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

differ from those of the horizontal system, primarily in their slow speed and restricted range of amplitudes.84'85'113'218 Vertical fusional movements to a step of disparity, for example, take seconds for completion and usually cannot overcome disparities of more than a degree or two. They are more robust for near viewing.75 In some patients with a vertical muscle imbalance, however, the vertical fusional range may be strikingly increased,158 and in normal adults, the vertical fusional range can be increased with training.68

Cyclodisparities elicit torsional fusional movements called cyclovergence, but just as

than the torsional position of each eye alone (i.e., cycloversion).242 This finding suggests that the relative alignment of the two eyes around the visual axis plays a role in certain types of depth perception, such as determining the slant of objects toward or away from the subject.86 So, for example, disturbances of the perception of slant accompany the cyclodeviation of superior oblique palsy and can be used as a diagnostic test.130 For a vertical bar, the top will appear closer to the subject. For a horizontal bar, the two images will be slanted with respect to each other, with the apparent intersection of the lines pointing toward the side of the affected, excylodeviated eye. Changes in the relative torsional alignment of the eyes also occur in normal subjects with near viewing; there is relative intorsion on upgaze and extorsion on downgaze.147'153'240 This finding can also be related to the orientation of Listing's plane.225a'225b With convergence, there is a relative temporal rotation of Listing's plane in each eye. In patients with intermittent exotropia, the added convergence needed to overcome the inherent exophoria is also associated with an increased temporal rotation of Listing's plane.238 The functional consequences of such

changes in relative eye orientation with vergence are not yet settled.22513'234

Most infants can make appropriate vergence movements within the first 3 months of life, although appropriate accommodative responses to blur occur later.74'231 Relatively little is known about the effect of

aging on vergence capabilities. Because of presbyopia, elderly subjects show diminution in convergence associated with a given accommodative stimulus. This leads to some compensatory adaptation in the linkage between convergence and accommodation.191'192 Many elderly individuals have poor convergence with simple bedside testing.

BLUR-INDUCED VERGENCE

Accommodative vergence responses may be studied independently of the effects of retinal disparity by covering one eye. In the classic experiment by Miiller,159 when the seeing eye changed fixation from a distant to a near target along the visual axis of that eye, the eye under cover converged. The seeing eye seemed not to move, although sensitive recording methods show that it is not alwaysperfectlystill; in some trials it makes small vergence

movements with corrective saccades (Fig. 8-1 ).3i,44,io8 when stimulus motion is

unanticipated, the reaction time for blurdriven vergence movements is about 200 msec.

Fusional vergence movements reduce the stimulus that produces them, retinal disparity, to a minimum; that is, they use negative visual feedback. However, the vergence movements associated with accommodation have no direct effect upon the retinal blur stimulus that evokes them. They are open-loop responses. Thus, in the Miiller experiment, once accommodation is adequate and retinal blur is quelled, accommodative vergence tone is held steady irrespective of whether or not the eye under cover points at the target. (Of course, under normal binocular viewing conditions, fusional vergence movements will precisely direct the lines of sight.)

THE NEAR TRIAD

Vergence is one part of the near triad.214 A second component is a change in the shape of the lens of the eye, accommodation. When the lens is focused to view objects at optical infinity, the lens is stretched by its

attachments. To focus on close objects, the ciliary muscle contracts to reduce the tension on the suspensory ligaments of the lens. The lens then becomes more spherical and is accommodated for near vision. Accommodation is measured in sphere diopters (D), which are related to the reciprocal of the viewing distance (Table 8-1). The third component of the near triad is pupillary constriction. Although it probably plays only a minor role in focusing near

objects, the degree of pupillary constriction is a useful clinical sign.

INTERACTIONS BETWEEN ACCOMMODATION

AND VERGENCE

The synkinetic relationship between accommodation (A) of the lens and accom-

modation-linked convergence (AC) can be expressed as a ratio (AC/A, expressed in prism diopters/sphere diopters). This ratio would be close to 6.0 (the average interpupillary distance in centimeters) if the amount of vergence linked to accommodation were equal to that required for binocular fixation at all viewing distances. In fact, the AC/A ratio is usually smaller (about 3.5). Hence, during binocular viewing of near objects, disparity-induced vergence must also be enlisted to align the visual axes correctly. Not only is convergence (C) causally linked to accommodation, but likewise, accommodation is linked to vergence (convergence-linked accommodation [CA]). The CA/C ratio— the amount of accommodation in sphere diopters induced per prism diopter of convergence—is typically about 0.1 to 0.15, being higher in younger subjects.50'112'152 This ratio should be about 0.16 if the amount of convergence-linked accommodation were just equal to that required for clear vision at all viewing distances.

