Abstract

It is well established that patients with hemispatial neglect present with severe visuospatial impairments, but studies that have directly investigated visuomotor control have revealed diverging results, with some studies showing that neglect patients perform relatively better on such tasks. The present study compared the visuomotor performance of patients with and without neglect after right-hemisphere stroke with those of age-matched controls. Participants were asked to point either directly towards targets or halfway between two stimuli, both with and without visual feedback during movement. Although we did not find any neglect-specific impairment, both patient groups showed increased reaction times to leftward stimuli as well as decreased accuracies for open loop leftward reaches. We argue that these findings agree with the view that neglect patients code spatial parameters for action veridically. Moreover, we suggest that lesions in the right hemisphere may cause motor deficits irrespective of the presence of neglect and we performed an initial voxel-lesion symptom analysis to assess this. Lesion-symptom analysis revealed that the reported deficits did not result from damage to neglect-associated areas alone, but were further associated with lesions to crucial nodes in the visuomotor control network (the basal ganglia as well as occipito-parietal and frontal areas).

Introduction

Right-hemisphere lesions, typically after damage to the inferior parietal lobe (Mort et al. 2003) or the superior temporal cortex, (Karnath et al. 2001, 2004) frequently cause hemispatial neglect. This puzzling and severe condition is characterized by a lack of awareness of the contralesional side of space in that patients behave as if the left side of the world ceased to exist (for a recent review see Parton et al. 2004).

A common way to diagnose neglect is to ask patients to mark the center of a horizontal line (line bisection) and individuals with neglect typically show a rightward bias in this task (e.g., Harvey et al. 1995; Milner and Harvey 1995). Milner and Goodale (1995, 2006, 2008), somewhat contentiously, argue that many of these perceptual symptoms reflect a failure in a high-level representational structure where the products of the ventral visual stream processing are integrated and made use of. On the other hand, they also predict that neglect patients should code spatial parameters veridically when performing goal-directed actions, as this would be accomplished by presumably intact dorsal visual stream areas.

In keeping with this, it is well established that neglect patients do not show the gross misreaching to visual targets that is observed in patients with optic ataxia. Such patients suffer from bilateral damage to superior areas of the posterior parietal cortex (PPC), overlapping in the medial and lateral part of the parietal–occipital junction (POJ; Karnath and Perenin 2005), thought to be part of the visual dorsal stream (see Culham and Valyear 2006; Culham et al. 2006; Milner and Goodale 2006, for a review). However, the hypothesis that neglect patients are relatively unimpaired when performing goal-directed actions has been considerably debated in the last decade.

In a recent controversial review Coulthard et al. (2006) concluded that many patients with hemispatial neglect are impaired when reaching towards the contralesional side of space. Their arguments were based on previous findings that such patients take more time to initiate and/or complete an action towards the contralesional side of space (Heilman et al. 1985; Husain et al. 2000; Mattingley et al. 1992, 1994; Mattingley, Husain, et al. 1998) and/or present increased rightward curved trajectories (Goodale et al. 1990; Harvey et al. 1994; Jackson et al. 2000).

Himmelbach et al. (2007) contested this by arguing that such studies contrasted the performance of neglect patients against healthy age-matched controls, a comparison that does not clarify whether these biases are neglect specific. They suggest that the critical comparison is between patients with and without neglect, as the motor abnormalities observed in neglect patients may simply be a consequence of “a phenomenon occurring with (so far not further identified) brain damage.” In other words, the presence or absence of such deficits may not depend on the presence of neglect, but rather, more generally, on the extent of damage to the visuomotor control network. In keeping with this, studies that have included patients without neglect after right-hemisphere lesions have failed to find any neglect-specific temporal or spatial inaccuracies in reaching or grasping (Karnath et al. 1997; Konczak and Karnath 1998; Harvey et al. 2002; Himmelbach and Karnath 2003). Moreover, it has been suggested that neglect patients are relatively unimpaired in reaching due to a functional dissociation within the PPC: while superior regions seem to be involved in rapid on-line visuomotor control, more inferior areas, like the ones damaged in neglect, seem to subserve longer lasting, explicit and multimodal representations (e.g., Himmelbach et al. 2007).

In a final reply, Coulthard et al. (2007) clarified their conclusions by agreeing that the reaching deficits observed in neglect may not be specific to the condition. We agree with this, as well as with Karnath and colleagues’ notion of the importance of adequate control groups. However, we would argue even more strongly, in line with Milner and Goodale (1995, 2006; Milner 1995), in that on-line reaches (even those into the left side of space) should be relatively unimpaired in neglect and we would extend this argument to open loop reaches.

So far results regarding the influence of visual feedback on the visuomotor abilities of neglect patients have been most inconclusive. While Goodale et al. (1990) reported that recovered neglect patients, when compared to healthy controls, presented large rightward deviations in gap bisection with visual feedback, Harvey et al. (1994) found rightward biases only for open loop reaches (in right-hemisphere lesioned patients without neglect). Moreover, Jackson et al. (2000), found large rightward deviations in pointing when neglect patients had full vision of the hand, but again others have not replicated this neither for pointing nor grasping (Karnath et al. 1997; Harvey et al. 2002) nor closed loop gap bisection McIntosh, McClements, Dijkerman and Milner (2004).

We therefore examined the performance of right-hemisphere lesioned patients with and without hemispatial neglect, as well as a group of healthy subjects, in both pointing and gap bisection, both with and without visual feedback. If Milner and Goodale (2006) are correct in claiming that the dorsal stream is relatively spared in hemispatial neglect, then neglect should not specifically affect pointing in either open or closed loop conditions, even when reaches are made towards the left side of space. Regarding gap bisection, we further predict no neglect-specific impairment, as the rightward bias frequently found in line bisection has been shown to be reduced when gaps are presented instead of filled lines, a finding deemed to result from cueing effects McIntosh, McClements, Dijkerman and Milner (2004).

