The role of the frontal eye fields in the oculomotor inhibition of reflexive saccades: evidence from lesion patients.

The current study investigated the role of the frontal eye fields (FEF) in the suppression of an unwanted eye movement ('oculomotor inhibition'). Oculomotor inhibition has generally been investigated using the antisaccade task, in which an eye movement to a task-relevant onset must be inhibited. Various lines of research have suggested that successful inhibition in the antisaccade task relies heavily on the FEF. Here, we tested whether the FEF are also involved in the oculomotor inhibition of reflexive saccades. To this end, we used the oculomotor capture task in which the to-be-inhibited element is task-irrelevant. Performance of four patients with lesions to the FEF was measured on both the antisaccade and oculomotor capture task. In both tasks, the majority of the patients made more erroneous eye movements to contralesional elements than to ipsilesional elements. One patient showed no deficits in the antisaccade task, which could be explained by the developmental origin of his lesion. While we confirm the role of the FEF in the inhibition of task-relevant elements, the current study also reveals that the FEF play a crucial role in the oculomotor inhibition of task-irrelevant elements.

Oculomotor integration in patients with a pulvinar lesion.

The pulvinar nucleus of the thalamus, with its connections to visual areas and to frontal and parietal oculomotor cortex, might serve as a nexus for integrating cortical control of voluntary eye movements with reflexive eye movements generated by the superior colliculus. To investigate this hypothesis, we tested five patients with a unilateral lesion of the pulvinar on the oculomotor capture paradigm. In this task, participants have to ignore a distractor item and make a saccade to a target in a visual search display. Results showed that the interference of the distractor was stronger when it was presented contralateral to their lesion compared to when it was presented in the ipsilesional visual field. These findings were confirmed by an additional single case experiment in which we measured saccade trajectory deviations as evoked by a single distractor. These results show that the pulvinar is involved in the successful influence of higher order signals (like our goals and intentions) on the guidance of our eye movements.

Neural fate of seen and unseen faces in visuospatial neglect: a combined event-related functional MRI and event-related potential study.

To compare neural activity produced by visual events that escape or reach conscious awareness, we used event-related MRI and evoked potentials in a patient who had neglect and extinction after focal right parietal damage, but intact visual fields. This neurological disorder entails a loss of awareness for stimuli in the field contralateral to a brain lesion when stimuli are simultaneously presented on the ipsilateral side, even though early visual areas may be intact, and single contralateral stimuli may still be perceived. Functional MRI and event-related potential study were performed during a task where faces or shapes appeared in the right, left, or both fields. Unilateral stimuli produced normal responses in V1 and extrastriate areas. In bilateral events, left faces that were not perceived still activated right V1 and inferior temporal cortex and evoked nonsignificantly reduced N1 potentials, with preserved face-specific negative potentials at 170 ms. When left faces were perceived, the same stimuli produced greater activity in a distributed network of areas including right V1 and cuneus, bilateral fusiform gyri, and left parietal cortex. Also, effective connectivity between visual, parietal, and frontal areas increased during perception of faces. These results suggest that activity can occur in V1 and ventral temporal cortex without awareness, whereas coupling with dorsal parietal and frontal areas may be critical for such activity to afford conscious perception.

Strategic control over saccadic eye movements: studies of the fixation offset effect.

We studied the strategic (presumably cortical) control of ocular fixation in experiments that measured the fixation offset effect (FOE) while manipulating readiness to make reflexive or voluntary eye movements. The visual grasp reflex, which generates reflexive saccades to peripheral visual signals, reflects an opponent process in the superior colliculus (SC) between fixation cells at the rostral pole, whose activity helps maintain ocular position and increases when a stimulus is present at fixation, and movement cells, which generate saccades and are inhibited by rostral fixation neurons. Voluntary eye movements are controlled by movement and fixation cells in the frontal eye field (FEF). The FOE--a decrease in saccade latency when the fixation stimulus is extinguished--has been shown to reflect activity in the collicular eye movement circuitry and also to have an activity correlate in the FEF. Our manipulation of preparatory set to make reflexive or voluntary eye movements showed that when reflexive saccades were frequent and voluntary saccades were infrequent, the FOE was attenuated only for reflexive saccades. When voluntary saccades were frequent and reflexive saccades were infrequent, the FOE was attenuated only for voluntary saccades. We conclude that cortical processes related to task strategy are able to decrease fixation neuron activity even in the presence of a fixation stimulus, resulting in a smaller FOE. The dissociation in the effects of a fixation stimulus on reflexive and voluntary saccade latencies under the same strategic set suggests that the FOEs for these two types of eye movements may reflect a change in cellular activity in different neural structures, perhaps in the SC for reflexive saccades and in the FEF for voluntary saccades.

