Functional Anatomy of Pursuit Eye Movements in Humans as Revealed by fMRI

Laurent Petit and James V. Haxby

Laboratory of Brain and Cognition, National Institute of Mental Health, Bethesda, Maryland 20892


    ABSTRACT
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Petit, Laurent and James V. Haxby. Functional Anatomy of Pursuit Eye Movements in Humans as Revealed by fMRI. J. Neurophysiol. 82: 463-471, 1999. We have investigated the functional anatomy of pursuit eye movements in humans with functional magnetic imaging. The performance of pursuit eye movements induced activations in the cortical eye fields also activated during the execution of visually guided saccadic eye movements, namely in the precentral cortex [frontal eye field (FEF)], the medial superior frontal cortex (supplementary eye field), the intraparietal cortex (parietal eye field), and the precuneus, and at the junction of occipital and temporal cortex (MT/MST) cortex. Pursuit-related areas could be distinguished from saccade-related areas both in terms of spatial extent and location. Pursuit-related areas were smaller than their saccade-related counterparts, three of eight significantly so. The pursuit-related FEF was usually inferior to saccade-related FEF. Other pursuit-related areas were consistently posterior to their saccade-related counterparts. The current findings provide the first functional imaging evidence for a distinction between two parallel cortical systems that subserve pursuit and saccadic eye movements in humans.


    INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Visually guided eye movements are of two distinct types, saccadic and smooth pursuit (Dodge 1903). The primary function of the saccadic system is to orient gaze to visual targets for foveal viewing, whereas the function of the pursuit system is to maintain visual targets within the fovea when either the stimulus or the individual is in motion.

Elements of the neurophysiological and anatomic organization of both the saccadic and pursuit systems have been identified in nonhuman primate studies (for review see Eckmiller 1987; Keller and Heinen 1991; Leigh and Zee 1991; Wurtz and Goldberg 1989). In particular, neurophysiological studies in monkeys have differentiated saccade- and pursuit-related neural activity in various cortical regions, including the frontal eye field (FEF) (Gottlieb et al. 1993, 1994; McAvoy et al. 1991; Tian and Lynch 1996a), the supplementary eye field (SEF) (Heinen 1995; Tian and Lynch 1995), and the intraparietal sulcus (IPS) (Bremmer et al. 1997a; Colby et al. 1993). Further, pursuit-related activity has been described in the monkey middle temporal (MT) and medial superior temporal (MST) areas in the superior temporal sulcus (Bremmer et al. 1997b; Komatsu and Wurtz 1988).

Numerous clinical (e.g., for review Pierrot-Deseilligny et al. 1995) and functional brain imaging studies [positron emission tomography (PET)] (Anderson et al. 1994; Fox et al. 1985; Kawashima et al. 1996; O'Driscoll et al. 1995; O'Sullivan et al. 1995; Paus et al. 1993; Sweeney et al. 1996) and functional magnetic resonance imaging (fMRI) (Darby et al. 1996; Luna et al. 1998; Müri et al. 1996; Petit et al. 1997a) have consistently demonstrated that the FEF, SEF, and IPS (also referred to as the parietal eye field, PEF) constitute the dorsal cortical areas subserving visually guided saccades in humans.

Clinical studies have described smooth pursuit deficits related to lesions in cortical regions overlapping the FEF, SEF, and PEF but have also indicated a role for the lateral occipitotemporal cortex (the monkey MT/MST-homologous areas) (Heide et al. 1996; Morrow and Sharpe 1993, 1995; Pierrot-Deseilligny 1994). In contrast to functional imaging studies of saccadic eye movements, little attempt has been made to use PET or fMRI to explore the functional anatomy of pursuit eye movements in healthy humans. Only one published fMRI study has described the activation of the lateral occipitotemporal cortex during smooth pursuit (Barton et al. 1996). To our knowledge, there is no published report of activation of frontal and parietal areas during pursuit eye movements in healthy humans. Aside from our preliminary report on FEF activation in the current study (Petit et al. 1997a), previous frontal and parietal pursuit-related activations have been reported only in abstract form (Berman et al. 1996; Brandt et al. 1997; Colby and Zeffiro 1990; Sweeney et al. 1998).

