Shared and distinct oculomotor function deficits in schizophrenia and obsessive compulsive disorder

Detailed analysis of oculomotor function phenotypes in antisaccade, smooth eye pursuit, and active fixation tasks was performed in a sample of 44 patients with schizophrenia, 34 patients with obsessive compulsive disorder (OCD), and 45 matched healthy controls. A common pattern of performance deficits in both schizophrenia and OCD emerged including higher antisaccade error rate, increased latency for corrective antisaccades, as well as higher rates of unwanted saccades in smooth eye pursuit compared to healthy controls. This common pattern could be related to the dysfunction of a network of cognitive control that is present in both disorders, including the dorsolateral prefrontal cortex, the posterior parietal cortex, and the anterior cingulate cortex. In contrast, only patients with schizophrenia showed a specific increase for correct antisaccade mean latency and the intrasubject variability of latency for error prosaccades as well as a decrease in the gain for smooth eye pursuit, suggesting a specific deficit in saccadic motor control and the frontal eye field in schizophrenia that is not present in OCD. A specific deficit in fixation stability (increased frequency of unwanted saccades during active fixation) was observed only for OCD patients pointing to a deficit in the frontostriatal network controlling fixation. This deficit was pronounced for OCD patients receiving additional antipsychotic medication. In conclusion, oculomotor function showed shared and distinct patterns of deviance for schizophrenia and OCD pointing toward shared and specific neurobiological substrates for these psychiatric disorders.     

Prediction in the oculomotor system: smooth pursuit during transient disappearance of a visual target

Summary Eye movements were recorded in human subjects who tracked a target spot which moved horizontally at constant speeds. At random times during its trajectory, the target disappeared for variable periods of time and the subjects attempted to continue tracking the invisible target. The smooth pursuit component of their eye movements was isolated and averaged. About 190 ms after the target disappeared, the smooth pursuit velocity began to decelerate rapidly. The time course of this deceleration was similar to that in response to a visible target whose velocity decreased suddenly. After a deceleration lasting about 280 ms, the velocity stabilized at a new, reduced level which we call the residual velocity. The residual velocity remained more or less constant or declined only slowly even when the target remained invisible for 4 s. When the same target velocity was used in all trials of an experiment, the subjects' residual velocity amounted to 60% of their normal pursuit velocity. When the velocity was varied randomly from trial to trial, the residual velocity was smaller; for target velocities of 5, 10, and 20 deg/s it reached 55, 47, and 39% respectively. The subjects needed to see targets of unforeseeable velocity for no more than 300 ms in order to develop a residual velocity that was characteristic of the given target velocity. When a target of unknown velocity disappeared at the very moment the subject expected it to start, a smooth movement developed nonetheless and reached within 300 ms a peak velocity of 5 deg/s which was independent of the actual target velocity and reflected a default value for the pursuit system. Thereafter the eyes decelerated briefly and then continued with a constant or slightly decreasing velocity of 2–4 deg/s until the target reappeared. Even when the subjects saw no moving target during an experiment, they could produce a smooth movement in the dark and could grade its velocity as a function of that of an imagined target. We suggest that the residual velocity reflects a first order prediction of target movement which is attenuated by a variable gain element. When subjects are pursuing a visible target, the gain of this element is close to unity. When the target disappears but continued tracking is attempted, the gain is reduced to a value between 0.4 and 0.6.Supported by grants DFG Be 783/1 and Be 783/2-1 (1), and NIH RR 00166 and EY 00745 (2)     

