The saccadic and neurological deficits in type 3 Gaucher disease

Our objective was to characterize the saccadic eye movements in patients with type 3 Gaucher disease (chronic neuronopathic) in relationship to neurological and neurophysiological abnormalities. For approximately 4 years, we prospectively followed a cohort of 15 patients with Gaucher type 3, ages 8-28 years, by measuring saccadic eye movements using the scleral search coil method. We found that patients with type 3 Gaucher disease had a significantly higher regression slope of duration vs amplitude and peak duration vs amplitude compared to healthy controls for both horizontal and vertical saccades. Saccadic latency was significantly increased for horizontal saccades only. Downward saccades were more affected than upward saccades. Saccade abnormalities increased over time in some patients reflecting the slowly progressive nature of the disease. Phase plane plots showed individually characteristic patterns of abnormal saccade trajectories. Oculo-manual dexterity scores on the Purdue Pegboard test were low in virtually all patients, even in those with normal cognitive function. Vertical saccade peak duration vs amplitude slope significantly correlated with IQ and with the performance on the Purdue Pegboard but not with the brainstem and somatosensory evoked potentials. We conclude that, in patients with Gaucher disease type 3, saccadic eye movements and oculo-manual dexterity are representative neurological functions for longitudinal studies and can probably be used as endpoints for therapeutic clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT00001289.     

A competitive integration model of exogenous and endogenous eye movements

We present a model of the eye movement system in which the programming of an eye movement is the result of the competitive integration of information in the superior colliculi (SC). This brain area receives input from occipital cortex, the frontal eye fields, and the dorsolateral prefrontal cortex, on the basis of which it computes the location of the next saccadic target. Two critical assumptions in the model are that cortical inputs are not only excitatory, but can also inhibit saccades to specific locations, and that the SC continue to influence the trajectory of a saccade while it is being executed. With these assumptions, we account for many neurophysiological and behavioral findings from eye movement research. Interactions within the saccade map are shown to account for effects of distractors on saccadic reaction time (SRT) and saccade trajectory, including the global effect and oculomotor capture. In addition, the model accounts for express saccades, the gap effect, saccadic reaction times for antisaccades, and recorded responses from neurons in the SC and frontal eye fields in these tasks.     

The Main Sequence of Saccades Optimizes Speed-accuracy Trade-off

In primates, it is well known that there is a consistent relationship between the duration, peak velocity and amplitude of saccadic eye movements, known as the ‘main sequence’. The reason why such a stereotyped relationship evolved is unknown. We propose that a fundamental constraint on the deployment of foveal vision lies in the motor system that is perturbed by signal-dependent noise (proportional noise) on the motor command. This noise imposes a compromise between the speed and accuracy of an eye movement. We propose that saccade trajectories have evolved to optimize a trade-off between the accuracy and duration of the movement. Taking a semi-analytical approach we use Pontryagin’s minimum principle to show that there is an optimal trajectory for a given amplitude and duration; and that there is an optimal duration for a given amplitude. It follows that the peak velocity is also fixed for a given amplitude. These predictions are in good agreement with observed saccade trajectories and the main sequence. Moreover, this model predicts a small saccadic dead-zone in which it is better to stay eccentric of target than make a saccade onto target. We conclude that the main sequence has evolved as a strategy to optimize the trade-off between accuracy and speed.     

Natural and drug-induced variations of velocity and duration of human saccadic eye movements: Evidence for a control of the neural pulse generator by local feedback

The present report considers goal directed human saccadic eye movements. It addresses the question how a given perceived target excentricity is transformed into the innervation pattern that creates the saccade to the target. More specifically, it investigates whether this pattern is an appropriately selected preprogram or whether it is continuously controlled by a local feedback loop that compares a non-visual eye position signal to the perceived target excentricity (a visual signal would be too slow). To this end, the relation between the accuracy of saccades aimed at a given target and their velocity and duration was examined. Duration and velocity were found to vary by as much as 60% while the amplitude showed no related variation and had an almost constant accuracy of about 90%. By administrating diazepam, the variability of saccade duration and velocity could be further increased, but still the amplitude remained almost constant. These results favour the hypothesis that saccadic innervation is controlled by a local feedback loop.This investigation was supported by Deutsche Forschungsgemeinschaft, SFB 70, Gruppe Ulm     

