Ординатура / Офтальмология / Английские материалы / The Neurology of Eye Movements_Leigh, Zee_2006

cribing more responsibility to central neural factors, for which there is electrophysiological evidence,430 or to the constraints imposed by the orbital mechanics, are being tested experimentally.253'412

Higher-Level Control of the

Saccadic Pulse Generator

It is now clear that several distinct cortical areas are involved in the voluntary control of saccades. The anatomical connections of these areas and the way that they project to the brain stem saccadic pulse generator are summarized in the text and displays of Chapter 6 and in Figure 3-8. Direct projections from the cortical eye fields to the PPRF and riMLF appear meager compared with those to the superior colliculus or to the cerebellum via NRTP.405 Thus, recent research has emphasized the role of the superior colliculus, which receives inputs from all the cortical eye fields and may coordinate the discharge of burst and omnipause neurons. Although pharmacological inactivation of the superior colliculi disrupts normal saccadic programing,232 destructive lesions here do not permanently abolish voluntary saccades,9 and so the cortical projection to NRTP and the cerebellum also seems important. However, the latter pathway is also not essential because saccades can still be made after frontal eye field lesions. A crucial finding is that bilateral lesions of the frontal eye fields and the superior colliculus cause an enduring, severe deficit of voluntary saccades.355 A similar defect occurs with combined bilateral lesions of the frontal and parietal eye fields.241 Thus, parallel descending pathways are involved in generating voluntary saccades, and it appears that each is capable of performing spatial- to-temporal and retinotopic-to-craniotopic transformations of neural signals.

Superior Colliculus

VISUAL AND MOTOR LAYERS OF THE SUPERIOR COLLICULUS

Anatomically, the superior colliculus consists of seven layers.262'263'338-396'454 Early

studies established that the dorsal layers of the superior colliculus are "visual" in terms of their properties and that the more ventral or "intermediate" layers are "motor."6'12 The dorsal layers contain an orderly retinal projection such that the visual field can be mapped onto its surface (Fig. 3-9A).82 These layers receive visual inputs directly from the retina and from the striate cortex and send efferents to the pretectal nuclei, lateral geniculate body, and pulvinar. The ventral layers contain a "motor map" (Fig. 3-9B), which has been defined by the eye movements that are produced by electrical stimulation.333 Although there are connections between the dorsal visual and the ventral motor layers,261-262 in primates, cortical projections to the ventral superior colliculus seem to be more important. Furthermore, visually induced activity in the dorsal layers does not necessarily lead to movement activity in ventral layers, and conversely, movement activity in ventral layers may occur without visual activity in the dorsal layers.248'454 Thus, the rest of this section deals with the connections and properties of the ventral layers of the superior colliculus.243

Important projections to the ventral layers arise from striate, extrastriate, and parietal cortex, and from the frontal lobes (Fig. 3-8). Thus, the frontal eye field, supplementary eye field, and dorsolateral prefrontal cortex project to the superior colliculus; some of these pathways are direct and some are via the basal ganglia, including the caudate nucleus and the pars reticulata of the substantia nigra. The superior colliculus has reciprocal connections with the central mesencephalic reticular formation263 and receives inputs from the nucleus prepositus hypoglossi.167 The rostral pole receives an input from the cerebellar fastigial nucleus.246 Serotonin, acetylcholine, and GABA have all been identified as transmitters in the ventral layers.

The ventral layers project to critical structures in the brain stem that generate the premotor commands for saccades. These include the PPRF and riMLF, the nucleus prepositus hypoglossi, the nucleus reticularis tegmenti pontis (NRTP), the central mesencephalic reticular formation,

and the vestibular nuclei. The ventral layers also send ascending projections to the central thalamus.366 Descending outputs from the ventral layers of the superior colliculus are carried via an ipsilateral tectopontine pathway and a contralateral tectoreticular pathway. The latter crosses in the dorsal tegmental decussation of Meyn-

ert and, as the predorsal bundle, lying ventral to the MLF, carries descending branches destined for the pontine and medullary reticular formation and ascending branches destined for the rostral midbrain.262'263 The functional anatomy of the superior colliculus has been elucidated by the technique ofmicrostimulation.

