Search

Systematic differences in circadian rhythmicity are thought to be a substantial factor determining inter-individual differences in fatigue and cognitive performance. The synchronicity effect (when time of testing coincides with the respective circadian peak period) seems to play an important role. Eye movements have been shown to be a reliable indicator of fatigue due to sleep deprivation or time spent on cognitive tasks. However, eye movements have not been used so far to investigate the circadian synchronicity effect and the resulting differences in fatigue. The aim of the present study was to assess how different oculomotor parameters in a free visual exploration task are influenced by: a) fatigue due to chronotypical factors (being a 'morning type' or an 'evening type'); b) fatigue due to the time spent on task. Eighteen healthy participants performed a free visual exploration task of naturalistic pictures while their eye movements were recorded. The task was performed twice, once at their optimal and once at their non-optimal time of the day. Moreover, participants rated their subjective fatigue. The non-optimal time of the day triggered a significant and stable increase in the mean visual fixation duration during the free visual exploration task for both chronotypes. The increase in the mean visual fixation duration correlated with the difference in subjectively perceived fatigue at optimal and non-optimal times of the day. Conversely, the mean saccadic speed significantly and progressively decreased throughout the duration of the task, but was not influenced by the optimal or non-optimal time of the day for both chronotypes. The results suggest that different oculomotor parameters are discriminative for fatigue due to different sources. A decrease in saccadic speed seems to reflect fatigue due to time spent on task, whereas an increase in mean fixation duration a lack of synchronicity between chronotype and time of the day.

Objective: The effects of 4-aminopyridine (4-AP) on downbeat nystagmus (DBN) were analysed in terms of slow-phase velocity (SPV), stance, locomotion, visual acuity (VA), patient satisfaction and side effects using standardised questionnaires., Methods: Twenty-seven patients with DBN received 5 mg 4-AP four times a day or placebo for 3 days and 10 mg 4-AP four times a day or placebo for 4 days. Recordings were done before the first, 60 min after the first and 60 min after the last drug administration., Results: SPV decreased from 2.42 deg/s at baseline to 1.38 deg/s with 5 mg 4-AP and to 2.03 deg/s with 10 mg 4-AP (p<0.05; post hoc: 5 mg 4-AP: p=0.04). The rate of responders was 57%. Increasing age correlated with a 4-AP-related decrease in SPV (p<0.05). Patients improved in the 'get-up-and-go test' with 4-AP (p<0.001; post hoc: 5 mg: p=0.025; 10 mg: p<0.001). Tandem-walk time (both p<0.01) and tandem-walk error (4-AP: p=0.054; placebo: p=0.059) improved under 4-AP and placebo. Posturography showed that some patients improved with the 5 mg 4-AP dose, particularly older patients. Near VA increased from 0.59 at baseline to 0.66 with 5 mg 4-AP (p<0.05). Patients with idiopathic DBN had the greatest benefit from 4-AP. There were no differences between 4-AP and placebo regarding patient satisfaction and side effects., Conclusions: 4-AP reduced SPV of DBN, improved near VA and some locomotor parameters. 4-AP is a useful medication for DBN syndrome, older patients in particular benefit from the effects of 5 mg 4-AP on nystagmus and postural stability.

A 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.

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 2010 Elsevier Ltd. All rights reserved.)

Previous studies have produced contradictory evidence on the nature of the visual search impairment in patients with Parkinson's disease (PD). Eye movements were measured during multi-target search in nine individuals with mild-to-moderate PD. Subjects were asked to click on a response button whenever they judged they were fixating a target for the first time. Compared to age-matched healthy volunteers, PD patients were impaired at efficient search (detecting "+"s amongst "L"s) but not inefficient search ("T"s amongst "L"s). However, these patients had normal memory for locations as indexed by their rate of re-clicking on previously inspected locations. We suggest that the pattern of gaze for efficient search may reflect impaired saliency processing in PD.

