Chapter 32 - Eye...

C H A P T E R

32Eye Movements

As we learned in Chapter 26, the photoreceptor mosaicof the vertebrate retina transduces light energy in the formof photons into neural activity, ultimately in the form ofaction potentials. The spatial resolution of this transduc-tion system is limited by the mosaic of photoreceptorsand the optics of the eye, but only if the eye is held station-ary with respect to the objects of interest in the externalworld. Thus, stabilizing the eyes with regard to the out-side world and aiming the eyes towardmoving or station-ary targets are critical challenges to effective vision.Evolutionary pressures have shaped the eye movementsystems of animals to meet this challenge in ways thatare tailored to the visual structures and behavioral needsof each species. In this chapter we examine the behavioraland neural systems used by vertebrates to control eyemovements in the support of vision.

As we shall see, the control of eye movements providesa window into several fundamental aspects of neu-roscience. Because the eyes are a relatively simplemechan-ical system, eye movements provide an excellent systemfor investigating the neural mechanisms of motor control,and also offer some of the clearest views of other complexprocesses, such as sensory-motor interactions, and thehigher-order control of behavior.

EYE MOVEMENTS ARE USEDTO STABILIZE GAZE OR TO

REDIRECT GAZE

Similar to the handling of a camera, the images that fallon the retina depend on how the eyes are held andmoved.The orientation of the eyes in the head and the orientationand position of the head in space together determine thegaze direction (i.e., gaze = eye + head) and, consequently,control the retinal image. These spatial arrangementsunderlie the two general classes of eye movements in

vertebrates. One class is responsible for stabilizing gaze.When animals move with respect to their surroundings,they risk degrading their visual acuity, because movingthe head necessarilymoves the eyes, and can cause imagesto streak across the retina. Gaze stabilization mechanismshave evolved to solve this problem. They maintain visualacuity during self-motion by stabilizing the retinal imageof the world with rotations of the eyes that exactly com-pensate for head and body movements. The neuralmechanisms for gaze stabilization are highly conservedacross vertebrates, reflecting thewidespreadneed to stabil-ize visual inputs despite other sensory and motor differ-ences between species. The second class is responsiblefor redirecting gaze. When animals visually inspect theirsurroundings, they may use these eye movements to aimthe line of sight at objects or features of particular interest,even when those items move. In contrast to stabilizinggaze, the process of redirecting gaze involves selectivelysampling the animal’s visual environment, because track-ing one visual object often causes the retinal images ofother objects to become blurred. Accordingly, themechan-isms for redirecting gaze are found only in animals thathave retinal specializations, such as the primate fovea, thatcan be used to examine a limited region of visual space at ahigher spatial resolution.

Stabilizing Gaze

There are two types of mechanisms for stabilizinggaze (Fig. 32.1): the vestibulo-ocular reflex (VOR) andthe optokinetic response (OKR). The VOR uses signalsfrom the vestibular labyrinth to counterrotate the eye-balls to keep retinal images stable during head move-ments. The rotational VOR is driven by head-rotationsignals from the semicircular canals and represents aphylogenetically old reflex present in all vertebratespecies. The fast transduction properties of the vestibular

697Fundamental Neuroscience, Fourth Edition. DOI: 10.1016/B978-0-12-385870-2.00032-9 © 201 Elsevier Inc. All rights reserved.3

Author’s personal copy

Fundamental Neuroscience, Fourth Edition, 2013, 697–714

http://dx.doi.org/10.1016/B978-0-12-385870-2.00032-9

periphery, combined with a direct 3-neuron pathway,give the rotational VOR a very short latency (<10ms).However, because the canals do not accurately trans-duce constant velocity head rotations, the output ofthe VOR decays over several seconds. Some vertebratesalso possess a translational VOR, which is driven byhead-movement signals from the otoliths. Unlike theimage motion caused by head rotations, which is uni-form across the visual field and can be fully compen-sated for by counterrotating the eyes, the imagemotion caused by translations are complex and can beonly partly eliminated by eye movements. This explainswhy the translational VOR is found only in animalswith central retinal specializations (e.g., foveal vision).

The optokinetic response (OKR) is driven by visual sig-nals about the en masse movement of images across theretina. Because of the slow transduction of visual signals,the OKR has a longer latency (50–100ms) than the VOR,but the use of visual motion signals makes it able to com-pensate for the constant motions and low speeds that theVOR cannot. The properties of the OKR therefore comple-ment those of the VOR in maintaining stable gaze duringmovements, and the visual signals used by the OKR playa major role in guiding adaptive changes in the VOR.Animals with foveal vision also possess an ocular followingresponse that is driven at very short latencies (~50ms) by

shifts in the retinal image, and that serves as the visualcomplement to the translational VOR (Miles, 1997).

Redirecting Gaze

Animals with foveal vision also possess several mechan-isms for redirecting gaze (Fig. 32.2). Saccadic eye move-ments act to quickly move the image of a visual targetfrom an eccentric retinal location to the center of the retinawhere it can be seen best. Saccades are very fast move-ments, reaching peak speeds greater than 500 deg/s andlasting only tens of milliseconds. Consequently, althoughsaccades are often triggered by visual stimuli (at typicallatencies of 150–250ms), the trajectory of saccades is notguided by visual feedback, but instead follows a stereo-typed profile that is largely determined by the size of themovement. Saccades do not require a visual stimulus, butcan be guided by othermodalities, and can even be directedtoward the location of imagined or remembered targets.

Smooth pursuit eye movements slowly rotate the eyes tocompensate for anymotion of the visual target and thus actto minimize the blurring of the target’s retinal image thatwould otherwise occur. Smooth pursuit is a relatively slowmovement whose trajectory is determined by the movingstimulus. Pursuit is triggered by visual stimuli at laten-cies similar to, but somewhat shorter than, the latencies

Surroundings Surroundings

Vestibulo-ocular reflex Optokinetic response

Line of sight remains fixed Line of sight follows surroundings

Counterrotationof eyes

Rotationof eyes

Visual motion ofsurroundingsHead rotation

Headrotation

TimeEye counterrotation

50−100 ms<10 ms

TimeEye rotationP

ositi

on

Pos

ition

FIGURE 32.1 Eye movements that stabilize gaze. The vestibulo-ocular reflex keeps the line of sight fixed in the world by counterrotating the eyesduring movements of the head. Here, the eyes rotate rightward at a short latency after the beginning of the leftward head movement. The optokineticresponse stabilizes the line of sight with respect to the moving visual surround, but does so after a longer latency.

698 32. EYE MOVEMENTS

V. MOTOR SYSTEMS



of saccades (typically 100–200 ms), and generates eyevelocities up to ~50 deg/s, continuously adjusted by visualfeedback about the target’s retinal image. Unlike saccades,pursuit cannot be generated in the absence of a stimulus,although moving targets that are sensed through modal-ities other than vision can also guide pursuit.

Saccades and smooth pursuit produce conjugate, oryoked, movements of the two eyes. These are also referredto as versional eye movements. In contrast, a third type ofmechanism for redirecting gaze, called vergence eye move-ments, produces disconjugate movements; the two eyesmove in opposite directions or by different amounts. Ver-gence eye movements act to change the depth at whichthe eyes’ lines of sight meet. When we look at a near objectour eyes converge (rotate inward), and when we look at afar object, our eyes diverge (rotate outward). Before redir-ecting our gaze to an object at a different distance, the pairof images produced by that object will be spatially mis-matched between the two eyes, causing binocular dispar-ity. Also, because the curvatures of the two eyes’ lensesare set to focus the currently viewed object, the image ofthe new object will also be blurred. These two signals,binocular disparity and blur, drive the combination of ver-gence eye movements and accommodation (which changesthe dioptric power of the lenses by contracting or relaxingthe ciliary muscle) that bring the new object into focuson the fovea of both eyes. Vergence and accommodationare tightly linked and are often referred to together as thenear response. When evoked by themselves (e.g., by binocu-lar disparity), vergence movements are very slow, takingup to 1 second to converge or diverge the eyes. However,

when they occur in combination with faster versional eyemovements such as saccades, vergence movements speedup, and interestingly, so does accommodation.

Fixation and Fixational Eye Movements

In between gaze movements, the eyes are actively heldsteady by a fixation mechanism. By preventing the eyesfrom redirecting gaze to another visual target, fixationmakes it possible to visually inspect a particular object atlength. Periods of fixation typically last about 200ms butvary depending on what the animal is doing. Fixationdoes not necessarily act to keep the eyes from moving,but to hold the eyes steady with respect to the environ-ment. For example, gaze stabilization mechanisms suchas the VOR are active during periods of fixation.