The aim of this study was to investigate the functional anatomy of pursuit eye movements with fMRI. Subjects were instructed to follow a visual dot moving back and forth across the horizontal axis with a constant velocity. In addition to the involvement of the occipitotemporal cortex during pursuit, we predicted that the location of pursuit-related activity would lie within the dorsal cortical areas involved in the execution of visually guided saccades, namely the FEF, SEF, and PEF. Subjects also performed a visually guided saccade task to identify the saccade-related dorsal cortical areas and to test the possible existence of two functional subregions, one for the pursuit and one for the saccadic eye movements, in FEF, SEF, and PEF.

Preliminary results from this study have appeared previously in abstract form (Petit et al. 1997b) and in a short report on FEF activation (Petit et al. 1997a).


    METHODS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Subjects

Five healthy right-handed volunteers (2 males, 3 females, mean age 23.8 ± 4.1 yr) participated in this study. All were free of neurological or psychiatric illness, and there were no abnormalities on their structural magnetic resonance images. All subjects gave written, informed consent.

Task design

fMRI scans were obtained while subjects alternately performed either pursuit or visually guided saccadic eye movements and baseline control tasks. During the pursuit task, subjects were asked to follow a visual dot starting at the primary central eye position and moving back and forth across the horizontal axis with a constant speed of 25°/s and with a maximal amplitude of 12° on both sides. During the saccadic task, subjects were asked to execute saccadic eye movements toward a visual dot. The dot appeared first at the primary central eye position for 500 ms and then jumped randomly to different eccentric positions on the horizontal axis with a frequency of 2 Hz. The number of left and right saccadic eye movements were equated, with an average amplitude of 12° in both directions (range, 5-20°). The visual dot size was 0.4°. During the control task, subjects were in total darkness and were asked to keep their eyes open and to avoid moving their eyes.

Visual targets were generated by a Power Macintosh computer (Apple; Cupertino, CA) with SuperLab (Cedrus; Wheaton, MD) (Haxby et al. 1993) and were projected with a magnetically shielded liquid crystal display video projector (Sharp; Mahwah, NJ) onto a translucent screen placed at the feet of the subject. The subject was able to see the screen by the use of a mirror system. An RK-416PC pupil infrared eye tracking system (ISCAN; Cambridge, MA) was used to record the subject's eye movements outside the magnet to ascertain that the subject correctly understood the oculomotor tasks. Figure 1A illustrates a subject's eye position during the performance of the pursuit task and during the execution of horizontal saccadic eye movements.



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Fig. 1. A: sample of horizontal eye movement recordings in 1 subject (S1) outside the magnet during performance of the control task and both pursuit (top) and saccadic (bottom) eye movements. B: view of the human brain that illustrates the volumes of interest defined in this study, namely the precentral (FEF), medial superior frontal (SEF), and intraparietal (PEF) cortex, the precuneus, and the lateral occipitotemporal cortex.

Imaging procedure

All imaging used a 1.5 T GE Signa magnet (Milwaukee, WI) with a standard head coil. Interleaved multislice gradient echo echo-planar imaging (EPI) was used to produce 26 contiguous, 5-mm thick axial slices covering the entire brain [repetition time (TR) = 3,000 ms; echo time (TE) = 40 ms, flip angle 90°, field of view = 24 cm, 64 × 64 matrix, voxel dimensions = 3.75 × 3.75 × 5 mm]. Each subject performed four series contrasting saccade and control tasks and four series contrasting pursuit and control tasks, counterbalanced across subjects. For each series, subjects alternated 15 s of a control task and 15 s of an oculomotor task. Each series consisted of 60 scans with a complete duration of 3 min. The scanner was in the acquisition mode for 12 s before each series to achieve steady-state transverse magnetization.

For all studies, high-resolution volume spoiled gradient recalled echo structural 2.5-mm thick axial images were also acquired at the same locations as the EPIs (TR = 13.9 ms, TE = 5.3 ms, flip angle 30°) to provide detailed anatomic information.

