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DOI: 10.1177/1073858404271196

2005 11: 124NeuroscientistRichard J. Krauzlis

The Control of Voluntary Eye Movements: New Perspectives

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124 THE NEUROSCIENTIST Voluntary Eye MovementsCopyright © 2005 Sage PublicationsISSN 1073-8584

Primates make two kinds of voluntary eye movements toplace the retinal images of objects of interest onto thefovea and to keep them there: saccades and pursuit.Saccades are discrete ballistic movements that direct theeyes quickly toward a visual target, thereby translatingthe image of the target from an eccentric retinal locationto the fovea within tens of milliseconds. Pursuit is a con-tinuous movement that rotates the eyes smoothly andslowly to compensate for any motion of the visual targetand thus minimizes the drift of the target’s image acrossthe retina that might otherwise blur the image and com-promise visual acuity.

Much of what we have learned about voluntary eyemovements over the past 40 years has involved treatingthese movements as visuomotor reflexes that act to min-imize visual “error” signals. Indeed, many species cangenerate smooth optokinetic eye movements, which helpstabilize the eyes during head and body movements byminimizing the motion of the entire visual surround.However, when we move about in most natural environ-ments, it is impossible to eliminate the slip of imagesacross the retina. Instead, choices need to be made aboutwhich visual inputs have top priority. Primates appear tobe unmatched in their ability to identify individualobjects within a complex, dynamic visual scene and totrack selected objects with their eyes. Voluntary eyemovements in primates are therefore not just a motorphenomenon but depend on the sophisticated sensory

and cognitive processing capabilities of the primate cen-tral nervous system. The importance of these higherorder processes, and the complexity of the underlyingmechanisms, pose both challenges and opportunities forusing voluntary eye movements as a model for under-standing the neural circuits involved in visuomotor con-trol. This review highlights some recent findings thatprovide new perspectives on the functional organizationof these voluntary motor systems.

The Neural Pathways for Pursuit and Saccades

Although the pursuit and saccadic systems have tradi-tionally been viewed as anatomically distinct, morerecent evidence indicates that there is considerable over-lap in the neural pathways for pursuit and saccades. Bothsystems involve a similar set of areas in the cerebral cor-tex (Fig. 1). For saccades, these cortical areas evaluateand update the locations of potential targets and providemotor commands for saccades and include the lateralintraparietal area (LIP), the frontal eye fields (FEFs),and the supplementary eye fields (SEFs). For pursuit,cortical areas are involved in processing the visualmotion and other control signals necessary for pursuitand include the middle temporal (MT) and medial supe-rior temporal (MST) areas and subregions of areas LIP,FEF, and SEF. Thus, many of the same cortical areas areinvolved in the control of both pursuit and saccades, buteach area contains separate subregions for the two typesof movements, and the corresponding subregions areinterconnected to form a closely matched pair of cortical

The Control of Voluntary Eye Movements: New PerspectivesRICHARD J. KRAUZLISSystems Neurobiology LaboratorySalk Institute for Biological Studies

Primates use two types of voluntary eye movements to track objects of interest: pursuit and saccades.Traditionally, these two eye movements have been viewed as distinct systems that are driven automatical-ly by low-level visual inputs. However, two sets of findings argue for a new perspective on the control ofvoluntary eye movements. First, recent experiments have shown that pursuit and saccades are not con-trolled by entirely different neural pathways but are controlled by similar networks of cortical and subcorti-cal regions and, in some cases, by the same neurons. Second, pursuit and saccades are not automaticresponses to retinal inputs but are regulated by a process of target selection that involves a basic form ofdecision making. The selection process itself is guided by a variety of complex processes, including atten-tion, perception, memory, and expectation. Together, these findings indicate that pursuit and saccadesshare a similar functional architecture. These points of similarity may hold the key for understanding howneural circuits negotiate the links between the many higher order functions that can influence behavior andthe singular and coordinated motor actions that follow. NEUROSCIENTIST 11(2):124–137, 2005. DOI:10.1177/1073858404271196

KEY WORDS Pursuit, Saccade, Eye movement, Attention, Perception

Address correspondence to: Richard J. Krauzlis, Salk Institute forBiological Studies, 10010 North Torrey Pines Road, La Jolla, CA92037 (e-mail: [email protected]).

REVIEW �



Volume 11, Number 2, 2005 THE NEUROSCIENTIST 125

networks (Tian and Lynch 1996a, 1996b). Functionalimaging studies in humans also support the idea of par-allel but distinct cortical pathways for pursuit and sac-cades (Petit and Haxby 1999; Rosano and others 2002).

These multiple cortical areas influence eye motor con-trol through several descending pathways. First, there aredirect projections to eye-movement-related structures inthe brain stem such as the superior colliculus (SC) andpremotor nuclei in the reticular formation (PMN). Thesepathways, which have figured prominently in the controlof saccades, have been recently demonstrated to exist forpursuit cortical areas as well (Yan and others 2001).There are also several less direct routes. One pathwaypasses through the pontine nuclei to eye movementregions of the cerebellum (oculomotor vermis, ventralparaflocculus [VPF]), which access the output motornuclei for eye movements by projections to the vestibu-lar nucleus and other brain stem motor nuclei (PMN).For pursuit, this cortico-ponto-cerebellar route has beentraditionally considered the primary control pathway,whereas for saccades, it has been viewed primarily as aregulatory side loop. There are also descending path-ways involving nuclei of the basal ganglia, such as thecaudate nucleus and the substantia nigra pars reticulata,which exert their influence on eye movements through

the SC. As with the direct projections to the brain stem,the pathways through the basal ganglia are well estab-lished for saccades but have only recently been demon-strated for pursuit (Cui and others 2003).

