Cross axis VOR induced by pursuit training in monkeys: further properties of adaptive responses

We have shown recently in alert monkeys that repeated interaction between the pursuit and vestibular systems in the orthogonal plane induces adaptive changes in the VOR. To examine further properties of adaptive cross axis VOR induced by pursuit training, sinusoidal whole body rotation was applied either in the pitch or yaw plane while presenting a target spot that moved orthogonally to the rotation plane with either 90 degrees phase-lead or 90 degrees phase-lag to the chair signal. After one hour of training at 0.5 Hz (+/- 10 degrees), considerable phase-shift was observed in orthogonal eye movement responses consistent with the training paradigms by identical chair rotation in complete darkness, with further lead at lower frequencies and lag at higher frequencies. However, gains (eye/chair) induced by phase- shift pursuit training was different during pitch and yaw rotation. Although frequency tuning was maintained during pitch in the phase-shift paradigms, it was not maintained during yaw, resulting in higher gains at lower stimulus frequencies compared to the gains during yaw. This difference may reflect otolith contribution during pitch rotation. To understand further the nature of signals that induce adaptive cross axis VOR, we examined interaction of pursuit, whole field-visual pattern and vestibular stimuli. Magnitudes of the cross axis VOR with a spot alone on one hand and with a spot and pattern moving together in the same plane on the other during chair rotation were similar, and when one of the two visual stimuli was stationary during chair rotation, our well trained monkeys did not induce the cross axis VOR. These results suggest that the cross axis VOR induced by pursuit training shares common mechanisms with the cross axis VOR induced by whole field-slip stimuli and that if conflicting information is given between the two visual stimuli, adaptive changes are inhibited. Horizontal GVPs were recorded in the cerebellar floccular lobe during pitch rotation coupled with horizontal pursuit stimuli. These GVPs did not respond to pitch in the dark before training, but responded after 60 min of pursuit training with eye velocity sensitivities similar to those before training. Adaptive change in the VOR was specific to smooth eye movements but not to saccades in our paradigms.     

Stabilization of the gaze in chameleons: visual and vestibular reflexes

Some visual, vestibular and proprioceptive reflexes which contribute to gaze (head + eye) stabilization were quantified in the chameleon. All the reflexes were analysed in the horizontal plane, and the visual reflexes were also studied in the vertical plane. In restrained-head animals, both the optokinetic nystagmus (OKN) and the vestibulo-ocular reflex (VOR) had low gains. In free-head animals, the head (opto-collic or vestibulo-collic reflex) and eye (OKN or VOR) responses added their effects, thus improving gaze stabilization, especially during vestibular stimulation. Cervical stimulation provoked both a cervico-ocular reflex (COR) in the compensatory direction and a large number of saccades. The saccadic response was especially marked in the presence of patterned visual surroundings.     

Automatic detection and removal of fast phases from nystagmographic recordings by optimal thresholding

Recording of ocular nystagmus during vestibular tests does not measure the true response of the vestibulo-ocular reflex (VOR), because the VOR response (so-called slow phase of nystagmus) is interrupted by resetting saccades (so-called fast phase of nystagmus). In order to extract the real VOR contribution, saccades must be removed. In most of the nystagmus processing algorithms, saccade removal requires a human operator to choose a suitable eye velocity threshold able to separate fast from slow nystagmus phases. In the present report a fully automatic removal system is presented which selects an optimal velocity threshold by computing the VOR frequency response and maximizing its coherence function.     

Human fast negative EEG potentials before express saccades

Fast negative EEG potentials preceding fast regular saccades and express saccades were studied by the method of backward averaging under conditions of monocular stimulation of the right and left eye. "Step" and "gap" experimental paradigms were used for visual stimulation. Analysis of parameters of potentials and their spatiotemporal dynamics suggests that, under conditions of the increased attention and optimal readiness of the neural structures, express saccades appear when the previously chosen program of the future eye movement coincides with the actual target coordinates. We assumed that the saccade latency decreases at the expense of the involvement of the main oculomotor areas of motor and saccadic planning in its initiation; an express saccade can be initiated also by means of direct transmission of the signal from the cortex to the brainstem saccadic generator passing by the superior colliculus. Moreover, anticipating release from the central fixation and attention distraction are necessary for the successful initiation of an express saccade.     

Computer simulation of overshoot in saccadic eye movements.