Looking for Discriminating Is Different from Looking for Looking’s Sake

Recent studies provide evidence for task-specific influences on saccadic eye movements. For instance, saccades exhibit higher peak velocity when the task requires coordinating eye and hand movements. The current study shows that the need to process task-relevant visual information at the saccade endpoint can be, in itself, sufficient to cause such effects. In this study, participants performed a visual discrimination task which required a saccade for successful completion. We compared the characteristics of these task-related saccades to those of classical target-elicited saccades, which required participants to fixate a visual target without performing a discrimination task. The results show that task-related saccades are faster and initiated earlier than target-elicited saccades. Differences between both saccade types are also noted in their saccade reaction time distributions and their main sequences, i.e., the relationship between saccade velocity, duration, and amplitude.     

Eye movements modulate visual receptive fields of V4 neurons

The receptive field, defined as the spatiotemporal selectivity of neurons to sensory stimuli, is central to our understanding of the neuronal mechanisms of perception. However, despite the fact that eye movements are critical during normal vision, the influence of eye movements on the structure of receptive fields has never been characterized. Here, we map the receptive fields of macaque area V4 neurons during saccadic eye movements and find that receptive fields are remarkably dynamic. Specifically, before the initiation of a saccadic eye movement, receptive fields shrink and shift towards the saccade target. These spatiotemporal dynamics may enhance information processing of relevant stimuli during the scanning of a visual scene, thereby assisting the selection of saccade targets and accelerating the analysis of the visual scene during free viewing.     

Saccades during Attempted Fixation in Parkinsonian Disorders and Recessive Ataxia: From Microsaccades to Square-Wave Jerks

During attempted visual fixation, saccades of a range of sizes occur. These “fixational saccades” include microsaccades, which are not apparent in regular clinical tests, and “saccadic intrusions”, predominantly horizontal saccades that interrupt accurate fixation. Square-wave jerks (SWJs), the most common type of saccadic intrusion, consist of an initial saccade away from the target followed, after a short delay, by a “return saccade” that brings the eye back onto target. SWJs are present in most human subjects, but are prominent by their increased frequency and size in certain parkinsonian disorders and in recessive, hereditary spinocerebellar ataxias. Here we asked whether fixational saccades showed distinctive features in various parkinsonian disorders and in recessive ataxia. Although some saccadic properties differed between patient groups, in all conditions larger saccades were more likely to form SWJs, and the intervals between the first and second saccade of SWJs were similar. These findings support the proposal of a common oculomotor mechanism that generates all fixational saccades, including microsaccades and SWJs. The same mechanism also explains how the return saccade in SWJs is triggered by the position error that occurs when the first saccadic component is large, both in the healthy brain and in neurological disease.     

The reliability of eye movement quantitative evaluation. I. Saccadic eye movements.

We adopted the estimate of the intraclass coefficient of reliability, R, to evaluate the reliability of saccadic eye movements quantitative analysis. At a one-week interval we recorded refixative saccadic eye movements twice from fifteen healthy subjects by means of the binocular electrooculographic technique. R was computed for the constants and the slopes of the amplitude/duration and the amplitude/peak velocity relationships, for the mean precision values and for the mean latency values adjusted for subject's age. Our data demonstrated that the reliability of saccade parameters is fairly good for the amplitude/peak velocity relationship, good for the precision and very good for the amplitude/duration relationship. Finally, we believe that the normal variability values we obtained can be usefully employed in neurophysiological longitudinal studies not only in normal subjects, but also in pathological condition provided the more reliable parameters and the more adequate strategies to compute normal variability values are chosen.     

Changes in the ocular saccade kinematics after a seven-day dry immersion

To assess the effects of long-term support unload on gaze control, five subjects were tested for the successful touch of a light target unpredictably emerging in the peripheral field of vision before and immediately after a seven-day dry immersion. The test did not set time requirements on gaze fixation on the target or motor task implementation. Ocular movements were recorded with an infrared eye image analyzer at 100 Hz. Modification of the dependences of the maximum velocity and duration of a saccade towards a homolateral target at the amplitude following immersion pointed to the speeding-up of the saccadic eye movements.     

