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Auditory sustained attention is a marker of unilateral spatial neglect
Neuropsychologia,Vol. 35, No. 12, pp. 1527 1532, 1997
~
Pergamon
PII: S0028 3932(97)00084 5
,~;: 1997 Elsevier Science Ltd. All rights reserved Printed in Great Britain 0028-3932/97 $17.00+0.00
Auditory sustained attention is a marker of unilateral spatial neglect IAN H. ROBERTSON,* TOM MANLY,* NICOLETTA BESCHIN,t ROBERTA DAINI,++ HILARY HAESKE-DEWICK,§ VOLKER HOMBERG,§ MERVI JEHKONEN,¶ GINO PIZZAMIGLIO,~ AGNES SHIELI] and EUGEN WEBER** *MRC Applied Psychology Unit, Addenbrooke's Hospital, Cambridge, CB2 2QQ, U.K.; tOsped Bellini, USL 6, Unita Operat Gallarate, Somma Lombardo, Vatican City, Italy; +Clinica S. Lucia, Rome, Italy; §Institut an der Heinrich-Heine-Universitat, Dusseldorf, Germany; ¶lDepartment of Neurology and Rehabilitation, Tampere University Hospital, Tampere, Finland; IlDepartment of University Rehabilitation, Southampton General Hospital, Southampton, U.K.; **Neurologische Rehabilitation Zentrum, Bonn, Germany
(Receh'ed 23 July 1996; accepted 22 May 1997) Abstract--The relationships between performance on a non-spatially-lateralized measure of sustained attention and spatial bias on
tests sensitive to unilateral neglect were considered in a group of 44 patients with right hemisphere lesions following stroke. As predicted from earlier studies showing a strong association between unilateral spatial neglect and sustained attention, performance on a brief and monotonous tone-counting measure formed a significant predictor of spatial bias across a variety of measures of unilateral visual neglect. This study provides further evidence for a very close link between two attentional systems hitherto regarded as being quite separate, namely a spatial attention system implicated in unilateral neglect and a sustained attention system. A close connection between these two systems was predicted by Posner, who argued that the right hemisphere-dominant sustained attention system provides a strong modulatory influence on the functioning of the lateralized posterior attention system. !© 1997 Elsevier Science Ltd. All rights reserved Key Words: stroke; parietal; lateralization; right hemisphere; frontal.
quent upon the dominance of this hemisphere in developing and maintaining an alert, 'ready to respond' state [8]. Making a more specific link between a system necessary to maintain attention and a system for directing attention in space, Posner [14] has argued that the sustained attention system exerts modulatory influence over the spatial attentional system via the right hemisphere-dominant neurotransmitter noradrenaline [12], which has particularly strong terminal innervations in parietal areas in rhesus monkeys [2]. Evidence for the existence of a right hemisphere localized sustained attention system has been produced in several positron emission tomography (PET) studies [3, 4, 13], as well as in evoked potential studies of sustained attention [26]. The role of norepinephrine in human sustained attention has also been demonstrated recently [22]. There is increasing behavioural evidence in humans for both an association and a modulatory relationship between sustained attention and lateralized spatial attention. Hjatlson et al. [9], for example, in considering patients with clinical manifestations of unilateral neglect,
Introduction
Many authors have argued that unilateral spatial neglect is associated with bilateral spatial, as well as unilateral spatial, attentional problems [8, 12, 15, 18, 23]. A number of explanations have been put forward to explain this, including that the right hemisphere is dominant for spatial attention across both right and left hemispace, while the left hemisphere only has partial responsibility for attention to the right spatial field [6]. By this argument, a right hemisphere lesion would result in a bilateral reduction in spatial attentional capacity in addition to the more striking poverty of attention to left hemispace. An alternative view sees the bilateral spatial deficits associated with right hemisphere lesions as being c o n s e -
* Address for correspondence: MRC Applied Psychology Unit, Rehabilitation Research Group, Box 58, Addenbrooke's Hospital, Cambridge CB2 2QQ, U.K.; tel.: +44 1223 355294 ext. 354; fax: +44 1223 516630; e-mail: ian.robertson(cLmrcapu.cam.ac.uk. 1527
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demonstrated a significant relationship between performance on two tests o f spatial bias and performance on a sustained attention task. Nigg et al. [11] examined the performance o f children who showed generalized attentional problems and demonstrated a significant bias in the detection o f left-sided stimuli on a spatially sensitive task. Recently, a b o y initially assessed for problems in detecting left-sided stimuli was found to have specific problems in maintaining attention to non-lateralized stimuli, despite generally high levels o f cognitive function [101. In terms o f a m o d u l a t o r y relationship, several studies have demonstrated that non-lateralized, and indeed nonvisual, attentional load can exaggerate the pathological bias in unilateral neglect (e.g., [16]). It has also been shown that improving alertness and sustained attention via a self-instructional procedure produces very significant and specific improvements in lateralized spatial attention in a group of unilateral neglect subjects [19]. While the precise nature o f a right hemisphere-dominant system for endogenously maintaining attention remains unclear, one class of measure which has received support across lesion, neuroimaging and factor analytic studies of attention is that o f maintaining a count of rather m o n o t o n o u s stimuli. Wilkins et al. [24] asked patients with focal neurological lesions to count a series o f tones and a series of tactile stimuli presentations. At longer interstimulus intervals (ISis), patients with lesions to the right frontal lobe were particularly impaired relative to left frontal and posterior patients. At shorter intervals, this difference disappeared. As, apart from presentation rate, the tasks remained identical, Wilkins et al. argued that the relative impairment at longer ISis was attributable to a failure to voluntarily sustain attention to the repetitive, m o n o t o n o u s stimuli. P a r d o et al. [13] supported the putative role o f a right hemisphere sustained attention system in counting tasks of this type with a P E T study of normals who were required to count brief interruptions in somatosensory stimulation over a 40-sec period. They showed that a right hemisphere frontal and parietal activation was associated with this sustained attention task. We have also shown that an adapted version of Wilkins et al.'s tone counting task (made more demanding by having variable intervals o f between 3 and 5 sec between each tone within a string) forms part of a separate sustained attention factor in a factor analytic study of attentional performance in 154 normal controls [21], and have further shown that improvements in neglect contingent u p o n improvements in sustained attention are closely associated with improvements on this tone counting task [19]. As both measures o f spatial bias and of sustained attention are particularly sensitive to right hemisphere damage, comparison o f left and right hemisphere patients on such measures could only serve, at best, to support this gross level o f anatomical association. Consideration of the relative patterns of impairment within a right hemi-
sphere-lesioned group, on the other hand, can provide more compelling support for a closer association o f these intuitively rather disparate functions. This study therefore considers the ability of a brief test o f sustained attention function to predict the occurrence and severity o f lateralized spatial bias in a right hemisphere-lesioned group.