The human horizontal eye movement system produces quick, precise, conjugate eye movements called saccades. These are important in normal vision. For example, reading tasks exclusively utilize saccadic eye movements. The majority of saccades have dynamic overshoot. The amplitude of this overshoot is independent of saccadic amplitude, and is such that it places the image of the stimulus within the retinal region of maximum acuity within a minimum of time. A computer based model of the saccadic mechanisms was used to study the origin of this overshoot. It was discussed that dynamic overshoot cannot be attributed to biomechanism properites of the eye movement mechanism, but must instead be explained by variations in the controlling nervous activity. The form of this neural controller signal is very similar to that required for a time optimal response of an inertial system.     

Covert Anti-Compensatory Quick Eye Movements during Head Impulses

Background

Catch-up saccades during passive head movements, which compensate for a deficient vestibulo-ocular reflex (VOR), are a well-known phenomenon. These quick eye movements are directed toward the target in the opposite direction of the head movement. Recently, quick eye movements in the direction of the head movement (covert anti-compensatory quick eye movements, CAQEM) were observed in older individuals. Here, we characterize these quick eye movements, their pathophysiology, and clinical relevance during head impulse testing (HIT).

Methods

Video head impulse test data from 266 patients of a tertiary vertigo center were retrospectively analyzed. Forty-three of these patients had been diagnosed with vestibular migraine, and 35 with Menière’s disease.

Results

CAQEM occurred in 38% of the patients. The mean CAQEM occurrence rate (per HIT trial) was 11±10% (mean±SD). Latency was 83±30 ms. CAQEM followed the saccade main sequence characteristics and were compensated by catch-up saccades in the opposite direction. Compensatory saccades did not lead to more false pathological clinical head impulse test assessments (specificity with CAQEM: 87%, and without: 85%). CAQEM on one side were associated with a lower VOR gain on the contralateral side (p<0.004) and helped distinguish Menière’s disease from vestibular migraine (p = 0.01).

Conclusion

CAQEM are a common phenomenon, most likely caused by a saccadic/quick phase mechanism due to gain asymmetries. They could help differentiate two of the most common causes of recurrent vertigo: vestibular migraine and Menière’s disease.     

On the predominance of anti-compensatory eye movements in vestibular nystagmus

The predominance of anti-compensatory eye movements in vestibular nystagmus recorded during sinusoidal and post-rotational tests is interpreted in terms of a mathematical model of the vestibulo-ocular system. Namely, a direct pathway between the vestibular nuclei and the saccadic mechanism is assumed. In the range of frequencies of natural head movements this pathway carries on a signal proportional to head angular velocity. Therefore, during active head movements the saccadic mechanism is forced to produce quick eye rotations in the direction of head movement and, thus, to cooperate in the task of picking up visual targets outside the visual field. During passive head movements giving rise to nystagmus the assumed pathway contributes to reduce the error in eye resetting due to the saccadic delay. Analytical considerations and simulation results seem to prove the adequacy of the proposed model.Work supported by the National Research Council (C.N.R.), Rome, Italy     

Different programming modes of human saccadic eye movements as a function of stimulus eccentricity: Indications of a functional subdivision of the visual field

1. Voluntary saccadic eye movements were made toward flashes of light on the horizontal meridian, whose duration and distance from the point of fixation were varied; eye movements were measured using d.c.-electrooculography.—2. Targets within 10°–15° eccentricity are usually reached by one saccadic eye movement. When the eyes turn toward targets of more than 10°–15° eccentricity, the first saccadic eye movement falls short of the target by an angle usually not exceeding 10°. The presence of the image of the target off the fovea (visual error signal) subsequent to such an undershoot elicits, after a short interval, corrective saccades (usually one) which place the image of the target on the fovea. In the absence of a visual error signal, the probability of occurrence of corrective saccades is low, but it increases with greater target eccentricities. These observations suggest that there are different, eccentricity-dependent modes of programming saccadic eye movements.—3. Saccadic eye movements appear to be programmed in retinal coordinates. This conclusion is based on the observations that, irrespective of the initial position of the eyes in the orbit, a) there are different programming modes for eye movements to targets within and beyond 10°–15° from the fixation point, and b_ the maximum velocity of saccadic eye movements is always reached at 25° to 30° target eccentricity. —4. Distributions of latency and intersaccadic interval (ISI) are frequently multimodal, with a separation between modes of 30 to 40 msec. These observations suggest that saccadic eye movements are produced by mechanisms which, at a frequency of 30 Hz, process visual information. —5. Corrective saccades may occur after extremely short intervals (30 to 60 msec) regardless of whether or not a visual error signal is present; the eyes may not even come to a complete stop during these very short intersaccadic intervals. It is suggested that these corrective saccades are triggered by errors in the programming of the initial saccadic eye movements, and not by a visual error signal. —6. The exitence of different, eccentricity-dependent programming modes of saccadic eye movements, is further supported by anatomical, physiological, psychophysical, and neuropathological observations that suggest a dissociation of visual functions dependent on retinal eccentricity. Saccadic eye movements to targets more eccentric than 10°–15° appear to be executed by a mechanism involving the superior colliculus (perhaps independent of the visual cortex), whereas saccadic eye movements to less eccentric targets appear to depend on a mechanism involving the geniculo-cortical pathway (perhaps in collaboration with the superior colliculus).     

