Continuous Auditory Feedback of Eye Movements: An Exploratory Study toward Improving Oculomotor Control

Relationship between eye acceleration and retinal image velocity during foveal smooth pursuit in man and monkey.

Long-term adaptive changes in primate vestibuloocular reflex. III. Electrophysiological observations in flocculus of normal monkeys.

Growing evidence suggests that orienting visual attention in space can influence the processing of numerical magnitude, with leftward orienting speeding up the processing of small numbers relative to larger ones and the converse for rightward orienting. The manipulation of eye movements is a convenient way to direct visuospatial attention, but several aspects of the complex relationship between eye movements, attention orienting and number processing remain unexplored. In a previous study, we observed that inducing involuntary, reflexive eye movements by means of optokinetic stimulation affected number processing only when numerical magnitude was task relevant (i.e., during magnitude comparison, but not during parity judgment; Ranzini et al., in J Cogn Psychol 27, 459-470, (2015). Here, we investigated whether processing of task-irrelevant numerical magnitude can be modulated by voluntary eye movements, and whether the type of eye movements (smooth pursuit vs. saccades) would influence this interaction. Participants tracked with their gaze a dot while listening to a digit. The numerical task was to indicate whether the digit was odd or even through non-spatial, verbal responses. The dot could move leftward or rightward either continuously, allowing tracking by smooth pursuit eye movements, or in discrete steps across a series of adjacent locations, triggering a sequence of saccades. Both smooth pursuit and saccadic eye movements similarly affected number processing and modulated response times for large numbers as a function of direction of motion. These findings suggest that voluntary eye movements redirect attention in mental number space and highlight that eye movements should play a key factor in the investigation of number-space interactions.

Twenty-four subjects were selected for the study. The activity of trunk and lower limb muscles (tibialis anterior, lateral gastrocnemius, medial gastrocnemius, vastus midialis obliques, vastus lateralis, biceps femoris, rectus abdominis, and erector spinae) and the COP (center of pressure) (surface area ellipse, length, and average speed) were measured to observe the effects of gaze fixation and different kinds of smooth-pursuit eye movements on the center of pressure and muscle activities during one leg standing. Before the experiment, a Gaze point GP3 HD Eye Tracker (Gazept, Vancouver, BC, Canada) was used to train eye movement so that the subjects would be familiar with smooth eye movement. Repeated each exercise 3 times at random. In order to avoid the sequence deviation caused by fatigue, the movement sequence is randomly selected. The center of pressure and muscle activities were increased significantly when the smooth-pursuit eye movement with one leg standing compared with gaze fixation with one leg standing. In smooth-pursuit eye movements, the changes in the center of pressure and muscle activities were increased significantly with eye and head movement. When the head and eyes moved in opposite directions, the center of pressure and muscle activities were increased more than with any other exercises. Smooth-pursuit eye movement with one leg movement affects balance. In particular, in the smooth-pursuit eye movement with one leg standing, there were higher requirements for balance when the eyes and head move in the opposite direction. Therefore, this movement can be recommended to people who need to enhance their balance ability.

1. Purkinje cell activity was recorded from lobules VI and VII of the cerebellar vermis during the performance of visuooculomotor tasks designed to dissociate the signals related to head, smooth-pursuit eye, and retinal image movements. Task-related modulations in the simple spike discharge rates of 157 cells were observed in three alert monkeys. 2. Of 65 Purkinje cells that were completely tested for all three signals, all exhibited smooth-pursuit eye movement-related activity. An additional vestibular or visual response was observed in 17 and 11% of the cells, respectively. Eye, head, and retinal image velocity signals were all recorded in the same unit in 52% of the Purkinje cells. The responses of 5% of the fully tested cells were associated with changes in the direction of eye, head, and retinal image movement. 3. The observed sensorioculomotor responses were direction selective in 98% of the Purkinje cells. For the Purkinje cells that were fully tested, 60% of the cells exhibited peak discharge rates for ipsilateral and 40% for contralateral eye velocity. Of these Purkinje cells, 45% exhibited eye, head, and retinal image velocity signals with equivalent direction preferences. 4. Of 42 Purkinje cells tested, 88% demonstrated some kinds of interactive responses during combined eye and sensory stimulation. The interaction of eye and head velocity signals has been discussed in a companion paper (38). The modulation in discharge rate observed during tracking in the presence of a random dot background pattern could be predicted from the dissociated responses to smooth pursuit in the dark and to movements of the background pattern during suppression of eye movements. 5. The sensitivity to smooth-pursuit eye velocity averaged 1.4 times the sensitivity to head velocity. In 80% of the Purkinje cells, however, the sensitivity to eye velocity exceeded the sensitivity to head velocity by an average of only 10%. The sensitivity to smooth-pursuit eye velocity averaged 1.6 times the sensitivity to retinal image velocity. 6. An increase in Purkinje cell discharge rate was observed during the open-loop period of the initiation of smooth-pursuit eye movements. This open-loop response was consistent with the presence of a visual signal during ocular pursuit, since these cells were also shown to be responsive to a dissociated retinal image velocity signal. Furthermore, the magnitude of the open-loop response indicated an enhancement of the sensitivity to retinal image velocity when visual information became behaviorally significant.(ABSTRACT TRUNCATED AT 400 WORDS)