The effect of saccades on threshold perception — A model study

The effect of saccadic eye movements on threshold perception is investigated theoretically. The proposed model considers eye movements by taking into account the shifting of the stimulus pattern on the retina during the occurrence of an eye movement. Saccades are characterized by high velocity and short duration. These motions cause overshoots in the response of linear filters to certain stimulus patterns. Therefore, the model predicts facilitation effects of saccades in the perception of low spatial frequency patterns and patterns flickering with high temporal frequencies. These results agree with experimentally obtained data presented in a subsequent paper. A simple approach is formulated which approximates the complex shifting function of a saccade by a switching of the pattern.     

Vision as oculomotor reward: cognitive contributions to the dynamic control of saccadic eye movements

Humans and other primates are equipped with a foveated visual system. As a consequence, we reorient our fovea to objects and targets in the visual field that are conspicuous or that we consider relevant or worth looking at. These reorientations are achieved by means of saccadic eye movements. Where we saccade to depends on various low-level factors such as a targets’ luminance but also crucially on high-level factors like the expected reward or a targets’ relevance for perception and subsequent behavior. Here, we review recent findings how the control of saccadic eye movements is influenced by higher-level cognitive processes. We first describe the pathways by which cognitive contributions can influence the neural oculomotor circuit. Second, we summarize what saccade parameters reveal about cognitive mechanisms, particularly saccade latencies, saccade kinematics and changes in saccade gain. Finally, we review findings on what renders a saccade target valuable, as reflected in oculomotor behavior. We emphasize that foveal vision of the target after the saccade can constitute an internal reward for the visual system and that this is reflected in oculomotor dynamics that serve to quickly and accurately provide detailed foveal vision of relevant targets in the visual field.     

Saccadic eye movements minimize the consequences of motor noise

The durations and trajectories of our saccadic eye movements are remarkably stereotyped. We have no voluntary control over these properties but they are determined by the movement amplitude and, to a smaller extent, also by the movement direction and initial eye orientation. Here we show that the stereotyped durations and trajectories are optimal for minimizing the variability in saccade endpoints that is caused by motor noise. The optimal duration can be understood from the nature of the motor noise, which is a combination of signal-dependent noise favoring long durations, and constant noise, which prefers short durations. The different durations of horizontal vs. vertical and of centripetal vs. centrifugal saccades, and the somewhat surprising properties of saccades in oblique directions are also accurately predicted by the principle of minimizing movement variability. The simple and sensible principle of minimizing the consequences of motor noise thus explains the full stereotypy of saccadic eye movements. This suggests that saccades are so stereotyped because that is the best strategy to minimize movement errors for an open-loop motor system.     

Differentiation between vergence and saccadic functional activity within the human frontal eye fields and midbrain revealed through fMRI

Purpose

Eye movement research has traditionally studied solely saccade and/or vergence eye movements by isolating these systems within a laboratory setting. While the neural correlates of saccadic eye movements are established, few studies have quantified the functional activity of vergence eye movements using fMRI. This study mapped the neural substrates of vergence eye movements and compared them to saccades to elucidate the spatial commonality and differentiation between these systems.

Methodology

The stimulus was presented in a block design where the ‘off’ stimulus was a sustained fixation and the ‘on’ stimulus was random vergence or saccadic eye movements. Data were collected with a 3T scanner. A general linear model (GLM) was used in conjunction with cluster size to determine significantly active regions. A paired t-test of the GLM beta weight coefficients was computed between the saccade and vergence functional activities to test the hypothesis that vergence and saccadic stimulation would have spatial differentiation in addition to shared neural substrates.

