditory space. Evidence from audiospatial neglect.
Submitted.
Kerkho€, G., Zoelch, Ch., 1998. Disorders of visuospatial orientation
in the frontal plane in patients with neglect following right
or left parietal lesions. Exp. Brain Res. 122, 108±120.
Kertzman, C., Robinson, D.L., Litvan, I., 1990. E€ects of physiostigmine
on spatial attention in patients with progressive supranuclear
palsy. Arch. Neurol. 47, 1346±1350.
Kinsbourne, M., 1987. Mechanisms of unilateral neglect. In:
Jeannerod, M. (Ed.), Neurophysiological and Neuropsychological
Aspects of Spatial Neglect. North-Holland, Amsterdam, pp. 69±
86.
Kinsbourne, M., 1993. Orientational bias model of unilateral neglect:
evidence form attentional gradients within hemispace. In:
Robertson, I.H., Marshall, J. (Eds.), Unilateral Neglect: Clinical
and Experimental Studies. LEA publishers, Hove, pp. 63±86.
Knudsen, E.I., Brainard, M.S., 1995. Creating a uni®ed representation
of visual and auditory space in the brain. Annual Review
of Neuroscience 18, 19±43.
Koehler, P.J., Endtz, L.J., Te Velde, J., Hekster, R.E.M., 1986.
Aware or non-aware. On the signi®cance of awareness for the
localizaion of the lesion responsible for homonymous hemianopia.
J. Neurol. Sci. 75, 255±262.
Kosslyn, S.M., Pascual-Leone, A., Felician, O., Camposano, S.,
Keenan, J.P., Thompson, W.L., Ganis, G., Sukel, K.E., Alpert,
N.M., 1999. The role of area 17 in visual imagery: convergent evidence
from PET and rTMS. Science 284, 167±170.
Ladavas, E., Petronio, A., UmiltaÁ , C., 1990. The development of
visual attention in the intact ®eld of hemineglect patients. Cortex
26, 307±317.
LaÁ davas, E., Zeloni, G., FarneÁ , A., 1998. Visual peripersonal space
centred on the face in humans. Brain 121, 2317±2326.
Laplane, D., Degos, J.D., 1983. Motor neglect. Journal of
Neurology, Neurosurgery, and Psychiatry 46, 152±158.
Lawson, I.R., 1962. Visual-spatial neglect in lesions of the right cerebral
hemisphere. Neurology 12, 23±33.
Lebrun, Y., 1987. Anosognosia in aphasics. Cortex 23, 251±263.
Levine, D.N., Warach, J.D., Benowitz, L., Calvanio, R., 1986. Left
spatial neglect: e€ects of lesion size and premorbid brain atrophy
on severity and recovery following right cerebral infarction.
Neurology 36, 362±366.
Lin, K.C., Cermak, S.A., Kinsbourne, M., Trombly, C.A., 1996.
E€ects of left-sided movements on line bisection in unilateral
neglect. JINS 2, 404±411.
Lohmann, W., 1911. Zur sehstoÈ rung der hemianopiker. Arch. f.
Ophthalmol 80, 270±279.
Lomber, S.G., Payne, B.R., 1996. Removal of two halves restores
the whole: reversal of visual hemineglect during bilateral cortical
or collicular inactivation in the cat. Vis. Neurosci 13, 1143±1156.
Maravita, A., 1997. Implicit processing of somatosensory stimuli disclosed
by a perceptual after-e€ect. NeuroReport 8, 1671±1674.
Marshall, J., Halligan, P., 1988. Blindsight and insight in visuospatial
neglect. Nature 336, 766±767.
Marzi C., Girelli M., Miniussi C., Smania N., Maravita A., 2000.
Electrophysiological correlates of conscious vision: evidence from
unilateral extinction. J. Cogn. Neurosci. in press.
Mattingley, J.B., Bradshaw, J.A., Bradshaw, N.C., 1994a. Recovery
from directional hypokinesia and bradykinesia in unilateral
neglect. J. Clin. and Exp. Neuropsychol. 16, 861±876.