A systematic study of visual extinction. Between- and within-field deficits of attention in hemispatial neglect.

Mechanisms of visual extinction were investigated in four patients with right hemisphere damage using a partial report paradigm. Different shapes (star or triangle) were displayed in one, two or four possible locations so that double simultaneous stimuli occurred either across the two hemifields or within the same hemifield. Patients attended either to the location (right, left or both), number (one, two or four) or shape (no, one or two stars among the shapes presented) of stimuli in three separate experiments using the same displays and exposure duration. Reporting the location (Experiment 1) produced marked contralesional extinction, although reaction time was delayed compared with unilateral right trials, indicating unconscious processing. Reaction time was also delayed on correct bilateral and unilateral left trials. In contrast, enumerating stimuli (Experiment 2) caused no significant contralesional extinction on bilateral displays and reaction time was similar on bilateral and unilateral right trials, suggesting that information from both fields was grouped in a single numerable percept in this task. However, patients often detected only one of two stimuli within the left field. Whereas similarity of shapes improved localization and did not affect enumeration, identifying stars among shapes (Experiment 3) revealed a severe inability to detect two similar targets between hemifields as well as within each of the hemifields. Distracting triangles were generally less detrimental to the perception of a concurrent target on either side, but slowed the reaction time regardless of whether they were in the same or the opposite field. Relative difficulty in ignoring distractors correlated with neglect severity on a cancellation task, and was most prominent in one patient with a large amount of frontal damage. These findings suggest that (i) allocation of attention to identical stimuli can be modulated by task demand; (ii) enumerating a small set of items across fields may not require attending to individual stimuli but relies on preattentive subitizing ability, as found in normal subjects; (iii) location information may be critical for attentional mechanisms subserved by the parietal cortex and pathological competition for awareness in extinction; (iv) extinction entails a bilateral deficit in attending to two concurrent similar targets when their features must be identified; and (v) the relevance of the stimuli can modulate the distribution of attention, possibly through frontal top-down control. These findings are consistent with recent neurophysiological evidence of parietal and frontal attentional influences on ventral visual pathways.

Inhibition of return in saccadic eye movements.

Inhibition of return (IOR) is a phenomenon in which responses generated to targets at previously attended locations are delayed. It has been suggested that IOR affords a mechanism for optimizing the inspection of novel locations and that it is generated by oculomotor reflexes mediated by the superior colliculus. In this investigation, we measured the effects of IOR on the metrics of saccadic eye movements made to novel and previously attended locations. Saccades made to cued target locations, as well as to other targets within the same hemifield, had longer latencies than saccades made towards the novel, uncued hemifield. We further found that the amplitudes of saccades towards the cued hemifield were more hypometric, but only when the amplitude could not be pre-programmed. These results provide evidence that IOR influences spatial, as well as temporal, parameters of saccadic eye movements and suggest that the exogenous orienting of attention, in addition to influencing target detection, also influences oculomotor programming.

Ipsilesional line bisection bias in patients with chronic parietal lesions.

The current study investigated whether an ipsilesional bias in line bisection, a conventional measure for diagnosing hemispatial neglect, persists even in the absence of this syndrome in patients with chronic lesions restricted to posterior association cortex or dorsolateral prefrontal cortex. Both left and right hemisphere parietal lesions produced ipsilesional bisection errors, and to a comparable degree. Patients with lesions in frontal cortex, on the other hand, did not show a consistent bias. We conclude that chronic parietal lesions produce an ipsilesional bias in line bisection, even in the absence of other clinical signs of neglect, and that left hemisphere lesions can affect line bisection to the same degree as right hemisphere lesions.

Components of reflexive visual orienting to moving objects.

Posner and Cohen (1984) and Maylor (1985) initially observed that a luminance change produces both facilitatory and inhibitory effects on subsequent detection. While Posner and Cohen claimed that the facilitatory effect was mapped in retinotopic coordinates, they showed that inhibition of return (IOR) was mapped in "environmental coordinates." Tipper and colleagues (Tipper, Driver, & Weaver, 1991; Tipper et al., 1997; Tipper, Weaver, Jerreat, & Burak, 1994) and Abrams and Dobkin (1994b) have recently reported that IOR can be object based, but contradictory results have also been reported (Müller & von Mühlenen, 1996). Here we report six experiments showing that an uninformative peripheral cue can generate either facilitatory or inhibitory object-based effects that can tag moving objects and that can persist for several hundred milliseconds. Although the boundary conditions determining which effect will be manifest remain to be defined, the present results suggest that facilitation and inhibition are generated independently, rather than being components of the same biphasic process.

Response channel activation and the temporoparietal junction.

