Neuronal responses in visual areas MT and MST during smooth pursuit target selection

We recorded the activity of single neurons in the middle temporal (MT) and middle superior temporal (MST) visual areas in two macaque monkeys while the animals performed a smooth pursuit target selection task. The monkeys were presented with two moving stimuli of different colors and were trained to initiate smooth pursuit to the stimulus that matched the color of a previously given cue. We designed these experiments so that we could separate the component of the neuronal response that was driven by the visual stimulus from an extraretinal component that predicted the color or direction of the selected target. We found that for all cells in MT and MST the response was primarily determined by the visual stimulus. However, 14% (8 of 58) of MT neurons and 26% (22 of 84) of MST neurons had a small predictive component that was significant at the P < or = 0.05 level. In some cells, the predictive component was clearly related to the color of the intended target, but more often it was correlated with the direction of the target. We have previously documented a systematic shift in the latency of smooth pursuit that depends on the relative direction of motion of the two stimuli. We found that neither the latency nor the amplitude of neuronal responses in MT or MST was correlated with behavioral latency. These results are consistent with a model for target selection in which a weak selection bias for the intended target is amplified by a competitive network that suppresses motion signals related to the nonintended stimulus. It is possible that the predictive component of neuronal responses in MT and MST contributes to the selection bias. However, the strength of the selection bias in MT and MST is not sufficient to account for the high degree of selectivity shown by pursuit behavior.     

Saccadic eye movements in families multiply affected with schizophrenia: the Maudsley Family Study

OBJECTIVE: Family studies have shown that abnormalities of smooth pursuit eye movement are increased in the adult relatives of schizophrenic probands as well as in the probands themselves. More recently, an inability of schizophrenic subjects to inhibit reflexive saccades reliably has been shown. This study aimed to test the hypothesis that the latter dysfunction is part of the extended schizophrenia phenotype. METHOD: With the use of infrared oculography, measurements of reflexive saccades and antisaccades were undertaken in 29 probands with schizophrenia, 50 of their nonpsychotic first-degree relatives, and 38 unrelated healthy volunteers. RESULTS: Probands, relatives, and healthy subjects showed no overall differences in the generation of reflexive saccades. However, in the antisaccade task, probands showed more saccadic distractibility when they were required to inhibit reflexive saccades. Analysis of corrective saccades showed that this was not due to failed comprehension or motivation. Relatives of the probands with high saccadic distractibility showed a higher distractibility rate than relatives of the probands with normal distractibility. Across all subjects, females showed a higher rate of distractibility errors than males. CONCLUSIONS: The ability to suppress reflexive saccades is an objective neurocognitive measure that is impaired in schizophrenic patients and in a proportion of their biological relatives. This antisaccade abnormality may be a vulnerability marker in a subset of schizophrenic patients and their families.     

Temporal properties of visual motion signals for the initiation of smooth pursuit eye movements in monkeys

1. Our goal was to assess whether visual motion signals related to changes in image velocity contribute to pursuit eye movements. We recorded the smooth eye movements evoked by ramp target motion at constant speed. In two different kinds of stimuli, the onset of target motion provided either an abrupt, step change in target velocity or a smooth target acceleration that lasted 125 ms followed by prolonged target motion at constant velocity. We measured the eye acceleration in the first 100 ms of pursuit. Because of the 100-ms latency from the onset of visual stimuli to the onset of smooth eye movement, the eye acceleration in this 100-ms interval provides an estimate of the open-loop response of the visuomotor pathways that drive pursuit. 2. For steps of target velocity, eye acceleration in the first 100 ms of pursuit depended on the "motion onset delay," defined as the interval between the appearance of the target and the onset of motion. If the motion onset delay was > 100 ms, then the initial eye movement consisted of separable early and late phases of eye acceleration. The early phase dominated eye acceleration in the interval from 0 to 40 ms after pursuit onset and was relatively insensitive to image speed. The late phase dominated eye acceleration in the interval 40-100 ms after the onset of pursuit and had an amplitude that was proportional to image speed. If there was no delay between the appearance of the target and the onset of its motion, then the early component was not seen, and eye acceleration was related to target speed throughout the first 100 ms of pursuit. 3. For step changes of target velocity, the relationship between eye acceleration in the first 40 ms of pursuit and target velocity saturated at target speeds > 10 degrees /s. In contrast, the relationship was nearly linear when eye acceleration was measured in the interval 40-100 ms after the onset of pursuit. We suggest that the first 40 ms of pursuit are driven by a transient visual motion input that is related to the onset of target motion (motion onset transient component) and that the next 60 ms are driven by a sustained visual motion input (image velocity component). 4. When the target accelerated smoothly for 125 ms before moving at constant speed, the initiation of pursuit resembled that evoked by steps of target velocity. However, the latency of pursuit was consistently longer for smooth target accelerations than for steps of target velocity.(ABSTRACT TRUNCATED AT 400 WORDS)     

