Immediate neural plasticity shapes motor performance.

The consolidation of motor skills necessitates long-lasting changes in the nervous system. For the most part, plasticity has been documented in motor systems after training and long-term adaptation. However, there has been no demonstration of immediate neural changes associated with the rapid adaptation of motor behavior required to interact with a dynamic environment. To address this issue, we explored the changes in performance (reaction time) of rhesus monkeys that executed saccadic eye movements to one of two visual stimuli while monitoring the preparatory activity of neurons in the superior colliculus, a structure close to the motor output. Similar to the well established sequential effects observed in human manual responses, each monkey displayed reaction times to target locations that were organized in a sequential pattern, becoming progressively shorter with each preceding repeated movement and longer with each preceding nonrepeated movement. This sequential pattern of performance modification was associated with concordant changes in the preparatory activity of superior colliculus neurons in advance of the saccadic target presentation. These data indicate that neural properties are continuously shaped by use-related experience in a manner consistent with the progressive adaptation of motor behavior.

Time course of a repetition effect on saccadic reaction time in non-human primates.

Repeated training in a stimulus response task can lead to adaptive changes in the resulting behavior. Using a simple saccade task, we investigated the effect that the location of the target in the preceding trial had on the saccadic reaction time (SRT) of the current trial. To determine the time course of this effect, we varied the intertrial interval (ITI). Finally, we examined the pretarget discharge of single neurons in the intermediate layers of the superior colliculus (SC) during the task. Our data reveal that monkeys have a robust repetition effect in which there was an overall decrease in SRT and increase in SC pretarget activity when the target of the previous saccade was in the same location as that of the current trial. Additionally, we have shown a robust time course of this repetition effect, revealing that it exists for only a limited amount of time.

Saccadic probability influences motor preparation signals and time to saccadic initiation.

One must be prudent when selecting potential saccadic targets because the eyes can only move to one location at a time, yet movements must occur quickly enough to permit interaction with a rapidly changing world. This process of efficiently acquiring relevant targets may be aided by advanced planning of a movement toward an upcoming target whose location is gathered via environmental cues or situational experience. We studied how saccadic reaction times (SRTs) and early pretarget neuronal activity covaried as a function of saccadic probability. Monkeys performed a saccadic task in which the probability of the required saccade being directed into the response field of a neuron varied systematically between blocks of trials. We recorded simultaneously the early pretarget activity of saccade-related neurons in the intermediate layers of the superior colliculus. We found that, as the likelihood of the saccade being generated into the response field of the neuron increased, the level of neuronal activity preceding target presentation also increased. Our data suggest that this early activity codes motor preparation because its activity was related to not only the metrics but also the timing of the saccade, with 94% (29/31) of the neurons tested having significant negative correlations between discharge rate and SRT. This view is supported by cases in which exceptionally high levels of pretarget activity were associated with anticipatory saccades into the response field of a neuron that occurred in advance of the target being presented. This study demonstrates how situational experience can expedite motor behavior via the advanced preparation of motor programs.

A neural correlate for the gap effect on saccadic reaction times in monkey.

1. The reduction in saccadic reaction time associated with the introduction of a period of darkness between the disappearance of an initial fixation point and the appearance of a new peripheral saccade target is known as the gap effect. Fixation cells in the rostral pole of the monkey superior colliculus have been implicated in the control of active visual fixation and suppressing saccadic eye movements. To determine whether specific variations of fixation cell discharge was correlated to the gap effect, we recorded the activity of fixation cells while a monkey generated visually guided saccades with various temporal gaps between the disappearance of the initial fixation point and the appearance of a peripheral saccade target. 2. The saccadic reaction times of the monkey were shortest with gap durations of 200-300 ms and increased with shorter or longer gap durations. The activity of fixation cells followed a similar time course, having a minimum discharge rate 200-300 ms into the gap, and increased activity at the time of target appearance with smaller or larger gap durations. 3. We propose that the activity of fixation cells in the monkey superior colliculus provide a neural correlate of the gap effect. The decrease in activity of fixation cells 200-300 ms into the gap weakens the powerful state of inhibition which they normally exert upon the saccade generating system, allowing targets to be acquired at shorter reaction times.

Neuronal activity in monkey superior colliculus related to the initiation of saccadic eye movements.

The introduction of a temporal gap between the disappearance of an initially fixated target and the appearance of an eccentric saccadic target results in a general reduction of saccadic reaction times (SRTs)-the gap effect-and often in the production of express saccades, the latencies of which approach the conduction time of the shortest neural pathways from the retina to the eye muscles. We investigated saccade initiation by recording neuronal activity in the superior colliculus in monkeys performing the gap paradigm. Fixation-related neurons reduced their discharge rate during the gap period, regardless of the SRT. This reduction in activity is consistent with the hypothesized release of ocular fixation that facilitates premotor processes and may contribute to the gap effect. In addition to saccade-related discharges, many saccade-related neurons displayed phasic target-related responses and/or low-frequency preparatory activity during the gap period. The level of this preparatory activity correlated with both SRT and express saccade occurrence when the saccade was made into the response field of the neuron. Evidence indicates that advanced motor preparation is required for express saccade generation, which may be subserved by specific increases in the preparatory activity of saccade-related neurons. Increased preparatory activity may allow the target-related responses to trigger short-latency express saccades directly. This study provides insights into the functional mechanism of saccade initiation and may be relevant to the generation of all voluntary motor responses.

