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1Smith-Kettlewell Eye Research Institute, San Francisco, California; 2Vision Performance Institute, College of Optometry, Pacific University, Forest Grove, Oregon; and 3Laboratoire de Neurophysiologie, Université Catholique de Louvain, Brussels, Belgium
Submitted 2 February 2007; accepted in final form 23 January 2008
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ABSTRACT |
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INTRODUCTION |
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; Wurtz and Goldberg 1989). When multiple objects are present that compete to be the target, a selection process is necessary (Arai and Keller 2005; Arai et al. 1994; Findlay and Walker 1999). Recent studies have shown that neural activity in many oculomotor regions evolves to signal which of competing targets will be selected [e.g., superior colliculus (SC): Li and Basso 2005; McPeek and Keller 2002, 2004; the frontal eye field (FEF): Thompson et al. 1996; and the basal ganglia: Basso and Wurtz 2002]. It is currently not clear, however, whether these are the areas making the selection or whether their activity reflects selection made by other areas.
Regions in the dorsomedial frontal cortex (DMFC), including the supplementary eye field (SEF) (Schlag and Schlag-Rey 1987) and the presupplementary motor area (pre-SMA) (Isoda 2004; Isoda and Hikosaka 2007; Isoda and Tanji 2002; Tanji 2001), might be good candidates for influencing saccade target selection. The SEF is located in the lateral DMFC, between the midline and the genu of the arcuate sulcus (for reviews, see Schall 1991; Tehovnik 1995). The SEF has direct connections to the SC (Fries 1985) and the brain stem (Hartmann-von Monakow et al. 1979; Shook et al. 1998, 2000), and low-current microstimulation here evokes contralateral saccades (Martinez-Trujillo et al. 2003; Park et al. 2005; Russo and Bruce 2000; Schiller and Chou 1998; Schlag and Schlag-Rey 1987; Tehovnik 1995; Tehovnik and Lee 1994). Some SEF neurons show heightened activity during countermanding (Stuphorn et al. 2000) and go/no-go tasks (Schall 1991), in which a visually guided saccade must be withheld based on task cues. SEF neurons are also active in the antisaccade task, in which a visually guided ipsilateral saccade is replaced with an endogenously generated contralateral one (Amador et al. 2004; Schlag-Rey et al. 1997). These findings suggest that the SEF plays a supervisory role in saccade generation (Schall et al. 2002) and may be involved in selecting between competing saccades plans.
Recent studies have shown that the pre-SMA, situated medial and ventral to the SEF, is also involved in top-down control of saccade initiation (Hoshi and Tanji 2004; Isoda 2004; Isoda and Tanji 2004; Nachev et al. 2005; Tanji 2001). This region does not have direct connections to the SC or the brain stem (Fries 1987; Hartmann-von Monakow et al. 1979), and stimulating here does not evoke saccades (Fujii et al. 2002). Rather, stimulation in the pre-SMA results in greater ipsilateral than contralateral delay (for observed facilitation effect, see Isoda 2004). Moreover, some pre-SMA neurons are more active when saccades are directed toward a newly cued location, compared with when saccades are made to the same location but without a change of cued location (Isoda and Hikosaka 2007). These results implicate the pre-SMA in supervising the selection of saccade targets, but not in directly triggering them.
The above-cited findings suggest that both areas are good candidates to participate in target selection. However, no studies have directly compared them in this regard, although they have been compared with respect to their roles in saccade planning (Fujii et al. 2002), and in resolving competing voluntary saccade plans (Nachev et al. 2005). To assess the specific contributions of the SEF and pre-SMA to saccade target selection, we applied electrical microstimulation to each structure around the time when visually guided saccades were being planned. Our rationale was that if a region participates in saccade target selection by signaling a preferred target location, the command elicited by stimulation should compete or cooperate with the saccade being planned to the visual target, and therefore either facilitate or inhibit that saccade.