In summary, although pursuit and saccades have his-torically been viewed as anatomically distinct systems,new data argue that they have a similar functional archi-tecture and involve many of the same brain regions,including the brain stem, cerebellum, superior collicu-lus, and the cerebral cortex. In this admittedly selectivereview of the recent literature, we will start at the circuitsthat form and regulate the motor commands and windour way up through the areas that evaluate and extractthe signals needed to trigger and guide the movements.

Brain Stem

It has been known for some decades that the motor com-mands for saccades are constructed primarily by a circuitin the brain stem that generates the burst of neural activ-ity necessary to cause the rapid changes in muscle force that propel saccades. The elements of this circuit are spread across several nuclei in the pons andmesencephalon—the paramedian pontine reticular for-mation (PPRF), the rostral interstitial nucleus of themedial longitudinal fasciculus (riMLF), and the nucleusraphe interpositus (nRIP)—and contain several classesof saccade-related neurons (Luschei and Fuchs 1972;Keller 1974; Sparks and Sides 1974; Henn and Cohen1976; Raybourn and Keller 1977; Van Gisbergen andothers 1981; Henn and others 1984). Short-lead burstneurons emit a burst of spikes whose precise timingdetermines the amplitude of the saccade. Long-leadburst neurons exhibit a prelude of activity before emit-ting a saccade-related burst. Pause neurons in the nRIPdischarge steadily but stop firing during some or all sac-cades (omnipause neurons [OPNs]). Several models(e.g., Scudder 1988) have suggested how these neuronsmight participate in saccade generation. A trigger signal,probably from the SC, causes OPNs to pause their firingmomentarily, which then disinhibits burst neurons. Thisdisinhibition evokes a burst whose duration correspondsto the amplitude of the saccade; the burst duration iscontrolled by a negative feedback circuit and is adap-tively regulated in conjunction with the cerebellum.

New evidence indicates that parts of this brain stemcircuit for saccades are also involved in the control ofpursuit. The primary brain stem nuclei for controllinghorizontal and vertical gaze (the PPRF, riMLF, andcMRF) all receive direct inputs from the pursuit subre-gion of the FEF as well as from the saccade-related sub-region (Yan and others 2001). Recent recording studieshave shown that subsets of the neurons in these nucleihave pursuit-related as well as saccade-related activity.For example, some burst neurons in the PPRF are activeonly during saccades, but a second category of burstneurons is active during both saccades and pursuit(Missal and Keller 2001). Similarly, in the riMLF of thecat, some burst neurons fire in relationship to eye veloc-ity not only during saccades but also during pursuit

Fig. 1. Outline of the pathways for pursuit and saccadic eyemovements. Schematic diagram of the descending pathwaysare depicted on a lateral view of the monkey brain. Shadedregions indicate specific areas within the cerebral cortex, basalganglia, cerebellum, and brain stem, and arrows indicate theanatomical connections between these areas. Regions demar-cated with dashed lines indicate structures normally covered bythe cerebral cortex. For clarity, not all relevant areas are depict-ed (e.g., ascending pathways are omitted), and arrows do notalways correspond to direct anatomical connections. CN = cau-date nucleus (basal ganglia); FEF = frontal eye field; LIP = later-al intraparietal area; MT = middle temporal area; MST = medialsuperior temporal area; PMN = brain stem premotor nuclei(PPRF, riMLF, cMRF); PON = precerebellar pontine nuclei; SC =superior colliculus (intermediate and deep layers); SEF = sup-plementary eye field; SNr = substantia nigra pars reticulate;Verm = oculomotor vermis (cerebellum, lobules VI and VII); VN =vestibular nuclei; VPF = ventral paraflocculus (cerebellum).



126 THE NEUROSCIENTIST Voluntary Eye Movements

(Missal and Keller 2001). Perhaps most surprising arethe recent findings suggesting that OPNs play a role inpursuit. About half of the OPNs show significantdecreases in activity during the onset of pursuit as wellas pauses for saccades; they do not completely stop fir-ing as for saccades but reduce their activity by aboutone-third (Missal and Keller 2002). Microstimulation inthe region of the OPNs has long been known to halt sac-cades, but recent experiments show that such microstim-ulation also strongly decelerates pursuit (Fig. 2),although it does not completely stop pursuit (Missal andKeller 2002).

These studies indicate that the construction of themotor commands for pursuit and saccades involvesshared circuitry in the brain stem, and Figure 3 showsone candidate scheme for how the motor circuits for thetwo movements might be related. Analogous to the waythat OPNs are believed to gate the occurrence of sac-cades through inhibitory effects on excitatory burst neu-rons, OPNs could regulate the gain of pursuit throughtheir inhibitory effect on pursuit neurons in the nucleusprepositus hypoglossi (NPH) and the medial vestibularnuclei (MVN). Another novel class of pursuit-relatedneurons, the burst neurons in the PPRF and riMLF,might acquire their smooth-eye-velocity modulationthrough excitatory inputs from the PNs. By inhibitingthe OPNs and completing a loop with the pursuit neu-rons in the NPH/MVN, these neurons might act to latchthe pursuit system in an “on” state.

Many important details about this putative gatingmechanism remain unknown, but a circuit with thesefeatures could account for several properties of pursuitand saccades. If the gating of pursuit and saccadesinvolved shared circuitry in the brain stem, this wouldprovide a straightforward way to coordinate and regulatethe triggering of pursuit and saccades, consistent withbehavioral evidence that there is a shared inhibitorymechanism for pursuit and saccades (Kornylo and others2003). On the other hand, the difference in the level ofdisinhibition associated with the two movements couldprovide flexibility in determining what is required totrigger the two types of movements, consistent with theobservations that pursuit generally has a shorter latencythan saccades and that pursuit and saccades usually butnot always agree in their choice of a target (Krauzlis andothers 1999; Liston and Krauzlis 2003). The graded inhi-bition of the OPNs during pursuit would also be predict-ed to produce a smoothly graded disinhibition of theNPH/MVN neurons, consistent with the suggestion frombehavioral experiments that there is a variable gain con-troller in the pathways for pursuit eye movements(Grasse and Lisberger 1992; Krauzlis and Lisberger1994a; Keating and Pierre 1996; Krauzlis and Miles1996c).