Although the conceptual distinction between voluntary and automatic acts seems intuitively obvious, its neural basis remains opaque. Assigning volition--or some paraphrase such as action selection--to discrete parts of the brain arguably tells us nothing about what volition actually is in neural terms. Equally, exploring the relative sensitivity of discrete brain areas to manipulations of action choice, including its asymptote--free choice--would only be informative if voluntary processes could thereby be reliably isolated. Unfortunately, such manipulations are subject to ineliminable confounds, such as the complexity of the underlying condition-action associations. Here we propose an adaptation of a classic oculomotor task--saccadic choice with asynchronous targets--where the processes engaged in free choice manifest as interference in the performance of an automatic task, thereby circumventing the difficulties in parameterising volition. We suggest that this task may be useful in probing deficits in voluntary action in pathological states.

Active vision 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 five 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 with switching between pro and anti saccades. However, follow-up experiments 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 saccades 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 are modulated by reward. We conclude that there are two systems for saccade 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.

Huntington’s disease (HD) is genetically determined but with variability in symptom onset, leading to uncertainty as to when pharmacological intervention should be initiated. Here we take a computational approach based on neurocognitive phenotyping, computational modeling, and classification, in an effort to provide quantitative predictors of HD before symptom onset. A large sample of subjects—consisting of both pre-manifest individuals carrying the HD mutation (pre-HD), and early symptomatic—as well as healthy controls performed the antisaccade conflict task, which requires executive control and response inhibition. While symptomatic HD subjects differed substantially from controls in behavioral measures [reaction time (RT) and error rates], there was no such clear behavioral differences in pre-HD. RT distributions and error rates were fit with an accumulator-based model which summarizes the computational processes involved and which are related to identified mechanisms in more detailed neural models of prefrontal cortex and basal ganglia. Classification based on fitted model parameters revealed a key parameter related to executive control differentiated pre-HD from controls, whereas the response inhibition parameter declined only after symptom onset. These findings demonstrate the utility of computational approaches for classification and prediction of brain disorders, and provide clues as to the underlying neural mechanisms. [ABSTRACT FROM AUTHOR]

Background Cognitive impairment is well recognized in Parkinson's disease (PD), but when it begins to develop is unclear. The aim of this study was to identify early signs of cognitive impairment along with abnormalities in saccadic behavior in newly diagnosed unmedicated PD patients. Methods Nineteen drug-naive PD patients and 20 controls were examined using a battery of tests, including an antisaccade task, phonemic and semantic verbal fluencies, and a switching and rule finding task. Results With simple tasks, no differences were found between the two groups. However, cognitive performance of the two groups diverged with more complex tasks, occurring independently of PD-related motor impairment. Patients exhibited higher antisaccadic error rates and switch costs in the task switching test, and performed significantly worse in the rule finding task. Conclusions Certain cognitive domains and saccadic parameters are already significantly impoverished in newly diagnosed Parkinson's patients, even before the initiation of medication. © 2015 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

The cortico- basal- ganglia circuit plays a critical role in decision making on the basis of probabilistic information. Computational models have suggested how this circuit could compute the probabilities of actions being appropriate according to Bayes' theorem. These models predict that the subthalamic nucleus (STN) provides feedback that normalizes the neural representation of probabilities, such that if the probability of one action increases, the probabilities of all other available actions decrease. Here we report the results of an experiment testing a prediction of this theory that disrupting information processing in the STN with deep brain stimulation should abolish the normalization of the neural representation of probabilities. In our experiment, we asked patients with Parkinson's disease to saccade to a target that could appear in one of two locations, and the probability of the target appearing in each location was periodically changed. When the stimulator was switched off, the target probability affected the reaction times (RT) of patients in a similar way to healthy participants. Specifically, the RTs were shorter for more probable targets and, importantly, they were longer for the unlikely targets. When the stimulator was switched on, the patients were still faster for more probable targets, but critically they did not increase RTs as the target was becoming less likely. This pattern of results is consistent with the prediction of the model that the patients on DBS no longer normalized their neural representation of prior probabilities. We discuss alternative explanations for the data in the context of other published results. [ABSTRACT FROM AUTHOR]

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]

