Early Video-assisted Thoracoscopic Surgery or Intrapleural Enzyme Therapy in Pleural Infection: A Feasibility Randomized Controlled Trial. The Third Multicenter Intrapleural Sepsis Trial-MIST-3.

Rationale: Assessing the early use of video-assisted thoracoscopic surgery (VATS) or intrapleural enzyme therapy (IET) in pleural infection requires a phase III randomized controlled trial (RCT). Objectives: To establish the feasibility of randomization in a surgery-versus-nonsurgery trial as well as the key outcome measures that are important to identify relevant patient-centered outcomes in a subsequent RCT. Methods: The MIST-3 (third Multicenter Intrapleural Sepsis Trial) was a prospective multicenter RCT involving eight U.K. centers combining on-site and off-site surgical services. The study enrolled all patients with a confirmed diagnosis of pleural infection and randomized those with ongoing pleural sepsis after an initial period (as long as 24 h) of standard care to one of three treatment arms: continued standard care, early IET, or a surgical opinion with regard to early VATS. The primary outcome was feasibility based on >50% of eligible patients being successfully randomized, >95% of randomized participants retained to discharge, and >80% of randomized participants retained to 2 weeks of follow-up. The analysis was performed per intention to treat. Measurements and Main Results: Of 97 eligible patients, 60 (62%) were randomized, with 100% retained to discharge and 84% retained to 2 weeks. Baseline demographic, clinical, and microbiological characteristics of the patients were similar across groups. Median times to intervention were 1.0 and 3.5 days in the IET and surgery groups, respectively (P = 0.02). Despite the difference in time to intervention, length of stay (from randomization to discharge) was similar in both intervention arms (7 d) compared with standard care (10 d) (P = 0.70). There were no significant intergroup differences in 2-month readmission and further intervention, although the study was not adequately powered for this outcome. Compared with VATS, IET demonstrated a larger improvement in mean EuroQol five-dimension health utility index (five-level edition) from baseline (0.35) to 2 months (0.83) (P = 0.023). One serious adverse event was reported in the VATS arm. Conclusions: This is the first multicenter RCT of early IET versus early surgery in pleural infection. Despite the logistical challenges posed by the coronavirus disease (COVID-19) pandemic, the study met its predefined feasibility criteria, demonstrated potential shortening of length of stay with early surgery, and signals toward earlier resolution of pain and a shortened recovery with IET. The study findings suggest that a definitive phase III study is feasible but highlights important considerations and significant modifications to the design that would be required to adequately assess optimal initial management in pleural infection.The trial was registered on ISRCTN (number 18,192,121).

Clinical application of eye movement tasks as an aid to understanding Parkinson's disease pathophysiology.

Parkinson's disease (PD) is a progressive neurodegenerative disorder of the basal ganglia. Most PD patients suffer from somatomotor and oculomotor disorders. The oculomotor system facilitates obtaining accurate information from the visual world. If a target moves slowly in the fronto-parallel plane, tracking eye movements occur that consist primarily of smooth-pursuit interspersed with corrective saccades. Efficient smooth-pursuit requires appropriate target selection and predictive compensation for inherent processing delays. Although pursuit impairment, e.g. as latency prolongation or low gain (eye velocity/target velocity), is well known in PD, normal aging alone results in such changes. In this article, we first briefly review some basic features of smooth-pursuit, then review recent results showing the specific nature of impaired pursuit in PD using a cue-dependent memory-based smooth-pursuit task. This task was initially used for monkeys to separate two major components of prediction (image-motion direction memory and movement preparation), and neural correlates were examined in major pursuit pathways. Most PD patients possessed normal cue-information memory but extra-retinal mechanisms for pursuit preparation and execution were dysfunctional. A minority of PD patients had abnormal cue-information memory or difficulty in understanding the task. Some PD patients with normal cue-information memory changed strategy to initiate smooth tracking. Strategy changes were also observed to compensate for impaired pursuit during whole body rotation while the target moved with the head. We discuss PD pathophysiology by comparing eye movement task results with neuropsychological and motor symptom evaluations of individual patients and further with monkey results, and suggest possible neural circuits for these functions/dysfunctions.

