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

For sinusoidal target motions, gain may be estimated from peak eye velocity/peak target velocity.The dependence of gain on peak target acceleration is a useful measure of the pursuit performance (see Models of Smooth Pursuit, above). Alternatively, using digitized data, it is possible to remove saccades and perform a Fourier transform of target and eye signals and thereby compute gain and phase.

A variety of indirect methods are commonly used to measure smooth-pursuit performance.3 Attempts to quantify smooth pursuit by measuring frequency and number of saccades are prone to error, since saccadic abnormalities (e.g., square wave jerks) may disrupt overall tracking but not necessarily imply impaired pursuit (i.e., pursuit gain may be normal): Similarly, power spectral measurements (e.g., natural logarithm of ratio of the power at target frequency to power at higher frequencies) or root-mean-square error values are estimates of overall tracking, not just smooth pursuit. Finally, qualitative rating scales of pursuit as relatively "normal" or "deviant" are of little value in determining the nature of the deficit.3 For quantitative aspects of smooth eye-head tracking, see the Evaluation of Eye-Head Movements in Chapter 7.

ABNORMALITIES OF

VISUAL FIXATION AND

SMOOTH PURSUIT

Here we discuss the pathological physiology of disordered fixation and smooth pursuit. In Chapter 10, these abnormalities are approached from the viewpoint of topological diagnosis.

Abnormalities of Visual Fixation

Steady fixation may be disrupted by slow drifts, nystagmus, or involuntary saccades. Since normal subjects show miniature movements of all three types (Fig. 4-1), determination of abnormal fixation behavior is sometimes dependent on statistical analysis of measured eye movements.

One specific example of the problem of determining what is abnormal concerns square-wave jerks (Fig. 10-16A, Chap. 10). These are small saccades (typically 0.5-5.0 deg) that take the eye away from the fixation point and after a period of about 200 msec, return it to the starting position. Many normal subjects show square-wave jerks when they attempt steady fixation.128'273 The frequency of these saccadic intrusions upon fixation is greater in older subjects. In some elderly subjects, the frequency of square-wave jerks is as great as that occurring in certain neurological conditions, notably progressive supranuclear palsy, Friedreich's ataxia, and focal cerebral lesions.275 Thus, such disruption of fixation is only suggestive of an underlying neurological condition. Square-wavejerks are discussed further in the section Saccadic Intrusions in Chapter 10.

Detection of nystagmus during attempted steady fixation is abnormal. If the slow-phase velocity or intensity of such nystagmus is similar both during fixation and when fixation is prevented (e.g., by Frenzel goggles or in darkness), then a disorder of the fixation system is inferred. If slow-phase velocity is reduced during attempted fixation, then the fixation system is at least partially functioningand another ocular motor disorder (e.g., imbalance of vestibular drives) is present. A variety of conditions may lead to nystagmus during attempted fixation and are discussed under A Pathophysiological Approach to Nystagmus in Chapter 10.

Disorders of the visual system lead to instability of gaze; the extreme example is blindness (see Fig. 10-10, Chap. 10).189 Monocular loss of vision may lead to unstable gaze in the affected eye, which is predominantly due to slow, low-frequency vertical drifts.187 These movements may reflect disturbance of a monocular fixation system or, perhaps, vergence.341 Binocular loss of vision causes loss of gaze stability and a continuous horizontal and vertical nystagmus develops (see VIDEO: "Eye movements with complete blindness"). This nystagmus characteristically changes direction over the course of seconds and minutes, a feature also encountered

following experimental cerebellectomy.262 Thus, the nystagmus that follows bilateral visual loss reflects a gaze-holding mechanism that has never been calibrated by visual inputs. Acquired lesions of the cerebellum without specific involvement of the visual pathways may disrupt fixation with saccadic intrusions and with slow drifts, especially in the vertical plane, that lead to nystagmus.13'2'242 These abnormalities may reflect the important role of the cerebellum in optimizing fixation to provide clearest vision.

As discussed in Models of Smooth Pursuit, the pathogenesis of pendular oscillations in association with visual loss is undetermined. Experimental deprivation of information on retinal slip velocity during development causes a 4- to 5-Hz pendular nystagmus.64'209 When pendular nystagmus occurs in association with optic nerve demyelination due to multiple sclerosis, the size of the oscillations tends to be greatest in the eye with worse vision.24 However, experimental studies (Fig. 4-10) indicate that visual delays cannot be the cause of their nystagmus.8

Abnormal maturation of binocular visual mechanisms may be responsible for disruption of steady fixation by latent nystagmus and, in some cases, by congenital nystagmus; these conditions are discussed below.