Oculomotor activities in monkeys with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced syndrome of parkinsonism

In twoMacaca rhesus monkeys that received repeated N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injections (single dose 0.2 mg/kg, i.m.; cumulative dose 11.2–13.3 mg), changes in characteristics of spontaneous saccadic eye movements and vestibulo-ocular reflex (VOR) were evaluated. With the development of severe behavioral disturbances, amplitude of spontaneous saccadic eye movements gradually decreased. Pronounced changes in duration of saccadic eye movements, frequency of spontaneous saccades, and their pattern were observed. No changes in parameters of VOR slow component were recorded, but high total MPTP doses suppressed fast phase of the reflex.Neirofiziologiya/Neurophysiology, Vol. 25, No. 3, pp. 184–190, May–June, 1993.     

The control of gaze (3). Neurological defects

Eye movements serve vision, which has two different aims: changing images using saccades, i.e. rapid eye movements, and stabilizing new images on the retina using slow eye movements. Eye movements are performed by ocular motor nuclei in the brainstem, on which supranuclear pathways--originating in the cerebral cortex, cerebellum and vestibular structures--converge. It is useful for the neurologist to know the clinical abnormalities of eye movements visible at the bedside since such signs are helpful for localization. Eye movement paralysis may be nuclear or infranuclear (nerves), involving all types of eye movements, i.e. saccades as well as the vestibulo-ocular reflex (VOR), or supranuclear, in which case the VOR is usually preserved. Lateral eye movements are organized in the pons, with paralysis of adduction (and preservation of convergence) when the lesion affects the medial longitudinal fasciculus (internuclear ophthalmoplegia), paralysis of conjugate lateral eye movements when the lesion affects the abducens nucleus (VI) and the "one-and-a-half" syndrome when both these structures are involved. Vertical eye movements are organized in the midbrain, with ipsilateral oculomotor (III) paralysis and contralateral paralysis of the superior rectus muscle when the third nerve nucleus is unilaterally damaged, supranuclear upward gaze paralysis when the posterior commissure is unilaterally damaged and supranuclear downward gaze paralysis (often coupled with upward gaze paralysis) when the mesencephalic reticular formations are bilaterally damaged. Numerous types of abnormal eye movements exist, of which nystagmus is the most frequent and usually due to damage to peripheral or central vestibular pathways. Cerebral hemispheric or cerebellar damage results in subtle eye movement abnormalities at the bedside, in general only detected using eye movement recordings, because of the multiplicity of eye movement pathways at these levels and their reciprocal compensation in the case of a lesion. Lastly, eye movements can also help the neuroscientist to understand the organization of the brain. They are a good model of motricity allowing us, using eye movement recordings, to study the afferent pathways of the cortical areas that trigger them, and thus to analyze relatively complex neuropsychological processes such as visuo-spatial integration, spatial memory, motivation and the preparation of motor programs.     

Analysis of the middle latency evoked potentials to angular acceleration impulses in man

The middle latency vestibular evoked potential (ML-VsEP) recorded with scalp electrodes in man in response to impulses of angular acceleration is dominated by a forehead positive peak at about 15 ms and a negative peak at about 20 ms; the peak amplitude of this component is about 30 μV. This is followed by slower, smaller amplitude activity. The latency of this initial peak is similar to the latency of the vestibulo-ocular reflex (VOR) in monkeys. The present study was undertaken to elucidate the possible relation between the ML-VsEPs and VOR. This included recordings from forehead-mastoid electrodes (sites used to record VsEP) and other scalp electrodes and the recording of potentials due to eye movement: the electro-oculogram. Direct recording of eye movements was also conducted using an infra-red reflection device in those experiments in which the head was not moved. The recordings were conducted in man during vestibular stimulation eliciting VsEPs, during voluntary eye movements and during caloric and optokinetic stimulation. These experiments indicated that the 15–20 ms component of the ML-VsEP was not due to movements of the eye (corneoretinal dipole). The large amplitude 15–20 ms component of the ML-VsEP was similar in general magnitude, waveform, polarity, duration and rise time to the highly synchronous pre-saccadic spike (neural and/or myogenic) which precedes nystagnys and voluntary saccades. It therefore probably represents vestibular-initiated electrical activity in motor units of the extra-ocular muscles which then produce anti-compensatory saccades.     

