A psychophysical study of visual extinction: ipsilesional distractor interference with contralesional orientation thresholds in visual hemineglect patients

Neuropsychologia 43 (2005) 530–541

A psychophysical study of visual extinction: ipsilesional distractor interference with contralesional orientation thresholds in visual hemineglect patients Sarah Geeraertsa , Christophe Lafosseb , Erik Vandenbusschec , Karl Verfaillied,∗ a Laboratory of Neuropsychology, University of Leuven, Belgium Scientific Unit Rehabilitation Centre ‘Hof ter Schelde’, Antwerp, Belgium c Laboratory of Neuropsychology, University of Leuven, Belgium Laboratory of Experimental Psychology, Department of Psychology, University of Leuven, Tiensestraat 102, B-3000 Leuven, Belgium b

d

Received 16 December 2003; received in revised form 16 July 2004; accepted 21 July 2004

Abstract Visual extinction was investigated in left (n = 15) and right (n = 25) brain-damaged patients with or without visual neglect, and in normal control subjects (n = 14), using a psychophysical paradigm. Orientation discrimination thresholds were determined for both left and right hemifield gratings presented either in isolation or simultaneously with a contralateral distractor grating. To minimize the influence of possible sensory-perceptual deficits, the luminances of both target and distractor gratings were chosen to be 20 times the luminances necessary to discriminate between horizontal and vertical grating orientations. The location of the target grating was always cued, making the distractor grating task irrelevant. Even after equalizing the visibility of left and right hemifield stimuli, neglect patients still displayed an increased interference effect from an ipsilesional distractor (and no interference from a contralesional distractor). Left or right brain-damaged controls did not show this asymmetric interference of irrelevant distractors, even the patients who demonstrated extinction on standard extinction testing. This suggests that visual extinction is a critical component of the visual neglect syndrome and that it involves an attentional deficit. © 2004 Elsevier Ltd. All rights reserved. Keywords: Attention; Orientation discrimination; Stimulus competition; Vision

1. Introduction Visual extinction describes a condition in which a patient who can reliably see a single stimulus opposite a brain lesion, fails to see the same stimulus when another stimulus is simultaneously presented on the non-affected side. In a more extended definition, ipsilesional stimuli interfere with the processing of contralesional stimuli (without making them invisible). It is the latter definition that forms the starting point for the present study. Visual extinction has been related to the hemineglect syndrome (Heilman, Watson, & Valenstein, 1993), the defective ability of patients with a unilateral cerebral lesion to explore the side of space contralateral to the ∗

Corresponding author. Tel.: +32 16 325966; fax: +32 16 326099. E-mail address: [email protected] (K. Verfaillie).

0028-3932/$ – see front matter © 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.neuropsychologia.2004.07.012

lesion. Visual hemineglect patients fail to attend or respond to contralesional visual stimuli. Both disorders are commonly observed after right parietal lobe lesions and extinction often persists as a residual symptom after recovery from neglect (Heilman et al., 1993; Robertson & Halligan, 1999). These similarities might suggest that neglect and extinction share a common underlying mechanism, an attentional deficit being the prime candidate (Kinsbourne, 1987; Posner, Walker, Friedrich, & Rafal, 1984). However, some evidence suggests that neglect and extinction should be considered as separate conditions (Bisiach, 1991; Di Pellegrino & De Renzi, 1995; Milner, 1997). They may have different anatomical bases, extinction appearing to be more frequent after subcortical lesions (Vallar, Rusconi, Bignamini, Geminiani, & Perani, 1994). Moreover, extinction and neglect can occur independently: both extinction without neglect (Ogden, 1985) and

