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

of the flocculus and paraflocculus are to

the ipsilateral superior and medial vestibular nuclei and to the y-group.167'216

The flocculus Purkinje cells may supplement vestibular nucleus neurons in generating compensatory eye movements during self-rotation,339 regulate the phase of the VOR,74'306 and contribute to the transformation of vestibular and visual signals into a common frame of reference.164 In addition, the floccular Purkinje cells play an important role in the adaptive control of the VOR.178 Parafloccular and floccular Purkinje cells discharge during smooth pursuit and combined eye-head tracking to encode gaze velocity.177'198

Experimental lesions of the flocculus and paraflocculus in monkeys produce a characteristic syndrome that is similar to that encountered clinically in patients with the Arnold-Chiari malformation (see Table 10-12).35° This includes impaired smooth pursuit and eye-head tracking, as well as impaired gaze holding (deficient neural integrator). The gaze-holding deficit probably reflects loss of the cerebellum's contribution to the fidelity of the brain stem neural integrator, which lies in the medial vestibular nuclei and the nucleus prepositus hypoglossi.49'197 Another

important deficit caused by floccularparafloccular lesions is loss of ability to adapt the properties of the VOR in response to visual demands.178

The nodulus, which is the midline portion of the flocculonodular lobe, lying immediately caudal to the inferior medullary velum, and the adjacent ventral uvula, receive afferents from the vestibular nuclei, nucleus prepositus hypoglossi, inferior

olivary nucleus, and vestibular nerve (Display 6-11).278'281'343 The nodulus and ven-

tral uvula project to the vestibular nuclei and control the velocity-storage mechanism of the VOR, by which the response of this reflex to low-frequency stimuli is enhanced.302'338 The effects of velocity storage are best illustrated by considering the duration of nystagmus that ensues following the onset of a sustained, constantvelocity rotation: this nystagmus lasts two or three times longer than can be accounted for by the mechanical properties of the cupula and endolymph. In monkeys, lesions of the nodulus and uvula maximize the velocity-storage effect; maneuvers that will usually reduce it, such as pitching the head forward during postrotational nystagmus, are abolished.338 Similar effects are seen in patients with midline

cerebellar tumors that involve the nodulus.116 In addition, when monkeys that have nodular lesions are placed in darkness, they may develop periodic alternating nystagmus.338 Evidence from patients with periodic alternating nystagmus supports a causative role of lesions of the nodulus and ventral uvula.

Contributions of the Dorsal Vermis and Fastigial Nucleus to Gaze Control

Lobules VI and VII of the vermis (parts of the declive, folium, tuber, and pyramis) (Display 6-12) receive mossy fiber inputs

from the paramedian pontine reticular formation (PPRF), nucleus reticularis tegmenti pontis (NRTP), dorsolateral and dorsomedial pontine nuclei, vestibular nuclei, and nucleus prepositus hypoglossi, as well as climbing fiber inputs from the inferior olivary nucleus.30'321'348 The projection from the NRTP may relay information necessary for the planning of saccades from the frontal eye field to the cerebellum,67'144'174 whereas those from the dorsolateral pontine nuclei seem more concerned with smooth pursuit.154'321

Purkinje cells in the dorsal vermis discharge before saccades122'227 and encode target velocity during smooth pursuit and combined eye-head tracking.316 Stimulation of the vermis produces saccades.277

With currents near to threshold, a topographic organization is evident: upward saccades are evoked from the anterior part, downward saccades from the posterior part, and ipsilateral, horizontal saccades from the lateral part.222 Lesions of the dorsal vermis produce saccadic dysmetria. Unilateral pharmacological decortication with bicuculline typically causes marked ipsilateral hypometria and mild contralateral hypermetria, with a gaze deviation away from the side of the inactivation.280 Lesions of the posterior vermis also impair smooth pursuit, predominantly towards the side of the lesion.332

The main projection of the Purkinje cells of the dorsal vermis is to the caudal part of the fastigial nucleus—the most medial of the deep cerebellar nuclei (Display 6-13).348 This fastigial oculomotor region (FOR) also receives climbing fiber inputs from the inferior olivary nucleus and axon collaterals from mossy fibers projecting to the dorsal vermis from pontine nuclei, especially NRTP.111'223'348 Thus, the fastigial nucleus receives a "copy" of the saccadic commands, which are relayed by NRTP from the frontal eye fields and superior colliculus.223 The main projection from the fastigial nucleus crosses through the other fastigial nucleus and enters the uncinate fasciculus, which runs in the dorsolat-

