The

Neurophysiology C.L.

and of Attention

Neuroanatomy

Colby,

PhD

Abstract a distributed process. The activity of neurons in many brain structures can be modulated by the attentional state of the animal. Attention directed toward a particular external stimulus is often reflected in an enhancement of the sensory response to that stimulus. Enhancement is spatially selective for neurons in many areas and explicitly eye-movement related in most. Attention directed toward the internal representation of a stimulus may be associated with a prolongation of neural activity. These modulations of neuronal responsiveness underscore the dynamic nature of neural processing. Competition between left- and right-brain structures in the control of attention is common. While attention is perceived as a unitary process, it is subserved by many brain structures. Given the wide distribution of attentional processes, it is not surprising that children diagnosed as having attentional deficits show considerable diversity in symptoms

Attention is

and

etiology. (J Child Neurol 1991;6(Suppl):S88-S116).

elective

attention is the process by which a source is highlighted for single action. potential Psychologists distinguish between

information

bottom-up

and

top-down processing

of external

stimuli, that is, processing determined primarily by

qualities of the stimulus itself versus processing driven by internal biases or instructional set.l2 In the following review, one main theme is the way in which the brain resolves the inherent conflict between these two types of processing. On the one hand, we need to be able to attend to stimuli selectively ; we cannot afford to orient toward and process every new stimulus. On the other hand, inhibition of unattended stimuli cannot be too severe since we need to be made aware of potentially important new events. There is a very large psychological literature dealing with the problems of selective and divided attention,3 and in this review I will consider specifically how various brain structures interact to achieve a balance between data-driven and

knowledge-driven processes. Response competition is a second, related theme. Having selected a stimulus, the brain must Received

April 23,

1989.

Accepted for publication August 30,

also select

a

response to it. This concept too has

long psychological history.4

With

regard

a

to brain

mechanisms, the clearest examples of response

com-

from studies of split-brain subjects.5 In petition neurophysiologic studies, mutual inhibitory interactions have frequently been described for structures on opposite sides of the brain (eg, between the two superior colliculi)6 that are responsible for directing attention to opposite sides of space. An imbalance of the competition between right and left brain structures appears to be fundamental in some disorders of attention,~-9 and in humans there is evidence for right hemisphere lateralization of attentional procome

cessing.1o,11 Finally, the third theme in this review is the widely distributed nature of attentional processes. While specific brain systems seem to be responsible for arousal of the organism, attention cannot be pinned down to a single set of structures. Indeed, there is hardly any region of cerebral cortex beyond the primary sensory and motor regions that cannot be shown to participate in some kind of attentional process.

1989.

Experimental Approaches to the Study

From the Laboratory of Sensorimotor Research, National Eye Institute, National Institutes of Health, Bethesda, MD. Address correspondence to Dr C. L. Colby, NEI-NIH, Building 10, Room 10C101, Bethesda, MD 20892.

of Attention The experimental analysis of visual attention has depended in large part on the relation between eye

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movements and attention.

and maintains this eye position throughout the trial. Neuroanatomy shapes the process of visual attention beginning at the retThe task is to detect the onset of a peripheral visual ina. The structure of the receptor surface itself deterstimulus. The locus of attention can be shifted to a mines that we must choose to look at one place particular location by having a cue appear briefly berather than another, to examine one stimulus rather fore the onset of the stimulus. When the cue corthan another. The concentration of receptor cells in rectly predicts the location of the subsequent the fovea requires that we select only one out of the stimulus (the valid condition), reaction times are multitude of stimuli impinging on the eye for further faster. When the cue incorrectly predicts the location of the stimulus (the invalid condition), reaction analysis and withdraw our attention from the remainder. Gaze direction and locus of attention nortimes are slowed. This task has been used to assess mally coincide. People with restricted attentional attentional processing in several patient populations as well as in normal and operated animals (see the processing, as in neglect, exhibit restricted eye and adults with attenarticle by Swanson et al in this issue). movements, 12-15 and children exhibit disturbed and and tional reading disorders Neural Basis of Attention erratic eye movements. 16-21 While the relation beMuch of what is known about neural mechanisms of tween eye position and locus of attention is noror visual in as attention is drawn from behavioral and single-neuclose tasks such search, reading mally there is not an obligatory correspondence between ron recording studies in alert monkeys. In most of the two. In many other cognitive tasks that demand these studies, operant conditioning techniques have been employed to train the animal to fixate a point attention there is only a loose linkage between eye on a screen in front of it and to respond in some position and attention,22-25 and they can be comtask measurable way to new stimulus events.38 Such condissociated design.26 pletely by appropriate in an role setrol over the animal’s behavior is essential for these important Sensory priming plays lective visual attention, and spatial cues in particular studies; since many parts of the brain are involved are efto form or color in the generation of eye movements, neuronal activ(as opposed cues) especially fective in guiding attention. 27 Spatial attention is one ity cannot be related to attentional processes unless of selective attention and most is type commonly eye movements are controlled. The primary method characterized as analogous to a zoom lens or spotfor dissociating eye movements from attention in which stimuli in a light highlights particular portion monkeys has been to use a peripheral attention task: of the visual field. Normally, this highlighted region the animal must maintain fixation while making an effort to detect the dimming of a peripheral target.39 corresponds to the central portion of the visual field. The size of the spotlight can be adjusted by instrucResults from single-unit recording during this task tional set, a top-down process; the attentional field help to reveal which parts of the brain are involved can be scaled up or down to accommodate a single in selecting a stimulus for further processing, as opcharacter or an entire word28-3o (but see Hughes posed to those involved in moving the eyes or in reand Zimba 31 for a dissenting view). There may also membering where a target has appeared. Attention be a trade-off between depth of processing at a is also required in tasks other than selecting a stimuand the functional location width of the field lus, such as localizing a target, orienting to a target, given of views. 32 and identifying a target. Studies employing such A fundamental problem in selective attention tasks will also be reviewed. has been to analyze the circumstances under which Attentional effects have been demonstrated in the spotlight moves from one location to another. many parts of the brain by use of the above tasks and their variants. These effects are measured as What causes a new target to be selected? How is the behavioral modulation, in the case of lesion and old target relinquished? What determines the speed with which attention can move to a new location drug studies, and neuronal modulation in the case of single-unit studies. Attentional control over senand how is the new target engaged? These questions have been studied by taking advantage of the fact sory and motor processes is reflected in facilitation or inhibition of neuronal responses. While attention that attention can be moved across space indepenis perceived as a unitary process, it is subserved by a dently of eye movements. 33-37 One task in which attentional shifts are dissociated from eye movements, large number of brain structures. These vary widely has been in the degree to which their functioning is under his Posner and colleagues, developed by used in animal as well as human studies. The subvoluntary control. Some structures, like the superthe of a screen ior colliculus, have traditionally been thought of as center a at fixates ject initially point ’

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reflexive centers devoted to orienting the organism toward objects of interest. 40,41 In contrast, prefrontal cortex has been characterized as the source of planned, sequential behavior specifying the order in which items will be processed under conscious contro1.42,43 The distributed nature of attentional processing within the brain poses a formidable challenge to understanding how the diverse mechanisms and structures involved produce the coordinated effort that allows us to direct attention at will.

for the These

generation of head and eye movedeeper layers receive direct cortical afferents, especially from the frontal eye fleldS,53,54 parietal cortex,55 and visual corteX,56 and they are also indirectly influenced by the cortex via the basal ganglia, most importantly by inputs from the substantia nigra pars reticulata. 57-59 Each of these three subcortical structures, the superior colliculus, the thalamus, and the basal ganglia, will be considered in the following sections.

sponsible ments. 48

Superior Colliculus Subcortical Mechanisms of Attention The superior colliculus, thalamus, and basal ganglia each contribute to the generation of saccadic eye movements and shifts of attention. The locations of these structures and their major interconnections are illustrated in Figure 1. Among these structures, the superior colliculus (SC) is closest to the final common pathway for eye movements. The retina provides direct inputs to both superficial and intermediate layers of the superior colliculus.44-4s The superficial layers of the SC in turn provide a major source of visual input to the pulvinar, a thalamic structure also implicated in the control of spatial attention.49-52 Neurons in the intermediate and deep layers of the SC project to brainstem structures re-

FIGURE 1 Location of

some subcortical structures involved in eye movements and shifts of attention in the monkey. The

caudate nucleus (C) projects to the substantia nigra pars reticulata (SN), which in turn projects to intermediate layers of the superior colliculus (SC). These layers have outputs to brain-stem eye movement centers while the superficial layers project to the thalamus (T).