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neglect without extinction (Cocchini, Cubelli, Della Sala, & Beschin, 1999; Liu, Bolton, Price, & Weintraub, 1992; Ogden, 1985; Stone, Halligan, Marshall, & Greenwood, 1998) have been reported. There are at least two possible explanations for the observation of extinction without neglect. First, extinction could be a mild form of neglect. In this scheme, extinction is the result of an attentional imbalance. Indeed, extinction occurs in patients without any obvious sensory deficits, it can be improved by directing attention to the contralesional side, and it can be observed between two stimuli in one hemifield (Di Pellegrino & De Renzi, 1995). Second, it is possible that, in some patients with extinction but without neglect, extinction is a consequence of a lower-order sensory rather than a higher-order attentional imbalance (Bender & Furlow, 1945; Farah, Monheit, & Wallace, 1991; Vallar et al., 1994). The observation of neglect without extinction is more difficult to explain. If extinction is the milder form of neglect, then neglect should always involve extinction. However, the neglect without extinction dissociation appears to be even more frequent than the extinction without neglect dissociation (Ogden, 1985; Vallar et al., 1994). Although other explanations have been suggested (Bisiach, Geminiani, Berti, & Rusconi, 1990; Cocchini et al., 1999; Liu et al., 1992), insensitive extinction testing and ceiling effects are plausible explanations for most of the observed dissociations (Driver et al., 1997). Typical extinction paradigms use detection or simple discrimination tasks and patients may be performing at ceiling in these tasks, even with bilateral stimulus presentation. An actually present extinction effect might not emerge because the task is not sensitive enough to pick up performance differences for unilateral versus bilateral stimulus presentations. In view of the above, the main purpose of the present study was two-fold. First, a more sensitive extinction paradigm than employed in standard testing, was used. More specifically, thresholds for orientation discrimination were measured psychophysically. Unilaterally brain-damaged patients with or without neglect were tested. Orientation sensitivity was determined for left and right hemifield gratings presented with or without a contralateral irrelevant distractor grating. Second, we developed a better control for possible lower-level sensory deficits.1 Contra-ipsilesional differences in stimulus visibility were eliminated by changing the luminance of the stimuli. More specifically, before administering the orientation 1 In typical extinction experiments, visual field defects are usually excluded by means of perimetric testing. However, more subtle sensory deficits, not manifest in perimetry, may still be present and are rarely ruled out. In studies in which sensory imbalances are not masked because unilateral performance is at ceiling, differences between unilateral left and right hemifield performances are indeed observed. Marzi et al. (1997) and Smania et al. (1998) demonstrated that single contralesional stimuli are detected with greater difficulty and longer latency compared to single ipsilesional stimuli in extinction and neglect patients. Moreover, Marzi et al. (1997) showed that the contra-ipsilesional differences correlated with the severity of extinction.

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discrimination task, we first measured luminance thresholds for left and right hemifield positions in a horizontal–vertical grating discrimination task. Gratings with luminances of 20 times these thresholds were then used in the orientation discrimination task, in which possible extinction effects were examined. The following predictions can be made for the patients with neglect. If previous reports of neglect without extinction can be traced back to insensitive extinction testing, our more sensitive extinction paradigm should reveal extinction in every neglect patient. Moreover, if neglect and extinction (in neglect patients) are based on the same underlying attentional deficit, then neglect patients are still expected to show extinction, even after sensory imbalances are eliminated by equating the visibility of ipsilesional and contralesional stimuli. To come to a better understanding of the attentional deficit, presumed to underly neglect and extinction, we explored whether extinction occurs because the patient has to process the ipsilesional distractor actively (and this interferes with processing the contralesional stimulus) or whether attention is attracted obligatorily and involuntarily to the ipsilesional distractor, even when the distractor does not have to be processed. On the one hand, some authors have suggested that a crucial determinant of extinction is that the ipsilesional stimulus needs to be processed (Di Pellegrino & De Renzi, 1995; Karnath, 1988). Indeed, in typical extinction paradigms, the ipsilesional stimulus is always relevant to the task in that it has to be reported or identified. On the other hand, the fact that cueing attention contralesionally, although improving neglect and extinction, never completely abolishes it, suggests that the ‘magnetic’, involuntary, and obligatory attraction of attention towards ipsilesional stimuli may be crucial (Mattingley, Bradshaw, Nettleton, & Bradshaw, 1994). This is supported by the frequent observation of an intact voluntary attentional system in some neglect patients with parietal lesions, who nevertheless exhibit an extinction effect (Ladavas, Carletti, & Gori, 1994; Riddoch & Humphreys, 1983). In the present study, the distractor stimulus was task irrelevant. Attention was always cued towards the target stimulus position and away from the distractor position. If the magnetic, involuntary attraction of the ipsilesional distractor underlies extinction, irrespective of the fact whether the ipsilesional stimulus has to be processed actively or not, we predict extinction effects, even with task-irrelevant distractors.

2. Methods 2.1. Subjects Fifteen right brain-damaged (RBD) patients with left visual neglect, 10 RBD patients without neglect, one left brain-damaged (LBD) patient with right visual neglect, 14 LBD patients without neglect, and 14 control subjects without brain damage or neglect were tested. Patients were

