Revisiting unilateral neglect

Unilateral neglect, a neurological disorder in which patients fail to detect or respond to contralesional stimuli, has long been considered a failure of attentional orienting mechanisms. This review provides a selective overview of the prominent biases in spatial orienting and exploratory motor behaviour observed in these patients before considering the impact of other factors on the presentation of the disorder and how those factors might inform current neurological models of neglect. In the latter part of the review, we intend to suggest that neglect is likely to be a combination of distinct but interacting impairments including biases in attentional orienting, exploratory motor behaviours and a deficit of spatial working memory. That is, we suggest that the cardinal symptom of neglect - a loss of awareness for contralesional stimuli and events - arises as a result of a combination of these impairments rather than being associated solely with the more dramatic and immediately evident biases in spatial attention.     

Hypermnesia in unilateral neglect

Thirteen right brain-damaged patients who were found to neglect pictures presented on the left of a display were presented the same stimuli, intermixed with foils, in a yes-no recognition test. Fifty per cent of patients claimed to have already seen one or more of the previously neglected pictures. This demonstrates that visual information that fails to access consciousness in neglect patients does retain the ability to surface as explicit memory at a later stage.     

Recovery from unilateral neglect

Spontaneous recovery of function occurs in the syndrome of hemisensory neglect in monkeys. We produced this syndrome in 13 macaques by unilateral operative resection of the frontal polysensory association cortex. Using standardized behavioral measures, we documented severe acute neglect and followed the course of its improvement. Using the 2-deoxy[¹⁴C]glucose autoradiographic method, we studied animals in the acute phase of neglect and found decrements in local glucose utilization in subcortical structures, but not in cortical regions with known frontal connections. After spontaneous behavioral recovery, mild local glucose utilization decrements remained, but only in nucleus medialis dorsalis of the thalamus. The findings suggest that acute behavioral symptoms are based on widespread depression of neuronal activity in uninjured structures with synaptic relations to damaged cortex, and that return of neuronal activity in those structures is accompanied by restitution of behavioral function.     

Ventriloquism in patients with unilateral visual neglect

Can visual stimuli that go undetected, because they are presented in the extinguished region of neglect patients' visual field, nevertheless shift in their direction the apparent location of simultaneous sounds (the well-known 'ventriloquist effect')? This issue was examined using a situation in which each trial involved the simultaneous presentation of a tone over loudspeakers, together with a bright square area on either the left, the right or both sides of fixation. Participants were required to report the presence of squares, and indicate by hand pointing the apparent location of the tone. Five patients with left hemineglect consistently failed to detect the left square, either presented alone or together with another square on the right. Nevertheless, on bimodal trials with a single undetected square to the left, their sound localization was significantly shifted in the direction of that undetected square. By contrast, in bimodal trials with either a single square on the right or a square on each side, their sound localization showed only small and non-significant shifts. This particular result might be due to a combination of low discrimination of lateral sound deviations with variable individual strategies triggered by conscious detection of the right square. The important finding is the crossmodal bias produced by the undetected left visual distractors. It provides a new example of implicit processing of inputs affected by unilateral visual neglect, and on the other hand is consistent with earlier demonstrations of the automaticity of crossmodal bias.     

Improvement of unilateral spatial neglect with numbering

We examined 8 patients with moderate to severe left unilateral spatial neglect by means of a series of line cancellation tasks. We asked the patients to cross out lines in the 1st trial, to number lines in the 2nd trial, and again to cross out lines in the 3rd trial. In the 2nd trial with numbering, all the patients showed improvement of left unilateral spatial neglect. Numbering involved the successive use of increasing numbers. This process seemed to motivate the patients to continue searching for another line, even at the point when they would be satisfied that they had completed the task if they used simple crossing-out. Insufficient motivation for visuospatial searching may play an important role in unilateral spatial neglect observed in cancellation tasks.     

