The effect of stimulus-response compatibility on cortical motor activation.

Stimulus-response compatibility (SRC) is a general term describing the relationship between a triggering stimulus and its associated motor response. The relationship between stimulus and response can be manipulated at the level of the set of stimulus and response characteristics (set-level) or at the level of the mapping between the individual elements of the stimulus and response sets (element-level). We used functional magnetic resonance imaging (fMRI) to investigate the effects of SRC on functional activation in cortical motor areas. Using behavioral tasks to separately evaluate set- and element-level compatibility, and their interaction, we measured the volume of functional activation in 11 cortical motor areas, in the anterior frontal cortex, and in the superior temporal lobe. Element-level compatibility effects were associated with significant activation in the pre-supplementary motor area (preSMA), the dorsal (PMd) and ventral (PMv) premotor areas, and the parietal areas (inferior, superior, intraparietal sulcus, precuneus). The activation was lateralized to the right hemisphere for most of the areas. Set-level compatibility effects resulted in significant activation in the inferior frontal gyri, anterior cingulate and cingulate motor areas, the PMd, PMv, preSMA, the parietal areas (inferior, superior, intraparietal sulcus, precuneus), and in the superior temporal lobe. Activation in the majority of these areas was lateralized to the left hemisphere. Finally, there was an interaction between set and element-level compatibility in the middle and superior frontal gyri, in an area co-extensive with the dorsolateral prefrontal cortex, suggesting that this area provided the neural substrate for common processing stages, such as working memory and attention, which are engaged when both levels of SRC are manipulated at once.

Choice and stimulus-response compatibility affect duration of response selection.

In general, for movements to visual targets, response times increase with the number of possible response choices. However, this rule only seems to hold when an incompatibility exists between the stimulus and response, and is absent when stimulus and response are highly compatible (e.g., when reaching toward the location of the stimulus). Stimulus-response (S-R) compatibility can be manipulated either at the level of stimulus and response characteristics, or at the level of the mapping between elements of the stimulus and response sets. The current study was undertaken to determine the extent of the interaction between choice and each of these two levels of S-R compatibility. Subjects used a joystick to move a cursor in response to two, four or eight possible cues, with S-R compatibility manipulated along two dimensions (type of stimulus, and mapping between stimulus and response sets) in separate blocks of trials. Choice effects were absent when S-R relationships were highly compatible, moderate when incompatible in either of the two dimensions, and greatest when incompatible in both dimensions. These results indicate that choice affects response selection at each stage in the decoding of S-R relationships. Similar but smaller effects were seen for trials in which the stimulus was the same as that presented in the immediately preceding trial, suggesting that repeated stimulus-response transformations are faster and more efficient due to the priming effects of previous trials.

Effects of movement predictability on cortical motor activation.

Humans have the ability to make motor responses to unpredictable visual stimuli, and do so as a matter of course on a daily basis. We used functional magnetic resonance imaging (fMRI) to examine the neural substrate of this behavior in six cortical motor areas. We found that five of these areas (premotor, cingulate, supplementary motor area, pre-supplementary motor area, and superior parietal lobule) showed increased activation in association with an unpredictable behavior compared to a predictable one; only the motor cortex remained unchanged. There was also a quantitative relation between the response time and functional activation in the premotor and cingulate cortex. There was less activation across all the motor areas with repetition of the motor tasks. With the exception of the pre-supplementary motor area, all areas were significantly lateralized, with a greater volume of activation in the hemisphere contralateral to the performing hand. In addition, a left hemisphere dominance was found in the activation of motor cortex and supplementary motor areas. Our results suggest that activation in motor areas is differentially and quantitatively related to higher order aspects of motor behavior such as movement predictability.

Interaction of the two frontal eye fields before saccade onset.