Methods Subjects
For the purpose of the first, correlational, analysis, a total of 44 right hemisphere CVA patients who were less than 1 year post-stroke and who had been assessed in a number of centres across the European Union were selected. The mean age of the subjects was 64.27 (S.D. 12.66), and they were a mean of 88.68 (96.6) days post-stroke. They had a mean left-sided motor impairment on the Motoricity Index [5] (see Procedure) of 37.04 (35.22). Two subjects showed aphasia, although this was not sufficient to prevent them from understanding task instructions. On the standardized assessment of visual fields (see Procedure), 17 subjects showed results consistent with left-sided hemianopia. For the 10 cases where this procedure was not completed, clinical reports suggest left-sided hemianopia in a further three cases. The mean deviation to the right on Line Bisection (see Procedure) was 6.10 mm (S.D. 13.40 mm). All 44 of these subjects had computer tomography (CT)- or magnetic resonance imaging-defined cortical or subcortical lesions. For the second factorial analysis, a subset of 30 of these subjects were selected on the basis of creating two groups, with and without unilateral neglect respectively, who were matched on significant demographic and neurological characteristics. As also shown in Table 1, patients showing neglect did not differ from the non-neglect subjects in age, extent of education, time post-stroke or degree of contralesional motor impairment. They did, however, differ significantly on two tests of unilateral neglect, as would be expected. Table 2 summarizes the lesion data for the subset of 30 subjects used in the second analysis. The groups did not differ in how many distinct brain regions were shown on CT to be affected by the stroke. Table 2 shows data on parietal and frontal involvement, together with the number of brain regions affected (broken down into frontal, parietal, temporal, occipital and subcortical--maximum possible number of regions affected = 5). There was no significant difference between groups on incidence of parietal or frontal lesions, nor on the total number of brain regions affected.
Procedure
All patients received a battery of tests of unilateral spatial neglect, as well as tests of auditory sustained attention, tests of motor and sensory function and tests of visual fields. Only the tests relevant to the present paper will be presented and these are as follows. Elevator Countin9 test of auditor)" sustained attention. This test consisted of two sequential presentations (forms 1 and 2 together) of the Elevator Counting test of the Test of Everyday Attention [20, 21]. The task is based on the tone counting procedure shown to be sensitive to right frontal lobe lesions [24]. It consists of 14 audiotape-presented strings of between three and 14 tones, with random intervals of between 3 and 5 sec between each tone. Subjects are presented with each string in turn and are simply required to count how many tones
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Table 1. Summary of demographic details for comparison groups RHN -
RHN +
M:F Age Time post-stroke (days) Years of education Contralesional Motor Impairment* (Motoricity Index) Star Cancellation (left detected targets/total detected targets)]:
11:6 60.6 (14.7) 74.0 (63.9) l l.0 (3.5) 58.9 (33.4) 0.5 (0.01)
9:4 68.8 (8.3) 62.2 (87.3) 8.9 (4.7) 43.2 (29.9) 0.24 (0.23)
Line Bisection (deviation from objective centre in mm; + = right of centre)
0.81 (3.49)
9.97 (16.44)
ns ns ns ns
ns t28=4.7 P<0.03 t2s= --2.2 P<0.03
*Reference [5]. tReference [25]. Table 2. Summary of lesion data for two comparison groups RHN Lesion extent (number of lobes showing damage 1:2:3: > 3) Parietal lobe involvement (yes : no) Frontal lobe involvement (yes:no)
occurred in each string. This number is produced in response to a standard verbal probe on tape. One point is awarded for each string, and hence the maximum score on this task is 14 and the minimum score is 0. This task is very easy for nonbrain-damaged controls, who seldom make errors on it [21]. Line Bisection. This test consisted of 10200 1.5mm black lines presented on A4 paper, and bisected by subjects with a pen. Star Cancellation. This subtest of the Behavioural Inattention Test (BIT) [25] requires subjects to mark small stars against competing non-targets. Figure and Shape Copying. This subtest of the BIT [25] requires subjects to copy a series of shapes presented. Representational Drawing. This subtest of the BIT [25] requires subjects to draw three objects from memory. Comb and Razor test of personal neglect. This test was adapted from a semi-structured measure of personal neglect devised by Zoccolotti and Judica [27]. It was adapted to a more quantifiable version [1, 18], involving counting the number of motor acts to the left and right of the body respectively during hair combing, shaving (in the case of men) or use of powder compact (in the case of women). Motoricity Index. The Motoricity Index assesses six limb movements. Weighted scores are given to each movement and these are summed to give a final numerical score of overall power. This is done for each side of the body [5]. Visual fields" confrontation assessment. Visual fields were assessed using standard confrontation testing, including catch trials and extinction trials where bilateral stimuli were presented. Ten left and 10 right single stimuli were presented.