Abnormalities of Smooth Pursuit

ABNORMALITIES OF

PURSUIT INITIATION

Here we will discuss disorders of smooth pursuit in terms of abnormalities of initiation, gain, and symmetry. The issue of disturbance of pursuit in latent and congenital nystagmus will also be reviewed. Like fixation, smooth pursuit can be disrupted by saccadic intrusions and, often, disease affecting the pursuit system also causes square-wave jerks and other saccadic abnormalities.

The advantages of studying the onset of pursuit were discussed above; in the case of cortical lesions, step-ramp stimuli are particularly valuable because they provide

a method of controlling the location of the visual stimulus on the retina (i.e., in the visual field). Because of the latency of the pursuit system (approximately 100 msec), the initial 100 msec of the response will reflect stimulation of the selected portion of retina. Thus, using step-ramp stimuli, it has been shown that experimental, unilateral lesions of striate cortex cause a loss of smooth pursuit for targets moving in the blind visual field;272 this deficit is not evident during pursuit of a predictably moving target partly because of preserved macular vision.131 In humans, bilateral occipital lobe lesions abolish or prevent the development of smooth pursuit.259

More important, it has been possible to identify distinct disturbances of ocular tracking due to lesions of secondaryvisual areas.220'301 One such disturbance was exemplified by a patient who complained of difficulties in seeing moving, but not stationary, objects in his right visual hemifield following a stroke (Fig. 4-8).184'301 Routine perimetric testing of his visual fields was normal. Furthermore, testing of pursuit with predictable, sinusoidal stimuli showed little abnormality. Nevertheless, with step-ramp stimuli, his ocular motor deficits reflected a loss of the ability to estimate the speed of moving objects in the right visual hemifield. Specifically, the initiation of pursuit and planning of saccades to targets moving to right or left within the right visual hemifield were impaired. In contrast, saccades made to static target displacements were normal (Fig. 4-8). Thus, these deficits are similar to those described in monkeys after lesions of the middle temporal visual area (MT): a retinotopic defect for the perception of motion. The lesion lay at the junction of temporo-occipital cortex (Fig. 4-8), suggesting it might involve the human homologue of area MT.

A second type of tracking deficit occurring with unilateral cerebral lesions consists of a directional pursuit deficit in which horizontal pursuit directed towards the side of the lesion is impaired compared with contralateral pursuit (Fig. 4-1 IB). Using step-ramp stimuli and measuring the onset of smooth pursuit, it has been demonstrated that this unidirec-

tional deficit occurs irrespective of the visual hemifield into which the stimulus falls (Fig. 4-11C).220'301 A retinotopic deficit such as that occurring with lesions of MT may or may not coexist. The unidirectional deficit may occur with lesions affecting posterior cortical areas and underlying white matter (Fig. 4-11A); this may be due to damage to the medial superior temporal visual area (MST) or its projections. In addition, a unidirectional defect of smooth pursuit may occur following lesions of the frontal lobes that affect the

frontal eye field222 or of the supplementary eye field.122'191

The initiation of pursuit has also been investigated in patients with latent nystagmus.308 By presenting step-ramp stimuli monocularly, it was possible to demonstrate a nasal-temporal asymmetry such that nasally directed target motion evoked a more vigorous onset of pursuit. This finding is evidence for maldevelopment of visual motion processing in patients with latent nystagmus and is discussed further below.

Another advantage offered by studying the initiation of smooth pursuit is that it measures the open-loop gain of the pursuit system; this is a sensitive index of

smooth pursuit dysfunction. Three examples of how this strategy has proven effective are in studying adaptive changes occurring following extraocular muscle palsy, identifying pursuit abnormalities in some cases of congenital nystagmus, and in confirming a disorder of pursuit in schizophrenia. Each example is discussed further below. It seems likely that in the future, the initiation of smooth pursuit will be tested in a variety of clinical conditions.

ABNORMALITIES OF PURSUIT TO SUSTAINED TARGET MOTION

Low gain pursuit is a common ocular motor abnormality. Recent attempts have been made to differentiate between a low steady-state pursuit gain in response to constant-velocity target motions (i.e., reduced gain at both low and high target velocities, termed velocity saturation) and a reduction of pursuit gain with accelerating targets (e.g., sine waves), so-called acceleration saturation. Low steady-state pursuit

Figure 4-11. Asymmetric impairment of horizontal smooth pursuit due to unilateral lesions of the cerebral hemispheres. (A) Computer-generatedthree-di- mensional reconstruction of the zones of lesion confluence associated with asymmetric reduction of pursuit gain in eight patients; ipsilateral pursuit velocities were consistently lower than contralateral velocities. The affected cortical areas included Brodmann 19 and the adjacent ventrocaudal aspect of area 39. (From Morrow MJ, Sharpe JA. Cerebral hemispheric localization of smooth pursuit asymmetry. Neurology 1990;40:284-292, with permission of Lippincott Williams and Wilkins.)