Finally, although we hypothesize that there is no neglect-specific impairment in action control, we expect that some patients will present deficits in the tasks, especially if their brain damage extends to crucial nodes in the visuomotor control network. Therefore, another aim of this study was to clarify the neural basis of motor deficits after right-hemisphere damage. Previous studies (Bisiach et al. 1990; Tegner and Levander 1991; for review see Vallar 2001) have reported that frontal and basal ganglia lesions produce increased reaction and movement times, but the mapping methods used did not allow a precise localization of the site of damage. Other studies argue instead that injury to the right posterior–inferior parietal lobe is associated with increased reaction times to left stimuli (Mattingley, Husain, et al. 1998; Husain et al. 2000). The recent development of voxel-based lesion-symptom analysis Rorden, Karnath, et al. (2007) thus provided us with a unique opportunity to conduct an initial exploratory investigation of the lesioned brain areas potentially associated with the temporal and spatial visuomotor abnormalities observed after right-brain lesions.

Materials and Methods

Participants

Eleven patients with left hemispatial neglect after right-hemisphere damage participated in the study (RH+; mean age 66.8, SD 7.7). Nine patients with right-hemisphere damage without neglect (RH−; mean age 67.2, SD 7.8) and 10 healthy participants (mean age 71.0, SD 4.8) served as control groups. The groups were age-matched and all participants were right-handed (Annett 1967). The healthy participants had normal or correct-to-normal visual acuity. On average patients took part in the experiment 8 months after stroke onset and there were no differences in onset times between the two patient groups.

Patients were included in the RH+ group if they scored below the cut-off on the conventional subtests of the Behavioral Inattention Test (BIT) (Wilson et al. 1987) or presented a significant rightward bisection error (Harvey et al. 1995) or were impaired in a lateralized manner in the subtest B of the Balloons Test (Edgeworth et al. 1998). Patient MMG was included in the neglect group despite scoring above the cut-off on the neglect assessment measures, because she showed typical signs of neglect as reported by family members and therapists/clinical staff (e.g., bumping into objects on the left). Importantly, none of the RH− patients ever showed signs of neglect on these tests.

Hemianopia and extinction were formally assessed using computerized perimetry and confrontation tests. In neglect patients AB, DF, FH, and NF extinction could not be assessed in a meaningful way as these patients were unable to report the presence of a single leftward stimulus. Demographic and clinical data of all patients are presented in Table 1.

Table 1

Demographic and clinical data of the right-brain–damaged patients

Group Patient Gender Age Scan Etiology Lesion location Lesion volume TO VFD Ext BIT Line bisection Balloons 
RH+ AB 70 MRI Infarct Temporo-occipital 100.7 Yes (−) 131 31 50 
 AM 63 CT Infarct Fronto-temporal-parietal-insular 85.3 Yes Yes 130 11 50 
 DS 64 MRI Infarct Fronto-temporo-occipital 56.5 Yes (−) 91 82 50 
 FH 80 MRI Hemorrhage Temporo-parietal 108.6 15 Yes (−) 103 75 27 
 JH 56 MRI Infarct Fronto-temporo-parietal 189.2 19 Yes Yes 139 25 43 
 JK 69 CT Infarct Fronto-temporal 50.9 No No 141 15 44 
 JM 55 MRI Infarct Fronto-parietal 169.5 Yes Yes 117 11 43 
 JS 76 MRI Infarct Temporal, insular cortex and periventricular white matter 105.2 28 Yes Yes 129 36 
 MM 72 CT Infarct Fronto-temporal-insular 18.0 No No 128 50 
 MMG 63 MRI Infarct Dorsal frontal, parietal, corona radiata 61.6 No No 142 59 
 NF 67 MRI Infarct Fronto-temporo-parietal 268.8 Yes (−) 143 29 
RH− AMI 60 CT Infarct Lentiform nucleus 1.36 No No 146 50 
 AW 64 MRI Infarct Basal ganglia 2.64 No No 145 −2 50 
 DM 78 MRI Infarct Fronto-temporal 59.56 No No 145 50 
 JC 76 CT Infarct Fronto-temporal 9.44 No No 146 53 
 JST 56 CT Infarct Dorsal frontal, posterior temporal, parietal 48.96 Yes No 146 53 
 LS 60 CT Infarct Caudate nucleus 1.76 No No 144 50 
 MP 66 MRI Infarct Basal ganglia 0.72 No No 146 53 
 RM 73 CT Infarct Lentiform nucleus 0.24 No No 141 46 
 SC 72 CT Infarct Frontal 16.16 13 No No 140 54 
Group Patient Gender Age Scan Etiology Lesion location Lesion volume TO VFD Ext BIT Line bisection Balloons 
RH+ AB 70 MRI Infarct Temporo-occipital 100.7 Yes (−) 131 31 50 
 AM 63 CT Infarct Fronto-temporal-parietal-insular 85.3 Yes Yes 130 11 50 
 DS 64 MRI Infarct Fronto-temporo-occipital 56.5 Yes (−) 91 82 50 
 FH 80 MRI Hemorrhage Temporo-parietal 108.6 15 Yes (−) 103 75 27 
 JH 56 MRI Infarct Fronto-temporo-parietal 189.2 19 Yes Yes 139 25 43 
 JK 69 CT Infarct Fronto-temporal 50.9 No No 141 15 44 
 JM 55 MRI Infarct Fronto-parietal 169.5 Yes Yes 117 11 43 
 JS 76 MRI Infarct Temporal, insular cortex and periventricular white matter 105.2 28 Yes Yes 129 36 
 MM 72 CT Infarct Fronto-temporal-insular 18.0 No No 128 50 
 MMG 63 MRI Infarct Dorsal frontal, parietal, corona radiata 61.6 No No 142 59 
 NF 67 MRI Infarct Fronto-temporo-parietal 268.8 Yes (−) 143 29 
RH− AMI 60 CT Infarct Lentiform nucleus 1.36 No No 146 50 
 AW 64 MRI Infarct Basal ganglia 2.64 No No 145 −2 50 
 DM 78 MRI Infarct Fronto-temporal 59.56 No No 145 50 
 JC 76 CT Infarct Fronto-temporal 9.44 No No 146 53 
 JST 56 CT Infarct Dorsal frontal, posterior temporal, parietal 48.96 Yes No 146 53 
 LS 60 CT Infarct Caudate nucleus 1.76 No No 144 50 
 MP 66 MRI Infarct Basal ganglia 0.72 No No 146 53 
 RM 73 CT Infarct Lentiform nucleus 0.24 No No 141 46 
 SC 72 CT Infarct Frontal 16.16 13 No No 140 54 