Even during periods of steady fixation of a stationaryobject, the eyes are not completely still. The eyes typicallymake tiny movements during fixation in seemingly ran-dom directions that cause very slight changes in howimages fall on the retinal mosaic but without displacingimages from the fovea. Microsaccades are very small sac-cades with amplitudes typically less than 0.1 degree ofvisual angle, and are interspersed with slow drifts (speedsless than ¼ degree per second) of similar amplitude. Thefunction of these movements remains unclear. However,like other larger saccades, they can prevent the adaptationof retinal signals that would occur with perfectly stabi-lized images, they are influenced by shifts of attention,and they can be strategically targeted or suppresseddepending on the task.

Saccades Smooth pursuit

Movingtarget

Continuous changein eye position

Rapid change ineye position

Newtarget

Oldtarget

Eye position

Eye position

Eye velocityEye velocity

~100 ms~100 ms

~20

deg

/s~

10 d

eg

~40

0 de

g/s

~10

deg

FIGURE 32.2 Eye movements thatredirect gaze. Saccades change the line ofsight to place the retinal image of visualtargets onto the fovea. They are character-ized by rapid changes in eye position(upward deflection in eye position trace)involving very high eye velocities (briefpulse in eye velocity trace). Smooth pur-suit continuously changes the line of sighttominimize blurring of the target’s retinalimage. These movements are character-ized by smooth and continuous changesin eye position (ramp in eye positiontrace) involving lower eye velocities(smooth step in eye velocity trace).

EYE MOVEMENTS ARE USED TO STABILIZE GAZE OR TO REDIRECT GAZE 699

V. MOTOR SYSTEMS



THE MECHANICS OF MOVINGTHE EYES

Each Eye Is Controlled by ThreePairs of Muscles

Moving the eye involves rotating the globe of the eye inthe orbital socket of the skull. Because the eye undergoesminimal translation during movement, it can be viewedas a spherical joint with an orientation defined by threeaxes of rotation (horizontal, vertical, and torsional). Corre-spondingly, the orientation and movement of each eye isaccomplished by three complementary pairs of extrao-cular muscles (Fig. 32.3). The lateral and medial rectusmuscles form an antagonistic pair that controls the hori-zontal position of the eye. Contraction of the lateral rectus(and commensurate relaxation of themedial rectus) causesthe eye to abduct, or rotate outward. Conversely, contrac-tion of the medial rectus (and relaxation of the lateral rec-tus) causes the eye to adduct, or rotate inward. The actionsof the other two pairs of muscles are more complex. Whenthe eye is centered in the orbit, the primary effect of thesuperior and inferior recti is to elevate (rotate up) ordepress (rotate down) the eye. However, when the eye isdeviated horizontally in the orbit, these muscles also con-tribute to torsion, the rotation of the eye around the line ofsite that determines the orientation of images on the retina.The primary effect of the superior and inferior obliques is

intortion (the top of the eye rotates toward the nose) orextortion (the top of the eye rotates away from the nose),but depending on the horizontal deviation of the eye,these muscles may also help determine the vertical orien-tation of the eye. Eye movements therefore involve rede-fining the 3-dimensional orientation of the eye bychanging the balance of forces applied to the globe by allthree pairs of extraocular muscles.

The mechanics of moving the eye may seem simple,but actually provide a computationally complex chal-lenge for the brain. Because the eye is free to rotate in3-dimensions, the final orientation of the eye dependson the order in which the rotations are carried out—for example, “turn-then-spin” gives a different outcomethan “spin-then-turn.” This property is referred to asnoncommutativity. In fact, when the eye moves, the final3-dimensional orientation of the eye and the axis of rota-tion used to get there are not arbitrary, but form anorderly set. Donder’s law states that the orientation ofthe eye is always the same when the eye is aimed in aparticular direction. Listing’s law specifies these orienta-tions by stating that the axes used to rotate the eye areconfined to a single plane, referred to as Listing’s plane.These orderly relationships are achieved, at least in part,by a mechanism that involves the muscles themselves(Klier, Meng, & Angelaki, 2011). The extraocular mus-cles consist of two distinct layers: global fibers, whichattach directly to the globe of the eye, and orbital fibers,

BOX 32.1

E Y E MOVEMENT S AND R EAD INGDuring reading, saccadic eye movements bring succes-

sive snippets of text images to the center of the retina. Theamplitude of the saccades depends on the letter size—a typi-cal reader makes saccades that shift the line of sight byabout 8 character spaces. In common situations—for exam-ple, viewing 12-point font at a distance of about 18 inches—each saccade is therefore only a couple of degrees in ampli-tude. The majority of saccades (~85%) form a forward pathalong the line of text (e.g., left to right for English readers),but a substantial minority of saccades (~15%), referred to asregressions, direct the line of sight back to text that has alreadybeen foveated.

The periods of fixation between saccades are crucial forreading comprehension, and typically last only about one-fifth of a second (~200 ms). Fixation provides the high-acuity input about individual letters—for example, tellingthe difference between “o” and “c”—that is necessary to cor-rectly identifywords. The number of letters that can be proc-essed during each fixation (the perceptual span) is a key factorin determining reading proficiency. In skilled readers, the

perceptual span stretches ahead of the currently fixatedpoint, covering about 14 letters forward and only about4 letters backward. Letters at the center of the perceptualspan are processed for meaning and identifying words; let-ters at the edges of the perceptual span appear to be impor-tant for parsing the text and perhaps determining thelanding points for upcoming saccades.

The skillful deployment of saccades and fixation for read-ing requires a great deal of practice, and represents animportant developmental milestone for visual-motor con-trol and cognition. In typical individuals, as text becomesharder to read, the amplitudes of saccades decrease, thenumber of regressions increase, and the duration of fixationsincrease. In reading disorders, such as dyslexia, these pat-terns are exaggerated, and accompanied by other unusualscan path features, such as targeting the beginning ratherthan the middle of words. This situation poses a chicken-or-the-egg problem: are reading disorders caused by a prob-lem with controlling eye movements, or are eye movementproblems caused by the reading disorder?


V. MOTOR SYSTEMS



which terminate in connective tissue that ensheathes thebody of the muscle and acts like a moveable pulley forthe global fibers. Because the pulleys themselves movewhen the muscle is contracted or relaxed, the pullingdirection of the extraocular muscles changes with eyeposition. These gaze-dependent mechanical changes inmuscle action largely account for Listing’s law (Demer,2006).

Interestingly, Listing’s law is obeyed during saccadesand smooth pursuit, but is violated during the VORand the OKR. This difference presumably stems fromthe different inputs for these movements. Saccades andsmooth pursuit may follow Listing’s law because theyinvolve local 2-dimensional retinal inputs that do notuniquely specify the orientation of the eye. In contrast,the VOR is driven by 3-dimensional inputs from thesemicircular canals for which the extra degree of freedomis not redundant. Thus, the mechanics of the eye musclesimpose kinematic constraints that are helpful duringvisually guided eye movements, but these constraintscan be altered or lifted by neural control signals duringgaze stabilization.

Central Control of the Extraocular Muscles

The six extraocular muscles are innervated by three ofthe bilaterally paired cranial nerves (Fig. 32.4). The oculo-motor nerve (cranial nerve III) innervates the medialrectus, the superior and inferior rectus, and the inferioroblique on one side of the head. The cell bodies for thesemotor neurons thus lie in the third cranial nerve nucleus.The oculomotor nerve also contains the fibers that controlaccommodation of the lens. The trochlear nerve (cranialnerve IV) innervates the superior oblique muscle, and theabducens nerve (cranial nerve VI) innervates the lateralrectus. These three pairs of nuclei, distributed throughthe brain stem, contain all of the oculomotor motor neu-rons and are heavily interconnected by a pathway calledthe medial longitudinal fasciculus (mlf). This interconnec-tion is crucial for the precise coordination of the extraocularmuscles that is necessary for the control of eye movements.

The firing rates of the oculomotor motor neurons deter-mine the forces applied by the extraocular muscles and,consequently, whether the eye moves or is held in place(Fuchs & Luschei, 1970). When the eye is stationary, the

Superior rectus(turns eye upward

and inward)Superior oblique

(turns eye downwardand outward)

Medial rectus(turns eye inward)

Lateral rectus(turns eye outward)

Inferior rectus(turns eye downward

and inward)Inferior oblique

(turns eye upwardand outward)

FIGURE 32.3 Muscles of the eye. Eyemovements are controlled by six extrao-cular muscles arranged in three pairs,shown here in a cutaway view of the eyein its socket, or orbit.

THE MECHANICS OF MOVING THE EYES 701

V. MOTOR SYSTEMS



firing rate of oculomotor motor neurons is proportional toeye position, because under static conditions the balanceof forces exerted on the globe determines the orientationof the eye (Fig. 32.5). Each motor neuron has a recruitmentpoint (an eye position at which themotor neuron begins tofire) and a characteristic slope (the change in firing rateas the eye rotates in the pulling direction of the relevantmuscle). Thus, as in the skeletal system, oculomotor motorneurons have a fixed recruitment order. When the eyemoves in the pulling direction of the motor unit, oculomo-tor motor neurons exhibit a high-frequency pulse of

activity that drives the high-velocity phase of the eyemovement. The high-frequency pulse is followed by a sus-tained step-like increase in firing rate appropriate for thenew static position of the eye. When the eye moves inthe opposite direction, the motor neurons pause their fir-ing during the movement and then resume their activityat a lower sustained level.

