Laboratorium voor Neuroen Psychofysiologie, Katholieke Universiteit Leuven, Belgium, , 1 MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, , 2 Wolfson Brain Imaging Centre, Cambridge, UK and , 3 Department of Nuclear Medicine, University Hospital Gasthuisberg, Leuven, Belgium
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Abstract |
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Introduction |
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In this study we examined whether either parietal or frontal activity is dependent on the frequency of spatial-attentional shifts within one hemifield. We hypothesized that parietal cortex is particularly sensitive to the direction of attention when spatial attentional shifts are required, as in the experiments reported by Corbetta et al. (Corbetta et al., 1993) and by Nobre et al. (Nobre et al., 1997
). This would fit with neuropsychological data indicating that parietal neglect patients are particularly deficient on tasks requiring shifts to or within the neglected hemifield (Baynes et al., 1986
; Posner et al., 1987
).
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Materials and Methods |
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Ten men between 40 and 65 years of age participated. All were strictly right-handed, free of psychotropic or vasoactive medication, had no neurological or psychiatric history, and had a normal brain magnetic resonance image. They gave their written informed consent in accordance with the Declaration of Helsinki. The experiment was approved by the Cambridge Local Research Ethics Committee.
Discrimination Conditions
Stimuli were displayed using a 20 in. Microtouch monitor at a viewing distance of 78 cm and mounted approximately perpendicular to the line of sight.
The experiment was run in blocks of 96 trials, trials within a block following one another in an uninterrupted series of ~144 s. Each trial had two parts: a cue display (Fig. 1A,B), indicating which of four display locations was to be attended on this trial, followed by a grating display (Fig. 1C
). The cue display lasted for 1000 ms (± random variation of 250 ms), and the grating display for 500 ms. The subject's task was to identify the orientation of the cued grating, making no response if it was horizontal or vertical (no go; 50% of trials), or pressing a key simultaneously with both thumbs if it was oblique (go; 50% of trials). The response window for any given trial extended from grating onset on this trial to grating onset on the following trial.
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A grating display followed the cue display. It consisted of four phase- randomized square-wave gratings (diameter: 3.0°; spatial frequency: 1 cycle/deg) (Fig. 1C). For each grating there were four possible orientations: the two canonical orientations, horizontal and vertical, and an oblique variant of each, rotated counterclockwise from the canonical. In each hemifield, one grating was horizontal or rotated from the horizontal axis and the other vertical or rotated from the vertical axis. The angle of rotation was adapted to each subject's performance during the training session. Between-block variations in location cueing defined the different discrimination conditions. Within one block only two locations were ever cued, those in the left (four blocks) or in the right (four blocks) visual field. Within a hemifield, either 20% (4 blocks) or 80% (4 blocks) of trials called for a switch of attended location from the preceding trial. Finally, the cued location could be marked either by a small circle among large circles (four blocks), or a large circle among small circles (four blocks). Complete crossing of these three factors produced eight unique conditions, each scanned once. Averaging across cue variants (small among large or large among small) produced two replications of each of the four main conditions: left field 20% shifts (L sust), left field 80% shifts (L shift), right field 20% shifts (R sust), right field 80% shifts (R shift). Such averaging removed confounding perceptual differences between the cue displays used during leftward or rightward attention conditions.
Before each run subjects were instructed explicitly to attend to either left or right. If the cue consisted of a small among large rings, they were instructed to attend to the small ring, and vice versa. Subjects were not informed about the proportion of shifts within each run.
Detection Control Conditions
During detection subjects responded with both thumbs on every trial, as soon as the grating display appeared. Rings presented in cue displays were all small (1.9°) in half of the detection blocks (Fig. 1D) and all large (3.0° ) in the other half (Fig. 1E
). Again, averaging between the two cue variants removed perceptual differences between cue displays used during detection or discrimination conditions.
Eye Movement Control
During training and scanning sessions horizontal eye movements were monitored with contact electrodes placed on the outer ocular canthi and a grounding electrode placed between the eyes. To ensure detection of gaze shifts at the onset or the end of the task, subjects were required to read aloud a digit appearing at the fixation point just before and just after the trial block. Electrooculographical recordings (EOG) were stored on disk. At the start of the experiment the EOG was calibrated for fixation and for horizontal saccades. After the session the EOG record from each trial block was inspected semiquantitatively for saccades or slow gaze drift.