Mattingley, J.B., Bradshaw, J.L., Bradshaw, J.A., 1994b. Horizontal
visual motion modulates focal attention in left unilateral spatial
neglect. JNNP 57, 1228±1235.
Mattingley, J.B., Philips, J.G., Bradshaw, J.L., 1994c. Impairments
of movement execution in unilateral neglect: a kinematic analysis
of directional bradykinesia. Neuropsychologia 32, 1111±1134.
Mattingley, J.B., Davis, G., Driver, J., 1997a. Preattentive ®lling-in
of visual surfaces in parietal extinction. Science 275, 671±674.
Mattingley, J.B., Driver, J., Beschin, N., Robertson, I.H., 1997b.
Attentional competition between modalities: extinction between
touch and vision after right hemisphere damage.
Neuropsychologia 35, 867±880.
McDowell, F.H., 1991. Activation of rehabilitation.
Arzeimittelforschung/Drug Research 41, 355±359.
McGlinchey-Berroth, R., Milberg, W.P., Verfaellie, M., Alexander,
M., Kildu€, P.T., 1993. Semantic processing in the neglected
visual ®eld: evidence from a lexical decision task. Cogn.
Neuropsych. 10, 79±108.
McGlynn, S.M., Schacter, D.L., 1990. Unawarenss of de®cits in neuropsychological
syndromes. J. Clin. and Exp. Neuropsychol. 11,
143±150.
McGlynn, S.M., Schacter, D.L., 1997. The neuropsychology of
insight Ð impaired awareness of de®cits in a psychiatric context.
Psych. Ann. 27, 806±811.
Mennemeier, M., Wertman, E., Heilman, K.M., 1992. Neglect of
near peripersonal space. Brain 115, 37±50.
Mennemeier, M., Chatterjee, A., Heilman, K.M., 1994. A comparison
of the in¯uences of body and environment centred reference
frames on neglect. Brain 117, 1013±1021.
Meredith, M.A., Stein, B.E., 1985. Descending e€erents from the superior
colliculus relay integrated multisensory information.
Science 227, 657±659.
Meredith, M.A., Stein, B.E., 1986a. Spatial factors determine the activity
of multisensory neurons in cat superior colliculus. Brain
Research 365, 350±354.
Meredith, M.A., Stein, B.E., 1986b. Visual, auditory, and somatosensory
convergence on cells in superior colliculus results in multisensory
integration. J. Neurophysiol. 56, 640±662.
Mesulam, M.-M., 1998. From sensation to cognition. Brain 121,
1013±1052.
Milner, A.D., 1995. Cerebral correlates of visual awareness.
Neuropsychologia 33, 1117±1130.
Milner, A.D., 1998. Neuropsychological studies of perception and
visuomotor control. Phil. Trans. Royal Soc. London B 353,
1375±1384.
Milner, A.D., Harvey, M., 1995. Distortion of size perception in
visuospatial neglect. Curr. Biol. 5, 85±89.
Milner, A.D., Harvey, M., Pritchard, C.L., 1998. Visual size processing
in spatial neglect. Exp. Brain Res. 123, 192±200.
Milner, A.D., Harvey, M., Roberts, R.C., Forster, S.V., 1993. Line
bisection errors in visual neglect: misguided action or size distortion.
Neuropsychologia 31, 39±49.
Moscovitch, M., Behrmann, M., 1994. Coding of spatial information
in the somatosensory system: evidence from patients with neglect
following parietal lobe damage. J. Cogn. Neurosci. 6, 151±155.
MuÈ ller, U., Von Cramon, D.Y., 1994. The therapeutic potential of
bromocriptine in neuropsychological rehabilitation of patients
with acquired brain damage. Prog.Neuro-Psychopharmacol. and
Biol.Psychiat. 18, 1103±1120.
Nico, D., 1999. E€ectiveness of sensory stimulation on tactile extinction.
Exp. Brain Res. 127, 75±82.
Nobre, A.C., Sebestyen, G.N., Gitelman, D.R., Mesulam, M.M.,
Frackowiak, R.S.J., Frith, C.D., 1997. Functional localization of
the system for visuospatial attention using positron emission tomography.
Brain 120, 515±533.