Continued onfollowing page

gain occurs with a variety of conditions, including old age,247>282'344 Parkinson's disease,327 progressive supranuclear palsy,303 and following large cerebral lesions.304 Impairment of smooth pursuit due to an abnormal acceleration saturation is seen with posterior cortical lesions,188'219 Alzheimer's disease,96 and schizophrenia.193

Studies of the effects of predictive aspects of smooth pursuit have shown impairment in schizophrenia193 but preservation in patients withAlzheimer's disease96 who have otherwise poor tracking. Large lesions of the cerebral hemispheres causing predominantly ipsilateral tracking deficits have been reported to impair,39 but not abolish,192 predictive aspects of smooth pursuit. Frontal lesions impair smooth pursuit more than posterior lesions.122 Smooth anticipatory eye drifts that precede predictable target stepping are absent in patients with cerebellar dis-

ease who have impaired smooth pursuit.223

Excessively high pursuit gain may reflect adaptive changes due to extraocular muscle palsy. If, for example, a patient with partial left abducens palsy is forced to use that eye (by patching the normal, right eye), increased innervation is sent to the weak muscle.244 If, after several days, the patch is switched so that the normal eye views again, smooth-pursuit gain of the right eye to the left is increased and tracking is unstable with pendular oscillations; the latter were most evident when the initiation of pursuit was studied using stepramp stimuli. These findings imply that

pursuit adaptation, rather than simple negative feedback, is used to optimize smooth-tracking performance.

An asymmetry of horizontal smooth pursuit is seen with lesions of certain portions of the pathway for smooth pursuit (Fig. 4-1IB). Thus, some patients with unilateral, lesions of the cerebral hemispheres show impaired tracking of targets moving towards the side of the lesion. This has been most commonly reported with lesions restricted to posterior cortical areas and underlying white matter (Fig. 4-11A),219'301 but it also occurs with frontal lobe lesions191'222 and is invariable with large lesions such as hemidecortication.276>304 Clinically, this pursuit deficit is

often brought out with hand-held optokinetic drums or tapes.17'55'65'97-163 This

impairment of smooth pursuit is independent of homonymous hemianopia or visual neglect.301 Use of step-ramp stimuli (Fig. 4-11C) has demonstrated that in patients with intact visual fields, this direc-

tional deficit is present for visual stimuli presented in either visual hemifield.184'220 After an acute large hemispheric lesion, there may be a defect of pursuit in craniotopic coordinates, with difficulty moving the eyes in the contralateral orbital hemirange. There may also be contralateral neglect, especially with right-sided lesions. However, within the remaining field of movement, pursuit responses to stimulus motion towards the intact hemisphere are

greater.217

In some patients with unilateral lesions of the cerebral hemispheres, pursuit away from the side of the lesion may also have reduced gain, though not usually so much as ipsilaterally.191'219 In other patients, particularly those with large lesions such as hemidecortication or involvement of the posterior internal capsule,253 pursuit eye movements away from the side of the lesion may be faster than the target (i.e., smooth pursuit gain exceeds 1.0). An example is shown in Figure 4-1 IB. One consequence of such increased gain for contralateral pursuit is that the moving target is held in the visual hemifield ipsilateral to the side of the lesion, where the ability to estimate target speed is likely to be normal;184 responses to moving stimuli presented into the visual hemifield contralateral to the side of the lesion may be impaired.

An ipsilateral pursuit deficit similar to that due to hemispheric disease may be encountered with unilateral lesions at lower points in the descending pursuit pathway (Fig. 4-7), such as in the thalamus,41 midbrain tegmentum,343 dorsolateral pontine nucleus,105'298 and cerebellum.326 However, because of the double decussation of the smooth-pursuit pathway (see Fig. 6-7, Chap. 6), lesions involving the vestibular nucleus or pontine projections to the cerebellum may cause a greater impairment of either ipsilateral322 or contralateral smooth pursuit.14-103'141

Disturbance of vertical smooth pursuit occurs with bilateral internuclear ophthalmoplegia (INO).254 Lesions affecting the brachium conjunctivum, which conveys pursuit signals from the y-group nucleus to the oculomotor nucleus, may also impair smooth pursuit.54'250 It has also been

reported that projections from the pontine nuclei to the cerebellum may affect vertical smooth pursuit. In three patients with cavernous angiomas involving the middle cerebellar peduncle, torsional nystagmus developed during vertical pursuit. This finding suggests that pursuit signals might be encoded in the same planes as the labyrinthine semicircular canals, perhaps during cerebellar processing.95 Lesions restricted to either the paramedian pontine or mesencephalic reticular formation impair saccades but spare horizontal and vertical smooth pursuit.121-127