-
7:3:3:0 7:6 3:11
RHN + 6:5:2:0 5:8 5:8
ns ns ns
a t t e n t i o n task, the m e a s u r e s o f unilateral neglect a n d the m e a s u r e o f c o n t r a l e s i o n a l m o t o r function. Table 3 shows the results. T a b l e 3 shows t h a t the hypothesis was s u p p o r t e d in t h a t strong and statistically significant c o r r e l a t i o n s existed between n o n - l a t e r a l i z e d a u d i t o r y sustained attention a n d lateralized spatial i n a t t e n t i o n in this g r o u p o f right h e m i s p h e r e - d a m a g e d patients. Significant correlations were evident with spatially biased p e r f o r m a n c e in the Star C a n c e l l a t i o n subtest o f the B I T ( r = 0 . 5 2 7 , P < 0.001), the Line Bisection t a s k (r = - 0.340, P < 0.05), the F i g u r e a n d S h a p e C o p y i n g a n d R e p r e s e n t a t i o n a l D r a w i n g subtests o f the B I T ( r = 0 . 5 3 6 , P < 0 . 0 0 1 ; r = 0 . 5 4 2 , P < 0 . 0 0 1 ) , a n d on b o t h C o m b a n d R a z o r subtests o f the C o m b a n d R a z o r task ( C o m b : r = 0 . 5 6 3 , P < 0 . 0 1 ; Razor: r = 0 . 5 1 5 , P < 0 . 0 1 ) . As p a r t i c i p a n t s with unilateral neglect were significantly m o r e i m p a i r e d in c o n t r a l e s i o n a l m o t o r func-
Table 3. Correlations between auditory sustained attention task and measures of unilateral neglect Tests in correlation with Elevator Counting
Correlation coefficient (r) 0.527*** -0.340* 0.536*** 0.542*** 0.563*** 0.515"*
Analysis 1
Star Cancellation Line Bisection (mean deviation) BIT Figure and Shape Copying BIT Representational Drawing Comb testt Razor testt
The h y p o t h e s i s a d v a n c e d in the I n t r o d u c t i o n was that unilateral neglect should be related to d i s o r d e r s o f sust a i n e d attention. The first analysis e x a m i n e d c o r r e l a t i o n s within the w h o l e g r o u p between the a u d i t o r y sustained
***P<0.001. **P<0.01. *P<0.05. tThis result is based on only 30 out of the 44 subjects who were given the test.
Results
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I.H. Robertson et al./Auditory sustained attention 14
P
12
[]
RHN-
[]
RI-IN+
o
l0 =
8
e~ = ©
6
4
2 0
Fig. 1. Sustained attention performance of right brain damaged groups with and without neglect.
tion than those with no neglect, and as motor function itself formed a significant correlate of the sustained attention measure, it was important to establish whether sustained attention formed an independent predictor of spatial function. To this end, each of the neglect measures which formed significant correlates of Elevator Counting scores were individually entered into a regression equation as dependents, with Elevator Counting as the independent measure. The relationships were then tested by entering contralesional m o t o r function as a second independent in a multiple regression. In isolation, Elevator Counting performance accounted for 27.8% (P<0.001) of the variance in lateralized Star Cancellation performance. The addition of contralesional motor function added a non-statistically significant further 7.9% (P=0.08) to the variance accounted for, while Elevator Counting remained a significant predictor (P < 0.01). Table 4 shows this and three other multiple regressions performed. A similar picture was apparent for the C o m b and Razor subtests, where initial variance explained by the sustained attention measure was 30.5% and 26.5% ( P < 0 . 0 1 , P < 0 . 0 1 ) respectively, and where the addition of motor scores added only a non-significant 4.2% and 3.3% (P = 0.25, P = 0.34 respectively) to the variance explained. For the Copying
subtest of the BIT, Elevator Counting in isolation accounted for 28.7% of the variance. Motoricity added significantly to the variance explained (Elevator Counting + Motoricity = 40.7%), although the Elevator Counting term remained statistically significant (P<0.01). Analysis of results from the Representational Drawing subtest of the BIT showed a similar pattern. Elevator Counting in isolation accounted for 29.4% of Drawing variance ( P < 0.001). This term remained significant when Motoricity Index scores were added (Elevator Counting P < 0.01, Motoricity P < 0.05). in combination, these two measures accounted for 42.6% of the Drawing test variance. For Line Bisection, on the other hand, the significant independent contribution from Elevator Counting scores disappeared when Motoricity scores were also entered into the regression, with neither the contribution of Elevator Counting nor Motoricity independently reaching statistical significance. It is of interest to note how well the sustained attention task correlated with performance on the neglect tests, in comparison to how well the neglect tests themselves intercorrelated. Table 5 shows the intercorrelations among the following tests: auditory sustained attention, Star Cancellation, Figure/Shape Copying, Representational Drawing and the measure of personal neglect, namely the C o m b and Razor task. Table 5 shows that the Elevator Counting test and the Star Cancellation test are the only measures with statistically significant correlations with all other measures. In contrast, personal neglect as measured by the C o m b task is non-significantly correlated with Line Bisection and the Figure Copying subtest of the BIT [25]. A further test of the relative independence of sustained attention performance as a predictor of unilateral neglect was pursued in a group comparison. F r o m the initial group of 44 right hemisphere-lesioned patients, a group of 30 were selected such that the subgroup who showed unilateral neglect did not statistically significantly differ in terms of m o t o r function from those who did not show neglect (see Table 1). A one-way analysis of variance showed a large group difference in sustained attention scores, with the group showing unilateral neglect achieving a mean correct score of 9.31/14 (S.D. 4.97), while the
Table 4. Multiple regressions of auditory sustained attention and contralesional motor function on selected measures of unilateral neglect
Independent variable 1. Elevator Counting Elevator Counting + left-sided 2. Elevator Counting Elevator Counting + left-sided 3. Elevator Counting Elevator Counting+ left-sided 4. Elevator Counting Elevator Counting +left-sided
Motoricity Index Motoricity Index Motoricity Index Motoricity Index
Dependent variable
Total explained variance (%)
Added variance (%)
Star Cancellation (left/total) Star Cancellation (left/total) Comb test Comb test Copying test (BIT) Copying test (BIT) Representational Drawing (BIT) Representational Drawing (BIT)
27.8 35.7 31.7 35.9 28.7 40.7 29.4 42.6
-7.9 -4.2 -12.0 -13.2
Significance of added variance ns -ns P<0.05 -P < 0.05
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I. H. Robertson et al./Auditory sustained attention Table 5. Correlations between auditory sustained attention and measures of spatial neglect Elevator Counting Elevator Counting Star Cancellation Line Bisection Figure/Shape Representational Drawing Comb test Razor test
Star Cancellation 0.527
Line Bisection -0.340 -0.472
non-neglect group had a mean correct score of 13.12/14 [S.D. 1.11, F1,2~=9.459; P<0.01; see Fig. 1].