These recent findings seemingly contradict clinicalobservations that damage to the brain stem reticular for-mation causes selective palsy for saccades (Hanson andothers 1986). However, the discrepancy is resolved whenone compares lesions of different sizes. Smaller brainstem lesions in humans and monkeys can result in

deficits of large saccades, with relative sparing of bothpursuit and small saccades (Henn and others 1984;Hanson and others 1986), but larger lesions of the retic-ular formation result in a conjugate gaze palsy thataffects both saccades and pursuit (Bogousslavsky andMeienberg 1987). Thus, depending on the size of thelesion, brain stem damage appears to limit the amplituderange of the eye movements that can be generated, ratherthan the type of eye movements.

Cerebellum

The cerebellar cortex and deep cerebellar nuclei play acrucial role in supporting the accuracy and adaptation ofvoluntary eye movements. Although several regionshave been implicated in the control of eye movements,two areas are especially well understood: the VPF andthe midline oculomotor vermis. Output neurons in theVPF project directly to oculomotor nuclei in the brainstem, whereas in the vermis, output neurons exert theireffect via projections to the fastigial oculomotor region(FOR), a deep cerebellar nucleus.

Damage to the cerebellum does not eliminate eyemovements but renders them highly variable and inaccu-rate. Ablation of the VPF and adjacent flocculus causeslarge and lasting deficits in smooth eye movements andthe ability to maintain fixation (Zee and others 1981;Rambold and others 2002). These dramatic effects mayreflect the close association of the VPF with the circuitin the brain stem that integrates eye position signals(Cannon and Robinson 1987). As illustrated by theexamples in Figure 4, lesions of the vermis or FOR dis-

Fig. 2. Microstimulation in the region of the omnipause neurons(OPNs) decelerates pursuit eye velocity. Average eye velocityon trials with microstimulation (thick solid line, n = 9) is com-pared to average eye velocity on trials without microstimulation(thin solid line, n = 8). During the period of microstimulation(indicated by the orange bar), eye velocity is reduced com-pared to the trials with no stimulation. Thinner lines and dashedlines indicate 95% confidence intervals of the mean eye veloc-ity. The vertical arrow indicates the onset of the 40 deg/s right-ward target motion. Adapted from Missal and Keller (2002, p 1889). Used with permission from the American PhysiologicalSociety.




rupt the timing, accuracy, and dynamics of saccades andalso the ability to adapt saccades (Robinson and others1993; Takagi and others 1998; Barash and others 1999).After damage to the vermis and FOR, saccades alsoexhibit a dysmetria that depends on eye position, sug-gesting that the cerebellar signals normally act to coun-terbalance the changing mechanical forces encounteredby the eye at different positions in the orbit.

The activity of neurons in the cerebellum providesinsight into how the motor commands for eye move-ments are shaped into their final forms. During pursuitand saccades, neurons in the FOR emit an early burst ofspikes for contraversive movements and a later burst ofspikes for ipsiversive movements (Ohtsuka and Noda1991; Fuchs and others 1993, 1994; Helmchen and oth-

ers 1994). These bursts reflect a push-pull arrangementin which the same neurons that provide an accelerativecommand for movements in one direction also provide abraking signal for movements in the other direction.Similarly, neurons in the VPF exhibit overshoots in fir-ing rate when pursuit eye velocity increases or decreas-es. These transient overshoots in the VPF also operate ina push-pull fashion and appear to reflect a calculated attemptto compensate for the sluggish mechanics of the eye mus-cles and orbital tissues (Krauzlis and Lisberger 1994b;Krauzlis 2000). The timing and size of these bursts changeafter adaptation of eye movements and for eye move-ments made from different orbital positions (Kleine andothers 2003; Scudder and McGee 2003), consistent withthe idea that the cerebellar output acts to maintain theaccuracy of eye movements under a variety of condi-tions. Although the discharge of individual cerebellarneurons is variable, the population response can providea motor command that is very precise; changes in thecontributions of individual neurons could therefore pro-vide a mechanism for adjusting the size and timing ofeye movements (Krauzlis 2000; Thier and others 2000).

Superior Colliculus

The SC has been traditionally described as a motor mapof saccade end points, but several lines of evidence arguethat the SC comprises a map of motor goals rather thanthe specific movement required to achieve that goal.

Fig. 3. Possible diagram of how oculomotor nuclei in the brainstem contribute to both pursuit and saccades. Excitatorysynapses are shown with small white circles; inhibitory synaps-es are shown with small black circles. Note that there are twodistinct types of inputs to the circuit: gating signals that areshared by pursuit and saccades and separate drive signalsconveying location and motion information. The omnipauseneurons (OPNs) play a crucial role in this circuit by regulatingwhen the descending drive signals are allowed to access thefinal motor pathways. EBN = excitatory burst neuron; NPH,MVN = pursuit-related neurons in the nucleus prepositushypoglossi and the medial vestibular nuclei; OMN = ocularmotor neurons; trig = interneuron that inhibits OPNs, therebytriggering a saccade and possibly pursuit; latch = interneuronthat putatively keeps OPNs inhibited during the saccade andpursuit movements.

Fig. 4. Disruption of the timing, accuracy, and adaptation ofsaccades after lesions of the cerebellar oculomotor vermis.Traces show horizontal eye position as a function of time(aligned with respect to saccade onset) during saccades beforeand after lesions of the oculomotor vermis. In this experiment,saccades were adapted by presenting a 10-degree forwardstep of the target, followed by a 3-degree backward step.Prelesion, the animal showed a decrease in saccade amplitudelate in adaptation (black arrow) as compared to early in adap-tation. Postlesion, there was a marked increase in the variabili-ty of saccade amplitudes (blue arrow) and an increase in laten-cy for corrective saccades (orange arrow). These effects persisted through the late phases of adaptation. From Takagiand others (1998, p 1925). Used with permission from theAmerican Physiological Society.