A normal environment often contains many objects of interest that compete to attract our gaze. Nevertheless, instead of initiating a flurry of conflicting signals, central populations of oculomotor neurons always seem to agree on the destination of the next saccade. How is such a consensus achieved? In a unit recording and microstimulation study on trained monkeys, we sought to elucidate the mechanism through which saccade-related cells in the frontal eye fields (FEF) avoid issuing competing commands. Presaccadic neuronal activity was recorded in one FEF while stimulating the contralateral FEF with low-intensity currents that evoked saccades. When an eye-movement cell was isolated, we determined: the movement field of the cell, the cell's response to contralateral FEF microstimulation, the cell's response when the evoked saccade was in the preferred direction of the cell (using the collision technique to deviate appropriately the evoked saccade vector), and the cell's response to a stimulation applied during a saccade in the cell's preferred direction, to reveal a possible inhibitory effect. Complete results were obtained for 71 stimulation-recording pairs of FEF sites. The unit responses observed were distributed as follows: 35% of the cells were unaffected, 37% were inhibited, and 20% excited by contralateral stimulation. These response types depended on the site of contralateral stimulation and did not vary when saccades were redirected by collision. This invariant excitation or inhibition of cells, seemingly due to hardwired connections, depended on the angular difference between their preferred vector and the vector represented by the cells stimulated. By contrast, 8% of the cells were either activated or inhibited depending on the vector of the saccade actually evoked by collision. These results suggest that the consensus between cells of oculomotor structures at the time of saccade initiation is implemented by functional connections such that the cells that command similar movements mutually excite each other while silencing those that would produce conflicting movements. Such a rule would be an effective implementation of a winner-take-all mechanism well suited to prevent conflicts.

Functional activation in motor cortex reflects the direction and the degree of handedness.

Handedness is the clearest example of behavioral lateralization in humans. It is not known whether the obvious asymmetry manifested by hand preference is associated with similar asymmetry in brain activation during movement. We examined the functional activation in cortical motor areas during movement of the dominant and nondominant hand in groups of right-handed and left-handed subjects and found that use of the dominant hand was associated with a greater volume of activation in the contralateral motor cortex. Furthermore, there was a separate relation between the degree of handedness and the extent of functional lateralization in the motor cortex. The patterns of functional activation associated with the direction and degree of handedness suggest that these aspects are independent and are coded separately in the brain.

Manual interception of moving targets. I. Performance and movement initiation.

We investigated the capacities of human subjects to intercept moving targets in a two-dimensional (2D) space. Subjects were instructed to intercept moving targets on a computer screen using a cursor controlled by an articulated 2D manipulandum. A target was presented in 1 of 18 combinations of three acceleration types (constant acceleration, constant deceleration, and constant velocity) and six target motion times, from 0.5 to 2.0 s. First, subjects held the cursor in a start zone located at the bottom of the screen along the vertical meridian. After a pseudorandom hold period, the target appeared in the lower left or right corner of the screen and traveled at 45 degrees toward an interception zone located on the vertical meridian 12.5 cm above the start zone. For a trial to be considered successful, the subject's cursor had to enter the interception zone within 100 ms of the target's arrival at the center of the interception zone and stay inside a slightly larger hold zone. Trials in which the cursor arrived more than 100 ms before the target were classified as "early errors," whereas trials in which the cursor arrived more than 100 ms after the target were classified as "late errors." Given the criteria above, the task proved to be difficult for the subjects. Only 41.3% (1080 out of 2614) of the movements were successful, whereas the remaining 58.7% were temporal (i.e., early or late) errors. A large majority of the early errors occurred in trials with decelerating targets, and their percentage tended to increase with longer target motion times. In contrast, late errors occurred in relation to all three target acceleration types, and their percentage tended to decrease with longer target motion times. Three models of movement initiation were investigated. First, the threshold-distance model, originally proposed for optokinetic eye movements to constant-velocity visual stimuli, maintains that response time is composed of two parts, a constant processing time and the time required for the stimulus to travel a threshold distance. This model only partially fit our data. Second, the threshold-tau model, originally proposed as a strategy for movement initiation, assumes that the subject uses the first-order estimate of time-to-contact (tau) to determine when to initiate the interception movement. Similar to the threshold distance model, the threshold-tau model only partially fit the data. Finally, a dual-strategy model was developed which allowed for the adoption of either of the two strategies for movement initiation; namely, a strategy based on the threshold-distance model ("reactive" strategy) and another based on the threshold-tau model ("predictive" strategy). This model provided a good fit to the data. In fact, individual subjects preferred to use one or the other strategy. This preference was allowed to be manifested at long target motion times, whereas shorter target motion times (i.e., 0.5 s and 0.8 s) forced the subjects to use only the reactive strategy.