Dopaminergic stimulation in unilateral neglect

OBJECTIVE—To explorethe hypothesis that dopaminergic circuits play a part in the premotorcomponents of the unilateral neglect syndrome, the effects of acutedopaminergic stimulation in patients with neglect were studied.
METHODS—Two tasks wereevaluated before and after subcutaneous administration of apomorphineand placebo: a circle crossing test and a test of target exploration (amodified version of the bell test), performed both in perceptual(counting) and in perceptual-motor (pointing) conditions.
SUBJECTS—Four patientswith left neglect.
RESULTS—Afterdopaminergic stimulation, a significant improvement was found comparedwith placebo administration and baseline evaluation, in the performanceof the two tests. Three of the patients had a more marked improvementin the perceptual-motor condition (pointing) of the task than theperceptual condition (counting).
CONCLUSIONS—Thefindings suggest that dopaminergic neuronal networks may mediate, indifferent ways, both perceptive and premotor components of theunilateral neglect syndrome.

     

Visuomotor adaptation is impaired in patients with unilateral neglect

Patients with unilateral neglect tend to ignore sensory information from their contralesional hemispace. Many symptoms of neglect can be reduced by exposing patients to rightward-shifting prism goggles. It was noted that the effects on neglect symptoms last for at least two hours. This seems surprising in light of the fact that the after-effect of prism adaptation in healthy subjects lasts only for a few trials. To account for this discrepancy Michel et al. (2003) referred to anecdotal observations which suggested that neglect patients show little awareness of prism-induced spatial errors. They argued that this lack of awareness might interfere with more conscious attempts to compensate for the prism goggles (called strategic control) and thereby enhance the effects of more implicit corrective mechanisms (called spatial realignment) leading to more pronounced and longer-lasting after-effects. We examined this hypothesis in a group of neglect patients, patients with right-hemispheric lesions but no neglect and a group of healthy age-matched controls. Our findings confirm that strategic control mechanisms are impaired in neglect patients. However, their after-effects seem neither reduced nor pathologically increased, thereby suggesting that the two mechanisms of prism adaptation, namely strategic control and spatial realignment are quite independent of each other. Furthermore we found that these deficits are quite specific for neglect since other patients with right-hemisphere lesions but no neglect are not impaired in this task. We discuss the implications of our findings for our understanding of visual neglect, prism adaptation and the perception and action model.     

Experimental remission of unilateral spatial neglect

Over the past several decades a growing amount of research has focused on the possibility of transiently reducing left neglect signs in right brain-damaged patients by using vestibular and/or visuo-proprioceptive stimulations. Here we review seminal papers dealing with these visuo-vestibulo-proprioceptive stimulations in normal controls, right brain-damaged (RBD) patients, and animals. We discuss these data in terms of clinical implications but also with regards to theoretical frameworks commonly used to explain the unilateral neglect syndrome. We undermine the effect of these stimulations on the position of the egocentric reference and extend the notion that the positive effects of these stimulation techniques may stem from a reorientation of attention towards the neglected side of space or from a recalibration of sensori-motor correlations. We conclude this review with discussing the possible interaction between experimental rehabilitation, models of neglect and basic spatial cognition research.     

Grouping influences in unilateral visual neglect

Effects of grouping on unilateral neglect were investigated in 8 neurological patients with right hemisphere damage. It is well documented that arranging items to form a group spanning the midline decreases the magnitude of neglect. In the present study we examined how clusters of groups within the left or right visual field affect neglect and whether isolated groups within the neglected field deflect attention from right-sided displays. We orthogonally varied the strength of grouping on the right and left sides of a display and measured the time to find a predesignated target in one of those groups. Groups on the neglected left side did not affect right-sided target detection any more than an empty left page. However, strength of grouping did affect left sided target detection. These findings are discussed as they relate to attention and preattention in unilateral visual neglect.     

Mirror images and unilateral spatial neglect

Responding correctly to a mirror image requires the creation of a rather peculiar form of dual representation. Mirror agnosia and mirror ataxia, i.e. a deficit in reaching an object reflected in a mirror, have been reported to be associated with parietal lobe lesions. This prospective study was conducted to investigate the capacity of subjects with neglect to identify the mirror image nature of visual information. Four consecutive brain-damaged patients with neglect, selected on the basis of specific criteria, and four control subjects performed grasping and object displacement tests under two response conditions (normal mirror and inverted mirror). Video recordings of the tests were analyzed to assess performance using the following criteria: (i) direction of the arm movement during the initial phase of movement, (ii) number of corrections of the hand position before grasping. The control subjects successfully grasped the objects in both experimental conditions. The patients (1) neglected the contralesional space, grasping objects correctly in the ipsilesional space (normal mirror condition) and (2) neglected the ipsilesional space, grasping correctly objects in the contralesional space (inverted mirror). Controls used real object-centered correction clues to modify the position and direction of their hand movement. The patients only produced horizontal displacements of the upper limb in the ‘healthy’ and neglected space. These results suggest that patients with neglect do not use the same clues and do not modify their procedures as they cannot recalibrate their spatial representations. These differences concerned non-mirror-image clues and directional and positional as well as attentional vectors. Theoretical and rehabilitative implications are discussed.     

