Optokinetic eye movements elicited by an apparently moving visual pattern in guinea pigs

Based on known anatomical and physiological properties, guinea pigs could be expected to show a lack of cortical impact on the basic properties of optokinetic nystagmus (OKN) such as eye movements elicited by a rotating striped drum. The present study aimed to clarify the question of whether the guinea pig's brainstem-mediated circuit is capable of generating horizontal OKN with the animal binocularly viewing a stationary stroboscopically illuminated striped pattern (apparent-motion OKN). A striped drum with a pattern periodicity of 2.37 degrees was rotated around the animal. The OKN buildup under real stimulation conditions was found to be largely devoid of a rapid initial rise in slow-phase eye velocity (direct OKN component). Only in a few recordings was a slight initially faster acceleration seen eliciting slow-phase eye velocities of 2 degrees/s at the most. The lack of a rapid initial rise proves that the optokinetic reflex loop does not possess a functionally significant cortically mediated component. To achieve apparent-motion OKN, initially in each recording real-motion OKN was elicited by the constantly illuminated rotating pattern. Then, 60 or 90 s later the drum was stopped and the illumination switched over from constant to flashing light. Following Grüsser and Behrens (1979), we calculated an apparent stimulus velocity (= flash frequency x 2.37 degrees) and an apparent OKN gain. We found that all animals continued in nystagmus under the flashing light condition. The slow-phase eye velocity was the same as under real pattern motion, with gain values of between 0.36 and 0.7. In two animals we produced an apparent gain close to unity by suddenly doubling the flash interval, i.e., halving the apparent drum velocity. This gain, however, did not remain at a high level: The slow-phase eye velocity decreased until the previous lower gain was reached again. The data indicate that cortical mechanisms are not necessary to produce nystagmus under apparent-motion stimulation and neither phi nor sigma phenomena of motion perception satisfactorily explain the apparent-motion OKN in the guinea pig. Our data provide evidence that the brainstem-located velocity storage mechanism plays a decisive role in keeping the eye in motion under apparent-motion stimulation.     

Electroencephalographic cortical oscillations and saccadic eye movements in humans

A model predicting different types of saccades has suggested that the presence of rhythmic brain activity determines whether a subject will produce regular or express saccades. We studied cortical oscillations preceding saccadic eye movements. Brain electrical activity was recorded in nine healthy adults continuously from 30 electrodes while subjects performed saccades. In a so-called gap condition multimodal latency distributions resulted. Express saccades were preceded by different oscillatory activity than regular saccades. This was a highly significant finding restricted to the alpha and beta bands of the EEG. Step-wise discriminant analysis showed that cortical oscillations measured from only few electrode sites allowed to predict reliably which type of saccade a subject will make. These findings support the notion that stimulus-induced oscillations of the human EEG may modulate thresholds for triggering saccades.     

Target size modulates saccadic eye movements in humans

The authors investigated mechanisms involved in transformation of spatially extended targets into saccadic eye-movement vectors. Human subjects performed horizontal saccades to targets of varying diameter, which contained no conspicuous elements within the target shape. With increasing target size, express saccades and saccades with fast regular latencies decreased in frequency, whereas frequency of saccades with slow regular latencies increased. For all targets, saccade amplitude distributions showed a peak close to the geometric center of the targets. However, with large targets, increased scatter of saccade amplitudes and increased undershoot of the target center was observed. These effects may reflect distinct subprocesses involved in sensorimotor transformation to spatially extended targets, and may result from modulation of neuronal activity in the superior colliculus.     

Motion processing for saccadic eye movements in humans

Summary 1. We studied the latencies and amplitudes of saccades to moving targets in normal human subjects. Targets underwent ramp or step-ramp motions. The goal was to determine how the saccadic system uses information about target velocity. 2. For simple ramp motion saccadic latency decreased as target speed increased. A threshold distance model, which assumes that the target has to move a minimum distance before saccadic processing starts, provided a good fit to the responses of all four subjects and explains discrepancies between previously published findings. 3. A double step experiment showed that target position may have some effect on saccadic amplitude when sampled 70 ms before saccade onset, but it must be sampled at least 140 ms before onset for an accurate saccade to occur. 4. Saccades to simple ramp targets approximated the target position 55 ms before saccade onset. Based on our double step results, this is more compensation than possible by a simple position estimate and implies extrapolation of target motion by the saccadic system. The lack of complete compensation may be due to an underestimate of the target speed and/or of the saccadic latency. 5. A delayed-saccade paradigm resulted in saccades with a longer, constant latency and allowed longer viewing of target motion. These saccades accounted for all but 20 ms of target motion, suggesting that with more processing time of target motion a better extrapolation may be generated. 6. In a step-ramp paradigm the target stepped in one direction, then moved smoothly in the opposite direction. Saccades in this paradigm could be made in either the direction of the step or in the direction of target motion: the direction and latency were determined solely by the time at which the target crossed the fixation point. This time must be calculated from target speed and position, implying that the saccadic system must use speed information to adjust latency or to cancel unnecessary saccades.     

