MRI brain scan analyses and neuropsychological profiles of nine patients with persisting unilateral neglect

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1 Neuropsychologia 40 (2002) MRI brain scan analyses and neuropsychological profiles of nine patients with persisting unilateral neglect Anne M. Maguire a,b,, Jenni A. Ogden c a Macquarie Centre for Cognitive Science, Macquarie University, Sydney NSW 2109, Australia b Australian National University, School of Psychology (Building 39), Canberra ACT 0200, Australia c Department of Psychology, University of Auckland, Auckland, New Zealand Received 4 September 2000; accepted 14 August 2001 Abstract Systematic individual neuroanatomical (MRI) and neuropsychological investigations were conducted for nine patients with unilateral neglect persisting at least 3 months after a cerebral vascular accident. The pattern of referrals, together with subsequent investigation, demonstrates that persisting neglect is rare in both right- and left-hemispheric lesioned patients. But while persisting neglect following a left-hemispheric lesion is even rarer than following a right-hemispheric lesion, it does occur. The neuroanatomical results indicate that persisting neglect may be associated with a different pattern of damage from acute neglect. In the nine patients investigated, persisting neglect reflected etensive lesions that involved three or more cortical lobes or subcortical regions. The results support previous findings that parietal lesions are common but not essential for persisting neglect. In the seven of nine neglect patients with parietal lesions, the rostral inferior parietal lobe and the parietal frontal junction were involved. Of note was the finding that the brain regions most commonly implicated were the basal ganglia and the superior dorsolateral prefrontal corte (including the frontal eye field). All of the patients with persisting neglect had a range of neuropsychological deficits, including etinction, personal neglect, and anosognosia for one or more aspects of their neglect. Although it was not possible to demonstrate a double dissociation with this pattern of results, the findings indicate that etinction and anosognosia are dissociable into function-specific forms. Most of the neglect patients also had sustained attention deficits, visual memory problems, and visuospatial constructional difficulties Elsevier Science Ltd. All rights reserved. Keywords: Cerebrovascular lesions; Neuroanatomy of visuospatial neglect; Etinction; Anosognosia 1. Introduction Unilateral neglect is a common finding if patients with unilateral cerebral lesions are assessed for the disorder in the days immediately following a cerebrovascular accident (CVA), or when symptoms of cerebral tumours are acute, with up to half of patients with unilateral lesions demonstrating some aspects of the disorder [10,24]. In the majority of cases, these acute neglect disorders rapidly resolve over the first 10 days, leaving approimately 10% of the original sufferers with a persisting neglect disorder [36,38]. The true incidence of persisting, post-acute neglect may be difficult to document accurately as neglect is a multifaceted disorder, which not only can occur across all modalities but also can take a number of forms within one modality (e.g. peripersonal and etrapersonal visual neglect, or visual neglect of the contralesional side of an object, the environment, or the viewer). Etinction is also considered a type of Corresponding author. Tel.: ; fa: address: anne.maguire@anu.edu.au (A.M. Maguire). neglect by some researchers, and indeed many of the more common tests for visual neglect, such as cancellation tasks, may be classified as tests of etinction given that the patient is viewing similar visual stimuli on both sides of the page simultaneously. What are the important differences between acute neglect and persisting neglect? Do the patients with persisting neglect have other cognitive deficits that constrain recovery from their neglect symptoms, or does the persisting neglect population have a different lesion distribution, or larger lesions than the acute neglect population? For eample, a number of researchers have hypothesised that although acute neglect may occur following a disruption to directionally-specific attentional or orienting systems located in both hemispheres, persisting neglect can only occur following damage to both this directionally-specific orienting system and the generalised sustained attentional system located principally in the right hemisphere [18,30,33]. The inferior parietal lobe at the temporal parietal junction of the right hemisphere is generally considered the most common site for lesions resulting in neglect [39], but /02/$ see front matter 2002 Elsevier Science Ltd. All rights reserved. PII: S (01)

2 880 A.M. Maguire, J.A. Ogden / Neuropsychologia 40 (2002) numerous other sites have also been implicated. Studies that have attempted specifically to define the neuroanatomical markers of persisting neglect, by testing patients at least 4 weeks post-cva, have demonstrated varying results, and more importantly, have failed to find an eclusive role for the parietal lobe [7,36,40]. These studies have instead emphasised the larger size of lesions in persisting neglect, and the finding that if tissue damage is confined to a single region that this region most likely involves either the basal ganglia [7] or the deep white matter below the collateral trigone of the temporal lobe [36]. The clearest difference between the acute and persisting neglect populations seems to be that whilst both right- and left-hemispheric lesions quite commonly result in neglect if the