Predictive eye and hand movements are differentially affected by schizophrenia

BACKGROUND: Schizophrenic patients are known to have problems suppressing reflexive eye movements. This is considered to indicate a dysfunction in prefrontal cortex. As the eye and hand motor systems are tightly coupled, we investigated whether predictive hand movements and eye-hand coordination are unimpaired in schizophrenic patients. METHODS: Saccades and hand movements of 19 patients during an acute schizophrenic episode and 19 controls were measured in a task in which the predictability of target timing was varied. RESULTS: Schizophrenic patients generated more anticipatory and less visually triggered saccades than controls with both non-predictable and predictable target timing. Anticipatory saccades in the wrong direction were clearly directed towards previous target positions, indicating that they are indicators of erroneous prediction rather than of fixation instability. In contrast to saccades, the number of anticipatory and visually triggered hand movements was the same in patients as in controls. As a consequence, patients took longer to initiate a hand movement after a saccade than controls. CONCLUSIONS: Schizophrenic patients show increased predictive saccadic activity, but no qualitative changes in predictive saccades. Since prediction itself was not disturbed, the patients' deficit rather lies in the suppression or gating of anticipatory saccades than in their generation. This may be explained by a selective dysfunction of the basal ganglia oculomotor loop. As predictive hand movements were unimpaired, the problems in eye-hand coordination as expressed by a longer initiation time of hand movements relative to saccades are a direct consequence of impaired predictive saccadic behaviour.     

Eye-hand coordination in essential tremor.

Patients with essential tremor (ET) or with cerebellar lesions have in common oculomotor abnormalities, with the exception of saccadic eye movements, which do not seem to be involved in ET. Since grasping is prolonged in ET and might be related to saccadic dysmetria, we tested whether simultaneous hand pointing could unmask it. Twelve ET patients and 14 controls performed saccades with and without simultaneous pointing movements to the same targets, and with and without a gap between the disappearance of the fixation point and the appearance of the target. Eye movements were recorded with the magnetic search-coil method, hand movements with an ultrasound-emitting probe. ET patients did not have saccadic dysmetria, and contrary to normal subjects their saccadic latency did not decrease during combined eye-hand movements compared with saccades performed in isolation. Hand movements had a longer duration in ET patients, with decreased peak acceleration, an increased latency of the peak velocity, and peak deceleration. In conclusion, this first study on eye-hand coordination in ET revealed abnormal kinematic changes in the early phase of pointing movements. These changes might be related to cerebellar disease but they are independent of the intention tremor component and saccade performance.     

Disturbance of predictive response initiation of eye and head movements in cerebellar patients

The predictability of target occurrence has influence upon the latency of motor initiation. Higher frequencies (>0.5 Hz) of periodically paced target presentation lead to decreased latencies of movement initiation. In this study we investigated the initiation of head movements and saccades during predictable and random target presentation in cerebellar patients. During the predictive condition, in particular during higher temporal frequencies and greater amplitudes, patients showed increased latencies compared to healthy subjects. The latencies between the onset of the agonistic and antagonistic muscle pulses were correlated with the severity of cerebellar impairment. We conclude that the cerebellum is involved in predictive response initiation of eye and head movements which is emphasized at higher temporal frequencies.     

Effects of lesions of the human posterior thalamus on ocular fixation during voluntary and visually triggered saccades

OBJECTIVE: To investigate the role of the posterior thalamus in controlling voluntary and visually triggered eye movements and ocular fixation. METHODS: The latency to initiate saccades to peripheral targets (visually triggered) and in response to verbal commands (voluntary) was measured in three patients with unilateral lesions of the posterior thalamus, in normal controls, and in neurological controls with Parkinson's disease. On half the trials a fixation point offset simultaneously with target onset, and on half it remained visible. RESULTS: Offset of the fixation point simultaneous with target onset decreased saccade latency for both voluntary and visually triggered eye movements in controls, but only for voluntary saccades in patients with thalamic lesions. CONCLUSIONS: These findings suggest that separate neural systems control fixation when making voluntary and visually triggered eye movements, and that the thalamus is involved in the control of fixation for visually triggered but not for voluntary saccades.     

