| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri
Submitted 28 February 2005; accepted in final form 13 April 2005
 |
ABSTRACT |
|---|
|
|
|
INTRODUCTION |
|---|
|
) and by the fact that either ablation or temporary inactivation results in a variety of deficits in both visually and memory-guided saccades (for a review, see Tehovnik et al. 2000).
FEF neurons are active around the time of onset of a visual stimulus ("visual" responses) and also immediately prior to a visually guided saccade ("movement" responses). This pattern is consistent with a role for the FEF in the sensory to motor transformation underlying visually guided eye movements (Bruce and Goldberg 1985). A subset of these neurons also responds in a delayed-saccade task in which the location of a transiently presented visual stimulus must be temporarily maintained for the execution of a memory-guided saccade (e.g., Funahashi et al. 1989). Such delay-period activity is often considered to be the neuronal substrate of spatial "short-term" or "working" memory (e.g., Fuster 1973; Fuster and Alexander 1971; Goldman-Rakic 1990).
Surprisingly, the role of visual, visuomovement, and movement neurons in memory-guided behavior has not been clearly defined. Funahashi and colleagues (1989) reported delay-period activity primarily in visual and visuomovement neurons, but this conclusion was based on a small sample of cells. More recently, Sommer and Wurtz (2000) found significant delay-period activity in 44% of the movement neurons with direct projections to the superior colliculus. This percentage approached the percentages found in visual and visuomovement neurons in the same study (47 and 57%, respectively). However, these responses were obtained late in a delay period and therefore may have been contaminated by anticipatory responses (e.g., Bruce and Goldberg 1985).
In the present study, we examined the role of FEF visual, visuomovement, and movement neurons in the maintenance of spatial information in a delayed-saccade paradigm. We quantified the response to the presentation of the visual target, the response during the delay period, and the response at the time of a memory-guided saccade. We found that the percentage of neurons with significant delay-period activity was similar across cell types. When neurons with significant delay-period activity were averaged together separately for each cell type, however, significant modulation was found in the population-averaged response of visual and visuomovement but not movement neurons. This seemingly contradictory finding was reconciled by the fact that the population of movement neurons was composed of two subclasses of neurons with complementary patterns of delay-period activity. Potential implications for the role of these subtypes in memory-guided behaviors are explored.
|
|
METHODS |
|---|
|
Animals were seated in a monkey chair (Crist Instrument, Hagerstown, MD). Stimuli were back projected by a CRT projector (Electrohome, Kitchener, Ontario, Canada) onto a touch panel located 25 cm in front of the animals. Unlike an LCD projector, a CRT projectorcasts no extraneous light, so that other than the visual stimuli, experiments took place in complete darkness.
Recordings were made from three adult male Rhesus macaques (Macaca mulatta). Recording chambers were placed flush with the skull at Horsley-Clarke coordinates of 25 mm anterior and 20 mm lateral. Structural MRI was used to confirm the placement of each chamber with respect to the arcuate sulcus and also to localize each recording site (Fig. 11; Caret and Surefit software packages; http://brainmap.wustl.edu/caret) (Van Essen et al. 2001).
|
) evoked a consistent saccadic eye movement were defined as FEF neurons. To make this determination, the animal began by fixating a blue target for 400 ms. The fixation target was extinguished and 100 ms later was followed with equal probability by either a 70-ms interval of stimulation or no stimulation. The fixation point reappeared 230 ms later on stimulation and no-stimulation trials. The animal was rewarded on every stimulation trial, and also on each no-stimulation trial in which the eyes remained within 4.5° of the extinguished fixation point. The same electrode was used for both microstimulation and unit recording within a given session.
Spatially selective FEF neurons were identified using a non-delayed saccade-plus-reach task. On a given trial, this task required the animal to execute a combined movement to one of 24 targets presented in one of eight directions at 14, 20, or 28° of eccentricity. The response field (RF) of each spatially selective neuron was then carefully mapped using a delayed-response task (Dickinson et al. 2003) (target-delay-cue task). In two animals, memory responses were then tested during interleaved delayed-saccade and -reach trials (only the results of delayed-saccade trials are presented; see following text). As a control, memory responses were also obtained during delayed-saccade trials in a third animal that had never been trained on reach-related tasks. In this animal, spatially selective neurons were identified and mapped using saccade-only trials.
