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A relative preservation of eye movements is notable in ALS, but saccadic functions have not been studied longitudinally. ALS overlaps with FTD, typically involving executive dysfunction, and eye-tracking offers additional potential for the assessment of extramotor pathology where writing and speaking are both impaired. Eye-tracking measures (including anti-saccade, trail-making and visual search tasks) were assessed at six-monthly intervals for up to two years in a group of ALS (n= 61) and primary lateral sclerosis (n= 7) patients, compared to healthy age-matched controls (n= 39) assessed on a single occasion. Task performance was explored speculatively in relation to resting-state functional MRI (R-FMRI) network connectivity. Results showed that ALS patients were impaired on executive and visual search tasks despite normal basic saccadic function, and impairments in the PLS patients were unexpectedly often more severe. No significant progression was detected longitudinally in either group. No changes in R-FMRI network connectivity were identified in relation to patient performance. In conclusion, eye-tracking offers an objective means to assess extramotor cerebral involvement in ALS. The relative resistance of pure oculomotor function is confirmed, and higher-level executive impairments do not follow the same rate of decline as physical disability. PLS patients may have more cortical dysfunction than has been previously appreciated. [ABSTRACT FROM AUTHOR]

The frontal cortex and basal ganglia form a set of parallel but mostly segregated circuits called cortico-basal ganglia loops. The oculomotor loop controls eye movements and can direct relatively simple movements, such as reflexive prosaccades, without external help but needs input from "higher" loops for more complex behaviors. The antisaccade task requires the dorsolateral prefrontal cortex, which is part of the prefrontal loop. Information flows from prefrontal to oculomotor circuits in the striatum, and directional errors in this task can be considered a measure of failure of prefrontal control over the oculomotor loop. The antisaccadic error rate (AER) is increased in Parkinson's disease (PD). Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has no effect on the AER, but a previous case suggested that DBS of the globus pallidus interna (GPi) might. Our aim was to compare the effects of STN DBS and GPi DBS on the AER. We tested eye movements in 14 human DBS patients and 10 controls. GPiDBS substantially reduced the AER, restoring lost higher control over oculomotor function. Interloop information flow involves striatal neurons that receive cortical input and project to pallidum. They are normally silent when quiescent, but in PD they fire randomly, creating noise that may account for the degradation in interloop control. The reduced AER with GPi DBS could be explained by retrograde stimulation of striatopallidal axons with consequent activation of inhibitory collaterals and reduction in background striatal firing rates. This study may help explain aspects of PD pathophysiology and the mechanism of action of GPi DBS. [ABSTRACT FROM AUTHOR]

total of 29 patients with homonymous visual field defects without neglect practised visual search in 20 daily sessions, over a period of 4 weeks. Patients searched for a single randomly positioned target amongst distractors displayed for 3 s. After training patients demonstrated significantly shorter reaction times for search stimuli (Pambakian et al. in J Neurol Neurosurg Psychiatry 75:1443-1448, 2004). In this study, patients achieved improved search efficiency after training by altering their oculomotor behaviour in the following ways: (1) patients directed a higher proportion of fixations into the hemispace containing the target, (2) patients were quicker to saccade into the hemifield containing the target if the initial saccade had been made into the opposite hemifield, (3) patients made fewer transitions from one hemifield to another before locating the target, (4) patients made a larger initial saccade, although the direction of the initial saccade did not change as a result of training, (5) patients acquired a larger visual lobe in their blind hemifield after training. Patients also required fewer saccades to locate the target after training reflecting improved search efficiency. All these changes were confined to the training period and maintained at follow-up. Taken together these results suggest that visual training facilitates the development of specific compensatory eye movement strategies in patients with homonymous visual field defects. [ABSTRACT FROM AUTHOR]

Abstract: Oculomotor capture can occur automatically in a bottom-up way through the sudden appearance of a new object or in a top-down fashion when a stimulus in the array matches the contents of working memory. However, it is not clear whether or not working memory processing can influence the early stages of oculomotor capture by abrupt onsets. Here we present clear evidence for an early modulation driven by stimulus matches to the contents of working memory in the colour dimension. Interestingly, verbal as well as visual information in working memory influenced the direction of the fastest saccades made in search, saccadic latencies and the curvature of the scan paths made to the search target. This pattern of results arose even though the contents of working memory were detrimental for search, demonstrating an early, automatic top-down mediation of oculomotor onset capture by the contents of working memory. [Copyright &y& Elsevier]