Under normal conditions of binocular viewing, accommodative and fusional drives work together to enable clear, single vision of close or distant objects. Maddox131 believed that the accommodative stimulus was the main contributor to vergence and that disparity-induced fusional vergence was a supplement. Current evidence, however, suggests that fusional vergence is the more important contributor to ocular alignment.98 In other words, accommodation of the lens is more strongly linked to disparity (vergence) than vergence to blur (accommodation).31'50'149'152 According to this view, the role of blur is to serve as the stimulus for the fine-tuning of accommodation. Some of the other stimuli that contribute to a sense of nearness, including size, texture, and looming, may also be important for stimulating vergence under conditions of natural viewing. The interactions between vergence and accommodation have been addressed in models that explicitly incorporate cross-coupling between accommodation and vergence (see Adaptive Mechanisms to Maintain Ocular Alignment and Phoria Adaptation, below).91'195'202

DYNAMIC PROPERTIES OF

VERGENCE EYE MOVEMENTS

Pure Vergence

The waveform of an isolated vergence movement, stimulated by a sudden (step) change in retinal disparity or in blur, approximates a negative exponential with a time constant in the range of the orbital plant (about 150 to 200 msec) (see Fig. 5-1, Chap. 5). This might suggest that the command signal for pure vergence movements is approximately a step (or tonic) change in innervation to the extraocular muscles.188 It has been shown, however, that during vergence movements, ocular motoneurons also receive a phasic command that is proportional to the velocity of the movement (see Motor Commands for Vergence, below).60 Analysis of vergence waveforms, using, for example, the phase plane plot (eye position versus eye velocity), shows that there is an initial fast, open-loop or preprogramed response, usually complete within several hundred milliseconds, which is followed by a slower response that completes the vergence movement and brings the image of the target to both foveae.216 Occasionally, two rapid vergence responses will occur to a single disparity, the second response being similar to a corrective saccade strategy in the conjugate system.3 Vergence movements to ramp stimuli may also show what appear to be two types of vergence responses: step-like to large disparities and ramp-like to small disparities.215 Whether these reflect different control modes comparable to saccadic and pursuit vergence or processing of disparity of different sizes by different channels is debatable.178 Particularly confusing in the literature is the use of the terms fast vergence and slow vergence to describe both the early and late components of a response to a step of disparity and the fast and slow responses during tracking of a ramp of disparity. There is still no proof that these distinct characteristics of vergence derive from identical mechanisms.

The peak velocity of vergence can be related to its amplitude in the same way as

the peak velocity of saccades is related to its amplitude, using a main sequence plot. The dynamic properties of vergence responses have been reported to be more variable than those of saccades. However, once the presence or absence of associated saccades (including vertical saccades) and blinks are taken into account and the analysis is restricted to the early preprogramed component of the vergence response, much of the variability disappears.90 The two eyes often show dynamic asymmetries during a pure vergence movement.823 In most studies, convergence has been reported to be faster than divergence.92'253 Finally, the relationship between vergence amplitude and disparity amplitude is under adaptive control.45 This can be shown by artificially altering the position of the target, using visual feedback, to make each initial vergence movement of an incorrect amplitude. After a training period, the vergence response is adjusted to correct for the artificially induced dysmetria.213

When targets are slightly displaced from the midline, and the task is to look from far to near, some subjects can make asymmetric, smooth adducting movements, with the dynamic properties of slow vergence. This brings both eyes to the target without requiring a saccade to change the conjugate position of the eyes.44 This type of response is akin to the asymmetric movements of the eyes recorded during pursuit of targets moving toward and away from the subject on an axis aligned with one eye.114 Both of these responses question the validity of an important corollary of Hering's Law of equal innervation. Hering's Law itself states that the yoking of the eyes arises because both eyes get their innervation from a single conjugate command. The corollary is that seemingly independent movements of the eyes are produced by summation of a pure vergence (disjunctive) command and a pure versional (conjugate) command. In contrast to convergence, when a pure divergence is called for it is usually accompanied by a saccade that initially brings one

eye (usually the dominant one) closer to the target.24'42'44'238a>253 Such a strategy

would allow rapid identification (albeit

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primarily based on information from one eye) of an object suddenly appearing in the visual field beyond a near point of regard.