Maladaptive anticipatory saccades in schizophrenia.

We compared the saccades made by 8 neuroleptic-treated and 7 drug-free schizophrenic inpatients with those made by 11 normal controls during two eye movement tasks. The first task was designed to elicit visually guided but not internally guided saccades. The second task was designed so that optimal performance required saccades be guided on the basis of an internal representation of target behavior. During the first task, schizophrenics made visually guided saccades that were as accurate as those made by control, but both drug-free and neuroleptic-treated schizophrenics made intrusive saccades at a significantly higher rate than control subjects. Most of these maladaptive saccades appeared to be premature attempts to anticipate target jump. During the second eye movement task, which for optimal performance required use of an internal representation to guide eye movements, most patients learned to anticipate target jump as well as controls. However, neuroleptic-treated patients made significantly smaller adaptive anticipatory saccades than either drug-free schizophrenic patients or normal subjects. These finding are discussed as they relate to the prefrontal cortex-basal ganglia circuits involved in the regulation of behavior by representational knowledge and the idea that the abnormal anticipatory saccades we observed represent a failure in the sensorimotor gating of information derived from internal representations.     

Hypometric primary saccades and increased variability in visually-guided saccades in Huntington's disease

Eye movement abnormalities can be distinctive and suggestive of a specific pathophysiology. To further investigate the deficits in the control of saccades in patients with Huntington's disease (HD), we investigated the ability of 11 HD patients and 11 matched controls to perform visually-guided saccades. We adopted reflexive saccade tasks involving predictable and unpredictable sequences, at different amplitudes of target step (10 degrees, 20 degrees, 30 degrees, 40 degrees ), as well as voluntary self-paced saccades. Prolongation of initiation was observed in the HD group as the target amplitude of predictable saccades increased. During the self-paced saccade task, the HD patients had increased intersaccadic intervals, performed fewer saccades in the allocated time and displayed an increased temporal variability in comparison to the controls. Furthermore, hypometric primary saccades, and an increased number of corrective saccades, were observed during both reflexive and voluntary saccades in the HD group. The delayed initiation of large saccades, deficits in voluntary, self-paced saccades, impaired saccadic accuracy and increased corrective saccades in HD, were interpreted in light of other ocular motor and limb studies, and appear to be due to damage to the fronto-striatal loop, including the supplementary eye fields, as well as possible brainstem and cerebellar involvement.     

Effects of cerebellar infarcts on cortical processing of saccades

The objective of the present study was to investigate cerebellar influences on cortical components of saccadic eye movement programming in human subjects. In 24 patients with a localized cerebellar lesion, saccadic eye movements were recorded in different reflexive (step, gap, overlap) and intentional (anti, memory, short memory sequences) tasks and compared to 23 healthy controls. The cerebellar lesions led to impairments in different saccade parameters. Cerebellar patients tended to show hypermetria and increased latencies compared to the control group. In particular, they executed significantly more erroneous saccades specifically in the memory task (suppression errors) but not in the anti task (pro-saccade errors). Moreover, while reproducing short sequences of saccades from memory, patients with cerebellar infarcts made more errors with regard to the sequence order than controls. The influence of cerebellar hemispheric lesions on the saccade latency, the task-specific lesion effects on the frequency of suppression errors, and the effects on the number of order errors suggest that the cerebellum is involved in cortical processes such as target selection and sequence reproduction.     