Open-loop simulations of the primate saccadic system using burst cell discharge from the superior colliculus

 Saccade-related burst neurons (SRBNs) in the monkey superior colliculus (SC) have been hypothesized to provide the brainstem saccadic burst generator with the dynamic error signal and the movement initiating trigger signal. To test this claim, we performed two sets of open-loop simulations on a burst generator model with the local feedback disconnected using experimentally obtained SRBN activity as both the driving and trigger signal inputs to the model. First, using neural data obtained from cells located near the middle of the rostral to caudal extent of the SC, the internal parameters of the model were optimized by means of a stochastic hill-climbing algorithm to produce an intermediate-sized saccade. The parameter values obtained from the optimization were then fixed and additional simulations were done using the experimental data from rostral collicular neurons (small saccades) and from more caudal neurons (large saccades); the model generated realistic saccades, matching both position and velocity profiles of real saccades to the centers of the movement fields of all these cells. Second, the model was driven by SRBN activity affiliated with interrupted saccades, the resumed eye movements observed following electrical stimulation of the omnipause region. Once again, the model produced eye movements that closely resembled the interrupted saccades produced by such simulations, but minor readjustment of parameters reflecting the weight of the projection of the trigger signal was required. Our study demonstrates that a model of the burst generator produces reasonably realistic saccades when driven with actual samples of SRBN discharges. Received: 25 October 1994/Accepted in revised form: 20 June 1995     

On identification of saccades from sinusoidal eye movement signals

Sinusoidal eye movements and potential saccadic eye movements are examined using the syntactic pattern recognition method presented previously. A few computer tests are presented for the verification of potential saccades from signals of sinusoidal eye movements. The technique was developed and tested with electro-oculographic signals. The verification of saccades consists of three tests: the estimation of average noise peaks in an eye movement signal; an angular velocity threshold; and the comparison between a sinusoidal eye movement signal and the corresponding stimulus signal. The technique is also efficient for noisy signals of eye movements, which were stimulated by both predictive and non-predictive sinusoidal stimulus movements.     

Attention governs action in the primate frontal eye field

While the motor and attentional roles of the frontal eye field (FEF) are well documented, the relationship between them is unknown. We exploited the known influence of visual motion on the apparent positions of targets, and measured how this illusion affects saccadic eye movements during FEF microstimulation. Without microstimulation, saccades to a moving grating are biased in the direction of motion, consistent with the apparent position illusion. Here we show that microstimulation of spatially aligned FEF representations increases the influence of this illusion on saccades. Rather than simply impose a fixed-vector signal, subthreshold stimulation directed saccades away from the FEF movement field, and instead more strongly in the direction of visual motion. These results demonstrate that the attentional effects of FEF stimulation govern visually guided saccades, and suggest that the two roles of the FEF work together to select both the features of a target and the appropriate movement to foveate it.     

Both Lexical and Non-Lexical Characters Are Processed during Saccadic Eye Movements

On average our eyes make 3–5 saccadic movements per second when we read, although their neural mechanism is still unclear. It is generally thought that saccades help redirect the retinal fovea to specific characters and words but that actual discrimination of information only occurs during periods of fixation. Indeed, it has been proposed that there is active and selective suppression of information processing during saccades to avoid experience of blurring due to the high-speed movement. Here, using a paradigm where a string of either lexical (Chinese) or non-lexical (alphabetic) characters are triggered by saccadic eye movements, we show that subjects can discriminate both while making saccadic eye movement. Moreover, discrimination accuracy is significantly better for characters scanned during the saccadic movement to a fixation point than those not scanned beyond it. Our results showed that character information can be processed during the saccade, therefore saccades during reading not only function to redirect the fovea to fixate the next character or word but allow pre-processing of information from the ones adjacent to the fixation locations to help target the next most salient one. In this way saccades can not only promote continuity in reading words but also actively facilitate reading comprehension.     