In some patients with asymmetry of pursuit, nystagmus is present during fixation with the eyes near to central position. Thus, horizontal nystagmus is reported in some patients with unilateral cerebral lesions, particularly those with increased gain of contralateral pursuit.276 This nystagmus is low amplitude, with slow phases drifting away from the side of the lesion at a few degrees per second. Such nystagmus has been hypothesized to indicate an imbalance of pursuit tone. Another circumstance in which an imbalance of pursuit drives has been postulated as a cause of nystagmus is with cerebellar or brain stem lesions.2'346 The nystagmus is present with the eyes close to primary position and may be downbeat, upbeat, or horizontal (see Fig. 10-7, Chap. 10). In such patients, the slow-phase velocity is unchanged in darkness and smooth pursuit is impaired. The more likely cause for nystagmus with cerebellar or brain stem disease is now thought to be an imbalance of central vestibular connections.12

Smooth Pursuit, Visual Fixation,

and Latent Nystagmus

Individuals with latent nystagmus,73 a congenital form of nystagmus (see VIDEO: "Latent nystagmus"), show abnormalities of smooth pursuit. This conjugate nystagmus is brought out or exaggerated by covering one eye (hence, "latent" nystagmus). The slow phases of this conjugate nystagmus are directed such that the viewingeye rotates towards the nose. Latent nystag-

mus is probably always associated with strabismus and lack of development of normal binocular vision.

Monkeys that are binocularly deprived of pattern vision early in life may develop latent nystagmus.306 A similar nystagmus can be produced in monkeys by surgically creating strabismus in the first 2 months of life.157 Such monkeys also show an asymmetry of smooth pursuit and optokinetic movements, with stronger responses for nasally than temporally directed target motion.305 In humans, the asymmetry of pursuit is more marked at the onset than during maintenance.308 Furthermore, if moving stimuli are briefly presented after pursuit is underway, nasally and temporally directed image motion is equally effective in modulating eye velocity.157 This suggests that the defect is more related to pursuit initiation than maintenance. Electrophysiological studies have shown that neurons in MT in strabismic monkeys have normal responses but are rarely driven binocularly.157 In NOT, neurons normally respond to visual stimuli presented to either eye,100 but in binocularly deprived monkeys, neurons are driven ex-

clusively or mainly by the contralateral eye 233,305 This contralateral eye domi-

nance seems to be relevant to the pathogenesis of LN. For example, during monocular viewing through the right eye, the left NOT will be activated preferentially, thus producing leftward smooth movements (slow phases of nystagmus). Support for this hypothesis comes from the finding that inactivation of the NOT abolishes LN in monkeys who have been deprived of binocular vision.233 Furthermore, lesioning the NOT abolishes flash nystagmus, which occurs during monocular stimulation with repetitive flashes of

light and has similarities to latent nystagmus.319

Whether binocular deprivation ofvision affects other brain stem targets of areas MT and MST, such as the pontine nuclei, remains unknown. It also seems likely that other factors, such as abnormal extraocular proprioception138 or disturbance of either directed visual attention or egocentric localization, play a role in the pathogenesis of LN.72'162 Thus, some sub-

jects can change direction of their nystagmus by "attempting" to view with one or the other eye, without change in visual inputs. Further discussion may be found in the section on latent nystagmus in Chapter 10.

Smooth Pursuit in Patients with Congenital Nystagmus

Some individuals with congenital nystagmus (see VIDEO: "Congenital nystagmus") maintain adequate foveation periods (periods when the image of the target is close to the fovea and eye velocity is similar to target velocity) during smooth pursuit.74 Other individuals pursue visual targets poorly, probably because of associated visual defects rather than the congenital nystagmus per se. Finally, some affected individuals appear to respond to a step-ramp pursuit stimulus with a reversal of their nystagmus slow phase that is in the direction opposite to the target ramp.152 Some individuals with congenital nystagmus seem to show an "inversion of smooth-pur- suit or optokinetic responses."120 For example, when they watch a hand-held opto-

kinetic drum, the quick phases are directed to the same side as that to which the drum rotates. It has been shown, however, that the velocity of the moving optokinetic stimulus does not influence the slow-phase velocity of the nystagmus.1 One interpretation of this last phenomenon is that smooth pursuit causes the nystagmus null point (i.e., orbital eye position at which eye velocity is zero) to shift to some other point.71'179 An alternative explanation is that in some individuals, velocity signals are processed incorrectly with an inversion of sign, leading to a wrongly-di- rected smooth-pursuit command.243

"Inversion of optokinetic responses" has also been found in albino rabbits when stimulation was limited to the anterior visual field (temporal retina).63 Such animals showed a spontaneous nystagmus when their posterior visual fields were covered. A variety of albino species show anomalies of their visual pathways.117-118 Evidence for abnormal decussation of tem-

poral retinal fibers has been found in patients with ocular albinism.66 Congenital nystagmus is a cardinal feature of human albinism.59 Absence of crossing of nasal fibers in achiasmatic patients6 or mutant sheep dogs75 is associated with congenital seesaw nystagmus. The relationship between these misroutings of the visual pathways and congenital nystagmus has yet to be determined.