The promise of new treatments for Huntington's disease (HD) has intensified interest in markers of preclinical onset and progression. Recent research has shown that elementary saccadic tasks may exhibit subtle preclinical abnormalities. Other studies have shown cognitive dysfunction to be a major component of early-HD phenotype. It was hypothesized that the synergistic combination of an oculomotor response with a cognitively demanding paradigm might therefore offer a functional marker that could be superior both to simpler saccadic paradigms and to conventional cognitive tests. The performance of 12 early-symptomatic HD patients and 17 presymptomatic gene carriers on three saccadic paradigms were studied: prosaccades, color-cued centrally triggered saccades and a second-order conditional rule task on which the direction of the saccade was cued by the combination of central and peripheral cues. Eye movements were recorded using a highly portable, patient-friendly infrared recording device. The analysis of the latency distributions showed that the second-order conditional rule task could discriminate between clinical groups, had a predictive potential within the presymptomatic group and appeared to be more sensitive than easier tasks. The simplicity of portable saccadometry, combined with the sensitivity of a complex oculomotor task, may therefore offer a promising functional marker in HD. [ABSTRACT FROM AUTHOR]

Active region is a dynamic process involving the Flexible coordination of different gaze strategies to achieve behavioral goals, although many complex behaviors rely on an ability to efficiently switch between gaze-control strategies, few studies to date have examined mechanisms of task level oculomotor control in detail. Here, we report few experiments in which subjects alternated between conflicting stimulus saccade mappings within a block of trials. The first experiment showed that there is no performance cost associated witch switching between pro and anti saccades. However, follow-up experiment demonstrate that whenever subjects alternate between arbitrary stimulus-saccade mappings, latency costs are apparent on the first trial after a task change. More detailed analysis of switch costs showed that latencies were particularly elevated for saccacdes directed toward the same location that had been the target for a saccade on the preceeding trial. This saccade "inhibition of return" effect was most marked when unexpected error feedbacks cued task switches, suggesting that saccade selection processes arc modulated by reward We conclude that there are two systems for arcade control that differ in their characteristics following a task switch. The "reflexive" control system can be enabled/disabled in advance of saccade execution without incurring any performance cost. Switch costs are only observed when two or more arbitrary stimulus-saccade mappings have to be coordinated by a "symbolic" control system. [ABSTRACT FROM AUTHOR]

We investigated the organisation of working memory processes by examining how a secondary memory task interferes with the accuracy of memory-guided saccades. A target was flashed at a random location, followed by a Kanji character. Subjects had to remember the location of the target and the Kanji character, and then they had to make a saccade towards the remembered target location. A second Kanji character was displayed and the subject had to decide if it was same or different. The performance of seven non-Kanji reader's were compared with six fluent Kanji readers in the task. Memorisation of Kanji characters was found to interfere with the accuracy of memory-guided saccades made by non-Kanji, but not by Kanji readers. These findings directly contradict accounts of working memory function which propose that spatial and visual object memory are functionally discrete. [ABSTRACT FROM AUTHOR]

The latency of 'reflexive' saccades (made in response to peripheral visual stimuli) was compared to that of 'voluntary' saccades performed in anti-saccade and symbolically cued paradigms. Manipulation of visual events at fixation was carefully controlled across all conditions. Reflexive saccade latency was significantly faster than the latency of all forms of voluntary saccades. Importantly, the latency of saccades made after presentation of a symbolic cue at central fixation (voluntary arrow-cue condition) was greater than that made in the anti-saccade paradigm that requires suppression of a reflexive response. It is suggested that the increase in latency of saccades made in the voluntary arrow-cue condition may reflect differences in programming a 'When' trigger signal for saccades made in the absence of a peripheral stimulus. [ABSTRACT FROM AUTHOR]

Objectives: The evaluation of novel disease modifying drugs requires biomarkers that are simultaneously sensitive to disease state but resistant to the effects of background symptomatic treatment. Saccadic eye movement parameters have been proposed as a neurophysiological biomarker for Parkinson's disease (PD) and so it is important to know how they are affected by dopaminergic medication. Studies to date are conflicting: some have concluded that medication prolongs saccadic latencies while others suggest they are shortened. We aimed to characterise the effects of antiparkinsonian medication on prosaccadic and antisaccadic parameters in a large cohort of PD patients and age matched healthy controls and to survey the current literature in comparison to the study findings.Methods: We studied saccades both off and on medication in 38 PD patients and 34 healthy controls (HC). Latencies, amplitudes, velocities, and directional errors were evaluated, using a published standardised protocol. We then combined this study and previously published literature in a meta-analysis of the effects of antiparkinsonian medication on prosaccadic latency (PSL).Results: PSL is significantly prolonged by dopaminergic medication in PD, from a mean of 222.7 ms in the OFF medication state to a mean of 236.0 ms in the ON medication state (p = 0.028). This effect size is comparable to the difference between PD OFF medication and healthy control values. There was no statistically significant change in any other saccadic parameter with medication. Of particular note, antisaccadic latency was almost exactly the same on and off medication (means of 414.9 ms and 417.2 ms respectively, p = 0.97), while being almost 20% longer in PD patients compared to healthy controls (HC mean 357.2 ms; PD ON vs HC p = 0.015; PD OFF vs HC p = 0.0066).Conclusion: PSL is significantly affected by dopaminergic medication which may complicate its use as a biomarker in drug trials. Antisaccadic latency is particularly interesting in this regard because it shows a large disease effect with no medication effect. [ABSTRACT FROM AUTHOR]