patient is assessed within a day or two of the CVA, right neglect following left-hemispheric lesions resolves rapidly and is thought to be so rare a condition that left-lesioned patients are almost never included in research studies on neglect and etinction [7,36,40]. One of the constraints on demonstrating precise lesion locations associated with the various forms of neglect is that most studies that include brain imaging (including very recent ones) only have computerised tomography (CT) brain scans available [24,36,40]. Even when studies do include high resolution Magnetic Resonance Imaging (MRI) these are usually single case reports and MRI scans may often be conducted as part of the patient s medical work-up, and not for the epress purpose of looking for lesions in the neuroanatomical areas hypothesised to be associated with neglect. The present study attempts to address the question what are the defining neuroanatomical and neuropsychological features of patients with persisting neglect? using the following methodology. Over an 18-month period all CVA patients living in the greater Auckland area (population of 1 million) and referred for rehabilitation were systematically assessed for unilateral neglect at 4 6 weeks post-cva. At 3 months post-cva, the nine patients who met the criteria for admission to the study received a wide range of neuropsychological tests to determine if visuospatial (perceptual and constructional) deficits, sustained attention deficits, eecutive impairments, or memory deficits were commonly found in patients with persisting neglect. These neglect patients also underwent an MRI eamination, with analyses focusing on all the lesion areas that have been implicated in neglect in the past. 2. Methods 2.1. Subjects At 4 6 weeks post-cva, occupational therapists assessed all patients admitted to the two Auckland stroke rehabilitation units (serving a population of 1 million) for unilateral neglect using the Behavioural Inattention Test (BIT) [43]. Only patients who were able to understand the test requirements were assessed; thus a small number of patients with severe language deficits or confusion were ecluded. As a result of this assessment, 13 individuals were referred to the study over an 18-month period. At a minimum of 3 months post-cva, these patients were assessed by one of the authors (AM) for inclusion into the study. The assessment including tests for unilateral neglect (using the BIT), etinction (visual, auditory, and tactile) on bilateral simultaneous stimulation, anosognosia and personal neglect using the observational ratings developed by Bisiach et al. [4], and hemiplegia [13]. Of the 13 patients referred, two with left neglect were ecluded as they had suffered a spontaneous subarachnoid haemorrhage and therefore may also have sustained diffuse damage, one patient with a right CVA and left neglect was ecluded because he spoke only Tongan, and the tests were available and normed for English speakers, one patient with a left-basal-ganglia haemorrhage and right neglect declined to participate in the study, and nine patients consented to participate. To aid with the construction of the neuropsychological profile, relevant information was gathered about work, education, family, social, and medical history. Medical information was obtained from the hospital file, which included the results of the CT scan taken on admission to hospital, routine neurological eamination, and diagnosis regarding visual field deficits. None of the participants had a visual field deficit on confrontation testing by a neurologist during their acute hospital admission or later while in the rehabilitation unit. The Edinburgh Handedness Inventory [26] was included to determine handedness, with the results demonstrating that all the participants were predominantly right handed, and had no familial history of left handedness. The nine consenting patients met the following criteria for inclusion in this study: (1) a unilateral brain lesion resulting from a CVA; (2) neglect or etinction on confrontation testing; (3) no previous history of abnormal brain development or diffuse brain damage; (4) aged between 16 and 65 years; (5) a minimum of 3 months post-cva; (6) absence of significant language and/or comprehension problems. The mean age of the nine participants was years, range years. Three were female and will be identified as F1, F2 and F3, and si were male and will be identified as M1 M6. F1 had a left CVA and all the other participants had a right CVA. All right-cva patients had suffered middle-cerebral artery-territory-strokes (MCA), with one eception: M4 had a right-basal-ganglia haemorrhage. All nine participants had been involved in an intensive inpatient neurorehabilitation program following the CVA, ranging in length from 63 to 183 days (F1 = 67, F2 = 67, F3 = 89, M1 = 183, M2 = 107, M3 = 132, M4 = 103, M5 = 116, and M6 = 63 days) MRI procedures MRI brain scans were conducted on a 1.5 T MRI system (Sigma Version 4.7, General Electric Medical Systems, Milwaukee, USA). A volumetric three-dimensional