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Visual, motor, and attention-related activity have all been described for cells in particular layers in the superior colliculus. Cells in the superficial layers have visual receptive fields organized in a retinotopic map. Neurons in the deeper layers fire before saccadic eye movements to a particular part of the contralateral visual field and may also respond to visual targets presented in that same location. There is thus a correspondence between the visual receptive field of a cell and its movement field.6o-62 While some of these visually responsive cells fire before spontaneous saccades, others discharge only in relation to visually triggered eye movements.63 Goldberg and Wurtz64 first showed that visual responses in even this low-level reflexive structure can be affected by the attentional state of the animal. The visual responses of single cells to a visual stimulus can be significantly altered by requiring the animal to pay attention to and use the visual information it provides. Figure 2 illustrates the basis for this conclusion. In panel A, the monkey’s task is simply to look at a fixation point at the center of the screen until it begins to dim, at which time the animal releases a lever. The peripheral visual stimulus, presented in the receptive field of the cell, is irrelevant to the animal’s behavior. The cellular response to the onset of the peripheral stimulus is a brief burst of action potentials followed by a quick return to baseline firing rate. This response is contrasted to that in a second task, illustrated in panel B. In this task, the animal must look at the peripheral stimulus and attend to its brightness, releasing the lever when the stimulus dims. In both A and B, the stimuli presented in the receptive field are identical, yet in B the response to the visual stimulus is significantly stronger, a phenomenon which Goldberg and Wurtz called &dquo;enhancement.&dquo; In the superior colliculus, cells with such enhanced responses do not fire in relation to eye movements per se. Further, enhancement occurs only for targets presented within the visual receptive field of the cell, indicating that

tention and are consistent with the failure of SC neurons to show enhancement in the absence of sac-

FIGURE 2 Visual responsiveness for a neuron in the superficial layers of a monkey’s superior colliculus is enhanced when the visual stimulus is used as the target for a saccade. Top left: in the fixation task in A, the monkey looks at the fixation point (FP) throughout the trial, as shown by the eye position traces (EOG). A visual stimulus appears in the receptive field (RF) during fixation. Top center: raster display of neuronal response shows a transient visual response to stimulus onset. Each horizontal row represents one trial, and each dot is one action potential. The vertical line indicates the time of stimulus onset. Top right: histogram of rasters shown in center panel illustrates rapid return to baseline firing rate. Bottom left: in the eye response task in B, the monkey makes a saccade to the visual stimulus. Bottom center and right: the visual response is both stronger and longer lasting than in A. Reproduced with permission from Wurtz and Mohler.39

the increased response is not simply a reflection of an increase in the animal’s level of arousal. Finally, these cells fail to show enhancement in the peripheral attention task where the monkey maintains central fixation while attending to the brightness of a peripheral stimulus to which he will not make a saccade. Rather, enhancement in the SC occurs specifically during selection of a stimulus as the target for an eye movement. This modulation may therefore represent a sensorimotor gating of the visual response rather than a purely attentional effect, like that observed in parietal cortex (see below). Superior colliculus neurons have been studied in a reaction time task in which the focus of attention is cued to a peripheral location while gaze is maintained at a central fixation point.65 While the animal’s behavioral response is similar to that described for humans in the Posner task, single cell responses in the superficial layers are apparently unaffected by the presence of cues indicating the location of the next stimulus. Specifically, reaction time is shorter for validly cued trials, but single cell response latency and amplitude are the same regardless of cue validity. These results argue against the idea that the superior colliculus is involved in covert shifts of at-

cadic eye movements.39 Recent experiments suggest, however, that the SC may play a role in facilitating shifts of attention. Each SC receives visual information from the contralateral visual field only, and there is mutual inhibition between the two colliculi.66 Unilateral inactivation of the SC could thus affect shifts of attention into the contralateral field and/or disengagement of attention in the ipsilateral field (through its inhibitory connections). Figure 3 illustrates the behavioral results obtained when a y-aminobutyric acid (GABA) agonist (muscimol) is injected into the superior colliculus, producing a local inactivation of neuronal firing. For validly cued trials (left), SC inactivation increases the reaction time to targets in the contralateral field. This difficulty in shifting attention into the contralateral field is even more pronounced for invalidly cued trials (right). In these trials, the animal shifts attention into the ipsilateral field, where the cue appeared, only to have the target appear in the contralateral field. The marked increase in reaction time in this situation suggests that

FIGURE 3 Effects of chemical inactivation of superior colliculus on reaction time to a cued visual stimulus. Cartoons indicate location of cue (large diamond) and target (small symbol) relative to the affected visual field (shading). Bar graph shows reaction time in normal (open) and drug (hatched) conditions. For valid trials (left), where the cue accurately predicts the location of the subsequent target, reaction time is longer when cue and target appear in the affected field. For invalid trials (right), where the cue does not predict the target location, reaction time is much longer when the target appears in the affected field after a cue in the unaffected field (C. Kertzman and D.L. Robinson, unpublished observations, 1988).

S93

there is

an

disengage

additional deficit in the animal’s ability to attention from the unaffected (ipsilateral)

field. While it has long been known that monkeys with SC lesions have transient deficits in making eye movements,66-70 these results suggest that they also have difficulty performing attentional shifts in the absence of eye movements. An alternate interpretation is that this slowing of the response reflects slower visual processing in the affected field. Humans as well as monkeys show deficits in changing the focus of visual attention as a consequence of midbrain damage. Posner and his colleagues have studied the effect of midbrain lesions on the ability to perform attentional shifts .71 In patients suffering from progressive supranuclear palsy, several midbrain structures, including the superior colliculus, exhibit degeneration, and patients experience difficulty in producing voluntary saccadic eye movements, especially vertical eye movements. Even though the Posner task itself does not require that any eye movements be made, these patients are significantly slower than normal in responding to the onset of a cued target, and are more impaired in responding to vertical than to horizontal targets. Because the reaction time is increased for both valid and invalid trials, the deficit is regarded as reflecting a problem with shifting attention per se, rather than with engagement or disengagement of attention from the cued location. Thalamus The superficial layers of the SC send ascending projections to the pulvinar nucleus of the thalamus, a visual structure that has several features in common with SC. Cells in the lateral and inferior divisions of the pulvinar have visual receptive fields, and their visual responses can be enhanced by requiring the monkey to make use of the stimulus as the target for a saccade .72 As is the case for cells in SC, the enhancement observed in pulvinar neurons is spatially selective, that is, it occurs only for targets presented within the receptive field of the cell. For cells in the lateral and inferior pulvinar, this enhancement occurs only in relation to a specific motor act, ie, saccadic eye movements. The dorsomedial division of the lateral pulvinar (Pdm) has different connections and somewhat different response properties. Pdm is connected with parietal cortex73 and does not receive direct SC input. In contrast to cells in the SC and in other divisions of the pulvinar, neurons in Pdm exhibit enhancement when the monkey simply attends to the visual stimulus without making an eye movement toward it, as demonstrated in the peripheral

S94

attention task (Figure 4). These results indicate that behavioral modulation of single cell responses in the pulvinar goes beyond that observed in the SC; selection of a target for further processing, whether attentional or motor, is accompanied by amplification of the visual response to that target in Pdm Pharmacological manipulations of the pulvinar, like those of the SC, affect the animal’s ability to

FIGURE 4 Enhancement of visual responsiveness in the pulvinar related to the shift of attention. The visual stimuli remain constant through all four conditions. In A, the monkey fixates a central point, and two visual stimuli are presented, one inside the visual receptive field (ST 2) and one outside the field (ST 1). If the RF stimulus is used as the target for an eye movement (B), or if the animal has to attend to it without making an eye movement (C), the visual response is enhanced. If the stimulus outside of the RF is used as an attentional target, there is no enhancement (D). In contrast to the superior colliculus, this enhancement is both spatially selective and independent of eye movement. It is produced by active use of a stimulus in a particular region of space, whether as a target for an eye movement or for attention. Reproduced with permission from Petersen et

ail. 72

shift attention to a new target. Reaction times to cued stimuli can be increased or decreased by local injection of particular drugs into the pulvinar. 74 When a GABA agonist (muscimol) is injected into

pulvinar on one side, the reaction time to a correctly cued contralateral stimulus is significantly slowed (Figure 5). As with the SC, this slowing is even more pronounced in the invalid condition: when a contralateral stimulus is incorrectly cued by a cue in the ipsilateral field reaction times become very long. These results might be interpreted as a general slowing of reaction time to contralateral stimuli. In contrast to SC, muscimol actually speeds the reaction time for stimuli presented ipsilateral to the injected side. The speeding up of reaction time the

both in the valid condition and the invalid condition. These pharmacological results suggest that GABA-related drugs injected into the pulvinar affect performance in the Posner task by inhibiting or facilitating cue-related shifts of attention. The complementary nature of the effects produced in each occurs

FIGURE 5 Effect of chemical inactivation of the pulvinar on reaction time to a cued visual stimulus. Conventions as in Figure 3. As in the SC, reaction times are longer for all stimuli in the affected field regardless of cue validity. Unlike the SC, reaction times are faster for stimuli in the unaffected field (S.E. Petersen and D.L. Robinson, unpublished observa-

tions, 1986).