Value of beat-to-beat blood pressure changes, detected by pulse transit time, in the management of the obstructive sleep apnoea/hypopnoea syndrome

BACKGROUND: Previous studies of oculomotor dysfunction in schizophrenia have tended to concentrate on abnormalities of smooth pursuit eye tracking in chronic medicated patients. We report the results of a study of smooth pursuit, reflexive and antisaccade performance in drug naive and antipsychotic treated first-episode schizophrenic patients. METHODS: Smooth pursuit and saccadic eye movements were recorded in 36 first-episode schizophrenic patients and 36 controls matched for age and estimated IQ. The schizophrenic patients were divided into drug-naive (N = 17) and antipsychotic treated groups (N = 19). RESULTS: Smooth pursuit velocity gain was significantly lower than controls only in the drug-naive patients. The treated patients did not differ significantly from either the controls or the untreated group. In an antisaccade paradigm both treated and drug-naive schizophrenic patients demonstrated an increased number of errors, but only drug-naive patients also demonstrated an increased latency in initiating correct antisaccades. CONCLUSIONS: These impairments are unlikely to be due to a generalized deficit in oculomotor function in the schizophrenic groups, as there were no differences between the groups in saccadic metrics on a reflexive saccade task. The results show that both smooth pursuit and saccadic abnormalities are present at the onset of schizophrenia and are integral to the disorder.     

Pursuit gain and saccadic intrusions in first-degree relatives of probands with schizophrenia.

Oculomotor functioning of 26 probands (aged 18–45 yrs) with schizophrenia, 12 spectrum and 46 nonspectrum 1st-degree relatives (aged 16–72 yrs), and 38 nonpsychiatric control Ss (aged 19–67 yrs) was evaluated. Spectrum relatives had more anticipatory saccades (ASs) and lower pursuit gain than nonspectrum relatives, who had more ASs and lower pursuit gain than control Ss. Probands also had lower pursuit gain than nonspectrum relatives and control Ss but did not differ from other groups on AS frequency. Control Ss had more globally accurate pursuit tracking (root mean square [RMS] error deviation) than both relative groups, whereas probands had the poorest RMS scores. Square wave jerk frequency did not differentiate the groups. Attention enhancement affected the frequency of ASs but did not affect either the other intrusive saccadic event or RMS scores. These results offer evidence that eye-movement dysfunction may serve as a biological marker for schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Smooth pursuit eye movement and schizotypy in the community.

Deficits in smooth pursuit eye movements are well documented in schizophrenia and schizotypic psychopathology. The status of eye tracking dysfunction (ETD) as an endophenotype for schizophrenia liability is relatively robust. However, the relation of ETD to schizophrenia-related deviance in the general population has not been confirmed. This study examined smooth pursuit eye tracking and schizotypal personality features in the general population. Smooth pursuit eye movement and schizotypal features were measured in 300 adult community subjects. The sample included both sexes, subjects with a wide age and educational range, and subjects with no prior history of psychosis. Primary outcome measures were peak gain (eye velocity/target velocity), catch-up saccade rate, and schizotypal feature scores. Total schizotypal features were significantly associated with decreased peak gain and were associated at the trend level with increased catch-up saccade rate. These associations were essentially unchanged after controlling for age, sex, and intellectual level effects. These data confirm a hypothesized association between schizotypal features and poorer eye tracking performance (principally, peak gain) in the general population as well as support the conceptualization of ETD as an endophenotype for schizophrenia liability. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Distinguishing schizophrenic patients from healthy controls by quantitative measurement of eye movement parameters

