Dynamics of Saccade Trajectory Modulation by Distractors: Neural Activity Patterns in the Frontal Eye Field.

The sudden appearance of a visual distractor shortly before saccade initiation can capture spatial attention and modulate the saccade trajectory in spite of the ongoing execution of the initial plan to shift gaze straight to the saccade target. To elucidate the neural correlates underlying these curved saccades, we recorded from single neurons in the frontal eye field (FEF) of two male rhesus monkeys shifting gaze to a target while a distractor with the same eccentricity appeared either left or right of the target at various delays after target presentation. We found that the population level of pre-saccadic activity of neurons representing the distractor location encoded the direction of the saccade trajectory. Stronger activity occurred when saccades curved toward the distractor, and weaker when saccades curved away. This relationship held whether the distractor was ipsilateral or contralateral to the recorded neurons. Meanwhile, visually responsive neurons showed asymmetrical patterns of excitatory responses that varied with the location of the distractor and the duration of distractor processing relating to attentional capture and distractor inhibition. During earlier distractor processing, neurons encoded curvature towards the distractor. During later distractor processing, neurons encoded curvature away from the distractor. This was observed when saccades curved away from distractors contralateral to the recording site and when saccades curved towards distractors ipsilateral to the recording site. These findings indicate that saccadic motor planning involves dynamic push-pull hemispheric interactions producing attraction or repulsion for potential but unselected saccade targets.Significant Statement This study not only advances our understanding of oculomotor function in dynamic environments but also has potential clinical relevance for diagnosing and understanding disorders characterized by abnormal saccade trajectories. Our research elucidates the neural mechanisms behind saccade trajectories that are not always linear due to the brain's integration of multiple visual cues and/or motor plans. By analyzing the frontal eye field (FEF) activity in rhesus monkeys, we found that saccade directionality and timing are influenced by the interaction between FEF visual neurons representing target and distractor stimuli. The FEF's role extends beyond a winner-takes-all approach, incorporating saccade vector averaging computations that produce curved saccades. Furthermore, ipsilateral visual neurons encode distractor suppression that drives curvature away from the distractor.

Comparative diffusion tractography of corticostriatal motor pathways reveals differences between humans and macaques.

The primate corticobasal ganglia circuits are understood to be segregated into parallel anatomically and functionally distinct loops. Anatomical and physiological studies in macaque monkeys are summarized as showing that an oculomotor loop begins with projections from the frontal eye fields (FEF) to the caudate nucleus, and a motor loop begins with projections from the primary motor cortex (M1) to the putamen. However, recent functional and structural neuroimaging studies of the human corticostriatal system report evidence inconsistent with this organization. To obtain conclusive evidence, we directly compared the pattern of connectivity between cortical motor areas and the striatum in humans and macaques in vivo using probabilistic diffusion tractography. In macaques we found that FEF is connected with the head of the caudate and anterior putamen, and M1 is connected with more posterior sections of the caudate and putamen, corroborating neuroanatomical tract tracing findings. However, in humans FEF and M1 are connected to largely overlapping portions of posterior putamen and only a small portion of the caudate. These results demonstrate that the corticobasal connectivity for the oculomotor and primary motor loop is not entirely segregated for primates at a macroscopic level and that the description of the anatomical connectivity of corticostriatal motor systems in humans does not parallel that of macaques, perhaps because of an expansion of prefrontal projections to striatum in humans.

Neural control of voluntary movement initiation.

When humans respond to sensory stimulation, their reaction times tend to be long and variable relative to neural transduction and transmission times. The neural processes responsible for the duration and variability of reaction times are not understood. Single-cell recordings in a motor area of the cerebral cortex in behaving rhesus monkeys (Macaca mulatta) were used to evaluate two alternative mathematical models of the processes that underlie reaction times. Movements were initiated if and only if the neural activity reached a specific and constant threshold activation level. Stochastic variability in the rate at which neural activity grew toward that threshold resulted in the distribution of reaction times. This finding elucidates a specific link between motor behavior and activation of neurons in the cerebral cortex.

Neuronal correlates of subjective visual perception.

Neuronal activity in the superior temporal sulcus of monkeys, a cortical region that plays an important role in analyzing visual motion, was related to the subjective perception of movement during a visual task. Single neurons were recorded while monkeys (Macaca mulatta) discriminated the direction of motion of stimuli that could be seen moving in either of two directions during binocular rivalry. The activity of many neurons was dictated by the retinal stimulus. Other neurons, however, reflected the monkeys' reported perception of motion direction, indicating that these neurons in the superior temporal sulcus may mediate the perceptual experience of a moving object.