Delayed-saccade task
Each delayed-saccade trial began when the animal fixated and, in two of the three animals, touched a central blue fixation point for 500 ms. A red target was then presented for 300 ms in one of two symmetric locations, chosen to fall either inside of the RF or on the opposite side of the fovea, outside of the RF. Eccentricity was adjusted based on the size of the stimulation-evoked eye movement and the responses during the saccade-plus-reach and mapping tasks. Each monkey was required to maintain central fixation throughout the delay period (800 ms in the 1st 2 animals; 1.4–5.6 s in the control animal). The end of the delay period was signaled by the offset of the fixation point. Each monkey then had 
700 ms to saccade to within 7° of the location at which the target had previously appeared. Saccade reaction time was 162 ± 33 (SD) ms in constant delay period trials (1st 2 animals) and 225.3 ± 14 ms in variable delay period trials where the timing of the movement could not be anticipated (3rd animal). Saccades terminated within 3.30 ± 1.34° (mean ± SD) of the target location.
Because the data reported in the present study were collected as a part of a larger study examining effector specificity in FEF, delayed-reach trials were interleaved with delayed-saccade trials in two monkeys. (Again, it is important to note that the 3rd animal performed only delayed-saccade trials.) Delayed-reach trials were similar to delayed-saccade trials but were signaled with a green rather than a red peripheral target and required a peripheral reach while maintaining central fixation. In the present study, however, we examine only the results from the delayed-saccade trials. In each animal, correct trials were rewarded and incorrect trials (e.g., trials on which the animal moved prematurely, moved too late, or landed outside the target window) were aborted (<20% of all trials). Aborted trials incurred a short (
1 s) time out. Animals performed 10 interleaved repetitions of each of two trial types (saccades into or out of the RF). Eye position was monitored using a scleral search coil (CNC Engineering, Seattle, WA). All tasks were conducted in a dark sound-attenuated room.
Data analyses
The classification of FEF neurons into visual, visuomovement, and movement cell-types was based on visual and motor responses in the delayed-saccade task. The visual response (the interval spanning 50–300 ms after target appearance) was measured relative to baseline activity (the interval spanning 200–400 ms before target appearance) and the peri-saccadic response (100-ms interval prior to saccade onset) was measured relative to late delay-period activity (the interval spanning 200–300 ms prior to saccade onset). Measurements of movement responses relative to late delay activity prevented prolonged delay-period responses from being misinterpreted as movement-related responses (see Sommer and Wurtz 2000 for a similar subtraction). Changes in the duration or alignment of the intervals used to measure the responses (e.g., 50 to 150 or 150 to 300 ms visual interval; 100 ms presaccadic interval aligned on the onset of the saccade or –100 to 100 ms interval surrounding the peak velocity of the saccade) had minimal effect on the classification of cell types and had no effect on the conclusions of the study.
A visuomotor index (Fig. 1 A) was then constructed for each neuron by calculating the contrast ratio between visual and motor responses ([motor–visual]/[motor+visual]). For this purpose, visual responses that were less than baseline and peri-saccadic responses that were less than the late delay-period activity were rounded to zero. In addition to this continuous measurement, we also employed a discrete categorization. Neurons with indices from –1.0 to –0.4 were classified as visual neurons, those between –0.4 and 0.4 as visuomovement neurons, and those from 0.4 to 1.0 as movement neurons (Fig. 1B). Visual neurons were largely responsive to the presentation of the target and were largely nonresponsive immediately prior to the saccade, whereas visuomovement neurons were equally responsive during both intervals. Movement neurons, in contrast, were largely nonresponsive to the presentation of the target but were largely responsive immediately prior to the saccade. It is important to note that although we separated continuous data into discrete categories, we would not argue that these categories necessarily represent three distinct subtypes of FEF neurons. Indeed, even Bruce and Goldberg (1985) noted in their classic paper, which defined visual, visuomovement, and movement neurons, that the categorization of these subtypes is somewhat arbitrary because the underlying distribution is continuous. It is also important to note that while the criterion value of ± 0.4 was selected post hoc to approximate previously reported percentages of each cell type (Bruce and Goldberg 1985), large changes in the criterion values used for classification (e.g., 0.1 or 0.8 instead of 0.4) had no effect on our conclusions (see RESULTS).