3 A.M. Maguire, J.A. Ogden / Neuropsychologia 40 (2002) sequence covering the whole brain was performed in the sagittal plane. One hundred and twenty four contiguous 1.3 mm thick slices were obtained using sagittal short TR/TE T1 weighted sequences, aial FSE long TR-short TE proton density, and long TR/TE T2 weighted sequences plus three-dimensional spoiled gradient recalled, heavily T1 weighted sequences. The MRI scans were read by an eperienced neuroradiologist, who was blind to the neuropsychological test results. He decided whether there was an abnormality in any of the areas listed by comparing the images to three atlases of brain CT and MRI images [12,19,29] Neuropsychological eamination Test administration was carried out with the eaminer sitting opposite the participant. The tests were placed on the desktop and always centred at the body midline. The participants were not permitted to move the position of the chair in which they were seated nor the stimulus paper in front of them, but they were allowed to move their eyes and head. Responses from participants were neither prompted nor cued and participants were asked to inform the eaminer when they had completed the task. If the participants did nothing for 15 s, and the eaminer was unsure about task completion, the eaminer asked if the task was complete: the answer yes ended the task and no resumed the wait for completion. With the eception of F3, who had time constraints imposed by outside circumstances, a full neuropsychological eamination of the nine consenting patients was carried out by one of the authors (AM) at 3 22 months post-cva (F1 = 4, F2 = 14, F3 = 21, M1 = 7, M2 = 10, M3 = 9, M4 = 14, M5 = 22, and M6 = 3 months). The assessment included: additional neglect tests (Battersby Reading test [20], Line Erasure task [21], and Schenkenberg s line bisection [37]); additional screening tests (National Adult Reading test NART II [23], information and orientation from the Wechsler Memory Scale-Revised WMS-R [42], geometric figures from Aphasia screening [32], the Cookie Theft picture from the Boston Diagnostic Aphasia Eamination BDAE [14]); tests of attention and eecutive function (mental control, digits forward/backward and spatial span from the WMS-R, the Test of Everyday Attention TEA [35], and Wisconsin Card Sorting Test WCST [15]); memory tests (logical memory from the WMS-R, Doors and People Test DPT [1], and the Rey Comple Figure [22]); tests of visuoperceptual and visuoconstructional function (Visual Object and Space Perception battery VOSP [41], Hooper Visual Organisation Test HVOT [17], representational drawing and figure and shape copying from the BIT, Rey figure, and the Ogden [24] and Gainotti [11] scenes). Most of the neuropsychological assessments were scored according to the original published scoring instructions. For the cancellation tasks, in order to obtain a fail, at least three targets were missed on the contralesional side relative to the ipsilesional side. The Rey figure was scored both by the traditional method of assessing visuoconstructional and visual memory deficits, and a second method specifically assessing the percentage of unilateral neglect demonstrated for the copy and recall conditions. For the neglect scoring method, the number of details missed on each side of the Rey figure is reported as a percentage of the total number of details for that side. 1 Thus, clear contralesional neglect is only evident if the percent of neglect of the contralesional side is significantly greater than for the ipsilesional side. If the participant had a generalised attentional disorder, details would be missed on both sides. 3. Results 3.1. MRI results All the lesions were large ( cm 3 ) with all the participants with a right CVA having a lesion of 42 cm 3 or larger. Every participant had a lesion that affected three or more major lobes and subcortical (thalamus and basal ganglia) structures of the brain. A notable finding was that the lesions sustained by F1 (right neglect) and F2 (left neglect) did not encroach on the parietal lobe, the area most commonly affected in individuals with neglect. The seven participants with parietal involvement specifically had rostral-inferior-parietal involvement, four participants also had caudal-inferior-parietal involvement, and only M4 had superior parietal involvement. The findings also indicated that all of the participants demonstrated some degree of basal-ganglia involvement, with the globus pallidus and putamen implicated in every case; all participants had some frontal-lobe damage, including the frontal eye field (within Brodmann area 8) in all participants ecept M4; and eight participants had some temporal-lobe involvement. In contrast, none of the participants had occipital-lobe involvement (Table 1) Neuropsychological results for assessment at 3 22 months post-cva Screening assessment All nine participants demonstrated persisting neglect, personal neglect, and some degree of anosognosia for at least one of the three deficits (motor, visual, and personal) tested. For eample, none of the participants were aware that they missed contralesional stimuli on visual confrontation testing (visual field), M6 denied that his hemiplegia would make his job as a builder more difficult (motor), and F1 was unaware that she put lipstick on only one side of her mouth when looking in a mirror (personal). All nine participants demonstrated persisting neglect on at least one subtest of the BIT, and visual etinction on 1 Interested readers may obtain eplicit scoring criteria for all of the assessments from the first author.

