COGNITIVE NEUROSCIENCE, 2010, 1 (4), 244–253
Multimodal temporal perception deficits in a patient with left spatial neglect
PCNS
Multimodal Temporal Deficits in Neglect
Colleen Merrifield, Marc Hurwitz, and James Danckert University of Waterloo, Waterloo, Ontario, Canada
We examined multisecond time estimation (up to 60 s) for visual and auditory events in a patient with left spatial neglect (RR), who grossly underestimated all durations in all tasks. In contrast, healthy controls and a patient with left hemisphere damage (HW) demonstrated accurate estimates of the same durations. These findings add to a growing body of literature suggesting that neglect cannot be understood simply in terms of a bias in orienting attention to one side of space. In addition, these data suggest that the right hemisphere parietal cortex may be important for the perception of time across multiple modalities.
Keywords: Temporal estimation; Parietal cortex; Neglect; Nonspatial deficits; Spatial attention.
INTRODUCTION Recent models of neglect emphasize the need to account for nonspatial impairments when explaining the cardinal symptom of the disorder—loss of awareness for contralesional events. That is, neglect patients also demonstrate impairments on nonspatial tasks indicative of a reduced capacity to allocate attention over time and impaired perception of time itself (Basso, Nichelli, Frassinetti, & di Pellegrino, 1996; Danckert et al., 2007; Harrington, Haaland, & Knight, 1998; Shapiro, Hillstrom, & Husain, 2002). Consequently, more recent models of neglect stress the need to account for nonspatial deficits in explaining the syndrome (Becchio & Bertone, 2006; Danckert & Ferber, 2006; Husain & Nachev, 2007). One critical nonspatial component shown to be impaired in neglect is the ability to accurately perceive the passage of time for both millisecond and multisecond events (Basso et al., 1996; Danckert et al., 2007). For example, we recently demonstrated that patients with left neglect massively underestimate
multisecond visual events (Danckert et al., 2007) compared to both healthy elderly controls and those with right brain damage without neglect (Danckert et al., 2007). Battelli, Pascual-Leone, and Cavanagh (2007) suggested that the right inferior parietal cortex, commonly lesioned in neglect, forms the crucial node of a third visual pathway in the human brain. So while the dorsal (i.e., V1 to superior parietal cortex) and ventral (V1 to inferior temporal cortex) pathways are important for visuomotor control and object recognition respectively (i.e., the “how” and “what” pathways; Goodale & Milner, 1992), a third pathway from V1 terminating in right inferior parietal cortex may be important for detecting onsets and offsets of salient visual events—what Battelli et al. (2007) call the ‘when’ visual pathway. Other neuropsychological studies investigating temporal perception have implicated the right inferior parietal cortex as an important substrate for time perception (Alexander, Cowey, & Walsh, 2005; Harrington et al., 1998). It seems clear then that right inferior parietal cortex plays an important role in temporal processing. This is not to suggest
Correspondence should be addressed to: James Danckert, Canada Research Chair (Tier II) in Cognitive Neuroscience, Department of Psychology, University of Waterloo, 200 University Avenue West, Waterloo, Ontario, Canada N2L 3G1. E-mail: [email protected] We are grateful to RR and HW for their time and effort through several testing sessions. This work was supported by Natural Sciences and Engineering Research Council of Canada (NSERC) Canada Research Chair and Discovery grants to JD, Heart and Stroke Foundation of Ontario Grant-in-aid to JD, NSERC Undergraduate and CGS-M Awards to CM, Ontario Graduate Scholarship in Science and Technology (OGSST) to CM, and an NSERC PGS-D award to MH.
© 2010 Psychology Press, an imprint of the Taylor & Francis Group, an Informa business www.psypress.com/cognitiveneuroscience DOI: 10.1080/17588921003759934
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that the right inferior parietal lobule is solely responsible for temporal perception and timing-related behaviors. Indeed, a great deal of research implicates the basal ganglia and cerebellum more directly in timing related behaviors (Matell & Meck, 2004; Meck, 2005). Some have suggested that at least two systems exist in the primate brain for timing automatic (subsecond) and controlled (multisecond) temporal events, the latter more directly involving right hemisphere fronto-parietal regions (Lewis & Miall, 2003, 2006). What we are suggesting here is that there is mounting evidence for involvement of the right inferior parietal cortex in both subsecond and multisecond temporal perception (Basso et al., 1996; Danckert et al., 2007; Harrington et al., 1998). In addition, since the right inferior parietal lobule represents association cortex, it likely acts to integrate various sources of information across multiple modalities. If disruption to this region interferes with this integrative function one might expect to observe the symptoms of neglect, including temporal perception deficits, in a number of modalities. To our knowledge, all studies to date that have examined temporal perception in neglect have investigated deficits in the visual modality only.1 Here we examined time within both the visual and auditory modalities, in a patient with left spatial neglect (RR). We compared his performance to a group of healthy controls (HC) and to a patient with left hemisphere damage resulting in high-level language comprehension deficits, hemianopia, and mild right neglect (HW).
METHOD Participants Clinical details and individual lesions of each patient are presented in Figure 1. Patients were classified as having neglect on the basis of line bisection, cancellation, and figure copying performance. Figure copying and cancellation (stars) were taken from the Behavioral Inattention Test (BIT; Wilson, Cockburn, & Halligan, 1987). The line bisection included 10 lines presented one at a time horizontally and aligned to the patient’s body midline. Lines were 236 mm in length and 4 mm in height. Patients were asked to place a mark where they thought the center of each line was. Neglect was considered to be present if two of these three criteria were met: Mean bisection marks deviated from center by more than 5% of total line length, there were at 1Note that of the patients with right parietal damage in the Harrington et al. (1998) paper, only 2 of 18 cases were reported as having neglect.
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least 10% omissions (i.e., failure to cancel targets) of contralesional targets on cancellation tasks, and there was evidence of contralesional omissions or distortions on figure copying (Figure 1). Neglect severity for each task was used to calculate an overall severity rating for each patient (i.e., the median severity score across tasks; Schindler, Clavagnier, Karnath, Derex, & Perenin, 2006). All participants gave informed consent prior to participating and the protocol received institutional ethics clearance. Patient RR RR was a 64-year-old man tested four months post-stroke. RR sustained an emoblic stroke with involvement of right fronto-parietal subcortical deep white matter, as well as right parietal cortex and rightside basal ganglia (Figure 1). RR suffered severe lef-sided paralysis. He exhibited normal hearing, corrected-to-normal vision and showed no speech impairments, nor any difficulty understanding instruction. Upon clinical examination, RR demonstrated moderate neglect (Figure 1). Patient HW HW was a 74-year-old man tested 14 months after a posterior cerebral artery stroke. Computed tomography (CT) scans revealed an area of hypodensity in the left medial temporal and occipital cortex, also involving the posterior thalamus and surrounding white matter (Figure 1). HW demonstrated normal hearing and corrected-to-normal vision. He also demonstrated impairments in reading, slowed speech, and difficulty comprehending and following high-level, multistep directions. With persistent instruction he understood all task instructions. Upon clinical examination HW was hemianopic and demonstrated mild right neglect (Figure 1). Healthy controls A group of nine (1 male; M = 67.3, SD = 5.7 years of age, all right-handed) neurologically healthy, older controls were recruited from the community.