SUMMARY

1.Smooth-pursuit eye movements enable continuous clear vision of ob-

jects moving within the environment. Smooth pursuit may have evolved to provide continuous foveal vision of a stationary object during self-motion. There is evidence for separate neural mechanisms that are more concerned with either visual fixation of a stationary target or smooth pursuit of a target that moves.

2.The principal stimulus for pursuit eye movements is the motion of the image of a target across the retina and especially the foveal and perifoveal region. In certain circumstances, the perception of image motion may be sufficient, and even nonvisual stimuli such as proprioception can generate smooth tracking movements. Smooth-pursuit responses are greatly influenced by the predictability of target motion.

3.Smooth pursuit can be quantified by measuring its onset and its maintenance. Step-ramp stimuli, presented in a nonpredictable sequence, can be used to measure the onset of smooth pursuit and especially the open-loop response, which is a sensitive index of pursuit malfunction. Step-ramp stimuli also permit one to assay the contribution of a specified portion of the retina (visual field) to the generation of the pursuit response. During maintenance of smooth pursuit, gain (eye velocity/target velocity) is the most useful measurement. If sinusoidal stimuli are used, the effects upon gain of increasing peak velocity

and peak acceleration of the stimulus can be determined.

4.The pursuit pathway (Fig. 6-7) be-

gins with a visual subsystem for analyzing movement; it starts at the retina and runs to the magnocellular portion of the lateral geniculate nucleus, the striate cortex, secondaryvisual areas (MT and MST), the dorsolateral pontine nucleus, cerebellum, vestibular nuclei, brain stem reticular formation, and the ocular motor nuclei. Study of discrete lesions along this pathway has provided insight into visual processing of moving targets. Unilateral lesions along this pathway produce a predominantly ipsilateral deficit of smooth pursuit. The frontal and supplementary eye fields also contribute to smooth pursuit and may be important in generating responses to predictable target motions. An accessory optic system and the nucleus of the optic tract may play a role in activating the transcor- tical-pontine-cerebellar pursuit pathway (Fig. 4-7).

5.The pursuit response shows considerable intersubjectvariability. Pursuit is influencedby alertness and by a variety of drugs, and it declines in old age. Impaired pursuit (reduced gain) is a nonspecific finding of many diffuse neurologic disorders. Corticallesions cause distinct deficits of smooth

pursuit (Fig. 4-11). Adaptive increases in pursuit gain may occur if it becomes necessary to track moving targets with a paretic eye. Abnormalities of smooth pursuit may be encountered in some individuals with congenital forms of nystagmus.

REFERENCES

1.Abadi RV, Dickinson CM. The influence of pre-existing oscillations on the binocular optokinetic response. Ann Neurol 1985;l7:578-86.

2.Abel LA, Dell'Osso LF. Horizontal pursuit defect nystagmus. Ann Neurol 1979;5:449-52.

3.Abel LA, Ziegler AS. Smooth pursuit eye movements in schizophrenics—what constitutes quantitative assessment? Biol Psychiatry 1988;24:747-61.

4. Accardo AP, Pensiero S, Dapozzo S, Perissutti

P.Characteristics of horizontal smooth pursuit eye movements to sinusoidal stimulation in children of primary school age. Vision Res 1995;35:539-48.

5.Andersen RA, Essick GK, Siegel RM. Encoding of spatial location by posterior parietal neurons. Science 1985;230:456-8.

6.Apkarian P, Bour LJ, Earth PG, WennigerPrick L, Verbeeten B. Non-decussating retinalfugal fibre syndrome—an inborn achiasmatic malformation associated with visuotopic misrouting, visual evoked potential ipsilateral asymmetry and nystagmus. Brain 1995; 118: 1195-216.

7.Atkinson J. Human visual development over the first 6 months of life. A review and hypothesis. Hum Neurobiol 1984;3:61-74.

8.Averbuch-Heller L, Zivotofsky AZ, Das VE, DiScenna AO, Leigh RJ. Investigations of the pathogenesis of acquired pendular nystagmus. Brain 1995;188:369-78.

9.Bahill AT, Harvey DR. Open-loop experiments for modeling the human eye movement system. IEEE Trans SMC 1986; 16:240-50.

10.Bahill AT, McDonald JD. Model emulates human smooth pursuit system producing zerolatency target tracking. Biol Cybern 1983;48: 213-22.

11.Bahill AT, McDonald JD. Smooth pursuit eye movements in response to predictable target motions. Vision Res 1983;23:1573-83.