hemifield by drug injections into the pulvinar may indicate that there is an inherent competition between right and left brain response mechanisms that is being unbalanced. Further evidence for this view comes from recent experiments on discrimination performance which suggest that monkeys are unable to ignore a distracting stimulus when the lateral pulvinar or superior colliculus on one side has been inactivated .75 This imbalance in responsiveness is reminiscent of the situation found in extinction: when two stimuli are presented simultaneously, only the stimulus ipsilateral to the lesion is responded to, even though a contralateral stimulus can elicit a response when presented alone. In each of these cases, unilateral damage has skewed the readiness to respond to stimuli in one hemifield. Thalamic structures other than the pulvinar have also been implicated in attentional deficits. Lesions of the intralaminar nuclei, a structure involved in eye movements, produce neglect in both cat and primate. 7,76 Clinical research also indicates that the thalamus is involved in attention. Humans with thalamic lesions exhibit a visual neglect comparable to that seen in patients with parietal lobe damage, 77-10 and specific eye movement deficits during visual search have been noted following pulvinar damage.$1 Patients with thalamic lesions have also been shown to be impaired on covert shifts of attention; in three patients with unilateral thalamic hemorrhage, reaction times were significantly slower for visual stimuli presented contralateral to the lesion.82 These results are consistent with those observed for inactivation of the pulvinar in a monkey by muscimol: in each case, reaction times to contralateral stimuli are substantially longer in both valid and invalid trials. The pulvinar has extensive reciprocal connections with temporal, parietal, and frontal cortices,83-85 and destruction of the pulvinar may affect attentional processing by interrupting corticothalamocortical interactions. Basal Ganglia The basal ganglia are a group of subcortical structures including the neostriatum (caudate nucleus and putamen), the globus pallidus, and the substantia nigra. All regions of neocortex project to the neostriatum. The primary output of the basal ganglia is to motor and associational divisions of the thalamus. 86 A second important output pathway is from the substantia nigra pars reticulata (SNpr) to the intermediate layers of the superior colliculus. 57,58 Cells in the SNpr show sensory, attentional, and memory-related modulation. 87-90 These neurons

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have a very high tonic discharge rate, and their response to sensory stimuli is a decrease in firing rate. Like cells in many other parts of the brain, those in SNpr yield enhanced responses (in this case, a stronger phasic inhibition) when a visual stimulus has been selected as the target for an eye movement (Figure 6). Enhancement effects in SNpr are similar to those observed in the SC. No enhancement of the visual response occurs when a saccade is made to a target outside the receptive field of the cell, indicating that this is a spatially selective effect, like that in SC. An interesting feature of enhancement in SNpr is that it can occur in relation to auditory as well as to visual targets. Some cells in the SNpr respond primarily to auditory stimuli, while others are bimodal or purely visual. For cells that respond to auditory stimuli, enhancement is seen when the monkey saccades to an auditory target. Cells in the SNpr differ from those in the colliculus in that some SNpr cells exhibit memory contingent responses. Figure 7 illustrates the response of a cell during the waiting period in a remembered saccade task. While the monkey is fixating, a target flashes on briefly in the periphery. The monkey must maintain central fixation until the fixation point disappears, at which time it must make a saccade to the location where the target had previously appeared. The decrease in firing rate typical of these

FIGURE 7 Tonic response in the substantia nigra while the monkey is waiting to make a saccade to a remembered location. In this task, the target (T) is flashed on briefly (for 50 ms) while the monkey is fixating. Several hundred ms later, the fixation point (F) is extinguished, signaling the monkey to make a saccade to the location where the target had appeared. Vertical tick marks on each row in the raster display indicate the time at which this saccade was made. The response begins with target onset and continues until the saccade. Reproduced with permission from Hikosaka and Wurtz.89

cells continues throughout the period during target location is being held in mind. These memory-contingent responses are thought to indicate that the activity of SNpr cells is related to the initiation of eye movements made in the absence of direct sensory control. Similar visual and memory-contingent responses have been observed in the caudate nucleus, the major source of input to substantia nigra.91-93 The destruction of these caudate cells is thought to account for the neglect found after ablation of the neostriatum.94-9’ The neglect observed after SN lesions may also be attributable to disruption of the output pathway for caudate neurons.

SNpr

which

FIGURE 6 Enhancement of visual responsiveness in the substantia nigra. Each panel shows: a cartoon of stimulus location (larger dot) and required eye movement (arrow); horizontal (H) and vertical (V) eye position traces; timing of fixation point (F), target (T), and control target (C) onset; individual rasters aligned on target onset; and cumulative and normal histograms. Cells in SN have a high tonic discharge rate; a decrease in the rate indicates a response. In A, a brief response follows target (T) onset during a fixation task. In B, this visual response is prolonged when the target is used for an eye movement. In C, the visual response is not enhanced prior to a saccade to a target in the opposite field. Reproduced with permission from Hikosaka and Wurtz.8?

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Subcortical Interactions tracing out the functional pathways from cortex to caudate nucleus to substantia nigra to superior colliculus to brainstem, it becomes evident that disrupIn

anywhere along this chain can produce attentional deficits. The orienting functions of the superior colliculus have long been known,40,41 but the degree to which the SC is under direct and tions

indirect cortical control has only recently been apA long-standing mystery in underrole of the SC in attention and the standing the origin of the Sprague efis behavior orienting fect. 102 In a cat rendered hemianopic by a large unilateral visual cortical lesion, transection of the commissure connecting the two colliculi restores visual orienting to a target in the affected hemifield. Cells in the SC ipsilateral to the cortical lesion are responsible for the recovery of visuomotor behavior in the contralateral field. It was originally thought that the recovery could be attributed to a release of inhibition resulting from the commissural transection; the colliculi mutually inhibit one another and the SC ipsilateral to the lesion, having been deprived of visual cortical input, can no longer compete with the colliculus on the intact side. When the commissure is severed, the inhibition is released, and orientation toward a visual target can be mediated by either colliculus. Although recent work indicates that the crossed inhibition may arise from the substantia nigra, rather than from the other colliculus, the principle of response competition between left and right brain remains central to the explanation of the Spra-

preciated .98- 101

gue effect. 103 Some of the physiological mechanisms which underlie erratic eye movements are now becoming clear. The basal ganglia exert significant control over eye movements through their output to the SC. This output from SNpr neurons to the superior colliculus is inhibitory so that a pause in their firing produces net excitation in the colliculus.59,104 Reciprocal changes in firing rate between a cell in the SC and one in the SNpr that projects to it are illustrated in Figure 8; when the tonic nigral inhibition is removed, discharge of the SC neuron is enabled. Inactivation of the SNpr input to the SC produces irrepressible saccades during fixation. In contrast, potentiation of SNpr input to the SC produces a selective deficit in the accuracy of saccades, especially memory-guided saccades.104 This finding is of particular interest in the context of attention deficit disorder (ADD) since multiple regressions during reading’6 and erratic eye movements may be characteristic of children with ADD.17,19-21 The inability to inhibit inappropriate eye movements may be related to increased distractability.

Cortical Mechanisms of Attention Like the subcortical structures discussed above, cortical areas involved in attention are densely interconnected. The primary pathways linking occipital,

FIGURE 8

Reciprocal activity in substantia nigra and superior colliculus neurons during a saccadic eye movement. Vertical line indicates onset of saccadic eye movement; tick marks indicate offset of fixation point. Top: raster and histogram of an SN cell response. Bottom: response of an SC cell recorded at corresponding point in the intermediate layers. Tonic inhibition from the SN neuron is shut down prior to the saccade, enabling the SC neuron to fire. Reproduced with permission from Hikosaka and Wurtz.90

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temporal, parietal, cingulate, and frontal cortex are illustrated in Figure 9. On the basis of anatomical findings, these areas have been described as cona network for attention and spatial memstitutin ory. 105, 06 Recent physiological results support this view. Modulation of single-cell sensory responses by central state has been observed in a variety of paradigms and interpreted in a number of different ways: as enhancement, spatial memory, or preparaetc. What these modulations have in comis an attentional component. The following sections will consider the functional organization of the visual cortex, attentional modulation of neuronal responses within the two parallel visual pathways, attentional functions of cingulate and frontal cortex, cortical and subcortical interactions in the control of attention, and the relation of these findings to attention deficit disorder.

tory set, mon

Functional Organization of Visual Cortex Current views of the organization of the visual cortex in the monkey indicate that there are approximately two dozen distinct visual areas. These areas are found in the occipital, parietal, and temporal cortex and cover more than half of the cortical surface

have been defined on the basis of several anatomical and physiological characteristics. 107,108 Ideally, an area can be distinguished from its neighbors on the basis of: (1) the existence of a single and relatively complete retinotopic map of the contralateral visual field; (2) singleunit response characteristics; (3) a unique pattern of connectivity with other visual and cortical areas; and (4) myelo-, chemo-, or cytoarchitectonic features. In the best case, all four of these criteria are met. The single most important criterion, at least at lower levels of the visual system, is the presence of a retinotopically organized map of the visual world. The use of these multiple criteria has radically changed our view of prestriate and extrastriate cortex. For instance, cytoarchitectonic areas 18 and 19 have been found to contain numerous representations of the visual field which are now considered distinct visual areas (V2, V3, V3A, V4, and PO), and the older cytoarchitectonic terms are no longer used in the mon-

in the

monkey.

