A R T I C L E S

Most real-world scenes are cluttered with many different potentialsaccade goals, so the selection of a single goal from many possibilitiesis an essential stage in the generation of these movements. Models ofsaccade target selection typically posit that selection is mediated bycompetitive interactions among potential stimuli, with the mostbehaviorally salient stimulus becoming the target1–5. In these models,behavioral salience is determined by both the visual salience and thebehavioral relevance of a stimulus. The SC, a brainstem structurelocated fairly close to the output of the saccadic system, is involved inthe production of saccadic eye movements and is often regarded as agateway for saccade-related signals from cortex to reach the brain-stem saccade generator6–9. Cortical oculomotor structures, as well asthe SC, are normally unselective for specific visual features9–13, butare modulated by the behavioral salience of potential movementgoals12–26, suggesting an involvement in saccade target selection.

Although neural activity in the SC is correlated with target selec-tion, this does not necessarily imply that the SC has an essential func-tional role in this process. One possibility is that the SC, instead ofinfluencing which target is selected, merely receives selection-relatedactivity from other brain structures in order to prepare movementsfor execution. In this scheme, the final saccade goal is imposed on theSC, and the function of the SC is to convert this goal into an appropri-ate movement command for the brainstem saccade generator.

Alternatively, it is possible that in addition to its role in saccade exe-cution, the SC participates in a network of brain areas that convergeson the choice of saccade target. Indeed, it has even been proposed thatthe SC itself may be the site of the final competitive selection of thesaccade goal2. To test whether the SC participates in saccade targetselection, we perturbed SC activity by microinjecting lidocaine ormuscimol, chemicals that temporarily depress neural activity in theregion of the injection. We then determined whether this perturba-

tion affected target selection (as it does in higher-level prefrontal27–29

and parietal30 cortices), or whether it only affected movement execu-tion. Using a visual search task, we found that after SC inactivation,when the target appeared in the inactivated field, saccades were oftenmisdirected to distractors. Control tasks indicated that this deficit wasnot due to a simple visual or motor impairment. Furthermore, theseverity of the deficit depended largely on the perceptual difficulty ofdiscriminating the target from distractors, which is consistent with atarget selection deficit, rather than a purely motor impairment.

RESULTSRhesus monkeys performed a color-oddity search task, in which a tar-get of one color, randomly positioned in one of four locations, was pre-sented simultaneously with three distractors of another color.Randomly interleaved with these search trials were single-stimulus tri-als in which the target was presented without distractors. The SC con-tains a topographical map of contralateral visual space9, and wearranged the target locations such that one of the locations was at thecenter of the region coded at the injection site in the SC for that session(the ‘inject’ location; Fig. 1a). The other three target locations were atthe same eccentricity, but separated by 90° in direction. The target loca-tion in the same hemifield as the inject location was designated the ipsi-lateral (‘ipsi’) location, and the corresponding location in the oppositehemifield was designated the contralateral (‘contra’) location. The tar-get location on the opposite side of fixation from the inject location wasdesignated the ‘opposite’ location.

Temporary inactivation of a portion of the SC was achieved byinjecting small quantities of lidocaine (21 sites) or muscimol (6 sites)into the deeper intermediate layers of the SC of three monkeys (see Methods). Lidocaine inactivates neural tissue by blockingsodium channels, whereas muscimol is a GABAA (γ-aminobutyric

The Smith-Kettlewell Eye Research Institute, 2318 Fillmore Street, San Francisco, California 94115, USA. Correspondence should be addressed to R.M.M.(rmm@ski.org).

Published online 13 June 2004; doi:10.1038/nn1269

Deficits in saccade target selection after inactivationof superior colliculusRobert M McPeek & Edward L Keller

Saccades are rapid eye movements that orient gaze toward areas of interest in the visual scene. Neural activity correlated withsaccade target selection has been identified in several brain regions, including the superior colliculus (SC), but it is not knownwhether the SC is directly involved in target selection, or whether the SC merely receives selection-related signals from cortex in preparation for the execution of eye movements. In monkeys, we used focal reversible inactivation to test the functionalcontributions of the SC to target selection during visual search, and found that inactivation resulted in clear deficits. When atarget appeared in the inactivated field, saccades were often misdirected to distractor stimuli. Control tasks showed that thisdeficit was not caused by low-level visual or motor impairments. Our results indicate that, in addition to its well-establishedinvolvement in movement execution, the SC has an important functional role in target selection.