Spatial updating is a process that enables us to constantly compute spatial relationships between ourselves and the surrounding environment during self-motion. Primates are able to spatially update saccade targets across intervening saccade or smooth pursuit (SP) eye movements. Various studies have demonstrated discrete remapping of visual responses, in several brain structures, before and after the saccade. However, no study to date has shown continuous updating of such responses during the eye movement, nor has anyone published a study of the neural mechanism of spatial updating for SP. In this study we recorded superior-colliculus unit activity from 2 monkeys. Animals were trained to spatially update the location of a saccade target across an intervening SP. Neurons were characterized (as visual, visuo-motor or motor neurons) and their visual / motor receptive fields (RF) were specified using a delayed saccade paradigm. After this each neuron was tested in the SP-saccade paradigm. Saccade target direction and pursuit ramp length were varied such that (across trials) the remembered saccade target passed approximately through the neuron’s RF at 2-5 different points on the SP ramp. Of the 50 neurons analyzed to date, every neuron that showed a visual response (n=47), whether it was a visual and visuomotor neuron, exhibited a clear and robust modulation in activity when the location of remembered target passed across the RF of the neuron during SP. In contrast, none of the motor neurons showed any updating related response, but instead only burst for an intended saccade. We conclude that 1) the superior colliculus visual memory response is continuously updated during SP eye movements in a gaze-centered coordinates, and 2) only visual responses (not motor) are involved in visuospatial memory. This may reflect a general mechanism for continuous updating during slow self-motion. Meeting abstract presented at VSS 2012

Aim Deficits in smooth-pursuit eye movements (SPEM) are often associated with mild traumatic brain injury(TBI). Eye tracking tests serve as a quick objective clinical tool to assess such predictive visual tracking. In this study, SPEM was assessed along circular, horizontal and vertical trajectories in adolescents with concussion and age-matched controls. Methods Ninety-one young adolescents with concussion and 140 visually healthy age-matched controls with a mean age of 14 years performed a computerized test of circular, horizontal and vertical tracking task using an eye tracker. Oculomotor tracking was assessed by computing the rate of fixation, saccades and SPEM made while performing the tasks. Results The predictive visual tracking task was able to differentiate the TBI group from the non-TBI group. The TBI group showed a significant difference in the fixation, saccades and SPEM percentages for circular tracking movement compared to the controls. There was a significant difference in fixation and SPEM % for horizontal and vertical tracking. Conclusions Predictive visual tracking, assessed using eye tracking technology, is able to differentiate deficits in oculomotor functions in individuals with and without concussion. The eye tracking technology may serve as a quick objective tool to detect and monitor neural deficits due to TBI.

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.