Note: TO = time since injury onset (months); VFD = visual field defect; Ext = extinction; BIT conventional subtests score (cut-off = 129); Line bisection represents the average error (in mm) obtained with 20 lines (200 mm length), no sign is equivalent to a rightward error and a negative sign is equivalent to a leftward error (cut-off = 6 mm, Halligan et al. 1990); balloons represent the lateralized index score in subtest B (patient is impaired when this index is lower than 45%); (−) unable to disentangle extinction from visual field deficit.

In addition, to assess the general cognitive status the following subtests of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) (Wechsler 1981) were administered to all patients: picture completion, vocabulary, block design, information, digit span, and object assembly. An analysis of variance with group (RH+ and RH−) as the between factor was performed on the scaled scores of each subtest. This revealed that neglect patients were significantly impaired on all performance subtests when compared to RH− patients (block design: F1,18 = 19.15, P < 0.001; picture completion: F1,19 = 10.34, P < 0.01; object assembly: F1,17 = 20.98, P < 0.001). This finding replicates our observations in a previous study (Rossit, Muir, Reeves, Duncan, Birschel, et al. 2009) and is almost certainly due to reduced processing of information on the left of the stimulus displays. No differences between the 2 groups were obtained for information, digit span and vocabulary scaled scores.

Ethical approval was granted by the South Glasgow University Hospitals Trust and the study was carried according to the Declaration of Helsinki. All participants gave their informed consent prior to participation in the study and were reimbursed for their travel expenses.

Stimuli and Procedure

Targets were white circles (diameter 7 mm) projected (HITACHI CP-X345 Multimedia LCD Projector, refresh rate of 60 Hz) onto a horizontal perspex box (77 cm width/97 cm length/30 cm height) via a reflection mirror (3 mm thick, 60 × 60 cm). The box was placed on top of a wooden table at which the subjects were comfortably seated. The target surface was 77 cm wide and 49 cm long. Targets were visible only when illuminated and no tactile information of their locations was available. The central target was located 40 cm in front of the start trigger and aligned with the centre of the box. At the start of each trial, the participant's right index finger rested on the start trigger, aligned with the subject's sagittal midline. Eye movements were unrestricted. The room was slightly darkened so that the targets were clearly visible when illuminated, yet not at any other time.

The design was adapted from Goodale et al. (1990). In the pointing condition, participants pressed the start trigger for 1000 ms after which a tone (800 Hz) cued the subjects to initiate the movement. The target remained visible until the end of the trial and participants were instructed to point to the target as quickly and as accurately as possible. In this condition, subjects were presented with three targets illuminated one at a time located at −10 (left hemispace), 0 (central), and 10 cm (right hemispace). In the gap bisection condition, on start trigger press two identical circles were presented simultaneously for 1000 ms after which a tone (800 Hz) cued the subject to point midway between these two circles as quickly and accurately as possible. In this case the two circles were presented simultaneously at three different positions, either in left (−15 and −5 cm), centrally (−5 and 5 cm) or right hemispace (5 and 15 cm). The dots varied randomly in location from trial to trial although the distance between them was fixed (10 cm). Note that the true midpoints in the gap bisection task were identical to the locations of the targets used in the pointing task (−10, 0, and 10 cm) and all movements were made with the right arm and hand.

As in Harvey et al. (1994), all participants reached under closed loop conditions first, yet the order of the bisection and pointing tasks was counterbalanced across participants. In the closed loop condition the room light permitted full vision of the arm and hand during the movement. In the open loop condition, subjects wore shutter glasses (PLATO Model S-3, Translucent Technologies, Inc., Toronto, Canada), which prevented vision of the arm, hand, and target during movement as the shutters closed as soon as the start trigger was released (c.f., Jackson et al. 2000). These manipulations resulted in four blocks of trials: closed loop pointing, closed loop gap bisection, open loop pointing and open loop gap bisection. Each block contained 6 practice trials (2 for each target position) and 36 experimental trials (12 for each target). Calibration coordinates were obtained at the end of the each session, by continuous illumination of each target, one by one, allowing the subjects to adjust their terminal fingertip position until they felt they had perfectly occluded the target. There were three calibration trials per target (−10, 0, 10) and three for the start position.

Pointing responses were recorded by sampling the position of a magnetic marker, attached to the tip of the right index finger, at a rate of 108 Hz, using an electro-magnetic motion analysis system (Minibird, Ascension Technology, Inc., Burlington, VT). The start trigger, the shutter glasses, the on-line recordings and the stimuli presentation were simultaneously controlled and timed by a PC, by means of a Virtual Instrument generated with LabView software (National Instruments, Newbury, UK).