4 882 A.M. Maguire, J.A. Ogden / Neuropsychologia 40 (2002) Table 1 MRI results: localisation of lesions a F1 F2 F3 M1 M2 M3 M4 M5 M6 Total volume (cm 3 ) Hemisphere Left Right Right Right Right Right Right Right Right Occipital lobe Temporal lobe Anterior temporal Posterior temporal Dorsolateral temporal Inferolateral temporal Medial temporal Parietal lobe Superior parietal lobule Rostral inferior parietal Caudal inferior parietal Temporal parietal junction Parietal occipital junction Parietal frontal junction Frontal lobe Anterior frontal Posterior frontal Orbital frontal Medial frontal Dorsolateral prefrontal corte Frontal eye field Midline frontal (anterior cingulate) Thalamus Anterior thalamus Posterior thalamus Lateral posterior nucleus Lateral dorsal nucleus Pulvinar nucleus Lateral geniculate nucleus Medial geniculate nucleus Ventral posterior nucleus Ventral lateral nucleus Ventral anterior nucleus Anterior nucleus Basal ganglia Globus pallidus Caudate head Caudate tail Putamen Midbrain etrageniculate Superior colliculus (superficial/deep) Tectal commissures Intertectal commissures Posterior commissure Peritectal Reticular formations Mesencephalic and caudal Midline raphe nuclei Nucleus locus coeruleus Retinotectal pathway Geniculostriate pathway a : MRI identified lesion. bilateral simultaneous stimulation in confrontation testing. Only five participants (M2, M4, M5, M6, and F3) demonstrated visual neglect on confrontation by failing to respond to single presentations in the left visual field. M1 and M6 demonstrated auditory etinction, and M4 demonstrated auditory etinction as well as auditory neglect to single stimuli in the left ear. This was supported by his family s observations that he did not answer the telephone when it was on his left, but did when it was on his right. M4 was also the only participant to eperience tactile neglect as well as

5 A.M. Maguire, J.A. Ogden / Neuropsychologia 40 (2002) etinction on bilateral simultaneous tactile stimulation of the dorsal surface of both hands. F1, M1, and M3 demonstrated tactile etinction but not tactile neglect Neuropsychological assessment The additional neglect and screening tests showed that none of the participants had difficulties with the general screening measures (NART, WMS-R, Aphasia screen, or Cookie Theft Picture), or had neglect on the Battersby Reading test or the Line Erasure task, but five of the nine showed severe neglect on the Schenkenberg s line bisection task. The findings from the tests of attention and eecutive function demonstrated that all but one participant (eception M4) had eecutive deficits, and all but one (eception F2) had an impaired score on at least one measure of sustained attention. The memory tests showed that M2, M4, and M6 demonstrated significant impairments on both the visual and verbal indices of the DPT, and that F2, M1, M3, and M5 demonstrated a visual verbal discrepancy, with visual memory showing the greater impairment for all but M5. All participants also demonstrated visual memory difficulties on the immediate and delayed recall trials of the Rey figure. In contrast, no participant had significant verbal memory impairments on the Logical Memory passages of the WMS-R. The results also demonstrated that the participants visuospatial difficulties were specific to visuospatial organisational and constructional skills (as measured by the HVOT, BIT, the Rey figure and/or the Ogden and Gainotti scenes), as opposed to visuospatial perceptual skills (as measured by the VOSP). All the participants demonstrated at least some impairment on the visuospatial organisational and constructional tasks but only F3 failed more than one of the VOSP subtests measuring visuospatial perceptual difficulties. 4. Discussion 4.1. Persisting unilateral neglect is a rare disorder Screening for neglect was carried out on all CVA patients in the years age range, referred over an 18-month period for rehabilitation to two stroke units serving a population of approimately 1 million. It is normal routine procedure to refer all patients who demonstrate unilateral neglect, hemiplegia, or other disabling disorders on discharge from their acute hospital admission to one of these two inpatient rehabilitation units. Thus, the finding that only 13 patients were identified with neglect, nine of whom were in this study, supports previous findings that persisting neglect is a rare condition. For eample, Samuelsson et al. [36] assessed 53 patients selected from 181 right-cva patients admitted to a stroke unit (128 were ecluded for various reasons) over a 40-month period. At 1 4 weeks post-cva, 18 had visuospatial neglect on the BIT, and by 6 months, si continued to demonstrate neglect, nine had recovered and three were lost to follow-up. In our study, we screened both right- and left-cva patients for neglect at 4 6 weeks post-cva, and found that 2 of the 13 patients with neglect (15.6%) had left-hemispheric lesions and right neglect. Although one of these patients chose not to participate in the full study, his CT brain scans were available. Both neglect patients with left lesions had basal-ganglia involvement, and F1s lesion also involved the frontal and temporal lobes and the thalamus, but not the parietal lobe. Thus, persisting neglect following left-hemispheric lesions, whilst even rarer than neglect following right-hemispheric lesions, does still occur. Given that the lesions that produce persisting neglect are usually large and involve a number of lobes of the brain [7], and given that a reasonable level of language comprehension is necessary before patients can be assessed for neglect, it seems likely that some patients with left lesions who are ecluded from neglect studies because of language deficits do have persisting neglect Lesion findings Neglect has been described following lesions to the left or right, anterior or posterior, and cortical or subcortical regions of the brain, but it is most often associated with damage to the inferior parietal lobe of the right hemisphere [39]. Recent findings demonstrate that the time post-cva (acute or post-acute stage) is important to consider in identifying the dominant lesion location in neglect. Some lesion location studies in the post-acute stage have failed to find an eclusive role for the parietal lobe [7,36], or have implicated other regions [36] or have concluded that the magnitude