|
|
|
RESULTS |
|---|
|
To examine the relationship between delay-period activity and FEF cell type, the activity on preferred trials was used to classify cells into visual, visuomovement, and movement categories, after Bruce and Goldberg (1985) (see METHODS). Visually related responses were quantified using the interval spanning 50 to 300 ms after the onset of the target. Motor-related responses were quantified using the 100-ms interval prior to the memory-guided saccade. Visuomotor index values, calculated as the contrast ratio between visual and motor responses, spanned the interval from –1 to +1, with peaks at +1, 0, and –1 (Fig. 1A). A random pairing of the FEF visual and movement responses would produce a bimodal distribution of indices with peaks at +1 and –1 (not shown). We tested the hypothesis that the seemingly tri-modal distribution that we observed reflected a nonrandom pairing of visual- and motor-related responses. Although the actual distribution was significantly different from uniform (Kolmogorov-Smirnov test, P = 0.003), it was not significantly different from the bimodal distribution that would be obtained by a random pairing (Kolmogorov-Smirnov, P = 0.87).
Neurons were further tested for the presence or absence of significant delay-period activity (assessed as the difference in activity between preferred and null trials in the 450–950 ms after target onset). Fifty-seven percent (17 of 30) of visual neurons, 32% (10 of 31) of visuomovement neurons, and 58% (15 of 26) of movement neurons had significant delay activity. The population-averaged time course of activity is presented for each cell type in Fig. 2. Responses from neurons with and without significant delay activity are separated (left and right, respectively). Solid traces represent activity on preferred trials and dashed traces represent activity on null trials.
|
At the population level, delay-period activity was strongest in visual neurons and weakest in movement neurons (Fig. 2, left). Delay activity in visual neurons was maintained at a constant level (preferred minus null = 15.0 ± 6.1 spike/s, P = 0.02) and continued through the execution of the saccade (top left). Visuomovement neurons maintained slightly weaker delay activity (12.6 ± 2.2 spike/s; P = 0.0003) that increased markedly just prior to the execution of the saccade (middle left). Surprisingly, despite the fact that the population-averaged response of movement neurons consisted of only those movement neurons with significant delay-period activity, the population-averaged response of these neurons was not significant (0.4 ± 2.2 spike/s, P = 0.87; bottom left).
What could account for the presence of delay activity in individual movement neurons, and the absence of delay activity in the population-averaged response of these neurons? To examine the activity of individual neurons more closely, we plotted the delay-period activity of individual neurons as a function of the visuomotor index (Fig. 3 A). Neurons with significant delay activity are represented by filled circles, whereas neurons without significant delay activity are represented by unfilled circles. There was a significant inverse correlation between delay-period activity and the visuomotor index among neurons with significant delay activity (r = –0.4; P = 0.01). Closer examination, however, reveals an interesting pattern. Overall, similar percentages of visual and movement neurons (60%) showed significant delay activity (Fig. 3B, unfilled bars). But whereas most visual and all visuomovement neurons had greater delay activity in the preferred than in the null direction (black bars), this was true of less than half of movement neurons. Fully 60% of the movement neurons with significant delay activity (9 of 15) were more active during the delay preceding saccades in the null direction than during the delay preceding saccades in the preferred direction (gray bars). We will refer to those neurons with greater delay activity in the preferred direction than in the null direction as "canonical" neurons (solid black circles and black bars in Fig. 3) and those neurons with the reverse pattern as "paradoxical" neurons (gray circles and gray bars). When only canonical cells were considered, there was no longer a significant relationship between delay activity and visuomotor index.