First, the locus of activity in the SC does not uniquelydetermine the amplitude of the eye movement that ismade. Neurons in the SC fire differently for saccadesmade to moving targets compared to saccades made tostationary targets, arguing that the SC neurons specifythe initial retinotopic location and that additional circuitsare responsible for getting the saccade to land accurate-ly on the target (Keller and others 1996). SC neuronsalso fire differently for saccades made to rememberedtargets compared to saccades made directly to visual tar-gets, again indicating that activity in the SC does notdetermine the exact metrics of the saccade (Stanford andSparks 1994).

SC activity also does not determine whether saccadeswill be accomplished with the eye alone or with a com-bination of the eye and head. When the head is immobi-lized, activity in the SC is associated with eye saccadeswith a specific direction and amplitude (Robinson 1972;Schiller and Stryker 1972). However, when the head isfree to move, SC neurons exhibit activity that is closelyrelated to the amplitude and direction of combined eye-head movements rather than to either the eye or headcomponent alone (Freedman and Sparks 1997). In theseunrestrained conditions, SC stimulation produces coor-dinated movements of both the eyes and head (Freedmanand others 1996). The amplitudes of these combinedmovements are larger compared to those evoked with thehead fixed because the evoked eye movements are thesame whether or not the head is free to move.Consequently, the standard depiction of the SC motormap obtained with the head restrained is distortedbecause it systematically underestimates the amplitudesof encoded gaze movements.

The SC also plays a role in the control of pursuit eyemovements. Activation and inactivation of the rostralSC, which represents the central visual field, modifiesthe metrics of pursuit, demonstrating a causal linkbetween SC activity and pursuit (Basso and others2000). Many neurons in the rostral SC modulate theirfiring rates during pursuit eye movements as well as dur-ing small saccades (Krauzlis and others 1997, 2000).This activity is not simply a visual response because itpersists in the absence of a visual target (Krauzlis 2001).This activity also does not convey motion signals forpursuit because although SC neurons respond to motionstimuli, they are not selective for the direction of motion(Krauzlis 2004). On the other hand, the complicated pat-tern of activity exhibited by these neurons during pursuit—and also fixation—can be explained by consid-ering the location of the tracked target within the neu-ron’s retinotopically organized response field (Krauzlisand others 1997, 2000). The distribution of activityacross the SC motor map therefore appears to provide areal-time estimate of the retinal location of the eye motorgoal for pursuit and fixation, as well as for saccades.

Recent experiments in cats have underscored this ideathat SC activity represents the motor goal and does notnecessarily specify the saccade end point. These experi-ments exploit the fact that cats tend to accomplish large

orienting movements with a series of smaller saccades inrapid succession rather than with a single large saccade.During these multistep movements, activity in the SC isinitially at the site corresponding to the retinal locationof the eccentric target and then progresses toward morecentral sites in a single sweep, even though the move-ment itself is achieved with multiple saccades. As aresult, the locus of activity in the SC does not match theamplitudes of the individual saccades used to acquire thetarget but instead indicates the remaining distance to thetarget (Bergeron and others 2003). The complementarypattern holds for neurons in the rostral SC, which repre-sent the central visual field and tend to be active duringfixation (Munoz and others 1991; Munoz and Wurtz1993). These rostral SC neurons remain inactive duringthe multistep movement, even though the movementpauses between each small saccade of the sequence,resuming their tonic activity only as the sequence drawsto a close and the target is acquired (Bergeron andGuitton 2002). Activity in the SC motor map thereforedoes not appear to be exclusively involved with control-ling saccade end points but serves a more general func-tion associated with specifying the goal for orientingmovements.

One possibility that has gained support is the idea thatthe SC plays a role in representing and selecting the tar-gets for orienting movements. For example, decreasingthe probability that a visual stimulus will be the target,by adding a variable number of irrelevant stimuli to thedisplay, decreases the visually-evoked and tonic activityof many SC neurons (Basso and Wurtz 1997, 1998).These changes are correlated with the latencies of thesaccades that follow but are not related to the amplitudeor peak velocity of the saccade. Similar effects are foundwith a single visual stimulus by varying the probability,between blocks of trials, that the target will appear in theneuron’s response field (Dorris and Munoz 1998). Theseeffects of stimulus probability are especially evidenteither before or soon after the visual stimuli are present-ed, indicating that prior information may be especiallyinfluential during the period of uncertainty that prevailsbefore unambiguous stimulus information is available toguide the eye movement choice.

During the latent period after the candidate targetshave been presented but before the movement is initiat-ed, SC neurons display a preference for the stimulus thatwill become the eye movement target. In a color-odditysearch task using saccades, some SC neurons discrimi-nate the target from the distractor with a delay that istime locked to stimulus onset, rather than saccade laten-cy, suggesting that they play a role in target selection inaddition to saccade preparation (McPeek and Keller2002). In contrast, other neurons discriminate the targetwith timing that is well correlated with saccade latency,suggesting that they are more directly involved with trig-gering saccades (McPeek and Keller 2002). In a match-to-sample task using pursuit and saccades, many SCneurons again exhibit selectivity for target stimuli, andthis selectivity can predict the timing of pursuit as well




as saccade choices (Krauzlis and Dill 2002). The signalindicating the correct choice emerges over time, forminga trade-off between speed and accuracy. The observedpursuit and saccade performances fall on different partsof the speed-accuracy curve predicted by neuronal activ-ity, supporting the idea that pursuit and saccades areguided by shared selection signals but involve differenttrade-offs between speed and accuracy (Krauzlis andothers 1999; Liston and Krauzlis 2003).