These

areas

key. Connectional anatomy has been crucial for the appreciation of the overall organization of the extrastriate cortex. Two principles of organization are now widely held to describe the functional architecture of visual cortex. The first principle of organization derived from anatomy is that of hierarchical order among visual areas. Visual cortical areas are reciprocally connected: area VI (striate cortex) projects to area V2, and V2 projects back again to VI. These connections can be assigned a direction by examining which cortical layers contain the cell bodies contributing to a particular projection and which layers receive that projection. 109-111 Projections which carry signals away from the primary sensory cortex typically derive from cells in the superficial layers and terminate in layer 4 of the recipient cortex. Projections from the higher-order cortex back toward the primary cortex originate in the deeper layers and terminate outside of layer 4. Maunsell and Van Essen112 used this principle to establish a hierarchy of visual areas in which each area is placed one level above the highest area from which it receives a forward-going projection. A current version of this hierarchy is illustrated in Figure 10. A second fundamental principle of visual cortical organization is its division into two parallel process-

FIGURE 9 Medial and lateral views of the monkey cortex with schematic representation of cortical connections. The occipital cortex projects through a chain of visual areas into both the temporal and parietal cortices. The parietal, frontal, and cingulate cortex are reciprocally connected.

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ing systems, one directed ventrally into the temporal lobe for object recognition and the other directed dorsally into the parietal lobe for spatial perception and visuomotor performance.113 The terms ventral and dorsal stream are used as a convenience; membership in a given stream is determined on the basis

parvocellular

and

magnocellular systems

respec-

tively.121-123 The different inputs to the two streams are reflected in the distinct sets of visual response properties observed in typical visual areas within each stream. 121 Cells in V4 (a ventral stream area) are responsive to stationary visual stimuli and are selective for orientation, size, shape, and COlor,125,126 and lesions of V4 produce selective deficits in pattern and hue discrimination. 127 In contrast, cells in the middle temporal (MT) area (a dorsal stream area), require a moving stimulus and are strongly selective for speed and direction of motion,128 and lesions of

impair motion detection.129 A final distinction between the two streams is seen in the relative emphasis on the central visual field for some ventral stream areas. Central field connections predominate in the projections from V4 to TEO to IT while dorsal stream areas process both central and peripheral visual field information.l3o In one of these dorsal stream areas, area PO, the peripheral visual field is actually overrepresented compared to other extrastriate areas. Area PO has widespread projections into the parietal lobe, reflecting the importance of peripheral field information for visuospatial behavior.131 The elucidation of these anatomically-derived principles of visual cortical organization has significantly advanced our understanding of the otherwise bewildering welter of connections among visual areas. Recent evidence from normal humans suggests that these principles may be applicable to the human visual cortex as well. Object identity and spatial location tasks produce quite distinct regions of activation in the human visual cortex as observed by positron emission tomography,132 and moving random dot patterns selectively activate a region which may be homologous to area MT. 133,134

MT

FIGURE 10 Connections among visual stream

areas

areas

in the

monkey.

Dorsal

MT, PO, FST, MST, VIP, and LIP project

ward posterior parietal cortex. Ventral stream and TEO project to inferior temporal cortex.

areas

to-

V4

of connections to other visual areas, not geographic location. Further, assigning an area to a stream does not imply that it is connected exclusively to other visual areas within that stream. As shown in Figure 10, cross-talk between the streams is the rule rather than the exception. The concept of streams is useful for identifying the major connectional and functional affiliations of cortical visual areas. Both streams originate in striate cortex, the primary receiving area for visual information from the parvocellular and magnocellular layers of the lateral geniculate nucleus. Neurons in parvocellular lateral geniculate nucleus have color-opponent receptive field organization and have low contrast sensitivity while magnocellular neurons are not color selective and have high contrast sensitivity. 114,115 Damage to the parvocellular layers produces deficits in color and pattern discrimination while damage to the magnocellular layers produces deficits in motion perception. 116,117 The majority of striate cells receive input from both divisions, but a substantial minority

only parvocellular or only magnocellular prosections. 118 These single-input populations may have distinct projections to segregated zones in extrastriate cortex-&dquo;’ In V2, for example, the parvocellularand magnocellular-recipient divisions are organized as a series of interdigitated stripes which project selectively to ventral stream and dorsal stream areas. 120 Physiological evidence on response latencies receive

in ventral and dorsal stream areas also suggests that they may be selectively affiliated with the

Attention in Visual Cortex Numerous single-unit studies in recent years have focused on attention in the visual cortex. Attentional effects have been observed in a wide variety of

tasks, including localizing a stimulus, identifying or matching a stimulus, and looking at or reaching toward a stimulus. In reviewing these studies I make use of the hierarchy to trace attentional modulation through the visual cortex, considering first the ventral stream to temporal cortex and then the dorsal stream to

parietal

cortex. In contrast to neurons in

subcortical visual structures like the SC and pulvinar, cells in areas VI and V2 do not show spatially selective enhancement of visual responses related to

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or to peripheral detection visually guided saccades 135-137 On the other hand, of changes in luminance.

reactivation of the visual rewhen active fixation stimulus peripheral of a central fixation point is interrupted.138 This reactivation is thought to reflect attentional processing because it is both spatially selective and independent of saccade generation. striate cells do show

sponse to

a

a

Within the ventral stream, V4 is the earliest level of the hierarchy at which significant attentional modulation has been observed. The primary ascending input to V4 arises from area V2. It is reciprocally connected with areas at its own level in the hierarchy (including dorsal stream area MT) and with higher-order areas in both the temporal (TEO, IT) and parietal cortex (lateral intraparietal area).139 The reciprocal projections from

Occipitotemporal System. area

these higher-order areas presumably provide the basis for the top-down control of sensory responsiveness observed in V4. Cells in area V4 show spatially selective enhancement effects similar to those described in the pulvinar and SC.111 When the animal is required to perform a difficult visual discrimination, V4 neurons respond more strongly and are more sharply tuned for color and orientation.141 Selective attention has been shown to affect single unit responses in both visual areas V4 and IT. Moran and Desimone142 showed that the response of a cell could be changed by the monkey’s attentional set even though the retinal stimulus remained the same. (Figure 11). Throughout the task, the monkey must maintain fixation on a central point. The cell is initially characterized to determine its preferred stimulus (eg, red or green). Two stimuli, one of which is known to be an effective stimulus and one which is known to be relatively ineffective in driving the cell, are then presented at separate locations within the receptive field of the cell. The monkey is instructed to attend to only one of these locations by using a delayed match-to-sample task: at the beginning of a trial, the monkey is shown a single stimulus (eg, a red bar) and, after a delay, the monkey is shown either a matching or a non-matching stimulus (eg, a green bar) and must signal whether or not a match occurred. The histogram on the left shows the cell’s response when the monkey is attending to the location of the effective stimulus. The histogram on the right shows the much reduced firing elicited during attention to the ineffective stimulus. The visual stimuli are identical under the two conditions: only the attentional condition has changed. These

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FIGURE 11

Attentional modulation of visual responsiveness in area V4. The same two stimuli are presented within the receptive field

each trial, and the animal is cued to atlocation (indicated by the spotlight). Attending to the location of the effective stimulus produces a strong response to both target onset and target offset while attending to the location of the ineffective stimulus produces a diminished response. Reproduced with permission from Desimone and Ungerlieder.124 tend

to

(RF)

on

one

results show that attentional set, presumably generated by higher-order centers, can affect single cell responses even at a relatively early stage in cortical

processing. Another line of attention research has also demonstrated the salience of instructional set for single unit responsiveness in visual cortex.143 In a delayed match-to-sample task in which the animal must respond to the visual stimulus which matches the orientation of an initial cue, some cells in area V4 signal information about the cue per se (ie, the stimulus that the monkey is looking for) rather than the stimulus currently present (Figure 12A). Even more surprising is the finding that cue-sensitive cells respond to a particular cue orientation regardless of the sensory modality through which the cue is presented; a somatosensory cue drives this visual cell just as well as a visual cue does (Figure 12B). Cells in V4 do not ordinarily respond to somatosensory stimuli, and the apparent response of these cells to tactile stimulation might be thought of as the cell holding an image of the stimulus that the animal must match. Although the pathway by which information about the tactile cue reaches visual cortex is unknown it presumably involves feedback projections from association cortex. A variety of these modulatory effects have been observed in V4.144,14S What these findings

mnemonic Finally, attentive fixation constricts the retinal area over which a stimulus is effective in activating IT cells.15’ This last attentional effect is reminiscent of that observed in humans: in a

process. 151,152

detection task, the functional size of the visual field can be reduced by requiring a discrimination at the fixation

peripheral

point.154

Within the dorsal stream, modulation have attentional different kinds of rather been described. The stimulus requirements of cells in the dorsal stream are quite distinct from those seen in ventral stream regions. The dorsal stream is concerned with detection of visual motion and localization of stimuli, in contrast to the ventral stream which is specialized for object identification. The goal of the dorsal stream is to provide information that enables the organism to act on a stimulus: attend to it, look at it, or reach for it. The output of the system is thus motor as much as it is cognitive and, in contrast to the ventral stream, the dorsal stream has substantial connections with the oculomotor sys-

Occipitoparietal System.