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acid) agonist. We tested performance before injection, immediatelyafter injection, and after recovery from injection, and observed simi-lar results with either lidocaine or muscimol injections.

Effects of SC inactivation on saccades to single stimuliThe single-stimulus trials allowed us to gauge the effects of SC inacti-vation on movement execution. As shown in earlier studies, injectionsof small amounts of lidocaine or muscimol resulted in fairly modestmotor deficits for saccades made into the affected part of the visualfield: saccade velocity and endpoint accuracy decreased, saccade trajectories became more variable, and saccade latencies werelonger31–34. Nevertheless, when the target was in the location represented by the injection site, saccades could still be made to the

target location in every trial (see Fig. 1b–d for results of an examplelidocaine injection). Saccades made to single stimuli in the otherthree target locations were relatively unaffected by SC inactivation atthis site (data not shown).

Previous studies have reported that saccade peak velocity is a sensi-tive measure of SC inactivation31–35, so we used this parameter to mapthe spatial extent of SC inactivation for each of the four target locationstested. Across the 21 lidocaine and 6 muscimol sites tested, saccadesmade to single stimuli at the inject location showed significantlyreduced peak velocities after either lidocaine or muscimol injection(Fig. 1e; t-tests, P < 0.0001). Peak velocities were also reduced for sac-cades to the ipsi location after muscimol injection (P < 0.01), consis-tent with earlier reports of a spread of muscimol inactivation toneighboring regions within the injected SC, but not to the contralateralSC33–35. The reduction in peak velocity likely resulted both from thegeneration of hypometric saccades and from an overall reduction inmovement velocity32–34. As expected from previous studies, after lido-caine or muscimol injections, saccade latency showed a significantincrease (Fig. 1f; P < 0.0001 for both lidocaine and muscimol injec-tions) and saccade amplitude a significant decrease (Fig. 1g; P < 0.001for lidocaine; P < 0.01 for muscimol) for the inject location. Consistentwith a spread of muscimol, saccade latency for the ipsi location alsoshowed a significant increase (P < 0.001) after muscimol injection, but

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Figure 2 Effects of SC inactivation on saccades in search trials. Sameinjection site as in Figure 1b–d. During testing, search and single-stimulustrials were randomly interleaved. Search responses have been sorted by target position for clarity. (a–d) Pre-injection performance in search was 100% correct. (e–h) Post-injection, monkeys tended to make moresaccades to distractors when the target appeared in the inject location (e), but not when it appeared elsewhere (f–h). (i–l) After recovery,performance returned to normal.

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saccade amplitude was not significantly reduced (P = 0.06) at the ipsilocation. No significant changes in saccade parameters to the otherlocations were found. The key point is that monkeys were able to makesaccades to single stimuli in the affected part of the field in every trial,with fairly mild motor deficits.

Effects of SC inactivation on target selectionWhen we shifted our analysis from this simple task to the interleavedsearch trials requiring target selection, an additional striking deficitemerged. Our trained monkeys normally performed the color searchtask correctly in 96% of trials, well above the chance level of 25%. Forthe example site (same site as in Fig. 1b–d), pre-injection perform-ance in search was 100% correct (Fig. 2a–d). If the SC were notinvolved in saccade target selection, and were merely involved inmovement execution, impairments in the search task would be simi-lar to those seen in the single-stimulus task, namely, a change inmovement parameters such as latency, velocity and amplitude. Wefound, however, that after SC inactivation, when the target was pre-sented in the part of the visual field affected by the injection, monkeysmade a considerable number of erroneous saccades to distractors(43% of saccades), suggesting a deficit in target selection (Fig. 2e).When the target was presented elsewhere, performance was unaf-fected (Fig. 2f–h), indicating that the deficit was spatially restricted tothe part of the field represented by the SC injection site.

