J Neurol (1997) 244 : 412–417 © Springer-Verlag 1997

S. Maeshima G. Truman D. S. Smith N. Dohi K. Nakai T. Itakura N. Komai

Received: 18 November 1996 Received in revised form: 14 March 1997 Accepted: 6 April 1997

S. Maeshima (Y) Department of Neurological Surgery, Wakayama Medical College, 27 Nanabancho, Wakayama 640, Japan Tel.: +81 734 26 8277 Fax: +81 734 33 5998 G. Truman · D. S. Smith Rehabilitation Studies Unit, University of Sydney & Royal Rehabilitation Centre, 227-259 Morrison Road, Ryde, NSW 2112, Australia Tel.: +61 2 9808 9236 Fax: +61 2 9809 9037 N. Dohi Hiroshima Prefectual College of Health Science & Welfare, Hiroshima, Japan K. Nakai · T. Itakura · N. Komai Department of Neurological Surgery, Wakayama Medical College, Wakayama, Japan

O R I G I N A L C O M M U N I C AT I O N

Is unilateral spatial neglect a single phenomenon? A comparative study between exploratory-motor and visual-counting tests

Abstract The aim of this study is to report the preliminary findings of a traditional battery of tests and our original battery capable of assessing the presence of components and extent of lesions in patients with unilateral spatial neglect. Thirty patients who had unilateral spatial neglect with a stroke in the right hemisphere were assessed for unilateral spatial neglect on exploratory-motor (E-M) tasks, visual-counting (V-C) tasks, and traditional neglect batteries at least 4 weeks after the onset. Other neuropsychological tests and computed tomography were also performed to investigate the relationship with neglect. A factor analysis showed that our tasks loaded significantly on three factors. E-M neglect was found in 16 patients, and V-C neglect in 22 patients with unilateral spatial neglect. There were high correlations between E-M neglect and motor paralysis, word fluency, back-

Introduction Unilateral spatial neglect is a phenomenon wherein the patient disregards objects existing in the left and, occasionally, the right spatial field. It is well known that this is multifactorial with respect to sensory input and motor output [9, 11]. Unilateral spatial neglect is usually associated with lesions in the parieto-occipital lobes of the non-dominant hemisphere [18]. However, there have been reports of unilateral spatial neglect following lesions in the frontal lobe [4, 5, 20, 23, 26–28], thalamus [25, 35], putamen [25, 35], and left hemisphere [24].

ward digit span and motor impersistence. There were high correlations between V-C neglect and visual-field defect, line bisection, line cancellation and figure copying. Lesions in the frontal lobe, caudate, insula, and anterior portion of the paraventricular white matter were commonly associated with E-M neglect. Lesions in the occipital lobe were also associated with V-C neglect. We suggest that unilateral neglect is not a single phenomenon, but rather involves several different components. We propose that E-M and V-C tasks are useful methods for evaluating the extent of lesions in patients with unilateral spatial neglect. Key words Unilateral spatial neglect · Frontal lobe · Cerebrovascular accident · Exploratory-motor tasks · Perceptual-sensory tasks

The mechanism of unilateral spatial neglect is still unclear, although various frameworks have been proposed, including conjugate gaze paresis [10], hypoattentional hypokinesia [17], amorphosynthesis [8], and disturbance in representational mapping [2], attention balance [22], attention arousal pathways [16], and directed attention. Mesulam [31] has proposed that the posterior region of the parietal lobe, the limbus in the cingulate gyrus, the frontal lobe, and the reticular formation in the midbrain are important areas that may form an integrated network for the modulation of directed attention, and has suggested that different types of neglect develop according to the location of a lesion in these areas. In particular, the

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frontal lobe coordinates the motor programs for exploration (motor representation), and thus damage to the frontal lobe might be expected to cause difficulties in tasks requiring exploration and manipulation of the contralateral hemispace. Recently, some authors have devised a specific line bisection [3, 15] and cancellation tasks [34] allowing uncoupling of the direction of visual attention from that of hand movement to isolate experimentally and to separate the motor and sensory components in unilateral spatial neglect. Unfortunately, line cancellation and line bisection tests, which are generally used to evaluate patients with unilateral spatial neglect, contain both perceptual and motor components. Consequently, these two components cannot be evaluated separately using these methods. Weintraub et al. [36] attempted to exclude the effects of a perceptual (visual) system by having patients perform an “exploratory-motor” task with their eyes closed. Using a similar task, Maeshima et al. [29] reported that “exploratory-motor neglect” was observed in patients with lesions in the frontal lobe and was related to frontal-lobe function tests. Thus, it is likely that unilateral spatial neglect could be divided into motor and sensory components. There have, however, been no reported investigations into the usefulness of a test battery that distinguishes between motor and sensory components of unilateral spatial neglect and defines the relationship between the component and the lesion site. In this study, we evaluated patients with unilateral spatial neglect using the “exploratory-motor test” and a “visual counting test” to distinguish the motor and sensory components of unilateral spatial neglect. We also compared the presence or absence of these components with other neuropsychological tests and lesions.