Apparatus and procedures All participants completed three time estimation tasks. Both patients also completed the covert orienting of visual attention task as a measure of spatial attentional impairment (Posner, Walker, Friedrich, & Rafal, 1984). All tasks were presented to participants on a laptop computer.
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Figure 1. Upper panel: Patient RR was a 64-year old male, 4 months post-stroke with moderate left neglect. RR’s line bisection performance was deviated 16.78% to the right of true center. On cancellation, he omitted 90% of left-sided and 31% of right-sided targets. CT images from RR’s brain with figure copying performance showing obvious neglect of the left side of each image are presented below. Lower panel: Patient HW was a 74-year old male, 14 months post-stroke with mild right neglect. HW’s line bisection performance was deviated 7.12% to the left of true center, and he did not omit any targets on the cancellation task. CT images from HW’s brain with figure copying performance are presented below. Mild distortions are evident on the copy of the tree and the flower to the right side of each image (see “Methods” for scan details of each patient).
Covert orienting of visual attention (COVAT) Previous research has shown that patients with either left or right parietal lesions are disproportionately slow
to respond to invalidly cued targets when the cue appears in the ipsilesional field requiring attention to be disengaged and reoriented towards contralesional space (Posner, et al., 1984; Striemer & Danckert,
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2007; Striemer et al., 2007). For our purposes, we wanted to determine whether or not each patient would demonstrate such a disengage deficit. In addition, if the patients show similar difficulties in orienting attention (perhaps commensurate with the level of neglect severity) but differ in terms of their performance on the temporal estimation tasks, this would provide some evidence to suggest that temporal deficits are not secondary to problems with attention. For the COVAT we used non-informative (i.e., 50% valid) abrupt-onset peripheral cues. Target locations were indicated by green circles subtending 2° of visual angle, presented 4° either side of fixation. Targets were filled red circles presented within the cue. On separate trials targets could appear at the cued location (i.e., valid trials) or at the opposite location (i.e., invalid trials; Posner et al., 1984). Response times were measured by external button press. Both patients were told to maintain fixation throughout a trial. Patients’ fixation was monitored visually by the experimenter and trials in which saccades were made were excluded from further analysis. Stimulus onset asynchronies (SOAs) of 50 ms and 150 ms were used. At both of these SOAs it is not possible to initiate a saccade to the cue prior to the appearance of the target. Thus, even in instances where saccades were made to targets, the cues were necessarily covertly attended. Trials in which targets appeared without any preceding cue were included to examine RTs for simple target detection. Targets in these “no-cue” trials were presented 250 ms after fixation onset. On invalid trials, targets appear in the opposite location resulting in an RT advantage (i.e., faster RTs) for validly cued vs. invalidly cued targets. This RT advantage was represented as a cue effect size (CES) by subtracting the RTs to validly cued targets from the RTs to invalidly cued targets (i.e., a positive CES indicates an RT advantage for valid targets). Only the patients (RR and HW) completed the COVAT. HW completed four blocks of 50 trials for a total of 200 trials (20 trials by two SOAs (50 and 150 ms) by two target types (valid and invalid) by two sides (left and right) leads to 160 trials, with the final 40 trials coming from 20 left-sided and 20 right-sided “no cue” trials). RR completed two blocks of 50 trials for a total of 100 trials (Figure 2). RR completed fewer blocks of trials due to the fact that he consistently neglected targets on the left.
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ensure attention to the task, high-frequency (1200 Hz) and low-frequency (340 Hz) tones were presented for 300 ms at pseudorandom temporal intervals within each white noise stimulus. Tones were verbally differentiated, out loud, as either “high” or “low” by participants. Constraints on the temporal intervals between tones were as follows: To ensure no distraction during critical processing periods, no tone sounded within the first or last 500 ms of a trial; the minimum duration between tones was 500 ms to allow sufficient processing time; and the maximum duration between tones was 1500 ms to allow for more than one tone to be presented during the shortest durations (Danckert et al., 2007). Within those constraints the time between tones varied randomly, as did the order of high or low tones. Verbal auditory time estimation task (VBL) Modified newspaper passages were pre-recorded and presented to patients and controls. Durations of the passages were 5, 15, 30, and 60 s. At the end of each trial, participants were asked to estimate the duration of the passage to the nearest whole second. As with the nonverbal task, high (1200 Hz) and low frequency (340 Hz) tones were presented within each passage. Again, participants were instructed to verbally identify these tones, out loud, as either “high” or “low,” to ensure attention to the task and prevent internal counting of durations. Temporal constraints for the tones were identical to those outlined for the nonverbal task. Visual time estimation task (VIS) This task was identical to that used by Danckert and colleagues (2007) in which participants estimated the duration of an illusory motion stimulus. The illusory motion stimulus was intended to be interesting enough to maintain patients’ attention throughout the task and lasted 5, 15, 30, or 60 s. At the end of each trial, participants estimated the duration of the visual stimulus to the nearest whole second (Danckert et al., 2007). To prevent internal counting of durations, single digits were presented at pseudorandom temporal intervals (i.e., using the same temporal constraints imposed on the tones in the first two tasks) in the center of the illusory motion display. Participants were instructed to read these digits aloud as they appeared on the screen.
Nonverbal time estimation task (NVBL) Durations of white noise lasting 5, 15, 30, or 60 s were presented to patients and controls. At the end of each trial participants were asked to estimate, to the nearest whole second, how long the stimulus had been present. To prevent internal counting of durations and to
Data analysis Group means were calculated based on the mean raw estimates for each participant, at each duration. Data for controls were then subjected to an analysis of variance
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Figure 2. Upper panel: Schematic representation of the covert orienting of attention paradigm. Participants fixate centrally throughout and respond to the presence of targets to the left and right of fixation that can be preceded by a cue in the same location (valid target) or a cue in the opposite location (invalid target). Middle panel: Mean reaction times (RTs) to valid targets, invalid targets, and no cue trials. The stimulus onset asynchrony (SOA) represents the time from cue onset to target onset. The difference between valid RTs and invalid RTs is highlighted by the gray area for left- and right-sided targets separately. Lower panel: Cue effect sizes (CES) calculated by subtracting RTs to valid targets from RTs to invalid targets. HW shows a disengage deficit for right-sided targets at both SOAs that is in the same range of magnitudes for disengage deficits demonstrated by left neglect patients in our previous work (see Striemer & Danckert, 2007; Striemer et al., 2007). The dotted horizontal line is for comparison purposes, to indicate that the two patients demonstrated a similar CES for ipsilesional targets.
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(ANOVA) with two factors of task (nonverbal, verbal, and visual) and time interval (5, 15, 30, 60 s).2 Mean raw estimates made by each patient were compared to controls with modified independent samples t-tests (Crawford, Howell, & Garthwaite, 1998), which treat the patient as an individual sample that does not contribute to the estimate of within-group variance. This method is more conservative than the conventional z-score approach, which tends to overestimate the abnormality of a patient’s score, especially with smaller control samples, by assuming the scores of the control group follow a normal distribution (Crawford et al., 1998). Nevertheless, where appropriate, z-scores were also presented for comparison. In addition, a least-squares regression analysis was carried out for each participant to determine the goodness of fit between an individual’s estimates and the actual durations. From these analyses, the patients’ mean r2 and slope values were compared to the control means using the same modified independent samples t-tests procedure described above (Crawford et al., 1998). Finally, mean signed error scores were calculated for each participant by subtracting the actual duration from each individual’s mean estimate, at each interval. Therefore, positive scores represent overestimation, whereas negative scores represent underestimation. Correlations across tasks were then calculated using these mean signed error scores for each individual to ascertain whether participants who underestimated (or overestimated) durations in one task would tend to do so across all three tasks.