The neural commands from these motor neurons there-fore take the form of a pulse-step during rapid eye move-ments such as saccades. The amplitude and durationof the pulse determine the speed and duration of the

Thalamus

Superiorcolliculus

MRF

lllIV

n.IV

mlf

MBn.III

Pontinenuclei

PPRF

n.VI

n.VIINPH

VN

Cerebellum

VI

iC

riMLF

FIGURE 32.4 Oculomotor nuclei inthe brainstem. Parasagittal section throughthe brainstem, cerebellum, and thalamusof a rhesus monkey, showing the locationof the major brainstem nuclei involvedin the control of eye movements. Motorneurons for the eye muscles are located inthe oculomotor nucleus (III), trochlearnucleus (IV), and abducens nucleus (VI),and reach the extraocular muscles via thecorresponding nerves (n. III, n. IV, n. VI).Premotor neurons for controlling eyemovements are located in the paramedianpontine reticular formation (PPRF), themesencephalic reticular formation (MRF),rostral interstitial nucleus of the mediallongitudinal fasciculus (riMLF), the inter-stitial nucleus of Cajal (IC), the vestibularnuclei (VN), and the nucleus prepositushypoglossi (NPH). The medial longitudi-nal fasciculus (mlf) is a major fiber tractcontaining the axons of these neurons.Other abbreviation: MB, mammillarybody of the hypothalamus.

Change in eye position

Lateralrectus

Spikes

Firing rate

Abducens N. (Vl) motor neuron activity

Oculomotor N. (lll) motor neuron activity

~100 ms

~40

0 sp

ikes

/s~

400

spik

es/s

Medialrectus

FIGURE 32.5 The firing rate patternsof eye movement motor neurons duringhorizontal eye movements. The rapidrightward change in eye position, indi-cated by the upward deflection in theeye position trace, involves contractionof the right lateral rectus and relaxationof the right medial rectus. This is accom-plished by a pulse-step increase in activityof the agonist motor neurons in the abdu-cens nucleus, and a pause-step decrease inactivity of the antagonist motor neuronsin the oculomotor nucleus.


V. MOTOR SYSTEMS



movement, and the amplitude of the step determines thefinal static eye position. The need for the pulse derivesfrom the sluggish dynamics of the eye and orbital tissues,which is dominated by the viscosity of the extraocularmuscles. If the eye were moved by only a step change inforce, it would take nearly a second for the eye to settleat its new orientation, which would obviously be incom-patible with the goal of supporting vision. Similarly, dur-ing slow eye movements such as smooth pursuit, theneural commands from the motor neurons consist of aramp-like change in activity to drive the smooth changesin eye position, plus an additional increment to overcomethe sluggish dynamics of the eye. These patterns of activ-ity are precisely adjusted by central mechanisms involvingthe brainstem and cerebellum, and illustrate a generalproblem in motor control—the need to convert desiredactions into appropriately formed motor commands.The solution appears to involve the use of internal modelsthat allow central mechanisms to take into accountthe dynamic properties of the body part or object to bemoved.

Oculomotor motor units are also unusual in severalways (Buttner-Ennever, 2007). Unlike skeletal motor units,eye motor neurons participate equally in all types of eyemovements, regardless of the speed involved. The extrao-cular muscles contain muscle spindles, but no Golgitendon organs, and there are no ocular stretch reflexes.Instead, eye proprioception appears to mainly come frompalisade endings on the eye muscle tendons. The functionof this input is unclear, but it is distributed via the trigem-inal nucleus tomany key structures in the oculomotor sys-tem (including the vestibular nuclei, cerebellum, superiorcolliculus, and frontal eye fields) and may play a role inthe long-term adaptive control of eye movements.

THE FUNDAMENTAL CIRCUITSFOR STABILIZING GAZE

The Vestibulo-Ocular Reflex (VOR) StabilizesGaze during Head Movements

The function of the VOR is to stabilize retinal imagesduring head movements by using head-motion signalsfrom the vestibular organs. A purely rotational VOR canbe elicited in complete darkness by rotating the headroughly about its center (e.g., the interaural axis). Headrotations stimulate the semicircular canals of the innerear (Chapter 29), which provide the sensory signals abouthead motion that drive this highly conserved mechanismfor counterrotating the eyes. During sustained rotationsof the head, the eyes cannot continue to counterrotate end-lessly in the orbit, but are intermittently and rapidly resetto a central position during the ongoing compensatory eyerotation. The profile of eye position over time during the

VOR therefore exhibits a characteristic sawtooth patternconsisting of the slow-phase counterrotations and quick-phase resetting eye movements. This pattern is callednystagmus, and is described by the direction of the quickphases (Fig. 32.6 is an example of right-beat nystagmus).

The speed of the slow phases during nystagmus indi-cates how effectively the VOR is compensating for thehead rotation. The degree of compensation is often charac-terized by the VOR gain, which is defined as the ratio ofslow-phase eye speed over the speed of head rotation. Per-fect compensation occurs when the eye rotates in theopposite direction at exactly the same speed as the headrotation, which corresponds to a gain of 1. The ability ofthe VOR to compensate for head motion is limited bythe dynamics of the signals from the semicircular canals,which act as “high-pass” sensors of head velocity. Thus,the VOR is very effective (its gain is near 1) for fast back-and-forth head rotations that take a second or less to com-plete (i.e., frequencies over 1Hz), but it is much less effec-tive for slow head rotations that continue over manyseconds (e.g., 0.1 Hz). Under natural conditions, this lim-itation of the VOR does not pose a problem for vision,because at these lower speeds visual signals can be usedto stabilize gaze very effectively through the optokineticresponse.

The fundamental neural mechanism for the VOR con-sists of brainstem circuits linking the vestibular afferentsto the extraocular muscles, including a direct 3-neuronarc pathway (Fig. 32.6). For example, during a rightwardhead rotation vestibular afferents from the horizontalsemicircular canal on the right side increase their firingrates, and this increase is passed on to neurons in the ves-tibular nucleus (VN) on the same side. These vestibularnucleus neurons, in turn, increase the activity of motorneurons and interneurons in the abducens nucleus (VI)on the opposite (left) side. Motor neurons in the abducensinnervate the lateral rectus of the left eye, completing the3-neuron arc. Interneurons in the abducens provide acrossed projection back to the right oculomotor nucleus,where motor neurons innervate the medial rectus of theright eye. By contracting both the left lateral rectus andthe right medial rectus, the two eyes rotate leftwardtogether in response to the rightward head rotation. Inaddition, because the vestibular afferents on the left sidedecrease their activity during a rightward rotation, a com-plementary circuit causes relaxation of the right lateralrectus and the left medial rectus. The VOR is thereforecontrolled in a push-pull fashion that yokes the move-ments of the two eyes through the bilateral symmetry ofthese basic circuits.

These direct pathways are key components of the VORmechanism, but the VOR also requires indirect pathwaysto function correctly. As discussed in the previous section,the firing rate of oculomotor motor neurons is primarilyrelated to eye position, but the afferent signals from

THE FUNDAMENTAL CIRCUITS FOR STABILIZING GAZE 703

V. MOTOR SYSTEMS



the semicircular canals are primarily related to the headvelocity. In order to construct the motor commandsneeded to hold, as well as move, the eyes during theVOR, the brain needs to transform the dynamic signalsprovided by the vestibular afferents into the combinationof dynamic and static commands found on motor neu-rons. Similar to the operation of mathematical integrationin calculus, this process involves the temporal integrationof velocity inputs into position signals.

The neural integrator for eyemovements is accomplishedby neurons in the vestibular nuclei and two other brain-stem nuclei—the nucleus prepositus hypoglossi (for hori-zontal components) and the interstitial nucleus of Cajal(for vertical)—and is fine-tuned by connections betweenthese brainstem nuclei and the vestibulocerebellum(Cannon & Robinson, 1987). The output from the neuralintegrator pathway sums with the signals from the directpathway to provide the motor neurons with the completeset of velocity and position commands needed to accom-plish the VOR. Importantly, all conjugate eye movementsalso use this same indirect integrator pathway. Thus,although the source of the velocity signals for the VOR,OKR, saccades, and pursuit are quite different, they appearto share a common brainstemmechanism for transformingthese signals into the final motor commands.