Impaired smooth-pursuit in Parkinson's disease: normal cue-information memory, but dysfunction of extra-retinal mechanisms for pursuit preparation and execution.

While retinal image motion is the primary input for smooth-pursuit, its efficiency depends on cognitive processes including prediction. Reports are conflicting on impaired prediction during pursuit in Parkinson's disease. By separating two major components of prediction (image motion direction memory and movement preparation) using a memory-based pursuit task, and by comparing tracking eye movements with those during a simple ramp-pursuit task that did not require visual memory, we examined smooth-pursuit in 25 patients with Parkinson's disease and compared the results with 14 age-matched controls. In the memory-based pursuit task, cue 1 indicated visual motion direction, whereas cue 2 instructed the subjects to prepare to pursue or not to pursue. Based on the cue-information memory, subjects were asked to pursue the correct spot from two oppositely moving spots or not to pursue. In 24/25 patients, the cue-information memory was normal, but movement preparation and execution were impaired. Specifically, unlike controls, most of the patients (18/24 = 75%) lacked initial pursuit during the memory task and started tracking the correct spot by saccades. Conversely, during simple ramp-pursuit, most patients (83%) exhibited initial pursuit. Popping-out of the correct spot motion during memory-based pursuit was ineffective for enhancing initial pursuit. The results were similar irrespective of levodopa/dopamine agonist medication. Our results indicate that the extra-retinal mechanisms of most patients are dysfunctional in initiating memory-based (not simple ramp) pursuit. A dysfunctional pursuit loop between frontal eye fields (FEF) and basal ganglia may contribute to the impairment of extra-retinal mechanisms, resulting in deficient pursuit commands from the FEF to brainstem.

Influence of predictability on control of extra-retinal components of smooth pursuit during prolonged 2D tracking.

We compared pursuit responses to 2D target motion in three separate conditions: predictable, randomised and randomised with timing cues. The target moved on a continuous quadrilateral path in which right-angle direction changes allowed anticipatory eye acceleration and deceleration in orthogonal axes to be assessed. Results indicated that whether the timing of direction changes was random or predictable, anticipatory acceleration, initiated by extra-retinal mechanisms, occurred in the new direction at approximately the same time as anticipatory deceleration in the terminating direction, but deceleration was of greater magnitude than acceleration. When path duration was randomised within a range of durations, the timing of acceleration and deceleration was almost constant irrespective of actual ramp duration but was dependent on the mean duration of the range. When ramp duration was predictable both deceleration and acceleration increased, the latter allowing peak velocity to be attained earlier than when randomised. When timing cues were given at a fixed time prior to direction change in randomised stimuli, this also resulted in higher anticipatory acceleration/deceleration. When both duration and velocity of sequential ramps were randomised, deceleration was dependent on target velocity, but acceleration remained constant. Altogether these findings show that although acceleration and deceleration in orthogonal axes occur almost simultaneously and are similarly affected by predictability, control of their magnitude is relatively independent. We suggest that deceleration and acceleration result from the switching off and on, respectively, of retinal and extra-retinal oculomotor components prior to direction change, with dynamics dependent on predictability of stimulus magnitude and timing.

Normal aging affects movement execution but not visual motion working memory and decision-making delay during cue-dependent memory-based smooth-pursuit.