The use of egocentric and exocentric location cues in saccadic programming.

Theoretically, the location of a visual target can be encoded with respect to the locations of other stimuli in the visual image (exocentric cues), or with respect to the observer (egocentric cues). Egocentric localization in the oculomotor system has been shown to rely on an internal representation of eye position that inaccurately encodes the time-course of saccadic eye movements, resulting in the mislocalization of visual targets presented near the time of a saccade. In the present investigation, subjects were instructed to localize perisaccadic stimuli in the presence or absence of a visual stimulus that could provide exocentric location information. Saccadic localization was more accurate in the presence of the exocentric cue, suggesting that localization is based on a combination of exocentric and egocentric cues. These findings indicate the need to reassess previously reported neurophysiological studies of spatial accuracy and current models of oculomotor control, which have focused almost exclusively on the egocentric localization abilities of the brain.

Haptic localization and the internal representation of the hand in space.

As the hand actively explores the environment, contact with an object leads to neuronal activity in the topographic maps of somatosensory cortex. However, the brain must combine this somatotopically encoded tactile information with an internal representation of the hand's location in space if it is to determine the position of the object in three-dimensional space (3-D haptic localization). To investigate the fidelity of this internal representation in human subjects, a small tactual stimulator, light enough to be worn on the subject's hand, was used to present a brief mechanical pulse (6-ms duration) to the right index finger before, during, or after a fast, visually evoked movement of the right hand. In experiment 1, subjects responded by pointing to the perceived location of the mechanical stimulus in 3-D space. Stimuli presented shortly before or during the visually evoked movement were systematically mislocalized, with the reported location of the stimulus approximately equal to the location occupied by the hand 90 ms after stimulus onset. This pattern of errors indicates a representation of the movement that fails to account for the change in the hand's location during somatosensory delays and, in some subjects, inaccurately depicts the velocity of the actual movement. In experiment 2, subjects were instructed to verbally indicate the perceived temporal relationship of the stimulus and the visually evoked movement (i.e., by reporting whether the stimulus was presented "before," "during," or "after" the movement). On average, stimuli presented in the 38-ms period before movement onset were more likely to be perceived as having occurred during rather than before the movement. Similarly, stimuli in the 145-ms period before movement termination were more likely to be perceived as having occurred after rather than during the movement. The analogous findings of experiments 1 and 2 indicate that the same inaccurate representation of dynamic hand position is used to both localize tactual stimuli in 3-D space and construct the perception of arm movement.

Oculomotor localization relies on a damped representation of saccadic eye displacement in human and nonhuman primates.

The oculomotor system has long been thought to rely on an accurate representation of eye displacement or position in a successful attempt to reconcile a stationary target's retinal instability (caused by motion of the eyes) with its corresponding spatial invariance. This is in stark contrast to perceptual localization, which has been shown to rely on a sluggish representation of eye displacement, achieving only partial compensation for the retinal displacement caused by saccadic eye movements. Recent studies, however, have begun to case doubt on the belief that the oculomotor system possess a signal of eye displacement superior to that of the perceptual system. To verify this, five humans and one monkey (Macaca nemestrina) served as subjects in this study of oculomotor localization abilities. Subjects were instructed to make eye movements, as accurately as possible, to the locations of three successive visual stimuli. Presentation of the third stimulus (2-ms duration) was timed so that it fell before, during, or after the subject's saccade from the first stimulus to the second. Localization errors in each subject (human and nonhuman) were consistent with the hypothesis that the oculomotor system has access to only a damped representation of eye displacement--a representation similar to that found in perceptual localization studies.

How the frontal eye field can impose a saccade goal on superior colliculus neurons.

Saccades were electrically evoked from the frontal eye field (FEF) of two trained monkeys while saccade-cells were recorded from the intermediate layers of the superior colliculus (SC). We found that FEF microstimulation, eliciting saccades of a given vector, excited SC saccade-cells encoding the same vector and inhibited all others. Such a mechanism can prevent competing commands from arising simultaneously in different structures.

