Quantitative analysis of smooth pursuit eye movements by personal computer. II. Evaluation of individual performance and clinical applicability

In a previous report on quantitative analysis of smooth pursuit eye movements (SPEM) we assessed two equations in order to describe the SPEM gain/target velocity relationship, and we demonstrated that this relationship is age-related. This report presents a method to evaluate normality of a single subject SPEM performance. Three points have been considered: 1) The control of gain asymmetries depending on target direction (leftward vs rightward SPEM) 2) The definition of age-related control values 3) The subject vs control values comparison An example to explain how our method actually works and its clinical applicability is shown. Finally, the reasons why no choice has been made between the two equations are discussed.     

Tests of a linear model of visual-vestibular interaction using the technique of parameter estimation

The goal of this study was to test whether a superposition model of smooth-pursuit and vestibulo-ocular reflex (VOR) eye movements could account for the stability of gaze that subjects show as they view a stationary target, during head rotations at frequencies that correspond to natural movements. Horizontal smooth-pursuit and the VOR were tested using sinusoidal stimuli with frequencies in the range 1.0–3.5 Hz. During head rotation, subjects viewed a stationary target either directly or through an optical device that required eye movements to be approximately twice the amplitude of head movements in order to maintain foveal vision of the target. The gain of compensatory eye movements during viewing through the optical device was generally greater than during direct viewing or during attempted fixation of the remembered target location in darkness. This suggests that visual factors influence the response, even at high frequencies of head rotation. During viewing through the optical device, the gain of compensatory eye movements declined as a function of the frequency of head rotation (P < 0.001) but, at any particular frequency, there was no correlation with peak head velocity (P > 0.23), peak head acceleration (P > 0.22) or retinal slip speed (P > 0.22). The optimal values of parameters of smooth-pursuit and VOR components of a simple superposition model were estimated in the frequency domain, using the measured responses during head rotation, as each subject viewed the stationary target through the optical device. We then compared the model's prediction of smooth-pursuit gain and phase, at each frequency, with values obtained experimentally. Each subject's pursuit showed lower gain and greater phase lag than the model predicted. Smooth-pursuit performance did not improve significantly if the moving target was a 10 deg × 10 deg Amsler grid, or if sinusoidal oscillation of the target was superimposed on ramp motion. Further, subjects were still able to modulate the gain of compensatory eye movements during pseudo-random head perturbations, making improved predictor performance during visual-vestibular interactions unlikely. We conclude that the increase in gain of eye movements that compensate for head rotations when subjects view, rather than imagine, a stationary target cannot be adequately explained by superposition of VOR and smooth-pursuit signals. Instead, vision may affect VOR performance by determining the context of the behavior. Received: 16 June 1997 / Accepted: 5 December 1997     

Altered velocity processing in schizophrenia during pursuit eye tracking

Smooth pursuit eye movements (SPEM) are needed to keep the retinal image of slowly moving objects within the fovea. Depending on the task, about 50%-80% of patients with schizophrenia have difficulties in maintaining SPEM. We designed a study that comprised different target velocities as well as testing for internal (extraretinal) guidance of SPEM in the absence of a visual target. We applied event-related fMRI by presenting four velocities (5, 10, 15, 20°/s) both with and without intervals of target blanking. 17 patients and 16 healthy participants were included. Eye movements were registered during scanning sessions. Statistical analysis included mixed ANOVAs and regression analyses of the target velocity on the Blood Oxygen Level Dependency (BOLD) signal. The main effect group and the interaction of velocity×group revealed reduced activation in V5 and putamen but increased activation of cerebellar regions in patients. Regression analysis showed that activation in supplementary eye field, putamen, and cerebellum was not correlated to target velocity in patients in contrast to controls. Furthermore, activation in V5 and in intraparietal sulcus (putative LIP) bilaterally was less strongly correlated to target velocity in patients than controls. Altered correlation of target velocity and neural activation in the cortical network supporting SPEM (V5, SEF, LIP, putamen) implies impaired transformation of the visual motion signal into an adequate motor command in patients. Cerebellar regions seem to be involved in compensatory mechanisms although cerebellar activity in patients was not related to target velocity.     

