Ipsilesional intentional neglect and the effect of cueing

BACKGROUND: Contralesional hemispatial neglect may be induced by an attentional deficit where patients are inattentive to or unaware of stimuli in contralesional hemispace, an intentional deficit where patients are unable to act in or towards contralesional hemispace, or both. The deficits associated with ipsilesional neglect have not been as well characterized. Because cueing may be used as a rehabilitative assistive device, we wanted to learn whether the efficacy of an attentional or intentional cue was related to the type of bias. METHODS: We studied a patient with a right frontotemporal stroke who had ipsilesional neglect by using a video apparatus that dissociates sensory-attentional and motor-intentional systems. We also performed a cueing experiment with primarily sensory-attentional cues (i.e., read the letter at the end of the line) and primarily motor-intentional cues (i.e., touch the end of the line). RESULTS AND CONCLUSIONS: Ipsilesional neglect was primarily a motor-intentional deficit with a motor-action bias to the left and a secondary sensory-attentional bias for stimuli to the right. With cueing we found a double dissociation: the rightwards motor-intentional cue improved the primary left-sided intentional bias and the leftwards sensory-attentional cue improved the secondary right-sided attentional bias. Effective rehabilitation strategies need to address both sensory-attentional and motor-intentional deficits in patients with neglect.     

Competition between simultaneous stimuli modulated by location probability in hemispatial neglect

Many aspects of spatial neglect can be explained as arising from competition for attentional selection, with salient ipsilesional stimuli emerging as the winner more often than contralesional stimuli. The outcome of the competition, however, can be affected both by bottom-up perceptual factors such as the gestalt properties of the display and by top-down factors such as expectancy or stimulus blocking. This study examines whether the competition for attentional selection can be modulated by manipulating the probability of the target's location in hemispatial neglect. Five patients with left-sided hemispatial neglect and a group of control participants performed a visual target discrimination task. In equal probability blocks, the target appeared randomly in any of six possible horizontal locations (three left, three right) whereas in biased blocks, the target appeared in the mid-location on the left on 50% of the trials and in each of the other locations on 10% of the trials. The target appeared either alone or was accompanied by a distractor on the opposite side. The results showed that the spatial bias facilitated detection of all left-sided targets in the neglect group, but was more spatially specific in the control group. Furthermore, while distractors on either side interfered with target processing in both groups, the patterns differed across the visual field. Finally, the magnitude of facilitation due to the bias was greatest in the condition with the most inhibition, i.e. a left-sided target accompanied by a right-sided distractor in the neglect group. These data underscore the competitive push-pull relationship between different bottom-up and top-down attentional factors, particularly within neglect patients, in whom a strong ipsilesional attentional bias already exists.     

Re‐fixation and perseveration patterns in neglect patients during free visual exploration

The literature suggests that neglect patients not only show impairments in directing attention toward the left, contralesional space, but also present with perseverative behavior. Moreover, previous studies described re‐fixations during visual search tasks, and interpreted this finding as an impairment of spatial working memory. The aim of the present study was to study re‐fixations and perseverations (i.e., recurrent re‐fixations to same locations) during free visual exploration, a task with high ecological validity. We hypothesized that: (1) neglect patient would perform re‐fixations more frequently than healthy controls within the right hemispace; and, (2) the re‐fixation behavior of neglect patients would be characterized by perseverative fixations. To test these hypotheses, we assessed 22 neglect patients and 23 healthy controls, measuring their eye movements during free exploration of naturalistic pictures. The results showed that neglect patients tend to re‐fixate locations within the ipsilesional hemispace when they freely explore naturalistic pictures. Importantly, the saliency of discrete locations within the pictures has a stronger influence on fixation behavior within the contralesional than within the ipsilesional hemispace in neglect patients. Finally, the results indicated that, for re‐fixations, saliency plays a more important role within the contralesional than the ipsilesional hemispace. Moreover, we found evidence that re‐fixation behavior of neglect patients is characterized by frequent recurrent re‐fixations back to the same spatial locations which may be interpreted as perseverations. Hence, with the present study, we could better elucidate the mechanism leading to re‐fixations and perseverative behavior during free visual exploration in neglect patients.     

