Abstract

A widely debated question concerns whether or not spatial and nonspatial components of visual attention interact in attentional performance. Spatial neglect is a common consequence of brain injury where individuals fail to respond to stimuli presented on their contralesional side. It has been argued that, beyond the spatial bias, these individuals also tend to exhibit nonspatial perceptual deficits. Here we demonstrate that the “nonspatial” deficits affecting the temporal dynamics of attentional deployment are in fact modulated by spatial position. Specifically, we observed that the pathological attentional blink of chronic neglect is enhanced when stimuli are presented on the contralesional side of the trunk while keeping retinal and head-centered coordinates constant. We did not find this pattern in right brain-damaged patients without neglect or in patients who had recovered from neglect. Our work suggests that the nonspatial attentional deficits observed in neglect are heavily modulated by egocentric spatial position. This provides strong evidence against models that suggest independent modules for spatial and nonspatial attentional functions while also providing strong evidence that trunk position plays an important role in neglect.

INTRODUCTION

The human visual system has a limited capacity. Only a small portion of the information captured by the retina enters our awareness, and numerous previous studies have examined the spatial and nonspatial properties that influence which information is selected. A widely debated question concerns whether or not these spatial and nonspatial components interact in attentional performance. A classic example of nonspatial, temporal visual attention is our inability to detect an object that is presented between 180 and 450 msec after a prior task-relevant stimulus. Raymond, Shapiro, and Arnell (1992) coined the term “attentional blink” (AB) to refer to this phenomenon. AB is usually observed in rapid serial visual presentation (RSVP), in which two targets are embedded in a stream of objects that are rapidly and sequentially presented. Evidence from electrophysiology and fMRI studies indicate that, during this dual-task bottleneck, the specific activity evoked by the second event is delayed or even absent (Dehaene & Changeux, 2011; Sigman & Dehaene, 2008; Dux, Ivanoff, Asplund, & Marois, 2006; Sergent, Baillet, & Dehaene, 2005). So far, AB has been widely used in the neuroscience field to characterize the temporal dynamics of human attention. On the other hand, spatial neglect has been considered to represent a neuropsychological disorder after brain injury, typically affecting spatial aspects of attention. When a target suddenly appears somewhere in space, neglect patients demonstrate disturbed detection and stimulus-driven orienting if it is located in contralesional direction (Niemeier & Karnath, 2003; Behrmann, Ghiselli-Crippa, & Dimatteo, 2001–2002; Walker & Findlay, 1996; Girotti, Casazza, Musicco, & Avanzini, 1983). Although spatial neglect research typically focuses on this spatial bias, some studies have described evidence to show that these patients often also experience deficits in temporal aspects of attention. Our goal was to investigate how these spatial and nonspatial deficits interact.

A seminal study by Husain, Shapiro, Martin, and Kennard (1997) revealed that patients with spatial neglect could suffer from pathologically long AB. They demonstrated that individuals with neglect suffer from abnormal temporal dynamics of attentional deployment, even when stimuli are presented at the same central spatial location. This study, along with other work in both neurological patients and healthy adults, has led some to speculate that posterior regions of the human cortex may be specialized for temporal processing (for reviews, see Battelli, Pascual-Leone, & Cavanagh, 2007; Husain & Rorden, 2003). Indeed, Battelli and colleagues (2007) refer to this region as a “when” pathway, situated between the well-established dorsal “where” and ventral “what” streams (Milner & Goodale, 1995). One strong interpretation of this view is that a distinct functional module governs temporal selection. Accordingly, patients with spatial neglect often exhibit temporal deficits because large strokes tend to damage both the spatial and temporal selection modules. Spatial deficits and temporal deficits thus could be completely independent of each other, with the magnitude of the temporal bias showing little modulation based on spatial position.

We investigated the interaction between spatial and temporal deficits in neglect by using Husain et al.'s (1997) original AB paradigm as a baseline and exploring whether trunk position influences the patients' temporal deficit. Indeed, there is evidence that spatial deficits in neglect are heavily modulated by position relative to the trunk, rather than relative to the position of fixation or of head orientation. For example, systematic variation of retinotopic, head-centered, and trunk-centered coordinates of visual stimuli have shown that the trunk appears to constitute the physical anchor for determining the behavioral bias along the horizontal dimension of space in neglect patients (Karnath, Christ, & Hartje, 1993; Karnath, Schenkel, & Fischer, 1991). Here, we had individuals point their head and eyes toward the center of a computer screen, which was alternately positioned either left or right of the participant's sagittal trunk midline. This design keeps the retinotopic and head-centered coordinates of the stimuli constant; we only manipulated its position relative to the participant's trunk. If there is a distinct “when” system in the brain, one would expect that this manipulation should not have any effect, as the stimuli are identical with regard to retinal magnification and low level perception. On the other hand, if the temporal deficits of neglect interact with spatial deficits, one would expect a more profound AB when stimuli are presented on the contralesional side of the body.