Training Session
Subjects were trained prior to the scanning session during a 2 h training session. Runs of 100 left-field and right-field discrimination trials as well as detection trials were administered four times each. During discrimination practice runs shifts were required in 50% of trials except for the two last discrimination runs, during which shifts were required in 20% or 80% of trials. During the first half of the training session the cue interval duration was 1500 ms and the orientation difference (rotation from canonical) 12°. In the second half the cue interval was shortened to 1000 ms. Depending on the subject's accuracy the orientation difference was sometimes reduced to 8°. Subjects who could not maintain fixation or who did not reach a fixed accuracy criterion at the end of the practice session were excluded.
Image Acquisition
Measures of regional cerebral blood flow (rCBF) were acquired by use of a GE Advance Scanner operated in three-dimensional mode. The subject's head was immobilized using a canoe helmet and positioned parallel to the canthomeatal line using laser alignment beams. A transmission scan with a germaniumgallium source was obtained to correct for attenuation. It was also used for verifying the correct head position. For each condition 9 mCi 15O-labelled H2O was injected over a period of 20 s. The task was started at the same moment as the infusion; image acquisition began 50 s later. The first 90 s of image acquisition were used for further analysis. The task ended shortly after the end of image acquisition. An interval of at least 12 min separated two successive injections. During this interval subjects received a practice run with the direction of attention and the type of cue display matched to the condition scanned next. During the practice run shifts occurred in 50% of trials. The scan order was approximately counterbalanced between conditions across subjects.
The data were corrected for scatter, randoms and attenuation prior to reconstruction using three-dimensionally filtered back-projection (Kinahan and Rogers, 1989) with a Colsher filter of cut-off frequency 0.12 per mm. The brain tissue radiation count rate was used as a measure of rCBF.
Analysis
All subsequent data analysis was performed using Statistical Parametric Mapping version SPM96 (Wellcome Department of Cognitive Neurology, Institute of Neurology, London). In one subject one detection condition was rejected due to technical failure. The scans from each subject were realigned and stereotactically normalized to the Montreal Neurological Institute PET template in the Talairach space (Talairach and Tournoux, 1988; Friston et al., 1995a
). Data were analyzed using a fixed-effects general linear model determining parameters estimates for each condition in each subject with one replication (SPM96 option multi-study design, single subject per study, replications). The replication was provided by studying each of the conditions of interest once with a small and once with a large cue. Differences in cue size between conditions were not modelled. Subject-specific effects as well as interactions between subject and condition were modelled explicitly. This approach allows one to look at individual subject as well as group results. It differs from a classical group analysis where parameter estimates are determined only for each condition but not for each subject. Global brain activity was used as a covariate of no interest fixed at 50ml/dl/min (Friston et al., 1995b
). A smoothing filter of 16 x 16 x 16 mm3 was applied.
First we defined a general network for peripheral orientation discrimination. We subtracted the mean blood flow pattern obtained during detection from the mean across all discrimination conditions [(L sust + L shift + R sust + R shift) det)]. Second, we compared the blood flow patterns during leftward attention conditions to those obtained during rightward attention conditions, in both directions (main effect of direction of attention) [(L sust + L shift) (R sust + R shift) and the inverse]. Third, we compared the blood flow patterns during the 20% shift conditions to those obtained during the 80% shift conditions, in both directions (main effect of attention shifting) [(L sust + R sust) (L shift + R shift) and the inverse]. Finally, we also determined the interaction effects between direction and shifting [(L sust L shift) (R sust R shift) and (L shift L sust) (R shift R sust)].
To assess changes occurring anywhere in the brain we used a significance threshold of P < 0.05 corrected for the entire search volume. In addition three cortical regions of a priori interest left frontal convexity, left parietal and right parietal convexity (Fig. 2) were delineated manually by means of ANALYZE (Mayo Clinic Foundation, Rochester, MN) software (Fig. 2
) using anatomical features. To assess significance of changes within these regions the significance threshold was set at P < 0.05 corrected for the region's size (Worsley et al., 1996
) following a procedure that takes into account the region's shape and the study's smoothness estimate (Worsley et al., 1996
). This led to a corrected P < 0.05 significance threshold corresponding to a Z score of 3.02 in the frontal region, and to a Z score of 3.67 in each of the parietal regions. The corrected significance threshold for the frontal region was calculated separately from that of the parietal regions since the frontal region was used to address a separate question concerning inter-individual differences in left lateral frontal direction-sensitivity (see below). Corrected significance thresholds for the two parietal regions were also calculated separately from one another in order to enhance sensitivity.
