Saccadic Pulse Research Articles

A model-based study of internuclear ophthalmoparesis and ocular-motor fatigue in multiple sclerosis.

Internuclear ophthalmoparesis (INO) in multiple sclerosis (MS) is due to demyelination of the medial longitudinal fasciculus (MLF). INO is typically modeled as an increased peak-velocity and peak-acceleration ratio of abducting to adducting eye (pulse-size ratio, PSR). PSR can be affected by fatigue during prolonged ocular-motor tasks (ocular-motor fatigue). We propose that an important component of horizontal disconjugacy in INO is due to a delayed delivery of the saccadic pulse to the adducting eye (pulse-time delay, PTD). We expanded a control-system model to account for both abnormal PSR and PTD reflecting faulty axonal transmission in INO and to provide a better understanding of possible changes induced by fatigue. Saccades were measured in 19 MS patients with INO and 10 controls, using a 10-min saccadic "fatigue test" consisting of repetitive back-to-back 20° saccades. In the horizontal saccades model the unitary MLF connection was partitioned into parallel sub-tracts representing progressive degrees of disease effect. INO patients showed baseline abnormal PSR and PTD with some changes during the fatigue test. Manipulations of gain and transmission delay in the model provided simulated saccades that closely resembled those of INO. Ocular-motor fatigue may be a heterogeneous phenomenon that involves inter-saccadic fluctuation of PSR and PTD and adaptation during demanding ocular-motor tasks. INO as a model of abnormal axonal conduction has a potential role in assessing efficacy of reparative therapies in MS.

Ocular dipping movements in an electrocution cardiac arrest survivor

Background : Abnormal eye movements can occur in patients with neurological diseases. These have been described in unconscious patients due to anoxic coma and often disappear as the patient regains consciousness. Ocular dipping movements are rarely seen in practice in pediatric patients. Methods : A one year old male patient was brought unconscious with electrocution injury. With resuscitation, he became hemodynamically stable. He could not recognize his mother or respond to visual/auditory stimuli; and had generalized hypertonia. Cranial nerves were normal. He showed abnormal involuntary conjugate vertical saccadic eye movements, consisting of slow downward movement (for 1-2 seconds) followed by a relatively faster return to the primary mid-position. These persisted continuously for 48 hours at irregular intervals of 1-2 seconds. The patient was awake but non-responsive and not interested in surroundings. Results : These eye movements are called ocular dipping (OD) . In a normal person, saccadic movements are meant for stable fixation and are maintained by pause-cell neurons positioned in the pontine raphe. These prevent the occurrence of unwanted saccadic pulses by inhibiting the saccadic premotor burst neurons in the paramedian pontine reticular formation and midbrain. Injury to pause cells leads to extraneous saccades without fixation. It appears that cortical and basal ganglia malfunction causes ocular dipping. OD is mainly seen in anoxic coma and creuztfelt Jacob disease. A 53-year-old man developed ocular dipping following prolonged hypotension.Our patient was in vegetative state with normal respiratory and cardiac function suggesting that major midbrain and medullary centers were intact. Conclusion : The self limiting nature of OD suggests that these are caused by diffuse dysfunction rather than a single structural locus.

Visual and ocular motor function in the atypical form of neurodegeneration with brain iron accumulation type I

Background/aimsNeurodegeneration with brain iron accumulation (NBIA) type I is a rare disease that can be divided into a classical or atypical variant, according to age of onset and clinical pattern....