FUNCTIONAL ANATOMY OF THE SUPERIOR COLLICULUS REVEALED BY STIMULATION

Saccades can be produced by electrical stimulation throughout the superior colliculus, but in the ventral layers this is possible at low-current thresholds.333'356

Within these ventral layers, the direction and size of the saccade are mainly functions of the site of stimulation rather than the strength of the stimulus or current position of the eye. Thus, once threshold has been reached, saccades occur in an all-or-none fashion, although the effects of stimulation are influenced by whether the animal is actively fixating a target.398 The smallest saccades are elicited rostrally, the largest, caudally. Saccades with upward components occur with more medial stimulation, those with downward components, with more lateral stimulation. Purely vertical saccades only occur with bilateral simultaneous stimulation of corresponding points. This motor map in polar coordinates (Fig. 3-9B) lacks threedimensional (i.e., torsional) information.428 Saccades of similar size (isoamplitude) correspond to lines running medial-to-lateral (largest with stimulation caudally), and saccades of similar direction (isodirection) correspond to lines running anterior to posterior (0° corresponding to a pure, horizontal, contralat-

eral saccade). Stimulation of the rostral pole of the motor map suppresses saccades; this "fixation zone" of the superior colliculus sends a monosynaptic excitatory projection to omnipause neurons,144 thereby suppressing saccades. Stimulation more caudally induces saccades at latencies that imply disynaptic connections with premotor burst neurons; it is sug-

gested that the long-lead burst neurons are interposed.258 Stimulation in the cau-

dal third of the ventral motor map produces combined eye-head gaze shifts; both eye and head movements are directed contralateral to the side stimulated.76 Consistent with these studies is the finding that the rostral pole of the superior colliculus projects to the omnipause region (nucleus raphe interpositus), whereas more caudal portions project to the premotor burst neurons.55

rior colliculus in monkeys trained to make saccades to visual targets revealed a variety of cell types that showed responses related to either the visual stimulus or the saccadic movement or to both.397 Some neurons that respond to visual stimuli do so in anticipation of a saccade that will bring a target into their receptive field444

register the amplitude and the direction of the upcoming required saccade (i.e., they encode the motor error signal necessary to acquire the target).402

Three populations of saccade-related cells have been defined in the ventral layers: fixation neurons and buildup neurons, which lie more ventrally, and col- licular-burst neurons, which lie more dorsally.243'453 The activity of collicularburst neurons during a saccade is in accordance with the motor map demonstrated by microstimulation. Thus, it is the location of the active population of collicularburst neurons that encodes the size and direction of the saccade, not the rate of discharge.270'271 The site of maximum ac-

tivity on the collicular motor map determines the desired change in eye position.

During the course of a saccade, the site of maximum activity of collicular-burst neurons does not change, but their discharge rate declines as the eye approaches its target. Although it has been postulated that the temporal discharge of collicular-burst neurons might encode motor error (the difference between current and desired eye position), current evidence suggests

that they are more likely to encode desired change in eye position.106'267 Their dis-

charge is also influenced by current eye position.429 Collicular-burst neurons located in the caudal part of the superior colliculus appear to encode a gaze displacement signal for a combined eye-head saccade.133

Fixation neurons lie at the rostral pole of the motor map and probably suppress

saccades via their projections to omnipause neurons;144-268-269 they may also inhibit collicular-burst neurons.266a Buildup neurons start to discharge when a visual stimulus becomes the target for a saccade.271 Like collicular-burst neurons, the location of build-up cell activity initially occurs at a site on the motor map related to the amplitude and direction of the upcoming saccade. However, unlike the location of discharging collicular-burst cells, which remains constant throughout the eye movement, there appears to be a rostral spread of activity of buildup neurons (a moving wave or hill) towards the fixation zone. This spread of activity among the buildup neurons population may contribute to the spatial-temporal transformation of signals that is needed to provide the reticular burst neurons with the saccadic command. When the spreading wave of activity reaches the fixation neurons at the rostral pole, the saccade ends.271 Not all studies, however, support this hypothesis.113 During the antisaccade task, prestimulus activity of build-up neurons is predictive of an error (prosaccade).117a