Short-term effects of botulinum toxin on the lateral rectus muscle of the cat

Botulinum toxin type A (BTX) is often used as an alternative to surgery for the treatment of strabismus and many other motor or cosmetic problems. Although numerous studies established BTX as a powerful transmission-blocking agent at the neuromuscular junction, no evaluation of extraocular muscle (EOM) contractile properties after administration of BTX exists. Some anatomical studies on EOM fiber types suggested a long-term preferential effect of BTX on orbital layer, singly innervated muscle fibers. In this study, we examined the short-term effects of BTX on the contractile properties of normal lateral rectus muscle to determine the functional effect of BTX on muscle-force output over time. Measurements of muscle tension and the corresponding EMG evoked by stimulation of nerve VI were made hourly for up to 18 h following BTX administration. An intramuscular BTX injection of 2 U caused a dramatic decrease in maximum twitch and tetanic tension of the muscle in response to different frequencies of stimulation. This suppression developed gradually over time, with a concomitant reduction of EMG amplitude. No significant changes in muscle-speed-related characteristics (e.g., twitch contraction time, fusion frequency) were found. The results suggest a functional effect of BTX on all muscle fiber types, although, with the dose used, we did not observe complete muscle paralysis within the time of recording. The time course of muscle tension suppression by BTX also was frequency dependent, with the lower stimulation frequencies being more affected, suggesting that implementation of higher frequencies could still produce adequate eye movements. Electronic Publication     

Afternoon sleep in sensory deprivation: an EEG and polygraphic investigation in man

This paper is concerned with modifications induced by sensory deprivation (SD) in afternoon sleep of normal subjects. EEG and polygraphy (eye movements, tonus, respiration, EKG and electrodermogram) were recorded in eight subjects. Recordings were visually analyzed, page by page, and sleep was divided into slow sleep (SS) and fast sleep (FS), the latter being subdivided into phasic (with REMs) and non-phasic (without REMs) FS. A quantitative analysis evaluated the slow eye movements (SEM) and the early variations of occipital frequency. In the SD situation, as compared to normal situation, sleep onset occurs later, SEMs during Stage 1 are more frequent, total sleep duration is slightly modified, SS lasting longer only when FS phases are present. The quantity of FS, particularly of phasic elements, and moreover the number of FS phases, increases in SD. SD does not radically modify the organization of afternoon sleep; if some changes (SEMs, FS) are similar to those found in night sleep in SD, others are quite the opposite (latency of the onset of sleep). So SD seems to determine rather steadfast modifications (SEM, sleep onset), but does not affect deeply the way in which other factors, such as metabolic and psychological factors, may interfere with the levels of vigilance.     

Prepulse inhibition of the acoustic startle reflex and oculomotor control

Prepulse inhibition and the suppression of reflexive saccades on the antisaccade task are thought to tap inhibitory function. Reports of a lack of association between these measures suggest that they reflect different facets of inhibition. This study aimed to reexamine this relationship in a large sample and investigate the association of prepulse inhibition with oculomotor tasks that require inhibition of a reflexive saccade with lower concurrent processing demands than antisaccades, namely the oculomotor delayed response and fixation with distractors tasks. One hundred and seven healthy volunteers took part. Prepulse inhibition was uncorrelated with oculomotor performance. The error rate was highest for antisaccades, intermediate for the delayed response task, and lowest for fixation with distractors, and was correlated across tasks. These findings provide no evidence of a relationship between prepulse inhibition and oculomotor inhibition. Failure in suppressing reflexive saccades toward a peripheral target may represent a common inhibitory component underlying these oculomotor tasks.     

Extraocular motor unit and whole-muscle contractile properties in the squirrel monkey. Summation of forces and fiber morphology

In order to understand the neural control of movement, many investigations have examined the contractile properties of single motor units contracting in isolation, and a great majority of those studies have been done in the cat. Fewer studies, again primarily in the cat, have examined motor units acting in concert in both hind-limb and extraocular muscles. It has been shown, in general, that when individual motor unit forces are added together they do not always add linearly, which makes our understanding of motor control somewhat more complicated. In addition, complex neuronal firing patterns can yield unexpected force outputs or muscle positions whether those patterns occur naturally or are induced through motoneuron stimulation. The current investigation extends these findings of nonlinearity to the primate extraocular system. In studies of the squirrel monkey lateral rectus muscle and its motor units, we show that individual units lose an average of 45% of their force output when they fire in concert with a small number of other motor units. Also, when individual motor units are stimulated at a constant rate of 100 Hz, the force output is most often dramatically different if that constant 100-Hz stimulation is preceded by brief (25 ms), high-frequency stimulation burst or pulse, as occurs during saccades. The force at 100 Hz is usually significantly higher than when no pulse is delivered. However, we now show that an identical stimulation pattern applied to a number of motor units simultaneously does not always yield these force differences. These "nonlinearities" are addressed in terms of the complex muscle architecture that we show in the squirrel monkey lateral rectus muscle. Muscle fibers do not always run in parallel from tendon to tendon. Instead, they may branch or attach to each other laterally or end to end, serially.     