Physiology and pathology of saccades and gaze holding

Foveation is the fundamental requirement for clear vision. Saccades rapidly shift the gaze to the interesting target while gaze holding ensures foveation of the desired object. We will review the pertinent physiology of saccades and gaze holding and their pathophysiology leading to saccadic oscillations, slow saccades, saccadic dysmetria, and nystagmus. Motor commands for saccades are generated at multiple levels of the neuraxis. The frontal and parietal eye field send saccadic commands to the superior colliculus. Latter then projects to the brain-stem saccadic burst generator. The brain-stem burst generators guarantee optimum signal to ensure rapid saccadic velocity, while the neural integrator, by mathematically integrating the saccadic pulse, facilitates stable gaze holding. Reciprocal innervations that ensure rapid saccadic velocity are prone to inherent instability leading to saccadic oscillations. In contrast, suboptimal function of the burst generators causes slow saccades. Impaired error correction, either at the cerebellum or the inferior olive, leads to impaired saccade adaptation and ultimately saccadic dysmetria and oculopalatal tremor. Impairment in the function of neural integrator causes nystagmus. Neurophysiology of saccades, gaze holding, and their deficits are well recognized. These principles can be implemented to define novel therapeutic and rehabilitation approaches.

The role of the medial longitudinal fasciculus in horizontal gaze: tests of current hypotheses for saccade-vergence interactions

Rapid shifts of the point of visual fixation between equidistant targets require equal-sized saccades of each eye. The brainstem medial longitudinal fasciculus (MLF) plays a cardinal role in ensuring that horizontal saccades between equidistant targets are tightly yoked. Lesions of the MLF--internuclear ophthalmoparesis (INO)--cause horizontal saccades to become disjunctive: adducting saccades are slow, small, or absent. However, in INO, convergence movements may remain intact. We studied horizontal gaze shifts between equidistant targets and between far and near targets aligned on the visual axis of one eye (Müller test paradigm) in five cases of INO and five control subjects. We estimated the saccadic component of each movement by measuring peak velocity and peak acceleration. We tested whether the ratio of the saccadic component of the adducting/abducting eyes stayed constant or changed for the two types of saccades. For saccades made by control subjects between equidistant targets, the group mean ratio (±SD) of adducting/abducting peak velocity was 0.96 ± 0.07 and adducting/abducting peak acceleration was 0.94 ± 0.09. Corresponding ratios for INO cases were 0.45 ± 0.10 for peak velocity and 0.27 ± 0.11 for peak acceleration, reflecting reduced saccadic pulses for adduction. For control subjects, during the Müller paradigm, the adducting/abducting ratio was 1.25 ± 0.14 for peak velocity and 1.03 ± 0.12 for peak acceleration. Corresponding ratios for INO cases were 0.82 ± 0.18 for peak velocity and 0.48 ± 0.13 for peak acceleration. When adducting/abducting ratios during Müller versus equidistant targets paradigms were compared, INO cases showed larger relative increases for both peak velocity and peak acceleration compared with control subjects. Comparison of similar-sized movements during the two test paradigms indicated that whereas INO patients could decrease peak velocity of their abducting eye during the Müller paradigm, they were unable to modulate adducting velocity in response to viewing conditions. However, the initial component of each eye's movement was similar in both cases, possibly reflecting activation of saccadic burst neurons. These findings support the hypothesis that horizontal saccades are governed by disjunctive signals, preceded by an initial, high-acceleration conjugate transient and followed by a slower vergence component.

Modifications in saccadic pulse and step components in Cuban ataxia SCA2 patients

Modifications in saccadic pulse and step components in Cuban ataxia SCA2 patients

Using fast eye movements to study fatigue in multiple sclerosis

To investigate whether internuclear ophthalmoparesis (INO) due to demyelination of the medial longitudinal fasciculus (MLF) provides a model for studying the poorly understood symptom of fatigue in multiple sclerosis (MS). We asked whether repetitive horizontal saccades increased eye movement disconjugacy in patients with MS with INO, but not in healthy subjects. We compared conjugacy of horizontal saccades in 9 patients with INO (4 bilateral, total 13) and 8 controls during minute 1 and minute 10 of a fatigue test; we measured the ratio of abducting/adducting peak velocity (versional disconjugacy index [VDI]). VDI values were greater in patients than controls. During the fatigue test, controls showed no changes of VDI, but patients did (p < 0.005) for 10/13 INOs, with increased ratios in 5 cases and a decrease in the other 5. Fatigue-induced worsening of conjugacy was observed in milder internuclear ophthalmoparesis (INO), and may reflect deteriorated fidelity of saccadic pulse transmission along demyelinated medial longitudinal fasciculus. Improved conjugacy was observed in the more severe INOs, and may be due to adaptive mechanisms, such as recruitment of vergence to aid gaze shifts. INO may provide an accessible, reductionist model to study how decreased neural transmission influences fatigue in multiple sclerosis, how the brain adapts to it, and whether drugs may prove therapeutic.