26
G. Kerkho€ / Progress in Neurobiology 63 (2001) 1±27
Olson, C.R., Gettner, S.N., 1995. Object-centered direction selectivity
in the macaque supplementary eye ®eld. Science 269, 985±988.
Olson, C.R., Gettner, S.N., 1996. Brain representation of object-centered
space. Curr. Opin. Neurobiol. 6, 165±170.
Pantano, P., Di Piero, V., Fieschi, C., Judica, A., Guariglia, C.,
Pizzamiglio, L., 1992. Pattern of CBF in the rehabilitation of
visuospatial neglect. Intern. J. Neurosci. 66, 153±161.
Paolucci, S., Antonucci, G., Guariglia, C., Magnotti, L., Pizzamiglio,
L., Zoccolotti, P., 1996. Facilitatory e€ect of neglect rehabilitation
on the recovery of left hemiplegic stroke patients Ð a crossover
study. J. Neurol. 243, 308±314.
Paolucci, S., Traballesi, M., Giallloretti, L.E., Pratesi, L., Lubich, S.,
Antonucci, G., Caltagirone, C., 1998. Changes in functional outcome
in inpatient stroke rehabilitation resulting from new health
policy regulations in Italy. European Journal of Neurology 5, 17±
22.
Pavlovskaya, M., Sagi, D., Soroker, N., Ring, H., 1997. Visual
extinction and cortical connectivity in human vision. Cogn. Brain
Res. 6, 159±162.
Payne, B.R., Lomber, S.G., Geeraerts, S., Van Der Gucht, E., 1996.
Vandenbussche E. Reversible visual hemineglect. Proc. Natl.
Acad. Sci. USA 93, 290±294.
Payne, B.R., Siwek, D.F., Lomber, S.G., 1991. Complex transcallosal
interaction in visual cortex. Vis. Neurosci. 6, 283±289.
Perenin, M.-T., 1997. Optic ataxia and unilateral neglect: clinical evidence
for dissociable spatial function in posterior parietal cortex.
In: Thier, P., Karnath, H.-O. (Eds.), Parietal Lobe Contributions
to Orientation in 3D Space. Springer, Heidelberg, pp. 289±308.
Perennou, D.A., Amblard, B., Leblond, C., Plissier, J., 1998. Biased
postural vertical in humans with hemispheric cerebral lesions.
Neurosci Lett. 252, 75±78.
Perennou, D., Benaim, C., Rouget, E., Rousseaux, M., Blard, J.M.,
Pelissier, J., 1999. Postural balance following stroke Ð towards a
disadvantage of the right brain-damaged hemisphere. Rev.
Neurol. (Paris) 155, 281±290.
Peru, A., Moro, V., Avesani, R., Aglioti, S., 1997. In¯uence of perceptual
and semantic con¯icts between the two halves of chimeric
stimuli on the expression of visuo-spatial neglect.
Neuropsychologia 35, 583±589.
Peru, A., Pinna, G., 1997. Right personal neglect following a left
hemisphere stroke: a case report. Cortex 33, 585±590.
Pizzamiglio, L., Cappa, S., Vallar, G., Zoccolotti, P., Bottini, G.,
Ciurli, P., Guariglia, C., Antonucci, G., 1989. Visual neglect for
far and near extra-personal space in humans. Cortex 25, 471±477.
Pizzamiglio, L., Frasca, R., Guariglia, C., Incoccia, C., Antonucci,
G., 1990. E€ect of optokinetic stimulation in patients with visual
neglect. Cortex 26, 535±540.
Pizzamiglio, L., Perani, D., Cappa, S.F., Vallar, G., Paolucci, S.,
Grassi, F., Paulesu, E., Fazio, F., 1998. Recovery of neglect after
right hemispheric damage - (h2o)-o- 15 positron emission tomographic
activation study. Arch Neurol. 55, 561±568.
Pizzamiglio, L., Vallar, G., Doricchi, F., 1997. Gravitational inputs
modulate visuospatial neglect. Experimental Brain Research 117,
341±345.
Pizzamiglio, L., Vallar, G., Magnotti, L., 1996. Transcutaneous electrical-stimulation
of the neck muscles and hemineglect rehabilitation.