Manipulation of the fixated visual stimulus can alsomodify target-related activity in the SC. Many neuronsin the SC increase their firing rate after the fixation stim-ulus is extinguished, even if a visual target has not yetappeared in their response field, and these changes arecorrelated with the latencies of both pursuit (Krauzlis2003) and saccades (Dorris and others 1997; Sparks andothers 2000; Krauzlis 2003). Conversely, neurons in therostral SC that are typically active during fixationdecrease their firing after the offset of the fixation spot(Dorris and Munoz 1995; Dorris and others 1997).These changes in activity indicate a shift in the distribu-tion of activity across the SC in favor of those neuronsthat are likely to represent the impending target. Bychanging the baseline activity, the subsequent volley ofactivity evoked by the appearance of the target can morereadily trigger an eye movement, providing a neural cor-relate for the shared effects on pursuit and saccade laten-cies observed in this paradigm (Krauzlis and Miles1996a, 1996b; Krauzlis 2003). From these results, it hasbeen suggested that the same signals in the rostral SCthat are involved in the covert preparation of saccadesmight also control the gating of inputs for pursuit(Krauzlis 2003). This type of shared control couldexplain the linkage that has been observed in the selec-tion of targets for pursuit and saccades (Gardner andLisberger 2001, 2002). Although the mechanism has notyet been identified, one possibility is that this sharedcontrol is exerted by a projection from the SC to brainstem OPNs, the gatekeepers for saccades that have alsobeen recently implicated in the inhibitory control of pur-suit (Missal and Keller 2002).

The idea that the SC is involved in target selection hasnow been directly tested in a pair of studies (Fig. 5). Onestudy used a visual search task in which the target wasdefined as the “oddball” element in an array of visualstimuli (McPeek and Keller 2004). When the region ofthe SC representing the target was focally inactivated,saccades were often misdirected to distractors appearingin unaffected areas of the visual field (Fig. 5A).Importantly, the amplitude of this deficit was largerwhen the task of identifying the target was harder, argu-ing for an effect at the stage of target selection beyondany effect on saccade motor execution. The other studyused a luminance discrimination task and showed thatweak activation of the SC (i.e., microstimulation that issubthreshold for evoking saccades) biased the selectionof targets toward the stimulated location not just for sac-cades but for pursuit as well (Carello and Krauzlis2004). Using the classic “step-ramp” paradigm, thestimuli for pursuit appeared in one hemifield before

moving toward and into the opposite hemifield(Rashbass 1961), making it possible to distinguishbetween the initial location of the target and the directionof the eye movement, a distinction that is not possiblewith saccades. Critically, the effect of SC activation wasbased on the target location, not the eye movement direc-tion. For example, as illustrated in Figure 5B, when thestimulated region of the SC matched the distractor loca-tion (right), pursuit was more likely to follow the dis-tractor, even though this required an eye movement inthe opposite direction (leftward). These results argue thatthe SC plays a role in target choice per se, distinct fromits traditional role in motor preparation.

One important issue left unresolved by these studies iswhether the SC participates in target selection by biasingthe selection of the response goal or by shifting the allo-

Fig. 5. Activation and inactivation of the superior colliculus (SC)affects target selection. A, Effects of SC inactivation on sac-cades during a visual search task. Under normal conditions,monkeys were able to identify the target based on its uniquecolor and make saccades directly to it (left). The pattern of sac-cades changed after a local area of the SC was inactivated byinjection of muscimol, corresponding to the portion of the visu-al field in which the target was located (blue ellipse). After localinactivation, the monkeys made many inappropriate saccadesto the distractor stimuli (right). Reproduced with permissionfrom McPeek and Keller (2004, p 758). B, Effects of SC activa-tion on pursuit during a discrimination task. Under normal con-ditions, monkeys were able to correctly identify the targetbased on its luminance and generate a pursuit movement (hor-izontal eye speed) to follow it (right). Performance was changedafter a local area of the SC was activated with microstimulation,corresponding to the portion of the visual field in which the dis-tractor was located (orange ellipse). With local activation, themonkeys generated many more inappropriate smooth eyemovements to follow the distractor (left). Note that in the caseof this pursuit experiment, the affected site in the SC corre-sponds to the location of the selected stimulus (the distractor ison the right), even though this requires an eye movement in theopposite direction (the eye moves smoothly to the left). FromCarello and Krauzlis (2004, p 577). Copyright 2004 by CellPress.




cation of visual attention. The visual responses of SCneurons show enhancement consistent with an effect ofattention (Goldberg and Wurtz 1972; Kustov andRobinson 1996), and many SC neurons are active duringcovert shifts of attention evoked by spatially precise cuesbut not by nonspatial symbolic cues (Ignashchenkovaand others 2004). These findings support the idea thatthere is a common network for controlling attention andsaccades, consistent with the premotor theory of atten-tion (Rizzolatti and others 1987; Sheliga and others1995). Together with the activation and inactivationresults, these studies raise the intriguing possibility thatthe SC not only receives the selection signal and appliesit toward implementing the motor choice but also helpsregulate the sensory-motor processing that leads to thatselection.