12.Baloh RW, Spooner JW. Downbeat nystagmus:

Atype of central vestibular nystagmus. Neu-

rology 1981;31:304-10.

13.Baloh RW, Yee RD, Honrubia V. Optokinetic nystagmus and parietal lobe lesions. Ann Neurol 1980;7:269-76.

14.Baloh RW, Yee RD, Honrubia V Eye movements in patients with Wallenberg's syndrome. Ann NY Acad Sci 1981;374:600-13.

15.Baloh RW, Yee RD, Honrubia V, Jacobson K. A

comparison of the dynamics of horizontal and vertical smooth pursuit in normal human subjects. Aviat Space Environ Med 1988;59: 121-4.

16.Banks MS, Ehrlich SM, Backus BT, Crowell JA. Estimates of heading during real and simulated eye movements. Vision Res 1996;36: 431-43.

17.Barany R. Zur Klinik und Theorie des Eisen- bahn-nystagmus. Acta Otolaryngol 1921;3: 260-5.

18.Barnes GR, Asselman PT. The mechanism of prediction in human smooth pursuit eye movements. J Physiol (Lond) 1991;439:439-61.

19.Barnes GR, Asselman PT. Pursuit of intermittently illuminated moving targets in the human. J Physiol (Lond) 1992;445:617-37.

20.Barnes GR, Donnelly SF, Eason RD. Predictive velocity estimation in the pursuit reflex response to pseudo-random and step displacement stimuli in man. J Physiol (Lond) 1987; 389:111-36.

21.Barnes GR, Goodbody S, Collins S. Volitional control of anticipatory ocular pursuit re-

sponses under stabilized image conditions in humans. Exp Brain Res 1995;106:301-17.

22.Barnes GR, Grealy M, Collins S. Volitional control of anticipatory ocular smooth pursuit after viewing, but not pursuing, a moving target: evidence for a re-afferent velocity store. Exp Brain Res 1997;! 16:445-55.

23.Barnes GR, Ruddock CJS. Factors affecting the predictability of pseudo-random motion stimuli in the pursuit reflex of man. J Physiol (Lond) 1989;408:137-65.

24.Barton JJS, Cox TA. Acquired pendular nystagmus in multiple sclerosis—clinical observations and the role of optic neuropathy. J Neurol Neurosurg Psychiatry 1993;56:262-7.

25.Barton JJS, SharpeJA, Raymond JE. Retinoptic and directional defects in motion discrimination in humans with cerebral lesions. Ann

Neurol 1995;37:665-75.

25a. Barton JJ, SharpeJA. Ocular tracking of stepramp targets by patients with unilateral cerebral lesions. Brain 1998; 121:1165-83.

26.Barton JJS, Simpson T, Kiriakopoulos E, Stewart C, Crawley A, Guthrie B, Wood M, Mikulis D. Functional MRI of lateral occipitotemporal cortex during pursuit and motion perception. Ann Neurol 1996;40:387-98.

27.Becker W, Fuchs AF. Prediction in the oculomotor system: smooth pursuit during transient disappearance of a visual target. Exp Brain Res 1985;57:562-75.

28.Behrens F, Collewijn H, Griisser O-J. Velocity step responses of the human gaze pursuit system. Experiments with sigma-movement. Vision Res 1985;25:893-905.

29.Behrens F, Griisser O-J. On the additivity of sigmaand phimovement in visual perception and oculomotor control. Hum Neurobiol 1982;l:121-7.

30.Belknap DB, Noda H. Eye movements evoked by microstimulation in the flocculus of the alert macaque. Exp Brain Res 1987;67: 352-62.

31.BogousslavskyJ, Regli F. Pursuit gaze defects in acute and chronic unilateral parieto-occipi- tal lesions. Eur Neurol 1986;25:10-8.

32.Boman DK, Braun DI, Hotson J. Stationary and pursuit visual fixation share similar behavior. Vision Res 1996;36:751-63.

33.Boman DK, Hotson JR. Stimulus conditions that enhance anticipatory slow eye movements. Vision Res 1988;28:1157-65.

34.Boman DK, Hotson JR. Motion perception prominence alters anticipatory slow eye movements. Exp Brain Res 1989;74:555-62.

35.Boman DK, Hotson JR. Predictive smooth pursuit eye movements near abrupt changes in motion direction. Vision Res 1992;32: 675-89.

36.Boussaoud D, Desimone R, Ungerleider L. Subcortical connections of visual areas MST and FST in macaques. Vis Neurosci 1992;9: 291-302.

37.Bradley DC, Maxwell M, Andersen RA, Banks MS, Shenoy KV. Mechanisms of heading perception in primate visual cortex. Science 1996; 273:1544-7.

