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The pontine and mesencephalic burst circuits provide the motor signals necessary to drive the muscles for saccades. However, among higher mammals eye movements are ultimately driven by cognitive behavior. The decision when and where to make a saccade that is behaviorally important is usually made in the cerebral cortex. A network of cortical and subcortical areas controls the saccadic system through the superior colliculus (Figure 39–10).
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The Superior Colliculus Integrates Visual and Motor Information into Oculomotor Signals to the Brain Stem
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The superior colliculus in the midbrain is a major visuomotor integration region, the mammalian homolog of the optic tectum in nonmammalian vertebrates. It can be divided into two functional regions: the superficial layers and the intermediate and deep layers.
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The three superficial layers receive both direct input from the retina and a projection from the striate cortex representing the entire contralateral visual hemifield. Neurons in the superficial layers respond to visual stimuli. In monkeys the responses of half of these vision-related neurons are quantitatively enhanced when an animal prepares to make a saccade to a stimulus in the cell's receptive field. This enhancement is specific for saccades. If the monkey attends to the stimulus without making a saccade to it—for example, by making a hand movement in response to a brightness change—the neuron's response is not augmented.
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Neuronal activity in the two intermediate and deep layers is primarily related to oculomotor actions. The movement-related neurons in these layers receive visual information from the prestriate, middle temporal, and parietal cortices and motor information from the frontal eye field. The intermediate and deep layers also contain somatotopic, tonotopic, and retinotopic maps of sensory inputs, all in register with one another. For example, the image of a bird will excite a vision-related neuron, whereas the bird's chirp will excite an adjacent audition-related neuron, and both will excite a bimodal neuron. Polymodal spatial maps enable us to shift our eyes toward auditory or somatosensory stimuli as well as visual ones.
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Much of the early research describing the sensory responsiveness of neurons in the intermediate layer was done in anesthetized animals. To understand how the brain generates movement, however, the activity of neurons needs to be studied in alert animals while they behave normally. Edward Evarts pioneered this approach in studies of the skeletomotor system, after which it was extended to the ocular motor system.
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One of the earliest cellular studies in active animals revealed that individual movement-related neurons in the superior colliculus selectively discharge before saccades of specific amplitudes and directions, just as individual vision-related neurons in the superior colliculus respond to stimuli at specific distances and directions from the fovea (Figure 39–11A). The movement-related neurons form a map of potential eye movements that is in register with the visuotopic and tonotopic arrays of sensory inputs, so that the neurons that control eye movements to a particular target are found in the same region as the cells excited by the sounds and image of that target. Each movement-related neuron in the superior colliculus has a movement field, a region of the visual field that is the target for saccades controlled by that neuron. Electrical stimulation of the intermediate layers of the superior colliculus evokes saccades into the movement fields of the stimulated neurons.
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Movement fields are large, so each superior colliculus cell fires before a wide range of saccades, although each cell fires most intensely before saccades of a specific direction and amplitude. A large population of cells is thus active before each saccade, and eye movement is encoded by the entire ensemble of these broadly tuned cells. Because each cell makes only a small contribution to the direction and amplitude of the movement, any variability or noise in the discharge of a given cell is minimized. Similar population coding is found in the olfactory system (see Chapter 32) and skeletal motor system (see Chapter 37).
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Activity in the superficial and intermediate layers of the superior colliculus can occur independently: Sensory activity in the superficial layers does not always lead to motor output, and motor output can occur without sensory activity in the superficial layers. In fact, the neurons in the superficial layers do not provide a large projection directly to the intermediate layers. Instead, their axons terminate on neurons in the pulvinar and lateral posterior nuclei of the thalamus, which relay the signals from the superficial layers of the superior colliculus to cortical regions that project back to the intermediate layers.
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Lesions of a small part of the colliculus affect the latency, accuracy, and velocity of saccades. Destruction of the entire colliculus renders a monkey unable to make any contralateral saccades, although with time this ability is recovered.
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The Rostral Superior Colliculus Facilitates Visual Fixation
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The most rostral portion of the superior colliculus contains a representation of the fovea. Neurons in the intermediate layers in this region discharge strongly during active visual fixation and before small saccades to the contralateral visual field. Because the neurons are active during visual fixation, this area of the superior colliculus is often called the fixation zone.
