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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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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. GPi DBS 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. Significance statement: Parkinson's disease causes symptoms including stiffness, slowness of movement, and tremor. Electrical stimulation of specific areas deep in the brain can effectively treat these symptoms, but exactly how is not fully understood. Part of the cause of such symptoms may be impairments in the way information flows from one circuit within the brain to another, as a result of overactivity of certain nerve cells. By demonstrating that stimulation of an area called the globus pallidus interna partially reverses deficits in voluntary control of eye movements, this study shows that stimulation can improve information flow between circuits, probably by calming down the overactive cells., (Copyright © 2015 the authors 0270-6474/15/3513043-10$15.00/0.)

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.)

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., (Copyright © 2014 the authors 0270-6474/14/3410844-09$15.00/0.)

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 © 2013 Elsevier Ltd. All rights reserved.)

We report a case of induced oscillopsia caused by deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN). Recent reports have described involuntary oscillopsia during DBS of the PPN that patients have described as trembling vision. Here we substantiate this observation using infra-red eye tracking. It has been suggested that this phenomenon might be used as an indicator of accurate targeting of the PPN with DBS. Our observations suggest that this phenomenon may not be related to a constricted anatomical structure and therefore such practise may be unwise. Scrutiny has led us to believe that the oscillopsia in our patient is not caused by direct stimulation of the oculomotor nerve as suggested in a previous report, but by stimulation of fibres in the uncinate fasciculus of the cerebellum and the superior cerebellar peduncle, which in turn stimulate the saccadic pre-motor neurones in the brainstem., (Copyright © 2012 S. Karger AG, Basel.)

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.

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.

We have taken 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 task. Control subjects and patients with idiopathic Parkinson's disease (PDs) viewed a series of pictures depicting two arrangements of coloured balls in pockets within the upper and lower halves of a computer display. The task was to plan (but not 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 number of moves required for problem solution. As problem complexity increased, control subjects spent proportionally more time fixating the Workspace region. This pattern was found regardless of whether subjects were instructed to solve problems by rearranging balls in the lower or upper visual fields. The distribution of gaze within the Workspace was also found to be problem dependent, with gaze being selectively directed towards the problem critical balls. In contrast, PDs were found to make more errors in the task and failed to show any dissociation in the amount of time fixating the two halves of the display. This pattern suggests that the patients had difficulty in encoding and/or maintaining current goals during problem solving, consistent with a role for fronto-striatal circuits in mechanisms of working memory and attention.

The oculomotor and manual motor systems were studied in a two-segment movement task in a group of patients with Parkinson's disease and in age matched normal controls. In order to avoid reflexive motor movements the selection of the correct motor sequence was derived from the interpretation of symbolic (coloured) cues. The latencies and dynamics of eye and hand (pointing) movements performed during the first (fixed) movement segment were measured and the planning and execution processes were manipulated by varying the complexity of the second movement segment relative to the first (with regard to direction and amplitude). The results showed that the eye and hand movements made by patients with Parkinson's disease were not impaired in the initiation of the first movement segment. Interestingly, both Parkinson's patients and controls showed increased eye and hand reaction time latencies for the first movement when the second movement was in the direction opposite to the first. This indicates that the complexity of the second movement influences the execution of the first movement, and importantly that complexity affects motor initiation and execution processes in both normal subjects and in patients with Parkinson's disease. The execution of hand movements was found to be impaired in patients with Parkinson's disease as indicated by a reduced peak velocity of manual pointing responses when compared to age matched controls. By contrast, no differences were found in the dynamics of saccadic eye movements. This dissociation is consistent with the notion that the skeletomotor loop passes through the functionally corresponding portions of the basal ganglia independently of the oculomotor loop. Together, these results demonstrate that Parkinson's patients are able to generate multiple non-reflexive eye and hand movements and that the observed (manual) motor deficits are specific to the processes of motor execution.

The search for specific patterns of impaired reaction time in Parkinson's disease has yielded conflicting results. We propose subtypes that exhibit different patterns of impairment and report the case of a patient, Jobe, whose simple and binary choice reaction times were tested repeatedly in a variety of stimulus-response paradigms over a period of 4 years. Jobe consistently failed to exhibit the normal simple reaction advantage even though his choice reaction times fell well within the normal range. While his general intellectual status was above average, he had great difficulty with some neuropsychological tests. He was seldom able to acquire a new category in the Wisconsin Card Sort Test and also had difficulty with the Tower of London Test. We ascribe Jobe's selective impairment of simple reactions to an inability to engage in the off-line preparatory processing that confers an advantage on simple reactions.