Right-hemisphere patients with left neglect often demonstrate abnormal visual search, re-examining stimuli to the right while ignoring those to the left. But re-fixations alone do not reveal if patients misjudge whether they have searched a location before. Here, we not only tracked the eye movements of 16 neglect patients during search, but also asked them to click a response button only when they judged they were fixating a target for the very first time. ''Re-clicking'' on previously found targets would indicate that patients erroneously respond to these as new discoveries. Lesions were mapped with high-resolution MRI. Neglect patients with damage involving the right intraparietal sulcus or right inferior frontal lobe ''re-clicked'' on previously found targets on the right at a pathological rate, whereas those with medial occipito-temporal lesions did not. For the intraparietal sulcus patients, the probability of erroneous re-clicks on an old target increased with time since first discovering it; whereas for frontal patients it was independent of search time, suggesting different underlying mechanisms in these two types of patient. Re-click deficits correlated with degree of leftward neglect, mainly due to both being severe in intraparietal cases. These results demonstrate that misjudging previously searched locations for new ones can contribute to pathological search in neglect, with potentially different mechanisms being involved in intraparietal versus inferior frontal patients. When combined with a spatial bias to the right, such deficits might explain why many neglect patients often re-examine rightward locations, at the expense of items to their left. [ABSTRACT FROM AUTHOR]

Parkinson's disease patients are known to suffer loss of dopaminergic input to the rostral caudate nucleus. Recent functional magnetic resonance imaging (fMRI) studies have implicated this structure in the transformation of spatial information in memory to guide action, suggesting that memory to motor transformations may be selectively impaired in Parkinson's disease. In order to investigate this possibility we tested a group of Parkinson's disease patients (PDs) using a memory-guided pointing task. Of interest was whether patients showed reduced accuracy in the task as a function of memory load. Twelve PD patients and 13 elderly controls were asked to recall single or four step target sequences with 2 time delays (500 and 3,500 ms). In all memory-guided conditions PD patients showed increased variability in memory-guided movement end-points. This effect was not affected by delay, number of items, or the sequence familiarity. The results are consistent with increased variability in memory-motor transformations in early PD, due to dopamine depletion within the rostral caudate nucleus. [ABSTRACT FROM AUTHOR]

In this paper, we describe a novel approach to the study of problem solving involving the detailed analysis of natural scanning eye movements during the "one-touch" Tower-of-London (TOL) task. We showed subjects a series of pictures depicting two arrangements of colored balls in pockets within the upper and lower halves of a computer display. The task was to plan (but not to execute) the shortest movement sequence required to rearrange the balls in one half of the display (the Workspace) to match the arrangement in the opposite half (the Goalspace) and indicate the minimum number of moves required for problem solution. We report that subjects are more likely to look towards the Goalspace in the initial period after picture presentation, but bias gaze towards the Workspace during the middle of trials. Towards the end of a trial, subjects are once again more likely to fixate the Goalspace. This pattern is found regardless of whether the subjects solve problems by rearranging the balls in the lower or upper visual fields, demonstrating that this strategy correlates with discrete phases in problem solving. A second experiment showed that efficient planners direct their gaze selectively towards the problem critical balls in the Workspace. In contrast, individuals who make errors spend more time looking at irrelevant items and are strongly influenced by the movement strategy needed to solve the preceding problem. We conclude that efficient solution of the TOL requires the capacity to generate and flexibly shift between control sets, including those underlying ocular scanning. The role of working memory and the prefrontal cerebral cortex in the task are discussed. [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]

Summary: Background: TRACK-HD is a prospective observational biomarker study in premanifest and early Huntington''s disease (HD). In this report we define a battery of potential outcome measures for therapeutic trials. Methods: We assessed longitudinal data collected at baseline, 12 months, and 24 months at sites in Leiden (Netherlands), London (UK), Paris (France), and Vancouver (Canada). Participants were individuals without HD but carrying the mutant HTT gene (ie, premanifest HD), patients with early HD, and healthy control individuals matched by age and sex to the combined HD groups. Data were collected with 3T MRI, clinical, cognitive, quantitative motor, oculomotor, and neuropsychiatric assessments. We estimated adjusted, between-group differences in rates of change in these measures and concomitant longitudinal effect sizes. Findings: Longitudinal data were available for 116 control individuals, 117 premanifest gene carriers, and 116 participants with early HD. Significantly greater progressive grey-matter, white-matter, whole-brain, and regional atrophy was recorded in the premanifest and early HD groups than in the control group. Effect sizes for atrophy rates between participants with early HD and controls were largest in the caudate (2·04, 95% CI 1·68 to 2·48) and white matter (1·70, 1·40 to 2·08). Functional, quantitative motor, and cognitive measures deteriorated to a greater extent in the early HD group than in controls, with the largest effect size in the symbol digit modality test (1·00, 0·67 to 1·27). In the early HD group, changes in structural imaging and various cognitive and quantitative motor scores were associated with worsening total motor score (TMS) and total functional capacity (TFC). In the premanifest group, despite significant declines in regional and overall brain volumes, few functional variables showed significant 24 month change compared with controls; TMS, emotion recognition, and speeded tapping were exceptions. Premanifest individuals with progression, predefined as an increase in TMS score of 5 points or more, any TFC decline, or a new diagnostic confidence score of 4, exhibited higher rates of brain atrophy and deterioration on some quantitative motor tasks compared with other premanifest participants. Interpretation: On the basis of longitudinal effect size, we recommend several objective outcome measures for clinical trials in participants with early HD. Hypothetical treatment effects defined by slower longitudinal changes in these measures would be detectable over a realistic timescale with practical sample sizes. The restricted 24 month cognitive or motor decline in the premanifest sample illustrates the greater challenge in trial design for this group. Funding: CHDI/HighQ Foundation Inc. [ABSTRACT FROM AUTHOR]