Coordination of a multi-joint movement in normal humans and in patients with cerebellar dysfunction

The contribution of the cerebellar cortex to coordination of a multi-joint throwing movement was studied by measuring various movement and EMG parameters while normal control subjects and patients with cerebellar cortical atrophy threw a ball at a target. Although patients did not throw as accurately as controls, several coordination measurements were normal in the patients. These included parameters used by us to assess elbow-wrist coordination and the coordination of hand opening with activation of more proximal arm muscles. Postural support for the movement at the shoulder was also normal in that the shoulder was not pushed backwards by the reaction forces resulting from the rapid forward acceleration of the forearm and hand. In contrast, however, patients were unable to coordinate the muscles so as to produce the same hand direction from trial to trial when throwing at the same target. In addition, EMG onset times were abnormal in the antagonist muscles relative to agonist EMG bursts and kinematic parameters of the movement. In conclusion, our patients with cerebellar cortical atrophy showed abnormalities in visual-motor coordination, in that they were unable to consistently produce the appropriate hand direction in response to a visual target. Agonist-antagonist relationships were also impaired. Other aspects of coordination, such as the relative timing of EMG onsets of agonist muscles, even when these were active at different joints, were normal.     

Eye movement abnormalities in essential tremor versus tremor dominant Parkinson’s disease

ObjectiveTo show that eye movement abnormalities differ between essential tremor (ET) and tremor dominant Parkinson’s disease (PD-T), and that these abnormalities reflect cerebellar dysfunction in ET and basal ganglia pathology in PD-T.MethodsIn this exploratory study, in 23 patients with ET, 21 age-matched patients with PD-T, and 19 age-matched healthy controls (HCs), we investigated visually guided saccades, antisaccades, and smooth pursuit eye movements (SPEM).ResultsWhile the ET group had a normal gain (saccade amplitude/target amplitude) and latency of saccades, the PD-T group had hypometric visually guided saccades, and a prolonged latency of visually guided saccades and antisaccades. The SPEM gain was similarly low in both ET and PD-T and was significantly lower in both patient groups than in the HC group.ConclusionsIn ET, SPEM gain was reduced in the presence of normal saccades, whereas in PD-T, the reduced SPEM gain was accompanied by delayed saccade initiation and hypometric saccades, in line with cerebellar dysfunction in ET and basal ganglia dysfunction in PD-T.SignificanceThese findings support the presumed cerebellar pathology in ET. In addition, the difference in saccade features may contribute to the groundwork for a quantitative diagnostic test to differentiate between these disorders.     

Cerebral events preceding self-paced and visually triggered saccades. A study of presaccadic potentials

The cerebral potentials preceding self-paced and visually triggered saccadic eye movements were studied using multichannel recording and spatio-temporal mapping techniques, and the contribution to these potentials of stimulus-evoked activity and the electro-oculographic field was investigated. A premotor positivity (PMP) and negativity (PMN) comparable to those associated with movements of the extremities were found with both self-paced and triggered saccades, but there were differences in the amplitude, duration and topography of these potentials in the different types of eye movement. The slope of the PMP was greater for visually triggered than for self-paced saccades and its slope and duration were influenced by the predictability of the triggering stimulus, the slope being greater and the duration shorter with predictable than with unpredictable stimuli. The characteristics of this potential are compatible with an origin from saccade-related and visually sensitive neurons in parietal and occipital cortex and it is suggested that in a visually triggered eye movement, the PMP may be a correlate of visuomotor interactions. A PMN was associated with both self-paced and visually triggered saccades, and in the case of triggered saccades is thought to reflect anticipation of the cuing stimulus in addition to preparatory movement-related activity. When the precise timing of the cuing stimulus was not known by the subject, a PMN still developed but then plateaued until the arrival of the stimulus and execution of the movement. In this situation the PMN therefore appears to reflect an increasing level of arousal and preparedness to move which is then maintained pending the final motor command.     