Results

Segregated functional activation was observed within the frontal eye fields where a portion of the functional activity from the vergence task was located anterior to the saccadic functional activity (z>2.3; p<0.03). An area within the midbrain was significantly correlated with the experimental design for the vergence but not the saccade data set. Similar functional activation was observed within the following regions of interest: the supplementary eye field, dorsolateral prefrontal cortex, ventral lateral prefrontal cortex, lateral intraparietal area, cuneus, precuneus, anterior and posterior cingulates, and cerebellar vermis. The functional activity from these regions was not different between the vergence and saccade data sets assessed by analyzing the beta weights of the paired t-test (p>0.2).

Conclusion

Functional MRI can elucidate the differences between the vergence and saccade neural substrates within the frontal eye fields and midbrain.     

A Mathematical Model of Optimal Saccadic Eye Movement by a Pair of Muscles

This paper presents a model of saccadic eye movements. Eye movements are considered as being ballistic, since saccades (rapid concurrent movements of both eyes) occur several hundred thousand times per day; visual perception of the environment is interrupted by a saccade. The optimal control was constructed for the motion considered in three consecutively refined assumptions. The controls included in the time-optimal problem were the resultant moment of force exerted by the extraocular muscles, individual moments of force exerted by either muscle of the agonist–antagonist pair, and finally, the rate of change of these moments. This approach is consistent with the view that is currently upheld by physiologists, who believe that a saccade is programmed by the central nervous system before the beginning of an eye movement and is scarcely adjusted during the movement itself. The solution of the optimal control problem and the results obtained by subsequent numerical modeling of saccadic trajectories were compared with the published experimental data. The saccadic trajectories were compared based on the main sequence, the known consistent relationship between saccade amplitude and duration, which is the most widely applied and commonly accepted way of describing saccade data. The main sequence of saccades obtained from the solution of the optimal control problem formulated in the most complete form agreed well with published experimental results.     

Saccadic adaptation to moving targets

Saccades are so called ballistic movements which are executed without online visual feedback. After each saccade the saccadic motor plan is modified in response to post-saccadic feedback with the mechanism of saccadic adaptation. The post-saccadic feedback is provided by the retinal position of the target after the saccade. If the target moves after the saccade, gaze may follow the moving target. In that case, the eyes are controlled by the pursuit system, a system that controls smooth eye movements. Although these two systems have in the past been considered as mostly independent, recent lines of research point towards many interactions between them. We were interested in the question if saccade amplitude adaptation is induced when the target moves smoothly after the saccade. Prior studies of saccadic adaptation have considered intra-saccadic target steps as learning signals. In the present study, the intra-saccadic target step of the McLaughlin paradigm of saccadic adaptation was replaced by target movement, and a post-saccadic pursuit of the target. We found that saccadic adaptation occurred in this situation, a further indication of an interaction of the saccadic system and the pursuit system with the aim of optimized eye movements.     

Effect of dopamine deficiency on the preparation of visually guided saccadic eye movements

Parameters of saccadic eye movements were studied in patients with Parkinson's disease and control subjects. In parkinsonian patients, the number of slow regular saccades was shown to be increased, and the number of express saccades was shown to be decreased. As a result the mean of saccade latency in patients was longer than in the control group. Moreover, the percentage of multistep saccades in patients with Parkinson's disease. In this case, not one but two or three saccades were performed with smaller amplitude to the target. We point, that the multistep saccades occurred mainly among the express saccades. Obviously, the dopamine deficiency distinguishing parkinsonian patients takes the primary part in the development of saccadic disorders. Degeneration of the nigrostriatal dopamine pathway results in imbalance in activity of the direct and indirect output pathways of the striatum. We suppose that this leads to inhibition of neurons activity in the superior colliculus during the saccade performance, which results in the early saccade interruption. In support of this reasoning, the mean of saccade latency and the percentage of the multistep saccades decreased in patients with Parkinson's disease after dopamine D2/D3 agonist (piribedil) treatment, due to activity restoration of the indirect pathway.     