The Optokinetic Response (OKR) UsesVisual Inputs to Stabilize Gaze

The OKR also functions to stabilize retinal images dur-ing head movements, but uses visual inputs to infer thedirection and speed of head motion rather than respond-ing directly to head-velocity signals. The optimal stimulusfor the OKR is full-field motion of the visual environmentthat, like head rotations, causes a saw-tooth pattern of eyemovements referred to as optokinetic nystagmus. Like theVOR, the slow phase movements during nystagmus com-pensate for the head rotation that presumably caused thefull-field motion. However, because the OKR is drivenby visual signals, which are processed much more slowlythan vestibular signals, the range of motions that are effec-tively compensated by the OKR is quite different from theVOR. The OKR is very effective (its gain is near 1) for slowrotations that continue over many seconds, but it is muchless effective for very fast back-and-forth rotations. Theseproperties of the OKR therefore complement those of theVOR and together, the two types of mechanisms can effec-tively stabilize gaze over a much wider range of speedsand behavioral conditions than either could achieve alone.

The interlocking nature of the two systems is also evi-dent in the neural pathways for the OKR, despite the

Time

Slowphases

Quickphases

Headrotation

Slowphase

Quickphase

Lateralrectus

Vl(abducens)

lll

Medialrectus

VN

Semicircularcanals

Rightward head turn

Line of sight remains fixed

Pos

ition

FIGURE32.6 The eyemovements and neural circuits for the VOR. During a sustained rotation of the head (here, rightward), the eyes rotate slowlyto the left (downward deflections in eye position trace labeled “slow phases”), and then abruptly shift rightward to reset the eyes toward a central posi-tion (upward deflections in eye position trace labeled “quick phases”). This is an example of right-beat nystagmus. The diagramof the basic VOR circuitshows the push-pull organization of the horizontal VOR.When the head rotates rightward, activity increases in the right semicircular canal, right ves-tibular nucleus (VN), and left abducens nucleus (VI). This leads to increased activation of the left eye lateral rectus and, through a crossed projection tothe oculomotor nucleus (III), increased activation of the right eye medial rectus. The complementary set of pathways (colored in gray) show decreasesin activity.


V. MOTOR SYSTEMS



difference in their input signals. In vertebrate specieswithout foveal vision, such as the rabbit, the visual proces-sing for the OKR is accomplished entirely within thebrainstem. Direction-selective retinal ganglion cells projectdirectly to a set of visual nuclei in the midbrain called thepretectum and accessory optic nuclei. In species withfoveal vision, the visual properties of these nuclei aredetermined not only by inputs from the retina, but are alsoshaped by inputs from visual areas of the cerebral cortex.Neurons in the accessory optic nuclei have very largereceptive fields and respond selectively to global visualmotion that would result from rotating the head about aparticular spatial axis. Remarkably, the selectivity of indi-vidual neurons is restricted to one of the three axes of rota-tion that are also detected by the semicircular canals. Thiscommon rotational coordinate system makes it easier tocombine visual reafferent signals about head motion fromthe accessory optic nuclei with the vestibular afferent sig-nals provided by the labyrinths. Accordingly, neurons inthe pretectum and accessory optic nuclei project to the ves-tibular nuclei and nucleus prepositus hypoglossi, wherethese visual signals join the same final pathways used bythe VOR. These nuclei also project to the vestibulocerebel-lum, where the visual signals contribute to the velocitycommands for the OKR and other smooth eye move-ments, and also act as feedback signals that play a criticalrole in the long-term adjustment of the VOR.

THE COMMANDS FOR REDIRECTINGGAZE ARE FORMED IN THE BRAINSTEM

The commands for redirecting gaze use the same finalmotor pathways that are used for stabilizing gaze, but thesignals and mechanisms giving rise to the movement com-mands are quite different. For smooth pursuit, they arebased on motion signals about the visual target that arefirst extracted in specialized areas of the cerebral cortexand then used to commandeer the brainstem and cerebellarpathways for the OKR. For saccades, which are not guidedby visual feedback, a specialized circuit in the brainstemreticular formation produces the stereotyped velocity com-mand that determines the trajectory of the saccade.

The Motor Commands for SaccadesAre Constructed in the BrainstemReticular Formation

The control signals for saccades descending fromhigher centers specify the location of the target, which isthen transformed by circuits in the brainstem reticular for-mation into the motor commands for saccades (Fig. 32.7).The horizontal and vertical components of saccades areformed by separate but interconnected circuits—the hori-zontal commands are formed in the paramedian pontine

reticular formation (PPRF), and the vertical commandsare formed in a part of the mesencephalic reticular forma-tion called the rostral interstitial nucleus of the mediallongitudinal fasciculus (riMLF).

Within these brainstem circuits, often referred to as thesaccadic burst generator, several different classes of neuronswork together to construct the saccade motor command(Keller, 1974). Burst neurons fire a high-frequency volley ofaction potentials that begins ~10ms before the onset ofthe saccade and ends slightly before the saccade lands onthe target. The firing rate during the burst is related to theinstantaneous velocity of the saccade, and the number ofspikes in the burst is related to the amplitude of the saccade.There are several types of burst neurons. Excitatory burstneurons (EBN), sometimes called “medium-lead burstneurons,” provide the velocity signal for the eye musclesthat will contract during the saccade, and specify the“pulse” portion of the saccade motor command. The EBNsprovide a copyof this velocity signal to the brainstemnucleiof the neural integrator, which then generates the “step”portion of the motor command, just like they do for othereye movements. EBNs also contact inhibitory burst neu-rons (IBN), which provide a crossed projection that inhibitsmotor neurons for the antagonist eyemuscles thatwill relaxduring the saccade. Finally, long-lead burst neurons(LLBN) show changes in their activity well in advance ofthe saccade, presumably reflecting inputs received fromhigher centers, andprovide an excitatory input to theEBNs.

The other major class of neurons in the saccadic burstgenerator is the omnipause neurons (OPN). These neuronsfire at a constant high rate (~100 spikes/s) during fixation,but completely pause their activity just before and duringsaccades in all directions. Because the OPNs directly inhi-bit burst neurons, their tonic activity prevents unwantedsaccades during fixation, and the pause in their activityunleashes the synchronized bursts of action potentials thatinitiate and drive the saccade. The onset of the pause inOPN activity appears to be triggered by inhibitory signalsoriginating from higher brain centers, but the duration ofthe pause does not determine when the saccade ends.Instead, stopping saccades involves another inhibitoryinfluence on burst neurons. One likely candidate is theoculomotor cerebellum (lobules VI and VII of the vermisand the caudal fastigial nucleus). The oculomotor vermisis interconnected with the saccadic burst generator andplays a crucial role in adjusting the metrics of saccadesso that the eyes land accurately on the target at the endof the gaze movement.

The Motor Commands for Pursuit AreFormed in the Brainstem and Cerebellum

The control signals for pursuit descending from highercenters continuously specify the motion of the target to befollowed with the eyes. Thus, in contrast to saccades,

THE COMMANDS FOR REDIRECTING GAZE ARE FORMED IN THE BRAINSTEM 705

V. MOTOR SYSTEMS



pursuit does not require motor circuitry to construct thevelocity command from scratch. Instead, the pursuit path-ways in the brainstem and cerebellum sculpt the descend-ing control signals to form an appropriately shapedvelocity command, and provide a copy of this velocity sig-nal to the neural integrator to generate the position com-ponent of the motor command.

The velocity commands for pursuit arise in areas of thecerebral cortex and reach the final motor circuits throughseveral routes (Fig. 32.8). One pair of pathways involvesprojections from the cerebral cortex to the cerebellum viaa large set of relay neurons on the floor of the brainstemcalled the basal pontine nuclei. Areas in extrastriate visualcortex provide signals related to visual motion throughthe dorsolateral pontine nuclei to a portion of the vestibu-locerebellum called the ventral paraflocculus. The frontalcortex provides signals related to target and eye velocitythrough the dorsomedial pontine nuclei, and the adjacentnucleus reticularis tegmenti pontis, to the oculomotor cer-ebellum (vermis), the same portion of the cerebelluminvolved in adjusting themetrics of saccades. Both of thesecerebellar regions provide inputs to parts of the brainstemmotor pathways that we have already discussed. The out-put of the ventral paraflocculus is closely related to eye

velocity and terminates in the vestibular nuclei, where itcontributes to the velocity command for pursuit, and alsoprovides an input to the neural integrator. The output ofthe oculomotor vermis is less well defined but appears tobe related to eye acceleration as well as eye velocity. Theoutputs of the vermis and the associated deep cerebellarnucleus (the caudal fastigial nucleus) are sent to neuronsin the brainstem reticular formation, and may play a rolein shaping the velocity command appropriately whenthe target motion changes.

Another route for conveying motion signals for pursuitinvolves the pretectum. As described above, the pretec-tum plays a key role in the OKR, but in primates the pre-tectum receives inputs from areas of the cerebral cortexthat are important for pursuit. Accordingly, some neuronsin the primate pretectum have smaller receptive fields andrespondwell to the small moving stimuli typically used toelicit pursuit. The pretectum provides an input to the cer-ebellum through the basal pontine nuclei, but also projectsdirectly to the vestibular nuclei and nucleus prepositushypoglossi, offering a relatively direct route to the finalmotor pathways.