Importantly, the erroneous saccades were not averaging movementsor grossly inaccurate attempts to reach the target. Instead, they werefairly accurate saccades that were simply directed to the wrong stimu-lus, indicating an error in target selection. These errors could not haveresulted from a simple motor impairment, as the interleaved single-stimulus trials show that saccades to a target in the affected field canstill be made in the absence of distractors (Fig. 1c). After recovery fromthe injection, performance returned to normal (Fig. 2i–l).

To summarize the effects on target selection across sites, we meas-ured the direction of the saccade made in each trial of the search task,and normalized saccade direction with respect to the location in thevisual field represented at the injection site. We then plotted his-tograms of normalized saccade endpoint direction. For the 21 lido-caine injections, 96% of pre-injection saccades were correctlydirected toward the target (Fig. 3a,b). After lidocaine injection, whenthe target was presented at the injection location, 53% of saccadeswere directed toward distractor locations (Fig. 3c). Performance atthe three other locations remained good (Fig. 3d). After recovery, sac-cades were again directed correctly toward the target in 97% of trials(Fig. 3e,f). A linear contrast testing the hypothesis that pre-injectionand recovery performances were equal, and that post-injection per-formance was significantly worse when the target appeared at theinject location, was highly significant across sites (P < 0.0001), andindividually significant for 18/21 sites (P < 0.01). When the targetappeared elsewhere, the linear contrasts were not significant acrosssites (P > 0.19 for each target location) and were individually signifi-cant (P < 0.01) for only 2/63 site-location combinations.

In a control condition, a comparable volume of saline, rather thanlidocaine or muscimol, was injected into the SC (three sites).Performance after saline injection was not significantly differentfrom pre-injection performance (Fig. 3g,h), indicating that thedeficit in target selection depends on the injection of an inactivatingsubstance into the SC (linear contrasts: P > 0.38 across sites for alltarget locations; for individual sites, P > 0.10 for all site-locationcombinations).

Similar results were obtained for the six muscimol injection sitestested (Fig. 4), except that the effects of muscimol tended to spreadwithin the injected SC, affecting the neighboring target location inthe same hemifield (ipsi location) as well as the inject location. Thisspread is consistent with earlier reports33–35 and was apparent inthe peak velocity and latency of saccades to the ipsi location (Figs. 1e,f and 5b). For this reason, for the muscimol experiments,the results for the inject and ipsi locations were plotted separately(Fig. 4a–f) from the results for the contra and opposite locations(Fig. 4g–i). The critical pattern of results was similar to that seenwith lidocaine injections: monkeys showed an increase in erro-neous saccades directed toward distractors after SC inactivationwhen the target was presented in the affected part of the field(inject and ipsi locations; Fig. 4b,e). Linear contrasts testing thehypothesis that pre-injection and recovery performance were thesame, and that post-injection performance was significantly worse,

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Visual control taskOne possible explanation of the observed tar-get selection deficit is that SC inactivationcauses low-level visual impairment, whichresults in search errors. Although the stimuliwere well above threshold, a sizable loss ofcontrast sensitivity would render the targetmore difficult to detect when it appeared inthe affected field, possibly resulting in sac-

cades to distractors. Previous studies have shown little effect of SClesions on vision in the monkey37–39. Nonetheless, we used a controltask to test the ability of monkeys to detect and make saccades to sin-gle, low-contrast stimuli in the affected field after SC inactivation. Thisconsisted of a two-alternative forced-choice detection task, in whichmonkeys detected and made a saccade to low-contrast single stimuli,presented in either the inject or opposite location. We tested perform-ance in the search task before and after testing in the visual controltask, to ensure that the search deficit was present both before and afterthe control task (Fig. 6a). We used signal detection theory40 to com-pute sensitivity (d' ) and decision bias (β) for the visual control task,and compared these parameters across the nine sites tested in thismanner (six lidocaine, three muscimol). We found no significantchange in d' as a consequence of the injections (Fig. 6b), indicatingthat SC inactivation did not result in a loss of contrast sensitivity (P = 0.76). We did, however, observe a significant shift in β (P < 0.01),the decision bias (or criterion) adopted by the monkeys to decidebetween the two possible target locations (Fig. 6c). This indicates thatafter injection, even though visual sensitivity was unchanged, monkeys