Neurobiology of unilateral spatial neglect.

Hemispatial neglect is a common and disabling consequence of stroke. Earlier studies aimed to identify a single area of the brain where damage caused neglect and sought a single disrupted process that could account for the symptoms. Recent studies have shifted toward identifying component processes and representations underlying spatial attention required for various tasks and identifying areas of the brain responsible for each component that together constitute the network of regions responsible for neglect. This review focuses on recent insights into the mechanisms of neglect, regions of neural dysfunction that cause disruption of particular components or forms of neglect, and potential means of ameliorating neglect. Converging evidence supporting these insights comes from new imaging modalities in acute stroke, functional imaging, transcranial magnetic stimulation, electrophysiological studies in humans, and single-cell recording studies in nonhuman primates.     

The multivariate nature of unilateral neglect

Abstract

It is almost certain that unilateral neglect has been observed for centuries. Presumably people have suffered brain injury from the beginning of our existence, yet broad interest in the behavioural phenomena associated with unilateral neglect has appeared relatively recently. So one of the questions surrounding this interest is what new scientific issues have emerged that make the study of neglect so intriguing? It seems to me that the main answer to this question is the renewed interest in cognition and consciousness, and the failure to explain consciousness in biological terms. The magnet that pulls researchers (at least this researcher) into the study of unilateral neglect is the astonishing phenomenology that a person can exhibit both consciousness and unconsciousness of the perceptual scene, perceptual object, or the self at the same moment.     

The mechanism of unilateral spatial neglect

We investigated a test for unilateral spatial neglect and discussed the mechanism of this symptom. Seventy eight patients with lesions on the right cerebral hemisphere were examined on line bisection, line cancellation, figure copying, clock drawing and location on the map. The statistical analysis revealed (1) there were no correlations between line bisection and clock drawing or between line bisection and location; (2) those with abnormal results on line bisection were apt to indicate normal results on line cancellation and figure copying, while in line cancellation, figure copying, clock drawing and location, normal results on one task meant normal results on the other. These results indicated clock drawing and location might include different factors from other tasks, line bisection was the most sensitive task for unilateral spatial neglect, and abnormality on line cancellation might be similar to that figure copying. Unilateral spatial neglect may be based on several disorders, and it may be assumed to have several aspects. One of these disorders may be defective searching. Unilateral spatial neglect may be more severe when there is sensory disturbance (hemianopsia) with a searching deficit. Other disorders, such as cognitive disturbance, memory disturbance and so on, may also be associated with unilateral spatial neglect, and it is necessary to consider the versatility of this symptom.     

Caloric stimulation and unilateral visual neglect

We studied performance on tests of visual neglect and left lateral gaze after caloric stimulation in 18 patients with left-sided visual neglect after strokes. Except for one patient with absent vestibulo-ocular responses, all improved during caloric stimulation on the left by cold (LC) or on the right by warm water (RW). Improvement seemed to depend on the facilitation of left lateral gaze and on past-pointing to the left. During LC and RW caloric stimulation, patients worked from left to right instead of their usual right to left. Caloric stimulation may be of use in training patients with hemispatial neglect to orient toward the affected hemispatial field.     

Context and crossover in unilateral neglect

Patients with left-neglect bisect horizontal lines to the right of true center. Their bisection bias is affected by line length, so that longer lines are bisected further to the right. Patients often crossover and bisect very short lines to the left of true center. We tested the hypothesis that the context in which lines are apprehended accounts for the crossover phenomenon. We replicated previous findings that a line is bisected further leftward when it is preceded by a longer line and further rightward when it is preceded by a shorter line. These contextual effects occur with relatively short and relatively long target lines. Bisection patterns in two different series of lines, one ranging from 10 to 150 mm, and the other from 110 to 250 mm, were investigated. If crossover bisections were simply due to contextual effects then left-sided errors would be observed on bisections of the shorter lines of both series. Our findings did not support this hypothesis. Crossover bisections occurred only with objectively short lines, those shorter than 40 mm. Even though we found significant contextual effects on line bisection biases, these effects per se do not account for the crossover phenomenon. Rather, our data suggest that the absolute length of the line is associated specifically with the crossover phenomenon.     