Manual tracking performance in patients with cerebellar incoordination: effects of mechanical loading

Manual tracking performance was studied in five patients with cerebellar incoordination due to unilateral cerebellar hemisphere lesions. The subjects were required to track a target on an oscilloscope screen by moving a cursor controlled by flexion-extension movements of the wrist. In comparison to normal subjects, the cerebellar patients, using their clinically affected arm, demonstrated irregular tracking patterns with inappropriate accelerations and decelerations, numerous high velocity peaks of movement, and an increased time lag between the cursor and the target. The addition of a viscous load provided by feeding back wrist velocity to a torque motor coupled to the apparatus resulted in significant improvement in tracking performance and suppression of the high velocity peaks. Increasing elastic stiffness by feeding back wrist position or inertial load by adding weights to the hand did not improve performance on this task. It is proposed that a hypotonic cerebellar limb behaves like an underdamped mechanical system. The addition of viscous loads helps restore more normal damping during voluntary movements of the arm.     

Saccade control and eye-hand coordination in optic ataxia

The aim of this work was to investigate ocular control in patients with optic ataxia (OA). Following a lesion in the posterior parietal cortex (PPC), these patients exhibit a deficit for fast visuo-motor control of reach-to-grasp movements. Here, we assessed the fast visuo-motor control of saccades as well as spontaneous eye-hand coordination in two bilateral OA patients and five neurologically intact controls in an ecological "look and point" paradigm. To test fast saccadic control, trials with unexpected target-jumps synchronised with saccade onset were randomly intermixed with stationary target trials. Results confirmed that control subjects achieved visual capture (foveation) of the displaced targets with the same timing as stationary targets (fast saccadic control) and began their hand movement systematically at the end of the primary saccade. In contrast, the two bilateral OA patients exhibited a delayed visual capture, especially of displaced targets, resulting from an impairment of fast saccadic control. They also exhibited a peculiar eye-hand coordination pattern, spontaneously delaying their hand movement onset until the execution of a final corrective saccade, which allowed target foveation. To test whether this pathological behaviour results from a delay in updating visual target location, we had subjects perform a second experiment in the same control subjects in which the target-jump was synchronised with saccade offset. With less time for target location updating, the control subjects exhibited the same lack of fast saccadic control as the OA patients. We propose that OA corresponds to an impairment of fast updating of target location, therefore affecting both eye and hand movements.     

Ocular contrapulsion in multiple sclerosis: clinical features and pathophysiological mechanisms

The objective was to describe in multiple sclerosis, a cerebellar eye movement syndrome that resulted from an acute episode of inflammatory demyelination. Contrapulsion is an ocular motor disturbance characterised by a triad of (1) hypermetric saccadic eye movements in a direction opposite from a precisely localised lesion within a specific white matter pathway, the uncinate fasciculus, at the level of the superior cerebellar peduncle (SCP); (2) hypometric saccades towards the side of the lesion; (3) oblique saccades directed away from the side of the lesion on attempted vertical saccades. Infrared oculography was used to demonstrate the characteristic features of contrapulsion in two patients with multiple sclerosis. Brain MRI showed lesions within the region of the uncinate fasciculus and superior cerebellar peduncle in both patients. Eye movement recordings showed saccadic hypermetria away from the side of the lesion and saccadic hypometria towards the side of the lesion. The hypometria decomposed into a series of stepwise movements as the eye approached the target. Oblique saccades directed away from the side of the lesion were seen on attempted vertical saccades.In conclusion, ocular contrapulsion can be seen in patients with multiple sclerosis and results from a lesion in the region of the SCP, involving the uncinate fasciculus.     