Smooth pursuit eye movement (SPEM) and antisaccade deficits are observed in the schizophrenia spectrum and have been used to study the pathophysiology as well as the genetic basis of this condition. The neurotransmitter acetylcholine has been implicated in a number of cognitive processes thought to underlie SPEM and antisaccade performance. This study investigates effects on eye movements of procyclidine, an anticholinergic drug often administered to schizophrenic patients. A total of 13 patients completed a double-blind placebo-controlled crossover design, receiving 15 mg procyclidine and placebo. Seven participants received procyclidine first and placebo second, six participants were tested in the reverse order. SPEM and antisaccade (as well as fixation and prosaccade) eye movements were recorded using infrared oculography. Results showed that procyclidine overall, relative to placebo, mildly worsened SPEM performance, as indicated by nonsignificantly reduced gain (p=0.08) and increased frequency of intrusive anticipatory saccades during pursuit (p=0.06). A significant interaction of group and order of administration indicated that procyclidine increased the rate of antisaccade reflexive errors only when administered first; the opposite pattern was observed when placebo was administered first, likely due to the operation of practice effects at second assessment. These findings indicate that acute administration of a clinically relevant dose of procyclidine leads to mild impairments in eye movement performance in schizophrenic patients, suggesting the need to consider this compound in oculomotor studies in schizophrenia. The action of this anticholinergic drug on oculomotor performance is consistent with the hypothesized role of the cholinergic system in the cognitive mechanisms of attention and working memory, processes thought to underlie SPEM and antisaccade performance. Effects of order of administration and practice on the antisaccade task suggest that these factors need to be taken into consideration in future pharmacological studies.

Recently we showed that sensitivity for chromatic- and high-spatial frequency luminance stimuli is enhanced during smooth-pursuit eye movements (SPEMs). Here we investigated whether this enhancement is a general property of slow eye movements. Besides SPEM there are two other classes of eye movements that operate in a similar range of eye velocities: the optokinetic nystagmus (OKN) is a reflexive pattern of alternating fast and slow eye movements elicited by wide-field visual motion and the vestibulo-ocular reflex (VOR) stabilizes the gaze during head movements. In a natural environment all three classes of eye movements act synergistically to allow clear central vision during self- and object motion. To test whether the same improvement of chromatic sensitivity occurs during all of these eye movements, we measured human detection performance of chromatic and luminance line stimuli during OKN and contrast sensitivity during VOR and SPEM at comparable velocities. For comparison, performance in the same tasks was tested during fixation. During the slow phase of OKN we found a similar enhancement of chromatic detection rate like that during SPEM, whereas no enhancement was observable during VOR. This result indicates similarities between slow-phase OKN and SPEM, which are distinct from VOR.

When tracking or reaching a visual target with the hand, retinal information is key to guide the hand. Although the contribution of extraretinal signals associated with saccades is established for reaching movements, less is known about extraretinal contribution during manual tracking in which smooth pursuit dominates. To fill this gap, we conducted a study in which eye and hand tracking performance were compared across multiple conditions in which eye and hand movements performed similar/dissimilar tasks. In the SINGLE condition, participants (n = 26) were asked to track a unique target with both eyes and hand. In the DOUBLE condition, their eyes and hand had to track separate targets that followed the same trajectory but displayed on separate hemifields. In the FIX condition, participants tracked one target with the hand while fixating eyes away from that target. We reasoned that if extraretinal information is key for manual tracking, it should be less altered in SINGLE and DOUBLE than FIX. Indeed, results showed that not only manual tracking was better in DOUBLE than FIX, but was nearly equivalent to SINGLE. Surprisingly, foveating the target provided only modest benefits to manual tracking. Finally, analyses confirmed that smooth pursuit contributed more than saccades to overall eye movements, making it the primary contributor to extraretinal information. Taken together, these results show that foveating the target is not mandatory for accurate manual tracking as long as eyes and hand perform congruent tracking/motion, and speak for a key role of extraretinal information provided by smooth pursuit.NEW & NOTEWORTHY The contribution of extraretinal information associated with saccades is well established for reaching movements. Here, by using a continuous manual tracking task in which smooth pursuit dominates, we examined the contribution of extraretinal information. Critically, our findings show that extraretinal information is more essential than foveating the target for hand tracking performance. More generally, these results highlight the key role of smooth pursuit in supplying extraretinal signals for guiding the hand during manual tracking.