38.Brandt SA, Dale AM, Wenzel R, Culham JC, Mendola JD, Tootell RBH. Sensory, motor and attentional components of eye movement induced cortex activation. Soc Neurosci Abstr 1997;23:2223.

39.Braun DI, Boman DK, Hotson JR. Anticipatory smooth eye movements and predictive pursuit after unilateral lesions in human brain. Exp Brain Res 1996;! 10:111-6.

40.Bremmer F, Distler C, Hoffmann K-P. Eye position effects in monkey cortex. II. Pursuitand fixation-related activity in posterior parietal areas LIP and 7A. J Neurophysiol 1997; 77:962-77.

41.Brigell M, Goodwin JA. Hypometric saccades and low-gain pursuit resulting from a thalamic hemorrhage. Ann Neurol 1984; 15:374-8.

42.Brindley GS, Gautier-Smith PC, Lewin W. Cortical blindness and the functions of the non-geniculate fibers of the optic tracts. J Neurol Neurosurg Psychiatry 1969;32:259-64.

43.Brodal P.The corticopontine projection in the rhesus monkey. Brain 1978;101:251-83.

44.Bucher SF, Dieterich M, Seelos KG, Brandt T. Sensorimotor cerebral activation during optokinetic nystagmus. A functional MRI study. Neurology 1997;49:1370-7.

45.Burman DD, Bruce CJ. Suppression of taskrelated saccades by electrical stimulation in the primate's frontal eye field. J Neurophysiol 1997;77:2252-67.

46.Burr DC, Ross J. Contrast sensitivity at high velocities. Vision Res 1982;22:479-84.

47.Butzer F, Ilg UJ, Zanker JM. Smooth-pursuit eye movements elicited by first-order and sec- ond-order motion. Exp Brain Res 1997; 115: 61-70.

48.Biittner U, Straube A, Spuler A. Saccadic dysmetria and "intact" smooth pursuit eye movements after bilateral deep cerebellar nuclei lesions. J Neurol Neurosurg Psychiatry 1994;57: 832-4.

49.Buttner-Ennever JA, Cohen B, Horn AKE, Reisine H. Efferent pathways of the nucleus of the optic tract in monkey and their role in eye movements. J Comp Neurol 1996;373:90-107.

50.Buttner-Ennever JA, Horn AK. Pathways from cell groups of the paramedian tracts to the floccular region. Ann NY Acad Sci 1996;781: 532-40.

51.Carl JR, Gellman RS. Human smooth pursuit: Stimulus-dependent responses. J Neurophysiol 1987;57:1446-63.

52.Carpenter RHS. The visual origins of ocular motility. In Cronly-Dillon JR, editor. Vision and Visual Function, Vol. 8. Eye Movements. London: MacMillan Press; 1991; p. 1-10.

53.Celebrini S, Newsome WT. Neuronal and psychophysical sensitivity to motion signals in extrastriate cortex area MST of the macaque monkey. J Neurosci 1994; 14:4109-24.

54.Chubb MC, Fuchs AF. Contribution of y group of vestibular nuclei and dentate nucleus of cerebellum to generation of vertical smooth eye movements. J Neurophysiol 1982;48:75-99.

55.Cogan DG, Loeb DR. Optokinetic response and intracranial lesions. Arch Neurol Psychiatry 1949;61:183-7.

56.Cohen B, Matsuo V, Raphan T. Quantitative analysis of the velocity characteristics of optokinetic nystagmus and optokinetic after-nys- tagmus. J Physiol (Lond) 197;270:321-44.

57.Cohen B, Reisine H, Yokota JI, Raphan T. The nucleus of the optic tract. Ann NY Acad Sci 1992;656:277-96.

58.Collewijn H. The Oculomotor System of the Rabbit and its Plasticity. New York: SpringerVerlag; 1981.

59.Collewijn H, Apkarian P, Spekreijse H. The oculomotor behavior of human albinos. Brain 1985;108:l-28.

60.Collewijn H, Curio G, Griisser O-J. Spatially selective visual attention and generation of eye pursuit movements. Hum Neurobiol 1982;!: 129-39.

61.Collewijn H, Tamminga EP Human smooth and saccadic eye movements during voluntary pursuit of different target motions on different backgrounds. J Physiol (Lond) 1984;351: 217-50.

62.Collewijn H, Tamminga EP. Human fixation and pursuit in normal and open-loop conditions: effects of central and peripheral retinal targets.] Physiol (Lond) 1986;379:109-29.

63.Collewijn H, Winterson BJ, Dubois MFW. Optokinetic eye movements in albino rabbits: inversion in the anterior visual field. Science 1978;199:1351-3.

64.Conway JL, Timberlake GT, Skavenski AA. Oculomotor changes in cats reared without experiencing continuous retinal image motion. Exp Brain Res 1981;43:229-32.