Association of Neuregulin 1 rs3924999 genotype with antisaccades and smooth pursuit eye movements

Neuregulin 1 (NRG1) has been identified as one of the leading candidate genes for schizophrenia. However, its functional mechanisms and its effects on neurocognition remain unclear. In this study, we used two well‐established oculomotor endophenotypes, the antisaccade (AS) and smooth pursuit eye movement (SPEM) tasks, to investigate the functional mechanisms of a single nucleotide polymorphism (SNP) in NRG1 (rs3924999) at the neurocognitive level in a healthy volunteer sample. A total of 114 healthy Caucasian volunteers completed genotyping for NRG1 rs3924999 and infrared oculographic assessment of AS and SPEM (at target velocities of 12°, 24° and 36° per second). Additionally, self‐report questionnaires of schizotypy, neuroticism, attention deficit hyperactivity and obsessive‐compulsive traits were included. A significant effect of rs3924999 genotype, with gender as a covariate, was found for AS amplitude gain (P < 0.01), with an increasing number of A alleles being associated with increasingly hypermetric performance. No statistically significant associations were found for other AS and SPEM variables or questionnaire scores. These findings indicate that NRG1 rs3924999 affects spatial accuracy on the AS task, suggesting an influence of the gene on the neural mechanisms underlying visuospatial sensorimotor transformations, a mechanism that has been previously found to be impaired in patients with schizophrenia and their relatives.     

Discrimination of Velocity and Spectral Composition of a Sound Stimulus during Its Movement in the Vertical Plane

Differential sensitivity to the velocity of a sound source image in the vertical plane was studied by using two signals with different spectral bandwidths: 0.25–4 kHz (signal 1) and 4–12.5 kHz (signal 2). Five subjects were tested. Sequential switching of loudspeakers with similar frequency characteristics simulated movement of a sound source. Differential velocity thresholds were determined for two reference velocities: 58 and 115°/s. Significant differences in the absolute values of these thresholds were found for signals with different spectral compositions. The threshold for signal 1 (0.25–4.0 kHz) exceeded that for signal 2 (4.0–12.5 kHz) twofold at 58°/s and 1.6-fold at 115°/s.     

Comparison of 4D Phase-Contrast MRI Flow Measurements to Computational Fluid Dynamics Simulations of Cerebrospinal Fluid Motion in the Cervical Spine

Cerebrospinal fluid (CSF) dynamics in the cervical spinal subarachnoid space (SSS) have been thought to be important to help diagnose and assess craniospinal disorders such as Chiari I malformation (CM). In this study we obtained time-resolved three directional velocity encoded phase-contrast MRI (4D PC MRI) in three healthy volunteers and four CM patients and compared the 4D PC MRI measurements to subject-specific 3D computational fluid dynamics (CFD) simulations. The CFD simulations considered the geometry to be rigid-walled and did not include small anatomical structures such as nerve roots, denticulate ligaments and arachnoid trabeculae. Results were compared at nine axial planes along the cervical SSS in terms of peak CSF velocities in both the cranial and caudal direction and visual interpretation of thru-plane velocity profiles. 4D PC MRI peak CSF velocities were consistently greater than the CFD peak velocities and these differences were more pronounced in CM patients than in healthy subjects. In the upper cervical SSS of CM patients the 4D PC MRI quantified stronger fluid jets than the CFD. Visual interpretation of the 4D PC MRI thru-plane velocity profiles showed greater pulsatile movement of CSF in the anterior SSS in comparison to the posterior and reduction in local CSF velocities near nerve roots. CFD velocity profiles were relatively uniform around the spinal cord for all subjects. This study represents the first comparison of 4D PC MRI measurements to CFD of CSF flow in the cervical SSS. The results highlight the utility of 4D PC MRI for evaluation of complex CSF dynamics and the need for improvement of CFD methodology. Future studies are needed to investigate whether integration of fine anatomical structures and gross motion of the brain and/or spinal cord into the computational model will lead to a better agreement between the two techniques.     

