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.

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.

Correlates of motor planning and postsaccadic fixation in the macaque monkey lateral geniculate nucleus.

There is significant controversy regarding the ability of the primate visual system to construct stable percepts from a never-ending stream of brief fixations and rapid saccadic eye movements. In this study, we examined the timing and occurrence of perisaccadic modulation of LGN single-unit activity in awake-behaving macaque monkeys while they made spontaneous saccades in the dark and made visually guided saccades to discrete stimuli located outside the receptive field. Our hypothesis was that the activity of LGN cells is modulated by efference copies of motor plans to produce saccadic eye movements and that this modulation depends neither on the presence of feedforward visual information nor on a corollary discharge of signals directing saccadic eye movements. On average, 25% of LGN cells demonstrated significant perisaccadic modulation. This modulation consisted of a moderate suppression of activity that began more than 100 ms prior to the initiation of a saccadic eye movement and continued beyond the termination of the saccadic eye movement. This suppression was followed by a large enhancement of activity after the eyes arrived at the next fixation. Although members of all three LGN relay cell classes (magnocellular, parvocellular, and koniocellular) demonstrated significant saccade-related suppression and enhancement of activity, more cells demonstrated postsaccadic enhancement (25%) than perisaccadic suppression (17%). In no case did the timing of the modulation coincide directly with saccade duration. The degree of modulation observed did not vary with LGN cell class, LGN receptive field center location, center sign (ON-center or OFF-center), or saccade latency or velocity. The time course of modulation did, however, vary with saccade size such that suppression was longer for longer saccades. The fact that activity from a percentage of LGN cells from all cell classes was modulated in relationship to saccadic eye movements in the absence of direct visual stimulation suggests that this modulation is a general phenomenon not tied to specific types of visual stimuli. Similarly, because the onset of the modulation preceded eye movements by more than 100 ms, it is likely that this modulation reflects higher order motor-planning rather than a corollary of mechanisms in direct control of eye movements themselves. Finally, the fact that the largest modulation is a postsaccadic enhancement of activity may suggest that perisaccadic modulations are designed more for the facilitation of visual information processing once the eyes land at a new location than for filtering unwanted visual stimuli.

Dynamic dissociation of visual selection from saccade programming in frontal eye field.

Previous studies of visually responsive neurons in the frontal eye fields have identified a selection process preceding saccades during visual search. The goal of this experiment was to determine whether the selection process corresponds to the selection of a conspicuous stimulus or to preparation of the next saccade. This was accomplished with the use of a novel task, called search-step, in which the target of a singleton visual search array switches location with a distracter on random trials. The target step trials created a condition in which the same stimulus yielded saccades either toward or away from the target. Visually responsive neurons in frontal eye field selected the current location of the conspicuous target even when gaze shifted to the location of a distractor. This dissociation demonstrates that the selection process manifest in visual neurons in the frontal eye field may be an explicit interpretation of the image and not an obligatory saccade command.

Pre-excitatory pause in frontal eye field responses.

We report a new characteristic of the presaccadic activity of the neurons in the frontal eye field of macaque monkeys. A fraction of neurons exhibited a significant pause in discharge rate preceding the excitatory visual or movement-related response. This pre-excitatory pause, which has been observed in striate and extrastriate visual areas, may represent a resetting of neural activation for detailed visual processing or saccade preparation.

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.

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.

Neural basis of deciding, choosing and acting.

The ability and opportunity to make decisions and carry out effective actions in pursuit of goals is central to intelligent life. Recent research has provided significant new insights into how the brain arrives at decisions, makes choices, and produces and evaluates the consequences of actions. In fact, by monitoring or manipulating specific neurons, certain choices can now be predicted or manipulated.

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.

Performance monitoring by the supplementary eye field.

Intelligent behaviour requires self-control based on the consequences of actions. The countermanding task is designed to study self-control; it requires subjects to withhold planned movements in response to an imperative stop signal, which they can do with varying success. In humans, the medial frontal cortex has been implicated in the supervisory control of action. In monkeys, the supplementary eye field in the dorsomedial frontal cortex is involved in producing eye movements, but its precise function has not been clarified. To investigate the role of the supplementary eye field in the control of eye movements, we recorded neural activity in macaque monkeys trained to perform an eye movement countermanding task. Distinct groups of neurons were active after errors, after successful withholding of a partially prepared movement, or in association with reinforcement. These three forms of activation could not be explained by sensory or motor factors. Our results lead us to put forward the hypothesis that the supplementary eye field contributes to monitoring the context and consequences of eye movements.

Neural control of behavior: countermanding eye movements.