RESULTS Covert orienting For patient RR, reaction times (RTs) were collected only for right-sided targets. That is, RR failed to respond to all left-sided targets. He did demonstrate the expected advantage for validly over invalidly cued targets in right space (right-sided CES: 50 ms SOA = 58.40; 150 ms
2
Healthy controls did not appear to be making categorical judgements of the temporal intervals to be estimated. In fact, they demonstrated mean underestimations at the 60 s intervals and substantial variability. Had they been making categorical judgements they may still have tended to underestimate (or overestimate) durations but would have shown far less variability. No single control (or patient) demonstrated behavior indicative of categorical judgements and in fact the variance scaled with the duration to be estimated (i.e., Weber’s law) as would be expected. As one example, for the 60-s duration of the nonverbal task, the healthy participants’ estimates ranged from 25-160 s. Similar variability was seen across all tasks.
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SOA = 79.18; Figure 2). Patient HW showed the classic disengage deficit for invalidly cued right- (contralesional) sided targets (Figure 2). That is, he was far slower to respond to invalid targets when his attention had first been drawn to a cue in left space. The CES for left targets at each SOA was clearly smaller than the CES for rightward shifts of attention (left-sided CES at 50 ms SOA = 74.20 ms, right-sided CES at 50 ms SOA = 121.29 ms; t(19) = –2.43, p < 0.05; left-sided CES at 150 ms SOA = 38.71 ms, right-sided CES at 150 ms SOA = 189.20; t(19) = 3.26, p < 0.01; Figure 2). In addition, HW demonstrated significantly slower RTs to right-sided “no cue” trials vs. left-sided “no cue” trials, t(19) = –2.65, p < 0.05; Figure 2). Importantly, the RT advantage that patient RR showed for right-sided validly over invalidly cued targets was within the same range as the advantage shown by HW for validly cued over invalidly cued targets in ipsilesional space. So at the very least, the patients demonstrated an equivalent ability to direct attention within ipsilesional space (Figure 2).
Time estimation performance A box and whisker plot constructed for the control group was used to identify values that fell 1.5 times the interquartile range below the 25th or above the 75th percentile. Removal of these outliers resulted in elimination of only 3.33% of trials for the controls. A 3 (task) × 4 (interval) ANOVA of the raw estimates made by controls with a Greenhouse-Geisser correction for lack of sphericity revealed a significant main effect of interval, F(1.60, 36.70) = 202.74, p < .001. Unsurprisingly, this indicated that as the duration to be estimated increased, so too did the mean estimates. No other significant effects were noted. Mean estimates made by patient RR (left spatial neglect), as expected, fell well below those of controls (Figure 3). Directly comparing RR to the control group using modified independent samples t-tests revealed that RR made significantly lower estimates at all but the shortest intervals, on each task (all t values > 1.94, all p values < .05). In stark contrast, comparisons of HW with controls using the same procedure revealed that HW’s mean estimates did not differ from controls at any interval on any task (all t values < 1.72, all p values > .12; Figure 3).3 Finally, when the performances of RR (left spatial neglect) and HW (right spatial neglect) were directly
3 While HW’s estimate is outside the 95% CI on the 60 s interval of the nonverbal TE task, it was not significantly different when compared using Crawford’s modified independent samples t-test.
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Figure 3. Control group mean estimates (s) and 95% confidence intervals (solid lines and shaded area) for the nonverbal, verbal, and visual temporal estimation tasks.
contrasted, independent samples t-tests indicated that RR showed significantly smaller mean estimates than HW at all durations on all tasks with the exception of the shortest (i.e., 5 s) duration (all t values > 3.66, all p values < .01; Figure 3).
Linear regression equations were found to be significant for each control participant, and for each patient’s data, on each task. That is, for every participant (including RR, who dramatically underestimated intervals in each task), their estimates systematically increased with increasing interval durations on all tasks. To compare estimates made by controls with those of the patients, r2 and slope values were calculated for each control. For each of these measures, each patient’s data were compared with the control mean using the modified independent samples t-tests (Crawford et al., 1998). For RR for each task, r2 and slope values were significantly lower than controls, indicative of shallower slopes and weaker relationships (indicated by the lower r2 values) between his estimates and the actual durations. Not surprisingly, for HW none of the values obtained on any task differed significantly from controls. Signed error values were calculated for each participant and patient for each task on a trial by trial basis. One-tailed Pearson correlations were calculated for controls, analyzing the relationship between error values on each of the TE tasks (Figure 4). Underestimations were coded as negative while overestimations were coded as positive. For controls, while performance on the visual time estimation task was significantly correlated with both the verbal and nonverbal tasks (rNVBL, VIS = .59, p = .05; rVBL, VIS = .63, p = .04), there was no relationship between the nonverbal and verbal time estimation tasks (rNVBL, VBL = .43, p = .13). A trial-by-trial correlational analysis of each patient’s error data indicated that, for RR, the magnitude of underestimation was significantly positively correlated on all three tasks (rNVBL, VBL = .99, p < .001; rNVBL, VIS = .99, p < .001; rVBL, VIS = .99, p < .001). A significant positive correlation was found between the magnitude of HW’s estimations on the nonverbal and verbal tasks (r =.71, p < .001); however, no relationships were found between the estimates of either the nonverbal or verbal tasks and the visual task (rNVBL, VIS = .32, p = .12; rVBL, VIS = –.05, p = .42).4 Finally, split-half reliability coefficients were calculated using the absolute error scores for each patient, to examine whether performance deteriorated over time for each task. No differences were found in the estimates of either patient in the first vs. the second half of any task (for RR: rnvbl = .11, p = .81; rvbl = –.18, 4 It should be noted that with a small sample size such as the one used here and the relatively accurate temporal estimates of both the control group and patient HW, correlations between signed error values may not necessarily reach significance. For example, a relationship between signed error values will cancel out when a participant slightly underestimates durations on one task and slightly overestimates in another task.
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Figure 4. Mean signed error values for each control participant and patient. Correlations between the nonverbal and verbal tasks (upper panel), between the nonverbal and visual tasks (middle panel) and between the verbal and visual tasks (lower panel). Dashed lines represent a linear regression fitted to the control data with the equations and r-squared values presented to the right of each figure.
p = .66; rvis = .07, p = .43; for HW: rnvbl = –.11, p = .79; rvbl = –.11, p = .80; rvis = –.20, p = .64).