Double saccadic pulses and macrosaccadic oscillations from a focal brainstem lesion

Double saccadic pulses (DSP) are saccadic intrusions that consist of an initial saccade away from a fixation followed immediately by a return saccade back to the fixation. DSP have been reported in patients with presumed multiple sclerosis and metabolic encephalopathy. However, DSP have not been described in a circumscribed brain lesion. We report a man who developed almost continuous DSP with intervening macrosaccadic oscillations from a circumscribed lesion in the dorsal pontine tegmentum which extended up to the midbrain level and spared the nucleus raphe interpositus where the pause cells reside. Damage to the projections from the superior colliculus to omnipause neurons and resultant dysfunction of omnipause neuron may be a mechanism of saccadic intrusions and oscillations observed in our patient with a circumscribed brainstem lesion.

Tests of Models for Saccade–Vergence Interaction using Novel Stimulus Conditions

During natural activities, two types of eye movements - saccades and vergence - are used in concert to point the fovea of each eye at features of interest. Some electrophysiological studies support the concept of independent neurobiological substrates for saccades and vergence, namely saccadic and vergence burst neurons. Discerning the interaction of these two components is complicated by the near-synchronous occurrence of saccadic and vergence components. However, by positioning the far target below the near target, it is possible to induce responses in which the peak velocity of the vertical saccadic component precedes the peak velocity of the horizontal vergence component by approximately 75 ms. When saccade-vergence responses are temporally dissociated in this way, the vergence velocity waveform changes, becoming less skewed. We excluded the possibility that such change in skewing was due to visual feedback by showing that similar behavior occurred in darkness. We then tested a saccade-related vergence burst neuron (SVBN) model proposed by Zee et al. in J Neurophysiol 68:1624-1641 (1992), in which omnipause neurons remove inhibition from both saccadic and vergence burst neurons. The technique of parameter estimation was used to calculate optimal values for responses from human subjects in which saccadic and convergence components of response were either nearly synchronized or temporally dissociated. Although the SVBN model could account for convergence waveforms when saccadic and vergence components were nearly synchronized, it could not when the components were temporally dissociated. We modified the model so that the saccadic pulse changed the parameter values of the convergence burst units if both components were synchronized. The modified model accounted for velocity waveforms of both synchronous and dissociated convergence movements. We conclude that both the saccadic pulse and omnipause neuron inhibition influence the generation of vergence movements when they are made synchronously with saccades.

Evaluating Large Saccades in Patients with Brain‐Stem or Cerebellar Disorders

Clinicians conventionally test saccades at the bedside by noting the accuracy, initiation time, and speed of large movements, with the patient's head stationary. Partly for methodological reasons, laboratory analysis of saccades has mainly focused on movements of 20 degrees or less. By measuring the velocity waveform of large saccades, it is possible to examine more closely the way in which brain stem and cerebellum guide the eye to the target. Large saccades made by healthy humans show a positively skewed velocity profile. Slow saccades made by patients with brain-stem disorders show a prolonged plateau of low velocity. Some patients with cerebellar disorders may show increased acceleration and deceleration of saccades. Each of these velocity waveforms can be modeled by changing the parameters that describe medium-lead burst neuron firing. In certain other brain-stem and cerebellar disorders, transient decelerations or premature terminations of saccades occur; such velocity waveforms cannot be modeled solely by changing the parameters that describe burst neuron firing. Instead, it is necessary to postulate dysfunction of the mechanism that normally inhibits pontine omnipause neurons, thereby permitting burst neurons to discharge until the saccade is completed. Analysis of large, abnormal saccades calls for application of novel techniques to identify the beginning and end of the saccadic pulse command.

