Eye Movement Latency Research Articles

The effects of an orally administered cholinergic agonist on REM sleep in major depression

Background: Centrally active cholinergic agents such as arecoline and physostigmine shorten rapid eye movement (REM) latency, reduce REM interval times, or both and do so preferentially in patients with depression. We tested an orally administered cholinergic agonist (donepezil HCL 10 mg [Aricept]) to determine whether this agent also alters REM timing in depressed patients (n = 8) compared with age- and gender-matched control subjects (n = 8).Methods: All subjects were studied for 3 consecutive nights in the sleep laboratory. The design was a fixed-order placebo-donepezil protocol to accommodate the long half-life of donepezil. Night 1 served as an adaptation night. On night 2, placebo was administered at 8:00 pm. On night 3, donepezil was administered at 8:00 pm.Results: The cholinergic challenge distinguished the groups. In depressed patients REM latency was reduced compared with baseline (47.6 vs. 64.4, p = .04) following administration of donepezil. Control subjects showed no response: REM latency after donepezil was virtually identical to baseline REM latency (71.7 vs. 69.3).Conclusions: These data indicate that donepezil is likely to be useful in testing hypotheses related to cholinergic function in mood disorders.

Adaptive changes in smooth pursuit eye movements induced by cross-axis pursuit-vestibular interaction training in monkeys.

The smooth pursuit system interacts with the vestibular system to maintain the accuracy of eye movements in space. To understand neural mechanisms of short-term modifications of the vestibulo-ocular reflex (VOR) induced by pursuit-vestibular interactions, we used a cross-axis procedure in trained monkeys. We showed earlier that pursuit training in the plane orthogonal to the rotation plane induces adaptive cross-axis VOR in complete darkness. To further study the properties of adaptive responses, we examined here the initial eye movements during tracking of a target while being rotated with a trapezoidal waveform (peak velocity 30 or 40 degrees/s). Subjects were head-stabilized Japanese monkeys that were rewarded for accurate pursuit. Whole body rotation was applied either in the yaw or pitch plane while presenting a target moving in-phase with the chair with the same trajectory but in the orthogonal plane. Eye movements induced by equivalent chair rotation with or without the target were examined before and after training. Before training, chair rotation alone resulted only in the collinear VOR, and smooth eye movement-tracking of orthogonal target motion during rotation had a normal smooth pursuit latency (ca 100 ms). With training, the latency of orthogonal smooth tracking eye movements shortened, and the mean latency after 1 h of training was 42 ms with a mean gain, at 100 ms after stimulus onset, of 0.4. The cross-axis VOR induced by chair rotation in complete darkness had identical latencies with the orthogonal smooth tracking eye movements, but its gains were <0.2. After cross-axis pursuit training, target movement alone without chair rotation induced smooth pursuit eye movements with latencies ca 100 ms. Pursuit training alone for 1 h using the same trajectory but without chair rotation did not result in any clear change in pursuit latency (ca 100 ms) or initial eye velocity. When a new target velocity was presented during identical chair rotation after training, eye velocity was correspondingly modulated by just 80 ms after rotation onset, which was shorter than the expected latency of pursuit (ca 100 ms). These results indicate that adaptive changes were induced in the smooth pursuit system by pursuit-vestibular interaction training. We suggest that this training facilitates the response of pursuit-related neurons in the cortical smooth pursuit pathways to vestibular inputs in the orthogonal plane, thus enabling smooth eye movements to be executed with shorter latencies and larger eye velocities than in normal smooth pursuit driven only by visual feedback.

Sleep polysomnography as a predictor of recurrence in children and adolescents with major depressive disorder.