DISCUSSION Results of the current study clearly indicate multimodal deficits in processing the passage of time in our patient with left neglect. Patient RR dramatically underestimated multisecond intervals in each of the
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modialities tested (Figures 2, 3, 4). Despite his dramatic underestimation, significant linear trends were observed for RR (and all other participants) such that longer estimates were given for longer durations (Figure 3), implying that all patients and participants understood the task. Importantly, the slope describing this relationship was shallowest for RR, with no significant difference between the healthy controls and our patient with left hemisphere damage (HW). We have previously demonstrated that although patients with right brain damage (RBD) also tended to underestimate temporal durations, they were far less impaired than a group of eight neglect patients, showing significant differences relative to the healthy controls at only the longest duration. So, although right hemisphere lesions led to underestimations in both RBD and neglect groups, this tendency was strongest in the neglect patients. Here we have demonstrated in one neglect patient that the perception of time is impaired across multiple modalities and may therefore form a critical component of the syndrome. It is becoming increasingly clear that the heterogeneous symptom profiles characteristic of neglect cannot be fully accounted for by reference to impaired spatial attention alone (Basso et al., 1996; Danckert & Ferber, 2006; Danckert et al., 2007; Pisella & Mattingley, 2004). In fact, the COVAT results, indicating that the ability to direct attention ipsilesionally was equivalent in the two patients, suggest that any differences in time estimation (especially for the auditory tasks, which do not have any spatial component) are unlikely to be due to differences in the ability to direct spatial attention. This is important, as many suggest that the right hemisphere involvement in time perception merely reflects a role for this hemisphere in attending to time rather than perceiving it per se (e.g., Harrington et al., 1998). This raises the question of whether impaired time perception plays a causative role in neglect or whether it merely exacerbates the spatial symptoms characteristic of the disorder (a suggestion made in a similar way by Husain & Rorden (2003) when discussing nonspatial deficits in neglect). We would not suggest that impaired temporal estimations of the kind observed here in patient RR cause neglect. In fact, such deficits alone cannot explain the cardinal symptom of neglect: the failure to respond to stimuli and events in contralesional space. Instead, it is likely that the full-blown neglect syndrome results from a combination of impairments in a range of cognitive domains (Danckert & Ferber, 2006). What is suggested here is that a convergence of spatial and nonspatial deficits is necessary for the full neglect syndrome to be evident. While deficits in
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sustained (nonspatial) attention may indeed exacerbate the spatial symptoms of neglect (Robertson et al., 1997), this is unlikely to fully account for the impaired perception of time demonstrated here. The split half analyses on the current data set, indicating that performance was no worse in the second vs. the first half of the task, suggest that levels of sustained attention did not change throughout the duration of the task. It is also worth noting that patient HW, who showed no deficits in time perception, also had a large lesion volume, indicating that time perception deficits observed in neglect are not simply due to the fact that neglect patients may typically have larger, more severe lesions. It is not being suggested here that the right temporo-parietal junction (commonly lesioned in left spatial neglect) is exclusively responsible for all forms of temporal processing. In fact, it has been convincingly demonstrated that many brain regions (predominantly the basal ganglia and cerebellum) are important for processing time (Ivry & Spencer, 2004; Matell & Meck, 2004; Meck, 2005). However, to our knowledge, work on the basal ganglia has not revealed lateralized impairments (or involvement) in time perception. As such, we would suggest that right hemisphere fronto-parietal regions likely play a crucial role in time perception, perhaps via connections from the medial temporal lobes to regions of the dorsal striatum and from there to parietal cortex. Although in our previous work right hemisphere lesions led to underestimations in both the RBD patients without neglect and the neglect group, this tendency was strongest in the neglect patients. Furthermore, the tendency towards underestimation seen in the RBD patients without neglect in that work was not evident in our left hemisphere patient presented here. Previous research has also demonstrated that right but not left hemisphere lesions lead to impaired temporal discrimination (Harrington et al., 1998). Taken together, we would suggest that deficits of timing behavior are likely to be more severe in patients with right hemisphere damage and most severe in patients with neglect following right parietal damage, although we recognize that much more work is needed on left hemisphere patients to determine the role of left parietal regions in timing-related behaviors (see Coull, 2004 for functional magnetic resonance imaging evidence of left parietal involvement in time perception). It does seem clear though, that time perception deficits in our neglect patient are not restricted to the visual domain. If time perception were a distributed function, we would have expected HW to perform poorly on the verbal task given the location of his lesion and his high-level comprehension difficulties.
In addition, if temporal processing was distributed and deficits in time perception, such as the ones previously reported by Danckert and colleagues (2007) in a group of eight neglect patients, were ascribed solely to visual neglect, we would have expected RR to perform well on the nonvisual tasks. Clearly, neither of these scenarios was supported here. It is more likely that interval time perception is centralized to a fronto-parietal network lateralized to the right hemisphere with extensive connections to the basal ganglia (Batelli et al., 2007). Finally, it is intriguing to consider the possibility that if the type of temporal perception examined here is in fact lateralized to the right temporo-parietal junction, a sparing of this component process in left hemisphere patients, such as HW, who showed mild right spatial neglect, may help to explain why their neglect symptoms are less severe. Of course, more research in right neglect patients (following left hemisphere lesions), while difficult, is necessary to address this controversial hypothesis.
CONCLUSION The finding here that a patient with left spatial neglect (RR) exhibited multimodal deficits in time perception suggests that impairments of temporal perception represent an important part of the neglect syndrome. It is becoming increasingly evident that models of neglect that refer solely to impaired attentional mechanisms are insufficient to fully explain the disorder. It seems clear that current models of neglect will need to consider nonspatial deficits, such as impaired temporal perception, in order to construct models that explain the full range and nature of impairments observed in the disorder. Manuscript received 7 December 2009 Manuscript accepted 5 March 2010 First published online 19 April 2010
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Becchio, C., & Bertone, C. (2006). Time and neglect: Abnormal temporal dynamics in unilateral spatial neglect. Neuropsychologia, 44, 2775–2782. Coull, J. T. (2004). fMRI studies of temporal attention: Allocating attention within, or towards time. Cognitive Brain Research, 21, 216–226. Crawford, J. R., & Howell, D. C. (1998). Comparing an individual’s test score against norms derived from small samples. Clinical Neuropsychologist, 12, 482–486. Crawford, J. R., Howell, D. C., & Garthwaite, P. H. (1998). Payne and Jones revisited: Estimating the abnormality of test score differences using a modified paired samples t test. Journal of Clinical and Experimental Neuropsychology, 20, 898–905. Danckert, J., & Ferber, S. (2006). Revisiting unilateral neglect. Neuropsychologia, 44, 987–1006. Danckert, J., Ferber, S., Pun, C., Broderick, C, Striemer, C., Rock, S., et al. (2007). Neglected time: Impaired temporal perception of mulitsecond intervals in unilateral neglect. Journal of Cognitive Neuroscience, 19, 1706–1720. Goodale, M. & Milner, A.D. (1992). Separate visual pathways for perception and action. Trends in Neuroscience, 15, 20–25. Harrington, D. L., Haaland, K. Y., & Knight, R. T. (1998). Cortical networks underlying mechanisms of time perception. Journal of Neuroscience, 18, 1085–1095. Husain, M., & Nachev, P. (2007). Space and the parietal cortex. Trends in Cognitive Sciences, 11, 30–36. Husain, M., & Rorden, C. (2003). Non-spatially lateralised mechanisms in neglect. Nature Reviews Neuroscience, 4, 26–36. Ivry, R. B., & Spencer, R. M. C. (2004). The neural representation of time. Current Opinion in Neurobiology, 14, 225–232. Lewis, P. A., & Miall, R. C. (2003). Distinct systems for automatic and cognitively controlled time measurement: Evidence from neuroimaging. Current Opinions in Neurobiology, 13, 250–255.