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recruited from two different rehabilitation units for stroke patients. Patients were only included in the study if they had a single, unilateral vascular lesion as revealed by CT/MRI and clinical symptoms and if they did not show hemianopia on perimetric testing. Moreover, in order to be included they had to obtain reliable thresholds in our luminance and orientation task conditions without distractors. Table 1 summarizes the clinical and demographic characteristics of the patients. Normal control subjects were volunteers without any neurological history. Six normal controls were female, seven were male. Their mean age was 53.6 years (range 31–70). 2.2. Standard neglect and extinction tests Visual neglect was diagnosed by two standard clinical tests (line bisection and star cancellation) and by observation of the patient’s behaviour during everyday activities in the revalidation unit. All neglect patients showed clear signs of neglect for at least two out of these three criteria. Control subjects did not show neglect symptoms on any of these criteria. For the line bisection test (Schenkenberg, Bradford, & Ajax, 1980) an average rightward deviation of more than 8% was indicative of neglect. For the star cancellation test (Behavioural Inattention Test, Wilson, Cockburn, & Halligan, 1987), three or more omissions indicated neglect. Neglect behaviour during everyday activities involved bumping into obstacles on the left-hand side or ignoring objects located on the left side. Visual extinction (on standard testing) was assessed with the clinical confrontation technique. Patients were required to detect movements of the examiner’s left or right index finger. Ten unilateral left, 10 unilateral right, and 10 bilateral stimuli were presented in a pseudo-random order. Patients were classified as showing extinction if they correctly detected more than 80% of the single left and single right stimuli, but failed to perceive the left stimulus in more than 30% of the trials with bilateral stimulation. Non-extinction subjects obtained a better than 80% correct detection in all the conditions. In the RBD with left neglect group 7 of the 15 patients showed extinction, in the RBD control group 2 out of 10, and in the LBD control group 2 out of 14 (Table 1).2 2.3. Visual perimetry All patients underwent binocular perimetric testing to make sure there were no visual field defects for the stimulus positions that were used in the psychophysical measurements. Patients were seated at a distance of 57 cm from the computer screen. Eye fixation was monitored with the 2 There is an ambiguity here. On the one hand, we predict visual extinction in every neglect patient, provided that extinction is tested with a sufficiently sensitive procedure. On the other hand, neglect patients are classified as showing extinction or not. Obviously, the latter classification refers to extinction as measured on standard testing. In fact, we predict that even neglect patients without extinction on standard testing will show signs of extinction in our more sensitive paradigm.

ASL 210 eye tracker (Applied Science Laboratories, Bedford, MA). While fixating a central red fixation point (diameter 0.15◦ of visual angle), the subject had to press a response key each time a stimulus was detected anywhere on the screen. Stimuli were white points (diameter 0.1◦ ; luminance 8.2 cd/m2 on a 0.01 cd/m2 background) that were presented randomly at positions of maximum 10◦ left, right, above or below the fixation point. Sixty-four stimulus trials and 16 catch trials without stimulus were presented. Stimulus duration was 200 ms. A stimulus that was not detected was repeated, first at the same luminance and a second time at a maximum luminance of 74 cd/m2 . Hemianopic subjects were excluded from the study. Four RBD left neglect patients suffered a left lower quadrantanopia and one LBD control patient a right lower quadrantanopia (Table 1). Since the grating stimuli were always presented in the upper parts of the visual field, these patients were included in the study. None of the other patients did show visual field defects, although some of them missed a few of the contralesional stimuli at first presentation. 2.4. Luminance thresholds Subjects were seated in front of the computer screen at a distance of 114 cm with the head restrained by a front and chin-rest. A central red fixation point (diameter 0.2◦ of visual angle) was presented throughout each trial, together with a peripheral cue, indicating the position of the next stimulus. The cue was a white circle (diameter 4.5◦ ), the centre of which was presented at 5◦ eccentricity from the fixation point on the 45◦ diagonal in either the left or right upper visual field quadrant. Stimuli were circular-shaped square-wave gratings (diameter 4.5◦ , spatial frequency 1 c/◦ ) with either horizontally or vertically oriented bars. The gratings were luminancemodulated with dark bars of a constant background luminance (0.001 cd/m2 ) and bright bars of luminances that varied according to the subjects’ performance. Bright bars were constructed from random noise patterns. The stimuli only appeared at the cued position (left or right upper quadrants). Luminance thresholds were determined with an adaptive staircase procedure (MUEST, Snoeren & Puts, 1997) converging around a performance level of 70% correct. The starting luminance was 0.04 cd/m2 . The threshold is the luminance for which the subject reaches a 70% correct discrimination between horizontal and vertical gratings. Each threshold estimation was based on 40 trials. Only subjects that reached a performance level between 65% and 75% correct (indicating a reliable threshold measurement) were included in the study. The experiment was carried out in a completely darkened room. The trial sequence was the following (Fig. 1). If central fixation was maintained for 500 ms, the cue circle was replaced by the grating stimulus for a period of 300 ms. The subject had to respond to the orientation of the grating by pressing a left response key for horizontal and a right response key for vertical orientations. Subjects were urged to

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Table 1 Clinical and demographic characteristics of patients Patients