Mechanisms of spatial working memory and eye movement control were investigated in eight mild to moderate Parkinson's disease patients (PDs). Subjects were presented with a sequence of four targets which had to be memorized and then recalled by moving their eyes to fixate the four locations in the correct order. Two variations on this procedure were used in which either a different sequence of lights was presented on each trial, or an identical sequence of lights was repeated on each trial. In both conditions subjects made memory-guided eye movements in the dark, without any visual cues to eye movement accuracy or the locations of the previously illuminated lights. Analysis of the amplitude of the primary eye movement and final eye position for each step in the sequence showed that PDs made several discrete saccadic eye movements of reduced amplitude before reaching the final eye position (multi-stepping). When a novel target sequence had to be memorized on each trial, the final eye position reached by PDs for each location was also found to undershoot relative to controls. In contrast, when an identical sequence of targets was repeated on each trial, PDs' final eye position was found to be normal, although primary movement amplitudes were still reduced. PDs showed no multi-stepping and normal final eye position gain under conditions for which the target lights in the sequence were illuminated during movement execution. PDs also made an increased proportion of overt errors in target sequence recall. Parallel neuropsychological testing in PDs and controls revealed that error rates in the sequential memory-guided saccade task were significantly correlated with performance in a task thought to be sensitive to spatial working memory dysfunction. The findings suggest that short-term spatial memory representations are disrupted in the early stages of PD.

The effect of increasing delay on the metrics of remembered saccades was studied in 10 subjects with mild Parkinson's disease, none of whom was receiving treatment with L-dopa, and nine age-matched control subjects. Delays of 1 msec, 250 msec, 1000 msec, 2500 msec, and 5000 msec were used, and reflexive saccades used as a control condition. Results were analyzed for the gain of the primary saccade and the accuracy of the final eye position (FEP gain). Reflexive saccades were normal in subjects with Parkinson's disease, but remembered saccades showed marked hypometria of primary saccade gain at all delays. FEP gain was unimpaired in Parkinson's disease, and primary saccade gain and FEP gain did not vary as a function of delay. Hypometria of primary saccades is compatible with dysfunction in striato-collicular inhibitory pathways in Parkinson's disease, arising as a functional consequence of dopamine deficiency in the basal ganglia. Maintenance of an accurate FEP gain suggests no deficit in oculomotor spatial working memory in Parkinson's disease, at least at delays of up to 5 sec.

Twelve patients with focal damage of the frontal cortex and 12 patients with mild, medicated, early stage Parkinson's disease switched between letter- and digit=naming tasks on every second trial of a task-switching paradigm. Compared with age- and IQ-matched control performance, patients with left-sided, but not right-sided, frontal damage exhibited markedly increased time costs associated with these predictable switches only when there was a general incidence of interference or 'crosstalk' between the tasks, and particularly so when the available task cues were relatively weak and arbitrary. The same patients also showed evidence of an increased sensitivity to the facilitatory and inhibitory effects of previous processing, when required to switch between tasks. Both groups of patients (with left- or right-sided frontal damage) exhibited slow, disorganized performance early in practice. In contrast to these frontal effects, the Parkinson's disease patients showed little indication of larger time costs of task switches but they did show progressive increases in the error costs, while age- and IQ-matched control subjects showed reductions. We propose that while both left and right frontal cortical areas are involved in the organization of cognitive and motor processes in situations involving novel task demands, only the left frontal cortex is involved in the dynamic reconfiguring between already-established task-sets, and specifically, that it is the site of an executive mechanism responsible for the modulation of exogenous task-set activity. Finally, dopaminergic transmission, along the nigrostriatal pathway, may be implicated in sustaining various cognitive and motor processes over prolonged periods, including the operation of those executive control mechanisms that accomplish reconfiguring between task-sets.