Neuro-ophthalmology of late-onset Tay–Sachs disease (LOTS)

Late-onset Tay-Sachs disease (LOTS) is an adult-onset, autosomal recessive, progressive variant of GM2 gangliosidosis, characterized by involvement of the cerebellum and anterior horn cells. To determine the range of visual and ocular motor abnormalities in LOTS, as a prelude to evaluating the effectiveness of novel therapies. Fourteen patients with biochemically confirmed LOTS (8 men; age range 24 to 53 years; disease duration 5 to 30 years) and 10 age-matched control subjects were studied. Snellen visual acuity, contrast sensitivity, color vision, stereopsis, and visual fields were measured, and optic fundi were photographed. Horizontal and vertical eye movements (search coil) were recorded, and saccades, pursuit, vestibulo-ocular reflex (VOR), vergence, and optokinetic (OK) responses were measured. All patients showed normal visual functions and optic fundi. The main eye movement abnormality concerned saccades, which were "multistep," consisting of a series of small saccades and larger movements that showed transient decelerations. Larger saccades ended earlier and more abruptly (greater peak deceleration) in LOTS patients than in control subjects; these changes can be attributed to premature termination of the saccadic pulse. Smooth-pursuit and slow-phase OK gains were reduced, but VOR, vergence, and gaze holding were normal. Patients with late-onset Tay-Sachs disease (LOTS) show characteristic abnormalities of saccades but normal afferent visual systems. Hypometria, transient decelerations, and premature termination of saccades suggest disruption of a "latch circuit" that normally inhibits pontine omnipause neurons, permitting burst neurons to discharge until the eye movement is completed. These measurable abnormalities of saccades provide a means to evaluate the effects of novel treatments for LOTS.

Characteristics of saccadic intrusions

Primary fixation is never perfectly stable, but is frequently interrupted by slow drifts, microsaccades and saccadic intrusions (SI). SI are involuntary, conjugate movements which take the form of an initial fast movement away from the desired eye position and followed after a short duration, by either a return secondary saccade or a drift. The purpose of this study was to examine the prevalence and metrics of SI in a population of 50 healthy subjects. Using both one and two dimensional recordings we find that all 50 members of the subject group exhibited SI. The SI were bilateral, conjugate and horizontal. No purely vertical SI were detected when examined in three subjects. SI amplitude mean and range was 0.6° ± 0.5°, 0.1°–4.1°; SI frequency mean and range was 18.0 ± 14.3 per min, 1.0–54.8 per min; SI duration mean and range was 225 ± 150, 20–870 ms. The mean SI amplitude and frequency when SI < 0.5° were removed was 0.97° ± 0.56° and 7.0 ± 11.4 per min respectively. Age was positively correlated with SI amplitude ( p < 0.01), but there was no correlation between age and SI frequency. Three of four types of SI monophasic square wave intrusions (MSWI), biphasic square wave intrusions (BSWI) and double saccadic pulses (DSP) were found to be exclusively saccadic, whilst the fourth type, the single saccadic pulses (SSP), were confirmed to exhibit a slow secondary component. MSWI were the most frequently observed SI occurring in 47 out of 50 (94%) of the subjects with a mean amplitude, frequency and duration of 0.7° ± 0.5°, 11.5 ± 11.6 per min, and 255 ± 147 ms respectively. Mean amplitudes and frequencies for BSWI ( n = 20), SSP ( n = 11) and DSP ( n = 34) were found to be 0.50° ± 0.2°, 1.2 ± 2.5 per min; 0.40° ± 0.20°, 0.4 ± 1.0 per min and 0.3° ± 0.4°, 5.0 ± 8.7 per min respectively. No differences in MSWI characteristics were found between binocular and monocular viewing. Possible explanations for SI occurrence include experimental viewing conditions, subject fatigue and covert shifts in attention.

Cerebellar contribution to saccades and gaze holding: a modeling approach.