Behavioral Analysis

Data obtained from the recordings were analyzed off-line. The start and end of each movement were defined by a velocity-based criterion of 40 and 50 mm/s, respectively. Based on the calibration coordinates, we calculated the terminal accuracy variables, absolute and signed angular error, relative to the ideal reach either to the target or to the location midway between the two targets. To analyze the movement path shape we computed the cumulative hand path curvature index (c.f. Himmelbach and Karnath 2003). First, the mean x coordinates for each 1-mm y coordinate were obtained for each subject, per target position and condition. Secondly, we computed the deviations in the x-axis of the subject's trajectory from a perfectly straight trajectory to the target. This was obtained individually for each participant based on the calibration coordinates. Finally, the deviations of the trajectories at each data point were added up using the sign to denote the direction of curvature. This cumulative value was then divided by the distance between movement start and end in the y-axis, providing us with a sensitive measure of systematic direction-specific changes. Reaction and movement times were also analyzed.

Lesion Analysis

Lesion data were available for all 20 patients (11 MRI scans and 9 CT scans; MRI scans could not be obtained for all patients due to clinical constraints). The extent and location of each patient's lesion was visualized and defined using the MRICRO software package (Rorden and Brett 2000; www.mricro.com). For each patient, the area of damage was determined by inspection of the digital brain image, slice by slice, by a clinical neurologist, who was blind to the design, group assignment and purpose of the experiment. Lesions were drawn on 11 axial slices of a T1-weighted template, corresponding to the Talairach z coordinates of −24, −16, −8, 0, 8, 16, 24, 32, 40, 50, 60 mm using the identical or closest matching transverse slices for each patient.

In Figure 1A,B we present the overlap of the reconstructed lesions for the RH+ and RH− patients respectively. The regions of maximal overlap (damage present in 9 patients) for the RH+ group were in the gray matter of the superior temporal gyrus (Talairach coordinates: 47, −10, 0), the insula gray matter (Talairach coordinates: 44, −7, 0; 43, −6, 0; 44, −10, 0; 43, −10, 0; 42, −10, 0; 44, −7, 0; 43, −7, 0; 43, −9, 0; 41, −7, 0; 43, −8, 0; 42, −9, 0; 42, −8, 0; 40, −8, 0), its surrounding white matter (45, −10, 0; 45, −8, 0; 39, −9, 0) and the white matter around the claustrum (Talairach coordinates: 37, −8, 0; 37, −9, 0; 36, −9, 0; 38, −9, 0). Regarding the patients without neglect there appeared to be no specific regions of lesion overlap, with lesions spanning over frontal, temporal and claustrum areas as well as the lentiform nucleus and the insula. Consistent with previous studies, the lesions of neglect patients were significantly larger in volume than those of the non-neglect group (F1,19 = 14.03, P = 0.001, see Table 1).

Figure 1.

(A and B) Lesion overlap map summarizing the degree of involvement for each voxel in the lesions of the neglect patients (n= 11; A) and the patients without neglect (n= 9; B). The range of the color scale is derived from the absolute number of patient lesions involved in each voxel. (C and D) Voxel-based lesion statistical map, in axial and sagittal view, revealing the right-brain–damaged areas significantly associated with increased terminal error in leftward open loop pointing and gap bisection (C) and increased reaction time to initiate a movement towards a leftward location (D). The legend (and colored areas) represent the range of Z scores that survived FDR threshold of P< 0.05.

Figure 1.

(A and B) Lesion overlap map summarizing the degree of involvement for each voxel in the lesions of the neglect patients (n= 11; A) and the patients without neglect (n= 9; B). The range of the color scale is derived from the absolute number of patient lesions involved in each voxel. (C and D) Voxel-based lesion statistical map, in axial and sagittal view, revealing the right-brain–damaged areas significantly associated with increased terminal error in leftward open loop pointing and gap bisection (C) and increased reaction time to initiate a movement towards a leftward location (D). The legend (and colored areas) represent the range of Z scores that survived FDR threshold of P< 0.05.

Finally similarly to recent papers (e.g., Sarri et al. 2008), whenever an impairment was observed, we implemented the voxel-based lesion–symptom mapping statistical approach using MRICROn software Rorden, Karnath, et al. (2007); www.sph.sc.edu/comd/rorden/mricron/). This analysis was performed with voxel-based maps of the Brunner–Munzel nonparametric statistic (BM; Brunner and Munzel 2000; Rorden, Bonilla, et al. (2007). This rank order test, essentially assumption free, relates lesions to behavioral performance in a continuous fashion without precategorizing patients into groups. Multiple comparisons were controlled by using the false discovery rate (FDR; P < 0.05). Throughout the paper, the position of x-, y-, and z- Talairach-space coordinates (in mm; Talairach and Tournoux 1988) is reported for significant results that survived the FDR thresholding.

Results

Means for each participant were computed per condition for each variable and target position. The descriptive statistics for terminal accuracy and kinematic variables are presented in Tables 2 and 3, respectively. All variables were analyzed with a 3 × 2 × 2 × 3 mixed analysis of variance with group (healthy, RH− and RH+) as a between-factor and visual feedback (closed loop, open loop), task (pointing, gap bisection) and target (left, centre and right) as within-subject effects. Post hoc comparisons were made with the Bonferroni method, P < 0.05. As the interest of this paper is in the potential group differences, to focus the results, significant effects are reported for such group differences only (although all variables were analyzed).