Adults with major depressive disorder (MDD) demonstrate certain sleep polysomnographic abnormalities, including sleep continuity disturbances, reduced slow-wave sleep, shortened rapid eye movement (REM) latency, and increased REM density. Findings of sleep EEG studies in depressed children and adolescents have yielded conflicting results, possibly because of methodological variations across the studies. Generally, however, studies have demonstrated that depressed children and adolescents exhibit less sleep continuity and non-REM sleep differences in comparison with control subjects than do adults. Thus, results from adult sleep polysomnography studies cannot necessarily be generalized to children and adolescents. Depressed adults who have reduced REM latency during the symptomatic episode appear more likely to have a relapse once treatment is discontinued than those with normal REM latency. No studies of the relationship between sleep polysomnographic variables and clinical course have been reported in depressed children and adolescents. Data for baseline clinical variables and 3 nights of sleep polysomnography were examined in 113 depressed children (< or = 12 yr; n = 51) and adolescents (> or = 13 yr; n = 62) (56 in-patients and 57 outpatients) where data was available on at least 1 yr of naturalistic follow-up. Subjects came from 2 studies of sleep polysomnography in children and adolescents with MDD. Clinical course was assessed using the Kiddie-Longitudinal Interval Follow-Up Evaluation (K-LIFE). This interview was used to define recovery from the index episode of MDD and recurrence, a new episode of meeting full criteria for MDD. Clinically, within 1 yr of initial evaluation 102/113 subjects had recovered from their index episode of depression (minimal or no symptoms for 60 d). Of the 102 subjects who recovered, 36 (35.3%) had a recurrence of MDD. The majority of subjects (55%) who had a recurrence were not on medication at the time of recurrence. Subjects who had a recurrence were more likely to report suicidal thoughts or attempts at baseline compared to those without a recurrence (67 vs. 37%; F = 8.77; p = 0.004). On baseline sleep polysomnography, subjects with a later recurrence had decreased sleep efficiency and delayed sleep onset (sleep latency > 10 min). Probability of recurrence at 12 months was 0.39 compared to 0.15 in subjects with non-delayed sleep onset (p = 0.005). Baseline suicidal ideation and sleep dysregulation on sleep polysomnography predicted recurrence in a large sample of depressed children and adolescents. Depression in children and adolescents is frequently a chronic, recurrent illness. Factors that can predict clinical course are important in increasing our understanding of depression in this age group.

Behavioral and Cortical Measures of Infants' Visual Expectations

AbstractFeatures of the habituation paradigm were combined with the visual expectation paradigm to examine behavioral and cortical indexes of infants' visual expectations. Eight 3‐month‐old infants watched an alternating picture sequence while their eye movements were videotaped and their cortical electrophysiological activity (event‐related potential [ERP]) was recorded. Two ERP epochs were examined: a 3,000‐msec stimulus‐locked epoch included 1,000 msec before stimulus onset through 1,000 msec after stimulus offset; and a 1,200‐msec response‐locked epoch included 700 msec before saccade onset through 500 msec after the saccade. All infants anticipated upcoming pictures, and eye movement latencies for pictures that were not anticipated were comparable to saccade latencies reported in other visual expectation studies of infants at this age. Three components were identified in the stimulus‐locked ERP waveform: a slowly developing negativity prior to picture onset, a postonset negative slow wave, and a late negative deflection that peaked about 750 msec after picture onset. All stimulus‐locked components were larger for familiar than for unfamiliar pictures; prestimulus negativity was also greater before anticipated pictures. The response‐locked waveform contained 2 prominent features: a slowly increasing negative shift (NS) that began about 500 msec before saccade onset and a positive presaccadic potential that occurred about 30 to 90 msec before the saccade. Response‐locked components were larger for anticipatory saccades at the frontal scalp site; for reactive saccades, response‐locked components were larger at the vertex. Results are informative about ERPs in infants, cortical control of eye movements, and the development of visual expectations.

Context-dependent smooth eye movements evoked by stationary visual stimuli in trained monkeys.

The appearance of a stationary but irrelevant cue triggers a smooth eye movement away from the position of the cue in monkeys that have been trained extensively to smoothly track the motion of moving targets while not making saccades to the stationary cue. We have analyzed the parameters that regulate the size of the cue-evoked smooth eye movement and examined whether presentation of the cue changes the initiation of pursuit for subsequent steps of target velocity. Cues evoked smooth eye movements in blocks of target motions that required smooth pursuit to moving targets, but evoked much smaller smooth eye movements in blocks that required saccades to stationary targets. The direction of the cue-evoked eye movement was always opposite to the position of the cue and did not depend on whether subsequent target motion was toward or away from the position of fixation. The latency of the cue-evoked smooth eye movement was near 100 ms and was slightly longer than the latency of pursuit for target motion away from the position of fixation. The size of the cue-evoked smooth eye movement was as large as 10 degrees /s and decreased as functions of the eccentricity of the cue and the illumination of the experimental room. To study the initiation of pursuit in the wake of the cues, we used bilateral cues at equal eccentricities to the right and left of the position of fixation. These evoked smaller eye velocities that were consistent with vector averaging of the responses to each cue. In the wake of bilateral cues, the initiation of pursuit was enhanced for target motion away from the position of fixation, but not for target motion toward the position of fixation. We suggest that the cue-evoked smooth eye movement is related to a previously postulated on-line gain control for pursuit, and that it is a side-effect of sudden activation of the gain-controlling element.