eral border of the brachium conjunctivum, to reach the brain stem. The main targets of the caudal fastigial nucleus are the omnipause neurons and burst neurons in the medulla, pons, and midbrain. In addition, the nucleus of the posterior commissure, the mesencephalic reticular formation, and the rostral pole of the superior colliculus receive inputs from the fastigial nucleus.189'223 Smaller projections to other structures—NRTP, the dorsolateral pontine nuclei, vestibular nuclei, the superior colliculus, and the nucleus

prepositus hypoglossi—have been re- ported.16-17'111

Neurons in the caudal fastigial nucleus also discharge in relation to saccades94'124'226 and smooth pursuit.95 Fastigial nucleus lesions are well known to produce marked hypermetria of saccades.298 Destructive lesions tend to be bilateral because of the crossing of axons destined for the brain stem within the fastigial nucleus itself. The nature of the defect has been clarified using muscimol to induce pharmacological inactivation of one side of the caudal fastigial nucleus. The main effect is markedly hypermetric ipsilateral saccades and hypometric contralateral saccades. Additionally, there is a tonic gaze deviation toward

the side of inactivation, and smooth pursuit is impaired for targets moving con-

tralaterally. These findings are similar to the lateropulsion encountered in Wallenberg's syndrome (lateral medullary infarction) (see VIDEO: "Wallenberg's syndrome"). In that disorder, interruption of olivocerebellar climbing fibers within the restiform body is postulated to cause increased activity of Purkinje cells in the ipsilateral dorsal vermis, which, in turn, inhibits the underlying fastigial nucleus.340

THE CEREBRALHEMISPHERES AND VOLUNTARY CONTROLOF EYE MOVEMENTS

Approaches to Studying the

Cerebral Control of Eye

Movements in Humans

In developing a hypothetical scheme for the voluntary control of eye movements in humans, we have drawn on several different lines of evidence, each of which has inherent strengths and weaknesses. Anatomic and electrophysiologic studies in monkeys have contributed substantial insights, but caution is required in extrapolating hypotheses from these data to account for pathways and behavior in humans.334 Functional scanning, including proton emission tomography (PET) and functional magnetic resonance imaging (fMRI), have held the promise of identifying cortical areas homologous to those that have been well defined in monkeys.333 However, such studies have often yielded discrepant results, partly reflecting the use of different test paradigms. Another pitfall of functional imaging is that inferred local changes in cerebral metabolism may represent excitation or inhibition. Furthermore, there is evidence that just thinking about eye movements, without actually making them, may cause metabolic changes in areas such as the frontal eye field.23'166 Direct electrical stimulation of cerebral cortex during or before operations has limited availability. The noninvasive technique of transcranial magnetic stimulation (TMS), which transiently perturbs local cortical activity, will

not induce eye movements, but it has provided information on the sequence of programing that takes place in different cortical areas. Of abiding importance are studies of the behavioral effects of discrete lesions, using paradigms that test specific aspects of the voluntary control of eye movements. Most useful are the behavioral changes that occur with acute lesions or pharmacological inactivation. However, the effects of adaptation and recovery may modify or abolish acute behavioral deficits.

Interpretation of studies of the role of the cerebral hemispheres in the control of eye movements requires consideration of several special factors. First, it is important to test a range of behaviors from pure reflex to most voluntary, since all may be affected by hemispheric lesions. For example, rapid eye movements include reflex quick phases of nystagmus, saccades that respond to the changing highlights of the environment, and premeditated saccadic refixations (see Table 3-1, Chap. 3). Second, voluntary eye movements depend on attentional factors, and electrophysiologic evidence has linked increased attention with enhanced neural performance.64'305 Thus, smooth ocular tracking of a large moving target, such as a mirror rotated in front of a subject's face, may seem almost reflexive, but tracking of a small target moving across a textured background requires focused visual attention. Third, association areas that receive disparate sensory signals (e.g., visual or vestibular) must transform these signals so that they are synchronized and in similar coordinates. These areas must also take into account the current position of eye, head, and body in space. Finally, although our scheme is presented as a series of operations by different cortical and subcortical centers, parallel-distributed processing of retinal, ocular motor, and limbic inputs may be necessary to achieve the extensive repertoire of voluntary eye movements.

Our approach here will be (1) to summarize the contributions of visual and vestibular cortical areas; (2) to review the role played by parietal cortex and the pulvinar; (3) to examine the properties of neu-

rons in several frontal areas and the thalamic nuclei to which they are connected; and (4) to discuss the parallel, descending pathways by which volition controls eye movements.