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Lewis, P. A., & Miall, R. C. (2006). A right hemispheric prefrontal system for cognitive time measurement. Behavioural Processes, 71, 226–234. Matell, M. S., & Meck, W. H. (2004). Cortico-striatal circuits and interval timing: Coincidence detection of oscillatory processes. Cognitive Brain Research, 21, 139–170. Meck, W. H. (2005). Neuropsychology of timing and time perception. Brain & Cognition, 58, 1–8. Pisella, L., & Mattingley, J. B. (2004). The contribution of spatial remapping to unilateral visual neglect. Neuroscience and Biobehavioral Reviews, 28, 181–200. Posner, M. I., Walker, J. A., Friedrich, F. J., & Rafal, R. D. (1984). Effects of parietal injury on covert orienting of attention. Journal of Neuroscience, 4, 1863–1874. Robertson, I. H., Manly, T., Beschin, N., Daini, R., HaeskeDewick, H., Hömberg, V., et al. (1997). Auditory sustained attention is a marker of unilateral neglect. Neuropsychologia, 35, 1527–1532. Schindler, I., Clavagnier, S., Karnath, H.-O., Derex, L., & Perenin, M.-T. (2006). A common basis for visual and tactile exploration deficits in spatial neglect? Neuropsychologia, 44, 1444–1451. Shapiro, K. L., Hillstrom, A. P., & Husain, M. (2002). Control of visuotemporal attention by inferior parietal and superior temporal cortex. Current Biology, 12, 1320–1325. Striemer, C., & Danckert, J. (2007) Prism adaptation reduces the disengage deficit in right brain damage patients. NeuroReport, 18, 99–103. Striemer, C., Blangero, A., Rossetti, Y., Boisson, D., Rode, G., Vighetto, A., Pisella, L., & Danckert, J. (2007). Deficits in peripheral visual attention in patients with optic ataxia. NeuroReport, 18, 1171–1175. Wilson, B., Cockburn, J., & Halligan, P. (1987). Development of a behavioural test of visuospatial neglect. Archives of Physical Medicine and Rehabilitation, 68, 98–102.
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Multimodal temporal perception deficits in a patient with left spatial neglect
PCNS
Multimodal Temporal Deficits in Neglect
Colleen Merrifield, Marc Hurwitz, and James Danckert University of Waterloo, Waterloo, Ontario, Canada
We examined multisecond time estimation (up to 60 s) for visual and auditory events in a patient with left spatial neglect (RR), who grossly underestimated all durations in all tasks. In contrast, healthy controls and a patient with left hemisphere damage (HW) demonstrated accurate estimates of the same durations. These findings add to a growing body of literature suggesting that neglect cannot be understood simply in terms of a bias in orienting attention to one side of space. In addition, these data suggest that the right hemisphere parietal cortex may be important for the perception of time across multiple modalities.
Keywords: Temporal estimation; Parietal cortex; Neglect; Nonspatial deficits; Spatial attention.
INTRODUCTION Recent models of neglect emphasize the need to account for nonspatial impairments when explaining the cardinal symptom of the disorder—loss of awareness for contralesional events. That is, neglect patients also demonstrate impairments on nonspatial tasks indicative of a reduced capacity to allocate attention over time and impaired perception of time itself (Basso, Nichelli, Frassinetti, & di Pellegrino, 1996; Danckert et al., 2007; Harrington, Haaland, & Knight, 1998; Shapiro, Hillstrom, & Husain, 2002). Consequently, more recent models of neglect stress the need to account for nonspatial deficits in explaining the syndrome (Becchio & Bertone, 2006; Danckert & Ferber, 2006; Husain & Nachev, 2007). One critical nonspatial component shown to be impaired in neglect is the ability to accurately perceive the passage of time for both millisecond and multisecond events (Basso et al., 1996; Danckert et al., 2007). For example, we recently demonstrated that patients with left neglect massively underestimate
multisecond visual events (Danckert et al., 2007) compared to both healthy elderly controls and those with right brain damage without neglect (Danckert et al., 2007). Battelli, Pascual-Leone, and Cavanagh (2007) suggested that the right inferior parietal cortex, commonly lesioned in neglect, forms the crucial node of a third visual pathway in the human brain. So while the dorsal (i.e., V1 to superior parietal cortex) and ventral (V1 to inferior temporal cortex) pathways are important for visuomotor control and object recognition respectively (i.e., the “how” and “what” pathways; Goodale & Milner, 1992), a third pathway from V1 terminating in right inferior parietal cortex may be important for detecting onsets and offsets of salient visual events—what Battelli et al. (2007) call the ‘when’ visual pathway. Other neuropsychological studies investigating temporal perception have implicated the right inferior parietal cortex as an important substrate for time perception (Alexander, Cowey, & Walsh, 2005; Harrington et al., 1998). It seems clear then that right inferior parietal cortex plays an important role in temporal processing. This is not to suggest
Correspondence should be addressed to: James Danckert, Canada Research Chair (Tier II) in Cognitive Neuroscience, Department of Psychology, University of Waterloo, 200 University Avenue West, Waterloo, Ontario, Canada N2L 3G1. E-mail: [email protected] We are grateful to RR and HW for their time and effort through several testing sessions. This work was supported by Natural Sciences and Engineering Research Council of Canada (NSERC) Canada Research Chair and Discovery grants to JD, Heart and Stroke Foundation of Ontario Grant-in-aid to JD, NSERC Undergraduate and CGS-M Awards to CM, Ontario Graduate Scholarship in Science and Technology (OGSST) to CM, and an NSERC PGS-D award to MH.
© 2010 Psychology Press, an imprint of the Taylor & Francis Group, an Informa business www.psypress.com/cognitiveneuroscience DOI: 10.1080/17588921003759934
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that the right inferior parietal lobule is solely responsible for temporal perception and timing-related behaviors. Indeed, a great deal of research implicates the basal ganglia and cerebellum more directly in timing related behaviors (Matell & Meck, 2004; Meck, 2005). Some have suggested that at least two systems exist in the primate brain for timing automatic (subsecond) and controlled (multisecond) temporal events, the latter more directly involving right hemisphere fronto-parietal regions (Lewis & Miall, 2003, 2006). What we are suggesting here is that there is mounting evidence for involvement of the right inferior parietal cortex in both subsecond and multisecond temporal perception (Basso et al., 1996; Danckert et al., 2007; Harrington et al., 1998). In addition, since the right inferior parietal lobule represents association cortex, it likely acts to integrate various sources of information across multiple modalities. If disruption to this region interferes with this integrative function one might expect to observe the symptoms of neglect, including temporal perception deficits, in a number of modalities. To our knowledge, all studies to date that have examined temporal perception in neglect have investigated deficits in the visual modality only.1 Here we examined time within both the visual and auditory modalities, in a patient with left spatial neglect (RR). We compared his performance to a group of healthy controls (HC) and to a patient with left hemisphere damage resulting in high-level language comprehension deficits, hemianopia, and mild right neglect (HW).