Cerebral hemispheric specialization for spatial attention: spatial distribution of search-related eye fixations in the absence of neglect

The "specialization" of the right hemisphere for spatial attention is widely accepted but poorly understood. While several theories have been supported by studies of patients with acute hemispatial neglect, generalizability beyond this population remains unclear. In this study, we compared the predictions of two attention models [Brain 119 (1996) 841; Trans. Am. Neurol. Assoc. 95 (1970) 143] when applied to data obtained from subjects with unilateral right- or left-cerebral lesions, but without clinical evidence of neglect during a visual search task. Both Left Lesion and Right Lesion subjects detected fewer targets in the contralesional hemispace. However, the Right Lesion subjects also made fewer visual fixations and longer saccades in the contralesional hemispace, suggesting a fundamental alteration in the architecture of visual search. The spatial distribution of fixations made by Right Lesion subjects more closely fits the prediction of a "salience" model than of the strict interpretation of a linear "gradient" model. These data support the long-standing notion of right hemisphere dominance for spatial attention, especially for the top-down processes entailed in self-directed visual search, and extend this to lesion patients without clinically evident neglect. A theoretical model based on the salience of extrapersonal space appears useful for understanding alterations of attentional allocation, particularly after recovery from stroke.     

Ipsilesional versus contralesional neglect depends on attentional demands

Right hemisphere injuries often produce contralesional hemispatial neglect (CN). In contrast to CN, some patients with right hemisphere damage can also show so-called ipsilesional neglect (IN). Previous reports found that patients tend to show IN on line bisection tasks but CN on other tasks such as target cancellation. To learn why these two tasks induce different spatial biases in patients with right hemisphere injury, conventional (i.e. solid) line bisection was compared with two novel bisection tasks consisting of horizontally aligned strings of characters. The subjects' task was to mark a target character that was at or closest to the true midpoint of the simulated line. Four of the 5 patients showed a dissociation whereby IN occurred for solid lines while CN was observed on character lines. The two patients assessed with an antisaccade paradigm showed a "visual grasp" for leftward stimuli. The present results suggest that neglect on line bisection may reflect two opposing forces, an approach behavior or "visual grasp" toward left hemispace and an attentional bias toward right hemispace.     

A review of the evidence for a disengage deficit following parietal lobe damage

We review the literature on response times to ipsilesional and contralesional targets following spatial precues in patients with damage involving the left- and right-parietal lobes with the aim of appraising the 'disengage deficit' reported initially by Posner and colleagues (Posner MI, Cohen A, Rafal RD. Neural systems control of spatial orienting. Proceedings of the Royal Society of London, B 1982;298:187-98). The data of individual subjects from a sub-sample of studies were submitted to analyses of variance, and data from all studies meeting our selection criteria were submitted to meta-analytic procedures (Hunter JE, Schmidt FL. Methods of meta-analysis: correcting error and bias in research. Newberg Park: Sagge Publications, 1990). Findings from both types of analysis conducted on data from patients with right-hemisphere lesions indicate that: (1) the disengage deficit phenomenon is robust following peripheral cues, but not following central cues; (2) the disengage deficit is large at shorter cue-target stimulus onset asynchronies (SOAs), and decreases as SOA increases; (3) the disengage deficit is larger in patients with a diagnosis of hemispatial neglect; and (4) although the magnitude of the disengage deficit appears to increase with increases in lesion size, multilobar vs unilobar involvement did not significantly alter the pattern of the disengage deficit. We also show that responses to validly cued targets in the contralesional hemispace were significantly slower than for validly cued targets in ipsilesional hemispace. Similar, but usually smaller, effects were observed in patients with homologous left-hemisphere damage. The implications of these results for current models of the role of the parietal lobes in attentional orienting are discussed.     