Table 2

Means and standard errors (in parenthesis) for the pointing condition dependent measures per group, visual feedback, and target position

Variable Group Closed loop pointing
 
Open loop pointing
 
  Left Center Right Left Center Right 
Reaction time (ms) Healthy controls 301.1 (58.0) 314.0 (54.0) 308.0 (55.0) 271.0 (18.8) 274.7 (14.8) 293.5 (20.9) 
 RH− 319.4 (24.8) 294.8 (23.7) 284.9 (21.5) 400.4 (32.5) 414.8 (43.0) 408.7 (23.2) 
 RH+ 459.9 (78.9) 399.1 (84.0) 369.6 (64.9) 391.5 (28.1) 384.1 (24.2) 376.9 (18.2) 
Movement time (ms) Healthy controls 613.0 (33.2) 576.3 (32.4) 563.1 (36.3) 725.4 (46.0) 699.9 (47.5) 678.6 (49.7) 
 RH− 651.0 (22.2) 615.0 (22.7) 608.3 (22.1) 809.6 (40.1) 767.1 (38.1) 728.8 (38.2) 
 RH+ 725.3 (34.4) 663.9 (29.6) 651.9 (25.7) 801.0 (47.3) 756.4 (48.1) 710.3 (43.1) 
Absolute angular error (degrees) Healthy controls 0.5 (0.0) 0.4 (0.0) 0.4 (0.0) 2.2 (0.4) 2.0 (0.5) 2.3 (0.6) 
 RH− 0.4 (0.0) 0.4 (0.0) 0.4 (0.0) 4.5 (0.9) 2.7 (0.6) 2.1 (0.3) 
 RH+ 0.4 (0.0) 0.4 (0.0) 0.4 (0.0) 3.6 (0.5) 2.6 (0.5) 2.6 (0.5) 
Hand path curvature index (mm) Healthy controls 13.3 (2.7) 9.1 (2.1) 9.9 (1.9) 12.2 (3.7) 9.2 (3.5) 15.0 (4.6) 
 RH− 15.0 (1.7) 4.0 (1.8) 4.8 (2.7) 0.9 (3.9) 0.0 (1.2) 7.7 (2.2) 
 RH+ 20.8 (2.4) 9.8 (2.1) 12.4 (1.5) 9.2 (3.5) 5.7 (4.5) 10.6 (4.4) 
Variable Group Closed loop pointing
 
Open loop pointing
 
  Left Center Right Left Center Right 
Reaction time (ms) Healthy controls 301.1 (58.0) 314.0 (54.0) 308.0 (55.0) 271.0 (18.8) 274.7 (14.8) 293.5 (20.9) 
 RH− 319.4 (24.8) 294.8 (23.7) 284.9 (21.5) 400.4 (32.5) 414.8 (43.0) 408.7 (23.2) 
 RH+ 459.9 (78.9) 399.1 (84.0) 369.6 (64.9) 391.5 (28.1) 384.1 (24.2) 376.9 (18.2) 
Movement time (ms) Healthy controls 613.0 (33.2) 576.3 (32.4) 563.1 (36.3) 725.4 (46.0) 699.9 (47.5) 678.6 (49.7) 
 RH− 651.0 (22.2) 615.0 (22.7) 608.3 (22.1) 809.6 (40.1) 767.1 (38.1) 728.8 (38.2) 
 RH+ 725.3 (34.4) 663.9 (29.6) 651.9 (25.7) 801.0 (47.3) 756.4 (48.1) 710.3 (43.1) 
Absolute angular error (degrees) Healthy controls 0.5 (0.0) 0.4 (0.0) 0.4 (0.0) 2.2 (0.4) 2.0 (0.5) 2.3 (0.6) 
 RH− 0.4 (0.0) 0.4 (0.0) 0.4 (0.0) 4.5 (0.9) 2.7 (0.6) 2.1 (0.3) 
 RH+ 0.4 (0.0) 0.4 (0.0) 0.4 (0.0) 3.6 (0.5) 2.6 (0.5) 2.6 (0.5) 
Hand path curvature index (mm) Healthy controls 13.3 (2.7) 9.1 (2.1) 9.9 (1.9) 12.2 (3.7) 9.2 (3.5) 15.0 (4.6) 
 RH− 15.0 (1.7) 4.0 (1.8) 4.8 (2.7) 0.9 (3.9) 0.0 (1.2) 7.7 (2.2) 
 RH+ 20.8 (2.4) 9.8 (2.1) 12.4 (1.5) 9.2 (3.5) 5.7 (4.5) 10.6 (4.4) 
Table 3

Means and standard errors (in parenthesis) for the gap bisection condition dependent measures per group, visual feedback and target position

Variable Group Closed loop gap bisection
 
Open loop gap bisection
 
  Left Center Right Left Center Right 
Reaction time (ms) Healthy controls 286.5 (43.7) 312.7 (50.4) 297.2 (44.7) 269.9 (20.0) 286.0 (22.0) 293.3 (21.7) 
 RH− 328.7 (38.4) 322.6 (32.2) 325.5 (37.6) 429.4 (23.9) 410.1 (29.7) 433.8 (35.6) 
 RH+ 394.1 (60.3) 338.0 (35.2) 348.6 (39.8) 386.0 (27.3) 380.4 (28.4) 361.4 (28.0) 
Movement time (ms) Healthy controls 650.0 (40.8) 611.3 (36.2) 588.9 (39.5) 733.1 (53.6) 704.7 (51.0) 672.4 (53.3) 
 RH− 692.2 (26.5) 647.6 (27.6) 632.6 (24.3) 860.7 (42.9) 781.0 (36.1) 763.3 (43.4) 
 RH+ 727.5 (39.3) 684.0 (39.4) 654.4 (32.1) 814.2 (49.7) 753.4 (51.1) 728.0 (55.7) 
Absolute angular error (degrees) Healthy controls 0.6 (0.1) 0.7 (0.1) 0.6 (0.1) 2.2 (0.4) 1.8 (0.3) 2.4 (0.3) 
 RH− 0.6 (0.1) 0.6 (0.1) 0.7 (0.1) 3.8 (0.6) 2.3 (0.4) 2.2 (0.4) 
 RH+ 0.9 (0.1) 0.7 (0.1) 0.8 (0.1) 3.8 (0.4) 3.6 (0.5) 2.6 (0.4) 
Hand path curvature index (mm) Healthy controls 10.7 (2.8) 8.5 (1.9) 14.0 (2.3) 9.5 (4.1) 10.1 (2.8) 14.7 (4.7) 
 RH− 9.9 (1.4) 1.7 (1.3) 5.5 (2.4) 5.0 (3.5) 1.5 (3.1) 7.2 (2.6) 
 RH+ 11.7 (2.6) 6.3 (2.0) 12.3 (2.0) 8.3 (5.1) 2.7 (4.7) 10.4 (3.9) 
Variable Group Closed loop gap bisection
 