METHOD Participants Clinical details and individual lesions of each patient are presented in Figure 1. Patients were classified as having neglect on the basis of line bisection, cancellation, and figure copying performance. Figure copying and cancellation (stars) were taken from the Behavioral Inattention Test (BIT; Wilson, Cockburn, & Halligan, 1987). The line bisection included 10 lines presented one at a time horizontally and aligned to the patient’s body midline. Lines were 236 mm in length and 4 mm in height. Patients were asked to place a mark where they thought the center of each line was. Neglect was considered to be present if two of these three criteria were met: Mean bisection marks deviated from center by more than 5% of total line length, there were at 1Note that of the patients with right parietal damage in the Harrington et al. (1998) paper, only 2 of 18 cases were reported as having neglect.
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least 10% omissions (i.e., failure to cancel targets) of contralesional targets on cancellation tasks, and there was evidence of contralesional omissions or distortions on figure copying (Figure 1). Neglect severity for each task was used to calculate an overall severity rating for each patient (i.e., the median severity score across tasks; Schindler, Clavagnier, Karnath, Derex, & Perenin, 2006). All participants gave informed consent prior to participating and the protocol received institutional ethics clearance. Patient RR RR was a 64-year-old man tested four months post-stroke. RR sustained an emoblic stroke with involvement of right fronto-parietal subcortical deep white matter, as well as right parietal cortex and rightside basal ganglia (Figure 1). RR suffered severe lef-sided paralysis. He exhibited normal hearing, corrected-to-normal vision and showed no speech impairments, nor any difficulty understanding instruction. Upon clinical examination, RR demonstrated moderate neglect (Figure 1). Patient HW HW was a 74-year-old man tested 14 months after a posterior cerebral artery stroke. Computed tomography (CT) scans revealed an area of hypodensity in the left medial temporal and occipital cortex, also involving the posterior thalamus and surrounding white matter (Figure 1). HW demonstrated normal hearing and corrected-to-normal vision. He also demonstrated impairments in reading, slowed speech, and difficulty comprehending and following high-level, multistep directions. With persistent instruction he understood all task instructions. Upon clinical examination HW was hemianopic and demonstrated mild right neglect (Figure 1). Healthy controls A group of nine (1 male; M = 67.3, SD = 5.7 years of age, all right-handed) neurologically healthy, older controls were recruited from the community.
Apparatus and procedures All participants completed three time estimation tasks. Both patients also completed the covert orienting of visual attention task as a measure of spatial attentional impairment (Posner, Walker, Friedrich, & Rafal, 1984). All tasks were presented to participants on a laptop computer.
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Figure 1. Upper panel: Patient RR was a 64-year old male, 4 months post-stroke with moderate left neglect. RR’s line bisection performance was deviated 16.78% to the right of true center. On cancellation, he omitted 90% of left-sided and 31% of right-sided targets. CT images from RR’s brain with figure copying performance showing obvious neglect of the left side of each image are presented below. Lower panel: Patient HW was a 74-year old male, 14 months post-stroke with mild right neglect. HW’s line bisection performance was deviated 7.12% to the left of true center, and he did not omit any targets on the cancellation task. CT images from HW’s brain with figure copying performance are presented below. Mild distortions are evident on the copy of the tree and the flower to the right side of each image (see “Methods” for scan details of each patient).
Covert orienting of visual attention (COVAT) Previous research has shown that patients with either left or right parietal lesions are disproportionately slow
to respond to invalidly cued targets when the cue appears in the ipsilesional field requiring attention to be disengaged and reoriented towards contralesional space (Posner, et al., 1984; Striemer & Danckert,
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2007; Striemer et al., 2007). For our purposes, we wanted to determine whether or not each patient would demonstrate such a disengage deficit. In addition, if the patients show similar difficulties in orienting attention (perhaps commensurate with the level of neglect severity) but differ in terms of their performance on the temporal estimation tasks, this would provide some evidence to suggest that temporal deficits are not secondary to problems with attention. For the COVAT we used non-informative (i.e., 50% valid) abrupt-onset peripheral cues. Target locations were indicated by green circles subtending 2° of visual angle, presented 4° either side of fixation. Targets were filled red circles presented within the cue. On separate trials targets could appear at the cued location (i.e., valid trials) or at the opposite location (i.e., invalid trials; Posner et al., 1984). Response times were measured by external button press. Both patients were told to maintain fixation throughout a trial. Patients’ fixation was monitored visually by the experimenter and trials in which saccades were made were excluded from further analysis. Stimulus onset asynchronies (SOAs) of 50 ms and 150 ms were used. At both of these SOAs it is not possible to initiate a saccade to the cue prior to the appearance of the target. Thus, even in instances where saccades were made to targets, the cues were necessarily covertly attended. Trials in which targets appeared without any preceding cue were included to examine RTs for simple target detection. Targets in these “no-cue” trials were presented 250 ms after fixation onset. On invalid trials, targets appear in the opposite location resulting in an RT advantage (i.e., faster RTs) for validly cued vs. invalidly cued targets. This RT advantage was represented as a cue effect size (CES) by subtracting the RTs to validly cued targets from the RTs to invalidly cued targets (i.e., a positive CES indicates an RT advantage for valid targets). Only the patients (RR and HW) completed the COVAT. HW completed four blocks of 50 trials for a total of 200 trials (20 trials by two SOAs (50 and 150 ms) by two target types (valid and invalid) by two sides (left and right) leads to 160 trials, with the final 40 trials coming from 20 left-sided and 20 right-sided “no cue” trials). RR completed two blocks of 50 trials for a total of 100 trials (Figure 2). RR completed fewer blocks of trials due to the fact that he consistently neglected targets on the left.
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ensure attention to the task, high-frequency (1200 Hz) and low-frequency (340 Hz) tones were presented for 300 ms at pseudorandom temporal intervals within each white noise stimulus. Tones were verbally differentiated, out loud, as either “high” or “low” by participants. Constraints on the temporal intervals between tones were as follows: To ensure no distraction during critical processing periods, no tone sounded within the first or last 500 ms of a trial; the minimum duration between tones was 500 ms to allow sufficient processing time; and the maximum duration between tones was 1500 ms to allow for more than one tone to be presented during the shortest durations (Danckert et al., 2007). Within those constraints the time between tones varied randomly, as did the order of high or low tones. Verbal auditory time estimation task (VBL) Modified newspaper passages were pre-recorded and presented to patients and controls. Durations of the passages were 5, 15, 30, and 60 s. At the end of each trial, participants were asked to estimate the duration of the passage to the nearest whole second. As with the nonverbal task, high (1200 Hz) and low frequency (340 Hz) tones were presented within each passage. Again, participants were instructed to verbally identify these tones, out loud, as either “high” or “low,” to ensure attention to the task and prevent internal counting of durations. Temporal constraints for the tones were identical to those outlined for the nonverbal task. Visual time estimation task (VIS) This task was identical to that used by Danckert and colleagues (2007) in which participants estimated the duration of an illusory motion stimulus. The illusory motion stimulus was intended to be interesting enough to maintain patients’ attention throughout the task and lasted 5, 15, 30, or 60 s. At the end of each trial, participants estimated the duration of the visual stimulus to the nearest whole second (Danckert et al., 2007). To prevent internal counting of durations, single digits were presented at pseudorandom temporal intervals (i.e., using the same temporal constraints imposed on the tones in the first two tasks) in the center of the illusory motion display. Participants were instructed to read these digits aloud as they appeared on the screen.