Aging affects virtually all functions including sensory/motor and cognitive activities. While retinal image motion is the primary input for smooth-pursuit, its efficiency/accuracy depends on cognitive processes. Elderly subjects exhibit gain decrease during initial and steady-state pursuit, but reports on latencies are conflicting. Using a cue-dependent memory-based smooth-pursuit task, we identified important extra-retinal mechanisms for initial pursuit in young adults including cue information priming and extra-retinal drive components (Ito et al. in Exp Brain Res 229:23-35, 2013). We examined aging effects on parameters for smooth-pursuit using the same tasks. Elderly subjects were tested during three task conditions as previously described: memory-based pursuit, simple ramp-pursuit just to follow motion of a single spot, and popping-out of the correct spot during memory-based pursuit to enhance retinal image motion. Simple ramp-pursuit was used as a task that did not require visual motion working memory. To clarify aging effects, we then compared the results with the previous young subject data. During memory-based pursuit, elderly subjects exhibited normal working memory of cue information. Most movement-parameters including pursuit latencies differed significantly between memory-based pursuit and simple ramp-pursuit and also between young and elderly subjects. Popping-out of the correct spot motion was ineffective for enhancing initial pursuit in elderly subjects. However, the latency difference between memory-based pursuit and simple ramp-pursuit in individual subjects, which includes decision-making delay in the memory task, was similar between the two groups. Our results suggest that smooth-pursuit latencies depend on task conditions and that, although the extra-retinal mechanisms were functional for initial pursuit in elderly subjects, they were less effective.

In pursuit of delay-related brain activity for anticipatory eye movements.

How the brain stores motion information and subsequently uses it to follow a moving target is largely unknown. This is mainly due to previous fMRI studies using paradigms in which the eye movements cannot be segregated from the storage of this motion information. To avoid this problem we used a novel paradigm designed in our lab in which we interlaced a delay (2, 4 or 6 seconds) between the 1(st) and 2(nd) presentation of a moving stimulus. Using this design we could examine brain activity during a delay period using fMRI and have subsequently found a number of brain areas that reveal sustained activity during predictive pursuit. These areas include, the V5 complex and superior parietal lobe. This study provides new evidence for the network involved in the storage of visual information to generate early motor responses in pursuit.

Cue-dependent memory-based smooth-pursuit in normal human subjects: importance of extra-retinal mechanisms for initial pursuit.

Using a cue-dependent memory-based smooth-pursuit task previously applied to monkeys, we examined the effects of visual motion-memory on smooth-pursuit eye movements in normal human subjects and compared the results with those of the trained monkeys. These results were also compared with those during simple ramp-pursuit that did not require visual motion-memory. During memory-based pursuit, all subjects exhibited virtually no errors in either pursuit-direction or go/no-go selection. Tracking eye movements of humans and monkeys were similar in the two tasks, but tracking eye movements were different between the two tasks; latencies of the pursuit and corrective saccades were prolonged, initial pursuit eye velocity and acceleration were lower, peak velocities were lower, and time to reach peak velocities lengthened during memory-based pursuit. These characteristics were similar to anticipatory pursuit initiated by extra-retinal components during the initial extinction task of Barnes and Collins (J Neurophysiol 100:1135-1146, 2008b). We suggest that the differences between the two tasks reflect differences between the contribution of extra-retinal and retinal components. This interpretation is supported by two further studies: (1) during popping out of the correct spot to enhance retinal image-motion inputs during memory-based pursuit, pursuit eye velocities approached those during simple ramp-pursuit, and (2) during initial blanking of spot motion during memory-based pursuit, pursuit components appeared in the correct direction. Our results showed the importance of extra-retinal mechanisms for initial pursuit during memory-based pursuit, which include priming effects and extra-retinal drive components. Comparison with monkey studies on neuronal responses and model analysis suggested possible pathways for the extra-retinal mechanisms.

Cognitive processes involved in smooth pursuit eye movements: behavioral evidence, neural substrate and clinical correlation.