Tuberculous granulomas are hypoxic in guinea pigs, rabbits, and nonhuman primates

Understanding the physical characteristics of the local microenvironment in which Mycobacterium tuberculosis resides is an important goal that may allow the targeting of metabolic processes to shorten drug regimens. Pimonidazole hydrochloride (Hypoxyprobe) is an imaging agent that is bioreductively activated only under hypoxic conditions in mammalian tissue. We employed this probe to evaluate the oxygen tension in tuberculous granulomas in four animal models of disease: mouse, guinea pig, rabbit, and nonhuman primate. Following infusion of pimonidazole into animals with established infections, lung tissues from the guinea pig, rabbit, and nonhuman primate showed discrete areas of pimonidazole adduct formation surrounding necrotic and caseous regions of pulmonary granulomas by immunohistochemical staining. This labeling could be substantially reduced by housing the animal under an atmosphere of 95% O(2). Direct measurement of tissue oxygen partial pressure by surgical insertion of a fiber optic oxygen probe into granulomas in the lungs of living infected rabbits demonstrated that even small (3-mm) pulmonary lesions were severely hypoxic (1.6 +/- 0.7 mm Hg). Finally, metronidazole, which has potent bactericidal activity in vitro only under low-oxygen culture conditions, was highly effective at reducing total-lung bacterial burdens in infected rabbits. Thus, three independent lines of evidence support the hypothesis that hypoxic microenvironments are an important feature of some lesions in these animal models of tuberculosis.     

Cancelling of pursuit and saccadic eye movements in humans and monkeys

The countermanding paradigm provides a useful tool for examining the mechanisms responsible for cancelling eye movements. The key feature of this paradigm is that, on a minority of trials, a stop signal is introduced some time after the appearance of the target, indicating that the subject should cancel the incipient eye movement. If the delay in giving the stop signal is too long, subjects fail to cancel the eye movement to the target stimulus. By modeling this performance as a race between a go process triggered by the appearance of the target and a stop process triggered by the appearance of the stop signal, it is possible to estimate the processing interval associated with cancelling the movement. We have now used this paradigm to analyze the cancelling of pursuit and saccades. For pursuit, we obtained consistent estimates of the stop process regardless of our technique or assumptions--it took 50-60 ms to cancel pursuit in both humans and monkeys. For saccades, we found different values depending on our assumptions. When we assumed that saccade preparation was under inhibitory control up until movement onset, we found that saccades took longer to cancel (humans: approximately 110, monkeys: approximately 80 ms) than pursuit. However, when we assumed that saccade preparation includes a final "ballistic" interval not under inhibitory control, we found that the same rapid stop process that accounted for our pursuit results could also account for the cancelling of saccades. We favor this second interpretation because cancelling pursuit or saccades amounts to maintaining a state of fixation, and it is more parsimonious to assume that this involves a single inhibitory process associated with the fixation system, rather than two separate inhibitory processes depending on which type of eye movement will not be made. From our behavioral data, we estimate that this ballistic interval has a duration of 9-25 ms in monkeys, consistent with the known physiology of the final motor pathways for saccades, although we obtained longer values in humans (28-60 ms). Finally, we examined the effect of trial sequence during the countermanding task and found that pursuit and saccade latencies tended to be longer if the previous trial contained a stop signal than if it did not; these increases occurred regardless of whether the preceding trial was associated with the same or different type of eye movement. Together, these results suggest that a common inhibitory mechanism regulates the initiation of pursuit and saccades.     