Abstract: Making flexible associations between what we see and what we do is important for many everyday tasks. Previous work in patients with focal lesions has shown that the control of saccadic eye movements in such contexts relies on a network of areas in the frontal cerebral cortex. These regions are reciprocally connected with structures in the basal ganglia although the contribution of these sub-cortical structures to oculomotor control in complex tasks is not well understood. We report the performance of patients with idiopathic Parkinsons disease (PDs) in a test which required learning and switching between arbitrary cue-saccade rules. In Experiment 1 feedback was given following each response which reliably indicated which of the two possible rules was correct. PDs were slower to learn the first cue-saccade association presented, but did not show increased error or reaction time switch costs when switching between two rules within blocks. In a follow up experiment the feedback given by the computer was adjusted to be probabilistic such that executing a response based upon the “correct” rule only resulted in positive feedback on 80% of trials. Under these conditions patients were impaired in terms of response latencies and number of errors. In all conditions PDs showed multi-stepping/hypometria of saccades consistent with a motoric deficit in executing actions based on cognitive cues. The findings are consistent with a role for the nigrostriatal dopamine system in the reinforcement of saccade-response-outcome associations. Intact performance of PDs when associations are not stochastically reinforced suggests that striatal learning systems are complemented by cognitive representations of task rules which are unaffected in the early stages of PD. [Copyright &y& Elsevier]

Abstract: Detailed measurements of saccadic latency – the time taken to make an eye movement to a suddenly-presented visual target – have proved a valuable source of detailed and quantitative information in a wide range of neurological conditions, as well as shedding light on the mechanisms of decision, currently of intense interest to cognitive neuroscientists. However, there is no doubt that more complex oculomotor tasks, and in particular the antisaccade task in which a participant must make a saccade in the opposite direction to the target, are potentially more sensitive indicators of neurological dysfunction, particularly in neurodegenerative conditions. But two obstacles currently hinder their widespread adoption for this purpose. First, that much of the potential information from antisaccade experiments, notably about latency distribution and amplitude, is typically thrown away. Second, that there is no standardised protocol for carrying out antisaccade experiments, so that results from one laboratory cannot easily be compared with those from another. This paper, the outcome of a recent international meeting of oculomotor scientists and clinicians with an unusually wide experience of such measurements, sets out a proposed protocol for clinical antisaccade trials: its adoption will greatly enhance the clinical and scientific benefits of making these kinds of measurements. [Copyright &y& Elsevier]

A saccade involves both a step in eye position and an obligatory shift in spatial attention. The traditional division of saccades into two types, the “reflexive” saccade made in response to an exogenous stimulus change in the visual periphery and the “voluntary” saccade based on an endogenous judgement to move gaze, is supported by lines of evidence which include the longer onset latency of the latter and the differential effects of lesions in humans and primates on each. It has been supposed that differences between the two types of saccade derive from differences in how the spatial attention shifts involved in each are processed. However, while functional imaging studies have affirmed the close link between saccades and attentional shifts by showing they activate overlapping cortical networks, attempts to contrast exogenous with endogenous (“covert”) attentional shifts directly have not revealed separate patterns of cortical activation. We took the “overt” approach, contrasting whole reflexive and voluntary saccades using event-related fMRI. This demonstrated that, relative to reflexive saccades, voluntary saccades produced greater activation within the frontal eye fields and the saccade-related area of the intraparietal sulci. The reverse contrast showed reflexive saccades to be associated with relative activation of the angular gyrus of the inferior parietal lobule, strongest in the right hemisphere. The frequent involvement of the right inferior parietal lobule in lesions causing hemispatial neglect has long implicated this parietal region in an important, though as yet uncertain, role in the awareness and exploration of space. This is the first study to demonstrate preferential activation of an area in its posterior part, the right angular gyrus, during production of exogenously triggered rather than endogenously generated saccades, a finding which we propose is consistent with an important role for the angular gyrus in exogenous saccadic orienting. [Copyright &y& Elsevier]