Evoked potentials of the cat inferior colliculus to acoustic stimuli simulating sound source movement with different velocities in opposite directions

Amplitude changes of inferior colliculus evoked potentials (EPs) in anaesthetized adult cats were studied under presentation of acoustic stimuli simulating both azimuth-moving and stationary sound source. The movement was simulated with gradual changes of interaural time delay between binaurally presented click trains. It was shown that the amplitude of EPs elicited by "moving" signals depended on the velocity of movement. Amplitude differences between EPs to "moving" and stationary stimuli were observed under motion velocities up to 320 deg./s. The greatest response amplitudes in different experiments took place under velocities within the range of 67-320 deg./s with most of them recorded under velocities of 170 and 125 deg./s. Amplitude of the responses to lateral-medial movement with any velocity were always greater than those to opposite direction of movement with the same velocity.     

Elasticity, strength, and water permeability of bilayers that contain raft microdomain-forming lipids

Bilayers composed of phosphatidylcholine (PC), sphingomyelin (SM), and cholesterol (CHOL) are commonly used as systems to model the raft-lipid domain structure believed to compartmentalize particular cell membrane proteins. In this work, micropipette aspiration of giant unilamellar vesicles was used to test the elasticities, water permeabilities, and rupture tensions of single-component PC, binary 1:1 PC/CHOL, and 1:1 SM/CHOL, and ternary 1:1:1 PC/SM/CHOL bilayers, one set of measurements with dioleoyl PC (DOPC; C18:1/C18:1 PC) and the other with stearoyloleoyl PC (SOPC; C18:0/C18:1 PC). Defining the elastic moduli (K_A), the initial slopes of the increase in tension (σ) versus stretch in lipid surface area (α_e) were determined for all systems at low (15°C) and high (32-33°C) temperatures. The moduli for the single-component PC and binary phospholipid/CHOL bilayers followed a descending hierarchy of stretch resistance with SM/CHOL > SOPC/CHOL > DOPC/CHOL > PC. Although much more resistant to stretch than the single-component PC bilayers, the elastic response of vesicle bilayers made from the ternary phospholipid/CHOL mixtures showed an abrupt softening (discontinuity in slope), when immediately subjected to a steady ramp of tension at the low temperature (15°C). However, the discontinuities in elastic stretch resistance at low temperature vanished when the bilayers were held at ∼1 mN/m prestress for long times before a tension ramp and when tested at the higher temperature 32-33°C. The elastic moduli of single-component PC and DOPC/CHOL bilayers changed very little with temperature, whereas the moduli of the binary SOPC/CHOL and SM/CHOL bilayers diminished markedly with increase in temperature, as did the ternary SOPC/SM/CHOL system. For all systems, increasing temperature increased the water permeability but decreased rupture tension. Concomitantly, the measurements of permeability exhibited a prominent correlation with the rupture tension across all the systems. Together, these micromechanical tests of binary and ternary phospholipid/CHOL bilayers demonstrate that PC hydrocarbon chain unsaturation and temperature are major determinants of the mechanical and permeation properties of membranes composed of raft microdomain-forming lipids.     

SPEM dysfunction and general schizotypy as measured by the SSQ: a controlled study

Background

SPEM dysfunction is a well-known phenomenon in schizophrenia. The principal aim of the present study was to examine whether SPEM dysfunction is already observable in subjects scoring high on a specific measure of schizotypy (SSQ General Schizotypy) that was selected because of its intimate relationship with schizophrenic prodromal unfolding.

Methods

Applying ANOVAs, we determined the relationship of subjects' scores on SSQ General Schizotypy and eye movements elicited by targets of different speed. We also examined whether there exists an association between our schizotypy measure and pupil size.

Results

We found more SPEM dysfunction in subjects scoring high on SSQ General Schizotypy than in subjects scoring average on that factor, irrespective of the speed of the target. No relationship was found between baseline pupil size and General Schizotypy.

Conclusion

The present study provides additional evidence that SPEM dysfunction is associated with schizotypic features that precede the onset of schizophrenia and is already observable in general population subjects that show these features.     

Effects of Attention to Auditory Motion on Cortical Activations during Smooth Pursuit Eye Tracking

Background

In contrast to traditional views that consider smooth pursuit as a relatively automatic process, evidence has been reported for the importance of attention for accurate pursuit performance. However, the exact role that attention might play in the maintenance of pursuit remains unclear.

