Herbert C. Goltz

Inhibition and generation of saccades: Rapid event-related fMRI of prosaccades, antisaccades, and nogo trials

Flexible, adaptive behavior often requires the inhibition of automatic responses in favor of voluntary response generation. The antisaccade task requires active inhibition of the automatic saccade to a peripheral stimulus followed by generation of a voluntary antisaccade to the opposite location. Previous studies demonstrated greater functional magnetic resonance imaging (fMRI) activation for antisaccades than prosaccades in cortical saccade areas but did not distinguish the relative contributions of saccadic inhibition and generation. To address this question, we compared prosaccades, antisaccades, and nogo trials in a rapid event-related fMRI experiment with ten human subjects (6 female, 4 male). Trials were compound, containing a colored fixation point to cue trial type, followed by a 200-ms gap and then peripheral stimulus presentation and response. Required responses for prosaccade, antisaccade, and nogo trials, respectively, were to generate a saccade to the stimulus, look away from it, and inhibit the automatic saccade while maintaining central fixation. Frontal and supplementary eye fields, anterior cingulate cortex, intraparietal sulcus, and precuneus, exhibited surprisingly similar activation patterns for prosaccade and nogo responses, suggesting that BOLD signal in cortical saccade regions might predominantly reflect visual detection and attention processes rather than saccade generation or inhibition. These regions displayed greater activation for antisaccade responses versus prosaccade or nogo responses, possibly due to visuospatial remapping or increased attention levels in the antisaccade task. In right superior frontal sulcus, right supramarginal gyrus, and posterior cingulate sulcus, activation was greater for nogo compared to prosaccade responses, suggesting a role in active saccadic inhibition.

Effects of anisometropic amblyopia on visuomotor behavior, I: saccadic eye movements.

PURPOSE Impairment of spatiotemporal visual processing is the hallmark of amblyopia, but its effects on eye movements during visuomotor tasks have rarely been studied. Here the authors investigate how visual deficits in anisometropic amblyopia affect saccadic eye movements. METHODS Thirteen patients with anisometropic amblyopia and 13 control subjects participated. Participants executed saccades and manual reaching movements to a target presented randomly 5° or 10° to the left or right of fixation in three viewing conditions: binocular, amblyopic, and fellow eye viewing. Latency, amplitude, and peak velocity of primary and corrective saccades were measured. RESULTS Initiation of primary saccades was delayed and more variable when patients viewed monocularly with their amblyopic eye. During binocular viewing, saccadic latency exhibited increased variability and no binocular advantage in patients (i.e., mean latency was similar to that during fellow eye viewing). Mean amplitude and peak velocity of primary saccades were comparable between patients and control subjects; however, patients exhibited greater variability in saccade amplitude. The frequency of corrective saccades was greater when patients viewed with their fellow eye than it was with binocular or amblyopic eye viewing. Latency, amplitude, and peak velocity of corrective saccades in patients were normal in all viewing conditions. CONCLUSIONS Saccades had longer latency and decreased precision in amblyopia. Once saccades were initiated, however, the dynamics of saccades were not altered. These findings suggest that amblyopia is associated with slower visual processing in the afferent (sensory) pathway rather than a deficit in the efferent (motor) pathway of the saccadic system.

Behavioral Training as New Treatment for Adult Amblyopia: A Meta-Analysis and Systematic Review.

PURPOSE New behavioral treatment methods, including dichoptic training, perceptual learning, and video gaming, have been proposed to improve visual function in adult amblyopia. Here, we conducted a meta-analysis of these methods to investigate the factors involved in amblyopia recovery and their clinical significance. METHODS Mean and individual participant data meta-analyses were performed on 24 studies using the new behavioral methods in adults. Studies were identified using PubMed, Google Scholar, and published reviews. RESULTS The new methods yielded a mean improvement in visual acuity of 0.17 logMAR with 32% participants achieving gains ≥ 0.2 logMAR, and a mean improvement in stereo sensitivity of 0.01 arcsec-1 with 42% of participants improving ≥2 octaves. The most significant predictor of treatment outcome was visual acuity at the onset of treatment. Participants with more severe amblyopia improved more on visual acuity and less on stereo sensitivity than those with milder amblyopia. Better initial stereo sensitivity was a predictor of greater gains in stereo sensitivity following treatment. Treatment type, amblyopia type, age, and training duration did not have any significant influence on visual and stereo acuity outcomes. CONCLUSIONS Our analyses showed that some participants may benefit from the new treatments; however, clinical trials are required to confirm these findings. Despite the diverse nature of the new behavioral methods, the lack of significant differences in visual and stereo sensitivity outcomes among them suggests that visual attention-a common element among the varied treatment methods-may play an important role in amblyopia recovery.