METHODS

Participants

Fifteen patients with right hemisphere stroke participated in this study. Each patient underwent clinical MRI or computerized tomography (spiral CT) at admission in the acute phase after stroke (<5 days poststroke). Patients with a left-sided stroke, individuals with a prior brain injury, patients with diffuse or bilateral brain lesions, as well as patients who were unable to follow the instructions to finish the experiment were excluded. All of the patients conducted the initial clinical testing, on average 5.1 days poststroke (SD = 4.5), and the second clinical testing in the chronic phase, on average 1042.1 days (SD = 415.1) poststroke. Five of them showed spatial neglect (NEG) in both acute and chronic phase, five of them showed spatial neglect in the acute phase but no longer in the chronic phase (neglect recovered, NR), and the other five did not show spatial neglect at any phase (right brain-damaged controls, RBD). Additionally, 15 age-matched healthy participants without neurological or psychiatric disorders were tested (non-brain-damaged controls, NBD). The study was approved by the local ethics committee of the University of Tübingen and carried out according to the ethical standards laid down in the 1964 declaration of Helsinki. All 30 participants gave their informed consent to participate in the study. Demographic and clinical data of all participants are presented in Table 1; simple lesion overlap maps in Figure 1.

Table 1. 

Demographic and Clinical Data of All 30 Participants

NEGNRRBDNBD
Number 15 
Sex (m/f) 3/2 3/2 3/2 5/10 
Age (years) 73.4 (1.52) 68.6 (7.3) 69 (7.55) 70 (4.42) 
Etiology 5 Infarct 3 Infarct 4 Infarct  
2 Hemorrhage 1 Hemorrhage 
Time since lesion (days) 1140.6 (461.4) 1169.6 (527.4) 816 (124.8)  
Visual field defects (% present) 0% 0% 0%  
Visual extinction (% present) 40% 0% 0%  
Spatial neglect scores 
 Letter Cancellation (CoC) Acute: 0.51 (0.24) Acute: 0.42 (0.25) Acute: 0.004 (0.01)  
Chronic: 0.07 (0.04) Chronic: 0 (0.02) Chronic: 0 (0.01) 
 Bells Test (CoC) Acute: 0.58 (0.29) Acute: 0.26 (0.14) Acute: −0.01 (0.02) 
Chronic: 0.17 (0.16) Chronic: 0.04 (0.04) Chronic: 0 (0) 
 Copying (% omitted) Acute: 62.5 (17.7) Acute: 47.5 (24.0) Acute: 0 (0) 
Chronic: 12.5 (10.2) Chronic: 0 (0) Chronic: 0 (0) 
NEGNRRBDNBD
Number 15 
Sex (m/f) 3/2 3/2 3/2 5/10 
Age (years) 73.4 (1.52) 68.6 (7.3) 69 (7.55) 70 (4.42) 
Etiology 5 Infarct 3 Infarct 4 Infarct  
2 Hemorrhage 1 Hemorrhage 
Time since lesion (days) 1140.6 (461.4) 1169.6 (527.4) 816 (124.8)  
Visual field defects (% present) 0% 0% 0%  
Visual extinction (% present) 40% 0% 0%  
Spatial neglect scores 
 Letter Cancellation (CoC) Acute: 0.51 (0.24) Acute: 0.42 (0.25) Acute: 0.004 (0.01)  
Chronic: 0.07 (0.04) Chronic: 0 (0.02) Chronic: 0 (0.01) 
 Bells Test (CoC) Acute: 0.58 (0.29) Acute: 0.26 (0.14) Acute: −0.01 (0.02) 
Chronic: 0.17 (0.16) Chronic: 0.04 (0.04) Chronic: 0 (0) 
 Copying (% omitted) Acute: 62.5 (17.7) Acute: 47.5 (24.0) Acute: 0 (0) 
Chronic: 12.5 (10.2) Chronic: 0 (0) Chronic: 0 (0) 

Data are presented as mean (SD). CoC = Center of Cancellation (Rorden & Karnath, 2010); NEG = right brain damage with spatial neglect in both acute and chronic phases of stroke; NR = right brain damage with acute spatial neglect but no chronic neglect; RBD = right brain damage without spatial neglect; NBD = non-brain damage; m = male; f = female.