|
|
|
). In our analysis, the area under a ROC curve reflects the accuracy of an "ideal observer," who uses the delay-period activity of individual neurons on individual trials to determine whether the target appeared inside or outside of the RF. This value is plotted for individual cells as a function of the visuomotor index in Fig. 6. As is evident in the figure, ROC analysis cleanly segregates neurons into canonical (black circles) and paradoxical (gray circles) subtypes. The mean ROC values for canonical visual, visuomovement, and movement neurons were 0.93, 0.86, and 0.86, respectively, whereas the mean ROC values for paradoxical visual and movement neurons were 0.91 and 0.81, respectively. (Because paradoxical neurons have greater activity in the null direction than in the preferred direction, the ROC value for paradoxical neurons is reported as 1 minus the ROC value. For graphical purposes, however, we did not perform this subtraction on paradoxical neurons in Fig. 6.) These results demonstrate that the amount of information conveyed by neurons with significant delay activity is relatively independent of cell type (visual, visuomovement, or movement) or subtype (canonical or paradoxical).
|
|
0.4 were classified as "movement neurons." However, as is evident in Fig. 8, shifting the criterion value anywhere from 0.0 to 0.9 neither changes the mean delay-period activity of canonical and paradoxical neurons nor changes the cancellation of delay-period activity in the population of movement neurons.
|
Although initial inspection of Fig. 7 suggests that canonical and paradoxical subtypes were otherwise functionally equivalent, closer inspection reveals that the onset of the presaccadic activity occurred earlier in canonical neurons than in paradoxical neurons. Because the onset of the saccade-related activity can be gradual and occurs around the same time as fluctuations in late delay-period activity, we instead quantified the peak of the saccade-related burst, which was completely unambiguous in both individual neurons and in the population responses. The peak of the saccade-related burst was determined as the point of maximal activity in the 300-ms interval surrounding the onset of the saccade. The results of this analysis indicated that the peak of the burst occurred 20 ms before saccade onset in the population of canonical neurons, but 38 ms after saccade onset in paradoxical neurons. These values, obtained at the population level, are similar to the mean values obtained across all individual canonical neurons (–19.0 ± 5.6 ms) and across all individual paradoxical neurons (34.7 ± 12.0 ms).
Cumulative histograms showing the timing of the peak of the saccade-related burst, relative to saccade onset, in individual movement neurons with canonical, paradoxical, and for additional comparison, nonsignificant delay-period activity, are presented in Fig. 9. These histograms reveal that 50% of canonical neurons reached peak activation 27 ms prior to the onset of the saccade, whereas 50% of paradoxical neurons reached peak activation 53 ms after the onset of the saccade. The relationship between percentage and timing was strikingly similar in nonsignificant and canonical movement neurons (21 ms prior to the onset of the saccade in nonsignificant neurons; notice the overlap in histogram traces at 50%), suggesting that nonsignificant and canonical movement neurons may be similarly involved in triggering saccades. Moreover, this similarity suggests that differences between canonical and paradoxical neurons in peak activation times are not merely a byproduct of differences in delay-period activity. Taken together, these results provide additional support for the hypothesis that paradoxical and canonical neurons reflect two distinct subpopulations of movement neurons. Moreover, these results suggest that, unlike nonsignificant and canonical movement neurons, paradoxical movement neurons may not be directly involved in triggering saccades.
|
Finally, we examined the possibility that the delay-period activity found in movement neurons was an artifact of the experimental procedure used in the present study. We tested two possibilities. First, because the duration of the delay period was constant, it is possible that the delay-period activity in movement neurons was due to the animals' anticipation of the upcoming movement. Second, the animals were also trained on a delayed-reach task, the trials of which were interleaved with delayed-saccade trials. Given the tight coupling between the saccade and reach systems (e.g., Abrams et al. 1990; Bekkering et al. 1994; Snyder et al. 2002), it is possible that either the training or the interleaving of delayed-reach trials may have influenced the pattern of neural activity during delayed-saccade trials. To rule out these two possibilities, we examined delay-period activity in a third animal in a delayed-saccade task with variable delay periods (1.4, 2.8, and 5.6 s). It is important to note that this control animal neither trained on, nor performed reach-related tasks of any kind. Otherwise, the procedure for the control animal was the same as the procedure used for the first two animals.