65.Cords R. Optisch-motorisches Feld und op- tisch-motorische Bahn. Ein Beitrag zur Physiologic und Pathologic der Rindeninnervation der Augenmuskeln. Graefe's Arch Ophthalmol 1926;117:58-113.

66.Creel D, O'Donnell FE Jr, Witkop CJ. Visual system anomalies in human ocular albinos. Science 1978;201:931-3.

67.Cushman WB, Tangney JF, Steinman RM, Ferguson JL. Characteristics of smooth eye movements with stabilized targets. Vision Res 1984; 24:1003-9.

68.Dallos PJ, Jones RW. Learning behavior of the eye fixation control system. IEEE Trans Automat Control 1963;AC-8:218-27.

69.Das VE, Leigh RJ, Thomas CW, AverbuchHeller L, Zivotofsky AZ, DiScenna AO, Dell'Osso LF. Modulation of high-frequency vestibulo-ocular reflex during visual tracking in humans. J Neurophysiol 1995;74: 624-32.

70.de Jong BM, Shipp S, Skidmore B, Frackowiak RS, Zeki S. The cerebral activity related to the visual perception of forward motion in depth. Brain 1994;! 17:1039-54.

71.Dell'Osso LF. Evaluation of smooth pursuit in the presence of congenital nystagmus. Neuroophthalmology 1986;6:383-406.

72.Dell'Osso LF, Abel LA, Daroff RB. Latent/ manifest latent nystagmus reversal using an ocular prosthesis. Implications for vision and ocular dominance. Invest Ophthalmol Vis Sci

1987;28:1873-6.

73.Dell'Osso LF, Schmidt D, Daroff RB. Latent, manifest latent, and congenital nystagmus. Arch Ophthalmol 1979;97:1877-85.

74.Dell'Osso LF, Van der Steen J, Steinman RM, Collewijn H. Foveation dynamics in congenital nystagmus. II: Smooth pursuit. Doc Ophthlamol 1992;79:25-49.

75.Dell'Osso LF, Williams RW. Ocular motor abnormalities in achiasmatic mutant Belgian sheepdogs: unyoked eye movements in a mammal. Vision Res 1994;35:109-16.

76.Deno DC, Crandall WF, Sherman K, Keller EL. Characterization of prediction in the primate visual smooth pursuit system. BioSystems 1995;34:107-28.

77.Deno DC, Keller EL, Crandall WF.Dynamical neural network organization of the visual pursuit system. IEEE Trans Biomed Eng 1989;36: 85-92.

78.Desimone R, Ungerleider L. Multiple visual areas in the caudal superior temporal sulcus of the macaque. J Comp Neurol 1986;248: 164-89.

79.Dichgans J, von Reutern GM, Rommelt U. Impaired suppression of vestibular nystagmus by fixation in cerebellar and noncerebellar patients. Arch Psychiat Nervenkr 1978;226: 183-99.

80.Dodge R. Five types of eye movement in the horizontal meridian plane of the field of regard. AmJ Physiol 1919;8:307-29.

81.Domann R, Bock O, Eckmiller R. Interaction of visual and non-visual signals in the initiation of smooth pursuit eye movements in primates. Behav Brain Res 1989;32:95-9.

82.Dubois MFW, Collewijn H. Optokinetic reactions in man elicited by localized retinal motion stimuli. Vision Res 1979; 19:1105-15.

83.Duffy CJ, Wurtz RH. Response of monkey MST neurons to optic flow stimuli with shifted

centers of motion. J Neurosci 1995;15:5192208.

84.Duffy CJ, Wurtz RH. Medial superior temporal area neurons respond to speed patterns in opticflow.J Neurosci 1997;17:2839-51.

85.Duffy CJ, Wurtz RH. Planar directional contributions to optic flow responses in MST neurons. J Neurophysiol 1997;77:782-96.

86.Duncker K. Uber induzierte Bewegung (induced motion). In: Ellis WD, editor. A Source Book on Gestalt Psychology. New York: Humanities Press; 1998; p. 180-259.

87.Diirsteler MR, Wurtz RH. Pursuit and optokinetic deficits following chemical lesions of cortical areas MT and MST. J Neurophysiol 1988; 60:940-65.

88.Diirsteler MR, Wurtz RH, Newsome WT Directional pursuit deficits following lesions of the foveal representation within the superior

temporal sulcus of the macaque monkey. J Neurophysiol 1987;57:1262-87.

88a. Eifuku S, Wurtz RH. Responses to motion in extrastriate area MST1: center-surround interactions. J Neurophysiol 1998;80:282-96.

89.Eizenman M, Hallett PE, Frecker RC. Power spectra for ocular drift and tremor. Vision Res 1985;25:1635-40.