Age-related changes in saccadic eye movements in healthy subjects and patients with Parkinson's disease

Age-related changes in characteristics of saccadic eye movements (latency, duration and percentage of multistep saccades) in healthy subjects and patients with Parkinson's disease were evaluated. Healthy volunteers were divided into 6 age groups (17-20 years, 21-30 years, 31-40 years, 41-50 years, 51-60 years, 61-75 years), parkinsonian patients into 3 age groups (41-50 years, 51-60 years, 61-75 years). According to our data, saccade characteristics depend upon age in both healthy subjects and parkinsonian patients. In healthy volunteers the percentage of multistep saccades and the mean saccade latency increase significantly after the age of 60. Values of these characteristics in patients with Parkinson's disease significantly exceed the values in the corresponding age groups of healthy subjects. The "disease" factor (MANOVA) has a greater influence on saccade latency and percentage of multistep saccades then the "age" factor. The duration of single saccades depends on age to a smaller extent and does not change in patients with Parkinson's disease. The peculiarities of neurodegenerative processes during normal aging and aging with Parkinson's disease are discussed.     

A novel interpretation for the collicular role in saccade generation

Recently, we found evidence that the activity of neurons in the deep layers of the monkey superior colliculus (SC) is modulated by initial eye position (gain fields). In this paper, we propose a quantitative model of the motor SC which incorporates these new findings. Inputs to the motor map represent the desired eye displacement vector (motor error), as well as initial eye position. A unit's activity in the motor map is described by multiplying a weak linear eye position sensitivity with a gaussian tuning to motor error. The motor map projects to several sets of output neurons, representing the coordinates of the desired eye displacement vector, the desired eye position in the head, and the three-dimensional ocular rotation axis for saccades in Listing's plane, respectively. All these signals have been hypothesized in the literature to drive the saccade burst generator. We show that these signals can be extracted from the motor map by a linear weighting of the population activity. The saccadic system may employ all coding strategies in parallel to ensure high spatial accuracy in many complex sensorimotor tasks, such as orienting to multimodal stimuli.     

Effect of seven-day dry immersion on the mechanisms of ocular saccadic movement generation

In order to evaluate the impact of prolonged support deprivation on the mechanisms of ocular saccadic movement generation, four volunteers were tested immediately before seven-day dry immersion and on the day of its completion. The task consisted of tapping random light stimuli emerging on the periphery of a sensory screen. During testing, the subject??s head was kept in a fixed position. The subjects could suppress the stimuli in two ways: (1) by touching an appropriate area on the screen with their fingers with gaze shifting and fixation accompanying coordinated hand movement or (2) by clicking the computer mouse button after gaze fixation on the stimulus. The movement pattern of each eye was recorded and analyzed in the infrared frequency of 200 Hz. It is assumed that the identical effects of immersion on the dependence of the peak saccade velocity on its amplitude in tests where the two methods of stimulus tapping were used suggest saccade acceleration after immersion as a direct effect of prolonged support deprivation.     

The composition of central programs subserving horizontal eye movements in man

A hypothesis is presented which describes, in biomechanical terms, the central programs underlying horizontal eye movements in man. It is suggested that eye movements are produced by means of programmed shifts of the so-called invariant muscle characteristics (static force vs angle of gaze). These shifts lead to a change of the equilibrium point resulting from the interaction of agnnist and antagonist muscles and, as a consequence, to movement and the attainment of a new position of gaze. A reciprocal or a coactivation command to agonist and antagonist muscles occurs when their characteristics shift with respect to the coordinate in the same or opposite directions, respectively. It is proposed that during pursuit and saccadic eye movements a supperposition of the both central commands occurs. During a saccade, the reciprocal command develops evenly up to a certain level. The initial and final levels of the reciprocal command dictate the respective position of gaze and therefore the size of the saccade. The coactivation command develops to a maximum level and is slowly switched off when the new position of gaze has been achieved. The magnitude of the coactivation command seems to be not connected with an absolute position of gaze. It provides probably a stability of the movement and, in particular, prevents overshoot and oscillation during the saccade. The same timing of these commands occurs during pursuit movements, but the magnitude of the coactivation command and the rates of the development of the both commands are less in this case and correlate with the velocity of the movement. This hypothesis enables the tension changes in the muscle during saccadic and pursuit movements to be simulated in qualitative accordance with unique experimental data obtained by Collins et al. (1975). The functional significance of superposition of these motor commands and similarity in the efferent organization of eye and limb movements are discussed.