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METHODS |
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Three juvenile male macaque monkeys (GU, CL, and VC) participated in the experiments. One of them (GU) was involved in an earlier smooth pursuit study (Missal and Heinen 2004), in which anticipatory pursuit facilitation was obtained from stimulating the DMFC. Surgeries were performed under aseptic conditions to implant a recording chamber, head holder, and a search coil to measure eye movements. With the monkey under isoflurane gas anesthesia, a 2-cm craniotomy was trephined in the skull. The chambers implanted on the monkeys were centered 24 mm anterior in Horsley–Clarke stereotaxic coordinates for GU and VC, and 24 mm anterior and 7.5 mm to the right for CL. A stainless steel recording chamber with an inner diameter of 1.4 cm was positioned over the craniotomy. The eye coil, constructed from Teflon-coated stainless steel wire, was implanted under the conjunctiva of one eye (Judge et al. 1980). The head holder was positioned on the midline. After surgery, the monkey was returned to its cage and allowed to recover fully before experiments began. Antibiotics and analgesics were administered under the direction of a veterinarian during the postoperative period. All procedures were approved by the California Pacific Medical Center Institutional Animal Care and Use Committee and were in compliance with the guidelines set forth in the U.S. Public Health Service Guide for the Care and Use of Laboratory Animals.
Experimental procedures
Stimulation was delivered through tungsten microelectrodes of 85–100 mm length (FHC) that were lowered to sites in the DMFC through a stainless steel guide tube. The impedance of each electrode at the beginning of each session was 1.0–2.0 M
; at the end of each session the impedance usually dropped significantly, often to <0.3 M. The stimulation trains consisted of biphasic pulses with a duration of 0.2 ms for each phase; the stimulation frequency was set at 300 Hz and pulse-train duration was usually 100 ms. These parameters provided the optimal change in saccade latency with low current. The current amplitude was set just above the threshold for causing a latency change, typically between 50 and 75 µA. For some sites, we varied stimulation duration (50–500 ms), current amplitude (25–600 µA), and target onset asynchrony (TOA) (–75 to +150 ms).
Monkeys were trained to make saccades to a 0.5° white spot that appeared at horizontal locations 10° to the left or right of the fixation point. Each trial began with the appearance of a fixation point at the center of the screen. The monkey had to acquire the fixation point and maintain fixation within a 3° window centered on it for 500 ms, after which time the fixation point was extinguished and a target was displayed peripherally at either horizontal location. After the target appeared, the monkey had 500 ms to acquire it and had to maintain fixation within a 4° window centered on it for an additional 500 ms. Liquid reward was given if the monkey successfully performed the trial. The intertrial interval was variable but always exceeded 400 ms.
In each experimental session, stimulation with –25-ms TOA and 75-µA current amplitude was first applied to search for effective facilitation sites along an electrode track. Stimulation with +75-ms TOA was then used to search the same track for delay sites. If an effect was found with either a –25- or +75-ms TOA, the other TOA was used to test the same site. Each site was categorized based on the type of initial effect. For example, if there was significant ipsilateral delay and contralateral facilitation with a –25-ms TOA, the site was classified as "–con/+ipsi," regardless of the effect later obtained with +75-ms TOA. When an effective site was found, the threshold current for affecting saccade latency was determined and the stimulation parameters and target locations were varied when necessary. Single-unit activity close to the effective site was recorded from neurons at some sites while the monkey was making saccades to targets 10° away from the fixation point horizontally or vertically. Only the activity of neurons isolated within 100 µm of the optimal depth for the stimulation effect was recorded and analyzed. The difference in neural signals was mostly moderate in response to targets appearing at the contralateral and ipsilateral locations.