Cells in the ventral layers of the superior colliculus also have auditory204'205-238 as well as somatosensory receptive fields,154 which are generally in register.446 The spatial map of auditory responses in the superior colliculus is dynamic, being a function of the initial position of the eye in the orbit. In this way, saccades made to auditory targets are still governed by the same retinotopically coded, change-in-position movement fields that underlie visually driven saccades. Studies in humans support this idea.238

THE EFFECTSOF PHARMACOLOGICAL INACTIVATION AND LESIONS OF THE SUPERIOR COLLICULUS

Insight into the role of the ventral layers of the superior colliculusin saccade generation has been gained by local injection of the GABA agonist muscimol, which increases normal GABA inhibition and thereby decreases neuronal activity; and the GABA antagonist bicuculline, which increases neuron activity by decreasing normal GABA inhibition. Injection of

muscimol into the rostral pole of the SC reduces saccadic latency, causing express saccades and disruption of steady fixation by saccadic intrusions. Conversely, bicuculline injected into this fixation zone increased saccadic latency and sometimes saccades were not generated. Injection of these same agents into more caudal re-

initiation of saccades, which are hypometric and slow.188'190-232 Bicuculline injections cause fixation instability, with saccadic intrusions. These findings support the suggestion that the fixation neurons at the rostral pole of the superior colliculus suppress saccades both through excitation of omnipause neurons55 and by inhibiting collicular burst neurons.453 However, inputs from structures other than the superior colliculus also influence omnipause neurons and the timing of saccadic onset.118 If muscimol is injected locally into the superior colliculus at a point corresponding to small saccades (Fig. 3-9B), and the monkey makes large saccades, the eye gets on target but by a curved trajectory.7 This finding supports the hypothesis that during saccades, activity in the

buildup cell layer sweeps forward but has to circumvent the area that has been pharmacologically inactivated.7

Conventional lesion studies have been less revealing than acute pharmacological inactivation, in part because of the effects of recovery and adaptation. However, certain persistent defects are noted with chronic lesions of the superior colliculus.9 Saccadic accuracy is mildly impaired with a small degree of hypometria. The frequency of spontaneous saccades is diminished during scanning of a visual scene but not in complete darkness. During fixation of a stationary target, the monkey without a superior colliculusis less easily distracted by peripheral stimuli and makes fewer saccades away from the fixation target. Most notably, the ability to generate express saccades is abolished after collicular lesions.355 When lesions of the superior colliculus are combined with lesions of the caudal medial thalamus10 or with the frontal eye field (see The Role of the

Frontal Eye Field in Saccade Generation, in the following section), more long-lasting ocular motor abnormalities are produced.

Lesions restricted to the superior colliculi are rare in humans. One patient who had undergone removal of an angioma from the right superior colliculus showed evidence of dorsal midbrain syndrome.179 Spontaneous horizontal saccades to the left occurred less frequently and were more commonly followed by corrective saccades; saccadic latency was normal. Another patient with a hematoma largely restricted to the right superior colliculus showed defects in latency and accuracy for contralateral saccades and increased numbers of inappropriate saccades (prosaccades) in the antisaccade task.317

Role of the Frontal Lobe in

Saccade Generation

The frontal eye field has been implicated in ocular motor control ever since Ferrier stimulated the premotor cortical area 8 of monkeys and elicited contralateral eye movements.124 In humans, electrical stimulation (experimental or epileptic) elicits contraversive deviation of the eyes.151'309 The location of the homologue of the frontal eye field in humans has been recently defined by functional imaging studies.305 Two other areas, the supplementary eye field and dorsolateral prefrontal cortex, have been shown to contribute to the voluntary control of saccades. The anatomical location and connections of these three areas are described in Chapter 6 and summarized in Figure 6-8, Display 6-19, Display 6-20, and Display 6-21. Here we summarize results of electrophysiological and lesion studies that have helped define the role that each area plays.