Understanding the self-control of action entails knowledge about how actions are initiated, how planned actions are canceled and how the consequences of actions are registered. We have investigated neural correlates of these processes using the countermanding paradigm--a task that required subjects to occasionally cancel a planned speeded response, and an analysis that provides an estimate of the time needed to cancel a planned movement. By monitoring the activity of single neurons in the frontal cortex of macaque monkeys performing this task we have distinguished signals responding to the visual stimuli, other signals that control the production of movements, and still other signals that seem to monitor behavior.

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.

Antecedents and correlates of visual detection and awareness in macaque prefrontal cortex.

We have investigated the neural basis of visual detection in monkeys trained to report the presence or absence of a visual stimulus that was rendered intermittently detectable by backward masking. Neurons were recorded in the frontal eye field (FEF), an area located in prefrontal cortex that is involved in converting the outcome of visual processing into a command to shift gaze. The behavioral and neuronal data were analyzed in terms of signal detection theory. We found that the initial visual responses in FEF provided signals that could form the basis for correct or erroneous detection of the target. A later phase of prolonged elevated activity occurred in many visual neurons and all movement neurons that was highly correlated with the monkey's report of target presence. When observed in movement cells that project to oculomotor structures, this period of activation is interpreted as a motor command leading to the behavioral response. When observed in visual cells that do not project to oculomotor structures, the later period of activation does not admit to the motor command interpretation. Because the visual neurons likely contribute to the feedback pathway to visual cortical areas, we hypothesize that the later selective activation in the prefrontal visual neurons interacts with ongoing activity in visual cortical areas contributing to the process by which a particular sensory representation receives enhanced activation and thereby engages attention and awareness.

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.

Neural selection and control of visually guided eye movements.

We review neural correlates of perceptual and motor decisions, examining whether the time they occupy explains the duration and variability of behavioral reaction times. The location of a salient target is identified through a spatiotemporal evolution of visually evoked activation throughout the visual system. Selection of the target leads to stochastic growth of movement-related activity toward a fixed threshold to generate the gaze shift. For a given image, the neural concomitants of perceptual processing occupy a relatively constant interval so that stochastic variability in response generation introduces additional variability in reaction times.

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.

Saccade target selection in macaque during feature and conjunction visual search.

To gain insight into how vision guides eye movements, monkeys were trained to make a single saccade to a specified target stimulus during feature and conjunction search with stimuli discriminated by color and shape. Monkeys performed both tasks at levels well above chance. The latencies of saccades to the target in conjunction search exhibited shallow positive slopes as a function of set size, comparable to slopes of reaction time of humans during target present/absent judgments, but significantly different than the slopes in feature search. Properties of the selection process were revealed by the occasional saccades to distractors. During feature search, errant saccades were directed more often to a distractor near the target than to a distractor at any other location. In contrast, during conjunction search, saccades to distractors were guided more by similarity than proximity to the target; monkeys were significantly more likely to shift gaze to a distractor that had one of the target features than to a distractor that had none. Overall, color and shape information were used to similar degrees in the search for the conjunction target. However, in single sessions we observed an increased tendency of saccades to a distractor that had been the target in the previous experimental session. The establishment of this tendency across sessions at least a day apart and its persistence throughout a session distinguish this phenomenon from the short-term (<10 trials) perceptual priming observed in this and earlier studies using feature visual search. Our findings support the hypothesis that the target in at least some conjunction visual searches can be detected efficiently based on visual similarity, most likely through parallel processing of the individual features that define the stimuli. These observations guide the interpretation of neurophysiological data and constrain the development of computational models.

Signal timing across the macaque visual system.

The onset latencies of single-unit responses evoked by flashing visual stimuli were measured in the parvocellular (P) and magnocellular (M) layers of the dorsal lateral geniculate nucleus (LGNd) and in cortical visual areas V1, V2, V3, V4, middle temporal area (MT), medial superior temporal area (MST), and in the frontal eye field (FEF) in individual anesthetized monkeys. Identical procedures were carried out to assess latencies in each area, often in the same monkey, thereby permitting direct comparisons of timing across areas. This study presents the visual flash-evoked latencies for cells in areas where such data are common (V1 and V2), and are therefore a good standard, and also in areas where such data are sparse (LGNd M and P layers, MT, V4) or entirely lacking (V3, MST, and FEF in anesthetized preparation). Visual-evoked onset latencies were, on average, 17 ms shorter in the LGNd M layers than in the LGNd P layers. Visual responses occurred in V1 before any other cortical area. The next wave of activation occurred concurrently in areas V3, MT, MST, and FEF. Visual response latencies in areas V2 and V4 were progressively later and more broadly distributed. These differences in the time course of activation across the dorsal and ventral streams provide important temporal constraints on theories of visual processing.

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.