The frontal eye field provides the goal of saccadic eye movement.

Microstimulation of oculomotor regions in primate cortex normally evokes saccadic eye movements of stereotypic directions and amplitudes. The fixed-vector nature of the evoked movements is compatible with the creation of either an artificial retinal or motor error signal. However, when microstimulation is applied during an ongoing natural saccade, the starting eye position of the evoked movement differs from the eye position at stimulation onset (due to the latency of the evoked saccade). An analysis of the effect of this eye position discrepancy on the trajectory of the eventual evoked saccade can clarify the oculomotor role of the structure stimulated. The colliding saccade paradigm of microstimulation was used in the present study to investigate the type of signals conveyed by visual, visuomovement, and movement unit activities in the primate frontal eye field. Colliding saccades elicited from all sites were found to compensate for the portion of the initial movement occurring between stimulation and evoked movement onset, plus a portion of the initial movement occurring before stimulation. This finding suggests that activity in the frontal eye field encodes a retinotopic goal that is converted by a downstream structure into the vector of the eventual saccade.

Saccades can be aimed at the spatial location of targets flashed during pursuit.

1. If an eccentric, stationary target is flashed while a subject is performing an eye movement in the dark, can this subject make a saccade to the location in space where the target briefly appeared? Different predictions result from alternative hypotheses regarding the manner in which saccade goals are determined. Retinal error being defined as the vector from the eye position at the time of the flash to the position of the target, the retinal-error hypothesis predicts that the saccade vector will be equal to the retinal-error vector. This hypothesis assumes that the oculomotor system ignores the eye displacement between target presentation and saccade. If so, the target will be missed. In contrast, the spatial-error hypothesis predicts that the eye displacement is taken into account by the brain to calculate the target's physical location to which, therefore, a correct saccade could be aimed. 2. At issue is the generality of a fundamental principle of ocular targeting. Previous studies have established that, if the movement is saccadic, eye displacement is used by the oculomotor system to calculate the target's physical location. In the case of pursuit, perceptual experiments on humans suggest that eye displacement is taken into account although its velocity is underestimated. However, in a recent study McKenzie and Lisberger reported that saccade trajectories starting during pursuit conform to the retinal error hypothesis. In other words, velocity underestimation is close to 100%. 3. Although McKenzie and Lisberger's results are very clear, they might have depended on particular experimental conditions. The issue was reinvestigated in a situation facilitating the discrimination of stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Interactions between natural and electrically evoked saccades. II. At what time is eye position sampled as a reference for the localization of a target?

Electrical microstimulation was applied at brain sites (thalamic internal medullary lamina complex and superficial layers of superior colliculus) of alert, trained monkeys to evoke fixed-vector saccades. When the stimulation was timed to occur during or after an eye movement, the evoked saccade had a modified trajectory, compensating for, at least, the last portion of the ongoing eye movement. The hypothesis proposed to explain this compensatory effect (Schlag-Rey et al. 1989) is that the electrical stimulation produces a saccade by generating a signal, equivalent to a retinal error, specifying the saccade goal at a fixed location with respect to some eye position (called reference eye position). If the eyes are moving at the time of stimulation, the reference eye position lies somewhere along the trajectory of the ongoing movement. In the present study, we tried to determine this reference eye position, and deduce from it the instant at which the goal was specified. A significant timing difference was observed between thalamic and collicular stimulations. The goal appeared to be referred to an eye position existing at stimulation onset in superior colliculus (SC), and 35-65 ms before stimulation onset in central thalamus. In the latter case, the results suggest that the evoked saccade was aimed at the spatial location that the brain computed by summing a retinal error signal (evoked by stimulation) with the eye position at the time such a signal would have been elicited by a real target. In contrast, the collicular results suggest that the evoked saccade was directed to the retinal location specified by the retinal error signal. The findings imply that if the eyes are not steady while the target position is calculated, signals conveyed in the superficial layers of SC (in contrast to the thalamus) cannot direct the eyes correctly to a visual target.