Due to the time limit of each experimental session, typically only one stimulation parameter was systematically manipulated at a site. In addition, in some sessions after a site was found, target position was manipulated to investigate the spatial tuning of the stimulation effect, with the threshold current amplitude and two TOAs (–25 and +75 ms). The target appeared at one of three eccentricities (5, 10, 15°) and one of 12 equally spaced radial angles; either one TOA or both TOAs were used in a single session depending on the session's duration. At effective sites we attempted to evoke saccades, while the monkey was in the dark, with the same threshold current used to alter saccade latency.
Data analysis
Effective stimulation sites were determined by on-line visualization of single and averaged eye position traces for stimulation and control trials. Vertical and horizontal eye position signals were digitized (1 kHz) and stored for off-line analysis. Eye velocity was obtained by digital differentiation with a filtering cutoff frequency of 50 Hz. Saccade onset was detected using a velocity threshold of 40°/s. Saccade landing error was obtained by computing the distance between target position and saccade endpoint. Maximum trajectory deviation was defined as the largest angular separation between a straight line that connected initial eye position and the target location, and a straight line that connected initial eye position and momentary eye position. Peak velocity was defined as the maximum radial eye velocity during the saccade.
To compare the magnitude of a given stimulation effect with various parameters and TOAs at different sites, we computed a t-value for the difference in saccade latency between control and stimulated trials. The mean latency obtained from control trials at each site was subtracted from that obtained from stimulated trials at the same site, and the difference in means was normalized against the SE of the difference. A t-value 
1.96 indicates a significant difference.
Directional tuning of neural activity at stimulation sites was measured using the following procedure. Neural activity was recorded while the monkey was planning a saccade to a target that appeared at one of four locations (10° up, down, left, and right of the central fixation point). A directional index (DI) was then derived from the vector sum of normalized mean spike rate for the 100 ms prior to saccade initiation. The mean spike rate for the four target locations was normalized against that for the location having the highest mean spike rate.
Gaussian curve fitting was implemented to compare the directional tuning of the stimulation effect across different types of stimulation sites. The location with the maximum latency change was first identified and the mean latency change for each target location of the same eccentricity was then normalized against the maximal latency change. A least-squares method was used to obtain the best fit. The SD of the curves for different stimulation sites was statistically compared using an F-test.
Matlab and its Signal Processing and Statistical Toolboxes (The MathWorks, Natick, MA) were used to implement all data analysis algorithms. The Matlab Statistics Toolbox and SPSS 13.0 (SPSS, Chicago, IL) were used to perform postexperimental statistical analyses. The significance of all observed effects underwent a t-test, with a statistical significance level (P value) set at 0.05.
Histology
After completion of the experiments, the monkeys were perfused and the brains were fixed with 10% formalin. For monkey VC, 5-µm-thick coronal slices were taken from the DMFC and stained (hematoxylin-and-eosin and Perl) to highlight the electrode tracks. In addition, before perfusing monkey VC, two electrical lesions were made with DC current located 2 mm laterally from the center of the chamber and 4.5 mm in depth. After perfusion, the reference lesions were revealed using cresyl violet staining. The recorded site depth and locations in experimental sessions were then aligned to these reference tracks.