BACKGROUND: Eye tracking dysfunction is a putative trait marker for susceptibility to schizophrenia; however, it cannot be recommended as an additional tool for the diagnosis of schizophrenia, due to low sensitivity and specificity. METHODS: To assess the diagnostic potentials of combinations of eye movement paradigms, four smooth pursuit experiments (1: constant velocity of 15 degrees/sec; 2 and 3: combination with either visual or auditory distractors; 4: constant velocity of 30 degrees/sec) and two saccadic eye movement experiments (1: reflexive saccades; 2: voluntary saccades) were conducted. Fourteen patients with residual schizophrenia and 17 healthy controls were studied. Two sets of discriminant analyses (each with the resubstitution and with the "leaving one out" method) were calculated. RESULTS: In the first set, all 10 characteristic variables were included, whereas for the second set, the three most powerful parameters were selected (two from smooth pursuit tasks and one from a voluntary saccade experiment). This procedure provided the best classification results, regarding concordance between clinical diagnoses and eye movement dysfunction (kappa = .67-.80). CONCLUSIONS: Schizophrenic patients of the residual subtype can be differentiated from healthy individuals with considerable criterion validity on the basis of paradigms from two different ocular motor systems.     

Neurophysiological markers of vulnerability to schizophrenia: Sensitivity and specificity of specific quantitative eye movement measures.

Eye-tracking deficits in schizophrenic patients and relatives have generated interest in using eye movements to mark schizophrenia liability. Efforts to develop specific quantitative measures have provided insight into the nature of the deficit and suggested what underlying neurophysiological mechanisms are involved. This study used receiver operating characteristic curve analyses to evaluate and compare the sensitivity, specificity, and overall accuracy of predicting disease liability using single and combined specific and global quantitative measures. Results indicate that measures of predictive pursuit and leading saccades significantly increased predictive accuracy compared with traditional global measures. Combining specific measures provided greater predictive accuracy compared with single measures. Implications for the use of specific eye movement measures to define schizophrenia-related phenotypes in genetic studies are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex differences in neuropsychological function in non-psychotic relatives of schizophrenic probands

Some recent studies suggest that men with schizophrenia may have greater neuropsychological deficits than women. It is not known, however, whether similar sex differences may be present in biological relatives of schizophrenic patients. We evaluated neuropsychological functioning of 54 relatives of schizophrenic patients and 72 normal volunteers. It was hypothesized that, if sex differences were present, they would be accounted for largely by deficits in male relatives. We were particularly interested in three neuropsychological functions that we previously identified as putative neuropsychological vulnerability indicators for schizophrenia: (1) abstraction/executive function; (2) verbal memory; and (3) auditory attention. There were significant group x sex interactions for verbal memory and motor function, and trends toward significant interactions for auditory attention and mental control/encoding. However, with the exception of motor function, it was the female relatives who accounted for most of the impairment. A speculative explanation for the findings is that women may have a higher threshold than men for developing schizophrenia. If so, female relatives might be able to withstand greater impairments than men before developing psychotic symptoms. Consequently, in a sample that was limited to non-psychotic relatives--as in the present study--there could be over-representation of both less impaired men and more impaired women. Alternative explanations and limitations of the study are also discussed.     

Anticipatory saccades during smooth pursuit eye movements and familial transmission of schizophrenia

BACKGROUND: Smooth pursuit eye movement (SPEM) abnormalities are a putative marker of genetic risk for schizophrenia. Accurate SPEM performance requires the subject to activate neural systems responsible for smooth pursuit tracking, while simultaneously suppressing activity of neurons responsible for saccadic movements that would move the eye ahead of the target. This study examined whether specific aspects of SPEM dysfunction cosegregate with genetic risk in parents of schizophrenic probands. METHODS: Eighteen probands and their parents had SPEM recorded. Parents with an ancestral history of schizophrenia were hypothesized to be more likely than their spouses without such a history to carry a genetic risk for schizophrenia. RESULTS: Ten families had a single parent with a positive ancestral history for schizophrenia. The frequency of anticipatory saccades, which were mostly small, and the fraction of total eye movement that they represented were the only measures that differentiated the more likely genetic carrier parents in these families from their spouses and age-matched normals. CONCLUSIONS: Failure to suppress saccadic anticipation of target motion during smooth pursuit appears an aspect of SPEM dysfunction related to presumed genetic risk for schizophrenia.     

