Human ocular torsion during parabolic flights: an analysis with scleral search coil

Summary Rotation of the eyes about the visual axis is known as ocular torsion. A lateral inclination (a roll) of the head induces ocular torsion in the opposite direction, a response known as ocular counterrolling. For six subjects, we recorded the static (head still) and dynamic (head in oscillatory roll motion) ocular torsion in normal 1 g condition and also during the microgravity and hypergravity periods of parabolic flight, using the electromagnetic scleral search coil technique. With the head still, the direction and magnitude of torsion that occured in response to microgravity and hypergravity differed substantially from one individual to another, but there was a significant difference in torsional magnitude between the microgravity and hypergravity periods, for all static head positions including the upright position. Under normal 1 g conditions, counterrolling compensated for about 16% of (voluntary) static head roll, while dynamic counterroll was much larger, up to 36% of head roll at 0.55 Hz. With increasing frequency of head oscillation between 0.33 Hz and 0.55 Hz, the gain of counter rolling increased and there was no change in the phase relationship. The gain of dynamic counterroll (in response to voluntary head rolling) was not significantly less in hypogravity, suggesting that on the ground at these frequencies the contribution of gravity and gravity receptors to this reflex is redundant: this reflex is probably driven by the semicircular canals. In some subjects, the torsional displacement in microgravity is accompanied by micro-torsional oscillatory motion.     

Head roll dependent variability of subjective visual vertical and ocular counterroll

We compared the variability of the subjective visual vertical (SVV) and static ocular counterroll (OCR), and hypothesized a correlation between the measurements because of their shared macular input. SVV and OCR were measured simultaneously in various whole-body roll positions [upright, 45° right-ear down (RED), and 75° RED] in six subjects. Gains of OCR were −0.18 (45° RED) and −0.12 (75° RED), whereas gains of compensation for body roll in the SVV task were −1.11 (45° RED) and −0.96 (75° RED). Normalized SVV and OCR variabilities were not significantly different (P > 0.05), i.e., both increased with increasing roll. Moreover, a significant correlation (R ² = 0.80, slope = 0.29) between SVV and OCR variabilities was found. Whereas the gain of OCR is different from the gain of SVV, trial-to-trial variability of OCR follows the same roll-dependent modulation observed in SVV variability. We propose that the similarities in variability reflect a common otolith input, which, however, is subject to distinct central processing for determining the gain of SVV and OCR.     

Torsional and horizontal vestibular ocular reflex adaptation: three-dimensional eye movement analysis

This study used visual-vestibular conflict to effect short-term torsional and horizontal adaptation of the vestibulo-ocular reflex (VOR). Seven normal subjects underwent sinusoidal whole-body rotation about the earth-vertical axis for 40 min (±37°/s, 0.3 Hz) while viewing a stationary radial pattern fixed to the chair (×0 viewing). During adaptation and testing in darkness, the head was pitched either up or down 35° to excite both the horizontal and torsional VOR. The eyes were kept close to zero orbital elevation. Eye movements were recorded with a dual search coil in a three-field magnetic system. VOR gain was determined by averaging peak eye velocity from ten cycles of chair oscillation in complete darkness. The gain of the angular horizontal VOR (response to rotation about the head rostral-caudal axis) was significantly reduced after training in both head orientations. Angular torsional VOR gain (head rotation about the naso-occipital axis) was reduced in both head orientations, but this reached statistical significance only in the head down position. These results suggest that torsional and horizontal VOR gain adaptation, even when elicited together, may be subject to different influences depending upon head orientation. Differences between head up and down could be due to the relatively greater contribution of the horizontal semicircular canals with nose-down pitch. Alternatively, different VOR-adaptation processes could depend on the usual association of the head down posture to near viewing, in which case the torsional VOR is relatively suppressed.     