Nonverbal time estimation task (NVBL) Durations of white noise lasting 5, 15, 30, or 60 s were presented to patients and controls. At the end of each trial participants were asked to estimate, to the nearest whole second, how long the stimulus had been present. To prevent internal counting of durations and to
Data analysis Group means were calculated based on the mean raw estimates for each participant, at each duration. Data for controls were then subjected to an analysis of variance
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Figure 2. Upper panel: Schematic representation of the covert orienting of attention paradigm. Participants fixate centrally throughout and respond to the presence of targets to the left and right of fixation that can be preceded by a cue in the same location (valid target) or a cue in the opposite location (invalid target). Middle panel: Mean reaction times (RTs) to valid targets, invalid targets, and no cue trials. The stimulus onset asynchrony (SOA) represents the time from cue onset to target onset. The difference between valid RTs and invalid RTs is highlighted by the gray area for left- and right-sided targets separately. Lower panel: Cue effect sizes (CES) calculated by subtracting RTs to valid targets from RTs to invalid targets. HW shows a disengage deficit for right-sided targets at both SOAs that is in the same range of magnitudes for disengage deficits demonstrated by left neglect patients in our previous work (see Striemer & Danckert, 2007; Striemer et al., 2007). The dotted horizontal line is for comparison purposes, to indicate that the two patients demonstrated a similar CES for ipsilesional targets.
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(ANOVA) with two factors of task (nonverbal, verbal, and visual) and time interval (5, 15, 30, 60 s).2 Mean raw estimates made by each patient were compared to controls with modified independent samples t-tests (Crawford, Howell, & Garthwaite, 1998), which treat the patient as an individual sample that does not contribute to the estimate of within-group variance. This method is more conservative than the conventional z-score approach, which tends to overestimate the abnormality of a patient’s score, especially with smaller control samples, by assuming the scores of the control group follow a normal distribution (Crawford et al., 1998). Nevertheless, where appropriate, z-scores were also presented for comparison. In addition, a least-squares regression analysis was carried out for each participant to determine the goodness of fit between an individual’s estimates and the actual durations. From these analyses, the patients’ mean r2 and slope values were compared to the control means using the same modified independent samples t-tests procedure described above (Crawford et al., 1998). Finally, mean signed error scores were calculated for each participant by subtracting the actual duration from each individual’s mean estimate, at each interval. Therefore, positive scores represent overestimation, whereas negative scores represent underestimation. Correlations across tasks were then calculated using these mean signed error scores for each individual to ascertain whether participants who underestimated (or overestimated) durations in one task would tend to do so across all three tasks.
RESULTS Covert orienting For patient RR, reaction times (RTs) were collected only for right-sided targets. That is, RR failed to respond to all left-sided targets. He did demonstrate the expected advantage for validly over invalidly cued targets in right space (right-sided CES: 50 ms SOA = 58.40; 150 ms
2
Healthy controls did not appear to be making categorical judgements of the temporal intervals to be estimated. In fact, they demonstrated mean underestimations at the 60 s intervals and substantial variability. Had they been making categorical judgements they may still have tended to underestimate (or overestimate) durations but would have shown far less variability. No single control (or patient) demonstrated behavior indicative of categorical judgements and in fact the variance scaled with the duration to be estimated (i.e., Weber’s law) as would be expected. As one example, for the 60-s duration of the nonverbal task, the healthy participants’ estimates ranged from 25-160 s. Similar variability was seen across all tasks.
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SOA = 79.18; Figure 2). Patient HW showed the classic disengage deficit for invalidly cued right- (contralesional) sided targets (Figure 2). That is, he was far slower to respond to invalid targets when his attention had first been drawn to a cue in left space. The CES for left targets at each SOA was clearly smaller than the CES for rightward shifts of attention (left-sided CES at 50 ms SOA = 74.20 ms, right-sided CES at 50 ms SOA = 121.29 ms; t(19) = –2.43, p < 0.05; left-sided CES at 150 ms SOA = 38.71 ms, right-sided CES at 150 ms SOA = 189.20; t(19) = 3.26, p < 0.01; Figure 2). In addition, HW demonstrated significantly slower RTs to right-sided “no cue” trials vs. left-sided “no cue” trials, t(19) = –2.65, p < 0.05; Figure 2). Importantly, the RT advantage that patient RR showed for right-sided validly over invalidly cued targets was within the same range as the advantage shown by HW for validly cued over invalidly cued targets in ipsilesional space. So at the very least, the patients demonstrated an equivalent ability to direct attention within ipsilesional space (Figure 2).
Time estimation performance A box and whisker plot constructed for the control group was used to identify values that fell 1.5 times the interquartile range below the 25th or above the 75th percentile. Removal of these outliers resulted in elimination of only 3.33% of trials for the controls. A 3 (task) × 4 (interval) ANOVA of the raw estimates made by controls with a Greenhouse-Geisser correction for lack of sphericity revealed a significant main effect of interval, F(1.60, 36.70) = 202.74, p < .001. Unsurprisingly, this indicated that as the duration to be estimated increased, so too did the mean estimates. No other significant effects were noted. Mean estimates made by patient RR (left spatial neglect), as expected, fell well below those of controls (Figure 3). Directly comparing RR to the control group using modified independent samples t-tests revealed that RR made significantly lower estimates at all but the shortest intervals, on each task (all t values > 1.94, all p values < .05). In stark contrast, comparisons of HW with controls using the same procedure revealed that HW’s mean estimates did not differ from controls at any interval on any task (all t values < 1.72, all p values > .12; Figure 3).3 Finally, when the performances of RR (left spatial neglect) and HW (right spatial neglect) were directly
3 While HW’s estimate is outside the 95% CI on the 60 s interval of the nonverbal TE task, it was not significantly different when compared using Crawford’s modified independent samples t-test.
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Figure 3. Control group mean estimates (s) and 95% confidence intervals (solid lines and shaded area) for the nonverbal, verbal, and visual temporal estimation tasks.
contrasted, independent samples t-tests indicated that RR showed significantly smaller mean estimates than HW at all durations on all tasks with the exception of the shortest (i.e., 5 s) duration (all t values > 3.66, all p values < .01; Figure 3).
Linear regression equations were found to be significant for each control participant, and for each patient’s data, on each task. That is, for every participant (including RR, who dramatically underestimated intervals in each task), their estimates systematically increased with increasing interval durations on all tasks. To compare estimates made by controls with those of the patients, r2 and slope values were calculated for each control. For each of these measures, each patient’s data were compared with the control mean using the modified independent samples t-tests (Crawford et al., 1998). For RR for each task, r2 and slope values were significantly lower than controls, indicative of shallower slopes and weaker relationships (indicated by the lower r2 values) between his estimates and the actual durations. Not surprisingly, for HW none of the values obtained on any task differed significantly from controls. Signed error values were calculated for each participant and patient for each task on a trial by trial basis. One-tailed Pearson correlations were calculated for controls, analyzing the relationship between error values on each of the TE tasks (Figure 4). Underestimations were coded as negative while overestimations were coded as positive. For controls, while performance on the visual time estimation task was significantly correlated with both the verbal and nonverbal tasks (rNVBL, VIS = .59, p = .05; rVBL, VIS = .63, p = .04), there was no relationship between the nonverbal and verbal time estimation tasks (rNVBL, VBL = .43, p = .13). A trial-by-trial correlational analysis of each patient’s error data indicated that, for RR, the magnitude of underestimation was significantly positively correlated on all three tasks (rNVBL, VBL = .99, p < .001; rNVBL, VIS = .99, p < .001; rVBL, VIS = .99, p < .001). A significant positive correlation was found between the magnitude of HW’s estimations on the nonverbal and verbal tasks (r =.71, p < .001); however, no relationships were found between the estimates of either the nonverbal or verbal tasks and the visual task (rNVBL, VIS = .32, p = .12; rVBL, VIS = –.05, p = .42).4 Finally, split-half reliability coefficients were calculated using the absolute error scores for each patient, to examine whether performance deteriorated over time for each task. No differences were found in the estimates of either patient in the first vs. the second half of any task (for RR: rnvbl = .11, p = .81; rvbl = –.18, 4 It should be noted that with a small sample size such as the one used here and the relatively accurate temporal estimates of both the control group and patient HW, correlations between signed error values may not necessarily reach significance. For example, a relationship between signed error values will cancel out when a participant slightly underestimates durations on one task and slightly overestimates in another task.