Eye movements, prematurity and developmental co-ordination disorder

Horizontal pursuit eye movements were investigated in two separate groups of children: One group exhibited developmental co-ordination disorder (n = 8) whilst another group of children were born prematurely (n = 8). Both studies found a reduced gain in pursuit eye movements when the respective populations were compared with control groups (n = 32). A difference was also found in the ability of some children to temporally synchronize their tracking response to the stimulus, which was indicative of poor predictive control rather than lags in the control system. We suggest that horizontal eye movements may be a sensitive indicator of more general motor deficits during childhood development.     

Antisaccade performance in patients with schizophrenia and affective disorder.

The authors examined psychotic patients with schizophrenia, major depression, and bipolar disorder; "normal" participants; and 1st-degree relatives of patients with schizophrenia on an antisaccade task in which participants were instructed to move their eyes in the opposite direction of a target that moved unpredictably and abruptly either to the left or right of central fixation. Patients with schizophrenia were found to make significantly more errors than their relatives, and the latter made more errors than the controls. The poor performance of the relatives could not be attributed to their having a psychiatric disorder. Comparison of the 3 patient groups indicated that antisaccade deficits were more pronounced in schizophrenia and bipolar disorder. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Directional organization of eye movement and visual signals in the floccular lobe of the monkey cerebellum

The floccular lobe of the monkey is critical for the generation of visually-guided smooth eye movements. The present experiments reveal physiological correlates of the directional organization in the primate floccular lobe by examining the selectivity for direction of eye motion and visual stimulation in the firing of individual Purkinje cells (PCs) and mossy fibers. During tracking of sinusoidal target motion along different axes in the frontoparallel plane, PCs fell into two classes based on the axis that caused the largest modulation of simple-spike firing rate. For "horizontal" PCs, the response was maximal during horizontal eye movements, with increases in firing rate during pursuit toward the side of recording (ipsiversive). For "vertical" PCs, the response was maximal during eye movement along an axis just off pure vertical, with increases in firing rate during pursuit directed downward and slightly contraversive. During pursuit of target motion at constant velocity, PCs again fell into horizontal and vertical classes that matched the results from sinusoidal tracking. In addition, the directional tuning of the sustained "eye velocity" and transient "visual" components of the neural responses obtained during constant velocity tracking were very similar. PCs displayed very broad tuning approximating a cosine tuning curve; the mean half-maximum bandwidth of their tuning curves was 170-180 degrees. Other cerebellar elements, related purely to eye movement and presumed to be mossy fibers, exhibited tuning approximately 40 degrees narrower than PCs and had best directions that clustered around the four cardinal directions. Our data indicate that the motion signals encoded by PCs in the monkey floccular lobe are segregated into channels that are consistent with a coordinate system defined by the vestibular apparatus and eye muscles. The differences between the tuning properties exhibited by PCs compared with mossy fibers indicate that a spatial transformation occurs within the floccular lobe.     

Clinicians'' decision making about involuntary commitment

When we make a smooth eye movement to track a moving object, the visual system must take the eye's movement into account in order to estimate the object's velocity relative to the head. This can be done by using extra-retinal signals to estimate eye velocity and then subtracting expected from observed retinal motion. Two familiar illusions of perceived velocity--the Filehne illusion and Aubert-Fleischl phenomenon--are thought to be the consequence of the extra-retinal signal underestimating eye velocity. These explanations assume that retinal motion is encoded accurately, which is questionable because perceived retinal speed is strongly affected by several stimulus properties. We develop and test a model of head-centric velocity perception that incorporates errors in estimating eye velocity and in retinal-motion sensing. The model predicts that the magnitude and direction of the Filehne illusion and Aubert-Fleischl phenomenon depend on spatial frequency and this prediction is confirmed experimentally.     