Figure 1. 

Simple lesion overlaps of the five chronic neglect patients (NEG), five recovered neglect patients (NR), and five right brain-damaged patients without neglect in both acute and chronic phases (RBD). Lesion boundaries were manually delineated on axial slices of the individual digital CT (n = 9) or digital MRI (n = 6) scans using MRIcron software (www.mccauslandcenter.sc.edu/mricro/mricron). Both the lesion map and the patient CT or MR image were subsequently transferred into stereotaxic space using the Clinical toolbox (Rorden, Bonilha, Fridriksson, Bender, & Karnath, 2012). The mean time between stroke-onset and imaging was 2.5 days (SD = 2.9).

Figure 1. 

Simple lesion overlaps of the five chronic neglect patients (NEG), five recovered neglect patients (NR), and five right brain-damaged patients without neglect in both acute and chronic phases (RBD). Lesion boundaries were manually delineated on axial slices of the individual digital CT (n = 9) or digital MRI (n = 6) scans using MRIcron software (www.mccauslandcenter.sc.edu/mricro/mricron). Both the lesion map and the patient CT or MR image were subsequently transferred into stereotaxic space using the Clinical toolbox (Rorden, Bonilha, Fridriksson, Bender, & Karnath, 2012). The mean time between stroke-onset and imaging was 2.5 days (SD = 2.9).

Clinical Assessment

All 15 brain-damaged patients were assessed in the acute and chronic phase of the stroke with the following clinical neglect tests: Letter Cancellation Task (Weintraub & Mesulam, 1985), Bells Test (Gauthier, Dehaut, & Joanette, 1989), and Copying Task (Johannsen & Karnath, 2004). All three tests were presented on a horizontally oriented 21 × 29.7 cm sheet of paper. For the Letter Cancellation Task and the Bells Test, we calculated the Center of Cancellation (CoC) using the procedure and software by Rorden and Karnath (2010). This measure is sensitive to both the number of omissions and the location of these omissions. CoC scores > 0.09 in the Letter Cancellation Task and the Bells Test were taken to indicate neglect behavior (cf. Rorden & Karnath, 2010). In the Copying Task, omission of at least one of the contralateral features of each figure was scored as 1, and omission of each whole figure was scored as 2. One additional point was given when contralesional figures were drawn on the ipsilesional side of the test sheet. The maximum score was 8. A score higher than 1 (i.e., >12.5% omissions) indicated spatial neglect (Johannsen & Karnath, 2004). For a firm diagnosis of spatial neglect in the acute phase of the stroke, that is, when the pathological behavior is most extreme, the patients had to fulfill the above criteria in at least two of the three tests. At the time of the second (chronic) assessment, patients were classified as showing chronic neglect when they fulfilled the above criteria in at least one of the three tests.

Visual field defects were examined by the common neurological confrontation technique. Visual extinction was examined by neurological confrontation as well as a computerized task. The latter task included four geometrical figures (square, circle, triangle, and diamond), each 0.7° in size, presented for 180 msec in random order, 4° left and/or right of a central fixation point presented on a PC monitor. Stimuli were generated and presented by E-Prime 1.0 software (Psychology Tools, Inc., Pittsburgh, PA) and displayed on a Lenovo ThinkPad (Beijing, China) laptop (type 8932), with a screen size of 1280 × 800 pixels. There were 10 trials with bilateral and 20 trials with unilateral left or right presentations. Patients were classified as showing visual extinction when they failed to report at least 50% of the contralesional stimuli during bilateral stimulation in the presence of correct detection of at least 90% of the contralesional stimuli during unilateral stimulation.

Stimuli and Procedure

Stimuli were generated using Matlab R2013a software (The MathWorks, Natick, MA) and were displayed on a Macbook Pro (Apple, Inc., Cupertino, CA) laptop with a screen size of 1280 × 800 pixels. The viewing distance was 60 cm, and fixation was positioned at the center of the monitor at eye height. The stimuli were comparable to those introduced by Husain et al. (1997). An RSVP stream of letters was presented at fixation (Figure 2). Each letter was presented for 131 msec, with an ISI of 49 msec. The size of the letter was 1.55° in height. All letters were black except the first target letter (T1), which was white. T1 could be any letter in the alphabet, except the letters X, Y, or Z. The background was uniform gray.