Another unresolved issue is how target-related activi-ty in the SC is read out to trigger the appropriate eyemovement choice (Krauzlis and others 2004). One help-ful approach to this problem introduces the assumptionthat firing rates are proportional to the likelihood thatthe target is present, and the decision is affirmed whenactivity reaches a particular significance level(Carpenter and Williams 1995; Gold and Shadlen 2001).As shown schematically in Figure 6, the relevant deci-sion signal for target selection might be based not onlyon the firing rate associated with possible new targets(represented by activity at caudal sites in the SC) butalso on the firing rate associated with the currentlyfoveated stimulus (represented by activity at the rostralSC). If these firing rates are proportional to target likeli-hood, then this comparison between caudal and rostralsites in the SC could amount to a likelihood ratio test(Gold and Shadlen 2001; Krauzlis and others 2004). Ingeneral, likelihood ratio tests are useful for testingwhether a more complex model (in this case, that the tar-get is at an eccentric location) provides a better descrip-tion of the data than the simpler model (that the target isalready foveated) because it gives values that are relatedto common test statistics such as the F test and the χ2. Inthis case, every decision by the SC to select an eccentrictarget would amount to a rejection of the null hypothe-sis. This type of decision framework also has the advan-tage of being very flexible because the source of theinformation does not really matter; what matters is howthe information improves the estimate of target likeli-hood. For example, target selection should be based notjust on visual evidence but also on information aboutprior probability and expected rewards (Platt andGlimcher 1999; Ikeda and Hikosaka 2003). If these dif-ferent processes gave their answers in the same units(e.g., something proportional to likelihood), it would bepossible to combine and exchange these differentsources of information on an equal footing and then readthe answer out from the SC in meaningful way.

Cerebral Cortex

The SC plays a pivotal role in the control of voluntaryeye movements, but ablation of the SC has surprisingly

mild effects (Albano and others 1982). However, com-bined damage to the SC and areas of the cerebral cortexcan eliminate voluntary saccades (Schiller and others1980), indicating the importance of the cerebral cortexin providing signals that trigger and guide voluntary eyemovements.

Frontal Eye Fields

The functional importance of the FEF is especially evi-dent when the outcome involves some degree of choice

Fig. 6. Hypothetical decision mechanism explaining how activ-ity in the superior colliculus (SC) might be read out to accom-plish target selection. In the top panel, the monkey is initiallyfixating the central stimulus (blue square) and is consideringwhether to make an eye movement to a possible new target inthe periphery (orange square). The middle panel showsschematically how activity corresponding to the two stimuli isdistributed across the SC, with activity related to the fixatedstimulus at the rostral end and activity for the new stimulus ata more caudal location. Available data suggest, but have notyet proved, that the firing rate (FR) of SC neurons is propor-tional to the likelihood that the target is in the response field ofthe SC neuron (Krauzlis and others 2004). If so, then compari-son of activity across the SC amounts to a comparison of alter-native hypotheses, and the difference in activity would indicatethe relative likelihood of one hypothesis over the other. Thedecision of whether to select the new target (“GO”) or remainfixating (“STAY”) could then be determined by comparing thedifference in firing rate between caudal and rostral neurons (theputative decision signal) to a threshold value.




or self-control. For saccades, lesions of the FEF produceonly mild and temporary deficits in saccades when per-formance is tested with solitary visual targets (Dias andothers 1995; Sommer and Tehovnik 1997; Dias andSegraves 1999). However, the deficits after FEF lesionsare much more severe when the target stimulus isaccompanied by other irrelevant distracter stimuli(Schiller and Chou 1998, 2000) or when the saccade isdirected to a remembered location (Dias and others1995; Sommer and Tehovnik 1997; Dias and Segraves1999). Similarly, disruption of FEF activity in humansusing magnetic stimulation disrupts performance invisual search tasks (Muggleton and others 2003). Forpursuit, the effects are somewhat more dramatic (Fig. 7).Inactivation of the smooth eye movement subfield of theFEF (FEFsem) scales down the pursuit motor of visualtargets to about 25% of its normal value (Shi and others1998), and lesions of the FEFsem eliminate the predic-tive component of pursuit eye movements (Keating1991; MacAvoy and others 1991).

Neurons in the FEF exhibit properties consistent withdetermining when voluntary eye movements are initiat-ed. For pursuit, neurons in the FEFsem exhibit direc-tionally selective responses appropriate for guiding pur-suit, and, in addition, many of them discriminate thedirection of motion before the onset of pursuit (Tanakaand Lisberger 2002b). For saccades, the trial-to-trialvariability in reaction times is related to the variability inwhen the firing rates of FEF neurons reach a relativelyconstant threshold value (Hanes and Schall 1996); whenan impending saccade is canceled, the firing rates drop(Hanes and others 1998), suggesting that FEF activitycan regulate when and if a saccade will be triggered. Asin the SC (McPeek and Keller 2002), the FEF appears tocontain at least two classes of saccade-related neurons:One type is time locked to the stimulus and thereforeappears to be associated with the process of target selec-tion, whereas a second type is time locked to the move-ment onset and therefore appears to be involved withtriggering the movement (Sato and Schall 2003). Indeed,some FEF neurons discriminate visual targets even in theabsence of saccades or saccades directed elsewhere, sug-gesting that their activity corresponds to the allocationof attention rather than the motor preparation of sac-cades (Thompson and others 1997; Murthy and others2001).

The interplay between eye motor planning and visualfunctions such as selection and attention has been high-lighted in several experiments. Stimulation of theFEFsem evokes smooth eye movements and is the onlycortical region in which pursuit can be evoked when the eyes are fixating, but in addition to introducing adirection-specific signal into the velocity command forpursuit, stimulation also changes the gain of the pursuitresponse to new visual motion inputs (Tanaka andLisberger 2001, 2002a). If saccades are evoked by FEFstimulation as monkeys perform a motion discriminationtask, the movement end points are shifted toward thedirection corresponding to the nascent perceptual judg-ment (Gold and Shadlen 2000). Importantly, the ampli-

tude of the shift depends on the strength of the visualsignal; this result argues that the perceptual evaluation ofthe stimulus and the motor preparation of the saccade arenot serial stages of processing but instead occur togeth-er and perhaps involve a common level of neural organ-ization. Conversely, the allocation of attention itselfappears to be altered by stimulation of the FEF.Stimulation within the FEF with currents too weak toevoke saccades can nonetheless enhance visual respons-es in extrastriate area V4 (Moore and Armstrong 2003)and improve performance on a visual discrimination task(Moore and Fallah 2004).