FIGURE 12

Sensitivity to cue orientation in area V4. A: Each raster display shows responses to a particular stimulus (columns) when a particular orientation (rows) had been cued. The large vertical line in each raster indicates time of target onset; the small tick marks indicate the time

at

which the animal responded to a match (diagonal). The histograms in the margins represent summed activity in response to a given stimulus (columns) or a given cue (rows). This neuron fired throughout the period during which the monkey was looking for a match to a particular cue (second row) regardless of the actual stimulus. It failed to respond to these same stimuli when other orientations were cued. B: Response of the same cell to tactile presentation of the cue. The monkey depresses a grooved plate (vertical line at beginning of rasters) and the cell fires tonically during the period between cue and visual stimulus (vertical line at end of rasters). The same cue orientation is preferred regardless of modality. Reproduced with permission from Haenny et ail. 143

have in common is that the animal is attending to the form or color of a stimulus. Since these are the properties most salient for single neurons in ventral stream areas, it is not surprising that attentional effects in V4 have been demonstrated along these particular dimensions. The inferior temporal cortex is the last purely visual area in the ventral stream. Cells here have very large receptive fields which always include the fovea and respond equivalently to a visual stimulus anywhere within the receptive field. 116,147 The response of a cell to a particular compound stimulus (eg, shape and texture), however, can be modified depending on which stimulus feature is relevant for the animal’s performance. 14’ Further, single cell responses are stronger to identical retinal stimuli when the animal performs a discrimination task as opposed to a detection task.149 In a delayed match-

to-sample

task with

long delay periods,

some

IT

cells remain active through the delay period and apinformation about the stimulus to parently encode be matched. 150 Recent findings suggest that this prolonged firing reflects an attentional rather than a

tem. 155-158 Area MT is the most intensively studied dorsal area. Like area V4, it receives its primary input from area V2 but, unlike V4, it also receives substantial direct projections from striate cortex,112,lS9,160 especially from the layers which have magnocellular lateral geniculate nucleus input.161 Area MT is connected to both dorsal stream (PO) and ventral stream (V4) areas at its own level but appears to send its forward-going projections exclusively to higher-level dorsal stream areas (MST, VIP).112,130 Cells in MT prefer moving stimuli and are selective for speed, direction, and disparity.127,162-164 Unlike visual cells in many other cortical areas, neuronal responses in MT are not enhanced when the monkey uses a visual stimulus as the target for a saccade.165 The earliest level of the dorsal stream at which modulation of visual responses has been observed is area MST.165 MST is adjacent to, and receives its primary input from, area MT. Like MT, cells in MST prefer moving visual stimuli and are strongly direction selective. The two areas differ physiologically primarily in the very large size of visual receptive fields in MST. In contrast to MT cells, neurons in MST fire during pursuit eye movements.165 This motor-related discharge is seen in addition to the purely visual response to moving stimuli that occurs when the monkey maintains central fixation while a stimulus passes through the receptive field. Examples of visual and motor discharges are illustrated in Figure 13. This cell fires during pursuit of a visual stream

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target in the preferred direction and

continues to fire the when the period target is blinked during off. Such cells do not respond to blinking off a stationary fixation point, so the continued firing during the period of total darkness indicates that the cell receives an extraretinal input. The second major projection of area MT is to area VIP, a visual area in the depths of the intraparietal sulcus.111 Cell response properties in this area strongly resemble those described for area MST: direction and speed selectivity; responsiveness to whole-field motion; and large receptive fields. Some motion selective cells in VIP also exhibit enhanced responses to stationary visual stimuli when they are the target for a subsequent saccade.166 Like MST neurons, some VIP cells also exhibit enhanced reeven

sponses during tracking of a visual stimulus. All three areas (MT, MST, and VIP) have robust projections to the superior colliculus.156,15’ One of the regions in which the dorsal and ventral streams may converge is the lateral intraparietal area (LIP), located on the lateral bank of the intraparietal sulcus. This area was defined by Andersen and his colleagues as the parietal zone which projects to prefrontal cortex. 167 LIP is connected to both ventral stream areas, including V4 and TEO, 111,139,168,169 and dorsal stream areas, in-

cluding PO, VIP,

and the

superior temporal

sul-

CUS.170,l71,131 It is strongly linked to dorsolateral prefrontal cortex 172-175 as well as to the frontal eye fields.167,176 Subcortically, LIP projects to the deep layers of the superior colliculus55 and to the

pons.1S8

FIGURE 13 Extraretinal influence on visual responsiveness in dorsal stream area MST. Dashed line indicates target position; solid line indicates eye position. A: Response during smooth pursuit of a small spot in the preferred direction. B: Pursuit-related response remains after passive visual stimulation has been eliminated by blinking off the pursuit target for 200 ms (short line under position trace). C: Response also continues when target is stabilized on the retina (long line under position trace). Both manipulations indicate that the pursuit response is independent of visual Reproduced with permission from Newsome et a1.16

inputs.

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Many physiological studies of parietal cortex have sampled properties of cells in the lateral bank of the intraparietal sulcus though it is not clear how many were confined to the area currently defined as LIP. More recent studies in LIP have uncovered cells with responses not unlike the memory-contingent responses observed in the substantia nigra. 177,178 An example of such a response is shown in Figure 14. The task requires that the monkey maintain fixation on a central point for a second or more. Near the beginning of this period, a visual target flashes on briefly in the periphery. At the end of the fixation period, the monkey has to make a saccade to the location where the target had previously appeared. The neuron fires throughout the period between target onset and performance of the saccade. There are several plausible interpretations of this activity. One, favored by Gnadt and Andersen,178 states that these cells represent a motor-planning signal encoding motor error. An alternate interpretation is that

superior temporal SUlCUS.170,180 The primary outto the cingulate cortex.181-183 This set of connections places the IPG in a unique position to participate in a distributed function such as

the

put of the IPG is

FIGURE 14 Tonic activity in

LIP. This neuron has both a visual (no saccade condition) and sactarget response cade-related activity (learned saccade condition). Tonic activity in the delayed saccade task begins with target onset (center panels) and continues through the saccade (right panels). The level of tonic activity decreases significantly when the target is continuously present, and the animal does not have to remember the target location. 177 to

area

onset

maintaining an image of the location of the These tonic responses in LIP may be anatarget. 177 to logous tonically responding cells in V4 selective for cue orientation.143 Posterior parietal cortex is the final predominantly visual area in the dorsal stream. A variety of cytoarchitectonic terms have been applied to regions within the parietal cortex. More recently, the parietal cortex has been divided according to functional and connectional differences. Significant discontinuities in both connections and single cell responses between the gyral cortex (inferior parietal gyrus, IPG) and the sulcal regions (intraparietal sulcus, IPS) suggest that these areas may be functionally distinct, and they will be considered separately. The primary inputs to the IPG arise from visual areas in the intraparietal and superior temporal sulci, including MST, VIP, and LIP, 168,171 and from visual areas on the medial surface of the hemisphere, PO and MDP.13’ The IPG is more densely connected with high-order regions of frontal, temporal, and cingulate cortex than are other districts of the parietal cortex. It has strong projections to the prefrontal cortex in and adjacent to the principal sulcus but is not connected to the frontal eye fields. 167,176,179 The gyral posterior parietal cortex is also connected to polymodal regions in

attention. These extensive connections with association cortices are reflected in the complex and attention-related response properties of single neurons in the IPG. Cells in the posterior parietal cortex, including both the IPG and IPS, have a wide variety of response properties including enhanced visual responses, memory-related responses, oculomotor responses, and attentive fixation responses. 177,184-197 Several of these investigations have noted that single cell responses in the parietal cortex can be modulated according to the motivational value of the stimulus. The enhancement effect observed in the parietal cortex is a prime candidate for the neural basis of spatial attention.198 Unlike enhancement effects anywhere else in cortex, enhancement in the parietal cortex can be completely dissociated from eye movements.199 This is illustrated in Figure 15. In the pe-

the cell is

FIGURE 15

of enhanced responses in the posterior parietal cortex and frontal eye fields. Raster display shows enhancement of the response to a visual stimulus in both the saccade task and in the peripheral attention task for a neuron in parietal cortex. Attending to the stimulus without making an eye movement toward it yields no enhancement for a neuron in frontal cortex. Reproduced with permission from Goldberg and Brute. 244