An example of a neuron with paradoxical activity from the control animal is presented in Fig. 10. Only data from trials with a 5.6-s delay period are shown. The presence of a pronounced presaccadic response for movements up and to the left, and the absence of a visual response for targets in any location, establishes this neuron as a movement neuron. During the delay, the cell was minimally active for movements in the preferred direction (up left) and maximally active for movements in the opposite, null direction (down right). The paradoxically opposed tuning of delay-period and saccade-related activity is evident in the tuning curve presented in the center of Fig. 10. Notice that those locations had the strongest saccade-related responses (thin line) also had the weakest delay-period responses (thick line), and vice versa. This pattern of tuning was independent of the delay interval (not shown). The presence of both canonical (not shown) and paradoxical neurons in the third monkey suggests that the results found in the first two monkeys were not due to fixed delay intervals or interleaved reach trials.
|
Structural MRI was used to confirm the placement of each chamber with respect to the arcuate sulcus and also to localize each recording site (Caret and Surefit software packages, http://brainmap.wustl.edu/caret) (Van Essen et al. 2001). To view the anatomical locations of recording sites on a single surface, MRI data from both monkeys were first warped to a common atlas space. Recording sites from both monkeys were then projected onto the common atlas (Fig. 11). These sites are color coded by cell type (left; visual neurons, blue; visuomovement neurons, green; movement neurons, yellow) and delay-period activity (right; canonical, red; paradoxical, white; nonsignificant delay activity, gray). To view recording sites in the sulci, a "flat map" was also constructed from the common atlas (bottom). With respect to medial-lateral topography, consistent with Sommer and Wurtz (2000), movement neurons tend to be clustered medially while visual neurons tend to be clustered laterally (Fig. 11, left). Because most paradoxical neurons were movement neurons, paradoxical neurons also tend to be clustered medially, whereas canonical neurons tend to be clustered laterally (Fig. 11, right). There was no obvious anterior-posterior topography by cell type or delay-period activity.
As is evident in Fig. 11, the majority of units were localized to the anterior bank of the arcuate sulcus (AS) and to the gyral surface just anterior to the AS. This localization of "low threshold" (i.e., <50 µA) recording sites is consistent with previous localizations of low-threshold FEF (e.g., Bruce et al. 1985). Although the continuation of low-threshold recording sites onto the gyral surface is consistent with previous accounts, the continuation of low-threshold recording sites to the posterior bank of the principle sulcus (PS) is not. It is likely, however, that the localization of recording sites proximal to the PS was the result of an artifact beneath the recording chambers of both animals in the structural MRI. This artifact effectively compressed the anterior extent of the gyral surface between the AS and the PS, resulting in the projection of anterior gyral recording sites onto the posterior-most aspect of the PS. Because this artifact was likely due to the absence of bone above the arcuate and principle sulci, we would suggest that for the most accurate reconstruction, the structural MRI be performed both before the craniotomy for accurate reconstruction and after the craniotomy for verification of the chamber location.
|
|
DISCUSSION |
|---|
|
In one subclass of movement neurons, the spatial tuning of delay-period activity was similar to that of presaccadic activity (Fig. 7A). More specifically, the spatial location that was associated with maximum delay-period activity evoked the maximum presaccadic response, whereas the spatial location that was associated with minimum delay-period activity evoked the minimum presaccadic response. The spatial alignment of excitatory responses is found not only in FEF (e.g., Chafee and Goldman-Rakic 1998; Funahashi et al. 1989), but also in many other areas of the brain. For example, visual, delay, and presaccadic activities in LIP neurons tend to be spatially aligned, both within and across tasks (Barash et al. 1991). Presaccadic activity in a delayed-saccade task and delay-period activity in a delayed-reach task are often aligned within PRR neurons (Snyder et al. 1998). The directions of greatest "build-up" and "burst" activity within single neurons in the superior colliculus are commonly aligned with one another (although dissociations are sometimes observed; see for example, Fig. 3, C and D, of Dorris et al. 1997); and all manner of visual, saccade-related, and reach-related responses are aligned within and across tasks in V6A neurons, a finding referred to as a "global tuning field" (Battaglia-Mayer et al. 2000). Many models of spatial memory capitalize on the idea that memory tuning is similar to that of visual and presaccadic tuning (for a recent review, see Constantinidis and Wang 2004). Because aligned tuning seems to be the rule and not the exception, we refer to neurons with such properties as "canonical" neurons.