Saccades of patients with mild Parkinson's disease (PD) are said to be abnormal in the absence of a concurrently visible target or when they are part of a rapid sequence of eye movements. We tested this hypothesis using a predictive saccade paradigm in which target visibility is withdrawn for a period. Three rates of target alternation were used (0.25 Hz, 0.5 Hz and 1.0 Hz). Withdrawal of target visibility brought out the extremes of primary saccade gain for both the controls and the patients with PD, most undershoot being displayed at the lowest frequency, whereas the gain was greatest at the highest frequency, actually overshooting the target location. These results demonstrate that the spatial error of parkinsonian saccades does not invariably take the form of hypometria when part of a rapid sequence of eye movements.

Two pairwise matched groups of patients with mild to moderate Parkinson's disease and a group of normal age matched controls were used to investigate the effects on simple and choice reaction time (RT) of brief withdrawal of levodopa therapy. Comparisons within and across these groups disclosed a selective effect of levodopa withdrawal. After about 12 hours of levodopa deprivation, patients exhibited an exaggeration of normal refractoriness, the well established tendency for RT to increase progressively as the delay between a response and the next imperative signal is reduced below 0.5 s. Increased refractoriness was at least as great for simple as choice RT. Choice RT on trials involving repetition (as opposed to alternation) of the previous response, however, showed no tendency towards greater impairment by brevity of the recovery period or by withdrawal of medication, eliminating an effector based account. With longer recovery periods, RT was unaffected by medication; indeed, unmedicated patients were as fast as normal subjects under these conditions. Even at the briefest delays, fully medicated patients did not differ from normal controls. The paper concludes with a critical review of chronometric studies of medication effects in Parkinson's disease.

This paper presents evidence in support of a serial reaction time (SRT) deficit associated with Parkinson's disease, and related to the acquisition or execution of serial-order information. Eleven patients with idiopathic Parkinson's disease, and 10 age-matched but otherwise healthy control subjects, were compared on a variant of the SRT task introduced by Nissen and Bullemer (Cognit. Psychol. 19, 1-32, 1987). The results of this study clearly demonstrate that PD patients produce a quite different pattern of RT performance to that of control subjects. Such a pattern of results may reflect either: (1) a deficit in the patients' ability to learn the temporal order information provided by a repeating sequence of target locations in the SRT task; or (2) a deficit in the patients' ability to express temporal order information provided by the repeating sequence of target locations in the SRT task.

This paper reports two experiments which examined the effects of Parkinson's disease (PD) upon the sensorimotor mechanisms used to control prehension movements. Transport and grasp kinematics for visually-guided and memory-guided prehension movements were examined in healthy control subjects and compared against those of patients with idiopathic PD. Two research questions were addressed: (1) Are patients with PD particularly susceptible to distraction by non-relevant objects? (2) Are patients with PD especially reliant on external feedback when executing goal-directed actions? The results indicated that the patient group were no more susceptible to distraction by non-relevant objects than the control group. In contrast, the patients with PD were shown to be significantly impaired when executing memory-guided reaches. Furthermore, the deficits exhibited by the PD group on memory-guided reaches were confined solely to those markers associated with the transport component of the prehension movement. That is, while both controls and patients with PD widened their grip aperture on memory-guided trials, the magnitude of this adjustment was comparable across the two groups. The implications of these findings for theories of visuomotor processing in sufferers of PD and the control of prehension movements more generally are discussed.

Postural control was assessed on a tilting platform system in 20 patients with idiopathic Parkinson's disease and 20 age-matched controls. The amount of information provided by vision and lower limb proprioception was varied during the experiment to investigate the influence of changes in sensory cues on postural control. The patient group with clinical evidence of impaired postural control (Hoehn and Yahr III) had significantly higher sway scores over all sensory conditions than either the Hoehn and Yahr II group or controls. The pattern of sway scores indicated that no obvious deficit in the quality, or processing, of sensory information was responsible for the postural instability observed in this group. The patients in both Hoehn and Yahr groups were also able to respond appropriately to potentially destabilising sensory conflict situations and significantly improved their sway scores when provided with visual feedback of body sway. The results indicate that in Parkinson's disease, the main site of dysfunction in postural control is likely to be at a central motor level.