Comparison

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attention task, the monkey must maintain central fixation and yet attend to a peripheral target in order to detect the instant at which it becomes dimmer. The enhancement of the visual response observed under this condition is comparable to that achieved when the monkey uses the same stimulus as the target for a saccadic eye movement. In both cases, the monkey must attend to the stimulus, in contrast to the fixation task in which the monkey is free to ignore the stimulus. Since the increased response is independent of the behavior which the animal will use to respond to the stimulus, it must be related to attentional factors. Damage to the parietal cortex results in substantial disruption of attentional mechanisms in both monkeys and human .210 Monkeys subjected to parietal lobe lesion do not display the full-blown and long-lasting neglect associated with such damage in humans, but they do show extinction to double simultaneous stimulation. In a quantitative study of response preference, Lynch and McLaren 201 showed that when stimuli are presented in both visual fields simultaneously, the monkey will invariably respond only to the one ipsilateral to the lesion; yet, when a stimulus is presented singly in the field contralateral to the lesion, the monkey can respond to it within a normal latency. Monkeys also do not display the asymmetry in attentional deficits typically observed in humans; left and right hemisphere lesions in

ripheral

monkeys produce equivalent deficits. 202 Deficits in the ability to attend to spatial cues have also been reported for monkeys with lesions of the parietal cortex.2o3 Unilateral lesion of the parietal lobe in the monkey substantially slows reaction times in a Posner task, as illustrated in Figure 16.204 Reaction times post-lesion are longer than normal in all conditions but are most affected for targets in the contralateral field when the animal has been cued to the ipsilateral field (Petersen and Robinson, personal communication). These findings correspond to those observed in studies of performance on Posner tasks after parietal lobe damage in humans. 205-208

Superior Temporal Sulcus. A region in which the occipitotemporal and occipitoparietal pathways may intersect is the superior temporal polysensory area (STP), within the superior temporal sulcus. Anatomically, this region receives visual inputs both from ventral stream areas V4 and IT and from dorsal stream areas MST and FST as well as from Lip Auditory and somatosensory inputs arise from the superior temporal gyrus (area 22) and the anterior inferior parietal lobule (area 7b) respectively. 180

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FIGURE 16 Effects of unilateral parietal lesion on reaction time to a cued visual stimulus. Reaction times postlesion (hatching) are increased for all conditions but are most affected for invalidly cued trials where the target appears in the field contralateral to the lesion (shaded) (S.E. Petersen and D.L.

Robinson,

unpublished observations, 1986).

the STP is predominantly a visual that can be driven is visually cell area; every responAbout half of the cells also respond to audisive. 20’ tory and/or somatosensory stimuli. The receptive fields of these cells are bilateral and very large, including virtually the entire visual field (and the entire body surface for somatosensory bimodal cells). Like cells in other dorsal stream areas, most STP neurons respond much better to moving than to stationary stimuli, and many are selective for direction or type of stimulus motion. A certain proportion of STP neurons, however, resemble IT neurons in their selectivity for complex visual stimuli such as faces . 210-213 STP neurons also respond to the complex visual motion of stimuli produced by body movementszl4 and presumably contribute to the perception of structure-from-motion. Lesions of the superior temporal sulcus impair both orientation to a visual stimulus and visuomotor perfor-

Physiologically,

mance. 215,216 Attentional properties of STP neurons have been observed in saccade tasks. 217 Some neurons in the STP exhibit a modulation of visual responsiveness that is related to the presence of a fixation point. One such cell is illustrated in Figure 17. Three different saccade tasks were used to examine the cell’s visual response. In each task, the monkey saccades to the target when the fixation point (FP) is extin-

the presence of a foveal visual stimulus. One way of interpreting this result is to consider such cells as having a visual response that is gated by attention. When a peripheral target appears during active fixation of another stimulus (the FP), the visual response is completely blocked. When attention is released from the fixation point at the same time that the target appears, a partial response is evoked. Finally, when attention has already been disengaged from the FP at the time of target onset, a strong visual response occurs. Visual responses gated by attention are a common feature of higherorder cortex and may reflect a top-down control of sensory processing by cognitive factors.

tally suppressed by

FIGURE 17

Visual/attentional interactions in the

superior temporal polysensory area (STP). In the standard task, fixation point (F) offset and target (T) onset are simultaneous. Rasters are aligned on target onset (bar beneath histogram). In the overlap task, fixation point and target overlap temporally. A saccade is permitted only when F is extinguished (arrow). No visual response occurs in relation to T or F offset. In the gap task, F goes off before T appears and the response is stronger than in other conditions (C. Colby, E. Miller, T. Albright, and C. Gross,

onset

unpublished observations, 1986). What varies is the

of FP offset and these two events task, target are simultaneous, and a moderate response is elicited in relation to these events. From this task alone, it is impossible to know whether this is a visual response, related to FP offset or to target onset, or whether it is related to the eye movement itself since all three events take place nearly simultaneously. Variants of the standard saccade task were used to determine the nature of the cell’s discharge. In the overlap task, the target appears while the fixation point is still on and the monkey must maintain central fixation until it goes off. In this task, the cell does not fire despite the fact that the same visual stimulus has been presented. One explanation for this surprising silence is that maintaining fixation (and/or attention) at the center point inhibits a visual response to the peripheral stimulus. This possibility is tested in a third task, the gap task. Here the FP goes off before the target appears. The monkey is required to maintain central fixation but is no longer looking at a central stimulus. In this case there is a substantial response when the target appears, larger even than that in the standard task. The conclusion is that this cell has a visual response that can be to-

guished.

timing

onset. In the standard

Cingulate Cortex The cingulate cortex is defined as the cortical zone which receives its major thalamic afferents from the anterior nuclei. 218-220 Contrary to traditional beliefs about the cingulate gyrus as the limbic projection zone in the cortex, limbic afferents to the cingulate cortex are relatively weak, while sensorimotor connections are strong.221 The cingulate cortex is the major source of cortical input to the posterior parietal cortex, and these projections are reciprocal. 181-183,222-224 Two major divisions within the cingulate cortex, posterior and anterior, have been recognized on the basis of connections. 222,225,226 Quantitative studies indicate that the cingulate receives less than 10% of its input from limbic structures (hippocampus,hypothalamus, amygdala), their associated thalamic nuclei (parataenial, paraventricular, reuniens), and their cortical projection zones (entorhinal, prepiriform, infralimbic).221 The primary inputs to the cingulate cortex derive instead from parietal and frontal cortex. Parietal connections are stronger for posterior cingulate cortex, and frontal connections are stronger for anterior cingulate cortex. 222, 226

Relatively little is known about the physiology of cingulate cortex. In accord with its weak limbic inputs, stimulation of the hippocampus fails to influence neuronal activity in the cingulate cortex. 227 The few single unit studies carried out to date indicate that cingulate neurons are visually responsive and the

have oculomotor-related firing.228-231 Neurons in the anterior cingulate cortex also fire during the delay period in a delayed-response task.7-32 In animals, lesions of the cingulate cortex produce deficits in spatial memory and contralateral neglect. 233,234 Selective posterior cingulate lesions produce a rela-

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tively mild neglect, in contrast to complete unilateral cingulectomies which yield a more profound neglect (R. Watson, personal communication). Cingulate damage in humans is also reported to result in spatial memory deficits.106

Given its extensive connections with both the parietal and frontal cortex, the cingulate cortex should provide fertile ground for future explorations of attentional mechanisms in cortex.

Frontal Cortex A wide variety of sensory, attentional, movement, and memory-related responses have been reported for neurons in frontal cortex. While these experiments are frequently difficult to interpret because of the lack of eye movement control in the tasks studied, the general conclusion is that prefrontal cortex is involved in the execution of goal-directed voluntary movements.235 Two restricted regions within the frontal cortex, the frontal eye fields (FEF), and the supplementary eye fields, are specifically involved in the generation of eye movements. Neurons in the FEF have visual receptive fields and discharge in relation to purposive saccades; these saccades can be to a visual target, an auditory target, or a remembered target, but FEF cells do not fire in relation to spontaneous saccades. 236-239 In contrast, cells in the supplementary eye fields do fire in relation to spontaneous saccadeS,240 and neuronal responsiveness is highly dependent on the specific training history of the animal.241 In other respects, the types of neuronal activity found in the supplementary eye fields and FEF are largely compara-

Neurons recorded in the FEF, also show

principal sulcus, adjaspatially selective enhancement prior to goal-directed saccades. A second cent to the

kind of behavioral modulation has been observed in these cells. Some cells show a reactivation of the visual response just prior to a saccade.246 Reactivation and enhancement are not the same; enhancement is an amplification of the initial visual response to target onset while reactivation is a renewal of the visual response at a later time. 140 It is not yet clear what the significance of this reactivation might be, but an anticipatory or attentional role is the most plausible. A third example of behavioral modulation of neuronal responsiveness has been described for cells in the principal sulcus.247 These neurons are active throughout the delay period in an oculomotor delayed response task (Figure 18). Like cells with visual receptive fields and spatially selective enhancement in posterior parietal cortex, these cells have spatially tuned memory fields; tonic activity is recorded during the delay period when a visual cue has been presented in specific sectors of the visual field. This tonic firing is reminiscent of that seen in

b le. 242

Several different kinds of behavioral modulation have been described for cellular responses in the frontal cortex. Like neurons in the superior colliculus and parietal cortex, visually responsive cells in the FEF yield enhanced responses to stimuli that will be the target for a saccadic eye movement, and this enhancement is spatially selective, ie, the target must be presented in the visual receptive field of the cell. 135 Unlike the enhancement seen in parietal cells, enhancement in FEF cells occurs only when the stimulus is used as the target for an eye movement. It does not occur in the peripheral attention task when attention is shifted to the target without an associated eye movement, as illustrated in Figure 15.243 The contrast between the roles of the parietal and frontal cortex in directing attention has been characterized as a difference between selecting a target and selecting a response, or visuospatial versus motor