Abstract: The functional–neuroanatomic relationship that describes the involvement of the parietal cortex in visual search was investigated using repetitive transcranial magnetic stimulation (rTMS; 10Hz, 500ms in duration). Twelve adult participants performed feature-based visual search for a unique letter—without eye movements—under conditions that involved manipulations of search efficiency (efficient versus inefficient) and target-selection demands (set-size: 4 versus 10). rTMS was applied over the right posterior parietal cortex at the onset of the search array for all factorial conditions (0–500ms); stimulation was additionally administered at 500ms post-array onset (500–1000ms) during inefficient search (set-size 10). Stimulation over the primary sensorimotor cortex served as a within-subjects control condition, and eye movements were monitored continuously. Significant increases in reaction time were restricted to parietal stimulation during inefficient search (set-size 10), with interference observed when rTMS was administered at the onset of the search array and at 500ms post-array onset. The early effect was confined to target-present trials and the late effect was confined to target-absent trials, which may indicate temporally dissociable parietal involvement in target detection and response-based selection and/or search termination, respectively. Error rates did not vary significantly as a function of any of the independent variables. Taken together, these results are consistent with evidence from functional magnetic resonance studies indicating that inefficient feature-based visual search requires an intact parietal cortex, and also indicate that the parietal cortex is involved in inefficient search later than has been previously reported. [Copyright &y& Elsevier]

Controversy surrounds the role of human medial frontal cortex in controlling actions . Although damage to this area leads to severe difficulties in spontaneously initiating actions , the precise mechanisms underlying such “volitional” deficits remain to be established. Previous studies have implicated the medial frontal cortex in conflict monitoring and the control of voluntary action , suggesting that these key processes are functionally related or share neural substrates. Here, we combine a novel behavioral paradigm with functional imaging of the oculomotor system to reveal, for the first time, a functional subdivision of the pre-supplementary motor area (pre-SMA) into anatomically distinct areas that respond exclusively to either volition or conflict. We also demonstrate that activity in the supplementary eye field (SEF) distinguishes between success and failure in changing voluntary action plans during conflict, suggesting a role for the SEF in implementing the resolution of conflicting actions. We propose a functional architecture of human medial frontal cortex that incorporates the generation of action plans and the resolution of conflict. [Copyright &y& Elsevier]

Visual orienting of attention and gaze are widely considered to be mediated by shared neural pathways , with automatic phenomena such as inhibition of return (IOR)—the bias against returning to recently visited locations—being generated via the direct pathway from retina to superior colliculus (SC) . Here, we show that IOR occurs without direct access to the SC, by using a technique that employs stimuli visible only to short-wave-sensitive (S) cones . We found that these stimuli, to which the SC is blind , were quite capable of eliciting IOR, measured by traditional manual responses . Critically, however, we found that S cone stimuli did not cause IOR when saccadic eye movement responses were required. This demonstrates that saccadic IOR is not the same as traditional IOR, providing support for two separate cortical and collicular mechanisms of IOR. These findings represent a clear dissociation between visual orienting of attention and gaze. [Copyright &y& Elsevier]