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Neurons here inhibit the movement-related neurons in the more caudal parts of the colliculus and also project directly to the nucleus of the dorsal raphe, where they inhibit saccade generation by exciting the omnipause neurons. With lesions in the fixation zone an animal is more likely to make saccades to distracting stimuli.
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The Basal Ganglia Inhibit the Superior Colliculus
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The substantia nigra pars reticulata sends a powerful GABAergic inhibitory projection to the superior colliculus. Neurons in the substantia nigra fire spontaneously with high frequency; this discharge is suppressed at the time of voluntary eye movements to the contralateral visual field (see Figure 39–11B). Suppression is mediated by inhibitory input from neurons in the caudate nucleus, which fire before saccades to the contralateral visual field.
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Two Regions of Cerebral Cortex Control the Superior Colliculus
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The superior colliculus is controlled by two regions of the cerebral cortex that have overlapping but distinct functions: the lateral intraparietal area of the posterior parietal cortex (part of Brodmann's area 7) and the frontal eye field (part of Brodmann's area 8). Each of these areas contributes to the generation of saccades and the control of visual attention.
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Perception is better at an attended place in the visual field than at an unattended place, as measured either by a subject's reaction time to an object suddenly appearing in the visual field or by the subject's ability to perceive a stimulus that is just noticeable. Saccadic eye movements and visual attention are closely intertwined (see Figure 39–1).
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The lateral intraparietal area in the monkey is important in the generation of both visual attention and saccades. The role of this area in the processing of eye movements is best illustrated by a memory-guided saccade. To demonstrate this saccade, a monkey first fixates a spot of light. An object (the stimulus) appears in the receptive field of a neuron and then disappears; then the spot of light is extinguished. After a delay the monkey must make a saccade to the location of the vanished stimulus. Neurons in the lateral intraparietal area respond at the onset of the stimulus and continue firing during the delay until the saccade begins (Figure 39–12A), but their activity can be also dissociated from saccade planning. If the monkey is planning a saccade to a target outside the receptive field of a neuron, and a distractor appears in the field during the delay period, the neuron responds as vigorously to the distractor as it does to the target of a saccade (Figure 39–12B).
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Lesioning of a monkey's posterior parietal cortex, which includes the lateral intraparietal area, increases the latency of saccades and reduces their accuracy. Such a lesion also produces selective neglect: A monkey with a unilateral parietal lesion preferentially attends to stimuli in the contralateral visual hemifield. In humans as well, parietal lesions—especially right parietal lesions—initially cause dramatic attentional deficits. Patients act as if the objects in the neglected field do not exist, and they have difficulty making eye movements into that field (see Chapter 17).
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Patients with Balint syndrome, which is usually the result of bilateral lesions of the posterior parietal and prestriate cortex, tend to see and describe only one object at a time in their visual environment. These patients make few saccades, as if they are unable to shift the focus of their attention from the fovea, and can therefore describe only a foveal target. Even after these patients have recovered from most of their deficits, their saccades are delayed and inaccurate.
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Compared to the neurons in the parietal cortex, neurons in the frontal eye field are more closely associated with saccades. Three different types of neurons in the frontal eye field discharge before saccades.
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Visual neurons respond to visual stimuli and half of these neurons respond more vigorously to stimuli that are the targets of saccades (Figure 39–13A). Activity in these cells is not enhanced when an animal responds to the stimulus without making a saccade to it. Likewise, these cells are not activated before saccades that are made without visual targets; monkeys can be trained to make saccades of a specific direction and amplitude in total darkness.
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Movement-related neurons fire before and during all saccades to their movement fields, whether or not they are made to a visual target. These cells do not respond to stimuli in their movement fields that are not targets of saccades. Unlike the movement-related cells in the superior colliculus, which fire before all saccades, movement-related neurons of the frontal eye field fire only before saccades that are relevant to the monkey's behavior (Figure 39–13B). These neurons, especially those whose receptive fields lie in the visual periphery, project more strongly to the superior colliculus than do the visual neurons.
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Visuomovement neurons have both visual and movement-related activity and discharge most strongly before visually guided saccades. Electrical stimulation of the frontal eye field evokes saccades to the movement fields of the stimulated cells. Bilateral stimulation of the frontal eye field evokes vertical saccades.