Lateral Intraparietal Area

The LIP also plays a key role in the process of visualselection. Inactivation of the LIP does not producedeficits in the latency or accuracy of saccades to singletargets but dramatically reduces the frequency of sac-cades to the affected visual field when competing stim-uli are present (Fig. 8) and increases the time required tofind the target during visual search (Wardak and others2002). The emergence of these deficits when there aremultiple choices indicates a competitive interactionbetween the candidate targets and indicates how animalmodels may be useful for addressing the visual neglect

Fig. 7. Deficits in pursuit eye velocity after inactivation of thesmooth eye movement portion of the frontal eye fields(FEFsem) by injection of muscimol. Top, Single trial of step-ramp tracking just before injection of muscimol into the rightFEFsem (dark solid line) superimposed on the first trial afterinjection (dashed line). At time 0 ms, the target stepped 4degrees to the left and moved at 40 deg/s to the right. In thepreinjection trial, the eye trajectory approximately matched thatof the target, whereas in the postinjection trial, the tracking wasaccomplished mostly by the saccades. Bottom, Eye velocityprofiles superimposed for several trials preinjection (solid lines)and postinjection (dashed lines). For all six preinjection trials,the peak velocity reached or exceeded that of the target,whereas for all six postinjection trials, the peak velocity was farbelow that of the target. Rapid upward and downward deflec-tions of the velocity traces correspond to saccades. From Shiand others (1998, p 460). Used with permission from theAmerican Physiological Society.




and extinction syndromes that occur in humans (Payneand Rushmore 2003).

The activity of LIP neurons is strongly affected byinformation relevant for visual selection. For example,as in the SC and FEF, neurons in LIP respond morestrongly when the stimulus in their response field is atarget or behaviorally relevant than when it is a distrac-tor or irrelevant (Platt and Glimcher 1997; Gottlieb andothers 1998). When monkeys are asked to discriminatethe direction of motion in a random-dot visual displayand subsequently report their answer with a saccade, LIPactivity changes during the viewing of motion in a waythat predicts the monkey’s upcoming perceptual decision(Shadlen and Newsome 2001). Like the FEF, changes inLIP activity related to attention and selection can be dis-tinguished from motor preparation. For example, LIPactivity is lower for a visual cue prompting a saccadethan for a visual cue indicating that a saccade should notbe made; this difference does not match the change inmotor plans but is compatible with the idea that suchchanges garner increased attention (Bisley and Goldberg2003).

The activity of LIP neurons is also modulated byreward. When the size of reward is varied across blocksof trials, LIP neurons are more active when the expectedreward is higher (Platt and Glimcher 1999).Interestingly, using a different experimental design, neu-rons in the FEF did not show a reward-related modula-tion (Leon and Shadlen 1999), raising the possibility thatthe presence or absence of reward-related information isa point of distinction between the two cortical areas.

The parietal cortex also plays some role in pursuit, butthis has been less studied. Stimulation of the LIP canevoke smooth eye movements as well as saccades(Kurylo and Skavenski 1991), and about half of the neu-rons in the LIP and the ventral intraparietal area exhibitdirection-specific activity during pursuit (Bremmer andothers 1997; Schlack and others 2003). The pursuit-related activity of many LIP neurons is also modulatedby eye position and other extraretinal signals (Bremmerand others 1997; Schlack and others 2003), consistentwith the idea that the parietal cortex represents the goalsfor movements in coordinate frames appropriate foreffector organs such as the eyes, head, and hands(Andersen and others 1997; Calton and others 2002).

Supplementary Eye Field

The SEF plays a less direct role in the control of sac-cades and pursuit than the FEF does, but it appears to beespecially important for movements that are guided byinternal factors, rather than driven by external events.During a saccade task in which monkeys are free tochoose either of two identical stimuli to receive theirrewards, neurons in the SEF, FEF, and LIP exhibit activ-ity that anticipates the upcoming choice, but this activi-ty is largest and occurs earliest in the SEF (Coe and oth-ers 2002). Neurons in the SEF are also strongly modu-lated during tasks in which the goal is defined byabstract instructions, such as saccades directed to a part

of an object rather than a spatial location (Olson andGettner 1995; Tremblay and others 2002), saccadesdirected to the location opposite the visual stimulus(“antisaccades”; Schlag-Rey and others 1997), and sac-cades that occur within learned combinations orsequences of saccades. During pursuit, SEF neuronsexhibit the largest changes in activity when the targetmotion changes, especially when the timing of thosechanges is predictable (Heinen and Liu 1997).Accordingly, as shown in Figure 9, stimulation of theSEF can facilitate smooth pursuit eye movements, andthis effect is largest if the stimulation is applied just as aperiod of fixation is predictably drawing to a close andthe signal to initiate pursuit is about to be given (Missaland Heinen 2001, 2004).

MT and MST Areas

The MT and MST areas are the major sources of visualmotion information that is critical for guiding pursuitand for adjusting the amplitudes of saccades to movingtargets (Newsome and others 1985; Dürsteler and Wurtz1988). Recent studies have clarified how visual process-ing in these areas changes over time and is related toprocesses such as attention and perception.