Data analysis

The fMRI time series data were analyzed with multiple regression (Haxby et al. 1998). Activity related to smooth pursuit and visually guided saccades was contrasted independently, relative to activity during the control task. Both contrasts were constructed a priori such that the sum of values over the time series equals zero and the cross products of all pairs of contrasts are equal to zero, demonstrating orthogonality. Each of the time series was convolved with a Gaussian model of the hemodynamic response to produce the two regressors used in the analysis. The same parameters for the Gaussian model were applied to all voxels (lag = 4.8 s, dispersion = 1.8 s) (Maisog et al. 1995). Multiple regression simultaneously calculates a weighting coefficient for each regressor such that the sum of two regressors multiplied by their weighting coefficient provides the best fit to the data. All statistical results have a single voxel Z threshold of 2.33 (degrees of freedom corrected for correlation between adjacent time points). Statistical significance (P < 0.05) of a region of activation was determined with an analysis based on the spatial extent of each region to correct for multiple comparisons (Friston et al. 1994). For each subject, z-score maps and structural images were transformed into the standard stereotactic Talairach space (Talairach and Tournoux 1988) with the three-dimensional version of SPM (Friston 1995).

Activated voxels in three bilateral and two midline volumes of interest (VOIs, Fig. 1B) were analyzed for the location and spatial extent of the FEF (precentral cortex), the SEF (medial superior frontal cortex), PEF (intraparietal sulcus), MT/MST (the lateral junction of the occipital and temporal cortex), and the precuneus. By using the Talairach normalized structural images, this parcellation was achieved for each subject with software (Voxtool; General Electric; Buc, France) designed for brain segmentation, reconstruction of the external surfaces of both hemispheres, and display of sections in any orientation.

The VOI delineating bilateral precentral regions encompassed the precentral gyrus and the precentral sulcus, including 5 mm on the anterior bank of the sulcus from the junction with the superior frontal sulcus to the lateral convexity. Its inferior limit corresponded to the plane 30 mm above the bicommissural plane (AC-PC). This inferior limit was chosen to delineate the part of the precentral cortex that contains the FEF (Luna et al. 1998; Paus 1996).

The VOI delineating the dorsomedial part of the superior frontal gyrus consisted of 15 mm of cortex on each side of the interhemispheric fissure anterior to the vertical plane passing through the posterior commissure (VPC) and extending forward to the anterior convexity. Its inferior limit corresponded to the cingulate sulcus in the posterior part and to the plane 45 mm above AC-PC in the anterior part. This inferior limit was chosen to delineate the medial part of Brodmann's area 6 that contains both the supplementary motor area and the SEF (Picard and Strick 1996).

The VOI delineating bilateral intraparietal sulcal regions (IPS) included the cortex on both banks of the sulcus, namely both superior and inferior parietal lobules, from the junction with the postcentral sulcus to the posterior convexity. Its inferior limit corresponded to the plane 30 mm above the AC-PC plane and thus included the deepest part of the intraparietal sulcus. The term IPS is used to refer to the anatomically defined VOI, and the term PEF is used to refer to the part of IPS that is involved in eye movements.

The VOI delineating bilateral regions at the lateral junction of the temporal and occipital cortex was centered on the junction of the ascending limb of the inferior temporal sulcus and the lateral occipital sulcus. Its anterior limit corresponded to the coronal plane 40 mm posterior to the VAC plane and extending backward to the coronal plane 85 mm posterior to the VAC. Its superior limit corresponded to the plane 12 mm above the AC-PC plane, and its inferior limit corresponded to the plane 4 mm below the AC-PC plane. This region was defined to include the area that is homologous to monkey MT/MST, also called V5 (Tootell et al. 1995; Watson et al. 1993; Zeki et al. 1991). The lateral junction of the temporal and occipital cortex refers to the anatomically defined VOI, and the term MT/MST refers to the functionally defined part of that cortex.

The VOI delineating the precuneus consisted of 15 mm of parietal cortex on each side of the interhemispheric fissure, posterior to the marginal ramus of the cingulate sulcus and extending backward to the posterior convexity. Its inferior limit corresponded to the plane 30 mm above the AC-PC plane.

For each subject in each VOI, we determined the clusters of significantly activated voxels on the z-score map for each task and calculated the mean location in Talairach coordinates for those voxels. We tested the significance of differences between the Talairach coordinates for pursuit- and saccade-related activation in each VOI with a t-test (2-sample assuming unequal variances) with a correction of degrees of freedom based on the original voxel size. We also determined the centroids of pursuit- and saccade-related activity as the grand mean (± SD) of the individual subject means of the Talairach coordinates for pursuit- and saccade-related activation.