Saccade-Vcrgcnce Interactions

Vergence eye movements have been conventionally taught as being slow, taking as long as a second for completion.184'188 This is the case when vergence movements are tested in a laboratory setting, such as by presenting isolated disparity stimuli under dichoptic viewing conditions (each eye sees a different image). Vergence movements seem much faster when tested under more natural conditions, using real targets or having the subject move toward a stationary target.49

Perhaps the most important circumstance in which the velocity of the vergence change is increased is when the target of interest changes its position across the visual field as well as in depth. A combined version and horizontal vergence movement is required, and the vergence component is several times faster when

conjoined with a horizontal or even a vertical saccade (Fig. 8-2).39'238a In other

words, much more of a change in alignment is accomplished when saccades and vergence are combined than when vergence is made alone.48 The degree to which the change in alignment appears to

be incorporated into the saccade depends on the distance of the target239 and the size

of the change in alignment; smaller disparities can be overcome entirely during the saccade.15 Also important is whether the change in gaze is self-generated to fixed targets, in which case the conjugate and disconjugate components of the change in alignment usually begin synchronously, or if the change in gaze is in response to an externally presented target, in which case some of the change in alignment usually precedes the onset of the saccade as a slow vergence movement. Curiously, accommodation, like vergence, is also speeded up when it occurs in association with saccades.208

The mechanism for facilitation of vergence by saccades and blinks is not settled.

One hypothesis suggests that the same pontine neurons (pause cells) that gate activity of saccadic burst neurons also gate vergence activity.253 During the time that pause-cell inhibition is lifted, not only can saccades occur but vergence would also be facilitated (Fig. 8-3).There is electrophysiological support for this hypothesis; stim-

Figure 8-3. Model of saccade-vergence interaction. Omnidirectional pause neurons (OPN) partially inhibit the activity of vergence velocity neurons (VVN) so that during a saccade, when OPN inhibition is completely removed, the gain of VVN increases from 1.0 to k + 1.0.This facilitates the vergence-driven change of alignment that occurs during the saccade. SEN, saccade burst neurons; CME, conjugate motor error; VME, vergence motor error; VVC, vergence velocity command; CVC, conjugate velocity co mand; RE, right eye;LE, left eye. (From Zee DS, FitzGibbon EJ, Optican LM. Saccade-vergence interactions in humans. Journal of Neurophysiology 1992;68:1624-41, with permision.)

ulation of pause neurons slows ongoing vergence.138 Pause cells also cease discharging during blinks, and this too would account for facilitation of vergence by blinks.173'177 Other hypotheses to explain

saccade-vergence interaction, which are not necessarily mutually exclusive, include

programing of saccades of different sizes in each eye15'25-42-239 and nonlinear interac-

tions between version and vergence at the level of the ocular motoneurons or in the eye muscles themselves.109 Indeed, neurophysiological evidence suggests that at the level of premotor commands (for example, in saccade burst neurons) there is a higher degree of separation of activity into right eye-related and left eye-related neurons than previously thought.259'260

Other findings that must be considered in interpreting saccade-vergence interaction include the transient change invergence (usually divergence in adults) that occurs even when saccades are made

gence).23'104'133'238a'253 In contrast, children younger than 10 years of age usually show a transient convergence during saccades.52 It has been suggested that these changes

in alignment during and immediately after saccades in normal subjects are a byproduct of inherent asymmetries in the

mechanical characteristics of the ocular plant (muscles and orbital tissues) and of the adaptive processes that attempt to compensate for them.52 Finally, saccades not only influence vergence but vergence influences saccades. Saccades associated with vergence are slower than saccades

made without vergence, except in the eye that is abducting and diverging.24'25'238a