Effects of stimulus-independent oculomotor activity on the occipital EEG

In order to assess the effects of oculomotor activity on the occipital alpha rhythm, 24 subjects performed each of 2 instructed tasks — random eye movement and eye movement suppression — under conditions of darkness (with eyes both open and closed) and illumination (eyes open in a Ganzfeld). Recordings of the occipital EEG indicated a general blocking of alpha during periods of oculomotor activity for 2 dependent measures, percent time alpha and mean duration of alpha bursts, by comparison with baseline intervals of relaxation. These results are interpreted as support for the activating effects of efferent, oculomotor processes on the alpha component of the EEG.     

In search of a reliable electrophysiological marker of oculomotor inhibition of return

Inhibition of return (IOR) operationalizes a behavioral phenomenon characterized by slower responding to cued, relative to uncued, targets. Two independent forms of IOR have been theorized: input‐based IOR occurs when the oculomotor system is quiescent, while output‐based IOR occurs when the oculomotor system is engaged. EEG studies forbidding eye movements have demonstrated that reductions of target‐elicited P1 components are correlated with IOR magnitude, but when eye movements occur, P1 effects bear no relationship to behavior. We expand on this work by adapting the cueing paradigm and recording event‐related potentials: IOR is caused by oculomotor responses to central arrows or peripheral onsets and measured by key presses to peripheral targets. Behavioral IOR is observed in both conditions, but P1 reductions are absent in the central arrow condition. By contrast, arrow and peripheral cues enhance Nd, especially over contralateral electrode sites.     

Gaze and smooth pursuit signals interact in parietal area 7m of the behaving monkey

Posterior parietal cortex is a region specialized for multimodal integration and coordinate transformations which converts sensory input to motor output. Eye position signals are crucial for such transformations, because they are needed to the inner reconstruction of a stable image of the outside world in spite of eye movements. Area 7m is a parietal area anatomically connected with oculomotor structures such as frontal eye field and superior colliculus. The aim of this study was to assess if neurons in area 7m possess activity related to eye movements, and if so, which sort of movements are processed. We recorded the extracellular activity of 7m neurons in two monkeys trained in both a smooth pursuit and a visually guided saccade task. The majority of neurons tested with the smooth pursuit task (16/17) showed directional selectivity influenced by the eye position. Moreover, these neurons were tuned to inward or outward pursuit with respect to the center of extra-personal visual space. About half of the cells (11/24) tested with the saccade task changed their activity during the pre-saccadic period. The majority of neurons presented post-saccadic activity: most of the cells showed a directionally-selective phasic response and a modulation by eye position during fixation (23/24). Overall, we observed that area 7m contains a population of neurons signaling smooth pursuit direction at certain eye position and saccade direction toward specific portions of the visual space. We hypothesize that area 7m might be involved in spatial map updating which can be used for spatial orientation. Supported by the Italian Ministry for University and Scientific Research (MURST).     