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RESULTS |
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Low-amplitude stimulation applied to 79 DMFC sites resulted in delay and/or facilitation of saccade initiation. Results from three example stimulation sites, obtained with current amplitudes of 50 to 75 µA and a duration of 100 ms, are shown in Fig. 1. Figure 1A shows results obtained from an ipsilateral delay site (VC 272, depth = 1.2 mm, A/P = –2 mm, M/L = –3 mm) (by convention, negative numbers will be used to refer to posterior and left site locations). The left panels show the horizontal eye position for trials in which –25- (Fig. 1A, top) and +75-ms (Fig. 1A, bottom) TOAs were used for saccades made toward targets at the two 10° horizontal locations. The bars below the eye traces indicate the stimulation period. Stimulated (red traces) and unstimulated control trials (blue traces) were intermixed randomly in the same block of trials. The right panel shows horizontal and vertical eye position traces from saccades evoked at the same site with the same current amplitude, obtained while the monkey was in the dark (mean latency = 78 ms; SD = 14.2 ms). No facilitation or delay was found with –25-ms TOA (top; ipsilateral: +14 ms, t = 1.65, P = 0.077; contralateral: +8 ms, t = 0.81, P = 0.23); ipsilateral saccades were significantly delayed by stimulation using a +75-ms TOA (bottom), whereas contralateral saccades were not significantly affected (ipsilateral: +60 ms, t = 61.75, P < 0.0001; contralateral: +10 ms, t = 1.94, P = 0.059). Here "+" indicates delay and "–" facilitation. Figure 1B shows results obtained from a bilateral delay site (VC 323, depth = 2.6 mm, A/P = –1 mm, M/L = –2 mm). Here, ipsilateral saccades were delayed with a –25-ms TOA (top; ipsilateral: +29 ms, t = 7.82, P = 0.0021; contralateral: +12 ms, t = 1.15, P = 0.13); delay in both directions was found with a +75-ms TOA (bottom; ipsilateral: +47 ms, t = 40.44, P < 0.0001; contralateral: +23 ms, t = 38.50, P < 0.0001). Stimulating here with the same threshold current amplitude (75 µA) did not evoke saccades. Figure 1C shows results from a contralateral facilitation site (VC 168, depth = 2.4 mm, A/P = 1 mm, M/L = –3 mm), for which contralateral saccades were facilitated but ipsilateral saccades were unaffected with a –25-ms TOA (top; ipsilateral: +14 ms, t = 0.06, P = 0.515; contralateral: –30 ms, t = –9.32, P < 0.01). With a +75-ms TOA (bottom), ipsilateral delay was observed but there was no contralateral facilitation or delay (ipsilateral: +26 ms, t = 6.27, P = 0.0076; contralateral: +5 ms, t = 0.52, P = 0.37). Saccades were evoked from this site with a mean latency of 86 ms (SD = 16.3 ms). Figure 1, D–F shows additional examples of horizontal eye traces in stimulated and control trials obtained from ipsilateral delay (Fig. 1D), bilateral delay (Fig. 1E), and contralateral facilitation sites (Fig. 1F). Note that a site was categorized based only on the initial effect observed (with either –25- or +75-ms TOA), not other effects found later at the same site with a different TOA.
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To characterize the topography of stimulation sites, we plotted the locations of the sites in monkey VC from which the most sites were obtained (Fig. 4A). Most sites where saccades were evoked were 3 mm from the midline, consistent with earlier findings (Park et al. 2005; Russo and Bruce 2000; Schlag and Schlag-Rey 1987; Tehovnik 1995); however, there is no clear topographic difference among the different types of sites.
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), is delineated with dashed lines. The different effects are marked by the same symbols as those in Fig. 4A. The depth was measured as the distance the electrode traveled from where neuronal activity was first encountered to where the stimulation effect was obtained. The measured locations and depths were aligned to those of the reference lesions (depth = 4.5 mm). A summary of site frequency in relation to the SEF and the pre-SMA is reported in columns 4 and 5 of Table 1. Figure 4B shows that most ipsilateral delay sites were located superficially within or close to the SEF, whereas bilateral delay sites were usually located within the pre-SMA or close to its boundary, and deep within the SEF. Note that all types of latency changes were observed in the SEF, but the effects obtained from pre-SMA stimulation were mostly bilateral. Figure 4C summarizes the mean depths of sites where facilitation and delay were obtained, for all sites from the three monkeys. The mean depths were 0.97 mm (ipsi+, SD = 0.25 mm), 2.1 mm (ipsi+/contra–, SD = 0.24 mm), 2.92 mm (ipsi+/contra+, SD = 0.27 mm), and 2.42 mm (contra+, SD = 0.22 mm), respectively. All three types of sites with bilateral effect were located deeper than ipsilateral ones (all P < 0.05).