Reflex suppression in the anti-saccade task is dependent on prestimulus neural processes.

Reflexive responses often must be suppressed to correctly execute a voluntary behavior. It is largely unknown why this control sometimes fails. To examine the neural processes responsible for these failures, we recorded single-neuron activity in the superior colliculus (SC) in behaving monkeys during an anti-saccade task in which they had to suppress a saccade to a visual stimulus that suddenly appeared in the periphery and generate a saccade to the opposite side. We found that the level and distribution of prestimulus activity of buildup neurons in the SC was highly predictive of whether a correct response or an error occurred. A high level of prestimulus activity in buildup neurons at the location in the SC where the visual stimulus was represented was associated with the generation of a reflexive saccade to the stimulus. These findings suggest that the successful suppression of reflexive saccades is dependent on prestimulus neural processes in the SC.

A model of saccade initiation based on the competitive integration of exogenous and endogenous signals in the superior colliculus.

Significant advances in cognitive neuroscience can be achieved by combining techniques used to measure behavior and brain activity with neural modeling. Here we apply this approach to the initiation of rapid eye movements (saccades), which are used to redirect the visual axis to targets of interest. It is well known that the superior colliculus (SC) in the midbrain plays a major role in generating saccadic eye movements, and physiological studies have provided important knowledge of the activity pattern of neurons in this structure. Based on the observation that the SC receives localized sensory (exogenous) and voluntary (endogenous) inputs, our model assumes that this information is integrated by dynamic competition across local collicular interactions. The model accounts well for the effects upon saccadic reaction time (SRT) due to removal of fixation, the presence of distractors, execution of pro- versus antisaccades, and variation in target probability, and suggests a possible mechanism for the generation of express saccades. In each of these cases, the activity patterns of "neurons" within the model closely resemble actual cell behavior in the intermediate layer of the SC. The interaction structure we employ is instrumental for producing a physiologically faithful model and results in new insights and hypotheses regarding the neural mechanisms underlying saccade initiation.

Comparison of the discharge characteristics of brain stem omnipause neurons and superior colliculus fixation neurons in monkey: implications for control of fixation and saccade behavior.

Fixation neurons (SCFNs) in the rostral pole of the superior colliculus (SC) and omnipause neurons (OPNs) in the nucleus raphe interpositus (rip) in the pons share similar discharge properties. Both types of neurons discharge tonically during periods of visual fixation and pause for saccadic eye movements, and their activation by electrical stimulation suppresses saccade generation. On the basis of these similarities and the projection from the rostral SC to the rip, it was hypothesized that SCFNs provide a major excitatory input to OPNs. We investigated the role and relationship of SCFNs and OPNs with respect to both fixation behavior and saccade generation by comparing their activity recorded in the same monkeys performing a gap saccade task. In this task, the central fixation point was extinguished 200 ms before the presentation of an eccentric saccadic target, and the discharges of OPNs and SCFNs were contrasted during visual fixation, nonvisual (gap) fixation, and saccade generation. During visual fixation, the mean discharge rate of OPNs was higher and more regular than that of SCFNs. During the gap period, SCFNs decreased their discharge rate before target appearance, whereas no change in discharge rate was observed in OPNs. For both SCFNs and OPNs, the activity level before target appearance was not correlated to saccadic reaction time. In contrast to SCFNs, several OPNs responded with a transient phasic increase in discharge immediately after the target presentation. Before their saccade-related pause, there was a gradual reduction in the activity of SCFNs, whereas OPNs had an abrupt cessation of discharge. SCFNs paused earlier than OPNs, but the OPN pause onset was better synchronized to saccade onset than the SCFN pause onset. OPNs resumed firing after their pause in activity earlier than SCFNs, and the OPN pause end was better synchronized to saccade end than the SCFN pause end. These physiological data reveal differences in the discharge properties of SCFNs and OPNs that are irreconcilable with the hypothesis that the discharge pattern of OPNs reflects simply the excitatory input from SCFNs. It is most likely that additional inputs to OPNs compensate for the reduction in discharge of SCFNs during these periods.

On your mark, get set: brainstem circuitry underlying saccadic initiation.

Saccades are rapid eye movements that are used to move the visual axis toward targets of interest in the visual field. The time to initiate a saccade is dependent upon many factors. Here we review some of the recent advances in our understanding of the these processes in primates. Neurons in the superior colliculus and brainstem reticular formation are organised into a network to control saccades. Some neurons are active during visual fixation, while others are active during the preparation and execution of saccades. Several factors can influence the excitability levels of these neurons prior to the appearance of a new saccadic target. These pre-target changes in excitability are correlated to subsequent changes in behavioural performance. Our results show how neuronal signals in the superior colliculus and brainstem reticular formation can be shaped by contextual factors and demonstrate how situational experience can expedite motor behaviour via the advanced preparation of motor programs.