of the right-hemispheric lesion may be the relevant factor in neglect recovery [7,16]. In our study, persisting neglect occurred following large lesions ( cm 3 ) that affected three or more major lobes and subcortical (thalamus and basal ganglia) structures of the brain Parietal lobe Our results demonstrated support for the findings that parietal lesions are common but not essential for persisting neglect. Two of the female participants (F1 and F2) did not demonstrate parietal (or parietal junction) involvement but did demonstrate neglect on a number of measures (see Table 2). For F1, who suffered a left-hemispheric lesion, these results support Ogden s [24,25] finding that left-anterior lesions are associated with neglect more often than left-parietal lesions. For all seven participants who did demonstrate parietal involvement, the rostral inferior parietal lobe and the parietal frontal-junction regions were lesioned. By specifically distinguishing between the rostral and caudal regions of the inferior parietal lobe, our results support previous findings that, if parietal involvement eists, the rostral inferior parietal lobe is the essential lesion site for neglect. But, in contrast to previous findings that also implicate a temporal parietal-junction lesion, in our study, only four participants had this lesion but all seven participants (with

6 884 A.M. Maguire, J.A. Ogden / Neuropsychologia 40 (2002) Table 2 Neuropsychological test results Unilateral neglect participants F1 F2 F3 M1 M2 M3 M4 M5 M6 Line crossing (BIT) a P P P P P P P P P Line bisection (BIT) a P P F F F P P F P Letter cancellation (BIT) a P P F P P P P P P Star cancellation (BIT) a F F F F F F F F F Representational drawing (BIT) a F P F F F F F F F Figure/shape copying (BIT) a F P F F F P F P P Visual field etinction a Auditory etinction a Tactile etinction a Anosognosia: visual field UN a Anosognosia: motor deficit a Anosognosia: personal UN a Personal neglect a Hemiplegia (% recovery) Edinburgh (% right handed) Battersby reading test a P P P P P P P P P Line erasure task a P P P P P P P P P Schenkenberg s line bisection a P P F F F P F F P NART b NA WMS-R (info. and orient.) a P P P P P P P P P Aphasia screen a P P P P P P P P P Cookie theft picture a P P P P P P P P P WMS-R (mental control) a P P P P P P P P P WMS-R (digit span-f/b) c 0/16 99/70 18/48 35/7 81/72 35/72 51/51 18/48 81/48 WMS-R (visual memory span-f/b) c 37/59 46/94 81/48 55/59 98/48 37/48 51/54 55/75 94/59 TEA (working memory) c 5 77 NA TEA (selective attention) c NA TEA (sustained attention) c NA TEA (attentional switching) c NA WCST (categories achieved) 3 2 NA WCST (% perseverative errors) NA WMS-R (logical memory I/II) c 40/68 93/95 11/53 67/85 92/53 88/79 94/93 63/48 92/98 DPT (overall score) c NA DPT (verbal) c NA DPT (visual) c NA Rey figure (copy) c <1 <1 <1 <1 <1 <1 <1 Rey (immediate-recall) c <1 2 < Rey (delayed recall) c 10 4 <1 4 < VOSP (object subtests) a P P F P F P P P P VOSP (space subtests) a P P F P P P P P P Shapes test (DPT) a P P NA P F P P P F HVOT a Rey figure (copy-contra/ipsilesional) d 10/0 0/0 60/60 70/10 30/0 20/10 50/0 10/0 10/0 Rey (immediate recall-contra/ipsilesional) d 75/60 40/40 90/65 90/50 85/80 55/40 75/30 80/60 35/30 Rey (delayed recall-contra/ipsilesional) d 75/50 55/40 80/55 80/60 90/60 50/50 85/40 70/30 25/50 Ogden scene task d Gainotti scene task d a P: pass or F: fail; 0: none; 1: mild; 2: moderate; 3: severe. b Scaled score (mean = 100; S.D. = 15). c Percentile equivalents of age-scaled scores. The 15.9th percentile was used as the cut-off for the lower limit of normal range performance. d Percent unilateral neglect. parietal involvement) had instead a parietal frontal-junction lesion Basal ganglia A striking finding was that all nine participants demonstrated basal-ganglia involvement, and four (F1, F3, M3, and M4) had basal ganglia lesions that were specific to the area of the globus pallidus and the putamen. Basal-ganglia lesions have been previously reported in the literature, but they are most often associated with neglect deficits that are not severe, or with large lesions that also include the posterior limb of the internal capsule [5,7,8]. The individuals in our study did not have internal capsule involvement, but one individual (M4) did have white-matter involvement: he had

7 A.M. Maguire, J.A. Ogden / Neuropsychologia 40 (2002) suffered a large right-basal-ganglia haemorrhage (49 cm 3 ) that required evacuation of a clot. The role of the basal ganglia in neglect may be eplained by the widespread projections, from the visual cortical areas and the association area of the parietal corte to the putamen and caudate nuclei of the basal ganglia. According to Vallar et al. [40], the disconnection of these projections results in difficulties with organising a motor response to sensory stimuli Thalamus Thalamic involvement has been implicated in neglect, but the results from our MRI investigation demonstrated that this was the case for only two participants with persisting neglect. More importantly, these participants (F1 and M4) had lesion histories that were not typical of the other neglect participants. F1 had suffered a left CVA and M4 had suffered a large right-basal-ganglia-white-matter haemorrhage Temporal lobe With the eception of M4, all of the neglect participants demonstrated temporal-lobe involvement. But in contrast with the previous findings linking persisting neglect with lesions in the white matter, the areas most commonly implicated in the present study were the anterior and medial temporal lobes Superior dorsolateral prefrontal corte Eight of the nine participants (eception M4) demonstrated