ROLE OF THE FRONTAL EYE FIELD IN SACCADEGENERATION

Effects of Microstimulation of the Frontal Eye Field

Microstimulation studies in the rhesus monkey have been crucial in defining the

extent of the frontal eye field (FEF)(along the posterior portion of the arcuate sulcus, part of Brodmann area 8)46 and have also given insights into FEF function. Stimulation at any site on the FEF elicits a saccade of a specific direction and amplitude. The latency from FEF stimulation to the onset of a saccade is about 30-45 msec, similar to that for stimulation in the superior colliculus. Usually, the movement is oblique, with a contralateral horizontal component; bilateral stimulation is required to elicit a purely vertical saccade. A motor map is present with larger saccades evoked from stimulation of the dorsomedial portion of the FEF and with smaller saccades from stimulation of the ventrolateral part.46 Stimulation of first one FEF and then the other elicits two successive saccades that take the eye to a position corresponding to single stimulation of the second site.137a Microstimulation can also suppress saccades if it is timed to coincide with the visual stimulus for the eye movement; this occurs at thresholds lower than those evoking saccades.47 Such suppression of saccades occurs when stimulation is applied deep within the anterior bank, close to the representation for small saccades, a region that projects to the fixation region at the rostral pole of the superior

colliculus and to omnipause neurons in the pons.47'405 Stimulation of one FEF af-

fects the activity of cells in the other con-

sistent with coordination between the two eye fields.358

Activity of Frontal Eye Field Neurons

Only occasional FEF neurons discharge before spontaneous saccades made in complete darkness, although many neurons discharge after such movements. The most useful information about the activity of single neurons in the FEF has been gained from experiments in which monkeys were trained to perform a variety of saccadic tasks for reward.45-152 Different subpopulations of FEF neurons encode the visual stimulus, the planned saccadic movement, or both. As in the superior colliculus and parietal eye fields, some cells with visual responsiveness anticipate the visual consequences of planned sac-

cades.422 Although the discharge of FEF neurons is related to the amplitude and direction of voluntary saccades, their discharge during saccades does not dynamically encode signals such as motor error (the difference between current and desired eye position).377 The FEF neurons also discharge for visual and motor aspects of memory-guided saccades.134 When monkeys perform a double-step task, in which two target lights are flashed in succession before the eye has time to move, most units discharge not in relation to the retinal location of the second target but according to the saccade needed to acquire it.152 Such cells behave similarly to quasivisual cells of the superior colliculus—their activity encodes the desired change in eye position. Neurons that appear to be concerned with disengaging fixation prior to a saccade increase their discharge when the fixation light is turned out, even before the new target becomes visible.92 Some FEF neurons show properties indicating that they contribute to selection of the target to which a saccade will be made,352 the decision whether to look at it or not,164 and the process of visual scanning of a complex visual scene.48

Effects of Frontal Eye Field Lesions on Saccade Generation

Acute destructive lesions of the FEF in monkeys produce an increase in latency for contralateral saccades and a decrease in latency for ipsilateral movements, i.e., an increase in express saccades ipsilateral to the side of the lesion.353 Acute pharmacological inactivation with muscimol causes a contralateral ocular motor scotoma with abolition of all reflex, visual, and voluntary saccades with sizes and directions corresponding to the injection site.93 Inactivation with lidocaine principally impairs contralateral saccades made to targets that are no longer visible.394 With muscimolinactivation of FEF, during attempted fixation there is a gaze shift towards the side of the lesion. In contrast, bicuculline produces irrepressible saccades.93 Thus, these results are similar to the effects of injecting these agents into the superior colliculus; inactivation of either structure causes

substantial defects in reflex visual and voluntary saccades.