Search efficiency but not response interference affects visual selection in frontal eye field.

Two manipulations of a visual search task were used to test the hypothesis that the discrimination of a target from distractors by visually responsive neurons in the frontal eye field (FEF) marks the outcome and conclusion of visual processing instead of saccade preparation. First, search efficiency was reduced by increasing the similarity of the distractors to the target. Second, response interference was introduced by infrequently changing the location of the target in the array. Both manipulations increased reaction time, but only the change in search efficiency affected the time needed to select the target by visually responsive neurons. This result indicates that visually responsive neurons in FEF form an explicit representation of the location of the target in the image.

Effects of similarity and history on neural mechanisms of visual selection.

To investigate how the brain combines knowledge with visual processing to locate eye movement targets, we trained monkeys to search for a target defined by a conjunction of color and shape. On successful trials, neurons in the frontal eye field not only discriminated the target from distractors, but also discriminated distractors that shared a target feature as well as distractors that had been the search target during the previous session. Likewise, occasional errant saccades tended to direct gaze to distractors that either resembled the current target or had been the previous target. These findings show that the frontal eye field is involved in visual and not just motor selection and that visual selection is influenced by long-term priming. The data support the hypothesis that visual selection can be accomplished by parallel processing of objects based on their elementary features.

The detection of visual signals by macaque frontal eye field during masking.

The neural link between a sensory signal and its behavioral report was investigated in macaques trained to locate an intermittently detectable visual target. Neurons in the frontal eye field, an area involved in converting the outcome of visual processing into motor commands, responded at short latencies to the target stimulus whether or not the monkey reported its presence. Neural activity immediately preceding the visual response to the mask was significantly greater on hits than on misses, and was significantly greater on false alarms than on correct rejections. The results show that visual signals masked by light are not filtered out at early stages of visual processing; furthermore, the magnitude of early visual responses in prefrontal cortex predicts the behavioral report.

From sensory evidence to a motor command.

New insight into how the brain makes a decision has come from a study of the effects of the decision-making process on an eye movement evoked by electrical stimulation of the frontal cortex. The accumulation of sensory evidence was found to cause a gradual commitment toward a choice.

Dynamics of saccade target selection: race model analysis of double step and search step saccade production in human and macaque.

We investigated how saccade target selection by humans and macaque monkeys reacts to unexpected changes of the image. This was explored using double step and search step tasks in which a target, presented alone or as a singleton in a visual search array, steps to a different location on infrequent, random trials. We report that human and macaque monkey performance are qualitatively indistinguishable. Performance is stochastic with the probability of producing a compensated saccade to the final target location decreasing with the delay of the step. Compensated saccades to the final target location are produced with latencies relative to the step that are comparable to or less than the average latency of saccades on trials with no target step. Noncompensated errors to the initial target location are produced with latencies less than the average latency of saccades on trials with no target step. Noncompensated saccades to the initial target location are followed by corrective saccades to the final target location following an intersaccade interval that decreases with the interval between the target step and the initiation of the noncompensated saccade. We show that this pattern of results cannot be accounted for by a race between two stochastically independent processes producing the saccade to the initial target location and another process producing the saccade to the final target location. However, performance can be accounted for by a race between three stochastically independent processes--a GO process producing the saccade to the initial target location, a STOP process interrupting that GO process, and another GO process producing the saccade to the final target location. Furthermore, if the STOP process and second GO process start at the same time, then the model can account for the incidence and latency of mid-flight corrections and rapid corrective saccades. This model provides a computational account of saccade production when the image changes unexpectedly.

Neural correlates of visual and motor decision processes.

Recent research has clarified and revealed characteristics of perceptual and motor decision processes in the brain. A democracy of sensory neurons discriminate the properties of a stimulus, while competition contrasts the attributes of stimuli across the visual field to locate conspicuous stimuli. Salience and significance are weighed to select an object on which to focus attention and action. Experimentally combining neural and mental chronometry has determined the contribution of perceptual and motor processes to the duration and variability of behavioral reaction time. Whereas perceptual processing occupies a relatively constant amount of time for a given stimulus condition, the processes of mapping particular stimuli onto the appropriate behavior and preparing the motor response provide flexibility but introduce delay and variability in reaction time.