Human cyclovergence as a function of stimulus frequency and amplitude

Summary By the use of scleral search coils a continuous record of human cyclovergence was obtained while two identical 80° textured patterns, presented dichoptically, oscillated in the frontal plane in counterphase through 1, 3 and 6° of cyclorotation at frequencies between 0.05 and 2 Hz. The amplitude and gain of the response decreased exponentially with increasing stimulus frequency. As stimulus amplitude increased, response amplitude also increased but gain was highest for low-amplitude cyclorotations. For an amplitude of 1° and a frequency of 0.05 Hz the gain reached 0.87 for two subjects. The phase lag increased from a few degrees at a frequency of 0.05 Hz to over 100° at a frequency of 2 Hz. These results suggest that cyclovergence is designed to correct for small, slow drifts in the stereoscopic alignment of the images in the two eyes. Although the disparity in the textured display was not interpreted as slant, it provided a strong stimulus for cyclovergence. The cyclovergence caused a transfer of cyclodisparity into a superimposed vertical line, which was then perceived as slanting in depth.     

Quantitative assessment of the static properties of the oculo-motor system by the photo-oculographic technique

The paper addresses the problems raised by the application of the photo-oculographic technique to the quantification of static orientations of the eye in ophthalmology. Eye orientations are determined from the relative positions of corneal reflex and pupil images. The relationship between the positions of these images and the angular rotations of the eye is studied with an optical model of the anterior chamber of the eye. This model is used to analyse the influence of technical and physiological variables and to evaluate the accuracy of different calibration procedures applicable to clinics.     

Human ocular responses to translation of the observer and of the scene: dependence on viewing distance

Recent experiments on monkeys have indithat-—the eye movements induced by brief translation of either the observer or the visual scene are a linear function of the inverse of the viewing distance. For the movements of the observer, the room was dark and responses were attributed to a translational vestibulo-ocular reflex (TVOR) that senses the motion through the otolith organs; for the movements of the scene, which elicit ocular following, the scene was projected and adjusted in size and speed so that the retinal stimulation was the same at all distances. The shared dependence on viewing distance was consistent with the hypothesis that the TVOR and ocular following are synergistic and share central pathways. The present experiments looked for such dependencies on viewing distance in human subjects. When briefly accelerated along the interaural axis in the dark, human subjects generated compensatory eye movements that were also a linear function of the inverse of the viewing distance to a previously fixated target. These responses, which were attributed to the TVOR, were somewhat weaker than those previously recorded from monkeys using similar methods. When human subjects faced a tangent screen onto which patterned images were projected, brief motion of those images evoked ocular following responses that showed statistically significant dependence on viewing distance only with low-speed stimuli (10°/s). This dependence was at best weak and in the reverse direction of that seen with the TVOR, i.e., responses increased as viewing distance increased. We suggest that in generating an internal estimate of viewing distance subjects may have used a confounding cue in the ocular-following paradigmthe size of the projected scene - which was varied directly with the viewing distance in these experiments (in order to preserve the size of the retinal image). When movements of the subject were randomly interleaved with the movements of the scene - to encourage the expectation of ego-motion - the dependence of ocular following on viewing distance altered significantly: with higher speed stimuli (40°/s) many responses (63%) now increased significantly as viewing distance decreased, though less vigorously than the TVOR. We suggest that the expectation of motion results in the subject placing greater weight on cues such as vergence and accommodation that provide veridical distance information in our experimental situation: cue selection is context specific.     

Human ocular responses to translation of the observer and of the scene: dependence on viewing distance