Age-related trends in saccade characteristics among the elderly

Eye movement recordings are useful for assessing neurological disorders, the prevalence of which increases with age. However, there is little rigorous quantitative data on describing oculomotor changes that occur during healthy aging. Here, we measured the ability of 81 normal elderly subjects (60-85 years) to perform two saccadic eye movement tasks: a pro-saccade task, requiring an automatic response to look towards a stimulus and an anti-saccade task, requiring inhibition of the automatic response to instead initiate a voluntary saccade away from the stimulus. Saccadic ability decreased with age: the oldest subjects were slower to initiate saccades and they made more direction errors (i.e., erroneous pro-saccades) in the anti-saccade task. Intra-subject variability in reaction time also correlated positively with age in both saccade tasks. Voluntary saccade control, as assessed by the anti-saccade task, was far more affected by aging than automatic control, as assessed by the pro-saccade task, suggesting that the mechanisms driving voluntary and automatic saccade performance deteriorate at different rates in the aging brain, and therefore likely involves different neural substrates. Our data provide insight into deficits due to normal brain changes in aging as well as a baseline to evaluate deficits caused by neurological disorders common in this age range.     

Modulation by horizontal eye position of the vestibulo-collic reflex induced by tilting in the frontal plane in the alert cat

Summary In alert cats, during sinusoidal rotations of head and trunk en bloc around a longitudinal axis, in darkness or in light, the vestibulo-collic reflex induces neck muscle contractions. The phase and gain diagrams are consistent, in the frequency range 0.2 to 1.2 Hz, with previous results from anesthetized or decerebrate cats. In addition, neck muscle contractions are modulated by horizontal eye position, as is the case for rotations in the horizontal plane, around the vertical (Z) axis. Neck muscle contraction is consequently under control of both eye position and head tilt angle. This synergy of eye and head could suppress the effects of vestibulo-collic reflex during orienting reactions.     

Modulation by eye position of neck muscle contraction evoked by electrical labyrinthine stimulation in the alert cat

Summary Modulation of vestibulo-spinal reflexes by gaze is a model system for studying interactions between voluntary and reflex motor activity. In the alert cat, the EMG of Splenius and Obliquus capitis muscles increases with ipsilateral gaze eccentricity during spontaneous eye movements. Labyrinth stimulation by current pulses evokes EMGs with latencies consistent with a three neuron vestibulocollic pathway. The amplitude of evoked activity increases with eye position. The directions in which eye movements increase EMG was usually the same for both spontaneous and induced EMG activity, namely, horizontal and ipsilateral. However, sometimes the increase in spontaneous EMG occurred with horizontal eye position, whereas the induced EMG changed with vertical eye position. Spontaneous and evoked EMG are then modulated by different eye position signals. Command signals reflecting eye position probably reach two different types of neurons in the vestibulo-collic pathway, most likely secondary vestibular neurons and neck muscle motoneurons.V.J. Wilson's participation was made possible in part by NIH grant NS02619 and in part by a fellowship from I. N. S. E. R. M.     

Velocity storage in the vestibulo-ocular reflex arc (VOR)

Summary Vestibular and optokinetic nystagmus (OKN) of monkeys were induced by platform and visual surround rotation. Vision prolonged per-rotatory nystagmus and cancelled or reduced post-rotatory nystagmus recorded in darkness. Presumably, activity stored during OKN summed with activity arising in the semicircular canals. The limit of summation was about 120 °/s, the level of saturation of optokinetic after-nystagmus (OKAN). OKN and vestibular nystagmus, induced in the same or in opposite directions diminished or enhanced post-rotatory nystagmus up to 120 °/s. We postulate that a common storage mechanism is used for producing vestibular nystagmus, OKN, and OKAN. Evidence for this is the similar time course of vestibular nystagmus and OKAN and their summation. In addition, stored activity is lost in a similar way by viewing a stationary surround during either OKAN or vestibular nystagmus (fixation suppression).These responses were modelled using direct pathways and a non-ideal integrator coupled to the visual and peripheral vestibular systems. The direct pathways are responsible for rapid changes in eye velocity while the integrator stores activity and mediates slower changes. The integrator stabilizes eye velocity during whole field rotation and extends the time over which the vestibulo-ocular reflex can compensate for head movement.     