Figure 4 Histograms of normalized saccadeendpoint direction across the six muscimolinjection sites. Conventions are the same as in Figure 3, except that results for both inject(a–c) and ipsi (d–f) target locations are plottedseparately, since the effects of muscimolinjections often spread to the ipsi location (seeFigs. 1e and 5b). (g–i) Results for contra andopposite locations. Endpoint direction is plottedfor saccades made before injection (a,d,g), afterinjection (b,e,h) and after recovery (c,f,i).

A R T I C L E S

were highly significant across the muscimol sites when the targetwas in the inject location and when it was in the ipsi location (P < 0.001 in each case). When the target appeared elsewhere, thelinear contrasts were not significant across sites (P > 0.38 for bothopposite and contra target locations). For individual sites, weobtained significant linear contrasts (P < 0.01) for 6/6 sites whenthe target was in the inject location and for 5/6 sites when the targetwas in the ipsi location. When the target appeared at the oppositeor contra locations, none of the sites reached significance. Theseresults with muscimol indicate that the target selection deficitresulted from inactivation of neurons in the SC rather than frominactivation of fibers of passage, as muscimol, unlike lidocaine,does not inactivate axons36.

For a more complete picture of saccadic performance in thesearch task, we examined the latency and the amplitude gain of sac-cades made in search before and after SC inactivation. The resultswere what one might expect, given the effects of SC inactivation onsaccades to single stimuli31–35: saccade latencies during search (Fig. 5a,b) were longer for movements made to target locations inthe affected part of the field (inject location for lidocaine, injectand ipsi locations for muscimol; P < 0.001 in all cases). In general,latencies of error saccades were slightly longer than latencies ofcorrect saccades, both before and after injection (P < 0.0001). Post-injection saccades into the affected part of the field during search(Fig. 5c,d) showed a slightly smaller amplitude gain than did pre-injection saccades to the same locations (P < 0.001 in all cases), asexpected from earlier studies with single stimuli32–35. Error sac-cades also showed smaller amplitude gain, both before and afterinjection (P < 0.0001).

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were biased toward selecting the location away from the injection sitewhen the target location was uncertain, consistent with the idea thatSC inactivation influences target selection.

Perceptual difficulty of target/distractor discriminationThe visual control task indicated that the deficits seen in the searchtask are unlikely to have been caused by a low-level visual impair-ment. The pattern of errors in search, consisting of fairly accurate sac-cades directed to the wrong stimuli (Figs. 2e, 3c and 4b,e), points to adeficit in target selection. As an additional test of this conclusion, insome experiments we manipulated the perceptual difficulty of thesearch task. In one manipulation (three lidocaine and three muscimolsites), we varied the difference in color between target and distractorstimuli, while keeping their luminances equal. In another series (threelidocaine and three muscimol sites), we used achromatic stimuli andvaried the contrast of the distractors. Both of these manipulationsaffected the difficulty of discriminating the target from the distrac-tors, without changing the motor requirements of the task. If SC inac-tivation affects only the motor processing that occurs after targetselection, then perceptual discriminability and SC inactivationshould have independent effects on performance. On the other hand,if SC inactivation affects the selection stage, we should observe aninteraction between the difficulty of target selection and SC inactiva-tion, resulting in markedly worse performance in the perceptuallymore difficult search conditions. We found that varying the strengthof the sensory cues distinguishing the target from the distractors hada modest, but systematic, effect on performance before injection and after recovery, and a pronounced effect during SC inactivation (Fig. 7). Two-way analyses of variance (ANOVA) on percentage cor-rect performance when the target appeared at the inject locationrevealed significant main effects of discriminability and SC inactiva-tion, as well as a significant interaction between inactivation and dis-criminability (P < 0.001) in both tasks, consistent with the idea thatSC inactivation affects the selection stage.