Reliability of macaque frontal eye field neurons signaling saccade targets during visual search.

Although many studies have explored the neural correlates of visual attention and selection, few have examined the reliability with which neurons represent relevant information. We monitored activity in the frontal eye field (FEF) of monkeys trained to make a saccade to a target defined by the conjunction of color and shape or to a target defined by color differences. The difficulty of conjunction search was manipulated by varying the number of distractors, and the difficulty of feature search was manipulated by varying the similarity in color between target and distractors. The reliability of individual neurons in signaling the target location in correct trials was determined using a neuron-anti-neuron approach within a winner-take-all architecture. On average, approximately seven trials of the activity of single neurons were sufficient to match near-perfect behavioral performance in the easiest search, and approximately 14 trials were sufficient in the most difficult search. We also determined how many neurons recorded separately need to be evaluated within a trial to match behavioral performance. Results were quantitatively similar to those of the single neuron analysis. We also found that signal reliability in the FEF did not change with task demands, and overall, behavioral accuracy across the search tasks was approximated when only six trials or neurons were combined. Furthermore, whether combining trials or neurons, the increase in time of target discrimination corresponded to the increase in mean saccade latency across visual search difficulty levels. Finally, the variance of spike counts in the FEF increased as a function of the mean spike count, and the parameters of this relationship did not change with attentional selection.

Relationships between ganglion cell dendritic structure and retinal topography in the cat.

The morphology of ganglion cell dendritic trees varies across the cat retina. Evidence is presented that the variation in two attributes of ganglion cell dendritic structure can be accounted for by specific aspects of the topography of the adult and developing retina. The first attribute considered was the displacement of the center of the dendritic field from the cell body in the plane of the retina. The results of this study provide evidence that most ganglion cell dendritic fields are displaced away from neighboring cells, i.e., down the retinal ganglion cell density gradient. Because of the systematic dendritic displacement locally, the centers of the dendritic fields are arranged in a more precise mosaic than are their cell bodies. The second attribute considered was the elongation and orientation of the dendritic fields. From approximately embryonic day 50 to postnatal day 10 the cat retina undergoes a process of maturation (reviewed by Rapaport and Stone: Neuroscience 11:289-301, '84) that begins at the area centralis and spreads over the retina in a horizontally elongated wave. We found that the elongation and orientation of retinal ganglion cell dendritic fields is significantly correlated with the shape of the wave of maturation. The orientation of a dendritic field is not predicted by the direction of its displacement nor is it directly related to the distribution of neighboring retinal ganglion cells. These results indicate that the displacement of a ganglion cell's dendritic field from its cell body results from mechanisms different from those responsible for the orientation of the dendritic field. Factors that may be responsible for these two attributes of ganglion cell dendritic morphology are discussed.

Structural basis of orientation sensitivity of cat retinal ganglion cells.

We investigated the structural basis of the physiological orientation sensitivity of retinal ganglion cells (Levick and Thibos, '82). The dendritic fields of 840 retinal ganglion cells labeled by injections of horseradish peroxidase into the dorsal lateral geniculate nucleus (LGNd) or optic tracts of normal cats. Siamese cats, and cat deprived of patterned visual experience from birth by monocular lid-suture (MD) were studied. Mathematical techniques designed to analyze direction were used to find the dendritic field orientation of each cell. Statistical techniques designed for angular data were used to determine the relationship between dendritic field orientation and angular position on the retina (polar angle). Our results indicate that 88% of retinal ganglion cells have oriented dendritic fields and that dendritic field orientation is related systematically to retinal position. In all regions of retina more that 0.5 mm from the area centralis the dendritic fields of retinal ganglion cells are oriented radially, i.e., like the spokes of a wheel having the area centralis at its hub. This relationship was present in all animals and cell types studied and was strongest for cells located close to the horizontal meridian (visual streak) of the retina. Retinal ganglion cells appear to be sensitive to stimulus orientation because they have oriented dendritic fields.

Relationship between preferred orientation and receptive field position of neurons in extrastriate cortex (area 19) in the cat.