    RESULTS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

All subjects demonstrated both pursuit- and saccade-related activity in FEF, SEF, PEF, precuneus, and MT/MST, except for subject S4, who did not show any pursuit-related activity in the FEF and left PEF. In each cortical region, the activation during pursuit eye movements was smaller than during saccades in terms of spatial extent. Figure 2A indicates the mean Talairach coordinates across subjects for each region plotted on mean spatially normalized axial structural images of the five subjects. Figure 2B illustrates the spatial extents of significant activity across subjects calculated in each VOI for both eye movement tasks. Tables 1-5 show the Talairach coordinates of the mean location of pursuit- and saccade-related activity in the five anatomically defined VOIs. Figure 3 illustrates both pursuit- and saccade-related activity in all the cortical regions in one subject (S5).



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Fig. 2. A: centroid and SD of pursuit- (red) and saccade-related (yellow) activity shown on mean spatially normalized axial structural images of the 5 subjects. B: mean spatial extent of pursuit- (red) and saccade-related (yellow) activity in each volumes of interest (VOI) (in cm3) (see RESULTS for details). L: left; R: right.


                              
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Table 1. Talairach coordinates of the mean location of the pursuit- and saccade-related activity in frontal eye field


                              
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Table 2. Talairach coordinates of the mean location of the pursuit- and saccade-related activity in supplementary eye field


                              
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Table 3. Talairach coordinates of the mean location of the pursuit- and saccade-related activity in intraparietal sulcus


                              
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Table 4. Talairach coordinates of the mean location of the pursuit- and saccade-related activity in precuneus


                              
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Table 5. Talairach coordinates of the mean location of the pursuit- and saccade-related activity at the junction of the occipitotemporal cortex



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Fig. 3. Results from a single subject (S5) for the pursuit- (red outline) and saccade-related (yellow outline) activity overlaid onto the subject's Talairach normalized axial structural images. Level above the bicommissural plane is indicated for each axial section. L: left; R: right.

Four of 5 subjects showed bilateral pursuit-related activity in the FEF, and all subjects showed saccade-related activity. The centroid of pursuit-related activity was inferior to the centroid of saccade-related activity [Fig. 2A, right: mean difference in 4 subjects = 4 mm; P < 0.05 in 2/4 subjects; the 2 remaining subjects (S1 and S2) showed the same trend, but the difference of 2 mm did not reach statistical significance; left: mean difference in 4 subjects = 3 mm, P < 0.05 in 3/4 subjects; the remaining showed the opposite difference, Table 1]. The pursuit-related centroid was also significantly lateral to the saccade-related centroid in the right hemisphere (Fig. 2A; mean difference in 4 subjects = 9 mm; P < 0.005 in 3/4 subjects; the remaining subject did not show any difference, Table 1). The same trend was observed in the left hemisphere (Fig. 2A; mean difference in 4 subjects = 3 mm) but was statistically significant in only one subject (S2; Table 1). The spatial extent of pursuit-related activity was significantly smaller than the spatial extent of saccade-related activity in the left hemisphere (Fig. 2B; 1.5 vs. 5.4 cm3, respectively, P = 0.03). The same trend was observed in the right hemisphere but failed to reach the statistical significance (Fig. 2B; 1.3 versus 4.9 cm3, respectively, P = 0.06). Note also that the spatial extent in the right and left hemispheres was equivalent for pursuit- (1.5 vs. 1.3 cm3, respectively) and saccade-related activity (5.4 vs. 4.9 cm3, respectively). These findings are consistent with our previous report based on the same data in which we examined the Talairach coordinates of the maximum of pursuit- and saccade-related activity in the FEF (Petit et al. 1997a).

All subjects showed activation of the SEF during the two oculomotor tasks (Table 2). The centroid of pursuit-related activity was significantly posterior to the centroid of saccade-related activity (Fig. 2A; mean difference in 5 subjects = 8 mm; P < 0.05 in all cases, Table 2). The spatial extent of pursuit-related activity was significantly smaller than the spatial extent of saccade-related activity (Fig. 2B; 0.7 vs. 4.3 cm3, respectively, P = 0.03).