Stimulation parameters
Differences in stimulation timing, current amplitude, and duration have been shown to affect saccade latency (Isoda 2004; Tehovnik 1995; Tehovnik and Lee 1993; Tolias et al. 2005). We systematically manipulated these parameters at some sites where latency effects were observed. Figure 5 reports the effect of varying TOA. Figure 5A shows the effect of stimulation with 65-µA current of 100-ms duration at one site (GU 26; depth = 2.2 mm, A/P = –2 mm, M/L = –3 mm), with TOAs between –75 and +125 ms. This site was chosen for its strong facilitation effect and because it was tested with the full set of TOAs. The ordinate indicates the difference in saccade latency between control and stimulated trials, where negative values correspond to facilitation and positive values to delay. Contralateral saccades were significantly facilitated as early as –75 ms; the effect dissipated at +50 ms. Ipsilateral saccades were delayed for most TOAs tested and delay was maximal with a +75-ms TOA. Figure 5B shows the effect of stimulating with different TOAs for four contralateral facilitation sites. The latency difference between control and stimulated trials is indicated by t-values and the dotted line shows the 95% confidence interval. Note that the facilitation effect dissipated for all four sites with later TOAs. Three of these sites were in the SEF. Figure 5C summarizes all six ipsilateral delay sites probed with different TOAs. Delay was not significant with a negative, –25-ms TOA, but positive ones produced delay that was maximal with TOAs of +50 and +75 ms. Overall, for all bilateral delay sites obtained with a +75-ms TOA (17 of 25 found in the pre-SMA), most of them (23 of 25) showed significant bilateral delay with a +75-ms TOA but no delay with a –25-ms TOA; only two sites showed significant ipsilateral but not contralateral delay with the –25-ms TOA.
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Saccade metrics
Since Isoda (2004) reported that saccade metrics and dynamics were altered for delayed saccades at some pre-SMA stimulation sites, we examined whether this occurred in our data. Figure 8A shows horizontal and vertical eye position and Fig. 8B shows horizontal velocity recorded during stimulation at three sites. No differences were found in saccade endpoint, trajectory deviation, or peak velocity between control and stimulated trials for any of the three sites. Figure 8, C–E summarizes the results for all sites where a significant effect on saccade latency was observed. Figure 8C shows that only occasionally (12/108) did the stimulation produce a significant difference in endpoint error. Furthermore, the latency change was not correlated with the change in endpoint [delay sites: r(91) = –0.032, P = 0.717; facilitation sites: r(17) = –0.337, P = 0.107]. Figure 8, D and E shows that stimulation only infrequently altered maximal trajectory deviation and peak velocity as well (trajectory deviation: 8/108; peak velocity, 11/108). Again, no significant correlations between latency change and trajectory deviation were found [delay sites: r(91) = –0.033, P = 0.695; facilitation sites: r(17) = –0.236, P = 0.302], nor between latency and peak velocity change [delay sites: r(91) = –0.088, P = 0.584; facilitation sites: r(17) = –0.209, P = 0.263]. These results suggest that the main effect of stimulation was on saccade latency and not on the computation of saccade metrics or dynamics.
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To estimate the spatial extent of the latency effect, at 21 of the 79 significant sites, stimulation (50 or 75 µA) was given while a saccade was being planned to a target randomly presented at one of 36 locations. Targets were displayed at 5, 10, or 15° eccentricity and in one of 12 directions spaced by 30° radial angles. A sufficient number of trials were obtained from four sites with a +75-ms TOA, two sites with a –25-ms TOA, and 15 sites with both –25- and +75-ms TOAs. A summary of the delay/facilitation results is shown in columns 6 and 7 of Table 1. Of the 19 sites where a +75-ms TOA was used, significant delay occurred for at least one target location at 14 sites and no sites produced facilitation. Of the 17 sites tested with a –25-ms TOA, significant facilitation was observed at one or more target locations at 9 sites. At 7 of these 9 sites, saccades were evoked with the same current amplitude when the monkey was in the dark.