The brainstem control of pursuit also appears to involvesome of the same neurons that are part of the saccadic

Medialrectus

Lateralrectus Change in eye position

Time

Pos

ition

MNMN

MN

lll

OPN

OPN

RIP LLBN

LLBN

EBN

IBN

IBN

EBN

IN

PPRF

VI

FIGURE32.7 The brainstem circuits for controlling saccadic eyemovements. This diagram of the saccade burst generator outlines themajor classesof neurons involved in constructing the motor command for horizontal saccades. Omnipause neurons (OPN) located near the midline in the nucleusraphe interpositus (RIP) tonically inhibit excitatory burst neurons (EBN) located in the paramedian pontine reticular formation (PPRF). When OPNspause, the EBNs emit a burst of spikes, which activatemotor neurons (MN) in the abducens nucleus (VI) innervating the lateral rectusmuscle. The burstalso activates interneurons (IN) which, in turn, activate motor neurons on the oculomotor nucleus (III) on the opposite side, innervating the medialrectus. Inhibitory burst neurons (IBN) show a pattern of activity similar to EBNs, but provide inhibitory inputs to decrease activation in the comple-mentary circuits and antagonist muscles. Long-lead burst neurons (LLBN) show activity long before movement onset and provide an excitatory inputto EBNs.


V. MOTOR SYSTEMS



burst generator. The EBNs and IBNs are not involved informing the pursuit motor command, but some of thelong-lead burst neurons in the brainstem reticular forma-tion increase their tonic firing during pursuit, and show abuildup of activity before the onset of pursuit and sac-cades. Even more surprisingly, OPNs—the “gatekeepers”for saccades—are also modulated during pursuit. Theydo not completely pause their activity as they do duringsaccades, but decrease their activity by about one-third.Moreover, electrical stimulation applied to theOPNs slowsdown pursuit eye movements, in addition to stopping sac-cades (Missal & Keller, 2002). The function of this overlapbetween saccades and pursuit in these premotor circuitsis not yet fully understood, but one possibility is that des-cending information about the target does not directly trig-ger saccades and pursuit, but instead a motor decisionprocess at the level of the brainstem and cerebellum deter-mines which type or combination of movements is mostappropriate under the particular circumstances.

GAZE MOVEMENTS ARE CONTROLLEDBY THE MIDBRAIN AND FOREBRAIN

The motor commands for gaze movements formed inthe brainstem depend on control signals descending fromhigher centers, in particular, from the superior colliculus

(SC) and several eye-movement related areas of thecerebral cortex (Fig. 32.9). These brain regions make itpossible to bring the well-honed motor circuits in thebrainstem under the control of higher-order processessuch as attention, perception, and cognition.

The Superior Colliculus Contains a RetinotopicMap for Controlling Gaze

The superior colliculus (SC) is a multilayered structurelying on the roof of the midbrain. In nonmammals, thehomologous structure is called the optic tectum, whichserves as the primary center for processing retinal inputsand for transforming sensory inputs into commands fororienting movements. In mammals, the SC has a similarfunctional role, and consists of superficial layers thatreceive direct inputs from the retina and striate cortex,and intermediate and deep layers that receive inputs fromextrastriate, parietal and frontal cortex, and the basalganglia. Neurons in the superficial layers have responsesto visual stimuli that are enhanced when the stimulus isthe target of a saccade. Neurons in the intermediate anddeep layers may also respond to visual stimuli, and alsoto auditory stimuli from corresponding locations, so thatthe visual and auditory maps of the animal’s surround-ings are in register. It is these intermediate and deep layersthat also possess the movement-related activity that plays

Movingtarget

Line of sight changesto track the target

Medialrectus

Lateralrectus

Cerebralcortex

Pretectum

Pontinenuclei

III

VIPPRF

CBLM

VNNPH

Midline

Eye position

Eye velocity

∼100 ms∼2

0de

g/s

∼10

deg

FIGURE 32.8 The brainstem and cerebellar circuits for controlling pursuit eye movements. During pursuit, the line of sight changes smoothly tofollow the motion of the target. The smooth changes in eye velocity are often accompanied by small “corrective” saccades, indicated by the upwarddeflection in the eye velocity trace (dotted lines). The diagram outlines the circuits involved in constructing the motor command for horizontal pursuit.Themajor pathways involve projections from areas of the cerebral cortex via the pontine nuclei to the cerebellum (CBLM), which thenmodulates activ-ity in nuclei associated with the VOR—namely, the vestibular nuclei (VN) and nucleus prepositus hypoglossi (NPH)—and also modulates activity innuclei associated with saccades, such as the paramedian pontine reticular formation (PPRF). A second pathway involves projections from the pretec-tum to the pontine nuclei, as well as a direct projection to the vestibular nuclei and prepositus hypoglossi.

GAZE MOVEMENTS ARE CONTROLLED BY THE MIDBRAIN AND FOREBRAIN 707

V. MOTOR SYSTEMS



a crucial role in the control of gaze movements (Wurtz &Goldberg, 1972). These movement-related layers providea major descending projection to the oculomotor nucleiin the brainstem reticular formation, and also a majorascending projection to the frontal cortex through themedial dorsal nucleus of the thalamus.

The most distinctive feature of the superior colliculus isthat it contains a retinotopic map of contralateral visualspace and this topography applies to the movement-related activity in the deeper layers as well as to the visualactivity in the superficial layers (Fig. 32.10). The signifi-cance of this retinotopic map becomes evident whenneural activity is artificially manipulated by passing smallamounts of electrical current through the tip of an elec-trode placed in the intermediate layers (Robinson, 1972).Such stimulation elicits a saccadic eye movement with anamplitude and direction that depends on the placementof the electrode in the map. If the stimulation is appliedas a long train, rather than as a brief pulse, a series of sac-cades is elicited, forming a “staircase” of eye movements,each with the same characteristic amplitude and direction.

Thus, activity in the superior colliculus map is related tochanges in eye position and not to absolute eye position,consistent with the organization of the superior colliculusin retinotopic (or oculocentric) coordinates.

During naturally occurring eye movements, activity inthe superior colliculus is not restricted to just the few neu-rons that best match the endpoint of the saccade, but isdistributed across a large number of neurons across theretinotopic map. This point was elegantly demonstratedby testing what happens to saccades when the injectionof chemical agents into the superior colliculus temporarilyinactivates neurons at a particular location in the map(Lee, Rohrer, & Sparks, 1988). Remarkably, it is still possi-ble to make saccades directed to the center of the inacti-vated region, because the broad distribution of activityacross the map leaves a halo of neurons that can still accu-rately guide the saccade. Moreover, saccades directed tolocations slightly beyond the inactivated site becomehypermetric (bigger than normal), because the inactiva-tion removes the contribution from neurons that codefor more proximal locations and smaller saccades. These

BOX 32.2

E Y E MOVEMENT D I S ORDER SDisorders of eye movements arise from damage to wide-

spread regions of the brain, and the symptoms reflect thecontributions of the affected structures to eye motor control.

One common disorder of eye motor control is strabismus,which occurs when the movements of the two eyes are notproperly yoked. This disorder typically occurs in childrenor infants (about 2% of children are affected), but can alsoaffect adults. Strabismus is caused by deficits in any of theseveral factors that are necessary to properly align the eyes,including problems with eye muscles or oculomotor nerves,the presence of a large refractive error in one or botheyes, and lesions in central structures. If strabismus occursduring infancy, while connections in the visual system aredeveloping, it can result in amblyopia, in which case visualinputs from the affected eye are mostly ignored.

Many eye movement disorders are caused by tumors,stroke, or other damage to the pathways responsible forforming the eye motor commands. Patients with damageto structures in the brainstem or cerebellum often have diffi-culty maintaining fixation, and exhibit nystagmus—a patternof involuntary drifts in eye position, interspersed with cen-tering saccades. Nystagmus can be caused by peripheraldamage to the vestibular labyrinth or the eighth cranialnerve that transmits signals about head motion to thecentral nervous system. The imbalance in signals receivedfrom the left and right vestibular organs causes a slow driftof the eyes, away from the damaged side. If the nystagmus

is caused by peripheral damage, then voluntary saccadesand smooth pursuit are mostly unaffected. However, nys-tagmus can also be caused by central damage to brainstemor cerebellar structures. In these cases, voluntary saccadesand smooth pursuit are also impaired, because the functionsof the neural integrator and final motor pathways areaffected.