Open loop gap bisection
 
  Left Center Right Left Center Right 
Reaction time (ms) Healthy controls 286.5 (43.7) 312.7 (50.4) 297.2 (44.7) 269.9 (20.0) 286.0 (22.0) 293.3 (21.7) 
 RH− 328.7 (38.4) 322.6 (32.2) 325.5 (37.6) 429.4 (23.9) 410.1 (29.7) 433.8 (35.6) 
 RH+ 394.1 (60.3) 338.0 (35.2) 348.6 (39.8) 386.0 (27.3) 380.4 (28.4) 361.4 (28.0) 
Movement time (ms) Healthy controls 650.0 (40.8) 611.3 (36.2) 588.9 (39.5) 733.1 (53.6) 704.7 (51.0) 672.4 (53.3) 
 RH− 692.2 (26.5) 647.6 (27.6) 632.6 (24.3) 860.7 (42.9) 781.0 (36.1) 763.3 (43.4) 
 RH+ 727.5 (39.3) 684.0 (39.4) 654.4 (32.1) 814.2 (49.7) 753.4 (51.1) 728.0 (55.7) 
Absolute angular error (degrees) Healthy controls 0.6 (0.1) 0.7 (0.1) 0.6 (0.1) 2.2 (0.4) 1.8 (0.3) 2.4 (0.3) 
 RH− 0.6 (0.1) 0.6 (0.1) 0.7 (0.1) 3.8 (0.6) 2.3 (0.4) 2.2 (0.4) 
 RH+ 0.9 (0.1) 0.7 (0.1) 0.8 (0.1) 3.8 (0.4) 3.6 (0.5) 2.6 (0.4) 
Hand path curvature index (mm) Healthy controls 10.7 (2.8) 8.5 (1.9) 14.0 (2.3) 9.5 (4.1) 10.1 (2.8) 14.7 (4.7) 
 RH− 9.9 (1.4) 1.7 (1.3) 5.5 (2.4) 5.0 (3.5) 1.5 (3.1) 7.2 (2.6) 
 RH+ 11.7 (2.6) 6.3 (2.0) 12.3 (2.0) 8.3 (5.1) 2.7 (4.7) 10.4 (3.9) 

Terminal Accuracy

The analysis of variance revealed a significant interaction between group and target (F2,54 = 3.15, P < 0.05) which was further qualified by the group, visual feedback and target interaction (F2,54 = 3.69, P = 0.01). Pairwise comparisons revealed that only for leftward targets, and only in the open loop condition, were RH− patients less accurate when compared to healthy controls (mean difference = 1.9°, P < 0.05). Interestingly, neglect patients (RH+) were as accurate as the healthy or RH− control groups (mean difference = 1.5° and −0.4°, respectively). In terms of directionality, as can be seen in Figure 2, the errors of the patients without neglect in response to left stimuli were overshoots. No significant interaction between group and task was observed.

Figure 2.

Mean directional angular error (in degrees) in the closed and open loop pointing and gap bisection per group and target position. Error bars represent standard errors.

Figure 2.

Mean directional angular error (in degrees) in the closed and open loop pointing and gap bisection per group and target position. Error bars represent standard errors.

To investigate which brain areas were critically associated with the reduced accuracy in the open loop pointing and gap bisection towards the left target, we performed the voxel-based lesion analysis on the mean absolute angular error for both tasks for the leftward targets. As seen in Figure 1C, this revealed that several cortical and subcortical areas were significantly associated with the impaired open loop reaching (z > 2.16, P < 0.05; BM range = −6.96, 6.88). The lesion mainly associated with poor accuracy was located subcortically in the lentiform nucleus (peak z = 6.88 [21, −9, 0]). Cortically, several occipito-parietal-frontal areas were associated with this deficit: the occipito-parietal white matter (peak z = 3.46 [19, −58, 32; 26, −42, 40]) near the precuneus, the inferior parietal lobe gray (peak z = 3.46 [42, −29, 40]) and surrounding white matter (peak z = 3.46 [32, −52, 40]), the parietal white matter near the postcentral gyrus (peak z = 3.46 [31, −32, 40]) and the precentral gyrus gray matter (peak z = 2.41 [60, −12, 32]). Importantly, lesion volume did not correlate with poor accuracy.

Hand Path Curvature

The analysis of variance did not reveal any significant effects of group. Right-brain–damaged patients with or without neglect did not show increased curvatures when compared to the healthy subjects, even when the target was presented in left space (see Tables 2 and 3).

Reaction Time

Although there was no significant main effect of group, the interaction between group and target was significant (F2,54 = 4.46, P < 0.01). Pairwise comparisons revealed that only for leftward reaches neglect patients had increased reaction times when compared to healthy controls (mean difference = 125.7 ms, P < 0.05), yet were no different from patients without neglect (mean difference = 38.4 ms). To investigate this further we performed correlation analyses between the BIT, the bisection errors, the lateralized index of the Balloons Test and the mean reaction times for leftward reaches for all right-brain–damaged patients. However no significant correlations with neglect severity were found.