More subtle changes in the generation of visually guided saccades are present with chronic experimental lesions of the FEF, including decreased frequency and size of movements,357 and defects of saccades made to paired or multiple targets that are presented asynchronously.353a Saccadic deficits after chronic FEF lesions in humans are relatively minor, consisting of increased latency and inaccuracy of visual and memory-guided saccades (see Display 10-36, Chap. 10).

ROLE OF THE SUPPLEMENTARY EYE FIELD IN

SACCADE GENERATION

The supplementary eye field (SEF) lies just anterior to the supplementary motor

cortex, in the dorsal medial portion of the frontal lobe.362 Like the FEF, the SEF con-

tains neurons that discharge prior to voluntary saccades. Stimulation in the SEF elicits saccades at low thresholds, though at a slightly longer latency than in the frontal eye fields.362 Initial studies using microstimulation seemed to indicate that the eye was driven to a specific orbital position.361 This was unlike the results of stimulation of the FEF, which produced an eye movement of specific size and direction, determined by the site stimulated. Thus, it was postulated that neurons in the SEF encoded saccadic eye movements in craniotopic rather than oculocentric (retinal) coordinates.361>416d Other studies have questioned this conclusion, however, and indicate that neurons in both the SEF and FEF encode visual targets and saccades retinotopically.349 This raises the question of what special contribution, if any, the SEF makes to the control of saccades. Neurons in the SEF show different activity than FEF neurons when monkeys are trained to make a learned sequence of saccades,63 a combined eye-arm task,274 or are required to cancel planned saccades.304 Neurons in the SEF also show different discharge characteristics before antisaccades,364 and cerebral event-related potentials recorded from the scalp of human subjects correlate with correct and-

saccade responses.119 This notion that the SEF is concerned with eye movements that are programed as part of learned, complex behaviors is supported by functional imaging studies in humans which have demonstrated increased activation during a series of memory-guided saccades.310 Studies of patients with lesions involving the SEF also indicate that the behavioral defect concerns the ability to make a re-

membered sequence of saccades to an array of visible targets.146 The effects of SEF

on human eye movements are summarized in Display 10-36.

ROLE OF DORSOLATERAL

PREFRONTAL CORTEX IN

SACCADE GENERATION

Although not a conventional eye field (as defined by low threshold for stimulation of saccades), neurons in the prefrontal cortex of monkey in the posterior third of the principal sulcus (see Fig. 6-8, Chap. 6), which lies on the dorsolateral convexity of the frontal lobe, corresponding to Walker's area 46, show an ability to hold in memory the location of a visual target to which a saccade is to be made (Display 6-21).141'168 Pharmacological inactivation of dorsolateral prefrontal cortex (DLPC) impairs the accuracy of monkeys to make contralateral memory-guided saccades.351 In humans, there is activation of DLPC when subjects make memory-guided saccades or antisaccades.284'414 Lesions affecting DLPC impair both of these saccadic functions.158'313 Repetitive transcranial magnetic stimulation over DLPC in normal subjects also impairs the accuracy of memory-guided saccades.41 Cingulate cortex and the hippocampus both appear to contribute to programing of single or multiple memory guided saccades; they are discussed further in Chapter 6.

Role of the Parietal Lobe in

Saccade Generation

The parietal lobe appears to influence the control of saccades in at least two ways. First, the posterior parietal cortex is im-

portant for shifts of visual attention, which may be accompanied by saccades. Second, the parietal eye fields (PEF) are directly involved in programing saccades to visual targets.

ROLE OF POSTERIOR PARIETAL CORTEX IN SACCADE GENERATION

In monkeys, area 7a of the inferior parietal lobule contains populations of neurons that respond to visual stimuli and discharge mainly after saccades have been made (Fig. 6-8).22 It appears that the activity of some of these neurons is influenced not just by visual stimuli but also by eye and head position.11-44 This finding has led to the hypothesis that a neural network of such cells could encode a visual target in spatial or craniotopic coordinates.11 Such a transformation of signals would seem to be essential for programing saccadic gaze shifts towards selected targets.