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Results |
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Depending on performance in the training session, the orientation difference in the PET session was set at 8° in eight subjects, and 12° in the remaining subjects. Hits and false alarms from discrimination conditions were converted into the non-parametric sensitivity measure A (Snodgrass and Corwin, 1988) individually for each cell for each participant. A values vary from 0 to 1 where 0.5 is chance and 1.0 indicates perfect performance. A three-way, repeated-measures ANOVA was performed on accuracy as well as reaction time data. Two blocked variables consisted of the proportion of attentional shifts within a condition (20% or 80%) and the attended hemifield (left versus right). A third variable consisted of whether or not an individual trial required a spatial shift. When a trial belonged to a condition containing 80% of shift trials, accuracy was significantly worse than when it belonged to a condition that required shifting only in 20% of trials [F(1,9) = 15.0, P < 0.005] (Table 1
). When attention was to the right, accuracy was significantly worse than when attention was to the left [F(1,9) = 9.4, P < 0.05] (Table 1
). When a trial required a spatial shift, accuracy tended to be worse than when it did not [F(1,9) = 5.00, P = 0.052] (Table 1
). Furthermore, in such trials reaction times were significantly longer than when the trial did not require a shift [F(1,9) = 8.60, P < 0.05] (Table 1
). Finally, accuracy data demonstrated a significant three-way interaction effect between the three variables [F(1,9) = 6.72, P < 0.05] (Table 1
).
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Results of the overall discrimination minus detection contrast are shown in Table 3. Discrimination yielded significantly higher blood flow levels than detection in left fusiform gyrus, in the intraparietal sulci bilaterally, in right middle frontal gyrus, right precentral sulcus, right thalamus and in cerebellar hemispheres bilaterally. This network resembles that described in earlier studies (Corbetta et al., 1993
; Coull et al., 1996
; Vandenberghe et al., 1996
, 1997
; Nobre et al., 1997
).
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Discussion |
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The current experiment confirmed our earlier findings that left lateral frontal activity changed significantly with the direction of spatial attention (Vandenberghe et al., 1997). The current study differs in several aspects from our previous experiments revealing frontal direction-sensitivity. These modifications were introduced with the purpose of determining the generality of our previous results. Subjects responded manually instead of verbally, the response rule was gono go instead of conditional-associative, stimuli were shown on the horizontal meridian and not on the diagonal. The experiment was also carried out using a different PET scanner at a different site and subjects were older than in earlier studies. Orientation was the discriminandum in the current experiment but both orientation and displacement have been studied previously (Vandenberghe et al., 1997
). None of these modifications significantly altered the basic findings. When attention is directed to the left, blood flow levels in left frontal convexity are significantly higher than when it is to the right. The current data also prove that the left frontal direction-sensitive effect is not limited to paradigms where relevant events occur at one fixed peripheral location. In contrast to the left side, the right lateral frontal cortex did not demonstrate an effect of the direction of attention, though a weak effect of this sort appeared in our previous work (Vandenberghe et al., 1997
). Most probably the present negative result can be explained by a general involvement of right prefrontal cortex in our tasks, regardless of the direction of attention (Table 3
). This general effect may be so strong that any further modulatory effects elicited by varying the direction of attention are no longer detectable.
At present, we can only speculate about the processes reflected by the left lateral frontal blood flow changes. Since subjects performed fine perceptual discriminations of peripheral stimuli while fixating the center of the screen, one possibility is active suppression of saccades towards the relevant stimuli. Left frontal activity could reflect suppression of saccades to the left visual field. This, however, seems unlikely: although frontal lesions can disinhibit reflexive saccades (Butter et al., 1988; Paus et al., 1991
), it is saccades into the contralateral, not the ipsilateral field that are affected. There is no apparent reason why leftward covert attention would require more inhibition of rightward saccades than of leftward saccades. Alternatively, frontal activation could potentially relate to suppression of perceptual signals arising from the ignored contralateral hemifield. Bilateral simultaneous stimulation with almost identical stimuli may impose a substantial requirement for endogenous suppression of signals from the ignored hemifield. Attentional deficits after right frontal lesions point towards a possible role in suppression of signal processing. Habituation to peripheral stimuli in the left visual field, as measured by use of the Troxler fading paradigm, is diminished (Mennemeier et al., 1994
) after right frontal lesions. It is not known whether this contralateral over-orienting also occurs after left frontal lesions and why other functional imaging studies of unilateral attention using bilateral stimuli (Mangun et al., 1997
) did not reveal frontal blood flow differences. Possibly, the effect depends upon the degree of similarity between attended and ignored stimuli. To our knowledge, no brain-mapping studies have directly compared conditions with and without bilateral competitors to test this hypothesis. Furthermore, while we contrasted left and right hemifield conditions it is currently not known whether similar effects can be obtained when the distractor is to the left or the right of the target within the same hemifield. Finally, the right prefrontal involvement in all our discrimination tasks might also possibly be related to suppression of distractors regardless of their location, while the hypothetical left prefrontal role in suppression of distractors might be restricted to the contralateral field only.