Rest. Neurol. Neurosci. 10, 197±203.
Posner, M.I., Driver, J., 1992. The neurobiology of selective attention.
Curr. Biol. 2, 165±169.
Posner, M.I., Walker, J.A., Friedrich, F.A., Rafal, R.D., 1984.
E€ects of parietal injury on covert orienting of attention. J.
Neurosci. 4, 1863±1874.
Pritchard, C.L., Milner, A.D., Dijkerman, H.C., MacWalter, R.S.,
1997. Visuospatial neglect: veridical coding of size for grasping
but not for perception. Neurocase 3, 437±443.
Rapcsak, S.Z., Watson, R.T., Heilman, K.M., 1987. Hemispacevisual
®eld interactions in visual extinction. JNNP 50, 1117±1124.
Redlich, F.C., Dorsey, J.F., 1945. Denial of blindness by patients
with cerebral disease. Arch. Neurol. Psychiatr 53, 407±417.
Remy, P., Zilbovicius, M., Degos, J.-D., Bachoudlevi-Le vi, A.-C.,
Rancurel, G., Cesaro, P., Samson, Y., 1999. Somatosensory cortical
activations are suppressed in patients with tactile extinction.
A PET study. Neurology 52, 571±577.
Riddoch, M.J., Humphreys, G.W., 1983. The e€ect of cueing on unilateral
neglect. Neuropsychologia 21, 589±599.
Rizzolatti, G., Fadiga, L., Fogassi, L., Gallese, V., 1997. The space
around us. Science 277, 190±191.
Rizzolatti, G., Matelli, M., Pavesi, G., 1983. De®cits in attention
and movement following the removal of postarcuate (area 6) and
prearcuate (area 8) cortex in macaque monkeys. Brain 106, 655±
673.
Robertson, I.H., 1999. Cognitive rehabilitation: attention and
neglect. Trends Cogn. Sci. 3, 385±393.
Robertson, I.H., North, N., 1993. Active and passive activation of
left limbs: in¯uence on visual and sensory neglect.
Neuropsychologia 31, 293±300.
Robertson, I.H., North, N., 1994. One hand is better than two:
motor extinction of left hand advantage in unilateral neglect.
Neuropsychologia 32, 1±11.
Robertson, I.H., Ridgeway, V., Green®eld, E., Parr, A., 1997. Motor
recovery after stroke depends on intact sustained attention Ð a
two-year follow-up-study. Neuropsychology 11, 290±295.
Robertson, I.H., Tegne r, R., Tham, K., Lo, A., Nimmo-Smith, I.,
1995. Sustained attention training for unilateral neglect: theoretical
and rehabilitation implications. J. Clin. and Exp.
Neuropsychol 17, 416±430.
Rode, G., Charles, N., Perenin, M.-T., Vighetto, A., Trillet, M.,
Aimard, G., 1992. Partial remission of hemiplegia and somatoparaphrenia
through vestibular stimulation in a case of unilateral
neglect. Cortex 28, 203±208.
Rode, G., Perenin, M.-T., 1994. Temporary remission of representational
hemineglect through vestibular stimulation. NeuroReport
5, 869±872.
Rode, G., Tiliket, C., Boisson, D., 1997. Predominance of postural
imbalance in left hemiparetic patients. Scand. J. Rehab. Med. 29,
11±16.
Rode, G., Tiliket, C., Charlopain, P., Boisson, D., 1998. Postural
asymmetry reduction by vestibular caloric stimulation in left
hemiparetic patients. Scand. J. Rehab. Med. 30, 9±14.
Rossetti, Y., Rode, G., Pisella, L., Farne , A., Boisson, D., Perenin,
M.-T., 1998. Prism adaptation to a rightward optical deviation
rehabilitates left hemispatial neglect. Nature 98, 166±169.
Rubens, A.B., 1985. Caloric stimulation and unilateral visual neglect.
Neurology 35, 1019±1024.
Schenkenberg, T., Bradford, D.C., Ajax, E.T., 1980. Line bisection
and unilateral visual neglect in patients with neurologic impairment.
Neurology 30, 509±517.