Ipsilesional neglect: behavioural and anatomical features

OBJECTIVE: To learn more about the behavioural and anatomical features of ipsilesional neglect. METHODS: Thirty consecutive patients with spatial neglect were tested on cancellation and line bisection tasks. To learn if patients with ipsilesional neglect demonstrate the sensory-attentional or motor-intentional type of neglect, a video apparatus was used that dissociates these determinants. RESULTS: Five patients showed evidence of ipsilesional neglect. This phenomenon was seen only on the line bisection task. All patients with ipsilesional neglect had lesions involving frontal-subcortical regions. Although ipsilesional neglect evolved from early in three of five cases, the other patients displayed ipsilesional neglect without initial contralateral neglect, suggesting that ipsilesional neglect cannot be fully attributed to a compensatory strategy. The results of the tests that used the video apparatus indicate that right sided frontal or subcortical injury may induce contralateral attentional or intentional "approach" behaviours. CONCLUSIONS: Ipsilesional neglect is most often associated with frontal-subcortical lesions, cannot be entirely attributed to a compensatory strategy, and may be induced by an attentional bias, an intentional bias, or both.     

Increased attentional load moves the left to the right

Introduction: Unilateral brain damage can heterogeneously alter spatial processing. Very often brain-lesioned patients fail to report (neglect) items appearing within the contralesional space. Much less often patients mislocalize items’ spatial position. We investigated whether a top-down attentional load manipulation (dual-tasking), known to result in contralesional omissions even in apparently unimpaired cases, might also induce spatial mislocalizations. Method: Nine right-hemisphere-damaged patients performed three computer-based tasks encompassing different levels of attentional load. The side of appearance of visual targets had to be reported either in isolation or while processing additional information (visual or auditory dual task). Spatial mislocalizations (from the contralesional hemispace towards the ipsilesional unaffected one) were then contrasted with omissions both within and across tasks, at individual as well as at group level. Results: The representation of ipsilesional targets was accurate and not affected by dual-tasking requirements. Contralesional targets were instead often omitted and, under dual-task conditions, also mislocalized by four patients. Three cases reported a significant number of left targets as appearing on the right (alloesthesia). Two of these patients perceived more targets (albeit to a wrong spatial location) under dual- than under single-task load. In a fourth patient, increased visual load resulted in synchiria, the (mis)perception of single, contralesional targets as being two (one on each side). Conclusions: When the neural circuitry subtending spatial processing is damaged, an increase in task load can lead to either a disregard or a bias in the processing of contralesional hemispace. The spatial bias subtending mislocalizations seems to index a more severe deficit than neglect, as if contralesional space would be completely erased rather than merely ignored.     

Directional hypokinesia: prolonged reaction times for leftward movements in patients with right hemisphere lesions and neglect

Patients with hemispatial neglect perform activities poorly in the hemispace contralateral to the lesion. We postulate that hemispatial neglect induced by right hemisphere lesions may be associated with a directional hypokinesia: initiation of movements toward the hemispace contralateral to the lesion is affected more than movements toward the lesion. We tested 6 patients with hemispatial neglect caused by right hemisphere damage, 7 with left hemisphere damage and no neglect, and 12 controls. Patients with left hemispatial neglect initiated responses to left hemispace more slowly than toward right hemispace.     

Posterior internal capsule infarction associated with neglect

A persistent hemispatial neglect developed in a patient following a small infarction of the posterior limb of the right internal capsule. This defect was restricted to tasks requiring spontaneous motor performance on the contralateral hemispace, especially when carried out under visual control. It was not associated with an extinction phenomenon. Verbal cues improved exploratory behavior, suggesting that hemispatial akinesia in this case was due to an intentional disorder. A pulvinar-parietal disconnection, depriving the right parietal cortex from relevant visuospatial information from the contralateral hemispace, was probably the anatomic basis of hemispatial neglect in this case.     