Effects of Anisometropic Amblyopia on Visuomotor Behavior, III: Temporal Eye-Hand Coordination during Reaching

PURPOSE To examine the effects of anisometropic amblyopia on the temporal pattern of eye-hand coordination during visually-guided reaching. METHODS Eighteen patients with anisometropic amblyopia and 18 control subjects were recruited. Participants executed reach-to-touch movements toward visual targets under three viewing conditions: binocular, monocular amblyopic eye, and monocular fellow eye viewing. Temporal coordination between eye and hand movements was examined during reach planning (interval between the initiation of saccade and reaching) and reach execution (interval between the initiation of saccade and reach peak velocity). The frequency and dynamics of secondary saccades were also examined. RESULTS Patients with severe amblyopia spent a longer time planning the reaching response after fixating the target in comparison with control subjects and patients with mild amblyopia (P = 0.029). In comparison with control subjects, all patients extended the acceleration phase of the reach after target fixation (P = 0.018). Secondary (reach-related) saccades were initiated during the acceleration phase of the reach and patients executed these saccades with greater frequency than control subjects (P < 0.0001). The amplitude and peak velocity of reach-related saccades were higher when patients viewed with the amblyopic eye in comparison with the other viewing conditions (P < 0.001). CONCLUSIONS This is the first study to show that patients with anisometropic amblyopia modified the temporal dynamics of eye-hand coordination during visually-guided reaching. They extended the planning and execution intervals after target fixation and increased the frequency of secondary, reach-related saccades. These may represent visuomotor strategies to compensate for the spatiotemporal visual deficits to achieve good reaching accuracy and precision.

Effects of Strabismic Amblyopia and Strabismus without Amblyopia on Visuomotor Behavior, I: Saccadic Eye Movements

PURPOSE It has previously been shown that anisometropic amblyopia affects the programming and execution of saccades. The aim of the current study was to investigate the impact of strabismic amblyopia on saccade performance. METHODS Fourteen adults with strabismic amblyopia, 13 adults with strabismus without amblyopia, and 14 visually normal adults performed saccades and reach-to-touch movements to targets presented at ± 5° and ± 10° eccentricity during binocular and monocular viewing. Latency, amplitude, and peak velocity of primary and secondary saccades were measured. RESULTS In contrast to visually normal participants who had shorter primary saccade latency during binocular viewing, no binocular advantage was found in patients with strabismus with or without amblyopia. Patients with amblyopia had longer saccade latency during amblyopic eye viewing (P < 0.0001); however, there were no significant differences in saccade amplitude precision among the three groups across viewing conditions. Further analysis showed that only patients with severe amblyopia and no stereopsis (n = 4) exhibited longer latency (which was more pronounced for more central targets; P < 0.0001), and they also had reduced amplitude precision during amblyopic eye viewing. In contrast, patients with mild amblyopia (n = 5) and no stereopsis had normal latency and reduced precision during amblyopic eye viewing (P < 0.001), whereas those with gross stereopsis (n = 5) had normal latency and precision. There were no differences in peak velocity among the groups. CONCLUSIONS Distinct patterns of saccade performance according to different levels of visual acuity and stereoscopic losses in strabismic amblyopia were found. These findings were in contrast to those in anisometropic amblyopia in which the altered saccade performance was independent of the extent of visual acuity or stereoscopic deficits. These results were most likely due to different long-term sensory suppression mechanisms in strabismic versus anisometropic amblyopia.

The Effect of Sensory Uncertainty Due to Amblyopia (Lazy Eye) on the Planning and Execution of Visually-Guided 3D Reaching Movements

Background Impairment of spatiotemporal visual processing in amblyopia has been studied extensively, but its effects on visuomotor tasks have rarely been examined. Here, we investigate how visual deficits in amblyopia affect motor planning and online control of visually-guided, unconstrained reaching movements. Methods Thirteen patients with mild amblyopia, 13 with severe amblyopia and 13 visually-normal participants were recruited. Participants reached and touched a visual target during binocular and monocular viewing. Motor planning was assessed by examining spatial variability of the trajectory at 50–100 ms after movement onset. Online control was assessed by examining the endpoint variability and by calculating the coefficient of determination (R2) which correlates the spatial position of the limb during the movement to endpoint position. Results Patients with amblyopia had reduced precision of the motor plan in all viewing conditions as evidenced by increased variability of the reach early in the trajectory. Endpoint precision was comparable between patients with mild amblyopia and control participants. Patients with severe amblyopia had reduced endpoint precision along azimuth and elevation during amblyopic eye viewing only, and along the depth axis in all viewing conditions. In addition, they had significantly higher R2 values at 70% of movement time along the elevation and depth axes during amblyopic eye viewing. Conclusion Sensory uncertainty due to amblyopia leads to reduced precision of the motor plan. The ability to implement online corrections depends on the severity of the visual deficit, viewing condition, and the axis of the reaching movement. Patients with mild amblyopia used online control effectively to compensate for the reduced precision of the motor plan. In contrast, patients with severe amblyopia were not able to use online control as effectively to amend the limb trajectory especially along the depth axis, which could be due to their abnormal stereopsis.