Recent experiments on monkeys have indicated that the eye movements induced by brief translation of either the observer or the visual scene are a linear function of the inverse of the viewing distance. For the movements of the observer, the room was dark and responses were attributed to a translational vestibulo-ocular reflex (TVOR) that senses the motion through the otolith organs; for the movements of the scene, which elicit ocular following, the scene was projected and adjusted in size and speed so that the retinal stimulation was the same at all distances. The shared dependence on viewing distance was consistent with the hypothesis that the TVOR and ocular following are synergistic and share central pathways. The present experiments looked for such dependencies on viewing distance in human subjects. When briefly accelerated along the interaural axis in the dark, human subjects generated compensatory eye movements that were also a linear function of the inverse of the viewing distance to a previously fixated target. These responses, which were attributed to the TVOR, were somewhat weaker than those previously recorded from monkeys using similar methods. When human subjects faced a tangent screen onto which patterned images were projected, brief motion of those images evoked ocular following responses that showed statistically significant dependence on viewing distance only with low-speed stimuli (10°/s). This dependence was at best weak and in the reverse direction of that seen with the TVOR, i.e., responses increased as viewing distance increased. We suggest that in generating an internal estimate of viewing distance subjects may have used a confounding cue in the ocular-following paradigm the size of the projected scene -which was varied directly with the viewing distance in these experiments (in order to preserve the size of the retinal image). When movements of the subject were randomly interleaved with the movements of the scene to encourage the expectation of ego-motion -the dependence of ocular following on viewing distance altered significantly: with higher speed stimuli (40°/s) many responses (63%) now increased significantly as viewing distance decreased, though less vigorously than the TVOR. We suggest that the expectation of motion results in the subject placing greater weight on cues such as vergence and accommodation that provide veridical distance information in our experimental situation: cue selection is context specific.     

Human express saccades: effects of randomization and daily practice

Summary When human subjects are asked to execute saccades from a fixation point to a peripheral target, if the fixation point is turned off some time (200 ms) before the target is turned on, the distribution of the saccadic reaction times is bimodal. The first peak occurs at about 100 ms and represents the population of express saccades. If the target location is kept constant the express saccades have reaction times of about 100 ms. If the target location is randomized between right and left (distance from fixation point constant at 4 deg) the reaction times of the express saccades are increased by about 15 ms. If the target location is randomized between 4 deg and 8 deg (direction constant to the right) no increase of the reaction time is observed. The proportion of express saccades increases with daily practice and their reaction times decrease slightly from 105 ms to 98 ms. If an anticipatory saccade was made after reaction times below 75 ms, it frequently undershot the target by more than 20% and was followed by a corrective saccade. The corrections could be executed at times where usually an express saccade would have occurred such that all of these corrections began at about the same time, i.e. 100 ms after target onset, implying intersaccadic intervals between 100 ms and zero (!)     

Human ocular following responses are plastic: evidence for control by temporal frequency-dependent cortical adaptation

Summary Optokinetic nystagmus (OKN) induced by wide-field visual stimulation was measured with and without prior adaptation to moving sinusoidal gratings. Under unadapted conditions the mean gains of the slow phases of OKN in the first 500 ms were 0.5–0.8, and the eye velocities and amplitudes had rise times with time constants of 0.1–0.2 s. By contrast, following adaptation to as little as 1 s of image motion, the magnitude of the initial gains fell and the rise times of the velocities and amplitudes increased markedly. The degree of adaptation depended on the adapting temporal frequency, the optimum adaptive frequencies being 1.7–3.4 Hz. In this range of temporal frequencies, the initial gains fell to 0.1–0.3 and the rise times for velocity and amplitude ranged from 0.4 to 7.0 s, depending on the length of the adapting period. Thus the observed changes in the time constant were up to 70-fold. Neither spatial frequency or image velocity had any marked influence on the level of adaptation. The dependence on temporal frequency rather than image velocity suggests that the motion detectors feeding the adaptive system respond to local motion-related changes in luminance. The adaptive effects were direction-selective, showing that this must also be the case for the motion detectors. The adaptive effects were observed both when the drift temporal frequency on the retina was established by artificially maintaining a fixed gaze or when the adapting temporal frequency was induced by retinal slip during OKN. Time constants for recovery from adaptation were similar to motion aftereffects measured by psychophysical and physiological methods. The results suggest a link between cortical motion adaptation and adaptive mechanisms effecting the oculomotor system.     