When we learn to make one motor response to one visual stimulus and a different motor response to another, representations of these stimulus-response associations must be maintained to efficiently transduce perception into action. When an irrelevant distractor is presented adjacent to a target stimulus, interference is observed when the two stimuli are associated with conflicting responses, presumably due to response channel activation by the incompatible information. We have explored the neural bases of these interference effects. In a previous study, patients with hemispatial neglect showed normal interference from contralesional flankers. In another study, patients with lesions of the lateral prefrontal cortex were found not to show interference from distractors presented in the contralesional hemifield. The current study provided a more anatomically detailed investigation of the effects of posterior association cortex lesions on flanker interference. Patients with chronic, unilateral lesions involving the temporoparietal junction (TPJ), two of whom had hemispatial neglect, were compared with patients with lesions of the posterior association cortex not involving the TPJ. All patients performed a color discrimination task at fixation while a congruent or incongruent colored flanker was briefly presented (16.7 ms) in the adjacent contralesional or ipsilesional hemifield. Patients with TPJ lesions showed no interference effects from the contralesional flankers. These results suggest that the TPJ, in combination with the dorsolateral prefrontal cortex, is involved in transducing perception into action.

Toward a functional analysis of the basal ganglia.

Parkinson patients were tested in two paradigms to test the hypothesis that the basal ganglia are involved in the shifting of attentional set. Set shifting means a respecification of the conditions that regulate responding, a process sometimes referred to as an executive process. In one paradigm, upon the appearance of each stimulus, subjects were instructed to respond either to its color or to its shape. In a second paradigm, subjects learned to produce short sequences of three keypresses in response to two arbitrary stimuli. Reaction times were compared for the cases where set either remained the same or changed for two successive stimuli. Parkinson patients were slow to change set compared to controls. Parkinson patients were also less able to filter the competing but irrelevant set than were control subjects. The switching deficit appears to be dopamine based; the magnitude of the shifting deficit was related to the degree to which 1-dopa-based medication ameliorated patients' motor symptoms. Moreover, temporary withholding of medication, a so-called off manipulation, increased the time to switch. Using the framework of equilibrium point theory of movement, we discuss how a set switching deficit may also underlie clinical motor disturbances seen in Parkinson's disease.

Spatial attention deficits in humans: a comparison of superior parietal and temporal-parietal junction lesions.

Although clinical evidence of spatial attention deficits, such as neglect and extinction, is typically associated with lesions of the right temporal-parietal junction, recent evidence has suggested an important role for the superior parietal lobe. Two groups of patients, selected for lesions at the temporal-parietal junction including the superior temporal gyrus (TPJ group), or for lesions involving the parietal but not the superior temporal region (PAR group), performed cued-target detection tasks in 2 experiments. An extinction-like response time pattern was found for the TPJ but not the PAR group. In addition, both groups were able to use expectancy information, in the form of cue predictiveness, suggesting that separate mechanisms mediate exogenous and endogenous processes during attention shifts.

Inhibitory tagging of locations in the blind field of hemianopic patients.

This study evaluated the potential contribution of extrageniculate visual pathways to oculomotor orienting reflexes in hemianopic patients. It tested whether extrageniculate pathways mediate inhibition of return (IOR)-a phenomenon characterized by slowed target detections at recently stimulated locations (Posner & Cohen, 1984). Because hemianopic subjects cannot overtly respond to stimuli presented within their hemianopic field, we utilized a spatial cueing paradigm that capitalized on the fact that IOR operates in spatiotopic coordinates. Subjects moved their eyes so that a cue and a target presented at the same spatial location were imaged successively onto blind and seeing portions of their retinas. One hemianopic patient showed a similar IOR effect from cues presented within both the seeing and the hemianopic fields. With a second hemianopic patient, only presentations of the cue to the subject's seeing field produced IOR. The explanation for this discrepancy is not evident. These observations highlight both the potential value and the pitfalls inherent in using "blindsight" as a window into human consciousness.

Transcranial magnetic stimulation of the prefrontal cortex delays contralateral endogenous saccades.

The contributions of the superior prefrontal cortex (SPFC) and the superior parietal lobule (SPL) in generating voluntary endogenous and reflexive visually guided saccades were investigated using transcranial magnetic stimulation (TMS). Subjects made choice saccades to the left or right visual field in response to a central arrowhead (endogenous go signal) or a peripheral asterisk (exogenous go signal) that were presented along with a single TMS pulse at varying temporal intervals. TMS over the SPFC increased latencies for saccades made in response to an endogenous go signal toward the contralateral hemifield. No effects were observed when the go signal was exogenous and TMS was over the SPFC or when TMS was over the SPL for either saccade type. The delayed contralateral endogenous saccades observed in this study are likely a consequence of disruption in the normal operations of the human frontal eye field.

Perception of geometric illusions in hemispatial neglect.