Age

Sex

Etiology

Lesion location

Months since lesion

Visual field defect

Line bisection

Star cancellation L

R

LN1

57

M

Infarct

1,1

No

+11,8

0

0

+

No

LN2 LN3 LN4 LN5 LN6 LN7

48 60 53 45 58 63

M M M M F F

Infarct Infarct Infarct Aneurysm ICB ICB

5,7 13,6 1,5 8,6 1,3 11,2

No LL quadr No No No No

+5,1 +12,9 +5,4 +7 +8,7 +21,2

5 3 1 3 5 3

0 2 1 2 3 0

+ + + + + +

Yes No No Yes Yes No

LN8 LN9

42 57

M F

Infarct Infarct

4,9 2,0

LL quadr No

+7 +4,4

10 2

4 2

+ +

Yes No

LN10 LN11 LN12

60 53 71

M F M

Infarct Infarct Infarct

4,3 7,0 14,9

LL quadr No LL quadr

+56,9 +13,1 +3,4

5 4 4

0 2 1

+ + +

No No Yes

LN13 LN14

66 72

M M

Infarct ICB

2,1 4,7

No No

+33,4 +14,8

18 0

4 0

+ +

Yes Yes

LN15

53

F

Infarct

R parieto-temp, caudate, caps.i. R parietal R fronto-parietal R temporo-parietal R fronto-parietal R periventricular R fronto-temporoparietal R parietal R par-temp, putamen, paraventr. R a.c.media R parieto-occipital R temporal-parietaloccipital R parietal R thalamus (bas.ganglia, caps.i.) R a.c.media

22,6

No

+13

3

2

+

No

RBD1

55

M

Infarct

1,0

No

+3,1

1

1

−

No

RBD2 RBD3 RBD4 RBD5

57 56 60 62

F F F M

Infarct Infarct Infarct Infarct

5,9 1,8 3,5 1,3

No No No No

−1,9 +2,9 −4,9 −0,2

0 0 0 0

0 0 0 0

− − − −

No Yes No No

RBD6

53

M

ICB

3,8

No

−0,6

0

0

−

No

RBD7 RBD8 RBD9 RBD10

56 64 63 45

M M F M

Infarct Infarct ICB Infarct

1,6 13,6 4,6 2,6

No No No No

+1,9 −1,5 −6,7 −3,2

0 1 0 0

0 1 0 0

− − − −

No Yes No No

LBD1 LBD2

42 48

M F

Infarct Infarct

6,2 4,0

No No

+1,5 −4,4

0 0

0 0

− −

No No

LBD3

69

F

Infarct

2,4

No

−1,9

0

0

−

No

LBD4 LBD5 LBD6

56 64 40

M M F

Infarct Infarct Infarct

2,0 4,4 3,1

RL quadr No No

−2 +3,6 −2,1

0 0 0

0 0 0

− − −

Yes No No

LBD7 LBD8 LBD9

21 66 39

M M F

Aneurysm Infarct Infarct

5,5 2,4 7,2

No No No

−0,6 −5 −1,5

0 0 0

0 0 0

− − −

No No No

LBD10 LBD11 LBD12

38 53 41

F M F

Infarct ICB Infarct

LBD13 LBD14

76 56

F F

RN1

49

F

R occipital, thalamus R temporal R fronto-parietal R parietal R temporal-(parietal) R parietal, bas.ganglia, caps.i. R temporal R front-par-temp R periventriculair R frontal

Neglect observation

Extinction on clinical testing

1,8 3,3 34,4

No No No

−6,5 −1,2 −7,9

0 0 1

0 0 0

− − −

No No Yes

Infarct Infarct

L a.c.media L a.c.media, a.c.anterior L temporal (frontal-parietal) L temporo-parietal L parietal L frontal, basal ganglia L frontal, temporal L basal ganglia L parietal, subinsulair, caps.i. L temporal L thalamus L temporo-parietal, bas.ganglia L a.c.media L parietal

1,7 3,9

No No

+0,5 −2,2

0 0

0 1

− −

No No

Infarct

L par-occ

8,2

No

−15,9

1

3

+

No

LN: right brain damage left neglect patient; RBD: right brain damage no neglect patient; LBD: left brain damage no neglect patient; RN: left brain damage right neglect patient; M: male; F: female; ICB: intracerebral bleeding; R: right lesion; L: left lesion; LL quadr: quadrantanopia in left lower visual field: RL quadr: quadrantanopia in right lower visual field; neglect observation +/−: typical neglect behaviour was/was not observed by the neuropsychologist or other trained therapists from the revalidation unit.

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Fig. 1. Schematic depiction of stimuli and trial sequences for the luminance threshold task.