The saccadic eye movements of nine patients with Parkinson's disease were compared to those of nine age-matched controls in two paradigms generating volitional saccades. In both paradigms, subjects had to make delayed saccades to peripheral LED targets: a peripheral target appeared 700 msec before a buzzer sounded, the buzzer being the signal to make a saccade to the target. In the first paradigm ("centre-off"), the fixation target was extinguished simultaneously with buzzer onset. In the second ("centre-remain") it was not extinguished until 1000 msec later. The results showed that for outward saccades in both paradigms, there was no difference between Parkinsonian patients and controls, but saccadic latencies were significantly shorter in the "centre-remain" paradigm. The initial outward saccades were indistinguishable from the normal, reflex saccades of the same subjects. However, saccades returning to the centre (a type of remembered target saccade) were hypometric and showed multistepping. Both effects were more pronounced in patients with Parkinson's disease. The significance of these findings in terms of current hypotheses about the nature of the Parkinsonian saccadic deficit is discussed.

Ten patients with mild to moderate Parkinson's disease were compared with ten age-matched normal controls in a series of saccadic paradigms in order to test various hypotheses relating to the origin of the Parkinsonian saccadic defect. The paradigms comprised a reflex saccade paradigm, a standard remembered saccade paradigm, a remembered saccade paradigm with delayed centre-offset, and a remembered saccade paradigm with a second target flash immediately prior to saccade execution. Finally, subjects executed both reflex and remembered saccades in a standard remembered paradigm (the "two-saccade" paradigm). As has been reported previously, Parkinsonian subjects demonstrated hypometria on all remembered saccade paradigms, particularly the "two-saccade" paradigm. There was, however, no significant difference between the first three remembered saccade paradigms. These studies serve to refute a simple attentional capture hypothesis, and a hypothesis that suggests that the abnormality of remembered saccades is due to concurrent reflex saccade suppression. On the basis of the results, further hypotheses are advanced in an attempt to explain all published work on Parkinsonian saccades.

Study 1 examined the reliability of the ratings assigned to the performance of five sign-and-symptom items drawn from tests of motor impairment in Parkinson's disease. Patients with Parkinson's disease of varying severity performed gait, rising from chair, and hand function items. Video recordings of these performances were rated by a large sample of experienced and inexperienced neurologists and by psychology undergraduates, using a four point scale. Inter-rater reliability was moderately high, being higher for gait than hand function items. Clinical experience proved to have no systematic effect on ratings or their reliability. The idiosyncrasy of particular performances was a major source of unreliable ratings. Study 2 examined the intercorrelation of several standard rating scales, comprised of sign-and-symptom items as well as activities of daily living. The correlation between scales was high, ranging from 0.70 to 0.83, despite considerable differences in item composition. Inter-item correlations showed that the internal cohesion of the tests was high, especially for the self-care scale. Regression analysis showed that the relationship between the scales could be efficiently captured by a small selection of test items, allowing the construction of a much briefer test.

Antisaccades were studied in ten patients with mild to moderate Parkinson's disease and ten age-matched normal controls. Remembered saccades and reflex saccades were assessed for comparison. In the population of patients who showed the previously reported abnormalities of remembered saccades, antisaccades were indistinguishable from those of controls in latency, gain and peak velocity. This finding implies that antisaccades are mediated through pathways which are unaffected by Parkinson's disease, and which are therefore presumably distinct from pathways mediating other voluntary saccades.

Eye-head movements to target steps of amplitude 3.75 degrees to 30 degrees were analyzed in 9 untreated patients with idiopathic Parkinson's disease. Testing was performed before and after the introduction of a dopamimetic drug (L-dopa or bromocriptine) and compared with 9 normal controls. The patients showed a significantly greater scatter of mean head latencies prior to treatment, although their mean latencies were not significantly prolonged. When compared to controls, the patients' head movements were of reduced peak velocity and gain. Treatment resulted in an improvement of gain but not velocity. Analysis of the frequency of gaze types showed no significant effect of treatment.

Disorders of eye movements have been described in diseases of the basal ganglia for over a century. Recent neurophysiological and clinical work has greatly clarified the oculomotor role of these structures: their major involvement appears to be in the generation of "voluntary" saccades, and in the suppression of "reflex" saccades. The observed abnormalities of saccadic eye movements in Huntington's (HD) and Parkinson's (PD) diseases conform very well to predictions based on a combination of known disease pathology and recent neurophysiological work. This is not quite the case for other types of eye movement, such as smooth pursuit, largely because the exact role of the basal ganglia in their generation has not been defined neurophysiologically. Several diseases other than HD and PD both involve the basal ganglia and have effects on eye movements; such diseases include progressive supranuclear palsy and Wilson's disease. Unfortunately, the pathological processes in these conditions are too widespread to allow comment on how well oculomotor abnormalities fit in with predictions.