Role of primate superior colliculus in preparation and execution of anti-saccades and pro-saccades.

We investigated how the brain switches between the preparation of a movement where a stimulus is the target of the movement, and a movement where a stimulus serves as a landmark for an instructed movement elsewhere. Monkeys were trained on a pro-/anti-saccade paradigm in which they either had to generate a pro-saccade toward a visual stimulus or an anti-saccade away from the stimulus to its mirror position, depending on the color of an initial fixation point. Neural activity was recorded in the superior colliculus (SC), a structure that is known to be involved in the generation of fast saccades, to determine whether it was also involved in the generation of anti-saccades. On anti-saccade trials, fixation during the instruction period was associated with an increased activity of collicular fixation-related neurons and a decreased activity of saccade-related neurons. Stimulus-related and saccade-related activity was reduced on anti-saccade trials. Our results demonstrate that the anti-saccade task involves (and may require) the attenuation of preparatory and stimulus-related activity in the SC to avoid unwanted pro-saccades. Because the attenuated pre-saccade activity that we found in the SC may be insufficient by itself to elicit correct anti-saccades, additional movement signals from other brain areas are presumably required.

Influence of previous visual stimulus or saccade on saccadic reaction times in monkey.

Influence of previous visual stimulus or saccade on saccadic reaction times in monkey. Saccadic reaction times (SRTs) to suddenly appearing targets are influenced by neural processes that occur before and after target presentation. The majority of previous studies have focused on how posttarget factors, such as target attributes or changes in task complexity, affect SRTs. Studies of pretarget factors have focused on how prior knowledge of the timing or location of the impending target, gathered through cueing or probabilistic information, affects SRTs. Our goal was to investigate additional pretarget factors to determine whether SRTs can also be influenced by the history of saccadic and visual activity even when these factors are spatially unpredictive as to the location of impending saccadic targets. Monkeys were trained on two paradigms. In the saccade-saccade paradigm, monkeys were required to follow a saccadic target that stepped from a central location, to an eccentric location, back to center, and finally to a second eccentric location. The stimulus-saccade paradigm was similar, except the central fixation target remained illuminated during presentation of the first eccentric stimulus; the monkey was required to maintain central fixation and to make a saccade to the second eccentric stimulus only on disappearance of the fixation point. In both paradigms, the first eccentric stimulus was presented at the same, opposite, or orthogonal location with respect to the final target location in a given trial. We measured SRTs to the final target under conditions in which all parameters were identical except for the location of the first eccentric stimulus. In the saccade-saccade paradigm, we found that the SRT to the final target was slowest when it was presented opposite to the initial saccadic target, whereas in the stimulus-saccade paradigm the SRT to the final target was slowest when it was presented at the same location as the initial stimulus. In both paradigms, these increases in SRTs were greatest during the shortest intervals between presentation of successive eccentric stimuli, yet these effects remained present for the longest intervals employed in this study. SRTs became faster as the direction and eccentricity of the two successive stimuli became increasingly misaligned from that which produced the maximal SRT slowing in each paradigm. The results of the stimulus-saccade paradigm are similar to the phenomenon of inhibition of return (IOR) in which human subjects are slower to respond to stimuli that are presented at previously cued locations. We interpret these findings in terms of overlapping representations of visuospatial and oculomotor activity in the same neural structures.

Combined eye-head gaze shifts to visual and auditory targets in humans.

We studied the characteristics of combined eye-head gaze shifts in human subjects to determine whether they used similar strategies when looking at visual (V), auditory (A), and combined (V + A) targets located at several target eccentricities along the horizontal meridian. Subjects displayed considerable variability in the combinations of eye and head movement used to orient to the targets, ranging from those who always aligned their head close to the target, to those who relied predominantly on eye movements and only moved their head when the target was located beyond the limits of ocular motility. For a given subject, there was almost no variability in the amount of eye and head movement in the three target conditions (V, A, V + A). The time to initiate a gaze shift was influenced by stimulus modality and eccentricity. Auditory targets produced the longest latencies when located centrally (less than 20 degrees eccentricity), whereas visual targets evoked the longest latencies when located peripherally (greater than 40 degrees eccentricity). Combined targets (V + A) elicited the shortest latency reaction times at all eccentricities. The peak velocity of gaze shifts was also affected by target modality. At eccentricities between 10 and 30 degrees, peak gaze velocity was greater for movements to visual targets than for movements to auditory targets. Movements to the combined target were of comparable speed with movements to visual targets. Despite the modality-specific differences in reaction latency and peak gaze velocity, the consistency of combinations of eye and head movement within subjects suggests that visual and auditory signals are remapped into a common reference frame for controlling orienting gaze shifts. A likely candidate is the deeper layers of the superior colliculus, because visual and auditory signals converge directly onto the neurons projecting to the eye and head premotor centers.