guess if not sure. Response time was unlimited. Feedback was given in the form of an auditory signal for incorrect responses. Only after a response was made and after a 2000 ms intertrial interval the next trial was initiated. Eye movements were monitored with the ASL 210 eye tracker. Trials with eye movements out of a 2◦ fixation window were discarded and repeated. Stimuli were presented in four blocks of 20 trials (not counting trials with eye movements). Within a block, the stimulus was always presented in the same position. Blocks with left and right hemifield stimulus positions were alternated. Thus, threshold estimation for each hemifield consisted of 40 trials. 2.5. Orientation thresholds Unless stated otherwise, the stimuli and procedures were the same as for the luminance threshold measurements. Stimuli could be either target gratings or distractor gratings, both of them having the same size and spatial frequency as the luminance gratings. Target gratings were always presented at the cued (left or right hemifield) position; distractor gratings were always presented in the opposite hemifield, at the homologue position (Fig. 2). To compensate for ipsi-contralesional sensory imbalances, the luminance of both target and distractor gratings was set at 20 times the luminance threshold that was obtained for their respective positions. Orientation thresholds were determined for target gratings in left and right visual fields, with and without the simultaneous presentation of a distractor grating. Subjects indicated whether the grating orientation deviated clockwise or anticlockwise from vertical. A contraversive tilt of the subjective visual vertical has been observed in patients with parietal lesions (Cramon & Kerkhoff, 1993) and more specifically in neglect patients (Kerkhoff, 1999). We used a constant stimuli paradigm so as to be able to separate orientation sensitivity from the point of subjective visual verticality. Via a short adaptive staircase procedure, five equally spaced and infor-

mative orientations spanning the estimated subjective visual vertical were obtained for each subject and separately for left and right hemifield positions. These orientations were then used as target stimulus orientations in the actual task. Distractor orientations were chosen randomly in each trial and could be any orientation between 0◦ and 360◦ . Blocks of 20 trials with a left hemifield target stimulus were alternated with 20 trial blocks with a right hemifield target. Within a block, the five target stimulus orientations were randomly presented. In half of the trials of each block (random) a distractor grating was presented simultaneously, for the same duration, and in the opposite hemifield of the target. Subjects were instructed to ignore the distractor as much as possible. The cue always indicated the position of the target to be presented. If the target orientation deviated clockwise from vertical, subjects had to press the right response key; for an anticlockwise deviation, the left response key had to be pressed. The experiment was carried out in a completely darkened room, so that there was no reference frame for comparison with the grating orientations. Trials with eye movements out of a 2◦ window were discarded and repeated. A total of 100 trials per condition (20 trials per orientation level, not counting trials with eye movements) had to be completed.

3. Results 3.1. Luminance thresholds The thresholds were log-transformed to homogenize variance. The mean left and right hemifield log-transformed luminance thresholds for the different subject groups are shown in Fig. 3. A two-way repeated measures analysis of variance (ANOVA) on these data (without the data for the single LBD right neglect subject) resulted in a main effect of hemifield (F(1,49) = 7.93; P < .007) and a significant interaction be-

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Fig. 2. Schematic depiction of stimuli and trial sequences for the orientation discrimination task.

Fig. 3. Mean log-transformed left and right hemifield 70% correct luminance thresholds (and standard deviations) for the different subject groups. RBD: right brain damage; LBD: left brain damage.

tween group and hemifield (F(3,49) = 6.02; P < .001). Normal and LBD control subjects obtained similar thresholds in their left and right hemifields; RBD neglect and RBD control groups obtained elevated left hemifield thresholds as compared to their right hemifield thresholds. A post-hoc unequal N HSD analysis indicated that the left–right difference was significant only in the RBD with neglect group (P < .001). The extinction patients in this group obtained slightly larger differences between left and right hemifield thresholds than

the neglect patients without extinction on standard testing. Because there were no significant differences between the two groups, data from patients with and without extinction on standard testing were analyzed together. 3.2. Orientation thresholds For each individual subject, and for the different conditions, the normalized percentages of “clockwise deviation

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Fig. 4. Performance of one representative subject from each of the different subject groups in the orientation discrimination task. Patient codes refer to those of Table 1. Normalized percentages of ‘clockwise deviation from vertical’ responses are plotted against the presented orientations. JNDs are estimated via linear regression analyses. The JND is an inverse measure of the slope of the regression line. Neglect patients show significant interference from an ipsilesional distractor with contralesional JNDs.

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Fig. 5. Mean log-transformed just noticeable differences (JNDs) in orientation and standard deviations, in left and right hemifield conditions with and without distractor, for the different subject groups. RBD: right brain damage; LBD: left brain damage.

from vertical” responses were plotted against the presented orientations (ordered from the largest anticlockwise to the largest clockwise deviation). Fig. 4 shows plots of one representative subject from each of the different subject groups. A significant correlation between grating orientation and normalized percentage clockwise responses was observed in each subject in the conditions without distractor (Pearson product moment correlations r > .80; P < .05) and in all of the control subjects in the conditions with distractor. However, 5 of the 15 neglect patients did not show a significant correlation (r < .60; P > .05) between orientation and percentage clockwise responses in the left target right distractor condition. These subjects were not able to perform the orientation discrimination task for the left target in the presence of a right distractor. Consequently, reliable thresholds could not be determined for these subjects. Subsequent group analyses only involved the 10 neglect patients that obtained reliable thresholds in the distractor conditions. Via least squares linear regression analyses, points of subjective visual verticality and just noticeable differences (JNDs) in orientation were estimated. The subjective visual vertical (SVV) corresponds to the intercept of the psychometric function. Although some neglect patients obtained clearly larger than normal contraversive SVV tilts (up to 16◦ counterclockwise), this was not the case for all of the neglect patients and no significant group differences were observed (Kruskal–Wallis ANOVA by ranks: P > .05 for all conditions).