Patients and methods Thirty patients who had unilateral spatial neglect with a stroke in the right hemisphere were assessed at least 4 weeks after the onset. The mean time from the onset of the stroke was 7.8, SD 1.4 weeks (range 4–32). Their ages varied from 36 to 76 years (mean age of 60.3, SD 12.8 yrs). Eighteen patients were men and 12 were women. All patients were right-handed prior to stroke onset. The cause of disease in these patients was cerebral haemorrhage in 14 patients, cerebral infarction in 11, and subarachnoid haemorrhage in the other 5. Procedures Exploratory-motor test We modified the “Exploratory-motor task” of Weintraub et al. [36] to detect exploratory-motor neglect (E-M neglect) [29]. The subjects were seated in front of a board (47 × 34 cm) on which a marble was placed in the centre. They were asked to move the marble to the right edge using their right hand. Next, they were blindfolded, and four blocks containing four marbles each were placed in the upper-right, upper-left, lower-right, and lower-left

quadrants of the board (a total of 16 marbles). Subjects were asked to move all of the marbles individually to the right edge and off the board without sweeping. When they thought that all marbles had been removed from the board, they were to say “finished”. If they stopped the exploration prior to completion and without saying anything, the test was performed again from the beginning following another explanation of the task. Marbles left on the board when the subjects had “finished” were regarded as errors. This test was performed two or more times to confirm its reliability. Subjects with errors two or more times were considered to have E-M neglect. A group of 15 age- and sex-matched, healthy adults (9 men and 6 women), aged 40–81 years, were able to complete this task without errors. Visual-counting test Subjects were seated in front of a board (47 × 34 cm) on which marbles were placed in four blocks containing four marbles each in the upper-right, upper-left, lower-right, and lower-left quadrants of the board (a total of 16 marbles). They were asked to count all of the marbles without touching them. The number of marbles reported by the subjects was subtracted from 16 and the difference considered errors. This test was performed two or more times to confirm its reliability. As with the E-M task, the group of healthy adults also performed with task without errors. The line-cancellation test, the line-bisection test, and the figure-copying test were used to select patients with unilateral spatial neglect [24, 25]. In the line-cancellation test, we prepared a sheet of white A4 (20 × 26 cm) paper with 40 lines drawn on it and asked patients to mark the lines. Failure to cancel less than onequarter of the A4 paper was assessed as mildly abnormal, less than half as moderately abnormal, and failure to cancel the left half of the paper and some lines on the right half was assessed as severely abnormal. In the line-bisection test, the patients were asked to bisect a 200-mm line drawn on A4 paper. Abnormalities were assessed as follows: 6.5–13 mm as mild, 13–19.5 mm as moderate, and more than 19.5 mm as severe. In the figure-copying test, patients were required to copy a picture of a 3D cube. Abnormalities were assessed as follows: shortfall or overshoot on the left side as mild, omission of a left plane as moderate, and omission of two left planes as severe. Motor impersistence [12] was also detected using a task in which eye opening is performed simultaneously with tongue protrusion [19]. When this was difficult for the patient to maintain for 30 s, the patient was considered to have motor impersistence. Other neuropsychological tests, that is, mini-mental state (MMS) examination [13], a word fluency test (number of animals named in 1 min), and a digit span test (forward and backward) were also performed. Patients were given a standard clinical neurological examination to assess motor, somatosensory and visual field deficits [25].