The removal of ocular artefacts from the electroencephalogram: a review

The causes of ocular artefacts (OAs) in the human electroencephalogram (EEG) are explained and methods for their removal and their effectiveness are discussed. Recommendations for the best procedures to adopt are given together with suggestions for future research. Analogue subtraction techniques are found to be inferior to time domain techniques based on parameter estimation using the method of least squares applied to a linear function of the electro-occulograms (EOGs). Ways of assessing the effectiveness of different models for time domain removal of OAs are discussed. It is concluded that autoregressive modelling of the error terms, or else differenced data, must be used to reduce the effects of correlation in the background EEG. The most generally suitable model for the removal of random eye and blink artefacts should contain terms proportional to the right vertical EOG and the two horizontal EOGs. The EOGs should be linearly filtered to remove noise frequency components in excess of 8 Hz. Adaptive methods are preferred as on line OA removal would be desirable but for the fact that this may result in distortion of stimulus-related responses present. A number of difficulties remain and there are some suggestions for future research.     

Stimulation and recording of dynamic pupillary reflex: the IRIS technique Part 2

The paper describes a newly developed method, called IRIS, for the recording of dynamic pupillary reflexes simultaneously in both eyes. The method is based on the principle of reflection of infra-red light by the iris/pupil boundary. IRIS incorporates a head-fixed. Maxwellian viewing-light stimulator driven by a function generator. IRIS enables pupillary constriction and dilation to be recorded in response to a pulsed light stimulus, thereby permitting determination of the latency times of constriction and dilation. Furthermore, the recording of natural pupil oscillations, the hippus, is possible. IRIS incorporates a clamp-box mode, permitting the study of stimulus-induced pupil oscillations and pupil cycle time. The compact and portable IRIS pupil system combines reliable and accurate recording with general versatility and ease of operation.     

Human express saccades: extremely short reaction times of goal directed eye movements

Summary Human subjects were asked to execute a saccade from a central fixation point to a peripheral target at the time of its onset. When the fixation point is turned off some time ( 200 ms) before target onset, such that there is a gap where subjects see nothing, the distribution of their saccadic reaction times is bimodal with one narrow peak around 100 ms (express saccades) and another peak around 150 ms (regular saccades) measured from the onset of the target. Express saccades have been described earlier for the monkey.     

Role of intralaminar thalamus in gaze mechanisms: evidence from electrical stimulation and fiber-sparing lesions in cat

Summary Information on eye movement related activity in the internal medullary lamina (IML) of the thalamus is consistent with an IML role in the control of eye movements, or with its serving to convey information to the forebrain on impending events in the oculomotor system. Interpretation is impeded by the fact that eye movements evoked by electrical stimulation of the IML might be triggered by antidromic activation of projections to the IML from brainstem preoculomotor centers. In order to address this issue, thesholds for the elicitation of eye movements and cortical recruiting responses (as a marker for IML integrity) were studied before and after destruction of IML neuronal populations by the fiber-sparing neurotoxin ibotenic acid. Experiments were performed in alert cats chronically implanted with a scleral search coil for the monitoring of eye movements and an electrode-cannula assembly that permitted threshold determinations and drug injections at the stimulating site without any movement of probes in the tissue. Drastic elevation of the threshold for cortical recruiting responses, but not for eye movements following ibotenic acid destruction of IML neurons uncomplicated by myelin damage at the site of stimulation suggests an antidromic route for eye movements elicited by IML stimulation.Supported by USPHS grant NS 4955     

Extraocular motor unit and whole-muscle contractile properties in the squirrel monkey. Summation of forces and fiber morphology