Whether the images seen by the two eyes are processed in the same or different cerebral hemispheres also influences how saccades and vergence are combined.51 When the images of the targets seen by the left eye and the right eye are in the same hemifield and processed by the same hemisphere, the resulting averaging saccade is made to a position nearly between the two targets (global effect). When the images are in opposite hemifields and processed by opposite hemispheres, however, the saccade is directed to just one of

the targets. Saccade latencies are also influenced by hemispheric localization. If in

the same hemisphere, saccade latency increases by about 2.5 msec per degree of disparity, with a baseline of 215 msec. If in opposite hemispheres, there is a different relationship. Latency is about 260 msec, with no dependence on disparity. Because of the relatively small distance between

the pupils, most naturally occurring saccades will be to targets seen by the same hemisphere. Hence it has been argued

that the global averaging effect on saccades, when they are combined with vergence, would allow for a symmetric

vergence movement to complete any necessary change in alignment when the cyclopean (average between the two eyes) saccade was completed.51

Because the eyes are horizontally separated, they must also rotate by different amounts when making vertical saccades between near targets that are separated vertically and off to one side (i.e., closer to one eye than the other). Even saccades made in darkness to the remembered locations of vertically displaced targets are disconjugate to nearly the same degree as if the visual targets were actually pres-

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ent.251 When vertical disparities are induced artificially with a prism or dichoptic display, the vertical saccades become more disconjugate when the stimuli appear to be close.239'251 When a subject is asked to wear a verticallyoriented prism in front of just one part of the visual field of one eye (for example, the lower field) for a day, there is an adaptive change in the vertical yoking of the eyes such that the degree of disconjugacy is appropriate to the visual demands created by the prism.251 These findings suggest that the brain develops a three-dimensional map (horizontal, vertical, depth) for vertical saccade yoking. This map is used to preprogram automatically the relative excursions of the eyes during vertical saccades according to the point of regard before and after the change in gaze. Other factors related to the relative pulling directions of the vertical muscles in the orbit may also contribute to this automatic disconjugacy,36'43 but central mechanisms, which are subject to adaptive modification, are clearly important.251 A facilitation of vertical vergence by horizontal saccades does not consistently occur in normal subjects,251 but it has been shown in a patient with the syn-

drome of dissociated vertical deviation (DVD).222

NEURAL SUBSTRATE OF

VERGENCE MOVEMENTS

Anatomic Substrate for Vergence

Studies of the oculomotor nucleus have shown that medial rectus motoneurons do not lie in one discrete location; the cells are distinctly segregated into different groups. Three distinct aggregates of medial rectus motoneurons have been identified: subgroup A, located ventral and rostral; subgroup B, located dorsal and caudal; and subgroup C, located dorsomedial and rostral (see Fig. 9-9B, Chap. 9). Subgroup C consists of the smallest cell bodies and can be labeled independently of the other subgroups by selective injections of radioactive tracer into the outer (orbital) layer of the medial rectus muscle.

Because the outer layer of the ocular muscles contains smaller muscle fibers, which are more likely to be involved in generating slower eye movements, it is tempting to speculate that the neurons in subgroup C have a selective function, perhaps in vergence.16 Nevertheless,there is as yet no physiologic evidence to support this hypothesis.

Motor Commands for Vergence

Neurophysiologic studies in monkeys have shown that almost all oculomotoneurons subserving the medial rectus and most neurons in the abducens nucleus discharge for both conjugate (version) and

disjunctive (vergence) eye movements(Fig. 8-4).106,107,140 Ocular motoneurons show a

velocity-position (phasic-tonic) change in discharge rate during vergence, as is the case for conjugate movements.60 Even though most of the motoneurons subserving the lateral and medial recti carry both version and vergence signals, the sensitivity of individual neurons to changes in eye position varies according to whether the

eye position is reached by a version or a vergence movement. In other words, there is evidence that different neurons play relatively smaller or larger roles in conjugate versus vergence eye movements.