Methodology/Principal Findings

We analysed the neuronal activity associated with healthy subjects executing smooth pursuit eye movements (SPEM) during concurrent attentive tracking of a moving sound source, which was either in-phase or in antiphase to the executed eye movements. Assuming that attentional resources must be allocated to the moving sound source, the simultaneous execution of SPEM and auditory tracking in diverging directions should result in increased load on common attentional resources. By using an auditory stimulus as a distractor rather then a visual stimulus we guaranteed that cortical activity cannot be caused by conflicts between two simultaneous visual motion stimuli. Our results revealed that the smooth pursuit task with divided attention led to significantly higher activations bilaterally in the posterior parietal cortex and lateral and medial frontal cortex, presumably containing the parietal, frontal and supplementary eye fields respectively.

Conclusions

The additional cortical activation in these areas is apparently due to the process of dividing attention between the execution of SPEM and the covert tracking of the auditory target. On the other hand, even though attention had to be divided the attentional resources did not seem to be exhausted, since the identification of the direction of the auditory target and the quality of SPEM were unaffected by the congruence between visual and auditory motion stimuli. Finally, we found that this form of task-related attention modulated not only the cortical pursuit network in general but also affected modality specific and supramodal attention regions.     

Positioning of the Human Forearm in Tracking Movements and Their Reproduction under Conditions of Limited Visual Control

In 14 healthy persons, we studied movements of the forearm with its positioning on a target level. A double trapezium was used as the command trajectory (flexion in the elbow joint from the state of full extension, 0°, with positioning on the level of 50 or 60° and further flexion to the 100° angle, and a similar reverse movement). We compared (i) tracking movements, when the subject tried to adequately reproduce the movement of the target along the command trajectory visualized on the monitor screen and obtained visual information about the performed movement (shifts of the second light point in time/joint angle coordinates), and (ii) reproduction of these movements under conditions of limitation of the visual feedback (when there was no information about the performed movement). Parameters of the tracking movements and of their reproductions (delays of initiation of the movement phases as compared with the command signal, durations of these phases, and angle velocities of the forearm movement), as well as the quality of positioning after oppositely directed movements, were compared. Positioning on the target level performed under proprioceptive control (when visual control was limited) was accompanied by systematic errors, whose sign in most test series performed by most subjects coincided with the direction of the preceding movement phase. The pattern of signs of systematic positioning errors after movements of opposite directions was quite individual (typical of a given subject) and demonstrated no dependence on the value of the extensor loading. Averaged intragroup systematic errors of positioning after movement phase 1 (flexion to the target level) and phase 3 (extension to the same level) under conditions of a minimum extensor loading (0.5-1.0 N · m) were 2.57° and 2.52°, respectively. When the loading was substantial (3.6-6.0 N · m), the respective errors were 3.85° and 3.48°. The nonlinear properties of muscle stretch receptors in the elbow flexors and extensors (responsible for the significant dependence of the parameters of afferent signals produced in these receptors on the movement prehistory) are considered the primary reason for systematic errors when positioning is performed exclusively under proprioceptive control. The influence of alpha-gamma co-activation in active muscles on the characteristics of the above signals is discussed.     

Muscle strength and myoelectric activity in prepubertal and adult males and females

The purpose of this investigation was to compare children and adults of both genders with respect to torque-velocity, electromyogram (EMG)-velocity and torque-EMG relationships during maximal voluntary knee extensor muscle actions. Four groups of ten subjects each were studied comprising 11-year-old girls and boys and female and male physical education students (22–35 years). Maximal voluntary eccentric (lengthening) and concentric (shortening) actions of the knee extensors were performed at the constant velocities of 45, 90 and 180° · s^–1. Average values for torque and EMG activity, recorded by surface electrodes from the quadriceps muscle, were taken for the mid 40° of the 80° range of motion. The overall shapes of the torque- and EMG-velocity relationships were similar for all four groups, showing effects of velocity under concentric (torque decrease and EMG increase) but not under eccentric conditions. Eccentric torques were always greater than velocity-matched concentric ones, whereas the eccentric EMG values were lower than the concentric ones at corresponding velocities. Torque output per unit EMG activity was clearly higher for eccentric than for concentric conditions and the difference was of similar magnitude for all groups. Thus, the torque-EMG-velocity relationships would appear to have been largely independent of gender and to be fully developed at a prepubertal age.     