Again to investigate which brain areas were critically associated with the increased reaction times for leftward reaches, we performed a voxel-based lesion analysis (see Fig. 1D). Several cortical and subcortical brain areas were significantly associated with the increased times for leftward movement initiation (z > 2.00, P < 0.05; BM range = −4.14, 12.73). Cortically, these included areas around the parietal–occipital fissure, affecting white matter regions near the superior occipital gyrus (z = 3.13 [34, −73, 24]) and precuneus (peak z = 12.73 [16, −56, 32]). In addition, this deficit was strongly associated with damage to the inferior parietal lobe (peak z = 12.73 [62, −38, 32]), the frontal white matter near the cingulate gyrus (peak z = 12.73 [21, −34, 32]), the middle and superior temporal gyri (peak z = 6.53 [59, −45, 0; 61, −59, 16]) and surrounding white matter (peak z = 6.53 [47, −70, 16]; peak z = 3.85 [50, −32, 16]). To a lesser extent, damage to the white matter near the inferior temporal gyrus (z = 3.16 [64, −50, −16]) and to the gray and white matter areas at the border between fusiform gyrus (z = 3.16 [34, −75, −16]) and the occipital lobe (z = 3.16 [52, −66, −16]) were also related with this impairment. Finally, also associated with this, were lesions in the inferior frontal gyrus gray (z = 2.42 [57, 42, 8]) and surrounding white matter (z = 2.42 [50, 29, 0]).

Subcortically, the statistical map revealed that lesions in the white matter surrounding the lentiform nucleus (peak z = 6.53 [32, −3, 0]), the caudate (peak z = 4.25 [35, −15, −8]) and nearby white matter (peak z = 4.25 [35, −17, −8]), the white matter close to the claustrum (z = 4.25 [33, −12, −8]) and the thalamus (z = 4.25 [23, −16, 8]) were associated with this deficit.

Again lesion volume did not correlate with increased leftward reaction times.

Movement Time

There were no effects of group; neither patient group took longer to complete their movements when compared to healthy controls, even when the target was presented on the left side of space.

Discussion

The current study aimed to clarify whether, compared to right-hemisphere lesioned patients without neglect, patients with hemispatial neglect were impaired, when reaching towards the contralesional side of space with or without visual feedback of the hand and target position. Furthermore, we also used computerized lesion-mapping techniques to further identify the set of brain regions potentially related to the motor abnormalities.

No Evidence for Neglect-Specific Deficits in Reaching after Right-Hemisphere Lesions

As expected, we found no neglect-specific impairment on either pointing or gap bisection, even when movements were made without visual feedback, and even when stimuli were presented on the left side of space. In fact, only the patients without neglect were less accurate than the healthy controls in open loop reaches towards the left side of space. These findings are in agreement with Harvey et al. (1994). However, in terms of directionality we did not find any rightward biases in the terminal errors, as these patients presented overshoot errors with respect to the ideal reach for both open loop tasks (see Fig. 2). In addition, and as reported by Karnath et al. (1997), neither patient group differed from healthy controls in terms of the hand path curvature. In particular for gap bisection, this finding is remarkable since 8 out of our 11 patients presented a significant rightward bias for line bisection (see Table 1). However, the data agree with McIntosh, McClements, Dijkerman and Milner (2004) findings and extends them to open loop reaches.

Regarding latency, neglect patients demonstrated increased reaction times towards contralesional stimuli when compared to healthy controls, but were no different from patients without neglect. Also, these latency increases did not correlate with neglect severity. Furthermore, we also did not find an increase in movement time after right-brain damage, as both patient groups did not even differ from healthy controls. A number of studies have already shown that there are no neglect-specific impairments in reaching (Konczak and Karnath 1998; Konczak et al. 1999; Himmelbach and Karnath 2003) and that is exactly what we have replicated here for both open and closed loop pointing and gap bisection. In a similar vein, it has also been previously shown that despite their rightward bias in perceptual tasks neglect patients can perfectly grasp leftward objects (Pritchard et al. 1997; McIntosh et al. 2002) even without visual feedback of the hand (Harvey et al. 2002), and that they are also able to avoid obstacles on the neglected side (Milner and McIntosh 2003; McIntosh, McClements, Dijkerman, Birchall, et al. 2004).

Although this evidence is consistent with Milner and Goodale's (1995, 2006) hypothesis that the visual dorsal stream is relatively spared in neglect, our findings nonetheless contradict those of Mattingley et al. (1992, 1994), Mattingley, Corben, et al. (1998), and Mattingley, Husain, et al. (1998). We believe that display complexity might explain the observed differences: in Mattingley et al.’s tasks, displays containing competing stimuli were used and so, the increased latencies observed may be a result of impaired stimulus selection rather than a deficit in motor planning and execution.

In a similar vein, we agree with Milner and Goodale who claim that neglect patients should be impaired when the visuomotor action depends on processing carried out by the ventral visual stream, that is, is “off-line” (2006; Milner 1995; Milner and Harvey 2006; see Goodale et al. 2004 for a review). In line with this, we have found very recently that whilst neglect patients are unimpaired when performing immediate/target-directed actions they present specific impairments when the action is delayed or when they are asked to point to the horizontal mirror position of the target (Rossit, Muir, Reeves, Duncan, Birschel, et al. 2009; Rossit, Muir, Reeves, Duncan, Livingstone, et al. 2008). Alternatively, as has been previously argued for the case of visual form agnosia (Schenk 2006), the distinction between allocentric versus egocentric visuospatial processing could potentially explain the observed neglect-specific deficits, in so far that allocentric but not egocentric coding may be impaired in such patients.

Motor Deficits after Right-Hemisphere Damage

Interestingly, right-hemisphere damaged patients (irrespective of neglect) presented increased reaction times for all leftward reaches as well as reduced accuracy in open loop leftward reaching, suggesting that the early motor planning and/or programming processes (i.e., target selection and/or target localization and/or computation of the motor command), are frequently impaired after right-hemisphere damage. However, we would argue that once the coordinates of a specific target have been acquired, the subsequent execution of the reach is functional, as we failed to observe any abnormalities in the closed loop condition. Thus, the absence of deficits in the closed loop condition suggests that visual on-line correction is not impaired after right-brain damage.