On automatic diagnosis of pathological saccadic eye movements

A syntactic technique is described for the recognition of saccadic eye movements to distinguish normal saccades from those distorted by brain stem lesions. A digitalized eye movement signal is transformed into a sequence of symbols. Eye movements are then found from this sequence by using a parser. This recognition method appropriately enlarged could be applied as a classifier of saccades to aid in diagnosis     

Afferent signals from pigeon extraocular muscles modify the vestibular responses of units in the abducens nucleus.

Although the extraocular muscles contain stretch receptors it is generally believed that their afferents exert no influence on the control of eye movement. However, we have shown previously that these afferent signals reach various brainstem centres concerned with eye movement, notably the vestibular nuclei, and that the decerebrate pigeon is a favourable preparation in which to study their effects. If the extraocular muscle afferents do influence oculomotor control from moment-to-moment they should exert a demonstrable effect on the oculomotor nuclei. We now present evidence that extraocular muscle afferent signals do, indeed, alter the responses of units in an oculomotor nucleus (the abducens, VI nerve nucleus, which supplies the lateral rectus muscle) to horizontal, vestibular stimulation induced by sinusoidal oscillation of the bird. Such stimuli evoke a vestibulo-ocular reflex in the intact bird. The extraocular stretch receptors were activated by passive eye movement within the pigeon's saccadic range; such movements modified the vestibular responses of all 19 units studied which were all, histologically, in the abducens nucleus. The magnitude of the effects, purely inhibitory in 15 units, depended both on the amplitude and the velocity of the eye movement and most units showed selectivity for particular combinations of plane (e.g. horizontal versus vertical) and direction (e.g. rostral versus caudal) of eye movement. The results show that an afferent signal from the extraocular muscles influences vestibularly driven activity in the abducens nucleus to which it carries information related to amplitude, velocity, plane and direction of eye movement in the saccadic range. They thus strongly support the view that extraocular afferent signals are involved in the control of eye movement.     

Frequency characteristics of the saccadic eye movement

Using a piecewise linear approach, individual saccadic eye movements have been Fourier decomposed in an attempt to determine the effect of saccadic amplitude on frequency characteristics. These characteristics were plotted in the traditional Bode plot form, showing gain and phase as a function of frequency for various eye movement amplitudes. Up to about one octave beyond the -3 db gain frequency, the limiting system dynamics represented by the saccadic trajectory of a given amplitude may be considered linear and second order. The -3 db gain frequency was used as a measure of bandwidth, and the -90 degrees phase crossover frequency was used as a measure of undamped natural frequency. These two quantities were used to calculate the damping factor. Both bandwidth and undamped natural frequency decrease with increasing saccadic eye movement amplitude. The damping factor shows no trend with amplitude and indicates approximate critical damping. When compared with the normal variation of characteristics for a given movement, the frequency characteristics of fixed-amplitude saccades showed no generalized trends with changes in direction or DC operating level of movement.     

Saccadic eye movements minimize the consequences of motor noise

The durations and trajectories of our saccadic eye movements are remarkably stereotyped. We have no voluntary control over these properties but they are determined by the movement amplitude and, to a smaller extent, also by the movement direction and initial eye orientation. Here we show that the stereotyped durations and trajectories are optimal for minimizing the variability in saccade endpoints that is caused by motor noise. The optimal duration can be understood from the nature of the motor noise, which is a combination of signal-dependent noise favoring long durations, and constant noise, which prefers short durations. The different durations of horizontal vs. vertical and of centripetal vs. centrifugal saccades, and the somewhat surprising properties of saccades in oblique directions are also accurately predicted by the principle of minimizing movement variability. The simple and sensible principle of minimizing the consequences of motor noise thus explains the full stereotypy of saccadic eye movements. This suggests that saccades are so stereotyped because that is the best strategy to minimize movement errors for an open-loop motor system.     

A competitive integration model of exogenous and endogenous eye movements

We present a model of the eye movement system in which the programming of an eye movement is the result of the competitive integration of information in the superior colliculi (SC). This brain area receives input from occipital cortex, the frontal eye fields, and the dorsolateral prefrontal cortex, on the basis of which it computes the location of the next saccadic target. Two critical assumptions in the model are that cortical inputs are not only excitatory, but can also inhibit saccades to specific locations, and that the SC continue to influence the trajectory of a saccade while it is being executed. With these assumptions, we account for many neurophysiological and behavioral findings from eye movement research. Interactions within the saccade map are shown to account for effects of distractors on saccadic reaction time (SRT) and saccade trajectory, including the global effect and oculomotor capture. In addition, the model accounts for express saccades, the gap effect, saccadic reaction times for antisaccades, and recorded responses from neurons in the SC and frontal eye fields in these tasks.