Discussion The above results show that (i) unilateral left neglect is highly correlated with performance on a spatially nonlateralized auditory sustained attention task; (ii) auditory sustained attention performance significantly discriminates between right hemisphere-damaged patients with and without neglect; (iii) these relationships are unlikely to arise on the basis of general factors such as lesion severity. The results are striking because a non-spatial attention measure is as powerful as certain standardized spatiallybased tests in discriminating unilateral neglect among right hemisphere patients. The results are perhaps even more surprising when the apparent simplicity of the sustained attention task is considered. All that is required of subjects is to maintain an internal count of up to a maximum of 14 tones which are separated by no more than 3-sec intervals. Due to its conceptual simplicity, the undemanding nature of the numericity judgement and the ease with which the tones can be discriminated [20], the challenging aspect of this task (approximately 86% of which consists of silence) lies almost entirely in keeping one's mind on it. That unilateral neglect patients are particularly poor at endogenously maintaining their attention in this way is entirely consistent with Posner's anatomically driven hypothesis that spatial orientation is mediated by a posterior orientation system and a right hemisphere-dominant alertness/sustained attention system [14]. He argued that the norepinephrine system mediates alertness and cites evidence that the strongest terminal projections of this system are in somatosensory areas of the parietal lobe implicated in unilateral neglect [2]. In short, patients who show auditory sustained attention system deficits as well as unilateral spatial neglect have a doubly compromised capacity for spatial orientation to the neglected side. The general point that interactions occur between spatial and non-spatial attentional systems has been bols-
Figure/ Shape 0.536 0.614 -0.297
Representational Drawing 0.542 0.636 -0.230 0.658
Comb test
Razor test
0.563 0.455 0.032 0.452 0.408
0.515 0.521 -0.075 0.343 0.350
Motoricity Index 0.388 0.431 -0.312 0.486 0.515
tered by studies showing that purely auditory attentional load causes deterioration in visual neglect [16]. Specific support for an interaction between systems necessary to endogenously maintain an alert 'ready to respond' state and spatial attention has come from experimental studies showing improvement in neglect when the sustained attention system is improved [19], as well as in correlational studies [9, 11]. What precisely is the nature of this link between an alertness/sustained attention system, on the one hand, and a spatial orientation system on the other? One possibility (consistent with Heilman's hypothesis [7]) is that the patient is hypoaroused because of the lesion to a right hemisphere-dominant alertness system, and that there is a general improvement in all functions, including neglect, when sustained attention/alertness improves. This nonspecific hypothesis can be contrasted with one which argues that it is particularly a parietal lobe-based spatial orientation system which is a privileged recipient of activation from the alertness/sustained attention system. The latter hypothesis, attributable to Posner [14], is supported by the PET study by Pardo et al. [13], showing that a sustained attention task caused right hemisphere frontal and parietal activation in normal subjects. This finding is of considerable importance theoretically and practically in understanding the nature of unilateral neglect. It has already been shown that neglect can be improved significantly by improving sustained attention [19], and that the non-lateralized aspect of right hemisphere attention deficit may be just as important in determining deficits in spatial attention as is the spatial bias itself.
Acknowledgement~This paper is dedicated to the memory of
Catherine Bergego, friend and colleague of all the authors. The authors would like to acknowledge the support of the European Union Biomed II programme for its support of this project. Many thanks also to colleagues involved in other aspects of the project, and in particular G6rard Deloche, Peter HaUigan, Florence Marchal, Franz Stachowiak, Richard T6gner and Pierliugi Zoccolotti. Particular thanks to Julia Darling for her careful preparation of this manuscript.