Figure 2. 

Schematic of the settings in the experiment. An RSVP stream of letters was presented at fixation, which was aligned with the center of the monitor. The horizontal position of the center of the presentation monitor was positioned in pseudorandom order either −40° left or +40° right of the participant's midsaggital trunk position at eye level. Participants were requested to orient head midline and gaze toward the fixation cross at the respective egocentric position while keeping trunk position stable.

Figure 2. 

Schematic of the settings in the experiment. An RSVP stream of letters was presented at fixation, which was aligned with the center of the monitor. The horizontal position of the center of the presentation monitor was positioned in pseudorandom order either −40° left or +40° right of the participant's midsaggital trunk position at eye level. Participants were requested to orient head midline and gaze toward the fixation cross at the respective egocentric position while keeping trunk position stable.

In all 15 brain-damaged patients, the experiment was conducted in the chronic phase of their stroke. Comparable to the procedure used by Husain et al. (1997), it was initiated by the experimenter pressing the spacebar (as described below). Each trial began with a 500-msec presentation of a black fixation cross with a size of 0.2°. The number of letters presented before T1 varied randomly between 7 and 15. T1 then was followed by a sequence of 10 letters. The second target letter (T2) was a black “X.” It appeared randomly in 75% of the trials and was presented as 1 of the 10 letters that followed T1. Thus, the SOA between the two targets, T1 and T2, was 180, 360, 540, 720, 900, 1080, 1260, 1440, 1620, or 1800 msec.

Participants were instructed to verbally identify the T1 and also to report verbally whether or not T2 was present (dual task). The experimenter recorded the answer through an external keyboard connected to the laptop. There were nine blocks of stimulus presentation in the whole experiment for each participant, with 24 trials in each block. The first block served as a training block and was conducted with the center of the presentation monitor at eye level and aligned with the participant's head and trunk midline straight ahead; data were not considered for later analysis. In the following eight experimental blocks, the horizontal position of the center of the presentation monitor was positioned in pseudorandom order (counter balanced between participants) either −40° left or +40° right of the participant's midsagittal trunk position at eye level. The participants were requested to orient head midline and gaze toward the fixation cross at the respective egocentric position while keeping trunk position stable. The retinotopic and head-centered coordinates of the RSVP stream of letters thus was kept constant throughout the whole experiment; only its position relative to the participant's trunk was manipulated. In total, four blocks with 96 trials were performed at each egocentric position. In 24 of these trials, no target letter T2 followed T1. The shortest and the longest SOAs (see above) were presented in four trials each; all other SOAs in eight trials each. One experimenter, situated opposite of the participant, controlled the maintenance of gaze and head position by observation. The experimenter only initiated a trial when the participant's head, trunk, and eye positions were aligned correctly.

RESULTS

The mean T1 identification accuracy was high in each group: For egocentric left and right positions, it was 97.5 (SD = 2.3) and 96.7 (SD = 3.5) in the chronic neglect (NEG) group, 95.8 (SD 9.3) and 93.3 (SD 5.6) in the neglect recovered (NR) group, 95.8 (SD 5.9) and 97.5 (SD 5.6) in the right brain-damaged control (RBD) group, and 99.2 (SD 2.3) and 99.1 (SD 2.7) in the non-brain-damaged control (NBD) group. For analysis, a two-way repeated-measures ANOVA was conducted using the within-subject factor Egocentric position (left, right) and the between-subject factor Group (NEG, NR, RBD, NBD). There was no significant interaction (F(3, 26) = 1.045, p = .389) or main effects (Egocentric position: F(1, 26) = 0.785, p = .384; Group: F(3, 26) = 1.423, p = .259), indicating that T1 identification was statistically comparable between the four groups at the two egocentric positions. However, we note that AB tasks often yield ceiling results for T1, and therefore caution should be used when interpreting this null result. There were no false alarm responses in the detection of T2 for any individual, regardless of group.