Our main interest, however, concerns orientation sensitivity (JND in orientation). The JND is an inverse measure of the slope of the psychometric function. The mean logtransformed JNDs in orientation for the different groups are plotted in Fig. 5. Compared to the control groups, the RBD left neglect group showed an increased right distractor interference with left hemifield JNDs and a decreased left distractor interference with right hemifield JNDs. The LBD right neglect patient displayed the opposite pattern of results, with an increased left and decreased right distractor interference. For control groups, the mean interference from left and right distractors seemed to be of the same magnitude. In sum, neglect patients displayed asymmetric distractor interference, control subjects symmetric distractor interference. A three-way repeated measures ANOVA on these data (without the data of the one LBD patient with right neglect) resulted in a significant three-way interaction between group, hemifield, and distractor condition (F(3,44) = 21.49; P < .000001). To further unravel this higher order interaction, two-way ANOVAs were performed for each group separately. For the left neglect group this yielded a main effect of hemifield (F(1,9) = 39.0; P < .0002), a main effect of distractor condition (F(1,9) = 179.4; P < .000001), and a significant interaction between hemifield and distractor condition (F(1,9) = 53.2; P < .00005). This interaction was not significant in any of the control groups. In the normal control group, only a main effect of distractor condition was observed (F(1,13) = 15.46; P < .002). LBD

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Table 2 Number of subjects showing significant or non-significant distractor interference from a right distractor with left hemifield orientation sensitivity (LHF) and/or from a left distractor with right hemifield orientation sensitivity (RHF) LHF

RHF

Normal controls (n = 14)

RBD left neglect (n = 15)

RBD no neglect (n = 10)

LBD no neglect (n = 14)

LBD right neglect (n = 1)

n.s. Sign. n.s. Sign.

n.s. Sign. Sign. n.s.

13 1 0 0

0 0 0 15

7 2 0 1

12 2 0 0

0 0 1 0

For each subject, factorial regression analyses were performed on the normalized percentage of “clockwise deviation from vertical” responses. Sign. = significant difference between distractor and non-distractor conditions (P < .05); n.s. = non-significant difference (P > .05).

and RBD control groups displayed main effects of distractor condition (F(1,13) = 6.44; P < .025 and F(1,9) = 15.35; P < .0035) and hemifield (F(1,13) = 13.78; P < .003 and F(1,9) = 13.12; P < .006). JNDs were higher in their contralesional hemifields. Increased contralesional as compared to ipsilesional JNDs were also observed in the left neglect group. Moreover, left neglect patients obtained higher JNDs in all conditions as compared to the control groups. Individual subjects were classified as showing significant or non-significant distractor effects from the left and/or the right distractor. To this end, factorial regression analyses were performed on the normalized percentage of “clockwise deviation from vertical” responses for each subject. This allowed us to determine whether there was a significant difference between the left target condition with distractor and the left target condition without distractor and/or between the right target condition with distractor and the right target condition without distractor. Table 2 summarizes the results obtained when using a significance level of P < .05. For all of the 15 RBD left neglect patients, a significant interference from the right distractor with left hemifield orientation sensitivity was observed, while none of these patients showed a significant interference from the left distractor with right hemifield orientation sensitivity. One subject of the RBD control group obtained a similar result. The LBD patient with right neglect displayed the opposite pattern of results, with only significant left distractor interference. The other RBD controls and all of the LBD and normal controls obtained either a significant interference from both distractors, or no significant interference at all. The magnitude of the distractor effects was determined for each subject by dividing the JNDs from the distractor conditions by the JNDs from the non-distractor conditions. A left hemifield distractor effect denotes the interference of a right distractor with left hemifield orientation sensitivity, a right hemifield distractor effect denotes the interference of a left distractor with right hemifield orientation sensitivity. In the control groups, the left hemifield distractor effect correlated positively with the right hemifield distractor effect (Spearman rank order correlation r = .62; t(36) = 4.7; P < .00004): people with a strong interference from a distractor in one hemifield, also exhibited a more pronounced interference effect from a distractor in the opposite hemifield. In the RBD left neglect group, in contrast, the correlation was