Spatial and temporal aspects of eye-hand coordination across different tasks.

The way in which saccadic eye movements are elicited influences their latency and accuracy. Accordingly, different tasks elicit different types of saccades. Using the tasks steps, gap, memory, scanning and antisaccade, we analyzed combined eye and hand movements to determine whether both motor systems share control strategies. Errors and latencies were measured to examine whether changes in eye motor behavior are reflected in hand motor behavior. Directional and variable errors of eye and hand changed differently according to the tasks. Moreover, errors of the two systems did not correlate for any of the tasks investigated. Contrary to errors, mean latencies of eye movements were organized in the same pattern as hand movements. A correlation of latencies indicates that both motor systems rely on common information to initiate movement. Temporal coupling was stronger for intentional tasks than for reflexive tasks.

Polysomnographic and Spectral Sleep EEG in Primary Alcoholics: An Interaction Between Alcohol Dependence and African‐American Ethnicity

Disturbances of sleep EEG are prominent in alcoholic patients, persist into recovery, and recently have been found to predict those alcoholics who are most likely to relapse. Increasing evidence indicates that there are ethnic differences in sleep EEG and that African-Americans may be at elevated risk for disordered sleep. This study compared polysomnographic and spectral sleep EEG measures in male primary alcoholic inpatients (n = 31) and age-matched comparison controls (n = 31) stratified by African-American and Euro-American ethnicity. African-American alcoholic patients showed more severe sleep abnormalities than Euro-American alcoholics, and the interaction between alcohol dependence and ethnicity uniquely contributed to prolonged sleep latency (p < 0.001), loss of delta sleep (p < 0.001), and short rapid eye movement (REM) latency (p < 0.001). Spectral EEG analyses confirmed polysomnographic findings of disordered sleep architecture in alcoholics. Compared with controls, alcoholics had lower delta (0.75-4.5 Hz) activity over the whole night (p < 0.05), reductions in mean spectral power (0.75-40 Hz, p < 0.05), and decreases of delta (p < 0.01) and theta (4.5-7.5 Hz,p = 0.05) activity during the first period of non-REM sleep, with African-American alcoholics having the lowest theta of the four groups. In view of the possible connection between relapse and poor sleep and the role of sleep in the maintenance of health, these data have implications for treatment and morbidity outcomes in African-American alcoholics.

Effects of informative peripheral cues on eye movements: Revisiting William James’ “derived attention”

Two experiments examined effects of peripheral information on the latency of saccadic eye movements. In Experiment 1, simple target stimuli were presented to the left or right visual field. Prior to each target, a pair of cue letters was presented for 40msec bilaterally. The relative location of the letters (W-S or S-W) was related to target location, but participants were not informed of this contingency. After a brief practice period, saccadic latencies were faster for targets at the likely location, as indicated by the letter pair. This derived peripheral cueing effect was related to participants' awareness of the relation between cue type and target location. Experiments 2A and 2B employed monocular viewing in order to compare performance across the nasal and temporal visual fields. The effect observed in Experiment 1 was confined to the nasal visual field. In a reflexive orienting condition, the effect of a unilateral letter cue was larger in the temporal visual field. It is concluded that the neurocognitive processes responsible for derived peripheral cueing are distinct from those involved in either reflexive or voluntary orienting.

The role of the gap effect in the orienting of attention: Evidence for express attentional shifts

The “gap effect” refers to the finding that saccadic latencies are typically reduced when the fixation point is removed just prior to the presentation of a target. One explanation for this effect is that the removal of the fixation point causes the disengagement of covert attention and allows for extremely rapid movements of attention (express attentional shifts). However, previous research regarding express attentional shifts has yielded equivocal results. The present study used a variation of a peripheral cueing paradigm with a discrimination task (Experiment 1) and a detection task (Experiment 2) to further examine this issue. The results from eye movement and keypress latencies indicated that there were express attentional shifts with the discrimination task but not in the detection task. This pattern of results may have been due to differences in how attention was allocated between the two tasks. Thus, evidence for express attentional shifts was found, but only under certain conditions.