The absence of any significant effect of shifting in the current study contrasts with neuropsychological evidence that parietal cortex is involved in disengagement of attention (Posner et al., 1987), which constitutes a critical component of shifting operations (Posner et al., 1987
). A functional imaging study in normals (Le et al., 1998
) has also provided evidence for a role of parietal cortex in non-spatial shifting. In that study subjects had to shift attention back and forth from color to shape each time a target occurred. This was compared to conditions where attention was sustained on a single stimulus feature. Intraparietal sulcus was activated bilaterally during the shifting condition. Other functional imaging studies of visuospatial shifting (Corbetta et al., 1993
; Nobre et al., 1997
; Gitelman et al., 1999
; Kim et al., 1999
) have reported parietal activation during spatial shifting of attention in comparison to baseline. However, in the absence of a condition requiring maintained attention within the same experiment these parietal activations cannot be specifically attributed to the shifting component.
Theoretically, subjects might have been dividing attention between the two gratings present in the attended hemifield rather than shifting and focusing depending on which grating was cued. Such a strategy would, however, lack efficiency: indeed, psychophysical experiments have demonstrated a behavioral cost during orientation-discrimination tasks when attention is divided between objects rather than focused on a single object (Duncan, 1993; Vandenberghe et al., 1997
; Morgan et al., 1998
). Most importantly, in the current experiment shifting trials were associated with slower responses and lower accuracies than maintaining trials (Table 1
). This provides strong behavioral evidence that subjects shifted attention during shifting trials relatively more so than during maintaining trials. Although the behavioral data indicate a distinction between shifting and maintaining trials, the absence of any parietal blood flow response to shifting in the current experiment must be interpreted with caution. First of all, the distinction between blocks of shifting trials and blocks of maintaining trials was only relative. We intentionally included 20% of shifting trials in the maintaining conditions and an equal proportion of maintaining trials in the shifting conditions so that predictability and working memory were entirely controlled for between the shifting and maintaining conditions. This may, however, have been at the expense of sensitivity. As a second experimental caveat, shifts between a peripheral location and the centre of the screen may have occurred between trials both during maintaining and shifting conditions. Such shifts may have gone undetected and have saturated any signal changes elicited by the difference between shifting and maintaining trials. To specifically discourage this possibility, cues appeared immediately after the offset of the previous grating display and remained on the screen until the onset of the next display, rendering shifts between periphery and centre less likely. As a final consideration, in the current, blocked-mode experiment, activity is integrated over a relatively long period of time. Even during shifting trials, subjects may spend a substantial amount of time maintaining their attention subsequent to the shifting operation. Event-related functional magnetic resonance imaging potentially provides us with a promising tool to investigate this possibility.
Likewise, the absence of an interaction between shifting and direction of attention must be interpreted with caution. We compared shifting within left or right hemifield but did not tease out the effects related to the direction of shifts, leftward or rightward. Parietal direction-sensitivity may be related to the direction of shifting and not only to the hemifield in which shifts occur (Mesulam, 1999).
To conclude, the current study provides further evidence that left frontal convexity is sensitive to the direction of spatial attention to the left or the right. Higher left frontal blood flow levels during leftward in comparison to rightward attention are a robust finding obtained across a variety of experimental conditions. The study also partially confirms previous findings of parietal direction-sensitivity (Corbetta et al., 1993; Nobre et al., 1997
). This parietal effect, however, is weaker than would be expected on the basis of neuropsychological data (Weintraub and Mesulam, 1987
). Also in contrast with predictions on the basis of neuropsychological evidence (Baynes et al., 1986
; Posner et al., 1987
; Posner and Petersen, 1990
), parietal responses were not significantly altered by the frequency of spatial-attentional shifts. The predicted responses may have gone undetected for experimental or methodological reasons. This said, strong parietal recruitment by attentional shifting is certainly questioned by these data.
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Notes |
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Address correspondence to Rik Vandenberghe, M.D., Ph.D., Cognitive Neurology and Alzheimer's Disease Center, Northwestern University Medical School, 320 East Superior Street Suite 11461, Chicago, IL 60611, USA. Email: r-vandenberghe{at}nwu.edu.
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