Table 1 Varimax rotated factor matrix Loading on factor

Factor I

Factor II

Factor III

Line cancellation Line bisection Figure copying E-M neglect V-C neglect Motor impersistence

1.00 0.62 0.85 0.05 –0.00 –0.03

–0.08 0.11 0.06 0.90 0.04 0.90

0.21 –0.34 –0.20 –0.05 0.97 0.05

Eigen-value Percentage of variance

2.70 45.1%

1.65 27.5%

0.69 11.6%

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Table 2 Relationship between the neglect groups and neuropsychological tests

Kruskal Wallis test * P < 0.05

Age (years) Duration (weeks) Mini-Mental State (/30) Word fluency (/min)* Digit span (forward) Digit span (backward)

None Mean (SD)

E-M group Mean (SD)

V-C group Mean (SD)

E-M and V-C group Mean (SD)

56.5 6.0 24.0 9.3 5.8 3.3

63.3 (18.3) 11.5 (4.1) 20.8 (6.7) 4.8 (3.4) 5.0 (1.6) 2.5 (1.0)

54.6 (14.9) 10.0 (7.8) 23.3 (3.6) 9.1 (4.1) 5.8 (0.8) 3.1 (0.7)

65.3 10.0 19.5 5.4 5.4 2.2

The site and extent of the lesion Computed tomography (CT) was also carried out to show the size of the lesion. In the patients with damage involving the cortex, the lesion site was determined by the method of Damasio and Damasio [6]. The deep structures involved were localized from the atlas of Matsui and Hirano [30]. Table 3 Correlation between neglect, neurological deficits and neuropsychological tests

Age Duration Visual field defect Paresis in upper limb Paresis in lower limb Superficial sensation Deep sensation Mini-Mental State Word fluency Digit span (forward) Digit span (backward) Line cancellation Line bisection Figure copying Motor impersistence Spearman’s correlation method * P < 0.05; ** P < 0.01 Fig. 1 The relationship between E-M neglect and lesion site (CN caudate nucleus, LN lenticular nucleus, ALIC anterior limb of internal capsule, GIC genu of internal capsule, PLIC posterior limb of internal capsule, PVWMA anterior portion of periventricular white matter, PVWMP posterior portion of periventricular white matter)

E-M neglect

V-C neglect

0.30 0.15 0.07 0.51** 0.43* 0.14 0.20 –0.36 –0.44* –0.25 –0.42* 0.00 0.10 0.04 0.86**

–0.14 0.23 0.41* 0.00 –0.11 –0.22 –0.15 0.22 0.22 0.03 0.10 –0.37* –0.52** –0.54** –0.20

(7.6) (2.8) (2.9) (2.6) (1.0) (0.5)

(8.8) (9.9) (4.7) (3.6) (1.2) (1.1)

Results A principal component factor analysis was carried out on the data (Table 1). The analysis extracts the orthogonal linear combinations that account for the largest proportion of the total variance. The rotated factor matrix showed three factors that accounted for 84.2% of total variance. The first factor had substantial loading from common neglect tests like the line-cancellation task. The second factor had a motor component that was represented by motor impersistence and E-M neglect. The third factor considered was the sensory component, which was represented by V-C neglect. E-M neglect was found in 16 patients and V-C neglect in 22 patients with unilateral spatial neglect. Four patients with E-M neglect did not have V-C neglect and 10 patients with V-C neglect did not have E-M neglect. Four patients did not show either E-M neglect or V-C neglect. There was a significant difference between the groups in word fluency using the Kruskal-Wallis test (H = 8.16, P < 0.05). The group that had E-M neglect tended to have lower word fluency scores. There were no differences among the groups in age (H = 5.14), duration (H = 2.95), MMS (H = 5.77), forward digit span (H = 1.44) or backward digit span (H = 5.86) using the Kruskal-Wallis test (Table 2). Table 3 shows the correlation between E-M task or V-C task and age, duration from the onset, neurological

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Fig. 2 The relationship between V-C neglect and lesion site

deficits, and results of neuropsychological tests. There were high correlations between E-M neglect and motor paralysis, word fluency, backward digit span and motor impersistence. There were high correlations between V-C neglect and visual-field defect, line bisection, line cancellation and figure copying. Localization of the neglect in these tasks Lesions in the frontal lobe, caudate, insula, and anterior portion of the paraventricular white matter were commonly associated with E-M neglect (Fig. 1). A lesion in the occipital lobe was associated with V-C neglect (Fig. 2). Twelve patients with E-M neglect had a frontal lesion. Only 1 of 9 patients without E-M neglect had a frontal lesion. Ten patients with V-C neglect had an occipital lesion. All 12 patients without V-C neglect did not have an occipital lesion.