In order to understand the neural control of movement, many investigations have examined the contractile properties of single motor units contracting in isolation, and a great majority of those studies have been done in the cat. Fewer studies, again primarily in the cat, have examined motor units acting in concert in both hind-limb and extraocular muscles. It has been shown, in general, that when individual motor unit forces are added together they do not always add linearly, which makes our understanding of motor control somewhat more complicated. In addition, complex neuronal firing patterns can yield unexpected force outputs or muscle positions whether those patterns occur naturally or are induced through motoneuron stimulation. The current investigation extends these findings of nonlinearity to the primate extraocular system. In studies of the squirrel monkey lateral rectus muscle and its motor units, we show that individual units lose an average of 45% of their force output when they fire in concert with a small number of other motor units. Also, when individual motor units are stimulated at a constant rate of 100 Hz, the force output is most often dramatically different if that constant 100-Hz stimulation is preceded by brief (25 ms), high-frequency stimulation burst or pulse, as occurs during saccades. The force at 100 Hz is usually significantly higher than when no pulse is delivered. However, we now show that an identical stimulation pattern applied to a number of motor units simultaneously does not always yield these force differences. These "nonlinearities" are addressed in terms of the complex muscle architecture that we show in the squirrel monkey lateral rectus muscle. Muscle fibers do not always run in parallel from tendon to tendon. Instead, they may branch or attach to each other laterally or end to end, serially.     

In vivo MRS for the assessment of mouse colon using a dedicated endorectal coil: initial findings

Inflammatory bowel disease is a common group of inflammation conditions that can affect the colon and the rectum. These pathologies require a careful follow‐up of patients to prevent the development of colorectal cancer. Currently, conventional endoscopy is used to depict alterations of the intestinal walls, and biopsies are performed on suspicious lesions for further analysis (histology). MRS enables the in vivo analysis of biochemical content of tissues (i.e. without removing any samples). Combined with dedicated endorectal coils (ERCs), MRS provides new ways of characterizing alterations of tissues. An MRS in vivo protocol was specifically set up on healthy mice and on mice chemically treated to induce colitis. Acquisitions were performed on a 4.7 T system using a linear volume birdcage coil for the transmission of the B₁ magnetic field, and a dedicated ERC was used for signal reception. Colon‐wall complex, lumen and visceral fat were assessed on healthy and treated mice with voxel sizes ranging from 0.125 μL to 2 μL while keeping acquisition times below 3 min. The acquired spectra show various biochemical contents such as α‐ and β‐methylene but also glycerol backbone and diacyl. Choline was detected in tumoral regions. Visceral fat regions display a high lipid content with no water, whereas colon‐wall complex exhibits both high lipid and high water contents. To the best of our knowledge, this is the first time that in vivo MRS using an ERC has been performed in the assessment of colon walls and surrounding structures. It provides keys for the in vivo characterization of small local suspicious lesions and offers complementary solutions to biopsies.     

Stimulus versus eye movements: Comparison of neural activity in the striate and prelunate visual cortex (A17 and A19) of trained rhesus monkey

Summary Visual responses were recorded from single cells in the parafoveal striate (A17) and prelunate (A19) cortex of awake rhesus monkeys while they were fixating a stationary or moving spot of light in the presence of a moving or stationary stimulus. Retinotopy and stimulus requirements were found to be less strict in A19 as compared to A17. Striate cells preferred slow stimulus movements and displayed a large amount of binocular interaction. Many prelunate cells responded well to fast stimulus movements, all were binocular but only a few showed binocular interaction. In both areas an overall deficit of visual responses during saccadic eye movements was observed which was mostly due to the cells' inability to respond to stimuli moving at saccadic velocities. Only in A19 were there cells which seemed to receive non-sensory signals reducing visual responses during rapid eye movements. We concluded that the prelunate cortex has access to input which does not use the geniculate-striate pathway. The additional observation of presaccadic activation of some cells supports the idea that activity in the prelunate cortex may be associated with events related to visually guided changes of the direction of gaze and/or attention.Supported by the DFG, Sonderforschungsbereich Hirnforschung und Sinnesphysiologie (SFB 70, Tp B7)     

Express-saccades of the monkey: Reaction times versus intensity,size, duration,and eccentricity of their targets

Summary Monkeys were trained to fixate a small spot of light (fixation spot) and to saccade to a peripheral target if and only if the fixation spot was turned off. If the offset of the fixation spot preceded the onset of the peripheral target by a temporal gap of more than 140 ms the animals could change their direction of gaze after saccadic reaction times of no more than 70–80 ms (express-saccades). The reaction times of the express-saccades depend on the luminance and the size of the target and decrease from about 120 ms for near threshold targets by about 50 ms in a range of 2,5 log units above threshold (gap duration 200 ms). The minimum reaction time and the target size for which the minimum is reached are functions of the retinal eccentricity of the target. Comparison with response latencies of afferent visual neurons suggests that the dependence of the reaction times of express-as well as regular-saccades on the physical parameters of the target is mostly determined by retinal factors. The short reaction times of the express-saccades are discussed in relation to the reaction times of other visually-guided goal-directed movements.     