Subthalamic stimulation improves orienting gaze movements in Parkinson’s disease

OBJECTIVE: To determine the effect of subthalamic stimulation on visually triggered eye and head movements in patients with Parkinson's disease (PD). METHODS: We compared the gain and latency of visually triggered eye and head movements in 12 patients bilaterally implanted into the subthalamic nucleus (STN) for severe PD and six age-matched control subjects. Visually triggered movements of eye (head restrained), and of eye and head (head unrestrained) were recorded in the absence of dopaminergic medication. Bilateral stimulation was turned OFF and then turned ON with voltage and contact used in chronic setting. The latency was determined from the beginning of initial horizontal eye movements relative to the target onset, and the gain was defined as the ratio of the amplitude of the initial movement to the amplitude of the target movement. RESULTS: Without stimulation, the initiation of the head movement was significantly delayed in patients and the gain of head movement was reduced. Our patients also presented significantly prolonged latencies and hypometry of visually triggered saccades in the head-fixed condition and of gaze in head-free condition. Bilateral STN stimulation with therapeutic parameters improved performance of orienting gaze, eye and head movements towards the controls' level CONCLUSIONS: These results demonstrate that visually triggered saccades and orienting eye-head movements are impaired in the advanced stage of PD. In addition, subthalamic stimulation enhances amplitude and shortens latency of these movements. SIGNIFICANCE: These results are likely explained by alteration of the information processed by the superior colliculus (SC), a pivotal visuomotor structure involved in both voluntary and reflexive saccades. Improvement of movements with stimulation of the STN may be related to its positive input either on the STN-Substantia Nigra-SC pathway or on the parietal cortex-SC pathway.     

Timing factors in the coordination of speech movements

Speech movement coordination involves substantial timing adjustments among multiple degrees of muscles and movement freedom. The present investigation examined the kinematic and muscle timing adjustments associated with the production of select speech movements. For oral closing movements, the timing of the upper lip, lower lip, and jaw peak velocities were found to be tightly coupled, apparently reflecting a coordinative strategy. In contrast, oral opening movements demonstrated reduced temporal coupling and inconsistent sequencing across subjects. Overall, it appears that the temporal organization of speech movements varies with the specific movement goals. In order to evaluate the coordinative patterns for oral closing in detail, the temporal adjustments of multiple perioral muscles associated with the systematic closing peak velocity relations were examined. The relative timing of muscle onsets and peak EMG amplitudes was found to be predictably related to the peak velocity timing variations, suggesting that the motor commands are temporally scaled to generate changes in speaking conditions. It was also found that the mechanical properties of the speech articulators influence movement coordination and can be exploited to maximize movement efficiency. The systematic change in muscle timing characteristics for all synergistic muscles apparently reduces the degrees of freedom to control, thereby facilitating the coordination process.     

Behavioural aspects of cerebellar function in adults with Asperger syndrome

Aside from social deficits, Asperger and autistic individuals also exhibit motor control abnormalities such as impaired gait, balance, manual dexterity and grip. One brain area that has consistently been reported on autopsy and imaging studies to be abnormal in such individuals is the cerebellum. As the cerebellum controls sensorimotor coordination and lesions here typically cause hypotonia, dysmetria and dyscoordination, we performed a series of quantitative tests aimed at investigating cerebellar function in Asperger individuals. Tests examining visually guided movement (rapid pointing), speeded complex movement (finger tapping, rapid hand turning), muscle tone (catching dropped weight), prediction, coordination and timing (balance, grip force and interval timing) were conducted on 12 Asperger subjects and 12 age and IQ matched controls. In comparison to control subjects, Asperger subject's demonstrated: (i) decreased pointing accuracy and rate, (ii) increased postural instability, and (iii) decreased timing accuracy. IQ was found to co-vary with some parameters of each of these tasks and no further impairments were found on the remaining tests. We suggest that these specific deficits reflect impairment in the ability to integrate sensory input with appropriate motor commands and are consistent with cerebellar dysfunction in Asperger syndrome.     

Saccade disturbances after bilateral lentiform nucleus lesions in humans.

OBJECTIVE--To determine the roles of the putamen and pallidum in ocular motor control. METHODS--Eye movements were recorded electro-oculographically in nine patients with bilateral focal lesions affecting the lentiform nucleus, and in 12 age matched control subjects. Reflexive visually guided saccades (gap task), antisaccades, memorised sequences of saccades, memory guided saccades (with visual input only, and with both visual and vestibular inputs), and predictive saccades (with and without gap) were studied. RESULTS--Latency and accuracy of visually guided saccades were normal. The percentage of errors in the antisaccade task and latency of correct antisaccades did not differ significantly from the results of controls. The percentage of errors in saccade sequences was significantly increased. Accuracy of the two types of memory guided saccades was impaired bilaterally. The percentage of predictive saccades was significantly decreased when a gap existed, but unchanged without a gap, compared with controls. Therefore, saccades made immediately in response to an external target (reflexive visually guided saccades and antisaccades) were performed without difficulty, whereas those requiring an internal representation of such a target (such as memory guided saccades, predictive saccades, and saccade sequences) were performed with significant disturbances. CONCLUSIONS--The lentiform nucleus influences the cortical areas involved in the control of saccades when the experimental paradigm requires the use of an internal representation of the target for correct planning and execution of the ensuing saccade.     