Right hemispatial ipsilesional neglect with chronic right hemisphere strokes

Background: Patients who present with spatial neglect after stroke often perform normally on tests for neglect after a few weeks. Whereas tests for neglect are often performed directly in front of a patient, in their actual environments many important stimuli may be present within their left or right hemispace. The presence and severity of neglect often depends on the hemisphere injured. It is possible, in chronic stroke, for spatial judgments to be influenced by an interaction of stroke laterality and the spatial location of stimuli. The objective of this study was to learn if unilateral hemispheric chronic strokes contribute to a spatial bias with laterally presented stimuli.

Method: There were 70 participants, 62 with unilateral chronic strokes (>6 months post onset) including 35 with left hemisphere damage (LHD), 27 with right hemisphere damage (RHD), and 8 demographically similar people without history of stroke. Participants were asked to bisect 300 lines presented with distractors on the left, right, or both sides of the line, or no distractor, on a touch-screen monitor in right, center or left hemispace.

Results: There was a significant interaction between the side of the hemispheric lesion and the side of the body where these lines were presented. Specifically, in right space, patients with RHD deviated leftward in comparison to the other groups. Furthermore, there was an interaction between group and distractor induced bias. All three groups approached the left distractor, and the patients with LHD also approached the right distractor.

Conclusions: Although spatial neglect is more severe in contralesional than ipsilesional hemispace in the period immediately following a stroke, over time patients with RHD may develop ipsilesional neglect that is more severe in ipsilesional than contralesional space. The mechanism underlying this bias is not known and may be related to attempted compensation or the development of a contralateral attentional/intentional grasp.     

Ipsilesional Attentional-Approach Neglect or Crossover Effect*

Patients with ipsilateral neglect (IN) bisect lines toward contralesional space. It has been posited that IN might be induced by an attempt at compensation, as part of the crossover effect, where patients with an ipsilesional bias when bisecting long lines, cross over and develop a contralesional bias on short lines or as a release of an approach (grasp) behavior that might be attentional or intentional. To test these alternative hypotheses we had a patient with IN from a right medial frontal lesion bisect lines that contained no cue, a left-sided cue, a right-sided cue, and bilateral cues. If this patient had ipsilateral neglect (IN) because of a crossover effect or compensation, right-sided cues should have influenced bisection more than left-sided cues. We, however, found that only left-sided cues induced a significant change (left-sided deviation) providing support for the attentional-approach (grasp) hypothesis. Further support of this contralesional attentional grasp hypothesis comes from the observation that this patient also had ipsilesional extinction to simultaneous stimuli.     

Ipsilesional attentional-approach neglect or crossover effect

Patients with ipsilateral neglect (IN) bisect lines toward contralesional space. It has been posited that IN might be induced by an attempt at compensation, as part of the crossover effect, where patients with an ipsilesional bias when bisecting long lines, cross over and develop a contralesional bias on short lines or as a release of an approach (grasp) behavior that might be attentional or intentional. To test these alternative hypotheses we had a patient with IN from a right medial frontal lesion bisect lines that contained no cue, a left-sided cue, a right-sided cue, and bilateral cues. If this patient had ipsilateral neglect (IN) because of a crossover effect or compensation, right-sided cues should have influenced bisection more than left-sided cues. We, however, found that only left-sided cues induced a significant change (left-sided deviation) providing support for the attentional-approach (grasp) hypothesis. Further support of this contralesional attentional grasp hypothesis comes from the observation that this patient also had ipsilesional extinction to simultaneous stimuli.     