All subjects showed bilateral activation of the PEF, except one subject (S4), who did not show any pursuit-related activity in the left IPS. The centroid of pursuit-related activity tended to be posterior to the centroid of saccade-related activity in both hemispheres [Fig. 2A, right: mean difference in 5 subjects = 13 mm; P < 0.005 in 3/5 subjects; 1 subject (S1) showed the same trend, but the difference of 2 mm did not reach the statistical significance, and the remaining subject (S2) showed the opposite difference; left: mean difference in 4 subjects = 4 mm, P < 0.005 in 2/4 subjects; 1 subject (S1) showed the same trend, but the difference of 3 mm did not reach statistical significance, and the remaining subject (S3) showed the opposite trend, Table 3]. The spatial extent of pursuit-related activity was significantly smaller than the spatial extent of saccade-related activity in the right hemisphere (Fig. 2B; 1.2 vs. 7.5 cm3, respectively, P = 0.02). The same trend was observed in the left hemisphere but did not reach statistical significance (Fig. 2B; 2.0 vs. 4.5 cm3, respectively, P = 0.08)

All subjects showed activation of the precuneus during both pursuit and saccade tasks. As illustrated in Fig. 2A, the centroid of pursuit-related activity was significantly posterior and inferior to the centroid of saccade-related activity (mean difference for the y-coordinates in 5 subjects = 10 mm; P < 0.05 in all cases; mean difference for the z-coordinates in 5 subjects = 7 mm; P < 0.05 in 4/5 subjects, Table 4). Although the spatial extent of pursuit-related activity was smaller than the spatial extent of saccade-related activity, they did not differ significantly (Fig. 2B; 2.6 versus 4.5 cm3, respectively, P = 0.2).

All subjects showed bilateral activation of the occipitotemporal cortex during both pursuit and saccade tasks. The centroid of pursuit-related activity was significantly posterior to the centroid of saccade-related activity in most subjects [Fig. 2A, right: mean difference in 5 subjects = 8 mm; P < 0.05 in 4/5 subjects; the remaining subject (S2) showed no difference; left: mean difference in 5 subjects = 6 mm, P < 0.05 in 4/5 subjects; the remaining subject (S5) showed the same trend, but the difference of 3 mm did not reach statistical significance, Table 5]. The spatial extents of both pursuit- and saccade-related activity did not differ significantly (left: 2.0 vs. 2.6 cm3, right: 3.2 vs. 4.9 cm3, respectively, P = 0.2; Fig. 2B).


    DISCUSSION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

The performance of pursuit eye movements induced activations in a set of cortical regions known to subserve the control of saccadic eye movements, namely the FEF, SEF, PEF, precuneus, and MT/MST. In addition, the current findings provide the first functional imaging evidence for a distinction between the functional anatomy of the two cortical networks subserving pursuit and saccadic eye movements.

FEF

Execution of both pursuit and saccadic eye movements induced bilateral activation located in the precentral gyrus. This anatomic location corresponds to the human FEF as previously identified (for review see Luna et al. 1998; Paus 1996; Petit et al. 1996). Further, the mean locations of pursuit-related activity were most often inferior to the mean locations of saccade-related activity and also tended to be more lateral. This result was included in our preliminary report on this study but with a different measure of location, namely peak activity (Petit et al. 1997a). The current findings thus provide evidence for two different subregions in the human FEF related to the execution of smooth pursuit and saccadic eye movements. Aside from our preliminary report, previous pursuit-related FEF activation in healthy humans has been reported only in abstract form (Berman et al. 1996; Brandt et al. 1997; Colby and Zeffiro 1990; Sweeney et al. 1998). Clinical studies have also recently described an impairment of smooth pursuit eye movements related to lesions that encompassed both precentral and posterior part of superior and middle frontal gyrus (Heide et al. 1996; Lekwuwa and Barnes 1996; Morrow and Sharpe 1995; Rivaud et al. 1994).

In monkeys, both single-cell recording and intracortical microstimulation have shown that the monkey FEF also contributes to the control of smooth pursuit (Gottlieb et al. 1994; Tian and Lynch 1996a,b). The pursuit-related area encompasses a small part of the monkey FEF territory, posterior to the dominant saccade-related area. This study also identified a smaller pursuit-related subregion in human FEF compared with the saccade-related FEF, which parallels results observed in the monkey.

SEF

Both pursuit- and saccade-related activity were observed in the SEF in each subject. The mean location of the saccade-related SEF activation in this study was similar to the location of medial superior frontal activation previously observed during the execution of different types of saccadic eye movements, PET (Anderson et al. 1994; Dejardin et al. 1998; Fox et al. 1985; Lang et al. 1994; O'Sullivan et al. 1995; Paus et al. 1993; Petit et al. 1993, 1996; Sweeney et al. 1996) and fMRI (Darby et al. 1996; Luna et al. 1998). This study provided the first functional imaging evidence of a specific SEF activation during smooth pursuit eye movements, in the posterior part of the SEF. A similar distinction has also been reported recently in abstract form (Sweeney et al. 1998). A role for the SEF in pursuit eye movements has also been documented recently in the clinical literature (Heide et al. 1996; Lekwuwa and Barnes 1996; Morrow and Sharpe 1995).