A patient with left hemispatial neglect, while completely unaware of features on the left side of figures, nevertheless perceived geometric illusions dependent on these features. Bisection errors were amplified not only by increasing line length, but also by perceived line length induced by these illusions. Bisection of Judd illusion figures was as much influenced by neglected features on the left as by perceived features on the right. These observations demonstrate that geometric illusions are generated through preattentive processes. They also suggest that in visual neglect there may be preattentive processing of location as well as shape information.

Axis-based neglect of visual shapes.

A new test of "object-centered" visual neglect uses equilateral triangles, with ambiguous principal axes that can be manipulated by context. Three left neglect patients detected gaps in such triangles. The location of the gap relative to the biased principal axis was varied, while maintaining the same egocentric locus. More gaps were missed on the left of the axis. This supports Driver and Halligan's (Cognit. Neuropsychol. 8, 475-496, 1991) claim that neglect can apply to the contralesional side of a shape's principal axis, while avoiding serious flaws in their method. The relation between axis-based neglect and other cases of object-centred neglect is discussed.

Reading of letters and words in a patient with Balint's syndrome.

A patient with bilateral parietal damage, and Balint's syndrome, named visual letters. These were presented individually or within four-letter strings. Solitary letters were identified very accurately. In the case of strings, more letters were correctly reported for words than for nonwords, and more for pronounceable than for unpronounceable nonwords. When required to read words as a whole, performance was better than predicted by letter-reports. These results extend the object-based limitation apparent in Balint's syndrome to the case of reading. The component letters of a string benefit when they form a familiar global object, rather than requiring representation as multiple separate objects. The patient occasionally made homophonic errors when listing the letters in a visual word. This suggests an attempt to bypass visual simultanagnosia by treating the string as a single object, deriving a holistic phonological code for it, and then decomposing this into component letters via spelling rules.

Shifting visual attention between objects and locations: evidence from normal and parietal lesion subjects.

Space- and object-based attention components were examined in neurologically normal and parietal-lesion subjects, who detected a luminance change at 1 of 4 ends of 2 outline rectangles. One rectangle end was precued (75% valid); on invalid-cue trials, the target appeared at the other end of the cued rectangle or at 1 end of the uncued rectangle. For normals, the cost for invalid cues was greater for targets in the uncued rectangle, indicating an object-based component. Both right- and left-hemisphere patients showed costs that were greater for contralesional targets. For right-hemisphere patients, the object cost was equivalent for contralesional and ipsilesional targets, indicating a spatial deficit, whereas the object cost for left-hemisphere patients was larger for contralesional targets, indicating an object deficit.

Neglect.

Neglect is a disorder of orienting in which patients are unaware of objects in their contralesional visual field. Yet their pre-attentive vision is still able to parse the scene to segregate figure from ground, group objects, and to define their primary axis. Therefore, it appears that perceptual processing may be intact up to the level of semantic classification, and that neglect only acts at the level of selection for action and access to awareness. Several mechanisms contribute to neglect, including disinhibited orienting to the ipsilesional field, a deranged representation of space, and deficits in disengaging attention, oculomotor corollary discharge, and representation of contralesional movement trajectories. Recent studies have begun to identify the neural substrates involved in these mechanisms.

Disinhibition of automatic word reading in Parkinson's disease.

The Stroop phenomenon was studied in patients with early and late onset Parkinson's disease (PD) and in normal controls to examine the effect of this disease on generating and controlling automatic mental processes. In the Stroop task subjects are presented with color or neutral words in various colors and asked to ignore the word and name its color as fast as possible. We examined the facilitory and interference effects of the irrelevant word upon naming the color by using computerized version of the Stroop test. Vocal reaction times of both early and late onset PD patients presented an augmented facilitory effect. In addition, error data of the late onset PD patients showed an enlarged interference effect. These effects are related to an impairment in the ability to control automatic-reflexive processes. The augmented facilitory effect is manifest early in the course of PD suggesting that the basal ganglia act to inhibit some automatic cognitive processes. The origin of the interference effect in late onset PD patients is less clear. It may reflect more severe basal ganglia dysfunction; or a decline in cortical inhibitory processes.

Visual extinction and stimulus repetition.

Abstract Five patients with visual extinction following unilateral brain injury were briefly presented with colored letters in either or both visual fields, and required to report and locate the colors or the shapes. On double simultaneous stimulation, they tended to miss the event contralateral to their lesion. This extinction was increased when the two stimuli were the same on the reported dimension, Similarity on the irrelevant dimension had no effect. These data suggest that extinguished colors and shapes may be correctly extracted by the visual system (when task-relaant) even though they are unavailable for verbal report. An analogy is made with the phenomena of "repetition blindness" in normal observers, and it is proposed that extinction may reflect failure in a token-individuation process for correctly extracted visual types.