Smooth-pursuit eye movements allow primates to track moving objects. Efficient pursuit requires appropriate target selection and predictive compensation for inherent processing delays. Prediction depends on expectation of future object motion, storage of motion information and use of extra-retinal mechanisms in addition to visual feedback. We present behavioral evidence of how cognitive processes are involved in predictive pursuit in normal humans and then describe neuronal responses in monkeys and behavioral responses in patients using a new technique to test these cognitive controls. The new technique examines the neural substrate of working memory and movement preparation for predictive pursuit by using a memory-based task in macaque monkeys trained to pursue (go) or not pursue (no-go) according to a go/no-go cue, in a direction based on memory of a previously presented visual motion display. Single-unit task-related neuronal activity was examined in medial superior temporal cortex (MST), supplementary eye fields (SEF), caudal frontal eye fields (FEF), cerebellar dorsal vermis lobules VI-VII, caudal fastigial nuclei (cFN), and floccular region. Neuronal activity reflecting working memory of visual motion direction and go/no-go selection was found predominantly in SEF, cerebellar dorsal vermis and cFN, whereas movement preparation related signals were found predominantly in caudal FEF and the same cerebellar areas. Chemical inactivation produced effects consistent with differences in signals represented in each area. When applied to patients with Parkinson's disease (PD), the task revealed deficits in movement preparation but not working memory. In contrast, patients with frontal cortical or cerebellar dysfunction had high error rates, suggesting impaired working memory. We show how neuronal activity may be explained by models of retinal and extra-retinal interaction in target selection and predictive control and thus aid understanding of underlying pathophysiology.

Facilitation of ocular pursuit during transient occlusion of externally-generated target motion by concurrent upper limb movement.

Smooth pursuit during prolonged occlusion is improved in the presence of sensorimotor signals when tracking self-generated target motion. The current study investigated whether concurrent arm tracking of externally-generated target motion conveys a similar facilitation to ocular pursuit of transiently occluded constant velocity (Experiment 1) or accelerating (Experiment 2) targets. Velocity characteristics and occlusion duration were arranged in random or blocked order, thus permitting a novel examination of the contribution from sensorimotor signals and predictive processes acting within the ocular system during transient occlusion. Consistent with previous investigations, smooth pursuit decayed during transient occlusion; but eye velocity was higher when trials were presented in blocked compared to random order, particularly for positively accelerating targets. For fast, constant velocity targets, concurrent arm movement facilitated smooth pursuit during transient occlusion. Nevertheless, even with increased predictability regarding the upcoming target motion in blocked-order trials and the presence of sensorimotor signals from concurrent arm movement, eye velocity always remained less than target velocity during occlusion. This contrasted with the manual response, which attained velocity close to target velocity, whether in blocked or random conditions. These findings are discussed with reference to recent models of ocular pursuit that incorporate short-term and/or long-term prediction to account for target extrapolation during occlusion.

The influence of cues and stimulus history on the non-linear frequency characteristics of the pursuit response to randomized target motion.

When humans pursue motion stimuli composed of alternating constant velocity segments of randomised duration (RD), they nevertheless initiate anticipatory eye deceleration before stimulus direction changes at a pre-programmed time based on averaging prior stimulus timing. We investigated, in both the time and frequency domains, how averaging interacts with deceleration cues by comparing responses to stimuli composed of segments that were either constant-velocity ramps or half-cycle sinusoids. RDs were randomized within 6 ranges, each comprising 8 RDs and having differing mean RD. In sine responses, deceleration cues could be used to modulate eye velocity for long-range stimuli (RD = 840-1,200 ms) but in the shortest range (RD = 240-660 ms) cues became ineffective, so that sine responses resembled ramp responses, and anticipatory timing was primarily dependent on averaging. Additionally, inclusion of short duration (240 ms) segments reduced peak eye velocity for all RDs within a range, even when longer RDs in the range (up to 1,080 ms) would normally elicit much higher velocities. These effects could be attributed to antagonistic interactions between visually driven pursuit components and pre-programmed anticipatory deceleration components. In the frequency domain, the changes in peak velocity and anticipatory timing with RD range were translated into non-linear gain and phase characteristics similar to those evoked by sum-of-sines stimuli. Notably, a reduction in pursuit gain occurred when high-frequency components associated with short duration segments were present. Results appear consistent with an adapted pursuit model, in which pre-programmed timing information derived from an internally reconstructed stimulus signal is stored in short-term memory and controls the initiation of predictive responses.

The neural correlates of inhibiting pursuit to smoothly moving targets.