In humans, unilateral posterior parietal lesions, especially acute right-sided lesions, cause contralateral inattention and may restrict saccades to the ipsilateral hemirange of gaze (see Display 10-35, Chap. 10).260 Chronic lesions cause increased latency of visually guided saccades;242 in humans this is especially the case with right-sided lesions.314 In addition, memory-guided saccades are inaccurate, possibly because posterior parietal cortex projects to DLPC.313 In normal human subjects, a defect of memory-guided saccades is produced if transcranial magnetic stimulation is applied to the posterior parietal area early during the memory period.273-301 Antisaccades are also delayed by transcranial magnetic stimulation over parietal cortex; a similar effect is possible over frontal cortex if the stimulus is delivered later, suggesting flow of information from posterior to anterior during presaccadic processing.4166 Bilateral posterior parietal lesions cause Balint's syndrome,312 features of which include difficulty initiating voluntary saccades to visual targets, and visual scanning.240 These deficits may reflect disruption of the normal mechanisms by which posterior pari-

etal cortex transforms visual signals into spatial coordinates.

ROLE OF THE PARIETAL EYE FIELD IN SACCADE GENERATION

In rhesus monkeys, the PEF lies adjacent to area 7a, in the caudal third of the lateral bank of the intraparietal sulcus, an area called LIP (Fig. 6-8). Electrical stimulation on the lateral wall of the intraparietal sulcus produces saccades of similar direc-

tion irrespective of the starting position of the eye.417 However, if the floor of the in-

traparietal sulcus and its underlyingwhite matter are stimulated, the direction of the resulting eye movements appears to depend on starting eye position. Thus, the summed output of the PEF may be concerned with making saccades to specified targets in spatial coordinates.417

Unlike area 7a, LIP neurons discharge prior to saccades.22'23 Like cells in area 7a, the response of LIP neurons isinfluenced by eye position.11 These cells in the LIP also show a shift of their visual response field that anticipates the consequence of the upcoming gaze shift.104 Another important property of LIP neurons is their ability to remain active while the monkey is required to withhold eye movements and remember the desired target location.23'303 Thus, the activity of these neurons corresponds to the size and direction of the required eye movement, a memory of motor error, and is similar to that of certain quasivisual cells found in the superior colliculus and frontal lobe. Furthermore, LIP neurons appear to encode not only the intended saccade but also reflect changes in the planned

movement and other cognitive fac-

tors.40'71-249'319'337

In humans, lesions of the PEF, which is located in cortex adjacent to the horizontal portion of the intraparietal sulcus,272 cause prolonged latency of visually guided saccades during gap or overlap stimuli (see Display 10-35, Chap. 10).314 These changes are more pronounced with rightsided lesions. A similar effect results in normal subjects if transcranial magnetic stimulation is applied to the PEF region.109 It has been suggested that the greater latency resulting when the fixation

light is left on indicates that the PEF is important for disengagement of fixation prior to generating a saccade.315 Parietal lesions impair the ability to make two saccades to two targets flashed in quick succession. In response to this double-step stimulus, the brain must take into account not only the retinal location of both targets but also the effect of the eye movements.105'169 Patients with right parietal lesions show errors when the first target appears in the left hemifield an'd the second target appears in the right; the first saccade may be accurate, but the second is not. This deficit may be present even though there is no inattention or difficulty responding to the reverse order of presentation or of making single saccades to leftsided targets. It appears that there has been disruption of the ability to monitor

the size of the first saccade using efference copy.105'169

To summarize, the influence of frontal and parietal cortex on the control of saccades appears to be via two parallel descending pathways (Fig. 3-8). One pathway is via the frontal eye field to the superior colliculus (directly and indirectly via the basal ganglia). This pathway appears to be more concerned with selfgenerated changes in gaze related to remembered, anticipated, or learned behavior. The other pathway is directly from posterior parietal cortex to the superior colliculus. This pathwayis more concerned with reorienting gaze to novel visual stimuli and in particular with shifting visual attention to the location of new targets appearing in extrapersonal space. However, there are strong interconnectionsbetween, and common projection sites of, the parietal and the frontal lobes, which precludes a strict separation of function between the two pathways.623-378 Thus, for example, lesions of both posterior parietal cortex and