Lorazepam-induced modifications of saccadic and smooth-pursuit eye movements in humans: attentional and motor factors

In a placebo-controlled, double-blind study, we measured the effects of low dose lorazepam on attentional and motor factors involved in saccadic and smooth pursuit eye movements. We manipulated the temporal interval between the extinction of the central fixation target and the appearance of a second eccentric target (gap/overlap step paradigm). The second target was either stationary (saccade trial) or moving in a direction opposite to the step (pursuit trial). Gap/overlap effects on the latency of saccadic and smooth pursuit eye movements were measured before and after oral intake of either lorazepam or placebo. Pharmacological effects on the dynamics and the accuracy of both types of eye movements were also investigated. In 14 healthy volunteers, we found that the temporal interval between fixation target offset and eccentric target onset modulates the latency of saccadic and smooth pursuit eye movements in a similar way. As compared to placebo, lorazepam significantly increased the latency of both types of eye movements, but did not modify the gap/overlap effect. Moreover, lorazepam significantly decreased the peak velocity of the first saccade towards the eccentric stationary target, as well as the gain of tracking towards the eccentric moving target. However, the overall accuracy of both behaviors was not significantly affected, indicating that systematic errors in foveating or tracking were detected and corrected by appropriate corrective or catch-up saccades, respectively. Results are discussed in terms of shared/different mechanisms for saccadic and pursuit systems in primates.

Biases in eye movements to threatening facial expressions in generalized anxiety disorder and depressive disorder.

The study investigated biases in selective attention to emotional face stimuli in generalized anxiety disorder (GAD) and depressive disorder, using a modified probe detection task. There were 4 face types: threatening, sad, happy, and neutral. Measures of attentional bias included (a) the direction and latency of the initial eye movement in response to the faces and (b) manual reaction time (RT) to probes replacing the face stimuli 1,000 ms after their onset. Results showed that individuals with GAD (without depressive disorder) were more likely to look first toward threat faces rather than neutral faces compared with normal controls and those with depressive disorder. They also shifted their gaze more quickly toward threat faces, rather than away from them, relative to the other two groups. There were no significant findings from the manual RT data. Implications of the results for recent theories of clinical anxiety and depression are discussed.

Age dependence of sensory and motor components in saccades

Humans usually perform about 3-4 saccades per second; hence, precision as well as latency and velocity of these fast eye movements are of crucial importance for analyzing complex and fast changing visual scenes, for example in traffic. Since visual performance is known to slowly decline with age, we investigated the effect of age on the most important characteristics of visually guided saccades. This investigation on age dependence of visually guided saccades included, for the first time, the gap condition, where the old fixation point disappears before the new one appears, allowing subjects to prepare for a saccade. Saccadic latencies and intersaccadic intervals increased with age, while their peak velocities and gains decreased, especially for threshold-adjusted luminance of the targets. The gap condition, however, improved reaction times (latencies) most pronounced in the older age groups, bringing performance for these groups close to the performance level of the young groups. This indicates that the slowing down of saccadic reaction times with age is not predominantly a motor problem, but, according to a common interpretation of the gap effect, a problem of disengaging attention from the old fixation spot.

Influence of vestibular input on visually guided saccades

A common pathway in the brainstem is thought to exist for the induction of visually guided saccades and rapid phase nystagmus (Ref. Ohki et al. 1988). This common pathway is often referred to as "the saccade generator" or "the burst generator." The presence of this pathway suggests that vestibular function can be examined by applying "visual stimuli" and "vestibular stimuli" at the same time. We therefore investigated whether caloric stimulation affects the latency, amplitude and velocity of saccadic eye movements and if so, how. Nine normal volunteers participated in the experiment. Eye movements were recorded using DC electrooculography. Caloric stimulation was applied to the right ear using an air caloric stimulator (10 degrees C) during saccades. Two experiments involving visually guided saccades were performed. Task 1: The subject was asked to fixate on a central fixation point. Another spot of light then randomly appeared at one of two different locations (20 degrees to the right or left). The subject was then asked to scan towards the second light as quickly as possible. Task 2: The procedure was the same as in Task 1, except that the target appeared only briefly and then later reappeared at the same location. The saccade latency was unaffected by caloric stimulation in Task 1, while the latency of the rightward saccades increased significantly in Task 2. The saccade amplitude and velocity increased significantly in both directions in Task 1, while the amplitude and velocity of the leftward saccades increased significantly in Task 2. These results can be explained by the synergistic activation of Burster-Driving Neurons by the saccade signal and the vestibular signals. The combinations of these saccade tasks and caloric stimulation, especially Task 2, may be useful in clinically examining vestibulo-oculomotor functions.