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Figure 4. Mean signed error values for each control participant and patient. Correlations between the nonverbal and verbal tasks (upper panel), between the nonverbal and visual tasks (middle panel) and between the verbal and visual tasks (lower panel). Dashed lines represent a linear regression fitted to the control data with the equations and r-squared values presented to the right of each figure.
p = .66; rvis = .07, p = .43; for HW: rnvbl = –.11, p = .79; rvbl = –.11, p = .80; rvis = –.20, p = .64).
DISCUSSION Results of the current study clearly indicate multimodal deficits in processing the passage of time in our patient with left neglect. Patient RR dramatically underestimated multisecond intervals in each of the
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modialities tested (Figures 2, 3, 4). Despite his dramatic underestimation, significant linear trends were observed for RR (and all other participants) such that longer estimates were given for longer durations (Figure 3), implying that all patients and participants understood the task. Importantly, the slope describing this relationship was shallowest for RR, with no significant difference between the healthy controls and our patient with left hemisphere damage (HW). We have previously demonstrated that although patients with right brain damage (RBD) also tended to underestimate temporal durations, they were far less impaired than a group of eight neglect patients, showing significant differences relative to the healthy controls at only the longest duration. So, although right hemisphere lesions led to underestimations in both RBD and neglect groups, this tendency was strongest in the neglect patients. Here we have demonstrated in one neglect patient that the perception of time is impaired across multiple modalities and may therefore form a critical component of the syndrome. It is becoming increasingly clear that the heterogeneous symptom profiles characteristic of neglect cannot be fully accounted for by reference to impaired spatial attention alone (Basso et al., 1996; Danckert & Ferber, 2006; Danckert et al., 2007; Pisella & Mattingley, 2004). In fact, the COVAT results, indicating that the ability to direct attention ipsilesionally was equivalent in the two patients, suggest that any differences in time estimation (especially for the auditory tasks, which do not have any spatial component) are unlikely to be due to differences in the ability to direct spatial attention. This is important, as many suggest that the right hemisphere involvement in time perception merely reflects a role for this hemisphere in attending to time rather than perceiving it per se (e.g., Harrington et al., 1998). This raises the question of whether impaired time perception plays a causative role in neglect or whether it merely exacerbates the spatial symptoms characteristic of the disorder (a suggestion made in a similar way by Husain & Rorden (2003) when discussing nonspatial deficits in neglect). We would not suggest that impaired temporal estimations of the kind observed here in patient RR cause neglect. In fact, such deficits alone cannot explain the cardinal symptom of neglect: the failure to respond to stimuli and events in contralesional space. Instead, it is likely that the full-blown neglect syndrome results from a combination of impairments in a range of cognitive domains (Danckert & Ferber, 2006). What is suggested here is that a convergence of spatial and nonspatial deficits is necessary for the full neglect syndrome to be evident. While deficits in
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sustained (nonspatial) attention may indeed exacerbate the spatial symptoms of neglect (Robertson et al., 1997), this is unlikely to fully account for the impaired perception of time demonstrated here. The split half analyses on the current data set, indicating that performance was no worse in the second vs. the first half of the task, suggest that levels of sustained attention did not change throughout the duration of the task. It is also worth noting that patient HW, who showed no deficits in time perception, also had a large lesion volume, indicating that time perception deficits observed in neglect are not simply due to the fact that neglect patients may typically have larger, more severe lesions. It is not being suggested here that the right temporo-parietal junction (commonly lesioned in left spatial neglect) is exclusively responsible for all forms of temporal processing. In fact, it has been convincingly demonstrated that many brain regions (predominantly the basal ganglia and cerebellum) are important for processing time (Ivry & Spencer, 2004; Matell & Meck, 2004; Meck, 2005). However, to our knowledge, work on the basal ganglia has not revealed lateralized impairments (or involvement) in time perception. As such, we would suggest that right hemisphere fronto-parietal regions likely play a crucial role in time perception, perhaps via connections from the medial temporal lobes to regions of the dorsal striatum and from there to parietal cortex. Although in our previous work right hemisphere lesions led to underestimations in both the RBD patients without neglect and the neglect group, this tendency was strongest in the neglect patients. Furthermore, the tendency towards underestimation seen in the RBD patients without neglect in that work was not evident in our left hemisphere patient presented here. Previous research has also demonstrated that right but not left hemisphere lesions lead to impaired temporal discrimination (Harrington et al., 1998). Taken together, we would suggest that deficits of timing behavior are likely to be more severe in patients with right hemisphere damage and most severe in patients with neglect following right parietal damage, although we recognize that much more work is needed on left hemisphere patients to determine the role of left parietal regions in timing-related behaviors (see Coull, 2004 for functional magnetic resonance imaging evidence of left parietal involvement in time perception). It does seem clear though, that time perception deficits in our neglect patient are not restricted to the visual domain. If time perception were a distributed function, we would have expected HW to perform poorly on the verbal task given the location of his lesion and his high-level comprehension difficulties.
In addition, if temporal processing was distributed and deficits in time perception, such as the ones previously reported by Danckert and colleagues (2007) in a group of eight neglect patients, were ascribed solely to visual neglect, we would have expected RR to perform well on the nonvisual tasks. Clearly, neither of these scenarios was supported here. It is more likely that interval time perception is centralized to a fronto-parietal network lateralized to the right hemisphere with extensive connections to the basal ganglia (Batelli et al., 2007). Finally, it is intriguing to consider the possibility that if the type of temporal perception examined here is in fact lateralized to the right temporo-parietal junction, a sparing of this component process in left hemisphere patients, such as HW, who showed mild right spatial neglect, may help to explain why their neglect symptoms are less severe. Of course, more research in right neglect patients (following left hemisphere lesions), while difficult, is necessary to address this controversial hypothesis.
CONCLUSION The finding here that a patient with left spatial neglect (RR) exhibited multimodal deficits in time perception suggests that impairments of temporal perception represent an important part of the neglect syndrome. It is becoming increasingly evident that models of neglect that refer solely to impaired attentional mechanisms are insufficient to fully explain the disorder. It seems clear that current models of neglect will need to consider nonspatial deficits, such as impaired temporal perception, in order to construct models that explain the full range and nature of impairments observed in the disorder. Manuscript received 7 December 2009 Manuscript accepted 5 March 2010 First published online 19 April 2010
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