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attention. 244,245

FIGURE 18 Spatially selective tonic activation in the principal sulcus. Visual cues are randomly presented at one of the eight locations shown in the center diagram. Vertical lines demarcate cue presentation, delay period and response. The monkey maintains central fixation until FP is extinguished then saccades to the location where the target appeared 3 seconds previously. Reproduced with permission from Funahashi et all

V4 during a match-to-sample task&dquo; and in the intraparietal sulcus during the delay period in a delayed saccade task. 177,178 The most immediately noticeable effect of frontal cortex lesions including the frontal eye fields is a area

clinical research suggests that there is an asymmetry in the contributions of the right and left hemispheres to the inhibition of inappropriate responses, with the right hemisphere having a domi-

keys,

nant

role. 256,257

deficit in the

generation of eye movements. Both saccadic67,68,248-250 and smooth pursuit2o’ eye movements are impaired though the former recover quickly while the latter sustain a more lasting impairment. The recovery of function is mediated by direct and indirect pathways from occipital and parietal cortex to the superior colliculus.68,251 A longerlasting deficit has been demonstrated for memoryguided saccades; animals make inaccurate and slow saccades to remembered targets.25° These findings,

long-lasting deficit in smooth pursuit eye movements, suggest that the FEF is important for generating eye movements whenever target location must be anticipated or remembered. Further, frontal lesions produce a profound impairment in the ability to suppress inappropriate saccades to visual targets which appear during fixation of a central target .250 This saccadic control impairment and the smooth pursuit deficit can be thought of as a failure to maintain attention on a stationary or moving fixation stimulus. A transient neglect of contralateral stimuli has also been noted after frontal eye field lesions.252 Somewhat longer lasting effects are seen on extinction behavior; at four weeks post-lesion, the neglect has resolved but the animal continues to respond preferentially to the ipsilesional target in a double simultaneous stimulation test. Response times to tactile stimuli presented on either side increase after unilateral FEF lesions. This increase has been interpreted as an impairment in the intention to act (motor neglect), as opposed to the sensory neglect found after posterior cortical lesions.253 Unilateral frontal lobe lesions in humans also produce transient neglect of contralateral stimuli.254 The effects on eye movements are more complex.255 Such patients have no difficulty generating visually triggered saccades. They have great difficulty, however, in suppressing saccades when instructed to look away from the target and cannot generate saccades to a cued location when the target is not visible. These deficits can be interpreted as revealing the importance of frontal lobe control over reflexive orienting behavior carried out by other brain structures. This impairment in performance of goal directed eye movements is comparable to that observed in monkeys with FEF lesions. In contrast to lesion results obtained in mon-

in combination with the

The Interactive Control of Attention This review has considered cortical and subcortical brain structures with attentional and eye movement related activity. In this final section, I review recent experiments on how these structures interact in the production of oculomotor and attentional behavior. As has been stressed in the above sections, attention and eye movements are not inevitably linked. The purpose of examining oculomotor interactions here is to provide an example of how multiple structures can act together in generating a single output. Anatomy has guided investigations of how these various structures interact, and electrical stimulation and lesion experiments have demonstrated the existence of at least two systems capable of generating saccadic eye movements. Like the two processing streams in the visual cortex which ultimately produce a unitary percept, the two oculomotor systems (tectal and extratectal) normally act in concert to produce eye movements and, presumably, attentional shifts. The point of the experimental manipulations described below is to demonstrate the functional contributions of each system.

Anatomical Interconnections Nearly all of the visual and oculomotor areas described above have been shown to be connected to each other, either directly or indirectly. The major pathways are illustrated in Figure 19. The hierarchically organized visual areas form two parallel pathways into the association cortex. Association areas in the parietal, temporal, and frontal cortex (as well as others not considered here like insula and entorhinal) are all reciprocally connected and have potential corticothalamocortical and corticostriatal-thalamocortical interactions. These cortical zones also have multiple outputs in common. 54 The dorsolateral prefrontal and posterior parietal cortex are reciprocally connected and have comparable sets of efferent connections to more than three dozen cortical and subcortical zones.~ Frontal and parietal projections to a given zone may be overlapping, interdigitated in adjacent columns, or complementary in relation to laminar termination. 15 Every part of the association cortex has a projection to the striatum. 86 Each dorsal stream visual area up to the intraparietal sulcus

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FIGURE 19 Connections of some of the cortical and subcortical structures involved in attention and eye movements.

and each ventral stream area up to area V4 projects to the superior colliculus, as do the frontal eye fields. 53-56,157 Finally, several visual and oculomotor cortical areas have projections to the p011S.53,155,158

Physiologic Interactions Eye movements can be elicited by electrical

stimula-

tion in any of several different brain structures

including superior colliculus,61,25a thalamuS,251 substantia nigra, 260 caudate nucleus,261 striate cortex,262 prestriate cortex ’263 parietal cortex,263,264 frontal eye fields , 239,264-266 and supplementary eye fields . 240 In some of these regions, closer to the motor end of the system, eye movements can be evoked by very low currents while in other primarily visual areas, higher currents are required. When all these areas are apparently capable of generating a signal to move the eyes, how is it that they act in concert? This may be comparable to asking about the coordination of shifts of attention bemost of these same areas show attentional modulation of neuronal activity. We cannot easily measure the effects of presenting contradictory attentional instructions to different brain structures, but it is possible to measure precisely the effects of presenting contradictory eye movement instructions. When two eye movement related brain sites are electrically stimulated simultaneously, a single eye movement results. The metrics of this resultant eye movement can be used to assay the relative contributions of each brain site to the generation of eye cause

movements.

The simplest dual-stimulation experiment is to stimulate two sites within a single structure. When

S108

this is done, for instance in the superior colliculus, the amplitude and direction of the resulting eye movement is the vector average of the movements coded at each stimulation site.258 The same is true when two structures on the same side of the brain, eg, the FEF and SC, are stimulated, as though each structure had equal influence over the final outcome.266 When structures on opposite sides of the brain are stimulated simultaneously, an averaging process again takes place. Since left brain structures normally control rightward eye movements and right brain controls leftward eye movements, stimulation at equivalent sites on the two sides results in cancellation of the horizontal components of the individual eye movements.265 Stimulation at nonequivalent sites produces an averaged eye movement.266 The most parsimonious explanation of these data is that dual stimulation produces an eye movement to the center of gravity of the eye movements represented at the two stimulated sites. These stimulation results are somewhat paradoxical; under normal visual circumstances we are confronted with many potential targets, and yet we make an eye movement to one of them, not to the center of gravity of them all (see, for instance, Luria 267). On the other hand, in special circumstances where visual stimuli are presented which may mimic the visual experience produced by electrical stimulation (ie, small spots), the eyes do move to a point between the targets. 268 One approach toward resolving this problem of how a single output is determined is to pit attention against stimulation. When a monkey actively fixates a visual stimulus, the eye movements elicited by stimulation of the FEF are changed; the threshold current for eliciting a saccade from stimulation at a given cortical location is increased, and the amplitude and velocity of the saccade are decreased.266,269 Fixation of a moving target during performance of smooth pursuit similarly elevates current thresholds for electrically evoked saccades elicited from FEF stimulation .270 The effect of attentive fixation does not depend on the presence of a visual fixation target ; stimulation during fixation when the fixation point is briefly turned off yields the same results.269 Increased thresholds for electrically elicited saccades during attentive fixation have also been found in the posterior parietal cortex and the superior colliculUS.263,271 One interpretation of these results is that the fixation signal is averaged with the eye movement signal, producing a reduced amplitude saccade.266 This interpretation assumes that attention is equivalent to an eye movement signal. A way to test

assumption might be to stimulate the FEF, parior SC during a peripheral attention task. Would the stimulation signal then be averaged with the current eye position signal (central) or with the current locus of attention (peripheral)? Such experiments could help to determine the mechanism by which atthis

etal,

tention achieves control

over

eye

movements.