Figure 3 illustrates the T2 identification rates of the four groups at each SOA after T1 was accurately identified. For statistical analysis, we calculated the mean T2 identification accuracy across all 10 SOAs for each participant and performed a two-way repeated-measures ANOVA using the within-subject factor Egocentric position (left, right) and the between-subject factor Group (NEG, NR, RBD, NBD). The interaction between the two factors was significant (F(3, 26) = 19.717, p < .0001). Post hoc paired t tests for the two egocentric positions (−40°, +40°) revealed a significantly worse T2 identification rate at egocentric position −40° compared with egocentric position +40° (t(4) = −4.73, p = .009) in the NEG group. In contrast, the difference between egocentric positions was not significant in the NR group (t(4) = 2.510, p = .066), the RBD group (t(4) = −1.513, p = .205), or the NBD group (t(14) = 1.326, p = .206).

Figure 3. 

Mean accuracy (and standard deviation) of the participants' responses to the second target (T2). Data obtained at the egocentric left position are characterized by dotted lines; data at the egocentric right position by continuous lines. NEG = chronic neglect patients; NR = recovered neglect patients; RBD = right brain-damaged patients without neglect in both acute and chronic phases; NBD = healthy controls.

Figure 3. 

Mean accuracy (and standard deviation) of the participants' responses to the second target (T2). Data obtained at the egocentric left position are characterized by dotted lines; data at the egocentric right position by continuous lines. NEG = chronic neglect patients; NR = recovered neglect patients; RBD = right brain-damaged patients without neglect in both acute and chronic phases; NBD = healthy controls.

We then conducted one-way ANOVAs for the factor Group separately for the two egocentric positions. For egocentric position left, there was a significant Group main effect (F(3, 26) = 29.185, p < .0001). For post hoc comparisons, Bonferroni correction was used for multiple testing. There were no significant differences for NBD versus RBD (p = 1.0), NBD versus NR (p = .604), or RBD versus NR (p = 1.0), but there were significant differences between the NEG group and the other three groups (all p < .0001). For egocentric position right, there was again a significant Group main effect (F(3, 26) = 7.95, p = .001). Post hoc tests with Bonferroni correction revealed again no significant differences for NBD versus RBD (p = 1.0), NBD versus NR (p = .252), or RBD versus NR (p = .182). In contrast, we found significant differences between the NEG group and NBD (p = .001) as well as RBD (p = .002); the difference between NEG and NR was not significant (p = .545).

The previous analyses focused on the overall performance of each patient group. We also performed an analysis based on each individual's computed mean AB duration. Although there are several formulas for this purpose (e.g., Cousineau, Charbonneau, & Jolicoeur, 2006), we used a simple but robust formula that attempts to deal with the difference performance between groups. Specifically, for each individual we normalized their performance from zero (time bin with worst performance) to one (time bin with best performance) and then measured the number of screen frames where performance was below 0.5 on this scale (using linear interpolation). A two-factor ANOVA with Egocentric position (two levels: left, right) and Group (NBD, RBD, NR, NEG) was conducted. This test revealed no difference for Position (F(1, 52) = 0.39), but effects for Group (F(3, 52) = 27.27, p < .0001) and the predicted interaction (F(3, 52) = 3, p < .03). To evaluate the Group effect, we conducted a Bonferroni-corrected analysis t test, which identified significant effects between the NEG group and each of the other groups (NBD, RBD, NR; t = 8.82, 6.96, 5.57, all ps < .0001), but no other surviving significant effects. To understand the interaction, we applied a one-tailed paired t test and found no difference in the NBD (239 vs. 282 msec blink, p < .13), RBD (259 vs. 302, p < .17), and NR (387 vs. 387, p < .49) groups, but a significant effect in the NEG group (1045 vs. 690, p < .027, numerically this effect was large for four of the five participants with the mean blink time of 1260, 660, 1476, 750, and 1080 msec compared with times of 960, 450, 900, 780, and 360 msec, respectively). This suggests that the observed interaction was driven by the reduced AB observed in the neglect group when the stimuli changed position relative to the participant's trunk.