superior-dorsolateral-prefrontal-corte involvement, which included the frontal eye fields. The frontal eye fields are believed to be responsible for generating endogenous or voluntary shifts of attention. Thus, lesions in this region result in an increase in saccade latency, which is distinguished from reaction-time responses which are increased to both endogenous and eogenous cues. It is noted that lesions either to the dorsolateral prefrontal corte, basal ganglia, or the temporal parietal junction are believed to affect voluntary allocation of covert attention [31] Co-eistence of neglect, etinction, and anosognosia Previous research has demonstrated double dissociations between neglect and etinction [9,40], neglect and anosognosia [4], and neglect and personal neglect [3,28]. The participants in the present study were assessed for neglect (including personal neglect), etinction, and anosognosia to test for the co-eistence of these deficits in individuals with persisting neglect, and to eamine the results for a possible relationship with previously implicated lesion locations. Since all of the participants in the present study had persisting neglect, personal neglect, and some degree of either etinction or anosognosia (mild, moderate, or severe) there was no prospect of demonstrating double dissociations. The results for etinction and anosognosia did, however, support the findings that have shown that etinction [40] and anosognosia [4] are dissociable into function-specific forms Etinction In support of recent findings from Vallar et al. [40] who tested patients in the acute stage (within 30 days of stroke), our testing results with patients in the post-acute stage (a minimum of 3 months post-cva) indicate that neglect and etinction do not necessarily co-occur, nor do visual and tactile etinction. For eample, all the participants in our study demonstrated persisting neglect and visual etinction, but there was some dissociation for the etinction deficit across the other modalities (auditory and tactile). F1 and M3 had visual and tactile etinction but not auditory etinction, and M6 had visual and auditory etinction but not tactile etinction. Only M1 and M4 had etinction across all three modalities. Our results also indicated that damage to the right-thalamic region might be implicated in the co-eistence of neglect and etinction across more than one modality. For eample, M4 was the only right-cva participant with any evidence of thalamic involvement, and was also the only participant who demonstrated neglect and moderate-to-severe etinction across all three modalities. Previous single case reports have demonstrated an association between contralesional auditory etinction and subcortical damage, specifically implicating caudate and lenticular lesions [6]. All of the participants in our study demonstrated lenticular-lesion involvement, five had caudate involvement, but only three had auditory etinction. The one participant (M4) with the greater evidence of both auditory neglect and etinction did not have caudate involvement, although the globus pallidus and the putamen were involved Anosognosia Our results on the assessment of anosognosia support previous findings that have shown that anosognosia is dissociable into function-specific forms [4]. Although our participants had anosognosia in at least two of the areas measured, they could also have severe anosognosia on one area and no anosognosia on another. For eample, F1 and M4 demonstrated no anosognosia of their motor deficit but a moderate-to-severe anosognosia of personal and visual field neglect, and F2 demonstrated anosognosia for personal neglect and motor deficits but not for her visual field neglect. Bisiach and Geminiani [2] claim that anosognosia for aspects of neglect usually appears at the very onset of the illness, that it is usually present only during the acute state, and that it often disappears within a few hours or a few days. This claim allows Bisiach to rebut accounts that appeal to a goal-directed denial of illness as an eplanation for anosognosia. But it would not be correct to draw the conclusion that anosognosia is rare or unknown in persisting neglect since all of the neglect participants in the present study had some form of anosognosia (i.e. anosognosia for a motor or visual field deficit or for personal neglect) which persisted for at least 3 months post-cva. Furthermore, it has been demonstrated that the absence or presence of anosognosia in the

8 886 A.M. Maguire, J.A. Ogden / Neuropsychologia 40 (2002) first few days post-cva may prove a successful predictor of neglect severity [38] Neuropsychological findings The finding that all our patients lesions were etensive ( cm 3 ) and involved three or more cortical lobes or subcortical structures of the brain could suggest that neglect may only persist over many months if a number of cognitive functions are impaired. One hypothesis is that deficits in non-directional attention, visual memory, visuospatial construction, or other deficits in addition to a directional spatial inattention or unilateral neglect disorder, are necessary to maintain the neglect disorder or to prevent the individual compensating for it [16]. The neuropsychological deficits demonstrated by this group of patients with persisting neglect could certainly support such a hypothesis Sustained attentional deficits Non-directional components of attention were included in the assessment because it was important to identify attentional difficulties that could impede performance on other neuropsychological measures, and to test the hypothesis that persisting neglect requires damage to both the directionally-specific attentional system and a