The possible role of the cerebellum for the control of saccades and gaze holding is reconsidered using a computational modeling approach. As suggested by previous research, control of gaze holding is assumed to be enhanced by the floccular lobe, whereas control of the saccadic pulse is governed by the oculomotor vermis and fastigial nucleus. In the present work, a negative feedback loop via the paramedian tract neurons and the floccular lobe that contains a forward model of the oculomotor plant is supposed to enhance the time constant of the brainstem integrator. Control of saccadic amplitude is hypothesized to be achieved by a more complex network: feedforward projections from the superior colliculus via the nucleus reticularis tegmenti pontis to the oculomotor vermis and fastigial nucleus cooperate with feedback connections from excitatory burst neurons to overcome the sluggishness of the assumed local feedback loop formed via the superior colliculus and to implement inverse dynamics of downstream neural and motor processing.

Effects of intravenous opioids on eye movements in humans: possible mechanisms

Oculomotor symptoms such as downbeat nystagmus can be due to side effects of drugs. We investigated the clinical effects as well as the eye movement symptoms after intravenous administration of opiates (pethidine and fentanyl). Eye movements were recorded with the magnetic search coil technique. All four normal subjects showed a transient disturbance of eye fixation with downbeat nystagmus, a range of saccadic intrusions and oscillations, including square wave jerks and saccadic pulses, lasting from 10 to 15 minutes. The gain of sinusoidal VOR and smooth pursuit was moderately decreased; in particular the vertical pursuit showed an upward velocity offset. On the basis of the clinical findings and of recent diprenorphine PET findings in humans, which detected opiod binding sites in the cerebellum and the known inhibitory action of opiates, we hypothesized that a cerebellar dysfunction occurs after opiate administration which could possibly be mediated by inhibition of the parallel fiber activation of the Purkinje cells. Furthermore, opiate binding sites in the vestibular nuclei could be responsible for the vertical vestibular tonus imbalance involved in the pathophysiolgy of downbeat nystagmus.

Transcranial Magnetic Stimulation Over the Cerebellum Delays Predictive Head Movements in the Coordination of Gaze

We investigated coordinated saccadic eye and head movements following predictive horizontal visual targets at - 30° by applying transcranial magnetic stimulation (TMS) over the cerebellum before the start of the gaze movement in 10 young subjects. We found three effects of TMS on eye-head movements: 1. Saccadic latency effect. When stimulation took place shortly before movements commenced (75-25 ms before), significantly shorter latencies were found between predictive target presentation and initiation of saccades. Eye latencies were significantly decreased by 45 ms on average, but head latencies were not. 2. Gaze amplitude effect. Without TMS, for the 60° target amplitudes, head movements usually preceded eye movements, as expected (predictive gaze type 3). With TMS 5-75 ms before the gaze movement, the number of eye movements preceding head movements by 20-50 ms was significantly increased ( p < 0.001) and the delay between eye and head movements was reversed ( p < 0.001), i.e. we found eye-predictive gaze type 1. 3. Saccadic peak velocity effect. For TMS 5-25 s before the start of head movement, mean peak velocity of synkinetic eye saccades increased by 20-30% up to 600°/s, compared to 350-400°/s without TMS. We conclude that transient functional cerebellar deficits exerted by means of TMS can change the central synkinesis of eye-head coordination, including the preprogramming of the saccadic pulse and step of a coordinated gaze movement.

Role of muscle pulleys in producing eye position-dependence in the angular vestibuloocular reflex: a model-based study.