DISCUSSION

Husain et al. (1997) suggested two components of neglect: one is the spatial bias to direct attention towards stimuli; the other is the deficit in temporal processing, regardless of where attention is directed. Our results replicate their finding of a deficit affecting the temporal dynamics of attention; at both egocentric positions, we found significant differences in T2 identification rates between the NEG group and contrast groups. However, we also clearly demonstrate that this deficit is not independent of spatial egocentric position. Specifically, the magnitude of the “nonspatial” AB was exaggerated when the stimuli were presented at a more contralesional versus ipsilesional trunk position. Note that the location of the stimuli was always identical with respect to eye and head coordinates. The only variation with respect to the original design by Husain et al. (1997) was that the computer monitor on which the stimuli were presented was located at two different egocentric (trunk-centered) positions, that is, either −40° left or +40° right of the participant's midsagittal trunk position. Because the participants were requested to orient head midline and gaze toward the fixation cross on the PC monitor, the retinotopic and head-centered coordinates of the RSVP stream of letters were kept constant. Furthermore, all stimuli in the current study were presented at the location where the participant was attending. Our results thus appear to challenge the notion that spatial and “nonspatial,” temporal attentions are completely independent mechanisms, as might be inferred by the claims of others (e.g., Battelli et al., 2007; Husain & Rorden, 2003). Rather, they demonstrate a tight coupling between the spatial and “nonspatial” deficits seen in neglect.

This study addresses confounds associated with the findings of three previous experiments that also appeared to question the purported strong dissociation between temporal and spatial deficits in right hemisphere stroke patients (Russell, Malhotra, Deidda, & Husain, 2013; Hillstrom, Husain, Shapiro, & Rorden, 2004; di Pellegrino, Basso, & Frassinetti, 1998). In these studies, the authors used a simple manipulation of Husain et al.'s (1997) original design: The second target letter did not always appear at fixation but rather was sometimes presented to the left or right of fixation. Intriguingly, the participants exhibited a particularly prolonged AB when the second target appeared on the contralesional (left) side of fixation. This appears to suggest that the spatial bias interacts with temporal deficits. However, two aspects of this design weaken the implications. First, the participants were always asked to detect a central target before the peripheral item. Therefore, the peripheral stimuli were presented at an unattended location, and a common explanation for the spatial deficits observed in neglect is a disability to disengage from the attended location towards the sudden onset of an item located in contralesional direction (Posner, Walker, Friedrich, & Rafal, 1984). Furthermore, note that the contralesional stimuli were presented on the left side in every frame of reference: with respect to fixation, head position, and to the left of the body. Therefore, this paradigm cannot disentangle the effects of primary vision (due to different retinal positions of first and second targets) from the effects related to nonretinal, egocentric (head- and/or trunk-centered) spatial processing in provoking the prolonged AB for targets left of fixation. These concerns are eliminated in our design.

Our findings directly challenge the conclusion of Rizzo, Akutsu, and Dawson (2001). Similar to Husain et al. (1997), they tested AB in a series of brain-injured patients, one of whom still had neglect at the time of testing. They found that the patients as a group exhibited prolonged AB and concluded that “the mechanisms of spatial attention that are disrupted in visual hemineglect syndrome differ from the mechanisms that underlie attentional blink”. Our work differs from this conclusion in two ways. First, similar to Husain et al. (1997), we did find that neglect patients tended to have more severe AB than patients without neglect. Moreover, our inclusion of a spatial manipulation reveals a unique interaction between spatial position and temporal processing that provides a signature of neglect. Therefore, although we do think it is logically possible that temporal deficits may be observed independently of neglect (though we did not observe this in our population), we assert that neglect patients show a unique pattern of temporal deficits (i.e., where the temporal deficits are influenced by trunk position).

In addition to the core disorder of neglect (Karnath, 2015; Karnath & Rorden, 2012), further symptoms of the neglect syndrome are often expressed differently across individuals. One intriguing possibility is that these symptoms are in fact dissociable, and the overall syndrome simply reflects the fact that large lesions often damage multiple distinct functional modules. This has led to a quest to associate individual symptoms with specific anatomy (Chechlacz, Rotshtein, & Humphreys, 2012; Karnath & Rorden, 2012; Verdon, Schwartz, Lovblad, Hauert, & Vuilleumier, 2010; Husain & Rorden, 2003). Although the present work does not provide anatomical data sufficient to draw conclusions on this debate, it still suggests that there is a strong functional interaction between deficits. Although this does not necessarily mean that there are no distinct modules, our behavioral findings suggest that interactions between these systems make disentangling these supposed modules difficult. It appears that the core spatial egocentric bias underlies or modulates the other symptoms of the neglect syndrome. Further evidence for this notion is provided in the next paragraph.