Scherder, E.J.A., Bouma, A., Steen, A.M., 1995. E€ects of shortterm
transcutaneous electrical nerve stimulation on memory and
a€ective behavior in patients with probable Alzheimer's disease.
Beh. Brain Res. 67, 211±219.
Schindler, I., Kerkho€, G., 1997. Head and trunk orientation modulate
visual neglect. NeuroReport 8, 2681±2685.
Schindler, I., Kerkho€, G., Karnath, H.-O., Keller, I., Goldenberg,
G., 1999. Neck muscle vibration and visual exploration training:
visual and crossmodal e€ects on neglect rehabilitation. Neural
Plasticity Suppl 1, 160±160.
Schwartz, A.S., Marchok, P.L., Flynn, R.E., 1977. A sensitive test
for tactile extinction: results in patients with parietal and frontal
lobe disease. JNNP 40, 228±233.
Sheliga, B.M., Riggio, L., Rizzolatti, G., 1995. Spatial attention and
eye movements. Exp. Brain Res. 105, 261±275.
Smania, N., Aglioti, S., 1995. Sensory and spatial components of

G. Kerkho€ / Progress in Neurobiology 63 (2001) 1±27 27
somethetic de®cits following right brain damage. Neurology 45,
1725±1730.
Smania, N., Martini, M.C., Gambina, G., Tomelleri, G., Palamara,
A., Natale, E., Marzi, C.A., 1998. The spatial distribution of
visual attention in hemineglect and extinction patients. Brain 121,
1759±1770.
Spinelli, D., Burr, D.C., Morrone, M.C., 1994. Spatial neglect is associated
with increased latencies of visual evoked potentials. Vis.
Neurosci. 11, 909±918.
Spinelli, D., Di Russo, F., 1996. Visual evoked potentials are a€ected
by trunk rotation in neglect patients. NeuroReport 7, 553±556.
Sprague, J.M., 1966. Interaction of cortex and superior colliculus in
mediation of visually guided behaviour in the cat. Science 153,
1544±1547.
Stein, B.E., Huneycutt, W.S., Meredith, M.A., 1988. Neurons and
behavior: the same rules of multisensory integration apply. Brain
Res 448, 355±358.
Steinmetz, M.A., 1998. Contributions of posterior parietal cortex to
cognitive functions in primates. Psychobiology 26, 109±118.
Steinmetz, M.A., Connor, C.E., Constantinides, C., McLaughlin,
J.R., 1994. Covert attention suppresses neuronal responses in
area 7a of the posterior parietal cortex. J. Neurophysiol. 72,
1020±1023.
Sterzi, R., Bottini, G., Celani, M.G., Righetti, E., Lamassa, M.,
Ricci, S., Vallar, G., 1993. Hemianopia, hemianaestesia, and
hemiplegia after right and left hemisphere damage. A hemispheric
di€erence. JNNP 56, 308±310.
Stoerig, P., Cowey, A., 1997. Blindsight in man and monkey. Brain
120, 535±559.
Stone, S.P., Wilson, B., Wroot, A., Halligan, P.W., Lange, L.S.,
Marshall, J.C., 1991. The assessment of visuo-spatial neglect after
acute stroke. JNNP 54, 345±350.
Sundquist, A., 1979. Saccadic reaction-time in parietal-lobe dysfunction.
The Lancet 870±870.
Tijssen, C.C., Gisbergen, J.A.M., 1993. van. Conjugate eye deviation
after hemispheric stroke. A contralateral saccadic palsy? Neuro-
Ophthalmology 13, 107±118.
Vallar, G., 1993. The anatomical basis of spatial neglect in humans.
In: Robertson, I.H., Marshall, J. (Eds.), Unilateral Neglect:
Clinical and Experimental Studies. Lawrence Erlbaum Associates,
Hove, UK, pp. 27±53.
Vallar, G., 1997. Spatial frames of reference and somatosensory processing:
a neuropsychological perspective. Phil. Trans.
Roy.Soc.,London, B B 352, 1401±1409.
Vallar, G., Guariglia, C., Nico, D., Bisiach, E., 1995a. Spatial hemineglect
in back space. Brain 118, 467±472.