A previous study has shown that actively pursuing a moving target provides a predictive motor advantage when compared with passive observation of the moving target while keeping the eyes still [Burke, M. R., & Barnes, G. R. Anticipatory eye movements evoked after active following versus passive observation of a predictable motion stimulus. Brain Research, 15, 74-81, 2008b]. By using a novel paradigm based on combining a smooth pursuit stimulus with a go/no-go task, we have been able to reveal significant differences in brain activity for the inhibition of pursuit during the presentation of a smoothly moving target. Areas that show specific inhibitory and retinocentric velocity storage activity for the passive (no-go) condition include the dorsolateral pFC, the caudate, and the posterior cingulate. The FEFs, the supramarginal gyrus, the medial occipital gyrus, and the superior parietal lobe were found to be more involved in both the acquisition and response generation during no-go trials when compared with go trials. The go trials revealed higher activity than the no-go during the acquisition phase in the uncus and posterior cingulate. Furthermore, higher motor-related activity in the go task was found in the cerebellum. In summary, the areas involved in inhibiting smooth pursuit are consistent with the findings from the saccade literature, providing further evidence in support of overlapping cortical control networks.

Extraction of visual motion information for the control of eye and head movement during head-free pursuit.

We investigated how effectively briefly presented visual motion could be assimilated and used to track future target motion with head and eyes during target disappearance. Without vision, continuation of eye and head movement is controlled by internal (extra-retinal) mechanisms, but head movement stimulates compensatory vestibulo-ocular reflex (VOR) responses that must be countermanded for gaze to remain in the direction of target motion. We used target exposures of 50-200 ms at the start of randomised step-ramp stimuli, followed by > 400 ms of target disappearance, to investigate the ability to sample target velocity and subsequently generate internally controlled responses. Subjects could appropriately grade gaze velocity to different target velocities without visual feedback, but responses were fully developed only when exposure was > 100 ms. Gaze velocities were sustained or even increased during target disappearance, especially when there was expectation of target reappearance, but they were always less than for controls, where the target was continuously visible. Gaze velocity remained in the direction of target motion throughout target extinction, implying that compensatory (VOR) responses were suppressed by internal drive mechanisms. Regression analysis revealed that the underlying compensatory response remained active, but with gain slightly less than unity (0.85), resulting in head-free gaze responses that were very similar to, but slightly greater than, head-fixed. The sampled velocity information was also used to grade head velocity, but in contrast to gaze, head velocity was similar whether the target was briefly or continuously presented, suggesting that head motion was controlled by internal mechanisms alone, without direct influence of visual feedback.

Oscillatory eye movements resembling pendular nystagmus in normal juvenile macaques.

PURPOSE: Juvenile monkeys being trained on smooth-pursuit tasks exhibit ocular oscillations resembling pendular nystagmus. The purpose of this study was to analyze these oscillations, the effects of gabapentin on them, and responses of cerebellar floccular neurons to understand possible neuronal mechanisms. METHODS: Four monkeys were trained for horizontal and vertical smooth pursuit; in two, saccades were also tested. Frequency, peak-to-peak eye velocity, and amplitude of the ocular oscillations were measured. In one monkey, the effect of gabapentin on the oscillations was measured, and oscillation-related neuronal discharge was recorded in the cerebellar floccular region. RESULTS: Ocular oscillations, with features of pendular nystagmus, appeared early during training of both horizontal and vertical pursuit in all four monkeys. Although these oscillations were observed both in the direction of pursuit and orthogonally, the velocity and amplitude of oscillation were larger in the direction of pursuit, implicating pursuit mechanisms in their generation. Corrective saccades were often superimposed on the oscillations during pursuit and fixation. Gabapentin suppressed oscillations in the monkey tested. Recordings in the floccular region revealed a subset of neurons discharged during both the oscillations and corrective saccades. Many of them exhibited burst-tonic discharge during visually guided saccades, similar to discharge of brain stem burst-tonic neurons, suggesting contributions of the neural integrator to the oscillations. CONCLUSIONS: The developmentally transient ocular oscillations occurring in monkeys during pursuit training has properties resembling pendular nystagmus. Both smooth pursuit and a neural integrator may contribute to these ocular oscillations. Analysis using an efference-copy pursuit model supports the interpretation herein.

The interaction of visual, vestibular and extra-retinal mechanisms in the control of head and gaze during head-free pursuit.