Figure 9A shows three-dimensional maps of the latency change obtained at one site and from all 36 target locations with –25- (Fig. 9A, top) and +75-ms (Fig. 9A, bottom) TOAs. The axes represent horizontal and vertical target locations and the colors indicate the magnitude of latency change, where negative values represent facilitation. With a –25-ms TOA, saccades were facilitated in a limited contralateral region and moderately delayed in a broader, ipsilateral region. With +75-ms TOA, saccades were significantly delayed toward most locations, but more so ipsilateral to the stimulated site. Note that facilitation did not occur with the +75-ms TOA. Figure 9B shows maps constructed from a bilateral delay site (VC 169). With a –25-ms TOA, there was no significant delay at any target location. With a +75-ms TOA, saccades were significantly delayed toward most locations, but more so for ipsilateral than for contralateral ones.
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To compare the spatial tuning of delay for superficial and deep sites, the 14 sites were divided into two groups based on their depth (superficial sites: <2 mm, mean depth = 1.5 mm, n = 8; deep sites: 2 mm, mean depth = 2.4 mm, n = 6), and the same procedure was used to compute the normalized scores for the two groups. Figure 9D shows the resulting scores and Gaussian-fitted curves. The Gaussian of the superficial delay sites had a significantly smaller variance than that of the deeper ones [F(12,12) = 2.42, P < 0.05]. In summary, facilitation was usually contralateral, narrowly tuned, and elicited with a –25-ms TOA. Delay on the other hand was usually stronger ipsilaterally, broadly tuned, and occurred with a +75-ms TOA. In addition, tuning for deeper delay sites was broader than that at superficial ones.
Evoked saccades at facilitation sites in the present study converged to a limited contralateral area, as some studies have shown in the past (Park et al. 2005; Tehovnik and Lee 1993). If saccade facilitation relies on the same signal for evoking saccades, their topography should be consistent with each other. To examine this, we computed the goal (mean endpoint) of evoked saccades for the facilitation site and compared it to the target locations at which the maximum facilitation and delay were found at the same site. Figure 10A shows the target location to which maximum facilitation occurred with a –25-ms TOA (red arrow), the target location to which maximal delay occurred with a +75-ms TOA (green arrow), and the endpoints of saccades evoked at the same site (squares). The goal of evoked saccades is indicated by the red cross and the opposite location by the green cross. Note that the goal of evoked saccades is consistent with the target location where maximum facilitation was observed.
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DISCUSSION |
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Note that in the present study facilitation sites were not all located within the SEF and bilateral delay sites were not all located in the pre-SMA; moreover, the type of sites found near the boundary of these two regions was mixed. Consistent with this, Isoda (2004) observed both bilateral delay and facilitation in the pre-SMA. Therefore it is likely that the transition from one type of sites to the other is gradual rather than abrupt.
Previous research distinguished the SEF and the pre-SMA based on their roles in saccade planning (Fujii et al. 2002) and in resolving competing voluntary saccade plans (Nachev et al. 2005), but not in saccade target selection. In them, the activity of SEF neurons appears to specify saccadic movements more than that of pre-SMA neurons (Fujii et al. 2002) and the rostral pre-SMA seems more involved in resolving conflict between voluntary saccade plans, whereas the SEF appears involved in successfully selecting a saccade target (Nachev et al. 2005). Our findings are consistent with these and, further, implicate both structures in playing different roles in saccade selection.