Co-ordination of breathing with rhythmic head and eye movements and with passive turnings of the body

In the present study, we investigated co-ordination of breathing with active horizontal head and eye movements and with passive body turnings. The main purpose was to compare co-ordination with active voluntary and with passive movements. Co-ordination was defined according to the relative phases (RPs) between breathing and additional rhythms. It was present when at least five consecutive RPs scattered less than 25% of breath duration or at least three consecutive RPs scattered less than 10%. Additionally, we studied the influence of factors such as size of active muscle groups, mechanical interactions or involuntary motor activities. In consecutive experimental conditions, 17 healthy volunteers performed voluntary rhythmic head (with eyes open and closed) and eye movements and were moved passively (also with eyes open and closed). Co-ordination occurred in all experimental conditions. The highest percentage of co-ordinated breaths was found during active head movements with closed eyes but the difference with other conditions was not significant. However, periods of stable entrainment were observed only in this condition. The results demonstrate that co-ordination is possible even in the absence of voluntary rhythmic movements. Size of active muscle groups or mechanical interactions do not necessarily affect the degree of co-ordination. On the other hand, involuntary motor activities such as reflex eye movements associated with vestibular stimulation may have a considerable influence on co-ordination between other motor processes. These results strongly support the theory of co-ordination as an unconscious nervous interaction that is not based on mechanical or intentional factors.     

Data entry on a computer terminal: Repetitive work strains on the oculomotor and central nervous systems

Summary Continuous telemetric recordings including E.K.G., E.O.G., and E.E.G. were carried out on two subjects during 4 working days: 1 day of reference work or classical clerical activities, 3 days of data entry work. Although the time allowed for the task was not limited, the performance assessed from oculomotor patterns remained stable throughout the day, from one day to the next and from one subject to another. This stability was reflected on the stereotyped E.E.G. patterns recorded during the work period, the differences occurring between reading and typing were more acute in the left cortical hemisphere than in the right. As a result of these stable patterns, the ultradian oscillations of the behavioural and physiological parameters were less during data entry than during work reference. The only possible time adjustments were the interruptions or breaks between two document pages and their variations could be considered as indicators of work load.This study was supported partly by a grant INRS 81/6360.570.001, and partly by the Department of Employment and by CNRS     

Otolithic-acoustic interaction in the control of eye movement

Summary In order to examine otolithic contribution to eye movements ten subjects were asked to track either a moving acoustic target or a stationary target during subect linear motion on a cart. The relative displacement between the subject and the target was the same in the two situations. Recordings of eye movements during subject lateral acceleration in the dark without any task, or with the task of tracking an imagined stationary target were made as a control.The frequencies ranged between 0.15 and 0.3 Hz and peak acceleration between 0.55 and 1.2 m/s². No lateral eye movements (L-nystagmus) were recorded in the dark. Only saccadic eye movements were recorded during the tracking of a moving acoustic target.Slow eye movements interspersed by saccades were observed when the moving subject tracked an imagined or an acoustic stationary target. Contribution of the slow phase to tracking was more important in the presence of an acoustic target than in the presence of imagined target. The results are interpreted in terms of an otolithic contribution to the central reconstruction of the acoustic target velocity, or in terms of an adaptive control of the otolithic-ocular reflex gain. A conceptual model accounting for these interpretations is proposed.Work supported by CNRS (France) and CNR (Italy)     

Influence of otolithic stimulation by horizontal linear acceleration on optokinetic nystagmus and visual motion perception

Summary Several studies in the past have demonstrated the existence of an Otolith-Ocular Reflex (OOR) in man, although much less sensitive than canal ocular reflex. The present paper 1 confirms these previous results. Nystagmic eye movements (L-nystagmus) appear in the seated subject during horizontal acceleration along the interaural axis in the dark for an acceleration level (1 m/s²) about ten times the perception threshold with a sensitivity of about 0.035 rad/m.When sinusoidal linear acceleration is combined with optokinetic stimulation, the recorded nystagmus slow phase velocity exhibits strong periodic modulation related to subject motion. This marked effect of linear acceleration on the optokinetic nystagmus (OKN) appears at a level (0.1 m/s²) close to the acceleration perception threshold and has a 4-fold higher sensitivity than L-nystagmus. Modulation of OKN can reach a peak-to-peak amplitude as great as 20 °/s; for a given optokinetic field size it increases with the velocity of the optokinetic stimulus, i.e. with the slow phase eye velocity. In parallel with changes in OKN slow phase velocity, linear acceleration induces a motion related decrease in the perceived velocity of the visual scene and modifications in selfmotion perception.The results are interpreted in terms of a mathematical model of visual-vestibular interaction. They show that sensory interaction processes can magnify the contribution given to the control of eye movements by the otolithic system and provide a way of exploring its function at low levels of acceleration.The present work has been presented at III European Neurosciences Meeting, Rome, September 1979     