Properties of memory-guided saccades toward targets flashed during smooth pursuit in human subjects

PURPOSE: This study in human subjects investigated whether or not the saccade system can monitor smooth changes of the eye position in total darkness. METHODS: The authors studied the properties of memory-guided saccades toward targets flashed during pursuit eye movements (target velocities of 15 degrees/s, 30 degrees/s, and 45 degrees/s) in four normal human subjects. Subjects were instructed to execute memory-guided saccades toward the position of the flashed target in total darkness when the pursuit target was extinguished. RESULTS: The vector of the saccade was more highly correlated with the vector of "spatial error" (the vector from the position of the eye at the time of the saccade to the position of the flashed target in space) than with the vector of "retinal error" (the vector from the position of the eye at the time of the presentation of the flashed target to the position of the flashed target). The amplitude and direction errors of memory-guided saccades were correlated with the amplitude of the retinal error but not with amplitude of eye deviation after the presentation of the flashed target. Pursuit velocity did not affect the error of the saccade. CONCLUSIONS: These findings suggest that the saccade system can monitor smooth changes of the eye position in total darkness, regardless of the velocity of pursuit, and that the accuracy of memory-guided saccades is dependent only on the amplitude of the retinal error.     

Spatial integration in human smooth pursuit

When viewing a moving object, details may appear blurred if the object's motion is not compensated for by the eyes. Smooth pursuit is a voluntary eye movement that is used to stabilize a moving object. Most studies of smooth pursuit have used small, foveal targets as stimuli (e.g. Lisberger SG and Westbrook LE. J Neurosci 1985;5:1662-1673.). However, in the laboratory, smooth pursuit is poorer when a small object is tracked across a background, presumably due to a conflict between the primitive optokinetic reflex and smooth pursuit. Functionally, this could occur if the motion signal arising from the target and its surroundings were averaged, resulting in a smaller net motion signal. We asked if the smooth pursuit system could spatially summate coherent motion, i.e. if its response would improve when motion in the peripheral retina was in the same direction as motion in the fovea. Observers tracked random-dot cinematograms (RDC) which were devoid of consistent position cues to isolate the motion response. Either the height or the density of the display was systematically varied. Eye speed at the end of the open-loop period was greater for cinematograms than for a single spot. In addition, eye acceleration increased and latency decreased as the size of the aperture increased. Changes in the density produced similar but smaller effects on both acceleration and latency. The improved pursuit for larger motion stimuli suggests that neuronal mechanisms subserving smooth pursuit spatially average motion information to obtain a stronger motion signal.     

A neural model of visually guided steering, obstacle avoidance, and route selection.

A neural model is developed to explain how humans can approach a goal object on foot while steering around obstacles to avoid collisions in a cluttered environment. The model uses optic flow from a 3-dimensional virtual reality environment to determine the position of objects on the basis of motion discontinuities and computes heading direction, or the direction of self-motion, from global optic flow. The cortical representation of heading interacts with the representations of a goal and obstacles so that the goal acts as an attractor of heading and obstacles act as repellers. In addition, the model maintains fixation on the goal object by generating smooth pursuit eye movements. Eye rotations can distort the optic flow field, complicating heading perception, and the model uses extraretinal signals to correct for this distortion and accurately represent heading. The model explains how motion processing mechanisms in cortical areas middle temporal, medial superior temporal, and posterior parietal cortex can be used to guide steering. The model quantitatively simulates human psychophysical data about visually guided steering, obstacle avoidance, and route selection. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Eye tracking dysfunction in schizophrenia: Characterization of component eye movement abnormalities, diagnostic specificity, and the role of attention.