Contributions of Posterior Cortical Areas to Gaze Control

PRIMARY VISUAL CORTEXAND GAZE CONTROL

Striate cortex (visual area VI, Brodmann area 17; Fig. 6-7 and Fig. 6-8) is of fundamental importance in the control of visually guided eye movements (Display 6-14). In monkeys, experimental, unilateral lesions of striate cortex impair eye movements because of the lack of visual input; saccadic and pursuit eye movements can still be made if the visual stimulus falls in the intact visual hemifield.296 If moving targets are presented in the visual hemifield contralateral to the lesion, however, saccades are inaccurate and no smooth pursuit is generated. Although monkeys tend to show some recovery from bilateral occipital lobe lesions, so they eventually regain some smooth-pursuit function,349 human beings with occipital lobe lesions show limited recovery.12 The deficit is greater with larger lesions, and smooth pursuit is impaired more than saccades.270 Complete, bilateral lesions of the occipital lobes that produce cortical blindness probably abolish optokinetic nystagmus in humans.335

CONTRIBUTIONS OF PERISTRIATE CORTEXTO GAZECONTROL

A separate visual pathway for the perception of motion has been demonstrated, starting in retinal ganglion cells that project via the magnocellular layers of the lateral geniculate nucleus to layer 4Ca of striate cortex.179 Some neurons in striate cortex respond to moving visual stimuli, but these cells have small receptive fields, respond only to motion in the frontal plane, and cannot encode higher image velocities. Further information processing is necessary before a pursuit or saccadic

eye movement can be programed; this is largely performed in the middle temporal visual area (MT or V5) and the medial su-

perior temporal visual area (MST) (Display 6-14 and Fig. 6-8).73'87'351 Striate cor-

tex projects both directly and indirectly to MT;328 in addition, MT receives inputs that bypass striate cortex,88 perhaps via the superior colliculus and pulvinar.275 Neurons in area MT have larger receptive fields than those in striate cortex and encode the speed and direction of target movements in three dimensions,73'160'187 and contribute to stereopsis.71a Experimental lesions in MT corresponding to extrafoveal retina cause a scotoma for motion in the contralateral visual field: stationary objects are perceived appropriately but motion perception is disrupted.220 The consequences of lesions of extrafoveal MT for eye movements are that saccades can still be made accurately to stationary targets in the affected visual field, but moving stimuli cannot be tracked accurately by saccades or smooth pursuit.83 Functional imaging studies have demonstrated the human homologue of area MT is located at the temporo-parieto-occipital junction, posterior to the superior temporal sulcus, at the junction of Brodmann areas 19, 37 and 39, close to the intersection of the ascending limb of the inferior temporal sulcus and the lateral occipital sul- cus.327-352 Patients with cortical lesions

have been described who appear to have perceptual11'13'356 or ocular motor200'323

deficits similar to those reported with MT lesions in monkeys.83'220

Visual area MT, in turn, projects to area MST,73'87 which contains neurons that not only encode moving visual stimuli but also appear to carry an eye movement signal.221 Area MST seems to be important for analyzing the optic flow that occurs during locomotion.78'114 Area MST is also important for the generation of smoothpursuit eye movements; lesions here or in the foveal representation of MT cause a deficit primarily of horizontal smooth pursuit for targets moving towards the side of the lesion. In addition, a retinotopic deficit for motion detection, similar to that with extrafoveal lesions of MT, is present for targets presented in the contralateral

visual hemifield.83 Thus, experimental lesions of MT produce a tracking deficit that

resembles the effects of certain posterior cerebral lesions in patients.200'323 The hu-

man homologue of area MST may lie adjacent to MT14 Other cortical regions, such as the superior temporal polysensory area,232 visual area 3a, and the superior parietal occipital region27 may also con-

tribute to processing of moving visual stimuli and directing visuospatial attention, but their homologous areas and contributions to human eye movements remain to be determined.

Cortical areas MT and MST are both important components of the neural substrate for smooth pursuit (Fig. 6-7),328 which projects ipsilaterally through the

retrolenticular portion of the internal capsule200 and the posterior portion of the cerebral peduncle to reach the dorsolateral pontine nuclei (DLPN).104>188>214 The pontine nuclei also receive inputs related to smooth pursuit from the frontal eye field. The dorsolateral pontine nuclei project to the dorsal paraflocculus105 and the dorsal vermis of the cerebellum.30 These cerebellar areas project in turn to the brain stem via the vestibular and fastigial nuclei.95'167 The effects of lesions at various points along this pursuit pathway are discussed in Chapter 4.

It has also been shown that areas MT and MST are important for mediating optokinetic nystagmus.83 Although a subcor-

tical visual pathway exists in human brain,92 and MT and MST project to nuclei in it,328 its functional capacity in adult humans with normal, binocular vision is uncertain. It may be important in the pathogenesis of latent nystagmus.