Comparison of rhythmic masticatory muscle activity during non‐rapid eye movement sleep in guinea pigs and humans

Rhythmic masticatory muscle activity can be a normal variant of oromotor activity, which can be exaggerated in patients with sleep bruxism. However, few studies have tested the possibility in naturally sleeping animals to study the neurophysiological mechanisms of rhythmic masticatory muscle activity. This study aimed to investigate the similarity of cortical, cardiac and electromyographic manifestations of rhythmic masticatory muscle activity occurring during non‐rapid eye movement sleep between guinea pigs and human subjects. Polysomnographic recordings were made in 30 freely moving guinea pigs and in eight healthy human subjects. Burst cycle length, duration and activity of rhythmic masticatory muscle activity were compared with those for chewing. The time between R‐waves in the electrocardiogram (RR interval) and electroencephalogram power spectrum were calculated to assess time‐course changes in cardiac and cortical activities in relation to rhythmic masticatory muscle activity. In animals, in comparison with chewing, rhythmic masticatory muscle activity had a lower burst activity, longer burst duration and longer cycle length (P < 0.05), and greater variabilities were observed (P < 0.05). Rhythmic masticatory muscle activity occurring during non‐rapid eye movement sleep [median (interquartile range): 5.2 (2.6–8.9) times per h] was preceded by a transient decrease in RR intervals, and was accompanied by a transient decrease in delta elelctroencephalogram power. In humans, masseter bursts of rhythmic masticatory muscle activity were characterized by a lower activity, longer duration and longer cycle length than those of chewing (P < 0.05). Rhythmic masticatory muscle activity during non‐rapid eye movement sleep [1.4 (1.18–2.11) times per h] was preceded by a transient decrease in RR intervals and an increase in cortical activity. Rhythmic masticatory muscle activity in animals had common physiological components representing transient arousal‐related rhythmic jaw motor activation in comparison to human subjects.     

Relationship between brain structure and saccadic eye movements in healthy humans

This study used structural magnetic resonance imaging (MRI) to investigate associations between brain structure and saccadic eye movements. Seventeen healthy subjects underwent structural MRI and infra-red oculographic assessment of a reflexive saccade task. Volumes of prefrontal, premotor, and occipitoparietal cortex, caudate, thalamus, and cerebellar vermis were used as predictors in multiple regression with prosaccade gain as a dependent variable, controlling for whole-brain volume. Using voxel-based morphometry (VBM), gain was entered into correlational analysis with grey matter density. Regression analysis indicated that vermis volumes predicted prosaccade gain. VBM replicated this finding: gain was correlated with grey matter in the left cerebellar hemisphere and vermis. These findings agree with previous studies on the role of the cerebellar vermis in saccadic gain and support the validity of structural neuroimaging methods in elucidating the neural correlates of saccadic eye movements.     

Neurophysiological aspects of eye and eyelid movements during blinking in humans

The neural relationships between eyelid movements and eye movements during spontaneous, voluntary, and reflex blinking in a group of healthy subjects were examined. Electromyographic (EMG) recording of the orbicularis oculi (OO) muscles was performed using surface electrodes. Concurrently, horizontal and vertical eye positions were recorded by means of the double magnetic induction (DMI) ring method. In addition, movement of the upper eyelid was measured by a specially designed search coil, placed on the upper eyelid. The reflex blink was elicited electrically by supraorbital nerve stimulation either on the right or the left side. It is found that disconjugate oblique eye movements accompany spontaneous, voluntary as well as reflex blinking. Depending on the gaze position before blinking, the amplitude of horizontal and vertical components of the eye movement during blinking varies in a systematic way. With adduction and downward gaze the amplitude is minimal. With abduction the horizontal amplitude increases, whereas with upward gaze the vertical amplitude increases. Unilateral electrical supraorbital nerve stimulation at low currents elicits eye movements with a bilateral late component. At stimulus intensities approximately two to three times above the threshold, the early ipsilateral blink reflex response (R(1)) in the OO muscle can be observed together with an early ipsilateral eye movement component at a latency of approximately 15 ms. In addition, during the electrical blink reflex, early ipsilateral and late bilateral components can also be identified in the upper eyelid movement. In contrast to the late bilateral component of upper eyelid movement, the early ipsilateral component of upper eyelid movement appears to open the eye to a greater degree. This early ipsilateral component of upper eyelid movement occurs more or less simultaneously with the early eye movement component. It is suggested that both early ipsilateral movements following electrical stimulation do not have a central neural origin. Late components of the eye movements slightly precede the late components of the eyelid movement. Synchrony between late components of eyelid movements and eye movements as well as similarity of oblique eye movement components in different types of blinking suggest the existence of a premotor neural structure acting as a generator that coordinates impulses to different subnuclei of the oculomotor nucleus as well as the facial nerve nucleus during blinking independent from the ocular saccadic and/or vergence system. The profile and direction of the eye movement rotation during blinking gives support to the idea that it may be secondary to eyeball retraction; an extra cocontraction of the inferior and superior rectus muscle would be sufficient to explain both eye retraction and rotation in the horizontal vertical and torsional planes.     