Full-field chromatic pupillometry for the assessment of the postillumination pupil response driven by melanopsin-containing retinal ganglion cells.

PURPOSE The postillumination pupil response (PIPR) is produced by intrinsically photosensitive retinal ganglion cells (ipRGCs). We aimed to refine the testing conditions for PIPR by investigating whether a greater PIPR can be induced using full-field light stimuli of shorter duration and lower intensity than that produced by existing protocols that use central-field stimuli. METHODS Pupil response was recorded with an eye tracker in 10 visually-normal subjects. Red and blue light stimuli were presented using a Ganzfeld system. In Experiment 1 (intensity trials), PIPR was induced using 1-second full-field stimuli of increasing intensities from 0.1 to 400 cd/m(2) (11 steps). For comparison, PIPR also was induced using a 60° × 90° central-field blue stimulus of 400 cd/m(2). In Experiment 2 (duration trials), PIPR was induced using 100 and 400 cd/m(2) full-field stimulus of increasing duration from 4 to 1000 ms (10 steps). RESULTS Results indicated that PIPR increased monotonically with increasing stimulus intensity. Full-field stimulation using blue light at 400 cd/m(2) intensity induced significantly more sustained PIPR than central-field stimulation (P = 0.001). In addition, PIPR increased as the stimulus duration increased from 4 to 200 ms; however, no further increase in PIPR was observed when the duration increased from 400 to 1000 ms. CONCLUSIONS Compared to existing central-field protocols, larger PIPR can be induced with a full-field stimulus with lower intensity and shorter duration, indicating that PIPR is a function of stimulus intensity, stimulus duration, and retinal area stimulated. The testing protocol can be refined with this new knowledge to target particular clinical populations.

On the role of extraretinal signals for saccade generation.

We investigated the accuracy of sequential saccadic eye movements, executed without visual feedback. We found evidence that the final error of one saccade is corrected during the next, which supports the existence of extraretinal inputs to the saccadic generator. The corrections, however, were incomplete, which suggests that extraretinal signals are only partially effective.

Interaction of Retinal Image and Eye Velocity in Motion Perception

When we move our eyes, why does the world look stable even as its image flows across our retinas, and why do afterimages, which are stationary on the retinas, appear to move? Current theories say this is because we perceive motion by summation: if an object slips across the retina at r degrees/s while the eye turns at e degrees/s, the objects perceived velocity in space should be r + e. We show that activity in MT+, the visual-motion complex in human cortex, does reflect a mix of r and e rather than r alone. But we show also that, for optimal perception, r and e should not summate; rather, the signals coding e interact multiplicatively with the spatial gradient of illumination.

Effects of induced monocular blur versus anisometropic amblyopia on saccades, reaching, and eye-hand coordination.

PURPOSE We previously showed that anisometropic amblyopia affects the programming and execution of saccades and reaching movements. In our current study, we investigated whether these amblyopia-related changes simply are due to a reduction in visual acuity alone by inducing artificial blur in one eye in visually-normal participants. METHODS Twelve visually-normal participants performed saccades and reach-to-touch movements to targets presented on a computer screen during binocular and monocular viewing. A contact lens was used to blur the vision of one eye to a mean acuity level of 20/50. Saccades and reaching kinematics were compared before blur, immediately after blur, and 5 hours after blur was induced. The 5 hours after blur kinematic data from visually-normal participants also were compared to those from 12 patients with anisometropic amblyopia who had comparable acuity in the amblyopic eye. RESULTS Primary saccades (latency, amplitude, peak velocity), reaching movements (reaction time, movement time, peak acceleration, duration of the acceleration phase), and eye-hand coordination (saccade-to-reach planning interval, saccade-to-reach peak velocity interval) were not affected by induced monocular blur in visually-normal participants, either immediately or 5 hours after blur. Compared to visually-normal participants after 5 hours of blur, patients with anisometropic amblyopia had significantly longer and more variable saccade latency during amblyopic eye viewing, lower peak acceleration, and a longer acceleration phase during reaching, and a different temporal pattern of eye-hand coordination. CONCLUSIONS Artificially-induced monocular blur in visually-normal participants did not affect saccades, reaching movements, and eye-hand coordination during a simple reach-to-touch task even after a period of blur exposure. In contrast, patients with anisometropic amblyopia demonstrated significantly different kinematics while performing the same task. These results indicate that loss of visual acuity alone cannot explain the kinematic changes seen in patients with mild anisometropic amblyopia.