DLPC may impair memory-guided saccades.313

Role of the Thalamus in

Saccade Generation

On the basis of animal experiments, it is clear that at least two parts of the thalamus contribute to the programing ofsac-

cades: the central nuclei of the internal medullary lamina and the pulvinar.

ROLE OF THE INTERNAL

MEDULLARY LAMINA IN

SACCADE GENERATION

Neurons scattered throughout the internal medullary lamina (IML), which is the fiber pathway separating the medial from the lateral thalamic mass, show saccaderelated properties.360'365'366 Electrical stimulation in the region of the IML elicits contralaterally directed saccades that may either be of fixed size and direction or directed to an orbital position. Neurons in the IML discharge in relation to spontaneous and visually guided, contralateral saccades. Consistent with the effects of stimulation is the observation that some units appear to encode saccades in craniotopic rather than retinotopic coordinates. Yet, other types of neurons in IML stop discharging during saccades but show a strong postsaccadic increase in activity, discharge in relation to eye position, or discharge during steady fixation.

In humans, functional imaging has confirmed activation of the thalamus during voluntary saccades.311 Because IML neurons receive inputs from cortical and brain stem structures concerned with eye movements but project only to the cortex and basal ganglia, it has been suggested that they might be a source of efference copy information to the cortical eye fields.366 In support of this hypothesis is the report that patients with lesions affecting the intralaminar nuclei show inaccuracy of memory-guided saccades only if gaze is perturbed during the memory period.146a

ROLE OF THE PULVINAR IN SACCADE GENERATION

Two separate parts of the pulvinar appear to each make distinctive contributions to saccades. Neurons in the inferior-lateral portions of the pulvinar respond to retinal image motion when it is produced by a moving stimulus, but much less so if it is due to a saccade.339 Thus, this region might contribute to the process of saccadic suppression. In the dorsomedial pulvinar, visually responsive neurons are

not retinotopically organized and seem more important for shifts of attention to-

wards salient features in the environment.32'292,336 injection of GABA antago-

nists and agonists into the dorsal medial portion of the lateral pulvinar facilitates or retards, respectively, the ability of an animal to shift its attention toward the contralateral visual field.340 Electrolytic lesions in the pulvinar of monkeys cause a paucity of saccades towards blank portions of the visual field, and gaze appears to be "captured" by visual stimuli.423 Other studies, however, have revealed relatively normal patterns of visual search after pulvinar lesions.31 Furthermore, after kainic acid lesions in the pulvinar, the latency and amplitude of saccades to singleand double-step targets are normal. Thus, the abnormalities that appear after electrolytic lesions of the pulvinar might be related to interruption of fibers of passage.

In humans, functional imaging supports the idea that the pulvinar is important for directing visual attention.227 Nonetheless, reports of the effects of lesions restricted to the pulvinar on saccades are rare. A patient with a left pulvinar lesion showed a paucity of spontaneous saccades into the contralateral field (there was hemispheric extension, but no visual field defect); latencies were increased for all saccades, but especially those directed into the contralateral field.468 Another patient had damage to the left pulvinar and showed a paucity of spontaneous eye movements and defective visual scanning into the contralateral field.285 A group of patients who underwent ventrolateral thalamotomy showed contralateral hemi-inattention.437 Taken together, these experimental and clinical results suggest that the predominant effect of pulvinar lesions in humans is a defect of the ability to shift visual attention. The effects of pulvinar lesions on saccadic suppression have yet to be evaluated.

Role of the Basal Ganglia in

Saccade Generation

Although the frontal lobe "eye fields" project directly to the superior colliculus, they