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References
1. Beschin, N. and Robertson, I. H., Personal and extrapersonal neglect following right hemisphere stroke. Cortex, 1997, 33, 379 384. 2. Brown, R. M., Crane, A. M. and Goldman, P. S., Regional distribution of monoamines in the cerebral cortex and subcortical structures in the rhesus monkey: concentrations in vivo synthesis rates. Brain Research, 1979, 168, 133 150. 3. Cohen, R. M., Semple, W. E., Gross, M., Holcomb, H. J., Dowling, S. and Nordahl, T. E., Functional localization of sustained attention. Neuropsychiatry, Neuropsychology and Behavioural Neurology, 1988, 1, 3-20. 4. Cohen, R. M., Semple, W. E., Gross, M., King, A. C. and Nordahl, T. E., Metabolic brain pattern of sustained auditory discrimination. Experimental Brain Research, 1992, 92, 165-172. 5. Collen, C. and Wade, D. T., Assessing motor impairment after stroke: a pilot reliability study. Journal of Neurology, Neurosurgery and Psychiatry, 1990, 53, 576-579. 6. Corbetta, M., Miezin, F. M., Schulman, G. L. and Peterson, S. E., A PET study of visuospatial attention. The Journal of Neuroscience, 1993, 13, 12021206. 7. Heilman, K. M. and Abell, T. V. D., Right hemisphere dominance for mediating cerebral activation. Neuropsychologia, 1979, 17, 315-321. 8. Heilman, K. M., Schwartz, H. D. and Watson, R. T., Hypoarousal in patients with the neglect syndrome and emotional indifference. Neurology, 1978, 28, 229-232. 9. Hjaltason, H., Tegn6r, R., Tham, K., Levander, M. and Ericson, K., Sustained attention and awareness of disability in chronic neglect. Neuropsychologia, 1996, 34, 1229 1233. 10. Manly, T., Robertson, I. H. and Verity, C., Developmental unilateral neglect: a single case study. Neurocase, 1997, 3, 19-29. 11. Nigg, J. T., Swanson, J. M. and Hinshaw, S. P., Covert spatial attention in boys with attention deficit hyperactivity disorder: lateral effects, methylphenidate response and results for parents. Neuropsychologia, 1997, 35, 165 176. 12. Oke, A., Keller, R., Mefford, I. and Adams, R., Lateralization of norepinephrine in human thalamus. Science, 1978, 200, 1411-1413. 13. Pardo, J. V., Fox, P. T. and Raichle, M. E., Localization of a human system for sustained attention by
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Pergamon
PII: S0028 3932(97)00084 5
,~;: 1997 Elsevier Science Ltd. All rights reserved Printed in Great Britain 0028-3932/97 $17.00+0.00
Auditory sustained attention is a marker of unilateral spatial neglect IAN H. ROBERTSON,* TOM MANLY,* NICOLETTA BESCHIN,t ROBERTA DAINI,++ HILARY HAESKE-DEWICK,§ VOLKER HOMBERG,§ MERVI JEHKONEN,¶ GINO PIZZAMIGLIO,~ AGNES SHIELI] and EUGEN WEBER** *MRC Applied Psychology Unit, Addenbrooke's Hospital, Cambridge, CB2 2QQ, U.K.; tOsped Bellini, USL 6, Unita Operat Gallarate, Somma Lombardo, Vatican City, Italy; +Clinica S. Lucia, Rome, Italy; §Institut an der Heinrich-Heine-Universitat, Dusseldorf, Germany; ¶lDepartment of Neurology and Rehabilitation, Tampere University Hospital, Tampere, Finland; IlDepartment of University Rehabilitation, Southampton General Hospital, Southampton, U.K.; **Neurologische Rehabilitation Zentrum, Bonn, Germany
(Receh'ed 23 July 1996; accepted 22 May 1997) Abstract--The relationships between performance on a non-spatially-lateralized measure of sustained attention and spatial bias on
tests sensitive to unilateral neglect were considered in a group of 44 patients with right hemisphere lesions following stroke. As predicted from earlier studies showing a strong association between unilateral spatial neglect and sustained attention, performance on a brief and monotonous tone-counting measure formed a significant predictor of spatial bias across a variety of measures of unilateral visual neglect. This study provides further evidence for a very close link between two attentional systems hitherto regarded as being quite separate, namely a spatial attention system implicated in unilateral neglect and a sustained attention system. A close connection between these two systems was predicted by Posner, who argued that the right hemisphere-dominant sustained attention system provides a strong modulatory influence on the functioning of the lateralized posterior attention system. !© 1997 Elsevier Science Ltd. All rights reserved Key Words: stroke; parietal; lateralization; right hemisphere; frontal.
quent upon the dominance of this hemisphere in developing and maintaining an alert, 'ready to respond' state [8]. Making a more specific link between a system necessary to maintain attention and a system for directing attention in space, Posner [14] has argued that the sustained attention system exerts modulatory influence over the spatial attentional system via the right hemisphere-dominant neurotransmitter noradrenaline [12], which has particularly strong terminal innervations in parietal areas in rhesus monkeys [2]. Evidence for the existence of a right hemisphere localized sustained attention system has been produced in several positron emission tomography (PET) studies [3, 4, 13], as well as in evoked potential studies of sustained attention [26]. The role of norepinephrine in human sustained attention has also been demonstrated recently [22]. There is increasing behavioural evidence in humans for both an association and a modulatory relationship between sustained attention and lateralized spatial attention. Hjatlson et al. [9], for example, in considering patients with clinical manifestations of unilateral neglect,
Introduction
Many authors have argued that unilateral spatial neglect is associated with bilateral spatial, as well as unilateral spatial, attentional problems [8, 12, 15, 18, 23]. A number of explanations have been put forward to explain this, including that the right hemisphere is dominant for spatial attention across both right and left hemispace, while the left hemisphere only has partial responsibility for attention to the right spatial field [6]. By this argument, a right hemisphere lesion would result in a bilateral reduction in spatial attentional capacity in addition to the more striking poverty of attention to left hemispace. An alternative view sees the bilateral spatial deficits associated with right hemisphere lesions as being c o n s e -
* Address for correspondence: MRC Applied Psychology Unit, Rehabilitation Research Group, Box 58, Addenbrooke's Hospital, Cambridge CB2 2QQ, U.K.; tel.: +44 1223 355294 ext. 354; fax: +44 1223 516630; e-mail: ian.robertson(cLmrcapu.cam.ac.uk. 1527
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demonstrated a significant relationship between performance on two tests o f spatial bias and performance on a sustained attention task. Nigg et al. [11] examined the performance o f children who showed generalized attentional problems and demonstrated a significant bias in the detection o f left-sided stimuli on a spatially sensitive task. Recently, a b o y initially assessed for problems in detecting left-sided stimuli was found to have specific problems in maintaining attention to non-lateralized stimuli, despite generally high levels o f cognitive function [101. In terms o f a m o d u l a t o r y relationship, several studies have demonstrated that non-lateralized, and indeed nonvisual, attentional load can exaggerate the pathological bias in unilateral neglect (e.g., [16]). It has also been shown that improving alertness and sustained attention via a self-instructional procedure produces very significant and specific improvements in lateralized spatial attention in a group of unilateral neglect subjects [19]. While the precise nature o f a right hemisphere-dominant system for endogenously maintaining attention remains unclear, one class of measure which has received support