In the other subclass of movement neurons, the spatial tuning of delay-period activity was opposite that of presaccadic activity (Fig. 7B). More specifically, the spatial location that was associated with maximum delay-period activity evoked little or no presaccadic response, whereas the spatial location that was associated with minimum delay-period activity evoked the maximum presaccadic response. In the latter case, minimal delay-period activity was often reduced to below baseline. Because it is difficult to reconcile this pattern with the simple idea that excitatory delay-period activity leads more or less directly to presaccadic activity, we refer to these neurons as "paradoxical." The term paradoxical has been used previously by Zhang and Barash (2000) to describe neurons that are responsive to the onset of a target that appears in the null direction, but signals a saccade in the preferred direction. Our use of the same term is not meant to imply that these are similar populations or effects.
The reduction of delay-period activity to a level below baseline is not, in itself, unusual. Inhibition of delay activity is a common finding in canonical FEF neurons, occurring on trials in which saccades are planned in the null direction (Funahashi et al. 1989). (Here and elsewhere we use "inhibition" to refer to a decrease in activity and not to the mechanism by which this decrease is accomplished.) In combination with excitatory delay activity on preferred direction trials, this inhibition creates a "push-pull" response pattern. Push-pull designs are familiar features of electronic circuits, where they are used to improve linearity or to minimize the effects of extraneous factors such as temperature on circuit elements. Push-pull responses have been described in many parts of the brain, ranging from the vestibular periphery (Wilson and Melvill-Jones 1979) to the primary motor cortex (Georgopoulous et al. 1993). In the brain, push-pull designs may improve spatial tuning (Funahashi et al. 1989), help drive agonist-antagonist muscle pairs or extend the range or signal-to-noise ratio of sensory systems. Thus the inhibition found in paradoxical neurons is not in itself unusual. What is unusual is the fact that the delay-period activity and presaccadic responses of paradoxical neurons are tuned in opposite directions.
Neurons with inhibitory delay-period activity and excitatory saccade-related activity in the same direction were previously described by Funahashi and colleagues (1989). The saccade-related activity of these neurons, however, unlike the presaccadic activity of paradoxical neurons, is entirely post-saccadic, occurring hundreds of milliseconds following the onset of the saccade (see Fig. 10 in Funahashi et al. 1989). This pattern of activity is consistent with that of canonical neurons, which often show an excitatory postsaccadic response for saccades executed in the null direction (e.g., Barash et al. 1991; Funahashi et al. 1989).
The pattern of activity found in paradoxical neurons is also inconsistent with the pattern of activity found in "don't look" neurons in FEF (Hasegawa et al. 2004). "Don't look" neurons respond in a nonmatch-to-sample task and appear to encode the direction in which a saccade is not to be executed. Paradoxical neurons, in contrast, appear to prevent a saccade in the direction in which a saccade will be made, albeit not immediately. This is suggested by the fact that canonical and paradoxical delay-period activities so neatly cancel one another (compare the 2 left-hand panels of Fig. 7 with the bottom left-hand panel of Fig. 2). By carrying a negative copy of the canonical delay-period signal, paradoxical neurons may represent an active mechanism to prevent the premature execution of a saccade. This notion assumes that a single read-out mechanism pools the responses of the two neuron types. This assumption could be tested by using anatomical or physiological methods to compare the projections of canonical and paradoxical neurons (e.g., Sommer and Wurtz 2000).
Canonical and paradoxical neurons differ not only in their spatial tuning characteristics, but also in the timing of their saccade-related activity (Figs. 7, A and B, and 9). Canonical neurons are likely involved in triggering memory-guided saccades. This view is supported by our finding that their peak saccade-related activity occurs before saccade onset and by the work of Schall and colleagues (Hanes and Schall 1996) showing that presaccadic FEF activity is tightly correlated with saccade onset. That peak activity occurs after saccade onset in paradoxical neurons, however, suggests that these neurons may not be directly involved in triggering memory-guided saccades. Because the paradoxical peak occurs, on average, 60 ms after the peak in canonical neurons, we speculate that the saccade-related activity of paradoxical neurons may reflect a corollary discharge. This signal could be driven directly by canonical neurons, or may reflect a canonical signal that has been passed through the superior colliculus back to FEF, perhaps via interneurons in the mediodorsal thalamus (Sommer and Wurtz 2004). The 60-ms timing difference, along with the fact that the early anticipatory build-up of activity that occurs late in the delay period of canonical neurons is nearly absent in paradoxical neurons, is consistent with a relatively indirect pathway.