Premotor Commands for Vergence

Neurons involved specifically in the control of vergence139 and presumably projecting to ocular motoneurons257 have been found in the mesencephalic reticular formation, 1 to 2 mm dorsal and dorsolateral to the oculomotor nucleus.99'137-141 Three main types of neurons can be found: those that discharge in relation to vergence angle (vergence tonic cells), to vergence velocity (vergence burst cells), and to both vergence angle and velocity (vergence burst-tonic cells). Many of these neurons also discharge with accommodation, although when vergence and accommodation are experimentally dissociated and pitted against each other, some

remain predominantly related to vergence.99^

Most vergence tonic cells increase their discharge directly in relation to the angle of convergence; they change their firing rate 10 to 30 msec before any detectable eye movements. A second, smaller group of cells increases the rate of discharge with divergence. The activity of both of these types of cells is unaffected by the direction of conjugate gaze.

Before and during vergence, vergence burst cells exhibit a burst of activity that is linearly related to the velocity of the vergence movement (Fig. 8-5).141 For most of these cells, the number of spikes within each burst (i.e., the integral of the rate of discharge) is correlated with the amplitude of the movement. These vergence burst neurons are analogous to the saccadic burst neurons that discharge in rela-

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tion to saccade velocity. There are both convergence and divergence burst neurons, with convergence neurons being more abundant.

Vergence burst-tonic cells combine vergence position and vergence velocity information in their output: the burst is related to vergence velocity and the tonic firing rate to vergence angle. Most of these cells are located next to the dorsolateral portion of the oculomotor nucleus.

The role of abducens internuclear neurons (see Display 6-1 and Fig. 6-1, Chap. 6) and oculomotor internuclear neurons in generating the vergence command is not well understood. Each of these interneurons has projections to the other nucleus, presumably via the medial longitudinal fasciculus (MLF). Clinically, lesions

in the MLF (internuclear ophthalmoplegia [INO]; see Display 10-22, Chap. 10) do not impair the ability to make vergence movements. The MLF, however, carries activity related to vergence.58 Furthermore, monkeys with an acute lidocaine-in- duced internuclear ophthalmoplegia show an increased AC/A ratio, implying that the MLF carries signals that inhibit vergence.19'59 The source of additional vergence inputs to the abducens nucleus is not certain, but there are cells close by in the pons that discharge with vergence in a way similar to that of the midbrain premotor vergence neurons.64 Commands to the abducens nuclei for changes in vergence may also be mediated in association with conjugate signals. Theoretical considerations, with some experimental support, suggest that vergence signals must be carried on neurons that also provide premotor conjugate commands, such as neurons

in the vestibular nuclei or nucleus prepositus hypoglossi.30'144

Cerebellar Control of Vergence

Historically, two observations have implicated the cerebellum in the control of ver-

gence. Holmes81 described a weakness of convergence in patients with acute cerebellar lesions. Westheimer and Blair247 showed that acute ablation of the cerebellum in the monkey leads to a transient paralysis of vergence. Paralysis of convergence, to both accommodative and disparity stimuli, has been reported in a single patient with a lesion involving the right cerebellum.169 Disorders of ocular alignment, including esodeviations (eyes turned inward) at distance viewing, and vertical skew deviations that sometimes alternate on right and left horizontal gaze, have also

been reported in patients with cerebellar lesions.156'243'252 By and large, however,

careful studies of vergence capabilities in humans with either focal or diffuse cerebellar lesions are lacking.

Studies in nonhuman primates also suggest that particular portions of the cerebellum have a role in vergence. The cerebellar flocculus has neurons that discharge in relation to the vergence angle.151

Whether these cells relate to vestibular function (e.g., adjusting the gain of the VOR as a function of target distance)151'225 or to some other aspect of vergence (e.g., vergence gaze holding, ocular alignment, or phoria adaptation) is not known. Nevertheless, monkeys with floccular lesions still are able to undergo adaptive changes in ocular alignment and the AC/A ratio.97