Vallar, G., Guariglia, C., Magnotti, L., Pizzamiglio, L., 1995b.
Optokinetic stimulation a€ects both vertical and horizontal de®cits
of position sense in unilateral neglect. Cortex 31, 669±683.
Vallar, G., Rusconi, M.L., Barozzi, S., Bernadini, B., Ovadia, D.,
Papagno, C., Cesarini, A., 1995c. Improvement of left visuospatial
hemineglect by left-sided transcutaneous electrical stimulation.
Neuropsychologia 33, 73±82.
Vallar, G., Guariglia, C., Rusconi, M.L., 1997. Modulation of the
neglect syndrome by sensory stimulation. In: Thier, P., Karnath,
H.-O. (Eds.), Parietal Lobe Contributions to Orientation in 3D
Space. Springer, Berlin, pp. 555±578.
Vallar, G., Perani, D., 1986. The anatomy of unilateral neglect after
right hemisphere stroke lesions. A clinical/CT-scan correlation
study in man. Neuropsychologia 24, 609±622.
Vallar, G., Rusconi, M.L., Bignamini, G., Geminiani, G., 1994.
Anatomical correlates of visual and tactile extinction in humans:
a clinical CT scan study. Journal of Neurology, Neurosurgery,
and Psychiatry 57, 464±470.
Vallar, G., Sandroni, P.R.M.L., Bignamini, L.G.G., Perani, D.,
1991. Hemianopia, hemianesthesia and spatial neglect: a study
with evoked potentials. Neurology 41, 1918±1922.
Vilkki, J., 1984. Visual hemi-inattention after ventrolateral thalamothomy.
Neuropsychologia 22, 399±408.
Volpe, B.T., Ledoux, J.E., Gazzaniga, M.S., 1979. Information processing
of visual stimuli in an `extinguished' ®eld. Nature 282,
722±724.
Von Giesen, H.J., Schlaug, G., Steinmetz, H., Benecke, R., Freund,
H.J., Seitz, R.J., 1994. Cerebral network underlying unilateral
motor neglect: evidence from positron emission tomography. J.
Neurol. Sci. 125, 29±38.
Vuilleumier, P., Valenza, N., Mayer, E., Perrig, S., Landis, T., 1999.
To see better to the left when looking more to the right: e€ects of
gaze direction and frames of spatial coordinates in unilateral
neglect. JINS 5, 75±82.
Walker, R., Findlay, J.M., Young, A.W., Welch, J., 1991.
Disentangling neglect and hemianopia. Neuropsychologia 29,
1019±1027.
Walker, R., 1995. Key issues: spatial and object-based neglect.
Neurocase 1, 371±383.
Wallace, M.T., Meredith, M.A., Stein, B.E., 1992. Integration of
multiple sensory modalities in cat cortex. Exp Brain Res. 91, 484±
488.
Ward, R., Goodrich, S., Driver, J., 1994. Grouping reduces visual
extinction: neuropsychological evidence for weight-linkage in
visual selection. Vis. Cogn 1, 101±129.
Weinberg, J., Diller, L., Gordon, W.A., Gerstman, L.J., Lieberman,
A., Lakin, P., Hodges, G., Ezrachi, O., 1979. Training sensory
awareness and spatial organization in people with right brain
damage. Arch. Phys. Med. Rehabil. 60, 491±496.
Weintraub, S., Da€ner, K.R., Ahern, G.L., Price, B.H., Mesulum,
M.-M., 1996. Right sided hemispatial neglect and bilateral cerebral
lesions. JNNP 60, 342±344.
Welman, A.J., 1969. Right-sided unilateral visual spatial agnosia,
asomatognosia and anosognosia with left hemisphere lesions.
Brain 92, 571±580.
Wilkinson, L.K., Meredith, M.A., Stein, B.E., 1996. The role of anterior
ectosylvian cortex in cross-modality orientation and
approach behavior. Exp. Brain. Res. 112, 1±10.
Zarit, S.H., Kahn, R.L., 1974. Impairment and adaptation in chronic
disabilities: spatial inattention. J. Nerv. Ment. Dis. 159, 63±72.