Factors affecting the longevity of a short-term velocity store for predictive oculomotor tracking

Fast (up to 30 degrees /s) anticipatory smooth pursuit eye movements can be built up with repeated transient motion stimuli. It is thought that such stimuli charge a putative internal store of velocity information that can then drive anticipatory movements in the absence of a target. The aim of this study was to investigate the longevity of this store. Previous experiments with single ramp stimuli (Wells and Barnes 1998) suggested that the store lasts for only a few seconds before decaying to a baseline level. In the current study we investigate the possibility that the store was not maximally charged by single stimuli, precipitating its decay. The magnitude of the anticipatory response was indexed by smooth eye velocity 100 ms after target onset ( V(100)). In experiment 1 the build-up of the anticipatory response was examined by presenting sets of stimuli (comprising from one to five ramps) within a tracking phase and leaving a dark period (the 'gap') of 9.6 s between successive tracking phases. Each ramp was preceded by an audio warning cue and was accompanied throughout its 480 ms duration by an audio tone. Audio cues continued during the gap to reinforce timing information. V(100) for the first and last ramps of each set increased as the number of ramps was increased from one to three but reached an asymptotic level thereafter, suggesting that the velocity store is maximally charged after three presentations. In experiment 2 the store was maximally charged by presenting five ramps in each tracking phase and its decay was examined by leaving gaps of either 7.2 s or 14.4 s between successive tracking phases. V(100) was not diminished after either gap interval. In experiment 3 the velocity store was less well consolidated during tracking phases comprising two ramps. V(100) for the first response after the gap was unaffected by the 7.2 s gap interval but was significantly reduced when the gap interval was 14.4 s. The interval between the warning cue and ramp onset strongly influenced the magnitude of the anticipatory response, the optimum level being elicited by a cue time of 600 ms. In conclusion, this study has shown that the internal velocity store can be sustained for periods as long as 14.4 s provided that it is initially charged to a sufficiently high level and that accurate external timing cues are provided. Furthermore, we provide evidence to suggest that this process may be controlled by a two-part sample and hold mechanism.     

Discharge properties of neurons in the monkey thalamus tested with angular acceleration,eye movement and visual stimuli

Summary Monkeys were trained to make visually evoked eye movements while undergoing simultaneous head rotation. Single units were recorded in the pregeniculate nucleus (PGN). PGN neurons discharged during each saccade, but there was no change in activity with horizontal head acceleration or with various combinations of head and smooth pursuit eye movements as previously described in the cat. Therefore, the anatomical homology between LGN_v and PGN does not appear to have a neurophysiological basis. Neurons in the oral part of VPL or occasionally in VPI discharged as a function of head velocity but not with saccades, smooth pursuit or fixation eye movements, nor after brief light flashes or during smooth pursuit across structured backgrounds. This suggests that VPL_o and VPI are only vestibular relay nuclei and not concerned with vestibular/visual or vestibular/oculomotor interactions.It is a pleasure to acknowledge the histological talents of Donna Simmons, the veterinary care provided by Stan Crossman and Margaret Price, the surgical assistance of Doug Hasund, the secretarial help of Jean Scalf, and the editorial comments of Kate Schmitt.On leave from Laboratoire de Neuropsychologie Expérimentale, INSERM U 94, 16, av. Doyen Lépine, 69500 Bron, FranceThis research was supported by grants RR00166, GM00260 and EY00745 from the National Institutes of Health, U. S. Public Health Service, and by a grant from INSERM.