DISCUSSIONPrevious studies have identified SC activity correlated with saccadetarget selection, leading to the hypothesis that the SC is involved intarget selection12,21–26. In most of these studies, selection-relatedactivity was distinguished from movement-related activity by

(i) examining its temporal relationship with the onset of the move-ment or (ii) correlating the activity with the strength of the sensorycues underlying the selection task. Logically, the presence of suchselection-related activity is necessary, but not sufficient, to establishthe involvement of the SC in saccade target selection. An alternativehypothesis is that the SC passively receives signals related to targetselection in preparation for generating movements, but does notitself have a functional role in target selection. The current resultsdemonstrate that perturbations in SC activity have systematic effectson the choice of saccade goal. This finding is at odds with the latteralternative, and establishes that the SC is functionally involved insaccade target selection.

In agreement with earlier studies31–35, we found that inactivation ofa portion of the SC resulted in relatively mild motor deficits for sac-cades made to single stimuli. However, when a target had to beselected from distractors, we observed a large additional deficit in tar-get selection. Monkeys tended to make erroneous saccades to distrac-tors when the target was presented in the part of the field affected bythe inactivation, even though they were consistently able to executesaccades to the target location in the absence of distractors. Theseerror saccades were fairly accurately directed to distractor stimuli,suggesting a deficit in target selection. A visual control task indicatedthat SC inactivation did not affect target selection by simply decreas-ing visual sensitivity in the affected region.

How, then, does SC inactivation affect target selection? Given whatwe know about color perception, it seems unlikely that SC inactiva-tion prevents the monkey from determining which stimulus is theodd-colored target. Indeed, recording studies have shown that oculo-motor areas are normally unselective for color or other visual fea-tures9–13. Instead, their activity seems to be modulated according tothe behavioral salience of stimuli, regardless of whether salience isdefined by color or by other characteristics12–26. Most models of target selection posit a competitive mechanism that selects thestimulus with the greatest behavioral salience as the saccade goal1–5.

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Figure 6 Performance in the visual control task. (a) Mean searchperformance (% correct saccades) across nine sites tested in the visualcontrol task. Performance when the target was in the inactivated field wasmeasured pre-injection, post-injection before testing in the visual control,and post-injection after testing in the visual control. Error bars show s.e.m.(b) Comparison of d′ (sensitivity) before and after injection for saccades to alow-contrast single stimulus for the same nine SC sites. (c) Comparison ofβ, the bias in responding toward (β < 1) or away (β > 1) from the injectionsite in the visual control task before and after SC inactivation.

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The present results could be accounted for if inactivating a portion ofthe SC effectively reduced the behavioral salience for the saccadic sys-tem of stimuli in the affected part of the field, placing them at a com-petitive disadvantage relative to other potential saccade goals. Whenthe target fell in the affected part of the field, even though visual areasproviding input to the oculomotor system presumably continued tosignal the correct location of the odd target, the target-related activityin the competitive map was weaker than it normally would be, due tothe inactivation. As a result, in some trials a distractor stimulus ‘won’the competition and became the saccade goal. The absence of averag-ing saccades directed between stimuli supports this interpretation.

We speculate that when it was perceptually more difficult to discrim-inate the target from the distractors (Fig. 7), the difference in activitybetween target and distractors in the competitive map was smaller, andhence, the competition was more susceptible to disruption by SC inac-tivation. Regardless of the exact mechanism, our results establish thatthe SC has a functional role in saccade target selection, most likely inconcert with pre-frontal and parietal cortical regions13–21,27–30.