Alternatively, since participants have to hold the target location in the mind during the open loop phase, errors in this condition could be related to a deficit in spatial working memory. This has previously been demonstrated for neglect patients and even right-hemisphere patients without neglect, who perform worse than healthy controls (Malhotra et al. 2004, 2005; Vuilleumier et al. 2007). It is also possible that the latency increase to the left stimuli is related to the presence of concomitant visual field deficits, yet a larger sample of patients without hemianopia than the one given here would be required to test this hypothesis.

Brain Regions Potentially Associated with Motor Deficits

Our findings suggest that both right-hemisphere lesioned patients with and without neglect were impaired when reaching towards the left side of space. What remains to be clarified is the anatomical basis of these deficits. While a more refined anatomical study would require a larger number of patients the present study allowed us to perform an initial exploration of this matter via voxel-based lesion-symptom analysis.

The lesion overlap analysis revealed that areas in the superior temporal gyrus, insula and claustrum were most frequently damaged in our neglect group. What is remarkable is that none of these areas were associated with the reduced accuracy for open loop reaches, which is in line with our claim that this deficit is not neglect-specific. Instead, the accuracy impairment was associated with damage to the lentiform nucleus, the occipito-parietal areas near the precuneus and the parietal–frontal areas located in the inferior parietal lobe and post- and precentral gyri. Similarly, increased reaction times to the leftward targets were also associated with damage near the lentiform nucleus, to the parietal-occipital fissure (superior occipital gyrus and precuneus) and the inferior frontal gyrus.

Of potential interest is the robustly highlighted basal ganglia region as it corroborates previous findings that lesions in this area produce increased reaction and movement times in neglect patients (Bisiach et al. 1990; Tegner and Levander 1991). Moreover in a recent anatomical study, Sapir et al. (2007) found that the maximum lesion overlap of neglect patients with directional hypokinesia was in the basal ganglia (putamen), the claustrum followed by the white matter in the precentral gyrus, the inferior frontal gyrus, the frontal operculum and the anterior insula. Like Sapir et al. (2007) we also found that motor deficits were associated with damage to the basal ganglia, the claustrum and more anterior areas (precentral and inferior frontal gyri).

Another cluster of voxels that was strongly associated with the motor abnormalities was located in the vicinity of the parietal–occipital fissure involving the white matter near the superior occipital gyrus and precuneus. This observation supports the neural underpinnings of optic ataxia (Karnath and Perenin 2005), but also concurs with previous neuroimaging studies in healthy participants implicating precuneus activation during reaching (Astafiev et al. 2003; Connolly et al. 2003) and those demonstrating POJ activation when subjects reach to a peripheral target or to a target that disappears before a saccade to its location is made (Prado et al. 2005). Although, our parietal–occipital voxels are located more inferiorly than the ones reported in these studies, we would suggest that areas surrounding the parietal–occipital fissure are involved in motor mechanisms.

Additionally, injury to the cingulate gyrus was associated with slower movement initiation, consistent with findings implicating the cingulate cortex in action planning (Cavina-Pratesi et al. 2006). Furthermore damage to the thalamus was also implicated in increased reaction time, which is in line with several anatomical studies that report the existence of recurrent neural pathways from cortical motor areas to the thalamus via basal ganglia and back to the cortex (see Sommer 2003 for review).

One surprising finding was that damage to temporal areas (middle and inferior temporal gyri) was also associated with increased reaction times. However, it has been suggested that the occipital lobe has direct connections with the frontal lobe through a white matter tract (inferior fronto-occipital fasciculus), which runs deeply in the temporal lobe (see Doricchi et al. 2008, for a review). Thus this finding may represent the effect of disconnection rather than temporal damage per se.

It is important to note that we do not claim that damage to one of these regions alone is responsible for visuomotor deficits after right-brain damage. Instead we propose that these deficits are not a consequence of damage to neglect-associated areas alone, but result from additional lesions to key nodes of the visuomotor control network. In particular, the consistent association of motor deficits with damage to the basal ganglia nuclei, occipital–parietal areas and motor areas in the frontal lobe suggests that these are the critical regions for the reaching deficits after right-brain damage. In line with this view, it has been found that basal ganglia lesions associated with neglect cause abnormal perfusion of the superior temporal gyrus, inferior parietal lobe and inferior frontal gyrus (Hillis et al. 2005; Karnath et al. 2005). Furthermore, it is well established that the PPC has critical white matter connections to the frontal lobe, the cerebellum and the basal ganglia (e.g., Rizzolatti and Luppino 2001). Thus, even a small lesion in a location where several antero-posterior connections traverse, might be sufficient to disrupt the visuomotor modules in both frontal and parietal cortices (Bartolomeo et al. 2007). Future work with a larger group of patients will be required to corroborate our present findings.

Conclusion

The current study shows that neglect per se does not produce impairments either in planning or execution of actions, which is in line with the proposal that the dorsal visual stream for on-line visuomotor control is relatively spared in these patients (Milner and Goodale 1995, 2006).

Moreover, we show that motor deficits emerge after right-hemisphere damage, irrespective of the presence of neglect. Voxel-based lesion-symptom analysis revealed that such deficits are associated with damage to the basal ganglia as well as to occipital–parietal and frontal areas, structures that are often associated with but not critical for hemispatial neglect (Mort et al. 2003; Karnath et al. 2004). We think that these results confirm the current view that neglect is not a single condition, but a complex syndrome of multiple deficits, which vary depending on the specific networks damaged (Husain and Nachev 2007).

Funding

Portuguese Foundation for Science and Technology grant (number SFRH/BD/23230/2005) to S. Rossit.

We wish to thank all the patients and healthy participants for their patience and willingness and Robert McIntosh for his helpful advice during the set-up stage. Conflict of Interest: None declared.

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