Eye-movement patterns do not mediate size distortion effects in hemispatial neglect: looking without seeing

Over the last decade a range of studies have shown that some patients with hemispatial neglect subjectively underestimate the size of objects presented in their contralesional hemispace. Recently, it has been suggested that the effect is simply due to either hemianopia [Brain 124 (2001) 527], or the combination of neglect and hemianopia [Neurology 52 (1999) 1845]. In the current study we asked right hemisphere lesioned patients with and without neglect and hemianopia as well as healthy controls to judge either two horizontal or vertical lines presented simultaneously in right and left hemispace and monitored their eye movements. Three out of the six patients showed the predicted size distortion effect for horizontal lines. We found no evidence that the effect was mediated by eye movements. The two neglect patients who showed the strongest left side underestimation showed symmetrical (left, right) scanning of the lines both in terms of number of fixations and fixation time, yet they still failed to judge the relative size veridically. In addition, we did not find strong evidence for a link with hemianopia. We therefore propose that the effect reflects a computational/representational failure of processing for horizontal extent.     

Multiple object tracking and pupillometry reveal deficits in both selective and intensive attention in unilateral spatial neglect

Introduction: Unilateral spatial neglect is typically associated with a spatial attention deficit, as neglect patients fail to respond to objects in their contralesional hemispace. However, growing evidence suggests that also nonspatial attention impairments (e.g., arousal) play a role and influences the recovery from this syndrome.

Method: Nonspatial and spatial attentional functions were assessed in 13 right-hemisphere stroke patients with neglect, 13 right-hemisphere stroke patients without neglect, and 26 healthy control participants, by investigating pupillary responses and performance on a multiple object tracking task (MOT)—that is, a dynamic task of divided attention where cognitive load can be manipulated precisely. The task was alternately presented in the left and right hemispace to assess spatial attention functioning.

Results: Results revealed smaller pupillary dilations in both patient groups than in controls, suggesting reduced attentional resources or arousal, and while patients without neglect and controls revealed significant effects of cognitive load on their pupillary responses, neglect patients did not. Both MOT and visual search (VS) tasks revealed spatial symptoms of neglect, while MOT performance measures additionally indicated reduced cognitive functioning in the ipsilateral hemispace. Moreover, the MOT task revealed severely reduced divided attention in neglect patients, as they only managed to track one target in the contralesional hemispace and occasionally two targets at the time in the ipsilesional hemispace.

Conclusion: Our results suggest that a stroke may lead to reduced attentional resources. Furthermore, as neglect patients showed no indications in their pupillary responses that they were able to regulate the allocation of resources in accordance with the varying task demands, it appears they additionally had impaired mechanisms for adjusting arousal levels. Our findings suggest that neglect involves nonspatial as well as spatial attention impairments, as also ipsilesional performance was reduced in this group.     

Effects of visible and invisible cueing on line bisection and Landmark performance in hemispatial neglect.

A total of 12 patients with hemispatial neglect (and two control groups) were tested to examine the effects of lateralized cues on line bisection and Landmark judgements. The experiment was designed to investigate whether bisection and landmark biases induced by cueing are simply a result of a direct perceptual lengthening of the cued part of the line caused by the fact that the cue is visible, thus creating a composite 'line plus cue' or whether cueing indeed induces an attentional bias. Secondly, earlier work by Harvey et al. [Harvey M, Milner AD, Roberts RC. An investigation of hemispatial neglect using the landmark task, Brain and Cognition 1995; 27: 59-78] has shown that in neglect patients cues work by inducing orientational biases rather than via the alteration of subjective length perception. An attempt was made to replicate this finding and extend it to cues that are not physically present. The bisection data clearly showed that cues bias attention rather than work via a direct lengthening of the line: both visible and invisible cues biased bisection performance equally well. The Landmark data, however, revealed much less clear-cut results and we failed to repeat the earlier observation by Harvey et al. that cues induce orientational biases. Even when the neglect patients were categorised into premotor and perceptual categories a clear effect failed to emerge. It is hypothesised that the earlier reported effect may be linked to neglect severity rather than to perceptual type neglect.     

Vertical bias in neglect: a question of time?