Our results are consistent with the hypothesis that the SEF is involved in selecting a specific saccade and that stimulation here likely activates a subthreshold endogenous command that facilitates the selected saccade. Facilitation might occur through an interaction of the SEF output with visually guided saccade planning in downstream structures to which it projects, such as the FEF or SC. Because the command is subthreshold, it does not directly trigger a saccade; rather, it shortens saccade latency when the target location and the preferred location of the SEF saccade command are consistent. The same stimulation could selectively delay a saccade to a target in a location different from that of the SEF endogenous movement command. Under this scheme, when selection of one from multiple saccade targets is required (McPeek and Keller 2002, 2004; Walker et al. 1994, 1997), the SEF could influence the selection.
In a recent study, SEF stimulation during a countermanding task resulted in saccade delay with a current amplitude lower than ours, but no facilitation was found (Stuphorn and Schall 2006). The absence of facilitation effect in their study is not surprising because we found that facilitation sites are relatively infrequent and depend critically on target location. Furthermore, stimulation produces the greatest amount of facilitation when given before target onset, but it was delivered after target onset in their countermanding experiment, possibly too late to cause an effect. Another potential reason that facilitation was not seen in that study is that the context of the countermanding paradigm, which resulted in longer saccade latency in general (as reported in Stuphorn and Schall 2006), might increase the level of fixation activity in visuomotor structures in both go and no-go trials. As a result, the threshold for stimulation-induced facilitation could have been elevated and the amount of current needed for generating delay would have been lower.
Our findings support the hypothesis that the pre-SMA is not directly involved in selecting a specific saccade but in delaying currently planned ones, consistent with its lack of direct connections to the SC and brain stem. Instead, it might influence saccade selection by delaying saccades bilaterally via other cortical or subcortical regions with which it has direct connections, such as the FEF (Huerta and Kaas 1990; Luppino et al. 1993). The pre-SMA might modulate fixation activity in the FEF to control the amount of delay, thereby allowing the preferred saccade to be selected by other structures, such as the SEF. Similar modulation of saccade latency by fixation signals has been suggested in recent computational and physiological work on saccade initiation times (e.g., Carpenter and Williams 1994; Schall and Hanes 1996).
Another study of the pre-SMA arrived at a different conclusion about this area's role in saccade selection (Isoda and Hikosaka 2007), in which, when a cue changed color to signal a switch in the desired direction of a planned saccade, neurons here were more active for switched saccades than for saccades in the same direction without a switch. Based on these results, the authors suggested that the pre-SMA facilitates saccades to preferred locations and suppresses saccades to nonpreferred ones. However, their study also showed that stimulating the pre-SMA in a go/no-go paradigm, although improving performance in the task, delayed saccades made in both go and no-go trials. This result is inconsistent with the idea that the pre-SMA facilitates saccade initiation, but rather supports our interpretation that neurons here suppress an unwanted saccade to allow a desired one to be selected by another structure such as the SEF.
Finally, with respect to the effect of stimulation timing, our findings suggest that current applied to the SEF must be delivered well before movement onset to reliably facilitate saccades. Early SEF stimulation may be necessary to affect saccade planning in other structures, given the long latency for evoking saccades from the SEF. In contrast, SEF stimulation delays saccades when delivered after target onset but before saccade initiation and its effect dissipates shortly after the end of stimulation, likely by directly activating spatially selective fixation neurons downstream. Pre-SMA stimulation, which also required later TOAs to delay saccades, could directly activate nonselective fixation neurons downstream. These two regions might have access to spatially selective or nonselective fixation neurons, respectively, such as those found in the FEF (Sommer and Wurtz 2000). In contrast with our results, an earlier study reported that SEF stimulation also resulted in bilateral suppression of FEF movement neurons (Sadeghpour et al. 1998). The discrepancy between their results and ours can be reconciled if their stimulation actually activated bilateral delay sites in the DMFC.
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GRANTS |
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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Address for reprint requests and other correspondence: S. Heinen, 2318 Fillmore Street, San Francisco, CA 94115 (E-mail: heinen{at}ski.org)
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0.05). C: data from 6 ipsilateral delay sites. Details as in B.