sustained attentional system located in the right hemisphere [18,30,33]. In support of previous findings, we found that, with the eception of F2 (right-hemispheric lesion), all of the participants had some sustained attention difficulties (as identified by the Elevator Counting, Telephone Search while Counting or Lottery subtests from the TEA). Robertson et al. [34] have indicated that the Elevator Counting subtest is significantly correlated with neglect performance on the BIT, but we found that the Lottery subtest was the best single predictor of persisting neglect, since only F2 performed normally on this task. Pardo et al. [27] propose that sustained attention deficits result from prefrontal or superior-parietal-corte lesions of the right hemisphere. The results from the present study demonstrate that F1 and F2 had the least difficulties with sustained attention, as measured by both the number of subtests failed and the overall percentile equivalents of age-scaled scores. F1 and F2 were also the only two participants without parietal involvement. M4, the neglect participant with the greatest sustained attention difficulties was the only participant with superior-parietal-corte involvement. These findings implicate the superior parietal lobe in sustained attention difficulties, since, with the eception of M4, all the participants had prefrontal-corte involvement, but they did not all have sustained attention deficits. 5. Conclusions This investigation was conducted for the purpose of developing a detailed neuropsychological profile for each of the nine participants with persisting symptoms of neglect. The profile of strengths and deficits was epected to reveal patterns of performance which would ultimately lead to the establishment of subgroups of individuals whose performance could then be linked to specific lesions sites as identified by MRI. The findings indicate that persisting unilateral neglect is more common following a right CVA than left CVA, but nevertheless, left lesions did result in long-term neglect. The lesions producing persisting neglect were etensive, and involved three or more cortical lobes or subcortical regions. The parietal lobe, although historically considered the cortical area most closely associated with neglect, was lesioned in only seven of the participants, with the rostral inferior parietal lobule affected in all seven. In all nine participants, the most common lesion sites were the globus pallidus and the putamen of the basal ganglia, and the frontal lobe, which in eight cases involved the posterior frontal lobe and/or the superior dorsolateral prefrontal corte (including the frontal eye field). The temporal lobe was also lesioned in eight of the nine participants, with the anterior and medial temporal lobe being most commonly affected. The thalamus, also a lesion often associated with neglect in other studies, was damaged in only two participants. The occipital lobe, in line with neglect research generally, was never lesioned. Somewhat unepectedly, none of the participants had a visual field deficit, and all had a hemiplegia, in many cases still severe many months following the CVA. Given the large lesions, it was not surprising that all the participants had a range of other neuropsychological deficits in addition to neglect (including personal neglect), etinction, and anosognosia for one or more aspects of their neglect. Most had some visuospatial constructional and organisational difficulties, sustained attention problems on one or more measures, and visual memory problems on either the visual inde of the DPT or the Rey figure. One possible conclusion that might be drawn from this profile of patients with neglect is that unilateral neglect persists past the acute stage of a CVA only if the patient has a number of other visuospatial or attentional neuropsychological deficits which interfere with recovery from the neglect. For eample, acute neglect may be a transient result of a sudden decrease in the patient s cognitive awareness of contralesional space (e.g. because of a decrease in the ability to focus attention contralesionally). In the majority of patients, as the damaged brain stabilises and adapts to its new lesioned state, the individual becomes aware of the absurdity of his or her neglect behaviours, and utilises other more intact cognitive abilities to compensate. In patients with large lesions which result in the impairment of a number of other important spatial and attention functions, full awareness, and/or full compensation is not possible, and the neglect persists.

9 A.M. Maguire, J.A. Ogden / Neuropsychologia 40 (2002) Acknowledgements The authors would like to thank Professor M.C. Corballis for helpful suggestions and Dr. John Wilson for interpreting the MRI brain scans. This research was supported in part by the New Zealand Neurological Foundation Incorporated Grant to M.C. Corballis and A.M. Maguire. References [1] Baddeley A, Emslie H, Nimmo-Smith I. Doors and people: a test of visual and verbal recall and recognition. Bury St. Edmunds: Thames Valley Test Company, [2] Bisiach E, Geminiani G. Anosognosia related to hemiplegia and hemianopia. In: Prigatano GP, Schacter DL, editors. Awareness of deficit after brain injury: clinical and theoretical issues. Oford: Oford University Press, [3] Bisiach E, Perani D, Vallar G, Berti A. Unilateral neglect: personal and etra-personal. Neuropsychologia 1986;24: [4] Bisiach E, Vallar G, Perani D, Papagno C, Berti A. Unawareness of disease following lesions of the right hemisphere: anosognosia for hemiplegia and anosognosia for hemianopia. Neuropsychologia 1986;24: [5] Damasio AR, Damasio H, Chang Chui H. Neglect following