In monkeys, the SEF was first defined as an area involved in saccadic eye movements (for review see Tanji and Shima 1996; Tehovnik 1995). Pursuit-related neurons were found in the monkey SEF (Heinen 1995; Schall 1991; Schlag et al. 1992), and smooth eye movements have been reliably evoked by microstimulation at low threshold (Tian and Lynch 1995, 1996a). To our knowledge, no topological relationship has been described between the pursuit- and saccade-related subregions in the monkey SEF. Most of the monkey SEF territory is concerned with saccadic eye movements, whereas only a single relatively small zone is responsible for pursuit eye movements. It is noteworthy that this study also identified a smaller pursuit-related area in human SEF than the saccade-related SEF, which parallels and extends results previously observed in the monkey.

PEF

Performing visually guided pursuit and saccadic eye movements induced distinct bilateral activation within the IPS, extending onto the gyral surfaces of both the inferior and superior parietal lobules, which identified the location of the PEF in each subject. To our knowledge, pursuit-related activity within the intraparietal sulcus has never been reported.

The mean location of the saccade-related PEF activation in this study was similar to the location of intraparietal activation previously observed during the execution of different type of saccadic eye movements, PET (Anderson et al. 1994; Kawashima et al. 1996; O'Sullivan et al. 1995; Paus et al. 1993; Petit et al. 1996; Sweeney et al. 1996) and fMRI (Darby et al. 1996; Luna et al. 1998; Müri et al. 1996). In patients, lesions overlapping IPS, in the superior part of the angular gyrus and supramarginal gyrus (area 39 and 40 of Brodmann), resulted in increased latency of visually guided saccades (for review see Pierrot-Deseilligny 1994, 1995). A recent clinical study also described an impairment of smooth pursuit eye movements related to lesions that encompassed the angular and supramarginal gyri and the adjacent occipitotemporal cortex (Heide et al. 1996).

In monkeys, it is well established that the PEF participates in both pursuit and saccadic eye movements (for review see Andersen and Gnadt 1989; Bremmer et al. 1997a; Colby et al. 1993; Lynch et al. 1977; Mountcastle et al. 1975; Sakata et al. 1983; Tian and Lynch 1996b). Tian and Lynch have recently demonstrated that there are two distinct groups of neurons labeled by injections in the pursuit- and saccade-related monkey FEF (Tian and Lynch 1996b). One group of PEF neurons, labeled by the pursuit-related FEF injection, is located dorsally and posteriorly to another group of PEF neurons labeled by the saccade-related FEF. It is noteworthy that this study also identified a pursuit-related area in human PEF that is posterior to the saccade-related PEF (Fig. 2).

MT/MST

Both pursuit- and saccade-related activations were observed bilaterally in the lateral occipitotemporal cortex along and at the junction of the ascending limb of the inferior temporal cortex and the lateral occipital sulcus, which is thought to be the human homologue of motion-sensitive MT/MST in the monkey and has also been called area V5 (Watson et al. 1993; Zeki et al. 1991). Although the location of the present MT/MST activation was not corroborated with a separate study at the response to visual motion without eye movements, its anatomic location and Talairach coordinates indicate that it corresponds to the motion-sensitive MT/MST (Corbetta et al. 1990; Tootell et al. 1995; Watson et al. 1993; Zeki et al. 1991). Our results provide the first evidence that MT/MST showed differential activity during the execution of smooth pursuit and saccadic eye movements.

A previous fMRI study showed that the lateral occipitotemporal cortex was more activated during smooth pursuit eye movement than during observation of a moving grating with the eyes still (Barton et al. 1996; see also in abstract form Brandt et al. 1997, 1998). Until now, however, visually guided saccade-related activity in the lateral occipitotemporal cortex has never been reported. A focal activation at the junction of parietal, temporal, and occipital cortex has only been reported recently during the execution of memory-guided saccades (Sweeney et al. 1998). Smooth pursuit deficits have been documented in the clinical literature (Heide et al. 1996; Lekwuwa and Barnes 1996; Pierrot-Deseilligny 1994), but no specific deficit during the generation of visually guided saccades has been described after occipitotemporal lesions (but see Heide et al. 1996). The extent to which the current saccade-related activity is only a response to moving targets and/or is related to extraretinal inputs such as eye movement signal during saccade cannot be resolved on the basis of current results and requires further investigation.