Is there a correlation between motor neglect and unilateral sensory neglect

Similarities between motor neglect and unilateral sensorial neglect are so striking that their mechanisms are likely to be almost the same. As the attentional interpretation is no longer possible for motor neglect, and the intentional interpretation may be dismissed in man because of the loss of automatic movements, the psychological interpretation must be abandoned. A purely physiological hypothesis is put forward for motor neglect. When applied to unilateral neglect, it suggests that sensorial signals treated by the right hemisphere do not reach a significant functional level. In such case, the left hemisphere assumed to be dominant for awareness of body and space would receive from the right hemisphere a message interpreted as nul and would neglect information coming from the left.     

Time and neglect: abnormal temporal dynamics in unilateral spatial neglect

Temporality enters our immediate experience as passage and becoming: the role time plays in the construction of a world of enduring entities tends to go unnoticed. This paper examines the relation between time and ontology in the context of unilateral neglect, a neuropsychological syndrome in which patients fail to perceive or respond to stimuli in the contralateral hemifield, behaving as if that half of space does not exist. Traditional models characterize neglect exclusively in spatial terms. Based on recent investigations suggesting abnormal temporal dynamics, here we highlight the impact of time factors on the presentation of the disorder. Neglect patients do not simply miss the presence of stimuli on the left: they also ignore the past as well as the future of neglected stimuli. We claim that, if this occurs, it is because time, and not only space, is impaired.     

Contralesional neglect in monkeys with small unilateral parietal cortical ablations

Transient contralesional spatial neglect, in addition to motor impairment in the contralesional arm, is sometimes seen in patients following cerebral infarction in the right hemisphere and is seen following experimental occlusion of the right middle cerebral artery in primates. To test whether contralesional visuospatial neglect arises from a disruption of the forward flow of information from the striate cortex through the dorsal territory of the middle cerebral artery, we made a small strip suction ablation in the right parietal cortex from the medial edge of the dorsal cortical surface to the posterior ventral edge of the superior temporal gyrus in marmoset monkeys. These monkeys did not exhibit a motor impairment, or misreaching, with the contralesional arm. When they were unrestrained and free to use either arm, they were impaired at finding rewards in their contralesional space and in choosing the nearer of two rewards hidden in ipsilesional space (i.e. they had an ultra-ipsilesional bias in ipsilesional space). Comparison of performance under four conditions in a task in which the monkeys were constrained to reach into each hemispace with each arm separately indicated that they were impaired at reaching into contralesional, but not ipsilesional, space with either arm but they did not exhibit any impairment confined to the contralesional arm. These impairments in contralesional space were transient suggesting that the monkeys were able to re-align their egocentric spatial coordinates to obviate these deficits.     

Hemispatial neglect in young children with early unilateral brain damage

Hemispatial neglect is commonly observed in adults following right-hemisphere brain lesions. Given the potential for reorganization in the developing brain, spatial neglect may not be apparent following early unilateral damage. This study aimed to determine whether infants who experienced pre- or perinatal focal brain lesions showed evidence of spatial neglect. Study participants were 33 infants/toddlers (22 males, 11 females; age range 6 to 48 months); 27 preschool children (14 males, 13 females; age range 28 to 75 months) with either left hemisphere (LH) or right hemisphere (RH) damage of pre- or perinatal onset (total 60), and 36 control individuals (15 females, 21 males; age range 28 to 75 months). Participants were assessed using two object-removal preference tasks. Control children showed no lateralized preference for object removal. Those with LH or RH damage preferentially removed objects from the side of the board ipsilateral to the lesion first and the contralateral side last. These results suggest that spatial neglect may be found in young children even after very early unilateral brain damage. Further, in contrast to the adult pattern, contralateral neglect is present for up to 6 years after either LH or RH damage. This pattern suggests that there may be a different distribution of attention to space in the developing brain as compared with the mature brain. The persistence of spatial neglect suggests that there are some limitations on plasticity in the developing human brain.