Because gaze movements are controlled by descendingsignals from the cerebral cortex and basal ganglia, eye move-ment disorders also occur in diseases that affect higher-orderbrain functions, including schizophrenia, Huntington’s dis-ease, and Parkinson’s disease. These disorders are character-ized by problems with voluntary eye movements, mostnotably a difficulty in suppressing unwanted saccades dur-ing fixation or smooth pursuit eye movements. In Hunting-ton’s disease, in addition to difficulty with suppressingunwanted saccades during fixation, patients also have diffi-culty initiating voluntary saccades. This problem can bepartly overcome by blinking at the same time, because thecircuits for controlling eye blinks and saccades overlap. Inschizophrenia, smooth pursuit eye movements do not cor-rectly match the speed of the moving target, and are inter-rupted by back-and-forth saccades that repeatedly take theeyes off the target. For reasons that are not yet understood,these deficits in smooth pursuit ability also occur in relativesof schizophrenics who are themselves asymptomatic for thedisease.


V. MOTOR SYSTEMS



results show that saccades are guided by the vectoraverage of population activity in the superior colliculus,and were the first demonstration of vector averaging in amammalian motor system.

The intermediate layers of the superior colliculus con-tain two main classes of neurons related to the control ofgaze (Munoz & Wurtz, 1995). Burst neurons in the super-ior colliculus fire a volley of action potentials that begins~20ms before the onset of saccades, somewhat earlierthan the burst neurons located downstream in the reticu-lar formation, and often also have a visual response tothe onset of visual targets. Unlike the burst neurons inthe reticular formation, those in the superior colliculus firefor saccades directed to a portion of the visual fieldreferred to as the neuron’s movement field, and the sizeof the burst depends on where the target falls with respectto the neuron’s movement field. Buildup neurons alsohave visual responses and saccade-related activity, butthey are distinguished by the presence of sustained activ-ity when the subject is required to delay their eye move-ment response after the presentation of a visual stimulus.This sustained activity typically increases over time asthe time of the saccade draws near, and is believed to beimportant for the preparation of saccades, perhaps byfacilitating the occurrence of the saccade-related burst.Recent results show that the activity of neurons in theselayers of the superior colliculus is not only involved inmotor preparation, but is also involved in the antecedent

SEF

FEF

CN

SNpr

LIP

MTMST

SCFN

OV

VPFRF

PNVN

FIGURE 32.9 The descending pathways for controlling gaze move-ments, depicted schematically on a lateral view of the monkey brain.The superior colliculus (SC), located on the roof of the midbrain, is amajor source of descending control signals. In the cerebral cortex, themajor areas involved are the frontal eye fields (FEF), supplementaryeye fields (SEF), lateral intraparietal area (LIP), middle temporal area(MT), and medial superior temporal area (MST). In the basal ganglia, acascade through the caudate nucleus (CN) and substantia nigra pars reti-culata (SNpr) provides inhibitory control over activity in the superior col-liculus. These descending control signals are then converted into motorcommands by circuits involving regions such as the reticular formation(RF), pontine nuclei (PN), vestibular nuclei (VN), and parts of the cerebel-lum such as the ventral paraflocculus (VPF), oculomotor vermis (OV),and fastigial nucleus (FN).

Superior colliculus

Stimulation-evoked saccades

25°

2°

5°

40°50°

−60° −40°−20°0°

Rostral

Caudal

4

2

0

Dis

tanc

e (m

m)

24

Distance (mm)MedialLateral

Rostral

Caudal

4

2

0

Dis

tanc

e (m

m)

24

Distance (mm)MedialLateral

Left side Left side

Oculocentric map

10°

20°30°

+60°

+40°+20°

FIGURE 32.10 The superior colliculus and its retinotopic (or oculocentric) map of saccades and target positions. The left plot shows that electricalstimulation in the superior colliculus causes eye movements whose direction and amplitude depend on the location. Each arrow corresponds to a sti-mulation site in the left superior colliculus, and the length and direction of the arrow indicate the metrics of the evoked saccade. The evoked saccadesare all directed rightward, but rostral sites are associated with smaller movements than caudal sites, and medial sites are associated with upwardmovements whereas lateral sites are associated with downward movements. The right plot summarizes these results in the form of a continuousmap of saccades and target positions. As in the visual cortex, the representation of the center of the visual field is amplified. Adapted from Robinson(1972).

GAZE MOVEMENTS ARE CONTROLLED BY THE MIDBRAIN AND FOREBRAIN 709

V. MOTOR SYSTEMS



step of selecting the visual target, and is part of the neuralcircuits that control visual attention.

The retinotopic map in the superior colliculus includesthe central visual field. Like the rest of the map, this partalso contains neurons that fire during saccades, althoughthe preferred saccades are smaller, as would be expectedfrom the topography, and even include microsaccades(Hafed, Goffart, & Krauzlis, 2009). However, these sameneurons can also show tonic activity during fixation andchanges in firing rate for pursuit eye movements. Theseneurons therefore appear to represent the foveal regionof a single “priority” map extending across the superiorcolliculus that supports multiple eye motor outputs.

The Frontal Eye Field Is the Primary CorticalArea for Controlling Gaze Movements

The frontal eye field (FEF) exerts its control on gazemovements through several descending pathways,including a direct projection to the intermediate layers ofthe superior colliculus, an indirect projection to the super-ior colliculus via the basal ganglia, and also projections tothe cerebellum and the brainstem reticular formation. TheFEF is best known for its role in the generation of saccades,but it also contains zones that are involved in the controlof pursuit and vergence eye movements. Like the superiorcolliculus, electrical stimulation of the FEF causes saccadesto a particular location in the contrateral visual hemifield,although the topography in the FEF is less orderly than inthe superior colliculus. Electrical stimulation of the pursuitzone of the FEF causes smooth eye movements towardsthe ipsilateral side, and is the only cortical area where sti-mulation can directly evoke smooth eye movements.Damage to the FEF produces deficits in saccades, andthe impairments are most noticeable when the targetstimulus is accompanied by irrelevant distracter stimuli.For pursuit, disruption of the FEF reduces pursuit eyevelocity and, in particular, affects the ability of pursuitto follow targets using prediction. The impairmentsafter FEF damage are usually temporary, but combineddamage to the FEF and SC results in a permanent deficitin the ability to generate voluntary gaze movements(Schiller, True, & Conway, 1980).

The FEF contains neurons with different combinationsof motor and visual activity. Movement-related neuronshave movement fields like those found in the superior col-liculus; they are active for saccades within a particularrange of directions and amplitudes. Movement-relatedneurons project to the superior colliculus and showchanges in activity that are related with when and ifvoluntary gaze movements will be initiated. In particular,the variability in the timing of saccade initiation is closelycorrelated with when the firing rates of these neuronsreach a fairly constant “threshold” value (Hanes & Schall,1996). In the pursuit zone of the FEF, neurons exhibit

directionally selective responses to moving visual stimulithat are appropriate for determining the velocity com-mand for pursuit eye movements.

Most neurons in the FEF also have visual responses,including a large class of visuo-movement neurons thatshow activity for both visual stimuli and the eye move-ments that follow. These visually responsive neuronsoften show activity related to the selection of the target.Prior to the gaze movement, the activity evoked by thenonselected stimulus is rapidly suppressed, whereas theactivity for the selected stimulus remains conspicuous.Some FEF neurons discriminate visual targets even inthe complete absence of an eye movement response, indi-cating that their activity is related to the allocation ofvisual attention rather than to the preparation of eyemovements.

Another region of frontal cortex, the supplementary eyefield (SEF), plays a less direct role in the control of saccadesbut is important for movements that are guided by cogni-tive factors. Neurons in the SEF are preferentially modu-lated in tasks that involve more abstract instructions,such as when saccades are directed to a particular side ofan object rather than to a spatial location, or when sac-cades are directed to the location opposite the visual sti-mulus (the “anti-saccade” task). During pursuit eyemovements, SEF neurons are especially active when thetarget moves along a predictable trajectory.

The Parietal Cortex Contributes to EyeMovements by Controlling Visual Attention

The lateral intraparietal area (LIP) plays a major role inthe process of visual selection that precedes the generationof gaze movements. Reversible inactivation of neurons inarea LIP does not cause large deficits in the timing or accu-racy of gaze movements, but it dramatically reduces thefrequency of movements toward the affected portions ofthe visual field, especially when competing stimuli arepresent elsewhere (Wardak, Olivier, & Duhamel, 2002).These deficits suggest a visual neglect of stimuli in theaffected region, rather than a motor deficit in the genera-tion of eye movements. Damage to the parietal cortex inhumans, especially to the right hemisphere, also producesa neglect syndrome with similar deficits in attention.

Neurons in LIP show activity related to visual attentionand to the intention to redirect gaze to particular locationsin visual space. When an attention-grabbing, but irrele-vant, distracter stimulus appears while the animal is pre-paring a saccade directed elsewhere, the activity of LIPneurons closely tracks the short-lived shift of attention tothe distracter and its subsequent return to the intendedlocation of the saccade. Activity in LIP is therefore oftendescribed as a salience map that helps to determine thelocation of spatial attention, as well as the endpoint ofgaze movements (Bisley & Goldberg, 2010).