Influence of arm movements on saccades in humans

When reaching for an object we usually look at it before we touch it with the hand. This often unconscious eye movement prior to the arm movement allows guiding of the final part of the hand trajectory by visual feedback. We examined the temporal and spatial coordination of this control system by psychophysical measurements of eye and arm movements of naive human subjects looking or looking and pointing as fast as possible to visual targets in physical and virtual-reality setups. The reaction times of saccades to a step-displaced target were reduced, and the number of corrective saccades decreased, when the subject had to produce a corresponding simultaneous hand movement to the same target. The saccadic reaction time was increased when saccade and hand movement went in opposite directions. In a double-step task the reaction time for the second saccade was longer than for the first. Co-use of the hand leads to an additional increase of saccadic reaction time. Taken together this study shows an improvement in initial saccades if they are accompanied by hand movements to the same target. This effect might ensure that the reach target is foveated early and accurately enough to support the visual feedback control of the hand near the target. Longer reaction times for the second saccade to double-step displaced targets might reflect a saccadic refractory time intensified by simultaneous arm movements. These results are discussed in the light of recent findings from our laboratory on saccade- and reach-related neurons in the superior colliculus of macaque monkeys.     

Learning of spatial and temporal patterns in sequential hand movements

Speed and accuracy in performing a complex movement sequence improve with practice. To examine how the temporal and spatial patterns of movement sequence are learned, the sequence of target locations and the consistency in the timing of target presentation were manipulated independently while subjects produced a series of visually guided hand movements. When the sequence of target locations and the timing of target presentation followed a consistent pattern, performance for a particular movement sequence improved with practice for both temporal and spatial movement parameters. However, when the same temporal and spatial patterns were recombined with a phase shift, there was a small but consistent deficit in performance. These results suggest that whereas spatial and temporal patterns in a learned movement sequence can be recombined flexibly, optimal performance is obtained for a specific spatio-temporal pattern of movement sequence. Whereas subjects were largely aware of the spatial and temporal patterns, they were unaware of the phase-shift, suggesting that learning of a specific spatio-temporal pattern was implicit.     

Control of visually guided saccades in multiple sclerosis: Disruption to higher-order processes

Ocular motor abnormalities are a common feature of multiple sclerosis (MS), with more salient deficits reflecting tissue damage within brainstem and cerebellar circuits. However, MS may also result in disruption to higher level or cognitive control processes governing eye movement, including attentional processes that enhance the neural processing of behaviourally relevant information. The attentional control of eye movement was investigated in 25 individuals with MS and a comparable number of neurologically healthy individuals matched for age and IQ. This entailed an evaluation of distractor-related effects on the generation of both unpredictable and predictable visually guided saccades, as well as an evaluation of the effects of presenting endogenous cues prior to target onset. For unpredictable saccades, we revealed an exaggerated distractor effect in MS, with saccade latencies prolonged and endpoints less accurate in the presence of a visual distractor. Predictable saccades tended to be hypometric for MS patients, although we found no significant distractor effects. For endogenously cued saccades, we found no group differences in latency following a valid cue, but an exaggerated increase in latency following invalid cues for MS patients. MS patients also generated a significantly greater proportion of erroneous responses to cue stimuli. These ocular motor characteristics demonstrate considerable sensitivity with respect to evaluating attentional deficits in MS, evident even in the absence of clinical signs of disease.