The present work nicely parallels our recent findings regarding the interaction between purported dissociations in the spatial deficits seen in individuals with neglect: specifically egocentric and allocentric neglect (Li, Karnath, & Rorden, 2014; Karnath, Mandler, & Clavagnier, 2011). Patients with neglect often fail to respond to the contralesional side of objects (allocentric contralesional side), regardless of the object's position with respect to the participant, that is, its egocentric position. Previous studies have suggested that these components can dissociate (e.g., Hillis et al., 2005), even though these symptoms tend to associate (Rorden, Bonilha, Fridriksson, Bender, & Karnath, 2012; Rorden, Hjaltason, et al., 2012; Yue, Song, Huo, & Wang, 2012). Interestingly, we have observed that object-based neglect varies with egocentric position (Li et al., 2014; Karnath et al., 2011). The neglect of an object's left side was more severe at contralesional egocentric, trunk-centered positions and ameliorated continuously toward more ipsilesional egocentric positions. Again, this work suggests that the symptoms associated with neglect tend to interact with each other.

Our work also is consistent with work in healthy participants, suggesting that perception reflects a synergistic influence of temporal and spatial expectations (Rohenkohl, Gould, Pessoa, & Nobre, 2014). More speculatively, our non-brain-damaged group showed a trend for the reverse pattern observed with neglect patients: tending to show less AB for information presented in their egocentric right space. If this proves to be a real effect, it might suggest that “pseudoneglect” (Jewell & McCourt, 2000) exhibits the same association between spatial and temporal biases. Although it is logically possible that the different symptoms of spatial neglect do reflect injury to distinct modules, if this is the case, these modules appear to be tightly interconnected with perception. Alternatively, we speculate that neglect may indeed be a unitary deficit. According to this view, the pathological temporal deficit is simply a consequence of the compromised perceptual processing that is the hallmark for the core deficit in neglect. In other words, visual perception in these participants is compromised throughout space, though in particular in the contralesional field (Driver & Pouget, 2000). Because the representation is weakened at all locations, there is limited capacity at all locations leading to a pathological AB on the contra- as well as on the ipsilesional side. However, because of the spatial gradient, this deficit is more exaggerated in contralesional space. Likewise, we speculate that variation in allocentric versus egocentric biases observed between patients may simply reflect different strategic choices made by the patient. In other words, individuals may choose to attend to the forest (egocentric frame of reference) or sequentially to each tree (allocentric frame of reference; see Baylis, Baylis, & Gore, 2004; Karnath & Niemeier, 2002).

Visual inspection of Figure 3 appears to suggest that the neglect recovered group (NR) does appear to perform more poorly than the other control groups in detecting the second stimulus at shorter SOAs. This effect was not detected by our statistical analyses, but this may reflect the sample size, heterogeneous nature of this group, and/or our measure for AB. It is possible that apparently recovered individuals still exhibit subtle deficits (Rengachary, d'Avossa, Sapir, Shulman, & Corbetta, 2009) that might impact demanding tasks.

In conclusion, our work clearly demonstrates that the “nonspatial” temporal dynamics of neglect are clearly biased by egocentric (trunk-related) spatial position. This indicates that these are not independent functional components, as some have suggested. This work supports our previous assertion (Karnath, 2015; Karnath & Rorden, 2012) that neglect includes a core deficit that reflects a trunk-based frame of reference. Although early visual processing maintains retinotopic coordinates, there is clear evidence that cells in association cortex are modulated by nonretinal egocentric position (e.g., Andersen, Lawrence, Snyder, & Bradshaw, 1997; Battaglini, Galletti, & Fattori, 1997; Andersen, Snyder, Li, & Stricanne, 1993; Galletti, Battaglini, & Fattori, 1993). Unlike retinotopic coordinates (which shift with each saccade), this coordinate system provides a relatively stable basis for acting in space. We feel that one of the crucial insights that neglect provides regarding the human perceptual system is the importance of this frame of reference (for a review, see Karnath, 2015).

Acknowledgments

This work was supported by the Deutsche Forschungsgemeinschaft (KA1258/20-1, KA1258/23-1) and the National Institutes of Health (NS054266, DC017863). Dongyun Li was supported by a scholarship under the State Scholarship Fund (China Scholarship Council, no. 2011638106). We thank Michaela Patoilo for copy editing this manuscript.

Reprint requests should be sent to Hans-Otto Karnath, Center of Neurology, University of Tübingen, Hoppe-Seyler-Str.3, 72076 Tübingen, Germany, or via e-mail: Karnath@uni-tuebingen.de.

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Author notes

*

Now at Children's Hospital of Fudan University, Shanghai, China.