It is important to note that paradoxical neurons are not simply neurons driven by inhibitory interneurons, which are in turn driven by canonical neurons; in this case, the very robust saccade-related responses of paradoxical neurons would be inhibitory rather than excitatory (Fig. 7, bottom left-hand panel). We suspect that there may be inhibitory interconnections between canonical and paradoxical neurons but that the strong excitatory movement response in paradoxical neurons is evidence of additional strong influences on these cells. Further experiments as well as computational modeling will be required to further explore these issues. Particular neural architectures could be simulated as well as tested to determine the most promising configurations. Finally, one might test the hypothesis that an imbalance in canonical and paradoxical delay-period activity could underlie the deficits in saccade inhibition seen in certain clinical populations (e.g., LeVasseur et al. 2001).
The present experiments demonstrate that visual, visuomovement, and movement neurons maintain roughly equal amounts of spatial information during the delay period of a memory-guided saccade task. This finding is inconsistent with previous suggestions that delay-period activity is primarily found in visual and visuomovement neurons (Funahashi et al. 1989). Delay-period activity may be problematic for movement neurons because activity above threshold may lead to the initiation of a saccade (Hanes and Schall 1996). We suggest that to prevent the premature initiation of a planned saccade, the activity of the population of paradoxical movement neurons effectively cancels out the activity of the population of canonical neurons during the delay period. This mechanism would allow spatial information to be maintained throughout the delay period without that activity reaching or even approaching the threshold for saccade initiation. During the delay, the spatial information may be used by canonical neurons to help prepare the upcoming saccade. The fact that paradoxical movement neurons are present in numbers just sufficient to balance the activity of canonical movement neurons, whereas paradoxical visual and visuomovement neurons are infrequent or absent, is further evidence for the special role of movement neurons in controlling the timing of the initiation of saccades.
|
|
GRANTS |
|---|
|
|
|
ACKNOWLEDGMENTS |
|---|
|
|
|
FOOTNOTES |
|---|
Address for reprint requests and other correspondence: B. M. Lawrence, Dept. of Anatomy and Neurobiology, Washington University School of Medicine, Box 8108, St. Louis, MO 63110 (E-mail: bonnie{at}eye-hand.wustl.edu)
|
|
REFERENCES |
|---|
|
Barash S, Bracewell RM, Fogassi L, Gnadt JW, and Andersen RA. Saccade-related activity in the lateral intraparietal area. I. Temporal properties: comparison with area 7a. J Neurophysiol 66: 1095–1108, 1991.
Bekkering H, Adam JJ, Kingma H, Huson A, and Whiting HT. Reaction time latencies of eye and hand movements in single- and dual-task conditions. Exp Brain Res 97: 471–476, 1994.[Web of Science][Medline]
Bruce CJ and Goldberg ME. Primate frontal eye fields. I. Single neurons discharging before saccades. J Neurophysiol 53: 603–635, 1985.
Constantinidis C and Wang XJ. A neural circuit basis for spatial working memory. Neuroscientist 10: 553–565, 2004.
Dias EC and Segraves MA. Muscimol-induced inactivation of monkey frontal eye field: effects on visually and memory-guided saccades. J Neurophysiol 81: 2191–214, 1999.
Dickinson AR, Calton JL, and Snyder LH. Nonspatial saccade-specific activation in area LIP of monkey parietal cortex. J Neurophysiol 90: 2460–2464, 2003.
Dorris MC, Pare M, and Munoz DP. Neuronal activity in monkey superior colliculus related to the initiation of saccadic eye movements. J Neurosci 17: 8566–8579, 1997.
Funahashi S, Bruce CJ, and Goldman-Rakic PS. Mnemonic coding of visual space in the monkey's dorsolateral prefrontal cortex. J Neurophysiol 61: 331–349, 1989.