Most of the directional information that can beextracted from MT neurons is conveyed within the first100 milliseconds of the neuronal response (Osborne andothers 2004). However, the precision of the directionalinformation conveyed by MT neurons is relatively poor,indicating that responses are probably pooled across thepopulation to match the direction discrimination of pur-suit. One possibility is that the pursuit system relies on

Fig. 8. Inactivation of the lateral intraparietal area (LIP) disruptssaccades to the affected visual field during a search task.Single-trial examples of visual search patterns after injection ofmuscimol into the right LIP. The small dots show eye positionsampled every 4 ms, large dots represent the search stimuli,and the open circle represents the location of the target. Whenthe target was in the ipsilateral visual field, unaffected by thelesion (right), the monkey typically found the target within asmall number of saccades. When the target was in the con-tralateral visual field, matching the site of the lesion (left), thenumber of saccades and overall search time dramaticallyincreased. Adapted from Wardak and others (2002, p 9882).Copyright 2002 by the Society for Neuroscience.




the center of mass of the population of MT neurons, andrecent studies have illustrated that an estimate of targetspeed can be obtained by taking a weighted average ofthe responses across the population of neurons(Churchland and Lisberger 2001; Priebe and Lisberger2004).

When the onset of a target stimulus is accompanied bya distractor, the initial activity of MT and MST neuronsexhibits very little selectivity for the target, and accord-ingly, the initial pursuit eye velocity mainly follows theaverage of the two motion signals (Ferrera and Lisberger1997; Recanzone and Wurtz 2000). The subsequentactivity of MT and MST neurons exhibits greater selec-tivity, and the eye movements elicited at these longerlatencies selectively follow one or the other stimulus,reflecting a winner-take-all mechanism (Recanzone andWurtz 2000). However, the changes in activity are rela-tively small and occur in only a minority of neurons, soit is not clear that these changes alone are sufficient toaccount for the selectivity of pursuit.

Solving the problem of computing motion signals fortracking appears to take some time. When multiple mov-

ing stimuli are presented that can be perceptuallygrouped as a single moving object, some MT neuronsinitially respond to the local motion of the stimulus com-ponents, but over the course of a few hundred millisec-onds, they begin to respond to the global motion of theobject as a whole. The changes in the directional tuningof the neural activity following a time course are similarto the changes in the direction of pursuit eye velocity(Pack and Born 2001). In behavioral experiments, sub-jects can readily perceive and track the veridical motionof partially occluded objects, despite the ambiguous andoften misleading local motions of the component edges(Stone and others 2000). The perceived and pursueddirections are initially more closely related to the aver-age direction of the local edge motions, but they con-verge to the veridical object motion direction after ~100milliseconds (Masson and Stone 2002). These findingsalso indicate that, over time, pursuit is guided by a sig-nal related to the perceived motion of the object, ratherthan the physical motion of the stimulus on the retina.This idea is supported by recent studies showing that themotion signals conveyed by some neurons in MST donot depend on retinal inputs (Ilg and Thier 2003) andthat they encode target motion in world-centered, ratherthan retina-centered, coordinates (Ilg and others 2004).

Conclusion and Outlook

Recent studies at a variety of levels have shown that thefunctional organization of the pursuit and saccadic eyemovement systems are much more similar than previ-ously recognized. Rather than composing two distinctsystems that operate as visuomotor reflexes, pursuit andsaccades are mediated by similar and sometimes over-lapping pathways and are guided by a variety of higherorder processes as well as by more direct sensory inputs(Fig. 10). The picture that emerges from these studies isquite different from that found in most textbooks, andeach point of departure from the traditional view raisesits own set of questions and challenges.

The overlap in the brain stem pathways argues that thegating of pursuit and saccades involves shared circuitrythat has been previously viewed as strictly part of thesaccadic system. Working out the brain stem wiring forsaccades alone has been difficult and is still not com-pletely resolved (Scudder and others 2002); it is unclearwhether extending it to pursuit will make it easier orharder to understand the functional states and transitionsaccomplished by this circuit.

Consistent with its role in other motor systems, ocu-lomotor regions of the cerebellum (VPF, vermis) appearto expertly tweak the commands for pursuit and saccadesto compensate for mechanical constraints and to adaptthe movements to changing circumstances. In addition tounderstanding how the cerebellar circuits accomplishthis function, there is also the conundrum that most ofthe descending signals that would appear relevant for thevisual control of pursuit and saccades go to the dorsalparaflocculus (Glickstein and others 1994) and not to theVPF and vermis.

Fig. 9. Activation of the supplementary eye fields (SEFs) canfacilitate anticipatory pursuit eye movements. On each trial,after a 500-ms fixation period (horizontal dashed lines), the tar-get was extinguished for 200 ms (gap in the dashed lines).When the target reappeared, it stepped to an eccentric positionand moved at a constant speed in the opposite direction. Top,Positions of the eye and target as a function of time from singletrials with and without stimulation. Bottom, The effect ofmicrostimulation was more evident in the traces of horizontaleye velocity and occurred even before the target was visible(orange arrow). The orange bar at the bottom indicates the peri-od of stimulation. From Missal and Heinen (2004, p 1258). Usedwith permission from the American Physiological Society.




In contrast to earlier descriptions of the pursuit andsaccade systems, the SC appears to be part of a sharedmechanism for selecting targets and perhaps triggeringthe two types of voluntary eye movements. It remains tobe clarified how this target-related activity is read out totrigger the appropriate motor commands, especiallybecause the SC does not mediate visual motion signalsfor pursuit (Krauzlis 2004). It is also unclear whether theSC simply applies a selection signal that is establishedelsewhere—for example, the cerebral cortex—orwhether it also plays a crucial role in the selectionprocess itself, perhaps by regulating shifts of visualattention.

Many of the signals that guide pursuit and saccadescome from a network of cortical areas and involve a vari-ety of processes important for the selectivity and guid-ance of voluntary eye movements: motor preparation,attention, perception, and expected reward. Under most

circumstances, these processes tend to give the sameanswer—attention and motor preparation are typicallydirected toward the most rewarding target—making itdifficult to tease them apart or to localize functions toparticular areas or classes of neurons. The broader chal-lenge is to move beyond identifying neural correlates ofprocesses we expect to find and instead to begin enu-merating the unique factors that operate in each regionand to explain how these factors interact across the net-work of neurons and brain regions.

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