V. MOTOR SYSTEMS



Motion-Processing Areas of Cortex ProvideCrucial Signals for Pursuit Eye Movements

The middle temporal area (MT) and the medial super-ior temporal area (MST) are the primary sources of visualmotion information that are used to construct the motorcommands for pursuit. This motion information is alsoused to adjust the size of saccades made to moving visualtargets. These cortical areas provide these inputs throughseveral pathways, including projections to other corticalareas involved in controlling gaze movements (in particu-lar, the FEF), descending projections to the vestibulocere-bellum via the basal pontine nuclei, and projections tothe pretectum, which contains neurons with activityrelated to the OKR and pursuit.

Neurons in MT and MST have activity related to thevelocity of visual stimuli. In MT, neurons have smallerreceptive fields and activity that depends on the presenceof a visual stimulus. Lesions inMT produce blind spots forseeing motion that affect the motor commands for pursuitand saccades, and the perception of motion as well. InMST, neurons have larger receptive fields and prefer morecomplex patterns of visual motion. Lesions in MST alsoproduce blind spots for motion, but in addition, cause adirectional deficit in pursuit for movements directed tothe ipsilateral side (Dürsteler & Wurtz, 1988). Stimulationof MT and MST can affect pursuit eye movements, butonly if pursuit is already ongoing, unlike the effects of stim-ulation in the FEF. Thus, MT and MST are crucial sourcesof the motion signals needed to drive pursuit eye move-ments, but other areas appear necessary to determinewhenand if the movement should be started.

The Basal Ganglia Regulate Saccades byInhibiting the Superior Colliculus

The caudate nucleus (CN) and the substantia nigra parsreticulata (SNpr) are parts of the basal ganglia that forman important circuit for controllingwhen gazemovementsare initiated. The SNpr applies tonic inhibition to thesuperior colliculus using GABA-ergic synapses, suppres-sing the response to the many excitatory inputs to thesuperior colliculus thatmight otherwise evoke gazemove-ments. When SNpr neurons reduce or pause their activity,there is a disinhibition of activity in the superior colliculus,which then permits gaze movements to be initiated. TheSNpr itself is under inhibitory control from the CN, whichcontains neurons that increase their activity with gazemovements. Together, this series of inhibitory connectionsthrough the basal ganglia acts to gate the generation ofgaze movements by the superior colliculus.

The basal ganglia appear to be especially importantfor gaze movements involving reward and motivation(Hikosaka, Nakamura, & Nakahara, 2006). For example,the visual responses of CN neurons are larger for stimulithat are associated with larger rewards. This modulation

in excitability may be caused by dopaminergic inputsfrom neurons in the substantia nigra pars compacta(SNpc), the same neurons whose degeneration is impli-cated in Parkinson’s disease.

The Thalamus Provides Feedback about theControl of Gaze Movements

In addition to these descending pathways, there are alsoascending pathways to eye movement-related areas of cor-tex fromnuclei in the central thalamus. These nuclei receiveinputs from awide range of oculomotor structures, includ-ing the superior colliculus, substantia nigra pars reticulata,cerebellum, the nucleus prepositus hypoglossi, and thebrainstem reticular formation. Feedback through the thala-mus appears to convey corollary discharge signals about thegaze movements that are executed by downstream motorstructures, and is used to update the control signals formedin the cortex. Thus, when the central thalamus is inacti-vated by chemical agents, single saccades can still be madeaccurately, even in the dark, but subsequent saccades arespatially inaccurate, as though the intervening movementhad not been taken into account (Sommer &Wurtz, 2002).

THE CONTROL OF GAZE MOVEMENTSINVOLVES HIGHER-ORDER PROCESSES

Saccades and Pursuit Are Coordinated duringRedirecting of Gaze

The functions of saccades and pursuit are distinct, andyet during normal gazemovements the two types of move-ments are tightly coordinated and almost always select thesame visual target. For example, when subjects are pre-sented with two moving stimuli simultaneously, theyalmost always begin smooth pursuit in a direction that isa weighted average of the twomotions. After a brief periodof this “vector average” pursuit, subjects make a saccadetoward one stimulus or the other and then pursue thatone selectively. However, pursuit can selectively followone stimulus in the presence of distracters without a target-ing saccade, showing that saccades are not strictly neces-sary for pursuit target selection. Pursuit and saccades alsoexhibit nearly the same tradeoff between speed and accu-racy, with saccades tending to be delayed and somewhatmore accurate. This suggests that target selection for thetwo movements is guided by the same decision signals,but saccades use a somewhatmore stringent decision criter-ion (Krauzlis, 2004).

Voluntary Gaze Movements Are TightlyLinked to Shifts of Visual Attention

A crucial aspect of voluntary gaze movements is thatthey are selectively guided by objects of interest to the

THE CONTROL OF GAZE MOVEMENTS INVOLVES HIGHER-ORDER PROCESSES 711

V. MOTOR SYSTEMS



observer, despite the fact that our surroundings usuallycontain many other distracting signals. This selectivity isachieved by a tight functional link between the control ofgaze movements and the mechanisms of visual attention.When gaze is redirected, the movement of the eyes isalways preceded by a shift of visual attention to the newlocation. For example, when subjects are asked to detectvisual targets that appear just before a saccade is made,performance is much better when the target and saccadelocations coincide than when they do not (Deubel &Schneider, 1996). Similarly during pursuit, subjects makemore accurate perceptual judgments about the stimulusthey are smoothly tracking with their eyes than aboutother, nontracked stimuli in the visual display. However,judgments about nontracked stimuli are still better thanchance, showing that the selection of targets for gazemovements can occur in parallel with the perceptual proc-essing of other visual stimuli. Also, although redirectinggaze typically requires visual attention, the converse isnot true: visual attention can shift to new locations in theabsence of gaze movements, and these are referred to ascovert shifts of attention.

The tight linkage between visual attention and theplanning of eye movements was a major rationale forthe premotor theory of attention, which posited that themechanisms for spatial attention and eye motor program-ming are essentially the same. Although it is generallyrecognized that the neural mechanisms for attention andeye movements are not identical, there is overlap in theircontrol. Specifically, stimulation within the FEF with cur-rents too weak to directly cause eye movements can none-theless enhance the visual responses of neurons locatedin other visual areas of cortex, and can improve thebehavioral performance on visual discrimination tasks

(Moore & Fallah, 2004). Also, reversible inactivation ofthe SC causes profound deficits in the performance of spa-tial attention tasks, even in the absence of targeting eyemovements (Lovejoy & Krauzlis, 2010).

Visual Perception and Cognition Contributeto the Control of Gaze Movements

Much of what we know about the neural control ofgaze movements was learned using very simple visual,often small bright spots in an otherwise dark room. Thesestudies made it possible to test and identify the basic feed-back mechanisms and motor circuits that control gaze.However, under more natural conditions eye movementsshow properties that are more complex and flexible. Onestriking set of examples is provided by the work of Yarbus(1967), who showed that the pattern of saccades madewhile looking at visual scenes depends heavily on theinstructions given to the observer (Fig. 32.11). Theseresults illustrate that gaze movements are normally notjust reactions to retinal events, but instead are guided bylonger-term goals and serve to collect relevant visualinformation from the environment.

Gaze movements also reveal properties of the visualprocessing steps required to segment and interpret thevisual scene. In one demonstration, a few lights areattached to the rim of a wagon wheel, which is then rolledalong in an otherwise dark display. Although the retinalstimulus consists of several spots each undergoing cycloidalmotion, subjects perceive the horizontal motion of thewheel and are able to easily track this motion with theireyes (Steinbach, 1976). More recent studies have examinedhow these processes evolve over time. For many movingobjects, the true trajectory of the object cannot be calculated

FIGURE32.11 Thescanpathdependson the goals of the observer. Among otherexperiments, Yarbus (1967) monitored theeyemovements of subjects as they viewedRepin’s painting The Unexpected Visitorand found that the pattern of eye move-ments depended on the task. When sub-jects were instructed to give the ages ofthe people, the scan path mostly settledon the faces, whereas when subjects wereinstructed to surmise what the family hadbeen doing, the scan path included manymore objects in the room.


V. MOTOR SYSTEMS



locally in the retinal image, but requires integratinginformation over regions of visual space. This integrationevidently takes some time (for example, ~100ms), andthe transition from local-motion signals to object-motionsignals can be found in both the eye motor output and per-ceptual judgments.

Visual perception is also changed during eye move-ments. In particular, the world is not perceived as movingduring saccadic eye movements, despite the rapid motionof the retinal image. You can demonstrate this to yourselfby watching yourself make saccades in a mirror: you cansee that your eyes change position, but you cannot seethem actually move. This perception of a stable world isachieved through a combination of mechanisms, includ-ing the use of a corollary discharge of the outgoing eyemotor command, saccadic suppression of visual signals dur-ing the eyemovement, and visual masking by the advent ofnew visual signals on the retina (Wurtz, 2008). Together,these mechanisms help the visual system reduce its sensi-tivity to the unreliable visual signals that occur duringgaze movements.