To characterize oculomotor components and diagnostic specificity of eye tracking abnormalities in schizophrenia, we examined a large consecutively admitted series of psychotic patients and matched controls. The most common abnormality in schizophrenic patients was low gain (slow) pursuit eye movements (47% of cases). Pursuit and saccadic eye movement abnormalities were no more severe in schizophrenic Ss than in those with affective psychoses, except that high rates of catch-up saccades were unique to schizophrenic Ss (17% of cases). These findings indicate that impaired pursuit eye movements are a major cause of eye tracking impairments in schizophrenia, that tracking dysfunctions commonly occur in affective psychoses, and that markedly high rates of catch-up saccades during eye tracking may be specific to schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Is eye movement dysfunction a biological marker for schizophrenia? A methodological review.

There is a high prevalence of eye movement dysfunction (EMD) in persons with schizophrenia and their first-degree relatives. Studies addressing the prevalence, stability, familial transmission, and psychological correlates of EMD in persons from both psychiatric and general populations offer suggestive evidence that this abnormality may serve as a biological marker for schizophrenia. Although these findings are promising, their significance for elucidating the diagnostic bandwidth, pathophysiology, and genetics of this disorder remains to be determined. More precise characterization of ocular motility, perhaps when used in conjunction with global measures of pursuit adequacy, may be essential for clarifying the pathophysiological and genetic significance of EMD for schizophrenia. Recent research efforts are beginning to identify particular abnormalities that could serve as more specific biological markers for schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Study of non-visually induced smooth pursuit eye movements and their predictability using pseudorandom target motion

It has been found that the smooth pursuit eye movements (SPEM) are elicited by not only visual stimuli but also non-visual information such as the subject's fingertip movement and a moving sound source. We have already reported the quantitative analysis of SPEM which were induced by somatosensory and acoustic information. In the previous study, we used a sinusoidal waveform that could be highly predictable. Since it is wellknown that predictive control has an important role in the normal SPEM, we expect the predictive control to function in non-visually induced SPEM (NVSPEM). We quantitatively analyzed NVSPEM and normal SPEM evoked by pseudorandom target motion in ten human subjects who had no ocular, oculomotor or vestibular disorders. NVSPEM were induced by the following two non-visual targets: 1, subjects' fingertip motion as a somatosensory target ("Somato"), 2, a small loudspeaker (3-cm diameter.) generating white noise with an intensity of about 60 dB (A) as an acoustic target ("Acoustic"). A servo-controlled swing arm of 50cm was used to drive the subject's fingertip and the acoustic target of the small loudspeaker. The horizontal motion of the swing arm was controlled by a personal computer. The pseudorandom target motion was generated by mixing four sinusoids (0.1, 0.2, 0.4, 0.8 Hz) of which the phases were randomly selected and the peak velocities were equally set at 19 deg/s. The mean peak velocity of the target was 26.2 deg/s and the amplitude was limited within 15 deg. Horizontal eye movements were recorded by DC electro-oculography and on an analogue datatape. The experiment was performed for 30 s in complete darkness so that the subjects' fingertip and loudspeaker as such remain invisible to the subject. Signals from the data recorder were smoothed by a low pass analogue filter of 20Hz, after digitization with a sampling frequency of 200 Hz and precision of 12 bits, and stored on a computer. The slow and quick eye movement components, both of which were present in each class of horizontal eye movement investigated, were identified and separated by a computer. Then we developed a method of automatic quantitative analysis of ocular tracking eye movement. Gain and phase values for the smooth pursuit eye movements were obtained in each condition. In the lower frequency area, the gain elicited by the pseudorandom stimulation was lower than the smooth pursuit gain for sinusoidal (predictable) stimulation in all conditions. In the highest frequency, gain values did not differ significantly among the three. For the sinusoidal stimulation, the phase of the smooth component of "Visual" always had a lag and that of "Somato" and "Acoustic" had a lead in lower frequencies. All conditions had a phase shift, decreasing with increasing frequency. For the pseudorandom stimulation the phase of the SPEM had a lead only in the lowest frequency (0.1 Hz). On the other hand, in the NVSPEM the phases of the three lower frequencies had a lead which had a tendency of a larger phase lead with decreasingly frequency. In the highest frequency (0.8 Hz), we could see a short phase lag. These findings support the idea that SPEM and NVSPEM have a mutual or similar physiologic system and overlap part of the anatomical pathway.