Species-dependent response to streptococcal lymphocyte mitogens in rabbits, guinea pigs, and mice.

Extracellular mitogen preparations from NY5 and S84 strains of streptococci induced different responses among rabbit, guinea pig, and mouse lymphocytes. Evidence of T-cell mitogenicity is presented.     

Blink effects on ongoing smooth pursuit eye movements in humans

Blinks are known to affect eye movements, e.g., saccades, slow and fast vergence, and saccade-vergence interaction, in two ways: by superimposition of blink-associated eye movements and changes of the central premotor activity in the brainstem. The goal of this study was to determine, for the first time, the effects of trigeminal evoked blinks on ongoing smooth pursuit eye movements which could be related to visual sensory or premotor neuronal changes. This was compared to the effect of a target disappearing for 100–300 ms duration during ongoing smooth pursuit (blank paradigm) in order to control for the visual sensory effects of a blink. Eye and blink movements were recorded in eight healthy subjects with the scleral search coil technique. Blink-associated eye movements during the first 50% of the blink duration were non-linearly superimposed on the smooth pursuit eye movements. Immediately after the blink-associated eye movements, the pursuit velocity slowly decreased by an average of 3.2±2.1°/s. This decrease was not dependent on the stimulus direction. The pursuit velocity decrease caused by blinks which occluded the pupil more than 50% could be explained mostly by blanking the visual target. However, small blinks that did not occlude the pupil (<10% of lid closure) also decreased smooth pursuit velocity. Thus, this blink effect on pursuit velocity cannot be explained by blink-associated eye movements or by the blink having blanked the visual input. We propose that part of this effect might either be caused by incomplete visual suppression during blinks and/or a change in the activity of omnipause neurons.     

Eyelid movements measured by Nightcap predict slow eye movements during quiet wakefulness in humans

A precipitous decline in eyelid movements (ELMs) has been shown to be a highly reliable indicator of sleep onset. While ELMs correlate well with eye movements during waking and rapid eye movement (REM) sleep, the eye sensor remains silent during the period of slow eye movements (SEMs) typical of sleep onset. If the ELM density (e.g. ELMs per minute) dropped simultaneously with the appearance of SEMs prior to sleep onset, it could be a promising tool for identifying decreases in alertness prior to overt sleep onset. The present study was designed to determine whether the presence of SEMs in the transitional period preceding stage 1 sleep is reflected in decreases in ELM density. ELM densities were computed for 2.5-s epochs with and without SEMs, as well as for 15-s epochs. Decreases in ELM density not only were an excellent correlate of the appearance of SEMs during wakefulness with closed eyes, but also a good predictor of their occurrence (c. 82% accuracy) at a time resolution of 2.5 s. Based on these results, we conclude that ELM density reliably predicts moderate changes in the level of alertness during quiet wakefulness.     

Effects of voluntary blinks on saccades,vergence eye movements,and saccade-vergence interactions in humans