Antisaccade eye movement abnormalities in Tourette syndrome: evidence for cortico-striatal network dysfunction?

Saccadic eye movements are rapid eye movements which act to redirect the eyes from one object of interest to another. Accurately and objectively measurable, their underlying neuroanatomical mechanisms have been extensively studied. The antisaccade task allows the study of the frontocortico-striatal network involved in the voluntary control of saccadic eye movements. In this task, the subject is instructed to inhibit a reflex eye movement towards a peripheral target light and, instead, to generate a movement in the equal and opposite direction. An error occurs when the subject fails to suppress reflexive saccades towards the target. Significantly high error rates and increased latencies in the antisaccade task have been reported in disorders associated with dysfunction of the frontocortico-striatal network. Increased saccadic eye movement latencies and error rates have been reported in Tourette syndrome patients (n = 4) who were receiving antipsychotic medication. To investigate this further, we tested the antisaccade task on six male Tourette syndrome patients. The results were compared with 18 age- and sex-matched mentally and physically healthy, medication/alcohol-free controls. Antisaccade latencies were (mean +/- SD; ms) 751.2+/-186.7 for the Tourette syndrome group and 417+/-75.3 for controls, and error rates were 59+/-14.3 for the Tourette syndrome group and 11.9+/-6.4 for controls, respectively. These significant results may further support dysfunction of the frontocortico-striatal network in Tourette syndrome.

The Cholinergic System in Schizophrenia Reconsidered:: Anticholinergic Modulation of Sleep and Symptom Profiles

The role of the cholinergic system in schizophrenia remains controversial. A series of investigations are reviewed that describe the effects of pharmacological manipulation of the cholinergic system on schizophrenia symptomatology and whether putative measures of the cholinergic system are altered in schizophrenia. The effects of biperiden (an anticholinergic agent) on positive and negative symptoms of schizophrenia and on rapid eye movement (REM) latency and other sleep measures were assessed. Biperiden produced a significant increase in positive symptoms and a decrease in negative symptoms. REM latency was significantly shorter in schizophrenic patients and increased in both groups following biperiden. REM density decreased in a dose-dependent manner following biperiden in schizophrenic patients, but not in normal controls. The slope of REM density plotted against biperiden dose was inversely related to plasma homovanillic acid (HVA), an index of dopamine (DA) activity, in schizophrenic patients. These results further implicate the cholinergic system in schizophrenia pathophysiology and suggest a role for DA-acetylcholine (ACh) interactions in the production of sleep abnormalities and expression of positive and negative symptoms in schizophrenia.

Short-latency primate vestibuloocular responses during translation.

Short-lasting, transient head displacements and near target fixation were used to measure the latency and early response gain of vestibularly evoked eye movements during lateral and fore-aft translations in rhesus monkeys. The latency of the horizontal eye movements elicited during lateral motion was 11.9 +/- 5.4 ms. Viewing distance-dependent behavior was seen as early as the beginning of the response profile. For fore-aft motion, latencies were different for forward and backward displacements. Latency averaged 7.1 +/- 9.3 ms during forward motion (same for both eyes) and 12.5 +/- 6.3 ms for the adducting eye (e.g., left eye during right fixation) during backward motion. Latencies during backward motion were significantly longer for the abducting eye (18.9 +/- 9.8 ms). Initial acceleration gains of the two eyes were generally larger than unity but asymmetric. Specifically, gains were consistently larger for abducting than adducting eye movements. The large initial acceleration gains tended to compensate for the response latencies such that the early eye movement response approached, albeit consistently incompletely, that required for maintaining visual acuity during the movement. These short-latency vestibuloocular responses could complement the visually generated optic flow responses that have been shown to exhibit much longer latencies.