Discussion We have examined patients with unilateral spatial neglect using traditional neglect tests like the line-cancellation task, the line-bisection task and figure copying together with new neglect tasks. This combination of the traditional neglect tests is not only popular with clinicians, but also useful to detect unilateral spatial neglect [24, 25]. Halligan et al. [14] emphasized that neglect was a single phenomenon based on a factor analysis of some traditional neglect tests. In our study, the factor analysis suggests that unilateral neglect is not a single phenomenon, and it is possible that there are some different components in combined unilateral spatial neglect. In other words, patients’ performances on the neglect battery suggest that

different tests were measuring aspects of different constructs. The constructs are likely to be motor-exploratory and visual-perceptual neglect. We included two new tasks, which were performed easily and took a few minutes to perform. The E-M task was originally developed by Weintraub et al. [36] in 1987. They attempted to exclude the effect of the perceptual system by using blindfolded manual exploration. Daffner et al. [4] reported a dissociation between E-M neglect and perceptual-sensory (P-S) neglect, by using extinction to detect P-S neglect. However, it is usual for neglect patients to have visual field defects that may confound examination of P-S neglect by extinction of visual stimuli. We therefore examined neglect patients for perceptual neglect using a V-C test, which can be performed independently of visual field defects. E-M neglect was not only correlated with motor paralysis, but also correlated with word fluency, backward digit span and motor impersistence. Although motor exploration is performed unilaterally, it is not clear whether E-M neglect results from unilateral motor impairment itself, such as hypokinesia, or from the continuation of movement. Our findings suggest that E-M neglect is related to motor impersistence. Motor impersistence represents an impairment of the continuation of movements and is associated with impaired motor control at the cortical level [12], a short attention span, and emotional liability [21]. Motor impersistence cannot be considered the same as E-M neglect because not all of our patients with motor impersistence demonstrated E-M neglect. Word fluency and digit span might be associated with attention and the initiation of motion. Robertson et al. [33] reported that digit span and word fluency in patients with unilateral spatial neglect did not load on any neglect-related variables using

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the principal components analysis. Our results suggest that these functions are also related to exploratory movement. Pizzamiglio et al. [32] examined a battery of tests to detect unilateral spatial neglect using cluster analysis. The test included tasks involving several modalities of spatial exploration: mapping perceptual, motor, attentional and personal or extrapersonal space dimensions. They concluded that areas contributing to perceptual and motor processes in exploratory tasks are contiguous in the human brain, thus reducing the likelihood of detecting dissociated cases. Unfortunately, they did not describe the localization of lesions in patients with unilateral spatial neglect. Binder et al. [1] reported that the combination of abnormal cancellation and normal line bisection was always associated with a frontal or basal ganglia lesion. Patients with posterior lesions deviated rightward on line bisection. Therefore they suggested that the separate components of neglect may be associated with damage to discrete areas of the non-dominant hemisphere. In fact, patients with a right frontal-lobe lesion who showed severe neglect on the line-cancellation task, revealed only mild impairment on line bisection [26–28]. Although it might be caused by different sensitivity of the traditional batteries, some investigators have suggested this as a clinical feature of neglect caused by frontal lobe lesions. Liu et al. [23] reported the difference between a patient with unilateral spatial neglect associated with a right frontal lesion and with a right parietal lesion. They sug-

gested that the result of the P-S task was worse in a patient with a parietal lobe lesion and the E-M test was worse in a patient with a frontal lobe lesion. In the current study, E-M neglect was related to an anterior lesion such as frontal lobe, caudate, insula, and anterior portion of subcortical white matter. Deiber et al. [7] suggested that willed actions were involved in the dorsolateral prefrontal cortex in the frontal lobe using positron emission tomography. We suspect that this may be the motor component of neglect and may be related to frontal lobe function. On the perceptual side, there are high correlations between V-C neglect and visual field defect, line bisection, line cancellation and figure copying. Neuroanatomically, V-C neglect was related to occipital lesions. We suggest that this may be the sensory component of neglect caused by posterior lesion. The reason that we found no evidence showing that parietal lesions were related to V-C neglect might be that patient selection was by traditional batteries in this study. In conclusion, we suggest that E-M and V-C tasks are useful methods for evaluating the nature and extent of lesions in patients with unilateral spatial neglect. Because we used traditional tests to select neglect patients, we were unable to detect a patient who has only E-M neglect or only V-C neglect without neglect on the traditional neglect batteries. We are now looking at broader stroke populations in order to confirm our postulation that these may be discrete subclasses of neglect.

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