Blinks are known to change the kinematic properties of horizontal saccades, probably by influencing the saccadic premotor circuit. The neuronal basis of this effect could be explained by changes in the activity of omnipause neurons in the nucleus raphe interpositus or in the saccade-related burst neurons of the superior colliculus. Omnipause neurons cease discharge during both saccades and vergence movements. Because eyelid blinks can influence both sets of neurons, we hypothesized that blinks would influence the kinematic parameters of saccades in all directions, vergence, and saccade-vergence interactions. To test this hypothesis, we investigated binocular eye and lid movements in five normal healthy subjects with the magnetic search coil technique. The subjects performed conjugate horizontal and vertical saccades from gaze straight ahead to targets at 20 degrees up, down, right, or left while either attempting not to blink or voluntarily blinking. While following the same blink instruction, subjects made horizontal vergence eye movements of 7 degrees and combined saccade-vergence movements with a version amplitude of 20 degrees. The movements were performed back and forth from two targets simultaneously presented nearby (38 cm) and more distant (145 cm). Small vertical saccades accompanied most vergence movements. These results show that blinks change the kinematics (saccade duration, peak velocity, peak acceleration, peak deceleration) of not only horizontal but also of vertical saccades, of horizontal vergence eye movements, and of combined saccade-vergence eye movements. Peak velocity, acceleration, and deceleration of eye movements were decreased on the average by 30%, and their duration increased by 43% on the average when they were accompanied by blinks. The blink effect was time dependent with respect to saccade and vergence onset: the greatest effect occurred 100 ms prior to saccade onset, whereas there was no effect when the blink started after saccade onset. The effects of blinks on saccades and vergence, which are tightly coupled to latency, support the hypothesis that blinks cause profound spatiotemporal perturbations of the eye movements by interfering with the normal saccade/vergence premotor circuits. However, the measured effect may to a certain degree but not exclusively be explained by mechanical interference.     

Anticipatory control of hand and eye movements in humans during oculo-manual tracking

Anticipatory activity of hand and eye has been examined during oculo-manual tracking of a constant velocity visual target with a hand cursor. Both target and cursor were presented briefly (< 480 ms), but repeatedly, at regular inter-stimulus intervals (ISI). In Expt 1, the build-up of hand and eye responses was examined for target velocities varying from 10–40 deg s⁻¹ with an ISI of 2.4 s. The velocity 100 ms after target onset (i.e. prior to visual feedback) for both hand and eye ( V ₁₀₀) progressively increased over the first four presentations but then attained a steady state (SS). SS V ₁₀₀ values for eye and hand increased in proportion to target velocity and were thus predictive of forthcoming movement. Hand velocity exceeded eye velocity but both exhibited similar anticipatory trajectories. In Expt 2, target velocity was constant (40 deg s⁻¹) but ISI varied from 0.48–3.74 s. Subjects made anticipatory eye movements for all ISIs but hand movements were often reactive at the longest ISI. If the target failed to appear as expected, subjects initiated predictive hand and eye responses with timing appropriate for the prevailing ISI. In Expt 3, predictive responses were compared with responses to randomised presentation. Peak hand velocity was greater in the randomised mode than in the predictive condition, whereas the converse was true for peak eye velocity. This difference is discussed in terms of the mechanisms of positional error correction in hand and eye. Results provide evidence of similar anticipatory mechanisms in hand and eye, using storage of velocity and timing to achieve rapid prediction of target motion.     

An fMRI study of optokinetic nystagmus and smooth-pursuit eye movements in humans

Both optokinetic nystagmus (OKN) and smooth-pursuit eye movements (SPEM) are subclasses of so-called slow eye movements. However, optokinetic responses are reflexive whereas smooth pursuit requires the voluntary tracking of a moving target. We used functional magnetic resonance imaging (fMRI) to determine the neural basis of OKN and SPEM, and to uncover whether the two underlying neural systems overlap or are independent at the cortical level. The results showed a largely overlapping neural circuitry. A direct comparison between activity during the execution of OKN and SPEM yielded no oculomotor-related area exclusively dedicated to one or the other eye movement type. Furthermore, the performance of SPEM evoked a bilateral deactivation of the human equivalent of the parietoinsular vestibular cortex. This finding might indicate that the reciprocally inhibitory visual–vestibular interaction involves not only OKN but also SPEM, which are both linked with the encoding of object-motion and self-motion. Moreover, we could show differential activation patterns elicited by look-nystagmus and stare-nystagmus. Look-nystagmus is characterized by large amplitudes and low-frequency resetting eye movements rather resembling SPEM. Look-nystagmus evoked activity in cortical oculomotor centers. By contrast, stare-nystagmus is usually characterized as being more reflexive in nature and as showing smaller amplitudes and higher frequency resetting eye movements. Stare-nystagmus failed to elicit significant signal changes in the same regions as look-nystagmus/SPEM. Thus, less reflexive eye movements correlated with more pronounced signal intensity. Finally, on the basis of a general investigation of slow eye movements, we were interested in a cortical differentiation between subtypes of SPEM. We compared activity associated with predictable and unpredictable SPEM as indicated by appropriate visual cues. In general, predictable and unpredictable SPEM share the same neural network, yet information about the direction of an upcoming target movement reduced the cerebral activity level.