Neglect is defined as the failure to attend and to orient to the contralesional side of space. A horizontal bias towards the right visual field is a classical finding in patients who suffered from a right-hemispheric stroke. The vertical dimension of spatial attention orienting has only sparsely been investigated so far. The aim of this study was to investigate the specificity of this vertical bias by means of a search task, which taps a more pronounced top-down attentional component. Eye movements and behavioural search performance were measured in thirteen patients with left-sided neglect after right hemispheric stroke and in thirteen age-matched controls. Concerning behavioural performance, patients found significantly less targets than healthy controls in both the upper and lower left quadrant. However, when targets were located in the lower left quadrant, patients needed more visual fixations (and therefore longer search time) to find them, suggesting a time-dependent vertical bias.     

Vestibular hemispatial neglect: patterns and possible mechanism

Recent reports have suggested that hemispatial neglect may be a vestibular disorder at the cortical level, based on the similarities of symptoms and neural correlates between the two phenomena. If this is the case, peripheral vestibulopathy may lead to hemispatial neglect. However, the etiology of hemispatial neglect in patients with unilateral peripheral vestibulopathy remains unclear. The aims of the present study were to investigate the following: (1) if unilateral peripheral vestibulopathy might cause hemispatial neglect, and if so, (2) whether hemispatial neglect in unilateral peripheral vestibulopathy might be induced by horizontal bias for eye position and body orientation or whether it is secondary to vestibular cortical dysfunction following unilateral peripheral vestibulopathy. Twenty-five consecutive patients with acute vestibular neuritis were recruited at the Dizziness Clinic of Pusan National University Hospital. All participants underwent neglect testing and measurements of horizontal bias for eye position and head and body orientation. Hemispatial neglect occurred in 32 % of patients with unilateral peripheral vestibulopathy. The frequency of contralesional neglect was equal to that of ipsilesional neglect. All patients with hemispatial neglect showed abnormal performance in bisection tasks. The incidence and severity of the horizontal bias of eye position and head and body orientation did not differ between patients with or without hemispatial neglect. Our study demonstrates that hemispatial neglect can develop after acute unilateral peripheral vestibulopathy. Hemispatial neglect after acute unilateral peripheral vestibulopathy may be attributed to damaged vestibular subnuclei, which receive afferents from both peripheral vestibular end organs and the vestibulocerebellum and project to the ipsilateral or contralateral thalamus and vestibular cortex.     

Ipsilesional line bisection bias in patients with chronic parietal lesions

The current study investigated whether an ipsilesional bias in line bisection, a conventional measure for diagnosing hemispatial neglect, persists even in the absence of this syndrome in patients with chronic lesions restricted to posterior association cortex or dorsolateral prefrontal cortex. Both left and right hemisphere parietal lesions produced ipsilesional bisection errors, and to a comparable degree. Patients with lesions in frontal cortex, on the other hand, did not show a consistent bias. We conclude that chronic parietal lesions produce an ipsilesional bias in line bisection, even in the absence of other clinical signs of neglect, and that left hemisphere lesions can affect line bisection to the same degree as right hemisphere lesions.     

Prismatic adaptation reduces biased temporal order judgements in spatial neglect

Visuomotor adaptation to rightward-deviating optical-wedge prisms reduces the clinical manifestations of spatial neglect after right hemisphere damage. We investigated whether this beneficial effect of prism adaptation is due to attenuation of the ipsilesional attentional bias that is common in spatial neglect. Five right hemisphere patients performed visual temporal order judgements before and after visuomotor adaptation to 15 degrees rightward-deviating prisms. The magnitude of patients' ipsilesional attentional bias on the temporal order judgement task was significantly reduced following adaptation. By contrast, the temporal order judgements of normal participants did not change following adaptation to either leftward- or rightward-deviating prisms. The findings suggest that prism adaptation helps to rebalance the distribution of spatial attention following right hemisphere damage.