It is well established that the head and eye velocity axes do not always align during compensatory vestibular slow phases. It has been shown that the eye velocity axis systematically tilts away from the head velocity axis in a manner that is dependent on eye-in-head position. The mechanisms responsible for producing these axis tilts are unclear. In this model-based study, we aimed to determine whether muscle pulleys could be involved in bringing about these phenomena. The model presented incorporates semicircular canals, central vestibular pathways, and an ocular motor plant with pulleys. The pulleys were modeled so that they brought about a rotation of the torque axes of the extraocular muscles that was a fraction of the angle of eye deviation from primary position. The degree to which the pulleys rotated the torque axes was altered by means of a pulley coefficient. Model input was head velocity and initial eye position data from passive and active yaw head impulses with fixation at 0 degrees, 20 degrees up and 20 degrees down, obtained from a previous experiment. The optimal pulley coefficient required to fit the data was determined by calculating the mean square error between data and model predictions of torsional eye velocity. For active head impulses, the optimal pulley coefficient varied considerably between subjects. The median optimal pulley coefficient was found to be 0.5, the pulley coefficient required for producing saccades that perfectly obey Listing's law when using a two-dimensional saccadic pulse signal. The model predicted the direction of the axis tilts observed in response to passive head impulses from 50 ms after onset. During passive head impulses, the median optimal pulley coefficient was found to be 0.21, when roll gain was fixed at 0.7. The model did not accurately predict the alignment of the eye and head velocity axes that was observed early in the response to passive head impulses. We found that this alignment could be well predicted if the roll gain of the angular vestibuloocular reflex was modified during the initial period of the response, while pulley coefficient was maintained at 0.5. Hence a roll gain modification allows stabilization of the retinal image without requiring a change in the pulley effect. Our results therefore indicate that the eye position-dependent velocity axis tilts could arise due to the effects of the pulleys and that a roll gain modification in the central vestibular structures may be responsible for countering the pulley effect.

Tests of two hypotheses to account for different-sized saccades during disjunctive gaze shifts.

Rapid shifts of the point of visual fixation between objects that lie in different directions and at different depths require disjunctive eye movements. We tested whether the saccadic component of such movements is equal for both eyes (Hering's law) or is unequal. We compared the saccadic pulses of abducting and adducting movements when horizontal gaze was shifted from a distant to a near target aligned on the visual axis of one eye (Müller paradigm) in ten normal subjects. We similarly compared horizontal saccades made between two distant targets lying in the same field of movement as during the Müller paradigm tests, and between targets lying symmetrically on either side of the midline, at near side of the midline, at near or far. We measured the ratio of the amplitude of the movements of each eye in corresponding directions due to the saccadic component, as well as corresponding ratios of peak velocity and peak acceleration. In response to a Müller test paradigm requiring about 17 degrees of vergence, the change in position of the unaligned eye was typically twice the size of the corresponding movement of the aligned eye. The ratio of peak velocities for the unaligned/aligned eyes was about 1.5, which was greater than for saccades made between distant targets. The ratio of peak acceleration for unaligned/aligned eyes was about 1.0 during shifts from near to far and about 1.3 for shifts from far to near, these values being similar to corresponding ratios for saccades between distant targets. These measurements of peak acceleration indicate that the saccadic pulses sent to each eye during the Müller paradigm are more equal than would be deduced by comparing the changes in eye position. We retested five subjects to compare directly the peak acceleration of saccades made during the Müller paradigm with similar-sized "conjugate" saccades made between targets at optical infinity. Saccades made during the Müller paradigm were significant slower (P < 0.005) than similar-sized conjugate saccades; this indicated that the different-sized movements during Müller paradigm are not simply due differences in saccadic pulse size but are also influenced by the concurrent vergence movement. A model for saccade-vergence interactions, which incorporates equal saccadic pulses for each eye, and differing contributions from convergence and divergence, accounts for many of these findings.