In monkeys, cortical area MT appears to be highly specialized for the analysis of visual motion (Komatsu and Wurtz 1988). Neural activity related to pursuit eye movements has been reported in both MT and MST areas (Komatsu and Wurtz 1988), and lesions of either MT or MST impair ocular pursuit area of moving targets (Dürsteler and Wurtz 1988). As emphasized recently (Tian and Lynch 1996b), there have been almost no studies that have investigated MT/MST areas in monkeys regarding their role in saccadic eye movement control.

It has been argued that the impairments of pursuit eye movements after MT/MST lesions could be due to degraded perception of the image motion of a target on the retina. However, MST also receives input related to eye movement during pursuit, but MT does not receive this extraretinal input (Newsome et al. 1988). MST therefore appears to be involved in the synthesis of the pursuit command, which requires information about both the motion of the target on the retina and current eye movement (Lisberger et al. 1987). In their fMRI study, Barton et al. (1996) concluded that pursuit-related activity in the lateral occipitotemporal cortex represented a combination of residual motion signals and extraretinal inputs, including both an attentional modulation and an eye movement signal during pursuit (Barton et al. 1996). The current findings are consistent with this conclusion.

Precuneus

Both pursuit- and saccade-related activity was observed in the precuneus in each subject. The mean location of the saccade-related precuneus activation was similar to the location of precuneus activation previously observed during the execution of saccadic eye movements (Anderson et al. 1994; Darby et al. 1996; Luna et al. 1998; Petit et al. 1996). The current study provided the first functional imaging evidence of a specific precuneus activation during smooth pursuit eye movements, posterior and inferior to the saccade-related precuneus activation. To our knowledge, no specific oculomotor role has been attributed to this medial cortical region.

In monkeys, a large area in the medial wall of the posterior parietal lobe [area 7m and the dorsomedial visual area (DM)] appears to play a role in oculomotor control (Cavada and Goldman-Rakic 1989a,b; Tian and Lynch 1996b). Both area 7m and DM appear to be involved in the transmission of visual motion information from the visual cortex to the FEF (Tian and Lynch 1996b). Although the homologies between areas in the posterior parietal cortex in monkeys and humans are still unclear, the current findings may parallel the organization of the medial part of the parietal cortex in monkeys.

Parallel corticocortical systems serving pursuit and saccadic eye movements

The current results support the hypothesis developed from monkey studies that there are two parallel corticocortical systems devoted to the control of purposeful eye movements (Tian and Lynch 1996b). One of these systems controls visual pursuit eye movements, and the other controls visually guided saccadic eye movements. Each system is composed of several interconnected subregions distributed across different cortical eye fields such as the FEF, SEF, PEF, MT/MST, and dorsomedial parietal visual areas. Within each cortical eye field, one group of neurons serves as a subregion in the network devoted to saccadic eye movements, and a second group, generally non overlapping, serves as a subregion devoted to pursuit eye movements (see Fig. 11 of Tian and Lynch 1996b).

The current fMRI study provides the first functional imaging evidence of such parallel corticocortical systems subserving pursuit and saccadic eye movements in healthy humans. Each network would be composed of the same cortical eye fields, namely the FEF, SEF, PEF, MT/MST, and precuneus, with different pursuit- and saccade-related subregions in each field. We observed some overlap between both pursuit and saccade-related subregions in each cortical eye field, which could be due to spatial resolution of fMRI. However, we have shown that pursuit-related areas could be distinguished from saccade-related areas in terms of both spatial extent and location.


    ACKNOWLEDGMENTS

We thank E. Hoffman, K. Keil, and J. Schouten for help with subject recruitment and scheduling; S. Courtney, J. Ingeholm, F. Lalonde, and V. Clark for assistance with eye movement and fMRI data acquisitions; and the staff of the National Institutes of Health in vivo nuclear magnetic resonance (MR) center for assistance with MR scanning.

This work was supported by the National Institute of Mental Health's Intramural Research Program. L. Petit was supported by the FYSSEN Foundation and Philippe Foundation.


    FOOTNOTES

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 20 May 1998; accepted in final form 3 February 1999.


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