across lesion, neuroimaging and factor analytic studies of attention is that o f maintaining a count of rather m o n o t o n o u s stimuli. Wilkins et al. [24] asked patients with focal neurological lesions to count a series o f tones and a series of tactile stimuli presentations. At longer interstimulus intervals (ISis), patients with lesions to the right frontal lobe were particularly impaired relative to left frontal and posterior patients. At shorter intervals, this difference disappeared. As, apart from presentation rate, the tasks remained identical, Wilkins et al. argued that the relative impairment at longer ISis was attributable to a failure to voluntarily sustain attention to the repetitive, m o n o t o n o u s stimuli. P a r d o et al. [13] supported the putative role o f a right hemisphere sustained attention system in counting tasks of this type with a P E T study of normals who were required to count brief interruptions in somatosensory stimulation over a 40-sec period. They showed that a right hemisphere frontal and parietal activation was associated with this sustained attention task. We have also shown that an adapted version of Wilkins et al.'s tone counting task (made more demanding by having variable intervals o f between 3 and 5 sec between each tone within a string) forms part of a separate sustained attention factor in a factor analytic study of attentional performance in 154 normal controls [21], and have further shown that improvements in neglect contingent u p o n improvements in sustained attention are closely associated with improvements on this tone counting task [19]. As both measures o f spatial bias and of sustained attention are particularly sensitive to right hemisphere damage, comparison o f left and right hemisphere patients on such measures could only serve, at best, to support this gross level o f anatomical association. Consideration of the relative patterns of impairment within a right hemi-
sphere-lesioned group, on the other hand, can provide more compelling support for a closer association o f these intuitively rather disparate functions. This study therefore considers the ability of a brief test o f sustained attention function to predict the occurrence and severity o f lateralized spatial bias in a right hemisphere-lesioned group.
Methods Subjects
For the purpose of the first, correlational, analysis, a total of 44 right hemisphere CVA patients who were less than 1 year post-stroke and who had been assessed in a number of centres across the European Union were selected. The mean age of the subjects was 64.27 (S.D. 12.66), and they were a mean of 88.68 (96.6) days post-stroke. They had a mean left-sided motor impairment on the Motoricity Index [5] (see Procedure) of 37.04 (35.22). Two subjects showed aphasia, although this was not sufficient to prevent them from understanding task instructions. On the standardized assessment of visual fields (see Procedure), 17 subjects showed results consistent with left-sided hemianopia. For the 10 cases where this procedure was not completed, clinical reports suggest left-sided hemianopia in a further three cases. The mean deviation to the right on Line Bisection (see Procedure) was 6.10 mm (S.D. 13.40 mm). All 44 of these subjects had computer tomography (CT)- or magnetic resonance imaging-defined cortical or subcortical lesions. For the second factorial analysis, a subset of 30 of these subjects were selected on the basis of creating two groups, with and without unilateral neglect respectively, who were matched on significant demographic and neurological characteristics. As also shown in Table 1, patients showing neglect did not differ from the non-neglect subjects in age, extent of education, time post-stroke or degree of contralesional motor impairment. They did, however, differ significantly on two tests of unilateral neglect, as would be expected. Table 2 summarizes the lesion data for the subset of 30 subjects used in the second analysis. The groups did not differ in how many distinct brain regions were shown on CT to be affected by the stroke. Table 2 shows data on parietal and frontal involvement, together with the number of brain regions affected (broken down into frontal, parietal, temporal, occipital and subcortical--maximum possible number of regions affected = 5). There was no significant difference between groups on incidence of parietal or frontal lesions, nor on the total number of brain regions affected.
Procedure
All patients received a battery of tests of unilateral spatial neglect, as well as tests of auditory sustained attention, tests of motor and sensory function and tests of visual fields. Only the tests relevant to the present paper will be presented and these are as follows. Elevator Countin9 test of auditor)" sustained attention. This test consisted of two sequential presentations (forms 1 and 2 together) of the Elevator Counting test of the Test of Everyday Attention [20, 21]. The task is based on the tone counting procedure shown to be sensitive to right frontal lobe lesions [24]. It consists of 14 audiotape-presented strings of between three and 14 tones, with random intervals of between 3 and 5 sec between each tone. Subjects are presented with each string in turn and are simply required to count how many tones
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Table 1. Summary of demographic details for comparison groups RHN -
RHN +
M:F Age Time post-stroke (days) Years of education Contralesional Motor Impairment* (Motoricity Index) Star Cancellation (left detected targets/total detected targets)]:
11:6 60.6 (14.7) 74.0 (63.9) l l.0 (3.5) 58.9 (33.4) 0.5 (0.01)
9:4 68.8 (8.3) 62.2 (87.3) 8.9 (4.7) 43.2 (29.9) 0.24 (0.23)
Line Bisection (deviation from objective centre in mm; + = right of centre)
0.81 (3.49)
9.97 (16.44)
ns ns ns ns
ns t28=4.7 P<0.03 t2s= --2.2 P<0.03
*Reference [5]. tReference [25]. Table 2. Summary of lesion data for two comparison groups RHN Lesion extent (number of lobes showing damage 1:2:3: > 3) Parietal lobe involvement (yes : no) Frontal lobe involvement (yes:no)
occurred in each string. This number is produced in response to a standard verbal probe on tape. One point is awarded for each string, and hence the maximum score on this task is 14 and the minimum score is 0. This task is very easy for nonbrain-damaged controls, who seldom make errors on it [21]. Line Bisection. This test consisted of 10200 1.5mm black lines presented on A4 paper, and bisected by subjects with a pen. Star Cancellation. This subtest of the Behavioural Inattention Test (BIT) [25] requires subjects to mark small stars against competing non-targets. Figure and Shape Copying. This subtest of the BIT [25] requires subjects to copy a series of shapes presented. Representational Drawing. This subtest of the BIT [25] requires subjects to draw three objects from memory. Comb and Razor test of personal neglect. This test was adapted from a semi-structured measure of personal neglect devised by Zoccolotti and Judica [27]. It was adapted to a more quantifiable version [1, 18], involving counting the number of motor acts to the left and right of the body respectively during hair combing, shaving (in the case of men) or use of powder compact (in the case of women). Motoricity Index. The Motoricity Index assesses six limb movements. Weighted scores are given to each movement and these are summed to give a final numerical score of overall power. This is done for each side of the body [5]. Visual fields" confrontation assessment. Visual fields were assessed using standard confrontation testing, including catch trials and extinction trials where bilateral stimuli were presented. Ten left and 10 right single stimuli were presented.