negative (r = −.7; t(8) = −2.75; P < .026): the stronger the interference from the right distractor, the less pronounced the interference from a left distractor was. In some patients with a robust right distractor interference, the left distractor interference disappeared or even tended to reverse (with a lower threshold in the presence of a distractor than without distractor). The single LBD right neglect patient displayed the mirror-image pattern of results, with an increased left and decreased right distractor interference. In sum, neglect patients showed asymmetric distractor interference, whereas control subjects showed symmetric distractor interference. The ratio of the left versus right hemifield distractor effects provided us with an asymmetry index that we correlated with other measures of asymmetry (Table 3). RBD patients obtained higher contralesional as compared to ipsilesional thresholds for both the luminance and orientation tasks without distractors. In the left neglect group, spearman rank order correlations between the asymmetry index and the ratio of left and right hemifield thresholds in the tasks without distractors were not significant. The correlation between the asymmetry index and line bisection deviation, on the other hand, was significant. Moreover, the correlation between asymmetry index and cancellation asymmetry (difference between number of left-sided and right-sided omissions) was close to significance. Contra-ipsilesional differences in non-distractor luminance or orientation tasks did not correlate significantly with line bisection deviation or cancellation asymmetry. None of the aforementioned correlations was significant in any the control groups. Table 3 Spearman rank order correlations (and significance levels) between different measures of asymmetry in the neglect group (n = 10) Correlation between

R

P-levels

AI and L/R luminance thresholds AI and L/R orientation thresholds AI and rightward line bisection deviation AI and cancellation asymmetry L/R luminance thresholds and line bisection deviation L/R luminance thresholds and cancellation asymmetry L/R orientation thresholds and line bisection deviation L/R orientation thresholds and cancellation asymmetry

−.45 −.54 .79 .61 .07 .21 −.31 −.05

.19 .11 .006∗∗ .06 .81 .45 .27 .86

LHF = left hemifield; RHF = right hemifield; AI = asymmetry index (ratio LHF and RHF distractor effects); L/R = ratio left and right thresholds. ∗∗ P < .01

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4. Discussion A psychophysical paradigm was used to study extinction in brain-damaged patients with or without neglect. First, we determined luminance thresholds for the discrimination of horizontal from vertical gratings. Contralesional thresholds were higher than ipsilesional thresholds in RBD patients, but this difference was only significant in the left neglect group. LBD patients and normal controls did not show differences between left and right hemifield thresholds. Because left posterior lesions often result in comprehension deficits and/or left–right confusion (Kolb & Whishaw, 1996), a selection bias in our patient group might have resulted in more anteriorly located lesions, and consequently, less sensory deficits. However, larger contra-ipsilesional differences in RBD as compared to LBD patients in detection tasks have also been observed by other authors (Sterzi et al., 1993; Smania et al., 1998), who interpreted these differences as resulting from attentional impairments being more frequent after RBD, rather than sensory deficits. Although in our study stimuli are always cued validly, we cannot exclude attentional explanations for these differences. Second, extinction, in our study, was defined as an asymmetric interference from left and right hemifield distractors with contralateral orientation thresholds. Individual subjects were classified as showing extinction when a significant ipsilesional distractor interference was observed combined with non-significant contralesional distractor interference. In all LBD and all but one RBD patients without neglect and in the normal control group, an equally large (symmetric) interference was observed from left and right hemifield distractors. Most importantly, extinction was present in all neglect patients, as evidenced by asymmetric distractor interference. This suggests that neglect without extinction is rare if not nonexistent. Previous studies that demonstrated neglect without extinction never tested extinction in such a sensitive way. In fact, using the standard extinction testing procedure, only 7 of our 15 neglect patients were diagnosed as having extinction. The neglect patients still showed extinction, even after sensory imbalances were eliminated by equating the visibility of ipsi- and contralesional stimuli. This may be important in the light of two reported findings. First, Marzi et al. (1997) observed, in extinction patients, a correlation between contra-ipsilesional differences in detection of unilateral stimuli and the severity of the extinction effect. On the basis of this finding, it could be predicted that, by eliminating the contra-ipsilesional differences, the extinction effect could also disappear. However, our results definitely show an extinction effect in the neglect patients. Second, an early, automatic orienting of attention towards ipsilesional stimuli in neglect patients has been demonstrated repeatedly. This was done in studies using RT paradigms (D’Erme, Robertson, Bartolomeo, Daniele, & Gainotti, 1992) or under free viewing conditions as the tendency to identify first those parts of chimeric or grey scale stimuli that are located