METHODSPhysiological methods. We used standard methods for monitoring eye move-ments, recording single neurons and microstimulating41 in three Macacamulatta. Microinjections were made through a metal cannula (33-gauge) withan attached microelectrode, similar to one described previously42. The locationof the cannula within the SC motor map was estimated by examining the end-points of saccades elicited by microstimulation. At each site, the current andduration of a 400 Hz stimulation train was varied to obtain the site-specificmaximal saccade amplitude43. Injections were made at depths in the SC atwhich saccade-related activity was recorded and saccades were reliably elicitedat low stimulating currents (less than 30 µA at 400 Hz). Injections consisted of0.25–1.25 µl of 2% lidocaine or 0.25–1 µl of muscimol dissolved in sterile saline(0.5 µg/µl). In some control experiments, 1.25 µl of saline alone was injected.Injections were delivered at a rate of 0.5 µl/min using a Hamilton syringedriven by a digital infusion pump (Harvard Apparatus). Testing before andafter injection, as well as during recovery, was conducted in the same session forlidocaine injections. For muscimol injections, recovery testing was conductedon the next day. All experimental protocols were approved by the InstitutionalAnimal Care and Use Committee at the California Pacific Medical Center andcomplied with the guidelines of the US Public Health Service policy onHumane Care and Use of Laboratory Animals.

Behavioral testing. Visual stimuli were presented on a video monitor. Eachtrial began with the appearance of a central fixation spot, which the monkeyfixated for 450–650 ms. Then, the spot was removed and four disc-shapedstimuli were presented at equal eccentricity from fixation, separated from eachother by angles of 90°. The stimuli were isoluminant (0.9 cd/m2 on a 0.1 cd/m2

background) and their size was scaled according to the cortical magnificationfactor in order to keep their salience constant across different eccentricities44.At an eccentricity of 15°, the stimuli subtended 2° of visual angle. The threedistractor stimuli were of the same color (either red or green), and the targetwas defined by being of the opposite color. The colors of the target and dis-tractors were switched from day to day, but were kept constant throughouteach day’s session. The target appeared randomly in one of four locations,selected for each injection site so that one location was at the center of theregion of visual space estimated (using microstimulation, see above) to be rep-resented at the injection site. In some experiments, the perceptual difficulty oflocating a red target was manipulated by presenting distractors that werecloser in color to the target (but still isoluminant) in randomly selected trials.In other experiments, the monkeys searched for a bright (99% contrast)achromatic target among dimmer achromatic distractors, and the contrast ofthe distractors was randomly selected in each trial to be 48%, 71% or 88%.

Single-stimulus trials were identical to search trials, except that the dis-tractors were absent. Search trials (75%) and single-stimulus trials (25%)were randomly interleaved. Monkeys were given liquid rewards for makinga single saccade to the target location within 50–750 ms after array onset.

To receive the reward, the saccade had to end within an invisible square cen-tered on the target, with side length equal to 66% of the eccentricity of thetarget from fixation. This ensured that monkeys were reliably rewarded forresponses toward the inactivated field, even when saccade endpoint wasaffected, but that rewards were not given for responses toward a distractor.

In the visual control task, a single red target was randomly presentedeither at the center of the region estimated to be represented at the injectionsite, or at a corresponding location on the opposite side of fixation. Thecontrast of the target was randomly varied among three levels using themethod of constant stimuli. The contrast levels used for each site wereselected in a pre-testing session conducted before injection. Signal detectiontheory40 was used to estimate d ′ and β, both pre- and post-injection, for thecontrast level that yielded performance closest to 75% correct in pre-injec-tion testing. At sites at which the visual control task was conducted, per-formance in the search task was separately measured in short blocks of trialsconducted (i) before injection, (ii) after injection but before testing in thevisual control and (iii) after injection and after testing in the visual control.This allowed us to verify that the search deficit was present both before andafter testing in the visual control task.

ACKNOWLEDGMENTSThis work was supported by National Eye Institute grants R01-EY014885 toR.M.M. and R01-EY08060 to E.L.K.

COMPETING INTERESTS STATEMENTThe authors declare that they have no competing financial interests.

Received 25 February; accepted 19 May 2004Published online at http://www.nature.com/natureneuroscience/

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