Orientation sensitivity is a characteristic of most retinal ganglion cells (Levick and Thibos, '82), most relay cells in the dorsal lateral geniculate nucleus (Vidyasagar and Urbas, '82), and most neurons in the visual cortex (Hubel and Wiesel, '62) in the cat. In the retina there is a systematic relationship between receptive field position (polar angle) and preferred orientation. Outside of the area centralis most retinal ganglion cells respond best to stimuli oriented radially, i.e., oriented parallel to the line connecting their receptive fields to the area centralis (Levick and Thibos, '82). This relationship is strongest along the horizontal meridian (the visual streak) and appears to reflect the innate, radial orientation of retinal ganglion cell dendritic fields (Leventhal and Schall, '83). A relationship between preferred orientation and polar angle also exists in cat striate cortex; outside of the area centralis representation most cells respond best to lines oriented radially. This relationship is strongest for S-type cells, the most orientation-selective cells, and cells in regions representing the horizontal meridian (Leventhal, '83). To determine if similar relationships exist in cat extrastriate cortex, the preferred orientations and receptive field positions of 226 neurons in area 19 were studied. We find that, as in area 17, most area 19 cells outside of the representation of the area centralis respond best to lines oriented radially; this relationship is strongest for the cells having the narrowest receptive fields and in regions subserving the horizontal meridian. Unlike in striate cortex, in area 19 the relationship between preferred orientation and polar angle is not dependent upon cell type (S or C) or to the degree of orientation sensitivity exhibited. Also, in area 19, but not in area 17, the relationship between preferred orientation and polar angle fails for the cells having the widest receptive fields.(ABSTRACT TRUNCATED AT 250 WORDS)

Ganglion cell dendritic structure and retinal topography in the rat.

The dendritic field size, the distribution of the dendrites relative to the cell body, and the overall shape of the dendritic field of type I ganglion cells in the rat retina were analyzed. These features of neuronal structure were related to the topography of the rat retina. As in the cat, the cell bodies of type I ganglion cells are arranged in a nonrandom mosaic. Previous work has demonstrated that the density of type I cells in the rat retina does not covary with the density of all ganglion cells. Type I dendritic field size varies over the retina; the increase in dendritic field size is accounted for better by the decrease in type I density than by the decrease in overall ganglion cell density. The center of the dendritic field of most type I cells is displaced in the plane of the retina from the cell body. Unlike in carnivore retina (Schall and Leventhal: J. Comp. Neurol. 257:149-159, '87), the dendritic fields in the rat are not displaced down the ganglion cell density gradient. Rather, there is a tendency for the dendritic trees, especially in temporal retina, to be displaced toward dorsal retina. Most of the dendritic fields are elongated, but the degree of elongation is less than that observed in carnivore or primate retina. Unlike in carnivore and primate retina (Leventhal and Schall: J. Comp. Neurol. 220:465-475, '83; Schall et al.: Brain Res. 368:18-23, '86), there is no relationship between dendritic tree orientation and position relative to any point on the retina in the rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Morphology, central projections, and dendritic field orientation of retinal ganglion cells in the ferret.

Retinal ganglion cells were studied in pigmented ferrets that received small electrophoretic injections of horseradish peroxidase (HRP) into the dorsal lateral geniculate nucleus (LGNd) or optic tract. Ferret retina contains a number of types of retinal ganglion cells of which the relative cell body sizes, dendritic field structures, and central projections correspond closely to those of retinal ganglion cell types in the cat. Ferret retina contains about the same proportion of alphalike cells, a lower proportion of betalike cells, and thus a high proportion of other types of ganglion cells than cat retina. Ferret retina has a visual streak and somewhat weaker area centralis than cat retina. Changes in ganglion cell morphology associated with eccentricity are less pronounced in the ferret than in the cat. The adult ferret retina is about 12.5 mm in diameter, and the nasotemporal division is about 2.7 mm from the temporal margin. Interestingly, virtually all alpha cells in the pigmented ferrets studied projected contralaterally. Studies of infant ferrets indicate that 4 days after birth (P4) the area of ferret retina is 25% that of the adult. The neonatal ferret retina contains numerous small, densely packed cells in the presumptive ganglion cell layer. At P4 these cells appear to be uniformly distributed across the retina. The area centralis and visual streak are not obvious as late as 8 days after birth.

Neural basis of saccade target selection.