-
7:3:3:0 7:6 3:11
RHN + 6:5:2:0 5:8 5:8
ns ns ns
a t t e n t i o n task, the m e a s u r e s o f unilateral neglect a n d the m e a s u r e o f c o n t r a l e s i o n a l m o t o r function. Table 3 shows the results. T a b l e 3 shows t h a t the hypothesis was s u p p o r t e d in t h a t strong and statistically significant c o r r e l a t i o n s existed between n o n - l a t e r a l i z e d a u d i t o r y sustained attention a n d lateralized spatial i n a t t e n t i o n in this g r o u p o f right h e m i s p h e r e - d a m a g e d patients. Significant correlations were evident with spatially biased p e r f o r m a n c e in the Star C a n c e l l a t i o n subtest o f the B I T ( r = 0 . 5 2 7 , P < 0.001), the Line Bisection t a s k (r = - 0.340, P < 0.05), the F i g u r e a n d S h a p e C o p y i n g a n d R e p r e s e n t a t i o n a l D r a w i n g subtests o f the B I T ( r = 0 . 5 3 6 , P < 0 . 0 0 1 ; r = 0 . 5 4 2 , P < 0 . 0 0 1 ) , a n d on b o t h C o m b a n d R a z o r subtests o f the C o m b a n d R a z o r task ( C o m b : r = 0 . 5 6 3 , P < 0 . 0 1 ; Razor: r = 0 . 5 1 5 , P < 0 . 0 1 ) . As p a r t i c i p a n t s with unilateral neglect were significantly m o r e i m p a i r e d in c o n t r a l e s i o n a l m o t o r func-
Table 3. Correlations between auditory sustained attention task and measures of unilateral neglect Tests in correlation with Elevator Counting
Correlation coefficient (r) 0.527*** -0.340* 0.536*** 0.542*** 0.563*** 0.515"*
Analysis 1
Star Cancellation Line Bisection (mean deviation) BIT Figure and Shape Copying BIT Representational Drawing Comb testt Razor testt
The h y p o t h e s i s a d v a n c e d in the I n t r o d u c t i o n was that unilateral neglect should be related to d i s o r d e r s o f sust a i n e d attention. The first analysis e x a m i n e d c o r r e l a t i o n s within the w h o l e g r o u p between the a u d i t o r y sustained
***P<0.001. **P<0.01. *P<0.05. tThis result is based on only 30 out of the 44 subjects who were given the test.
Results
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I.H. Robertson et al./Auditory sustained attention 14
P
12
[]
RHN-
[]
RI-IN+
o
l0 =
8
e~ = ©
6
4
2 0
Fig. 1. Sustained attention performance of right brain damaged groups with and without neglect.
tion than those with no neglect, and as motor function itself formed a significant correlate of the sustained attention measure, it was important to establish whether sustained attention formed an independent predictor of spatial function. To this end, each of the neglect measures which formed significant correlates of Elevator Counting scores were individually entered into a regression equation as dependents, with Elevator Counting as the independent measure. The relationships were then tested by entering contralesional m o t o r function as a second independent in a multiple regression. In isolation, Elevator Counting performance accounted for 27.8% (P<0.001) of the variance in lateralized Star Cancellation performance. The addition of contralesional motor function added a non-statistically significant further 7.9% (P=0.08) to the variance accounted for, while Elevator Counting remained a significant predictor (P < 0.01). Table 4 shows this and three other multiple regressions performed. A similar picture was apparent for the C o m b and Razor subtests, where initial variance explained by the sustained attention measure was 30.5% and 26.5% ( P < 0 . 0 1 , P < 0 . 0 1 ) respectively, and where the addition of motor scores added only a non-significant 4.2% and 3.3% (P = 0.25, P = 0.34 respectively) to the variance explained. For the Copying
subtest of the BIT, Elevator Counting in isolation accounted for 28.7% of the variance. Motoricity added significantly to the variance explained (Elevator Counting + Motoricity = 40.7%), although the Elevator Counting term remained statistically significant (P<0.01). Analysis of results from the Representational Drawing subtest of the BIT showed a similar pattern. Elevator Counting in isolation accounted for 29.4% of Drawing variance ( P < 0.001). This term remained significant when Motoricity Index scores were added (Elevator Counting P < 0.01, Motoricity P < 0.05). in combination, these two measures accounted for 42.6% of the Drawing test variance. For Line Bisection, on the other hand, the significant independent contribution from Elevator Counting scores disappeared when Motoricity scores were also entered into the regression, with neither the contribution of Elevator Counting nor Motoricity independently reaching statistical significance. It is of interest to note how well the sustained attention task correlated with performance on the neglect tests, in comparison to how well the neglect tests themselves intercorrelated. Table 5 shows the intercorrelations among the following tests: auditory sustained attention, Star Cancellation, Figure/Shape Copying, Representational Drawing and the measure of personal neglect, namely the C o m b and Razor task. Table 5 shows that the Elevator Counting test and the Star Cancellation test are the only measures with statistically significant correlations with all other measures. In contrast, personal neglect as measured by the C o m b task is non-significantly correlated with Line Bisection and the Figure Copying subtest of the BIT [25]. A further test of the relative independence of sustained attention performance as a predictor of unilateral neglect was pursued in a group comparison. F r o m the initial group of 44 right hemisphere-lesioned patients, a group of 30 were selected such that the subgroup who showed unilateral neglect did not statistically significantly differ in terms of m o t o r function from those who did not show neglect (see Table 1). A one-way analysis of variance showed a large group difference in sustained attention scores, with the group showing unilateral neglect achieving a mean correct score of 9.31/14 (S.D. 4.97), while the