The ability to co-ordinate the eyes and head when tracking moving objects is important for survival. Tracking with eyes alone is controlled by both visually dependent and extra-retinal mechanisms, the latter sustaining eye movement during target extinction. We investigated how the extra-retinal component develops at the beginning of randomised responses during head-free pursuit and how it interacts with the vestibulo-ocular reflex (VOR). Subjects viewed horizontal step-ramp stimuli which occurred in pairs of identical velocity; velocity was randomised between pairs, ranging from ±5 to 40 deg s−1. In the first of each pair (short-ramp extinction) the target was visible for only 150 ms. In the second (initial extinction), after a randomised fixation period, the target was extinguished at motion onset, remaining invisible for 750 ms before reappearing for the last 200 ms of motion. Subjects used motion information acquired in the short-ramp extinction presentation to track the target from the start of unseen motion in the initial extinction presentation, using extra-retinal drive to generate smooth gaze and head movements scaled to target velocity. Gaze velocity rose more slowly than when visually driven, but had similar temporal development in head-free and head-fixed conditions. The difference in eye-in-head velocity between head-fixed and head-free conditions was closely related to head velocity throughout its trajectory, implying that extra-retinal drive was responsible for countermanding the VOR in the absence of vision. Thus, the VOR apparently remained active during head-free pursuit with near-unity gain. Evidence also emerged that head movements are not directly controlled by visual input, but by internal estimation mechanisms similar to those controlling gaze.

Oculomotor prediction of accelerative target motion during occlusion: long-term and short-term effects.

The present study examined the influence of long-term (i.e., between-trial) and short-term (i.e., within-trial) predictive mechanisms on ocular pursuit during transient occlusion. To this end, we compared ocular pursuit of accelerative and decelerative target motion in trials that were presented in random or blocked-order. Catch trials in which target acceleration was unexpectedly modified were randomly interleaved in blocked-order trials. Irrespective of trial order, eye velocity decayed following target occlusion and then recovered towards the different levels of target velocity at reappearance. However, the recovery was better scaled in blocked-order trials than random-order trials. In blocked-order trials only, the reduced gain of smooth pursuit during occlusion was compensated by a change in saccade amplitude and resulted in total eye displacement (TED) that was well matched to target displacement. Subsidiary analysis indicated that three repeats of blocked-order trials was sufficient for participants to modify eye displacement compared to that exhibited in random-order trials, although more trials were required before end-occlusion eye velocity was better scaled. Finally, we found that participants exhibited evidence of a scaled response to an unexpected change in target acceleration (i.e., catch trials), although there were also transfer effects from the preceding blocked-order trials. These findings are consistent with the suggestion that on-the-fly prediction (short-term effect) is combined with memorized information from previous trials (long-term effect) to generate a persistent and veridical prediction of occluded target motion.

Predicting the unpredictable: weighted averaging of past stimulus timing facilitates ocular pursuit of randomly timed stimuli.

In motor control, prediction of future events is vital for overcoming sensory-motor processing delays and facilitating rapid and accurate responses in a dynamic environment. In human ocular pursuit this is so pervasive that prediction of future target motion cannot easily be eliminated by randomizing stimulus parameters. We investigated the prediction of temporally randomized events during pursuit of alternating constant-velocity (ramp) stimuli in which the timing of direction changes varied unpredictably over a given range. Responses were not reactive; instead, smooth eye velocity began to decelerate in anticipation of each target reversal. In the first experiment, using a continuous-motion stimulus, we found that the time at which this occurred was relatively constant regardless of ramp duration, but increased as mean ramp duration of the range increased. Regression analysis revealed a quantitative association between deceleration timing and the previous two or three ramp durations in a trial, suggesting that recent stimulus history was used to create a running average of anticipatory timing. In the second experiment, we used discrete motion stimuli, with intervening periods of fixation, which allowed both target velocity and reversal timing to be varied, thereby decoupling ramp duration and displacement. This enabled us to confirm that the timing of anticipatory deceleration was based on the history of timing, rather than displacement, within the stimulus. We conclude that this strategy is used to minimize error amid temporal uncertainty, while simultaneously overcoming inherent delays in visuomotor processing.