Coordination of hand movements and saccades: evidence for a common and a separate pathway

Summary We studied the reaction times and initial directions of hand movements and saccades of human subjects who fixated and pointed as quickly as possible at eccentric targets which were presented unexpectedly. The targets were positioned on a horizontal bar which was placed in front of the subject. Different stimulus conditions were used in the experiments. Knowledge of the target position or the presence of an auditory co-stimulus slightly affected the reaction times of saccades in response to visual stimuli. Auditory co-stimuli reduced the reaction times considerably when the targets were presented after a delay of 200 ms after extinction of the central fixation point. Similar reductions were observed in the reaction times of the hand movements. However, these reductions were seen in hand responses to undelayed as well as delayed target presentations. The saccades were always made in the correct direction when the target was presented without delay. When the target was delayed about 50% of the saccades were made in the wrong direction. Even for undelayed targets the hand sometimes made mistakes. The number of mistakes increased to 35% when the target presentation was accompanied by the sound pulse. For delayed targets the proportion of wrong hand movements was about 50%. For such targets saccades and hand movements were practically always made in the same direction. If visual information is available, saccades and hand movements are generated independently of each other. However, if visual information is not present at the appropriate time and the target position has to be guessed, saccades and hand movements are generated on the basis of shared information. We suggest that saccades can be generated by two different mechanisms. One mechanism uses only visual information while the other one uses visual as well as cognitive information. The first mechanism is exclusively used for the generation of saccades while the second one has a more general purpose and is used for the generation of saccades as well as hand movements.     

Improving patient prostate cancer risk assessment: Moving from static,globally-applied to dynamic,practice-specific risk calculators

Clinical risk calculators are now widely available but have generally been implemented in a static and one-size-fits-all fashion. The objective of this study was to challenge these notions and show via a case study concerning risk-based screening for prostate cancer how calculators can be dynamically and locally tailored to improve on-site patient accuracy. Yearly data from five international prostate biopsy cohorts (3 in the US, 1 in Austria, 1 in England) were used to compare 6 methods for annual risk prediction: static use of the online US-developed Prostate Cancer Prevention Trial Risk Calculator (PCPTRC); recalibration of the PCPTRC; revision of the PCPTRC; building a new model each year using logistic regression, Bayesian prior-to-posterior updating, or random forests. All methods performed similarly with respect to discrimination, except for random forests, which were worse. All methods except for random forests greatly improved calibration over the static PCPTRC in all cohorts except for Austria, where the PCPTRC had the best calibration followed closely by recalibration. The case study shows that a simple annual recalibration of a general online risk tool for prostate cancer can improve its accuracy with respect to the local patient practice at hand.     

A new allele of ocular retardation: Early development and morphogenetic cell death

Summary The inheritance and some developmental effects of a new allele of ocular retardation (or ^J) are described. Affected animals, at 12 days of gestation, show reduced cell death in the eye cup and thickening of the inner wall of the optic fissure. At 11 to 13 days of gestation or ³/or ^J eyes grafted to the testis do not produce retina as their or ^J+ littermates do. Adult animals have small eyes with closed lids, abnormal retinal layers, and no optic nerve.This investigation was supported in part by NIH Research Grant CA 02662 from the National Cancer Institute. The Jackson Laboratory is fully accredited by the American Association for Accreditation of Laboratory Animal Care.The assistance of Miss Erni and Dr Groscurth in preparing the EM pictures is ackowledged.