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on the right side of the stimulus (Mattingley et al., 1994). However, using a grey scale task, Tant, Kuks, Kooijman, Cornelissen, & Brouwer (2002) observed the same attentional bias in hemianopic patients without neglect, suggesting that sensory deficits can be the source of the attentional bias. In the present study, imbalances in the salience of the stimuli were eliminated and we still observed asymmetric interference effects. Third, even when attention was cued to the left side, significant interference from an irrelevant right hemifield distractor was observed. Although cueing has been shown to improve or even abolish extinction (Di Pellegrino & De Renzi, 1995; Karnath, 1988), our results demonstrate that part of the extinction effect persists. Apparently, cueing cannot overcome the ‘magnetic’ attraction of attention towards ipsilesional stimuli. This magnetic attraction can take several, not necessarily mutually exclusive, forms. Indeed, it has been suggested repeatedly that neglect could be characterized by several attentional deficits. First, it is possible that, when target and distractor gratings popped up, attention was oriented automatically to the ipsilesional distractor (Mattingley et al., 1994). Second, neglect patients might exhibit a deficit in disengaging attention from the ipsilesional distractor grating and reorienting attention to the contralesional target grating (Posner et al., 1984). Third, extinction could be the result of a general attentional imbalance between the two hemispheres (Duncan, Humphreys, & Ward, 1997; Kinsbourne, 1993). When the right hemisphere is damaged, the competition is biased towards one side; stimuli towards the left side suffer and those towards the right side benefit. Such an attentional or spatial gradient might emerge from a contra- to ipsilesional gradient of mutually inhibitory cell populations (Pouget & Driver, 2000; Rizzolatti & Berti, 1990).3 What are the possible implications of our findings for underlying mechanisms of extinction and neglect? First, as far as the neglect patients are concerned, we collected evidence for extinction in every patient. The neglect patients not only suffered an increased interference from an ipsilesional distractor when they had to attend to and evaluate the orientation of the contralesional stimulus. Compared to the control groups, neglect patients also tended to experience less interference from a contralesional distractor when the orientation of an ipsilesional stimulus had to be reported. In addition, the negative correlation between the left and right hemifield distractor effects in left neglect patients was significant. These findings suggest that the decreased left and 3 Note that in each of these deficits in a component of attention, it is supposed that the deficit is lateralized. Based on the observation of extinction in patients without neglect, Duncan (1999) suggested that extinction or lateral bias is a very widespread consequence of unilateral brain injury, and that neglect might be the combination of this general lateral bias (probably influenced by sensory deficits) with a nonlateralized attentional deficit (general reduction in the uptake of visual information). The results of the present study, however, indicate that a lateralized attentional deficit is typical for neglect patients.

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increased right distractor interference effects are two manifestations of the same underlying deficit. These results fit very well with competitive accounts of neglect (Duncan et al., 1997; Kinsbourne, 1993). Evidence for the hypothesis that neglect and extinction (in neglect patients) share a common underlying mechanism is provided by the observation that the extinction effect (asymmetry indexes) correlates with rightward line bisection deviation, which is assumed to be a sensitive measure of neglect (Halligan & Robertson, 1992). Left–right hemifield asymmetries observed in the luminance and non-distractor orientation tasks, on the other hand, did not correlate with line bisection deviation. Thus, extinction and neglect seem to be more related to the asymmetry caused by competition between two simultaneously presented stimuli, than to the contra-ipsilesional (sensory or attentional) asymmetry between unilaterally presented stimuli. Second, as far as the unilaterally brain-damaged patients without neglect are concerned, only one of the RBD patients without neglect (RBD4 in Table 1) displayed extinction. However, the interference effect from the ipsilesional distractor was smaller than in the neglect patients (factor 1.6 compared to factors between 2.1 and 3.5). This effect might represent the residual of a minor, recovered neglect. None of the other RBD, LBD, or normal controls displayed the typical extinction pattern of results. Striking is that even the four subjects who demonstrated extinction in the standard extinction test, did not show asymmetric distractor interference after adaptation of the luminances. They did, however, show larger contra-ipsilesional luminance threshold differences than the other control subjects, larger even than many of the neglect patients. This suggests that extinction effects on standard testing in these patients could be traced back to sensory imbalances. Vallar et al. (1994) already demonstrated lesions in the afferent sensory pathways in many extinction patients without neglect. Extinction is often defined as unawareness for contralesional stimuli (Vuilleumier et al., 2001; Rees et al., 2000). However, our results show that extinction not necessarily involves the total disappearance of the contralesional stimulus. Reliable orientation thresholds were obtained in 10 neglect patients even with an ipsilesional distractor. This implies that the patients were able to perceive and identify the left stimulus. They did make use of the cue and did not respond to the ipsilesional stimulus. Extinction is not an all-or-none phenomenon or not merely the failure to detect a contralesional stimulus in the presence of an ipsilesional stimulus but, rather, reflects the relative inhibition of the contralesional by the ipsilesional stimulus, resulting in a degraded representation (Ptak, Valenza, & Schnider, 2002). The degree of inhibition may depend on lesion size and task conditions. If patients are unaware of stimuli, this might be because there is also a sensory deficit apart from the attentional deficit, or because the ipsilesional stimulus is relevant and attention is more strongly attracted to it.

Acknowledgements We wish to thank all the patients and control subjects for their participation. We also thank rehabilitation centre ‘Hof ter Schelde’, Karla Michiels and Dr. C. Kiekens (Physical Medicine and Revalidation, U.Z. Pellenberg) for the neuropsychological data and referrals of patients.

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