Saccade target selection must be understood in relation to the obvious fact that vision naturally occurs in a continuous cycle of fixations interrupted by gaze shifts. The guidance of eye movements requires information about what is where in the visual field. The identities of objects are derived from their visible features. Single neurons in the visual system represent the presence of specific features by the level of activation; the reliability of the discriminating signal from single neurons varies over time. Each point in the visual field is represented by many populations of neurons activated by all types of features. Topographic representations are found throughout the visual and oculomotor systems; neighboring neurons tend to represent similar visual field locations or saccades. Selecting one out of many stimuli to which to direct gaze requires comparing stimulus attributes across the visual field. The existence of retinotopic maps of the visual field makes possible local interactions to implement such comparisons /41/. For example, a lateral inhibition network can extract the location of the most conspicuous stimulus in the visual field /30,40,81/. Coordinated with this parallel visual processing is activation in structures responsible for producing the movement such as FEF and the superior colliculus. A saccade is produced when the neurons at one location within the motor maps become sufficiently active. One job of visual processing, then, is to ensure that only one site within a movement map becomes activated. This is done when the neurons signalling the location of the desired target develop enhanced activation while the neurons responding to other locations are attenuated. Saccade target selection often converts an initially ambiguous pattern of neural activation into a pattern that reliably signals one target location. The ambiguity may be reduced through prior knowledge of the likely target location or identity, and extraretinal signals reflecting such expectations can modulate the responsiveness of afferent visual neurons. Specifying the metrics of a saccade and triggering the movement are coordinated but dissociable processes. Speed-accuracy trade-offs can thereby be produced allowing the visuomotor system to produce a saccade that is inaccurate because it is premature relative to the target selection process. While there are many gaps in our knowledge, the questions to ask seem reasonably clear. Because saccade target selection involves visual processing and eye movement programming combined with mnemonic influences, only continued experimental ingenuity will disentangle the various and variable contributions of individual neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Continuous processing in macaque frontal cortex during visual search.

A central issue in mental chronometry is whether information is transferred between processing stages such as stimulus evaluation and response preparation in a continuous or discrete manner. We tested whether partial information about a stimulus influences the response stage by recording the activity of movement-related neurons in the frontal eye field of macaque monkeys performing a conjunction visual search and a feature visual search with a singleton distractor. While movement-related neurons were activated maximally when the target of the search array was in their movement field, they were also activated for distractors even though a saccade was successfully made to the target outside the movement field. Most importantly, the level of activation depended on the properties of the distractor, with greater activation for distractors that shared a target feature or were the target during the previous session during conjunction search, and for the singleton distractor during feature search. These results support the model of continuous information processing and argue against a strictly discrete model.

Functional streams in occipito-frontal connections in the monkey.

It is known that the prestriate cortical regions that project to area LIP in parietal cortex and to areas TEO and TE in temporal cortex are mostly separated. Two separate streams of information transfer from occipital cortex can this be distinguished. We wished to determine whether the parietal and temporal streams remain segregated in their projections to frontal cortex. Paired injections of retrograde fluorescent tracers were placed in parietal and temporal cortex, or in the lateral and medial parts of the frontal eye field (FEF). The cortical regions containing retrogradely labeled cells were reconstructed in two-dimensional maps. The results show that temporal cortex mainly projects to lateral FEF (area 45). Parietal cortex sends projections to medial FEF (area 8a) and to lateral FEF, as well as to area 46. Thus, the parietal and temporal streams converge in lateral FEF. Most of the occipital regions projecting to medial FEF are the same as those projecting to parietal cortex, whereas lateral FEF receives afferents from the same occipital regions as those sending projections to temporal cortex. Thus, one can distinguish two interconnected networks. One is associated with the inferotemporal cortex and includes areas of the ventral bank and fundus of the superior temporal sulcus (STS), lateral FEF and ventral prestriate cortex. This network emphasizes central vision, small accades and form recognition. The other network is linked to cortex of the intraparietal sulcus. It consists of areas of the upper bank and fundus of STS, medial FEF and dorsal prestriate cortex. These areas encode peripheral visual field and are active during large saccades.

Normal somatotopy in SI of a tyrosinase-negative albino cat.

Because of known abnormalities in both the visual and auditory pathways of tyrosinase-negative albino cats, we mapped the primary somatosensory cortex (SI) in one such cat electrophysiologically. We detected absolutely no sign of abnormality in terms of somatotopy, and conclude that if anomalies do exist in the albino somatosensory system, they are either very subtle or lie outside SI.