Contributions of the Temporal

Lobe to Gaze Control

Localization of the site of human vestibular cortex175 in the posterior aspect of the superior temporal gyrus, the parieto- insular-vestibular cortex (PIVC) (Fig. 6-8), has been achieved using functional

imaging during vestibular and optokinetic stimulation,25'273'343'763'93 and by studying

the effects of cortical lesions (Display 6_l5).28,29,i46,i75 This localization confirms

the stimulation studies of Penfield.243 Clinical lesions affecting this area of temporal cortex cause contraversive tilts of the subjective visual vertical,29 abolish the sense of self-rotation (circularvection) that normally occurs with optokinetic stimulation,315 and impair memory-guided saccades if patients are rotated to a new position during the memory period.146 It seems likely that, as in monkey, other cor-

tical areas also receive vestibular inputs, so more than one vestibular area may exist.25'175 Reported effects of parietotemporal lesions on fixation-suppression of vestibular eye movements (such as those induced by caloric stimulation) probably reflect impaired smooth pursuit due to involvement of secondary visual areas, such as MT and MST.

Contributions of the Parietal Lobe to Gaze Control

The parietal lobe has an important influence on all classes of eye movements by virtue of its role in directing visual attention to objects in extrapersonal space. In addition, the parietal eye field (PEF) has a direct role in programing saccades. Substantial progress has been achieved in understanding parietal lobe contributions to the control of eye movements in the rhesus monkey. However, caution is necessary

in extrapolating these results to parietal lobe function in humans, because differences in anatomy exist between the two species,333 and humans have developed right hemisphere dominance for directing spatial attention. In general, the parietal lobes are important in programing saccades concerned with reflexive exploration of the visual environment.

CONTRIBUTIONS OF THE POSTERIOR PARIETAL CORTEX TO GAZE CONTROL

The inferior parietal lobule of the mon-

key, specifically the caudomedial portion that has been called area 7a or PG,4'5'9'185

contains populations of neurons that respond to visual stimuli and discharge during a range of eye movements (see Fig. 6-8A and Display 6-16). In monkeys, these neurons receive inputs from secondary visual areas, such as MST, the pulvinar, superior colliculus, cingulate cortex, and the intralaminar thalamic nuclei.5'55'219 Parietal area 7a projects to dorsolateral prefrontal cortex and to the cingulate gyrus, but only weakly to the frontal eye field.5 A homologous area in the human brain, corresponding to portions of Brodmann areas 39 and 40, may lie in the inferior parietal lobule (see Fig. 6-8B). Functional imaging studies suggest that the adjacent superior parietal lobule is also important for shifting attention in humans.65

Area 7a contains a variety of neurons that discharge during active visual fixa-

tion, in relation to saccades, or during smooth pursuit.9 The visual receptive fields of neurons in area 7a are large and often cross the midline. Neurons that respond to moving stimuli in the periphery of vision may be important for processing the optic flow that occurs during locomotion.312 Neurons that discharge in relationship to saccades usually do so after the eye movement is made.9 Furthermore, cells that are active during smooth pursuit

seem more concerned with directing attention to the visual stimulus than with re-

cording its dynamic properties.185 Thus, it seems that posterior parietal cortex is more concerned with shifts of attention than with eye movements per se.311 In fact, eye movements are not necessary to shift the focus of attention.262 On the other hand, difficulties in initiating saccades may occur if attention cannot be shifted from one location to another.263 For posterior parietal cortex to be able to synthesize a signal that can direct visual attention towards an object in extrapersonal space, one must take account of not only the retinal coordinates of the stimulus but also the direction of gaze (eye position in space). Thus, an important finding is that the discharge of some neurons in area 7a is influenced not just by visual stimuli but also by eye and head position.6'31 Area 7a

has been shown to receive vestibular inputs,86 and eye position could be signaled by efference copy. It has been postulated that a neural network of such cells could encode a visual target in spatial or headcentered coordinates.6

Similar properties have been demonstrate in another subdivision of the parietal lobe, the ventral intraparietal area (VIP), which lies in the fundus of the intraparietal sulcus in monkeys (Fig. 6-8A).

Some neurons here encode the location of visual stimuli in a head-centered frame of reference79 and respond to somatosensory stimuli. Thus, VIP may be important for building an internal, multisensory representation of extrapersonal space.81

Clinically, unilateral posterior parietal lesions, especially right-sided ones, cause contralateral inattention and may produce ipsilateral gaze deviation or preference and partially restrict saccades and smooth pursuit to the ipsilateral hemirange of gaze.24'199 Even after the acute phase, latency of visually guided saccades remains bilaterally increased, especially with rightsided lesions.184'256 In addition, memoryguided saccades are inaccurate.255 A similar defect of memory-guided saccades is produced in normal subjects if TMS is applied to the posterior parietal area early during the memory period.212-234