A comparison was made of predictive eye movements of both the saccadic and pursuit ocular motor systems in parkinsonian patients and aged-matched normal controls. In a predictive task our patients, who were mildly or moderately affected, showed a reduced tendency to make anticipatory saccades compared with normal controls. Although there was some impairment of pursuit during a nonpredictive task as shown by an increased phase lag, a normal amount of improvement took place with a predictive task. This difference between prediction in the saccadic and pursuit system is possibly explained by an increased reliance on a visual input by parkinsonian patients which prevents them making use of verbal instruction to generate anticipatory (eye in advance of target) saccades. Improvement of pursuit with a predictive target track is possible in such patients since normally in these circumstances the target is mainly followed rather than anticipated. The metrics of saccadic and smooth pursuit eye movements (saccadic velocity and pursuit turnover velocity) were normal.

A quantitative analysis of unpredictable saccadic and smooth pursuit ocular motor and manual tracking was performed in 15 mildly affected, previously untreated subjects suffering from Parkinson's disease and in age-matched normal controls. The patients' ocular saccades were characterised by an increased variability of their latencies and reduced accuracy, with normal velocity profiles apart from saccadic duration. Their smooth pursuit had a decreased velocity gain. Similar abnormalities were found with manual tracking. Clinical improvement with dopaminergic drugs was associated with an improvement of saccadic accuracy and smooth pursuit gain. It is postulated that the ocular motor changes seen in Parkinson's disease are contingent upon functional dopamine levels in the basal ganglia.

Rapid eye movements (saccades) were examined in 7 patients with idiopathic Parkinson's disease (PD) and a matched group of normal control subjects. The effect of instructional and stimulus conditions used to elicit saccades was examined using 3 experimental paradigms. Eye movements directly elicited by a novel peripheral target were unimpaired in patients with PD as compared with control subjects. Saccades to a remembered target location, however, were dysmetric in the PD group and showed a characteristic multistepping pattern. The PD impairment was not caused by a loss of information on target location since their final eye position was close to the target at all eccentricities. Peak velocity, duration, and latency did not distinguish between PD patients and controls. These results support the view that for saccades which are not directly elicited by a visual target there is a neural pathway that can be distinguished from structures involved in the generation of visually elicited (or 'reflexive') saccades. The finding that in PD saccades to a remembered target are selectively impaired suggests that structures in the basal ganglia play a crucial role in this alternative pathway.

In a coincidence timing task, Parkinsonian patients and a control group were instructed to synchronize a keypress with the onset of a visual signal which had been preceded by a regular train of warning signals. Although the Parkinsonian group had previously exhibited slower reactions in a conventional simple reaction-time task, they were able to generate predictive responses that fell as close to the target onset as the controls' but showed greater variability. In a second experiment, Parkinsonian patients and controls made saccadic eye movements to a visual target that stepped at regular intervals between two fixed locations. After a few trials all the subjects tended to make predictive saccades that were initiated before the target excursion. However, the Parkinsonian group were slower to develop this strategy and when they did their saccades became considerably more hypometric than those of the controls. Both groups were able to maintain predictive responding even when the visual target disappeared and responses were paced by a buzzer. We concluded that Parkinsonian patients are capable of initiating predictive responses of the eye and the hand, at least in some circumstances, but such responses tend to be inaccurate in execution. This, in turn, may dispose the Parkinsonian patient against predictive movement.

Sleep and respiration during sleep were studied in patients with idiopathic Parkinson's disease, patients with Parkinsonism with autonomic disturbance, and normal age and sex matched controls. Patients with idiopathic Parkinson's disease showed significantly reduced REM sleep, and more frequent and prolonged waking throughout the night. Hypoventilation and sleep apnoea did not occur in the idiopathic Parkinson's disease or normal groups, but respiration was disorganised with frequent central and obstructive apnoeas in the autonomic disturbance group. Respiratory rate during non rapid eye movement sleep was similar in the idiopathic Parkinson's disease and normal groups, but patients with idiopathic Parkinson's disease showed tachypnoea awake and during REM sleep.