The Spectral Main Sequence of Human Saccades

Despite the many models of saccadic eye movements, little attention has been paid to the shape of saccade trajectories. Some investigators have argued that saccades are driven by a rectangular "bang-bang" neural control signal, whereas others have emphasized the similarity to fast arm movement trajectories, such as the "minimum jerk" profile. However, models have not been tested rigorously against empirical trajectories. We examined the Fourier transforms of saccades and compared them with theoretical models. Horizontal saccades were recorded from 10 healthy subjects. The Fourier transform of each saccade was accurately computed using a padded fast Fourier transform (FFT), and the frequencies of the first three minima (M1, M2, M3) in each energy spectrum were measured to a precision of 0.12 Hz. Each subject showed near-linear trends in the relationships among M1, M2, and M3 and the reciprocal of duration (1/T), which we call the "spectral main sequence." Extrapolation of plots did not pass through the origin, indicating a subtle departure from self-similarity. Bivariate confidence regions were established to allow for slope-intercept variability. The nonharmonic relationships seen cannot arise from a rectangular saccadic pulse driving a linear ocular plant. The relationships are also incompatible with minimum acceleration, minimum jerk, or higher-order minimum square derivative trajectories. The best fits were made by trajectories that minimize postmovement variance with signal-dependent noise (). It is concluded that the spectral main sequence is exquisitely sensitive to the saccade trajectory and should be used to test objectively all present and future models of saccades.

Multi-system signs and symptoms in X-linked ataxia carriers

Neurological, auditory, vestibular and ocular motor examinations were performed on 3 definite and 3 possible heterozygous carriers of a previously described X-linked multi-system disorder with early childhood onset, rapid progression and a fatal outcome (Arts et al., 1993). The symptoms i.e., delayed motor development, ataxia, hearing loss and subnormal intelligence, were so evident in 2 of the possible carriers that they could be redesignated as probable carriers. Other symptoms in the definite and probable carriers were clubfeet, dysarthria, intention tremor and abnormal gait, while their signs included dysdiadochokinesia, ataxic paraplegia, abnormal muscle tendon reflexes and extensor plantar responses. All the symptomatic carriers developed moderate-to-severe sensorineural hearing loss with normal stapedial reflexes and brain stem auditory evoked potentials (BAEPs) in those in whom this could be evaluated. Speech discrimination was disproportionally poor unilaterally in one case from whom no BAEPs could be obtained because of her degree of hearing loss. Various combinations were found of high gain of the vestibulo-ocular reflex, spontaneous nystagmus and directional preponderance of vestibularly evoked nystagmus, slowing, hypometria or multi-stepping of saccades, saccadic intrusions of eye movements (macro square wave jerks, double saccadic pulses), impairment of smooth pursuit eye movements and optokinetic nystagmus, and failure of visual fixation suppression of vestibularly evoked nystagmus. Such findings indicate major involvement of the (vestibulo)cerebellum and the vermis. MRI in one carrier showed mild cerebellar atrophy.

Bypassing the Saccadic Pulse Generator: Possible Control of Head Movement Trajectory by Rat Superior Colliculus.

Saccades produced by electrical stimulation of the superior colliculus in primates are influenced primarily by the location of the stimulating electrode, with the suprathreshold intensity or frequency of the stimulating pulse train having little effect. Any given collicular site produces a characteristic movement of relatively fixed amplitude and velocity. In accordance with this finding, in models of the saccadic eye movement system the superior colliculus specifies the change of eye position: the velocity of movement components are determined by 'pulse generators' located between the superior colliculus and the oculomotor neurons. Previous findings in rodents, however, have suggested that eye and head movements induced by stimulation at some collicular sites may be critically dependent on stimulation parameters, implying that in these animals the superior colliculus has access to a non-saccadic control system. To investigate this possibility, rats with electrodes implanted into the lateral intermediate layers were stimulated with pulse trains of varying frequency and duration, and the resultant head movements analysed from video tape. At seven of the nine sites studied, amplitude of the horizontal component of the head movement was linearly related to stimulating frequency for fixed-duration trains, in some cases over a ten-fold range. Subsequent variation of train duration showed that amplitude was affected not by frequency as such, but by the number of pulses in the train; frequency was related to the mean velocity of the movement. By appropriate setting of these parameters, independent control of head movement amplitude and velocity could be achieved. These results suggest that the rodent superior colliculus may be able to control head movement without recourse to a pulse generator, and thus influence the trajectory of the movement directly. If so, it may prove to be a useful preparation for testing theories of trajectory formation.