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The frontal eye field controls the superior colliculus through two pathways (see Figure 39–10). First, the movement-related neurons project directly to the intermediate layers of the superior colliculus, exciting movement-related neurons there. Second, movement-related neurons form excitatory synapses on neurons in the caudate nucleus that inhibit the substantia nigra pars reticulata. Thus, activity of movement-related cells in the frontal eye field simultaneously excites the superior colliculus and releases it from the inhibitory influence of the substantia nigra. The frontal eye field also projects to the pontine and mesencephalic reticular formations, although not directly to the burst cells.
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Two other cortical regions with inputs to the frontal eye field are thought to be important in the cognitive aspects of saccades. The supplementary eye field at the most rostral part of the supplementary motor area contains neurons that encode saccades in terms of spatial referents other than direction. For example, a neuron in the left supplementary eye field that ordinarily fires before rightward eye movements will fire before a leftward saccade if that saccade is to the right side of the target. The dorsolateral prefrontal cortex has neurons that discharge when a monkey makes a saccade to a remembered target. The activity commences with the appearance of the stimulus and continues throughout the interval during which the monkey must remember the location of the target.
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We can now understand the effects of lesions of these regions on the generation of saccades. Lesions of the superior colliculus in monkeys produce only transient damage to the saccade system because the projection from the frontal eye field to the brain stem remains intact. Animals can likewise recover from cortical lesions if the superior colliculus is intact. However, when both the frontal eye field and the colliculus are damaged, the ability to make saccades is permanently compromised. The predominant effect of a parietal lesion is an attentional deficit. After recovery, however, the system can function normally because the frontal eye field signals are sufficient to suppress the substantia nigra and stimulate the colliculus.
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Damage to the frontal eye field alone causes more subtle deficits. Lesions of the frontal eye field in monkeys cause transient contralateral neglect and paresis of contralateral gaze that rapidly recover. The latter deficit may reflect the loss of frontal eye field control of the substantia nigra; this loss of control means that the constant inhibitory input from the substantia nigra to the colliculus does not get suppressed, and the colliculus is unable to generate any saccades. Eventually the system adapts, and the colliculus responds to the remaining parietal signal. After recovery the animals have no trouble producing saccades to targets in the visual field but have great difficulty with memory-guided saccades. Bilateral lesions of both the frontal eye fields and the superior colliculus render monkeys unable to make saccades at all.
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Humans with lesions of the frontal cortex have difficulty suppressing unwanted saccades to attended stimuli. This is easily shown by asking subjects to make an eye movement away from a stimulus. When the stimulus appears the subject must attend to it, without turning the eyes toward it, and use its location to calculate the desired saccade. Patients with frontal lesions cannot suppress the saccade to the stimulus, even though they can make normal saccades to visual targets.
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As we have seen, neurons in the lateral intraparietal area of monkeys are active when the animal attends to a visual stimulus whether or not the animal makes a saccade to the stimulus. In the absence of frontal eye field signals this undifferentiated signal is the only one to reach the superior colliculus. In humans the failure to suppress a saccade is therefore to be expected if the superior colliculus responds to a parietal signal that generates attention to the stimulus, without the frontal-nigral control that normally prevents saccades in response to parietal signals.
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The Control of Saccades Can Be Modified by Experience
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Quantitative study of the neural control of movement is possible because the discharge rate of a motor neuron has a predictable effect on a movement. For example, a certain frequency of firing in the abducens motor neuron has a predictable effect on eye position and velocity.
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This relationship can change, however, if the muscle becomes weak through disease. The brain can compensate to some degree for such changes. For example, a diabetic patient may have an abducens-nerve lesion affecting one eye and a retinal hemorrhage in the other. He is forced to use the eye with the weak lateral rectus muscle because he experiences poor vision in the eye with the normal abducens nerve. If the latter eye is patched to prevent double vision, the influence of the weak eye increases, such that the weak eye is eventually able to make accurate saccades. The influence of the patched eye also increases, causing that eye to make excessively large saccades. This is of little importance to vision, however, because the patched eye does not contribute to vision. This change in the motor response depends on the fastigial nucleus and vermis of the cerebellum.