Table 4. Multiple regressions of auditory sustained attention and contralesional motor function on selected measures of unilateral neglect
Independent variable 1. Elevator Counting Elevator Counting + left-sided 2. Elevator Counting Elevator Counting + left-sided 3. Elevator Counting Elevator Counting+ left-sided 4. Elevator Counting Elevator Counting +left-sided
Motoricity Index Motoricity Index Motoricity Index Motoricity Index
Dependent variable
Total explained variance (%)
Added variance (%)
Star Cancellation (left/total) Star Cancellation (left/total) Comb test Comb test Copying test (BIT) Copying test (BIT) Representational Drawing (BIT) Representational Drawing (BIT)
27.8 35.7 31.7 35.9 28.7 40.7 29.4 42.6
-7.9 -4.2 -12.0 -13.2
Significance of added variance ns -ns P<0.05 -P < 0.05
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I. H. Robertson et al./Auditory sustained attention Table 5. Correlations between auditory sustained attention and measures of spatial neglect Elevator Counting Elevator Counting Star Cancellation Line Bisection Figure/Shape Representational Drawing Comb test Razor test
Star Cancellation 0.527
Line Bisection -0.340 -0.472
non-neglect group had a mean correct score of 13.12/14 [S.D. 1.11, F1,2~=9.459; P<0.01; see Fig. 1].
Discussion The above results show that (i) unilateral left neglect is highly correlated with performance on a spatially nonlateralized auditory sustained attention task; (ii) auditory sustained attention performance significantly discriminates between right hemisphere-damaged patients with and without neglect; (iii) these relationships are unlikely to arise on the basis of general factors such as lesion severity. The results are striking because a non-spatial attention measure is as powerful as certain standardized spatiallybased tests in discriminating unilateral neglect among right hemisphere patients. The results are perhaps even more surprising when the apparent simplicity of the sustained attention task is considered. All that is required of subjects is to maintain an internal count of up to a maximum of 14 tones which are separated by no more than 3-sec intervals. Due to its conceptual simplicity, the undemanding nature of the numericity judgement and the ease with which the tones can be discriminated [20], the challenging aspect of this task (approximately 86% of which consists of silence) lies almost entirely in keeping one's mind on it. That unilateral neglect patients are particularly poor at endogenously maintaining their attention in this way is entirely consistent with Posner's anatomically driven hypothesis that spatial orientation is mediated by a posterior orientation system and a right hemisphere-dominant alertness/sustained attention system [14]. He argued that the norepinephrine system mediates alertness and cites evidence that the strongest terminal projections of this system are in somatosensory areas of the parietal lobe implicated in unilateral neglect [2]. In short, patients who show auditory sustained attention system deficits as well as unilateral spatial neglect have a doubly compromised capacity for spatial orientation to the neglected side. The general point that interactions occur between spatial and non-spatial attentional systems has been bols-
Figure/ Shape 0.536 0.614 -0.297
Representational Drawing 0.542 0.636 -0.230 0.658
Comb test
Razor test
0.563 0.455 0.032 0.452 0.408
0.515 0.521 -0.075 0.343 0.350
Motoricity Index 0.388 0.431 -0.312 0.486 0.515
tered by studies showing that purely auditory attentional load causes deterioration in visual neglect [16]. Specific support for an interaction between systems necessary to endogenously maintain an alert 'ready to respond' state and spatial attention has come from experimental studies showing improvement in neglect when the sustained attention system is improved [19], as well as in correlational studies [9, 11]. What precisely is the nature of this link between an alertness/sustained attention system, on the one hand, and a spatial orientation system on the other? One possibility (consistent with Heilman's hypothesis [7]) is that the patient is hypoaroused because of the lesion to a right hemisphere-dominant alertness system, and that there is a general improvement in all functions, including neglect, when sustained attention/alertness improves. This nonspecific hypothesis can be contrasted with one which argues that it is particularly a parietal lobe-based spatial orientation system which is a privileged recipient of activation from the alertness/sustained attention system. The latter hypothesis, attributable to Posner [14], is supported by the PET study by Pardo et al. [13], showing that a sustained attention task caused right hemisphere frontal and parietal activation in normal subjects. This finding is of considerable importance theoretically and practically in understanding the nature of unilateral neglect. It has already been shown that neglect can be improved significantly by improving sustained attention [19], and that the non-lateralized aspect of right hemisphere attention deficit may be just as important in determining deficits in spatial attention as is the spatial bias itself.
Acknowledgement~This paper is dedicated to the memory of
Catherine Bergego, friend and colleague of all the authors. The authors would like to acknowledge the support of the European Union Biomed II programme for its support of this project. Many thanks also to colleagues involved in other aspects of the project, and in particular G6rard Deloche, Peter HaUigan, Florence Marchal, Franz Stachowiak, Richard T6gner and Pierliugi Zoccolotti. Particular thanks to Julia Darling for her careful preparation of this manuscript.
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