damage to frontal lobe and basal ganglia. Neuropsychologia 1980;18: [6] De Renzi E, Gentilini M, Pattacini F. Auditory etinction following hemisphere damage. Neuropsychologia 1984;22: [7] Egelko S, Gordon WA, Hibbard MR, et al. Relationship among CT scans, neurological eam, and neuropsychological test performance in right brain damaged stroke patients, Journal of Clinical and Eperimental Neuropsychology 1988;10: [8] Ferro JM, Kertesz A, Black SE. Subcortical neglect: quantitation, anatomy, and recovery. Neurology 1987;37: [9] Findlay JM, Walker R. Visual attention and saccadic eye movements in normal human subjects and in patients with unilateral neglect. In: Zangemeister WH, Stiehl HS, Freksa C, editors. Visual attention and cognition. North-Holland: Elsevier, [10] Gainotti G, D Erme P, Monteleone D, Silveri MC. Mechanisms of unilateral spatial neglect in relation to laterality of cerebral lesions. Brain 1986;109: [11] Gainotti G, Messerli P, Tissot R. Qualitative analyses of unilateral spatial neglect in relation to laterality of cerebral lesions. Journal of Neurology, Neurosurgery and Psychiatry 1972;35: [12] Gerhardt P, Frommhold W. Atlas of anatomic correlation in CT & MRI. Thieme Medical Publishers Inc., [13] Gialanella B, Mattioli F. Anosognosia and etrapersonal neglect as predictors of functional recovery following right hemisphere stroke. Neuropsychological Rehabilitation 1992;2: [14] Goodglass H, Kaplan E. Boston diagnostic aphasia eamination (BDAE). Philadelphia: Lea and Febiger, [15] Heaton RK, Chelune GJ, Talley JL, Kay GG, Curtiss G. Wisconsin card sorting test manual: revised and epanded. Odessa: Psychological Assessment Resources Inc., [16] Heir DB, Mondlock J, Caplan LR. Recovery of behavioural abnormalities after right hemisphere stroke. Neurology 1983;33: [17] Hooper HE. Hooper visual organisation test. Los Angeles: Western Psychological Services, [18] Karnath H-O. Deficits of attention in acute and recovered visual hemineglect. Neuropsychologia 1988;26: [19] Kretschmann H-J, Weinrich W. Neuroanatomy and cranial computed tomography. Thieme Medical Publishers Inc., [20] Lezak M. Neuropsychological assessment. New York: Oford University Press, [21] Mark VW, Kooistra CA, Heilman KM. Hemispatial neglect affected by non-neglect stimuli. Neurology 1988;38: [22] Meyers JE, Meyers KR. REY comple figure test and recognition trial. Odessa: Psychological Assessment Resources Inc., [23] Nelson HE, Willlison JR. National adult reading test (NART): test manual (Part II). Windsor, UK: NFER-Nelson Publishing Company Limited, [24] Ogden JA. Anterior posterior interhemispheric differences in the loci of lesions producing visual hemineglect. Brain and Cognition 1985;4: [25] Ogden JA, The neglected left hemisphere and its contribution to visuospatial neglect. In: Jeannerod M, editor. Neurophysiological and neuropsychological aspects of spatial neglect. North-Holland: Elsevier, [26] Oldfield RC. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 1971;9: [27] Pardo JV, Fo PT, Raichle ME. Localisation of a human system for sustained attention by positron emission tomography. Nature 1991;349:61 4. [28] Peru A, Pinna G. Right personal neglect following a left hemisphere stroke: a case report. Corte 1997;33: [29] Pomeranz S. MRI total body atlas neuro MRI-EFI, vol. 1. MRI Education Foundation Inc., [30] Posner MI, Petersen SE. The attention system of the human brain. Annual Review of Neuroscience 1990;13: [31] Rafal R. Visual attention: converging operations from neurology and psychology. In: Kramer AF, Coles MGH, Logan GD, editors. Converging operations in the study of visual selective attention. Washington, DC: American Psychological Association, [32] Reitan RM, Wolfson D. The Halstead Reitan neuropsychological test battery: theory and clinical interpretation. Tucson, AZ: Neuropsychology Press, [33] Robertson IH. The relationship between lateralised and non-lateralised attentional deficits in unilateral neglect. In: Robertson IH, Marshall JC, editors. Unilateral neglect: clinical and eperimental studies. East Susse: Lawrence Erlbaum Associates Ltd., [34] Robertson IH, Manly T, Beschin N, et al. Auditory sustained attention is a marker of unilateral spatial neglect, Neuropsychologia 1997;35: [35] Robertson IH, Ward T, Ridgeway V, Nimmo-Smith I. The test of everyday attention (TEA). Bury St. Edmunds: Thames Valley Test Company, [36] Samuelsson H, Jensen C, Ekholm S, Naver H, Blomstrand C. Anatomical and neurological correlates of acute and chronic visuospatial neglect following right hemisphere stroke. Corte 1997;33: [37] Schenkenberg T, Bradford DC, Aja ET. Line bisection and unilateral visual neglect in patients with neurologic impairment. Neurology 1980;30: [38] Stone SP, Patel P, Greenwood RJ, Halligan PW. Measuring visual neglect in acute stroke and predicting its recovery: the visual neglect recovery inde. Journal of Neurology, Neurosurgery and Psychiatry 1992;55: [39] Vallar G. The anatomical basis of spatial hemineglect in humans. In: Robertson IH, Marshall JC, editors. Unilateral neglect: clinical and eperimental studies. East Susse: Lawrence Erlbaum Associates Ltd., [40] Vallar G, Rusconi ML, Bignamini L, Geminiani G, Perani D. Anatomical correlates of visual and tactile etinction in humans: a clinical CT scan study. Journal of Neurology, Neurosurgery and Psychiatry 1994;57: [41] Warrington EK, James M. The visual object and space perception battery (VOSP). Bury St. Edmunds: Thames Valley Test Company, [42] Wechsler D. The Wechsler memory scale-revised. San Antonio: The Psychological Corporation, [43] Wilson B, Cockburn J, Halligan P. Behavioural inattention test. Fareham: Thames Valley Test Company, 1987.