Behavioral Interactions A final attempt to resolve the problem of coordinating the multiple inputs to the oculomotor system has been made with lesion studies. Schiller and col-

leagues have proposed that there are two distinct pathways to the brain-stem oculomotor system: a tectal pathway and an extratectal pathway. Both pathways originate in the visual cortex. The tectal pathway involves all of the visual and oculomotor inputs which are filtered through the superior colliculus, including the pathway from frontal eye fields to the SC. The extratectal pathway also passes through the FEF but is independent of the SC. The existence of two independent routes to the brainstem is suggested by the finding that lesions of either the FEF or SC alone result in rapid recovery of saccidic eye movements, with more subtle long-lasting deficits. In contrast, a combined lesion of both structures is devastating: eye movements are abolished and

never

recover.68 The

nature of the deficits

produced by single lesions provides important clues to the function of each of these systems. Since the frontal cortex is involved in both pathways, lesions or inactivation of the frontal cortex can affect both

the tectal and extratectal pathways. Such manipulations are useful, however, in that they serve to highlight the functions of the superior colliculus. As described above, frontal cortex lesions produce increased distractability in humans and diminish the ability to suppress saccades to inappropriate targets. Of the several cell types found in the FEF, only those with motor-related firing project to the SC.10’ These corticotectal cells are thought to provide an excitatory input to the intermediate layers of the SC. The projection from the FEF to SC is topographically organized&dquo;, 157 so that FEF cells which code a certain movement may have an excitatory input specifically to SC cells which code the same movement. This arrangement provides a mechanism by which the FEF could impose on the SC a desired

saccade. 245,272

The general conclusion from these physiological and ablation studies is that the FEF normally suppress unwanted saccades and program desired saccades by exerting control over the SC. Anatomical

and trol

studies indicate that this conbe manifest through two different pathways. The first is the direct pathway from the FEF to the intermediate layers of the SC. This is an excitatory pathway; the end product is phasic excitation. The second is an indirect pathway from the FEF to the caudate nucleus, which in turn projects via the substantia nigra to the SC. This pathway also produces a net excitation in the SC, but it does so by providing a phasic release from inhibition. The pathway from the frontal cortex to the caudate is excitatory ; the output from the caudate to the SNpr is inhibitory, as is the projection from the SNpr to the SC. The net product of this double negative is excitation ; when the SNpr is inhibited by output from the caudate nucleus, the SC is released from inhibition, providing a temporal window of opportunity during which saccades can be more readily generated. Frontal cortex output to the oculomotor system is thus both instructive and permissive; the direct pathway excites cells in the intermediate layers while the indirect pathway releases cells in these same layers from tonic inhibition. Anatomical studies demonstrate that frontal and nigral afferent pathways converge on discrete zones within these

pharmacological can

layers. 273 Evidence on the function of the indirect pathway from pharmacological studies of the interaction between the superior colliculus and the substantia nigra.59,104 The projection from the SNpr to the SC uses GABA as its principal neurotransmitter. Injections of GABA-related substances into the SC can therefore mimic the effect of SNpr input. Injections of muscimol, a GABA agonist, suppress saccades to sites represented within the affected region of the SC while injections of bicuculline, a GABA antagonist, facilitate such saccades. After this latter injection, which presumably abolishes the normal comes

tonic inhibition provided by the SNpr, the monkey can no longer maintain fixation of a central target. Irrepressible saccades drive the eye toward the site represented at the affected location. Similar effects

observed

following pharmacological manipulaSNpr. Saccades to remembered targets are particularly vulnerable to disruption by irrepressible saccadic jerks.104 The frontal cortex by no means provides the only input to the tectal oculomotor pathway, and frontal lesions do not permanently abolish eye movements (see Figure 19). The posterior cortex, imcluding the visual and posterior parietal cortex, provides the remaining input to the tectal system. When both the posterior parietal and the FEF are reare

tions of the

S109

movements are abolished, implying that visual input from occipital cortex must go through the parietal or frontal cortex .211,21’ Removal of the posterior parietal cortex by itself produces only modest impairments in saccadic eye movements, comparable to those seen after FEF lesions alone .201 The reflexive nature of the saccades produced following FEF lesions suggests that parietal cortex does not have the same degree of control over the generation or selection of saccadic eye movements. The extratectal pathway, like the tectal pathway, originates in the visual cortex and passes through the frontal cortex, but it reaches oculomotor brain-

moved, eye

stem structures

through pathways

not

including

SC.68 The functions of this extratectal pathway

the can

be studied

by observing oculomotor and attentional behavior following SC lesion. In contrast to the increased distractibility observed following disruption of the fronto-tectal pathways, monkeys are less distractible after tectal lesions.69 Inactivation of the SC by muscimol likewise produces slower and less frequent saccades toward the contralateral side.lo4 Visual cortex input to the SC derives exclusively from the magnocellular system,99 and the SC is necessary for the production of express saccades while the FEF are not. 274 The emerging picture from this line of research is one in which the magnocellular system provides direct and indirect input to the SC, used for short-latency orienting responses effected via the tectal system, while frontal cortex controls purposive eye movements and deliberate shifts of attention through both tectal and extratectal outputs. In humans, the existence of tectal and extratectal pathways for the production of eye movements has yet to be demonstrated. Behavioral studies of eye movements suggest however that express saccades can be generated only when attention has been disengaged from any other visual stimulus. 275-277 Simple instructions to &dquo;pay attention&dquo; or &dquo;do not pay attention&dquo; (to a fixation point) can dramatically affect saccadic reaction times. 278,279 Summary The interaction among the many brain structures involved in the control of eye movements and attention is an example of how the brain can achieve a balance between reflexive (data-driven) and goal-oriented (knowledge-driven) behavior. Different neural mechanisms come into play depending on whether the source of information selected for attentional processing is external (a current sensory stimulus) or internal (a representation of a previous stimulus).

S110

The process of highlighting a particular external information source is reflected in the enhancement of neuronal responsiveness that has been observed in

several cortical and subcortical structures. This

en-

hancement is evoked under different circumstances in different brain structures; it is spatially selective in many cases and explicitly eye-movement related in others. Its most attentionlike manifestation is in parietal cortex where enhancement is independent of

response modality. A second attentionlike phenomenon related to balancing top-down and bottom-up processing is the tonic firing observed during the delay period in delayed match-to-sample tasks. This tonic discharge may reflect the maintenance of an image in short term memory to which attention is directed. Such top-down attentional processing can also produce a contraction of the receptive field, analogous to the psychological contraction of the spotlight of attention. This contraction limits the degree to which bottom-up processing of stimuli outside the spotlight can occur.

A different kind of balance must be maintained between the two sides of the brain. Response competition is evident in the results from lesion studies in both animals and humans. Performance on tasks requiring an attentional shift without overt eye movements demonstrates that unilateral lesion of any of several attention-related structures can result in attenuated responsiveness to contralateral stimuli. The physiological balancing of activity in paired structures constitutes the neural basis for such competitive interactions. This review has emphasized the distributed nature of attentional processing. While it is sometimes convenient to think of different structures as having separate functions, no one structure operates independently of the others in the intact nervous system. Recent investigations have made use of reversible inactivation techniques to dissect out the contributions of particular structures to performance of particular tasks but it is evident that attention is an integrated process resulting from the activity of multiple structures connected through multiple

pathways. Relation to Attention Deficit Disorder Given the number of different brain structures and systems involved in attention, it is not surprising that children diagnosed as having attentional deficits fail to show a single etiology or single locus of damage. 280-282 ADD children show a wide range of

symptoms including heightened sensitivity

to

re-

contingencies,283 and there is some question as to whether this can be considered a single disorder. 284 One reasonably consistent observation how~6-21 ever is a deficit in control of eye movements. Children with ADD are less able to maintain steady fixation on a target, and make more regressive saccades during reading. They show irregular pursuit of a moving target, making more and larger saccades away from the path of the target. This latter problem does not represent a primary pursuit deficit, as seen in other populations, because the deficit is greater at lower stimulus velocities where it is normally easier to maintain eye position on the target. In an attentional task (detecting the dimming of a moving fixation point), ADD children showed a specific deficit in attending to the continuous stimulus, and this

ward

improved with drug treatments. 17 This failure to maintain attentive engagement with the stimulus is suggestive of a frontal lobe deficit. Increased distractibility and lack of impulse control characterize both patients with frontal lobe damage and children with ADD. 285-217 The frontal and parietal cortex normally interact in the production of tracking eye movements, and specific pursuit deficits arise from frontal and/or parietal lesions in monkeys249,288,289 and humans.29o-293 Saccadic as well as smooth pursuit eye movements are affected in ADD, and in both cases multiple brain structures may be involved. From the pathways described above, it is apparent that damage anywhere in the systems that provide direct or indirect cortical control over eye movements could produce the oculomotor symptoms found in ADD. Cortical lesions in any of a number of different areas, including the frontal, parietotemporal, and occipitoparietal cortex, can produce impairments in fixation in the form of irrepressible microsaccades (square wave jerks).294 Further, damage to frontal

change and not through any change in reading ability per se. In dyslexic adults, treatment with methylphenidate also improves reading ability and abolishes square wave jerks.298 Both the dyslexia and the square wave jerks may be manifestations of an underlying attentional disorder. Visual hemineglect is associated with deficits in eye movements, 166,299 and recent evidence indicates that chil-

ioral

dren with ADD show evidence of neglect.3oo The eye movement deficits found in both ADD children and patients with neglect lend support to the view that these conditions have something in common. Further, there is evidence both for ADD and for gaze paresis in neglect of selective right-hemisphere involvement.11,301 A question for future research is whether oculomotor deficits in ADD can be specifically related to the underlying attentional disorder.

deficit

corteX255

or

striatum295 produces irrepressible

sac-

cades in humans like those produced by frontal eye field lesion 250 or substantia nigra inactivation in monkeys. 104 In the absence of frontal control, extraneous movements are evoked by stimuli which could otherwise be ignored.245 One hint that such a deficit may contribute to ADD is the reduced blood flow in the frontal cortex and caudate nucleus observed in these children.296 There is some evidence that these eye movement deficits are functionally related to ADD. Children with ADD who are treated with methylphenidate show improvements in reading. 297 These improvements are thought to be mediated by behav-

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