Fuster JM. Unit activity in prefrontal cortex during delayed-response performance: neuronal correlates of transient memory. J Neurophysiol 36: 61–78, 1973.
Fuster JM and Alexander GE. Neuron activity related to short-term memory. Science 173: 652–654, 1971.
Georgopoulos AP, Taira M, and Lukashin A. Cognitive neurophysiology of the motor cortex. Science 260: 47–52, 1993.
Goldman-Rakic PS. Cellular and circuit basis of working memory in prefrontal cortex of nonhuman primates. Prog Brain Res 85: 325–335, 1990.[Medline]
Hanes DP and Schall JD. Neural control of voluntary movement initiation. Science 274: 427–430, 1996.
Hasegawa RP, Peterson BW, and Goldberg ME. Prefrontal neurons coding suppression of specific saccades. Neuron 43: 415–425, 2004.[CrossRef][Web of Science][Medline]
LeVasseur AL, Flanagan JR, Riopelle RJ, and Munoz DP. Control of volitional and reflexive saccades in Tourette's syndrome. Brain 124: 2045–2058, 2001.
Lewis JW and Van Essen DC. Mapping of architectonic subdivisions in the macaque monkey, with emphasis on parieto-occipital cortex. J Comp Neurol 428: 79–111, 2000.[CrossRef][Web of Science][Medline]
Metz CE. Basic principle of ROC analysis. Semin Nuclear Med VIII: 283–298, 1978.
Munoz DP. Commentary: saccadic eye movements: overview of neural circuitry. Prog Brain Res 140: 89–96, 2002.[Web of Science][Medline]
Schiller PH and Chou I. The effects of frontal eye field and dorsomedial frontal cortex lesions on visually guided eye movements. Nat Neurosci 1: 248–253, 1998.[CrossRef][Web of Science][Medline]
Snyder LH, Batista AP, and Andersen RA. Change in motor plan, without a change in the spatial locus of attention, modulates activity in posterior parietal cortex. J Neurophysiol 79: 2814–2819, 1998.
Snyder LH, Calton JL, Dickinson AR, and Lawrence BM. Eye-hand coordination: saccades are faster when accompanied by a coordinated arm movement. J Neurophysiol 87: 2279–2286, 2002.
Sommer MA and Tehovnik EJ. Reversible inactivation of macaque frontal eye field. Exp Brain Res 116: 229–249, 1997.[CrossRef][Web of Science][Medline]
Sommer MA and Wurtz RH. Composition and topographic organization of signals sent from the frontal eye field to the superior colliculus. J Neurophysiol 83: 1979–2001, 2000.
Sommer MA and Wurtz RH. What the brain stem tells the frontal cortex. I. Oculomotor signals sent from superior colliculus to frontal eye field via mediodorsal thalamus. J Neurophysiol 91: 1381–1402, 2004.
Tehovnik EJ, Sommer MA, Chou IH, Slocum WM, and Schiller PH. Eye fields in the frontal lobes of primates. Brain Res Brain Res Rev 32: 413–448, 2000.[CrossRef][Medline]
Van Essen DC, Dickson J, Harwell J, Hanlon D, Anderson CH, and Drury HA. An integrated software system for surface-based analyses of cerebral cortex. J Am Med Inform Assoc 8: 443–459, 2001.
Wilson VJ and Melvill Jones G. Mammalian Vestibular Physiology. New York: Plenum, 1979.
This article has been cited by other articles:
|
|
 |
|
  B. M. Lawrence and L. H. Snyder The Responses of Visual Neurons in the Frontal Eye Field Are Biased for Saccades J. Neurosci., November 4, 2009; 29(44): 13815 - 13822. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Curtis and J. D. Connolly Saccade Preparation Signals in the Human Frontal and Parietal Cortices J Neurophysiol, January 1, 2008; 99(1): 133 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Lawrence and L. H. Snyder Comparison of Effector-Specific Signals in Frontal and Parietal Cortices J Neurophysiol, September 1, 2006; 96(3): 1393 - 1400. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
TOP
ABSTRACT
INTRODUCTION