Abnormalities of smooth pursuit eye movement (SPEM) have been estimated, mainly using the wave form on an electro-oculogram, in a qualitative way. Many methods for quantitative analysis of SPEM have been designed, though most are still uncommon in present clinical use. Using a personal computer, we developed a method of automatic quantitative analysis of ocular tracking eye movement recorded by electro-oculography (EOG). The design concept of this method is based on the observation that eye movement during ocular tracking consists of two different kinds of eye movements, one is SPEM and the other is saccade. The combination of SPEM and saccade (composite eye movement: CEM) commonly appears during ocular tracking. These two kinds of eye movement are essentially different not only in behavior but also about involved neural pathway in the central nervous system. From this point of view, we believe that the two kinds of eye movements involved in ocular tracking should be evaluated separately. The analysis method is outlined as follows. A horizontal sinusoidally moving visual target was employed to elicit ocular tracking eye movements. The test frequencies were set at 0.1, 0.2, 0.4 and 0.8Hz, and the amplitude of target motion was 15 deg at each frequency. The 20 seconds of eye movement data measured by EOG were fed into the computer through a digital-analog converter for further analysis. Using our original saccade detection algorithm, based on the physiological behavior of saccades, the saccadic components were detected and removed from the eye movement wave. The remaining parts, fragments of SPEM, were connected by means of interpolating defective parts. The reconstructed wave was a slow cumulative eye position curve (SCEP). Sinusoidal target motion, CEM and SCEP were processed by the FFT (Fast Fourier Transformation) method. Bode plots were applied to summarize the gain and phase of responses to SCEP and the target motion wave. These processes enable us to estimate abnormalities of SPEM such as low gain, abnormal phase shift and large trends in tested duration. We conclude that the method described here is useful for quantitative estimation of SPEM in clinical neuro-otological examinations.

The neural basis of smooth pursuit eye movements in the rhesus monkey brain

The premotor pathways subserving saccades and smooth-pursuit eye movements are usually thought to be different. Indeed, saccade and smooth-pursuit eye movements have different dynamics and functions. In particular, a group of midline cells in the pons called omnipause neurons (OPNs) are considered to be part of the saccadic system only. It has been established that OPNs keep premotor neurons for saccades under constant inhibition during fixation periods. Saccades occur only when the activity of OPNs has completely stopped or paused. Accordingly, electrical stimulation in the region of OPNs inhibits premotor neurons and interrupts saccades. The premotor relay for smooth pursuit is thought to be organized differently and omnipause neurons are not supposed to be involved in smooth-pursuit eye movements. To investigate this supposition, OPNs were recorded during saccades and during smooth pursuit in the monkey (Macaca mulatta). Unexpectedly, we found that neuronal activity of OPNs decreased during smooth pursuit. The resulting activity reduction reached statistical significance in approximately 50% of OPNs recorded during pursuit of a target moving at 40 degrees /s. On average, activity was reduced by 34% but never completely stopped or paused. The onset of activity reduction coincided with the onset of smooth pursuit. The duration of activity reduction was correlated with pursuit duration and its intensity was correlated with eye velocity. Activity reduction was observed even in the absence of catch-up saccades that frequently occur during pursuit. Electrical microstimulation in the OPNs' area induced a strong deceleration of the eye during smooth pursuit. These results suggest that OPNs form an inhibitory mechanism that could control the time course of smooth pursuit. This inhibitory mechanism is part of the fixation system and is probably needed to avoid reflexive eye movements toward targets that are not purposefully selected. This study shows that saccades and smooth pursuit, although they are different kinds of eye movements, are controlled by the same inhibitory system.

The pharmacokinetics and pharmacodynamics of lamotrigine (LTG), a new antiepileptic drug (AED), were studied in healthy volunteers. In an open dose-escalating study, LTG 240 mg produced peak plasma concentrations of around 3 micrograms/mg with no significant adverse events. Subsequent pharmacokinetic studies revealed complete oral absorption, first-order kinetics with a mean half-life of approximately 1 day, and elimination mainly as a glucuronide in the urine. Early studies in patients with epilepsy revealed more rapid metabolism when given with enzyme-inducing AEDs and delayed metabolism by valproate. A placebo-controlled, double-blind study compared LTG 120 and 240 mg with phenytoin (PHT) 500 and 1,000 mg, and diazepam (DZP) 10 mg. Visual analogue scales showed sedation after PHT 1,000 mg and DZP 10 mg, but not after LTG. Smooth pursuit eye movements and adaptive tracking were impaired by DZP and PHT 1,000 mg. LTG did not affect these variables. A comparison of LTG 150 and 300 mg and carbamazepine (CBZ) 200, 400, and 600 mg demonstrated impairment of smooth pursuit and saccadic eye movements by CBZ 600 and 400 mg, but not by LTG. Additionally, CBZ 600 mg impaired adaptive tracking and increased body sway and heart rate. These studies have shown LTG to have desirable and predictable pharmacokinetic properties for an AED. Pharmacodynamic effects were absent, suggesting a high therapeutic index.