Target acceleration can be extracted and represented within the predictive drive to ocular pursuit.

Given sufficient exposure to stimulus presentation, the oculomotor system generates a representation of the stimulus characteristics, which is then used to predict the upcoming target motion. In addition to compensating for the perceptual-motor delay, these predictive processes perpetuate eye motion during a transient occlusion and compensate for the loss of visual input. At present, however, it is not well understood whether and how the oculomotor system extracts and represents target acceleration for subsequent predictive control. To this end, we used a target occlusion paradigm where both position and velocity of the target during the occlusion and at reappearance could not be predicted without extracting target acceleration before target disappearance. We found that the oculomotor response during the blanking period was not influenced by target acceleration when the initial exposure was 200 ms. However, smooth and saccadic eye movements did discriminate between the different levels of acceleration after an initial 500- or 800-ms exposure. In the event that the smooth response during the occlusion did not match well the target trajectory and thus eliminate a developing displacement error, there was an increased saccadic displacement. Still, the combined response during the blanking period did not eliminate retinal slip and position error at target reappearance. These results indicate that information on target acceleration can be extracted on-line, during pursuit of a visible ramp, and then used to drive a predictive oculomotor response in the absence of visual input.

Sequence learning in two-dimensional smooth pursuit eye movements in humans.

Sequence learning is common to all motor systems and is an essential aspect of human behavior necessary for the acquisition of motor skill. Many previous studies have demonstrated the ability to observe, store, and repeat sequences in a variety of modalities resulting in reduced reaction time. Recently, it has been found that subjects can make predictive smooth eye movements to a sequence of discrete horizontal target motions (C. J. Collins & Barnes, 2005). The present study extends that paradigm into two dimensions of motion in order to investigate qualitative and quantitative differences in sequences of vertical (V) and horizontal (H) eye movements. The subjects performed sequences of four discrete velocity ramps repeated either four or eight times in succession. Baseline measurements were obtained to discrete individual smooth pursuit velocity ramps to H and V predictable (PRD) and randomized (RND) targets. We found that subjects could rapidly learn and anticipate individual components of a four-ramp sequence in two dimensions. The results showed clear asymmetries in the eye movements made to horizontal and vertical targets. We found that the latencies to H targets were shorter than latencies to V targets in both the PRD and RND conditions. We also found higher initial eye velocity (50 ms after target onset) to H targets than vertical targets during the PRD condition. Because these differences in H and V eye movements are present in both RND and PRD trials, this suggests that the observed differences are not due to retention of information but are inherent asymmetries within the system.

Smooth ocular pursuit during the transient disappearance of an accelerating visual target: the role of reflexive and voluntary control.

This study examined the extent to which human subjects predict future target motion for the control of smooth ocular pursuit. Subjects were required to pursue an accelerating target (0, 4 or 8 degrees/s2) that underwent a transient occlusion, and consequently reappeared with the same or increased velocity. Presentations were received in a random or blocked order. Subjects exhibited anticipatory smooth pursuit prior to target motion onset, which in blocked presentations was scaled to the velocity generated by the target acceleration. In random presentations subjects also exhibited anticipatory smooth pursuit, but this was reflected in a more generalized response. During the transient occlusion all subjects exhibited a reduction in eye velocity, which was followed in the majority by a recovery prior to target reappearance. In random presentations, eye velocity decayed and recovered to a level that followed on from the response to the initial ramp. In blocked presentations, there was evidence of improved scaling throughout, which culminated in a significant increase in eye velocity between the start and end of the transient occlusion (8 degrees/s2 only). These findings are difficult to reconcile with reflexive accounts of oculomotor control that perpetuate current eye motion, and hence generate a simple form of prediction using a direct efference copy ("eye-velocity memory"). Rather, they are more consistent with the scaling of smooth pursuit eye movements by means of a more-persistent velocity-based representation, which plays a significant role in both random and blocked stimulus presentations.