The effect of earplugs on sleep measures during exposure to simulated intensive care unit noise

Sleep deprivation may contribute to impaired immune function, ventilatory compromise, disrupted thermoregulation, and delirium. Noise levels in intensive care units may be related to disturbed sleep patterns, but noise reduction has not been tested in this setting. To measure the effect of a noise reduction intervention on the sleep of healthy subjects exposed to simulated intensive care unit noise. After digital audiotape recording of noise and development of the noise reduction intervention, 5 nocturnal 8-hour periods of sleep were measured in 6 paid, healthy volunteers at 7-day intervals in a sleep disorders center. Polysomnographic data were collected by experienced sleep disorders technicians and scored by certified raters. After the first 3 quiet nights, earplugs were randomly assigned to be worn on the fourth and fifth nights during exposure to the recorded noise. Sound pressure levels were measured during all 5 nights. Sleep architecture and sound measurements on quiet nights did not differ significantly. Sound levels were significantly lower on quiet nights than on noise nights. Exposure to the noise increased the number of awakenings, percentage of stage 2 sleep, and rapid eye movement latency and decreased time asleep, sleep maintenance efficiency index, and percentage of rapid eye movement sleep. Earplugs worn during exposure to the noise produced a significant decrease in rapid eye movement latency and an increase in the percentage of rapid eye movement sleep. The results provide a reasonable basis for testing the effects of earplugs on the sleep of critically ill subjects.

Circadian system and sleep anomaly in depression

AbstractAbnormalities of circadian rhythms in depressed patients have been noted, including decreased amplitude, distorted waveform, day-to-day instability, and unusual 48 hour periods. Consistent electroencephalographic sleep recording in these patients show a shortened rapid eye movement latency and slow-wave sleep (stages 3 and 4), resulting in an increase in rapid eye movement sleep. This phenomenon appears to be a dependable, measurable marker for diagnosing primary depression. Total sleep deprivation appears to significantly improve mood in a high percentage of depressed patients. Current pharmacological research suggests that drug treatment such as lithium would not affect the intra sleep cycles of the REM stagebut would shift the phase backward and lithium would also shift the phase of circadian rhythm of the daytime sleepiness backward. This paper highlights some of the new approaches for investigating the molecular substrate for the control of circadian rhythmicity and sleep in man and critically examines the hypothesis of the alteration of this mechanism in psychopathology, particularly depression. What is known of the endogenous clock mechanism is discussed with known molecular circadian mechanisms with a view towards understanding how circadian information is transmitted to the rest of the central nervous system and how it is affected in depression.

Grating and plaid chrominance motion influences the suppressed ocular following response.

Involuntary eye movements to foveal stimulation were measured in a monkey while it performed a fixation task. Second-order plaid motion generated higher velocities of eye movements than did first-order gratings, yet the latency of the early following response was no different for grating or plaid motion. Nevertheless, early suppressed ocular following responses to isoluminant motion continue to be titrated by stimulus velocity and spatial frequency. Motion defined by 60% luminance contrast gratings and plaids generated a motion signal gain of 60% over chrominance motion. The 20% longer latency of eye movements to chrominance motion may reflect the longer conduction latency of the parvocellular channel and an additional stage in cortical processing en route to motion areas and eye movement control.

Effects of low-dose isoflurane on saccadic eye movement generation.

The effects of 0.15% quasi-steady-state end-tidal isoflurane on two saccadic eye-movement tests were examined in five volunteers using a newly devised computer-based recording system. The tests were saccadic latency and a countermanding task, the latter being an indicator of the highest levels of conscious performance. A moving light-emitting diode target was displayed on a screen and in the saccadic-latency task the latency of eye movement to the target was measured. In all five subjects the latency increased with anaesthetic by an amount which varied from 8 to 45 ms. This result was significantly different (p < 0.05) from subjects without anaesthetic. In the countermanding task, the subject had to voluntarily inhibit movement to the target. Again anaesthetic increased the latency of response, which varied from 6 to 33 ms. This result was significantly different (p < 0.05) from subjects without anaesthetic. In these studies it appeared that two tasks, one a simple latency test and the other, the countermanding task, requiring higher cortical processing were equally impaired at subanaesthetic concentrations of isoflurane.