CONCLUSIONS

Eyemovements serve two different functions. First, eyemovements stabilize gaze when animals move about intheir environment. Unpredictable high-speed rotations ofthe head, which are producedwhenever an animalmoves,change the line of gaze and, by smearing the opticalimage, reduce the resolution of the visual system. Thesehigh-velocitymovements are compensated for by counter-rotations of the eyes generated by the VOR. Working intandemwith the VOR is the optokinetic system. The opto-kinetic system compensates for the slower movements ofthe head, which happen so gradually that the vestibularsystem cannot accurately detect them. Second, in animalswith retinas that have a small region of high resolution,eye movements redirect gaze to aim the line of sight atobjects or features in the visual scene that are of particularinterest. Saccades are fast, discrete movements thatquickly move the image of a visual target to the center ofthe retina where acuity is best. Pursuit is a slow, continu-ous movement that compensates for the motion of thevisual target, minimizing the blurring that would other-wise limit acuity. Although the properties of saccadesand pursuit are distinct, the two types of movements areclosely coordinated during visual search of the environ-ment and both are tightly linked to visual attention.Together, the different types of eye movements make itpossible to efficiently gather the visual information thatis important for achieving other, longer-term behavioralgoals.

Eye movements are controlled by circuits that span thebrain. The eyes themselves are a relatively simple motor

apparatus, and they are controlled by a final motorpathway in the brainstem that is shared by all classes ofeye movements. The construction of the motor commandsinvolves generating an eye velocity command to move theeyes, and an integrated version of this command to holdthe eyes at their new position. These motor commandsare constructed by circuits in the brainstem reticular forma-tion, and fine-tuned by additional circuits involving sev-eral parts of the cerebellum. The descending controlsignals that drive these motor commands are providedby multiple brain regions, but the superior colliculus inthe midbrain and the frontal eye fields in the cortex areespecially important. These brain regions help integratesensory inputs with a variety of higher-order influencesso that eye movements are directed to the appropriatevisual stimuli. Overall, eye movements provide a windowinto the brain mechanisms that accomplish motor control,and they also involve sensory-motor interactions andhigher-order processes like attention and perception.

ReferencesBisley, J. W., & Goldberg, M. E. (2010). Attention, intention, and priority

in the parietal lobe. Annual Review of Neuroscience, 33, 1–21.Buttner-Ennever, J. A. (2007). Anatomy of the oculomotor system.

Developments in Ophthalmology, 40, 1–14.Cannon, S. C., & Robinson, D. A. (1987). Loss of the neural integrator of

the oculomotor system from brain stem lesions in monkey. Journal ofNeurophysiology, 57, 1383–1409.

Demer, J. L. (2006). Current concepts of mechanical and neural factorsin ocular motility. Current Opinion in Neurology, 19, 4–13.

Deubel, H., & Schneider, W. X. (1996). Saccade target selection andobject recognition: evidence for a common attentional mechanism.Vision Research, 36, 1827–1837.

Dürsteler, M. R., & Wurtz, R. H. (1988). Pursuit and optokinetic deficitsfollowing chemical lesions of cortical areas MT and MST. Journal ofNeurophysiology, 60, 940–965.

Fuchs, A. F., & Luschei, E. S. (1970). Firing patterns of abducens neu-rons of alert monkeys in relationship to horizontal eye movement.Journal of Neurophysiology, 33, 382–392.

Hafed, Z. M., Goffart, L., & Krauzlis, R. J. (2009). A neural mechanismfor microsaccade generation in the primate superior colliculus.Science, 323, 940–943.

Hanes, D. P., & Schall, J. D. (1996). Neural control of voluntary move-ment initiation. Science, 274, 427–430.

Hikosaka, O., Nakamura, K., & Nakahara, H. (2006). Basal ganglia ori-ent eyes to reward. Journal of Neurophysiology, 95, 567–584.

Keller, E. L. (1974). Participation of medial pontine reticular formationin eye movement generation in monkey. Journal of Neurophysiology,37, 316–332.

Klier, E. M., Meng, H., & Angelaki, D. E. (2011). Revealing the kine-matics of the oculomotor plant with tertiary eye positions and ocu-lar counterroll. Journal of Neurophysiology, 105, 640–649.

Krauzlis, R. J. (2004). Recasting the smooth pursuit eye movement sys-tem. Journal of Neurophysiology, 91, 591–603.

Lee, C., Rohrer, W. H., & Sparks, D. L. (1988). Population codingof saccadic eye movements by neurons in the superior colliculus.Nature, 332, 357–360.

Lovejoy, L. P., & Krauzlis, R. J. (2010). Inactivation of primate superiorcolliculus impairs covert selection of signals for perceptual judg-ments. Nature Neuroscience, 13, 261–266.

CONCLUSIONS 713

V. MOTOR SYSTEMS



Miles, F. A. (1997). Visual stabilization of the eyes in primates. CurrentOpinion in Neurology, 7, 867–871.

Missal, M., & Keller, E. L. (2002). Common inhibitory mechanism forsaccades and smooth-pursuit eye movements. Journal of Neurophy-siology, 88, 1880–1892.

Moore, T., & Fallah, M. (2004). Microstimulation of the frontal eye fieldand its effects on covert spatial attention. Journal of Neurophysiology,91, 152–162.

Munoz, D. P., &Wurtz, R. H. (1995). Saccade-related activity in monkeysuperior colliculus. I. Characteristics of burst and buildup cells. Jour-nal of Neurophysiology, 73, 2313–2333.

Robinson, D. A. (1972). Eye movements evoked by collicular stimula-tion in the alert monkey. Vision Research, 12, 1795–1808.

Schiller, P. H., True, S. D., & Conway, J. L. (1980). Deficits in eye move-ments following frontal eye field and superior colliculus ablations.Journal of Neurophysiology, 44, 1175–1189.

Sommer, M. A., & Wurtz, R. H. (2002). A pathway in primate brain forinternal monitoring of movements. Science, 296, 1480–1482.

Steinbach, M. (1976). Pursuing the perceptual rather than the retinalstimulus. Vision Research, 16, 1371–1376.

Wardak, C., Olivier, E., & Duhamel, J. R. (2002). Saccadic target selec-tion deficits after lateral intraparietal area inactivation in monkeys.Journal of Neuroscience, 22, 9877–9884.

Wurtz, R. H., & Goldberg, M. E. (1972). Activity of superior colliculusin behaving monkey: III. Cells discharging before eye movements.Journal of Neurophysiology, 35, 575–586.

Wurtz, R. H. (2008). Neuronal mechanisms of visual stability. VisionResearch, 48, 2070–2089.

Yarbus, A. L. (1967). Eye movements and vision. New York: Plenum.

Suggested ReadingsAngelaki, D. E., & Hess, B. J. M. (2005). Self-motion-induced eye

movements: effects on visual acuity and navigation. Nature ReviewsNeuroscience, 6, 966–976.

Fuchs, A. F., Kaneko, C. R. S., & Scudder, C. A. (1985). Brainstem controlof saccadic eye movements. Annual Review of Neuroscience, 8, 307–337.

Gandhi, N., & Katnani, H. A. (2011). Motor functions of the superiorcolliculus. Annual Review of Neuroscience, 34, 205–231.

Kowler, E. (2011). Eye movements: the past 25 years. Vision Research,51, 1457–1483.

Krauzlis, R. J. (2005). The control of voluntary eye movements: newperspectives. Neuroscientist, 11, 124–137.

Leigh, R. J., & Zee, D. S. (2006). The neurology of eye movements (4th ed.).Philadelphia, PA: F.A. Davis.

Lisberger, S. G. (2010). Visual guidance of smooth-pursuit eyemovements:sensation, action, and what happens in between.Neuron, 66, 477–491.

Purcell, B. A., Heitz, R. P., Cohen, J. Y., Schall, J. D., Logan, G. D., &Palmeri, T. J. (2010). Neurally constrained modeling of perceptualdecision making. Psychological Review, 117, 1113–1143.

Schutz, A. C., Braun, D. I., & Gegenfurtner, K. R. (2011). Eye move-ments and perception: a selective review. Journal of Vision, 11, 1–30.

Sommer, M. A., &Wurtz, R. H. (2008). Brain circuits for the internal mon-itoring of movements. Annual Review of Neuroscience, 31, 317–338.

Sparks, D. L. (2002). The brainstem control of saccadic eye movements.Nature Reviews Neuroscience, 3, 952–964.

Richard J. Krauzlis


V. MOTOR SYSTEMS



Chapter 32 - Eye...

Documents

Transcript of Chapter 32 - Eye...