The posterior interposed nucleus, corresponding to the globose and emboliform nuclei in humans, and the posterior portion of the fastigial nucleus (FOR or fastigial oculomotor region) have cells that discharge in relation to vergence (and accommodation).255'256 Those in the posterior interposed nucleus appear to be related to a far response (divergence), and those in the FOR to a near response (convergence). Inactivation of the FOR interferes with convergence.63 The FOR and posterior interposed nucleus have reciprocal anatomic connections with the midbrain areas containing neurons that convey premotor vergence commands to the oculomotor nuclei.136 The projection from the deep nuclei is predominantly contralateral, whereas the projection to them is predominantly ipsilateral. Some neu-

rons within the medial portion of the nucleus reticularis tegmenti pontis (NRTP) discharge in relation to either convergence (near response) or divergence (far response); stimulation in this region can produce convergence or divergence.57 Inactivation here leads to impaired holding of angles of convergence.61 These ver- gence-related cells lie close to other neurons in the NRTP that discharge with saccades (see NRTP in Chap. 3). Electrical stimulation sometimes produces saccades combined with vergence. Hence, some aspects of saccade-vergence interactions may be mediated by this area. The NRTP projects to the oculomotor vermis of the cerebellum (lobules VI and VII), the interposed and fastigial nuclei, and the cerebellar flocculus, and hence could be a source of vergence (and disparity) information to the cerebellum. The NRTP receives projections from many structures, including the frontal lobes; this may be one source of premotor vergence com-

mands to the NRTP and cerebellum (see next section).62 The cerebellar cortex overlying the FOR and posterior interposed nucleus may also play a role in vergence. As expected, lesions in the oculomotor vermis produce the reciprocal of those in the FOR. Monkeys develop an esodeviation after vermal ablations.229 Positron emission tomography (PET)shows an increase in activity in the cerebellar vermis in humans performing a binocularity discrimination task.72 The effects of cerebellar lesions on vergence responses in humans have not been quantified (see also Phoria Adaptation, below).

Cerebral Control of Vergence

Information about the role of cortical structures in vergence is relatively sparse. In alert cats, stimulation in area LS(lateral suprasylvian), an extrastriate area roughly comparable to areas MT (middle temporal) and MST (medial superior temporal) in the monkey (see Display 6-14 and Fig. 6-8, Chap. 6), produces various components of the near response.7'232 Single-unit recordings in this region have revealed some neurons that discharge with vergence; lesions here interfere with vergence eye movements.228

Some neurons in area LIP (see Display 6-17) on the lateral bank of the intraparietal sulcus discharge not only in relation to saccades but also when the saccade is combined with a vergence movement to take the eyes to a particular depth plane.65 In the frontal lobes (area 8), there is a region in the prearcuate cortex, just in front of the saccade-related area in the anterior bank of the arcuate sulcus, in which neurons discharge with the near or far response and also with the tonic angle of vergence.62 These neurons may be one source of vergence premotor commands to the brain stem and cerebellum.

Finally, one wonders if the organization of the cerebral control of vergence is comparable to that for saccades (see HigherLevel Control of the Saccadic Pulse Generator, Chap. 3), with more reflexive, stimulus-bound movements being generated by the posterior hemispheres and

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more volitional, self-initiated movements by the frontal lobes.62

Visual Physiology of Disparity-

Induced Vergence

What is known about the sensory stimuli that drive vergence eye movements? In a number of areas of the visual cortex of the monkey, cells have been identified that are sensitive to binocular stimulation.179 Some of these neurons show a binocular response over a narrow depth range about the fixation point (called tuned-zero neurons or near-zero neurons). These cells may be involved in fine stereopsis. They may also play a role in the generation of the ultra- short-latency (60-85 msec) vergence responses to small disparities in a large field of view.14'150 Such movements could help stabilize the visual scene during selfmotion. Other cells (called tuned-far and near cells) respond to binocular stimuli that are nearer or farther than the fixation point. These cells may participate in coarse stereopsis. They may provide sensory input for fusional vergence movements to large disparities associated with voluntary changes in the depth plane of focus. The activity of some disparitysensitive cells in the primary visual cortex (VI) changes as a function of target distance (and vergence angle), even though the disparity stimulus on the retina is the same.233 These cells could be calculating the distance of an object from the observer.182 Extraretinal signals, either proprioceptive or corollary discharge based on monitoring of internal commands, help to shape the activity of these neurons, allowing them to signal the actual depth of the target. In spite of extensive psychophysical and neurophysiological investigations and theorizing, however, there is still no consensus on the physiological un-

derpinnings of stereopsis and depth per-

ception.171'179'183'246

Other areas in monkey cerebral cortex also have neurons that discharge in relation to disparity. They include the MT (middle temporal) and MST (medial superior temporal) areas in the superior tern-