Beyond origami: using behavioural observations as a strategy to improve trap design

In contrast to ad hoc methods of developing traps for pest monitoring systems, a systematic approach using direct observation of animals allowed a greater understanding of the reasons why trap catch was significantly different in traps of basically similar design. The information gained using this approach could then be used to guide the further development of the trap. The same feature on two related designs of cockroach trap was varied: the slope of the ramp leading into the trap was either 60°, 30°, or 0°. The 30° ramp version of both traps caught significantly more Blattella germanica (L.) (Dictyoptera: Blattellidae). The 60° and 0° ramp versions both caught equal, lower, numbers but observation showed that these net catches were achieved by quite different means; few insects entered over the 60° ramps but none escaped, whereas all entered over the 0° ramps but half escaped. Similar approaches could be applied to other insect-trap systems.     

On the modeling and interpretation of oxygen uptake kinetics from ramp work rate tests

Ramp work rate tests have been used to estimate aerobic parameters in exercise stress testing. Previous studies have suggested an assumption of a linear dynamic system for O2 uptake kinetics. The implication is that model parameters estimated from ramp tests should be similar to those estimated from other dynamic tests. In nine healthy subjects, we found that model parameters used to characterize O2 consumption ramp data were not consistent with those used to characterize step data, when the comparison was made on a subject-to-subject basis. Furthermore the ramp data model parameter values were highly dependent (P less than 0.0001) on the ramp slope. A linear dynamic system interpretation of the ramp data model does not appear to be appropriate, suggesting that caution is needed in the interpretation of ramp data aerobic parameters. The data may be better described by nonlinear or higher order function. Ramp exercise testing is not suitable for assessing dynamic control properties of the cardiorespiratory response to exercise.     

An S-System Parameter Estimation Method (SPEM) for biological networks

Advances in experimental biology, coupled with advances in computational power, bring new challenges to the interdisciplinary field of computational biology. One such broad challenge lies in the reverse engineering of gene networks, and goes from determining the structure of static networks, to reconstructing the dynamics of interactions from time series data. Here, we focus our attention on the latter area, and in particular, on parameterizing a dynamic network of oriented interactions between genes. By basing the parameterizing approach on a known power-law relationship model between connected genes (S-system), we are able to account for non-linearity in the network, without compromising the ability to analyze network characteristics. In this article, we introduce the S-System Parameter Estimation Method (SPEM). SPEM, a freely available R software package (http://www.picb.ac.cn/ClinicalGenomicNTW/temp3.html), takes gene expression data in time series and returns the network of interactions as a set of differential equations. The methods, which are presented and tested here, are shown to provide accurate results not only on synthetic data, but more importantly on real and therefore noisy by nature, biological data. In summary, SPEM shows high sensitivity and positive predicted values, as well as free availability and expansibility (because based on open source software). We expect these characteristics to make it a useful and broadly applicable software in the challenging reconstruction of dynamic gene networks.     

The dynamics of the subtalar joint in sudden inversion of the foot

The human subtalar joint was modelled as a quasi-linear second-order underdamped system to simulate sudden inversion motion of the foot relative to the shank. The model was fed with experimental data obtained from six subjects on a specially constructed apparatus. A total of 35 deg inversion was produced on the tested leg rapidly enough (lasting less than 40 ms) in order to ensure that the protective muscles are not activated. The parameters of the joint were evaluated and the following ranges were obtained at 35 deg inversion: elastic stiffness 14-52 Nm rad-1, damping coefficient 1.4-2.9 Nms rad-1, and natural frequency 78-125 Hz. The effects on the test parameters of weight bearing amount, foot dominance, and protective footwear were studied on one subject.     

Studies on cold pressor response of subjects who suffered from frostbite at high altitude

Seven lowlander soldiers who had 1st to 3rd degree of frostbite and 8 lowlander soldiers who recovered from high altitude pulmonary oedema were tested for cold pressor response at 260 m, 26°C, 6.8°C and 4,085 m, 26°C, 6.8°C. 8 lowlander soldiers (Control subjects) of comparable age group were tested for their cold pressor response at 260 m, 26°C and 3,300 m, 26°C. Another group of control subjects from the laboratory were also tested at 2,121 m, 26°C. There was a highly significant decrease in cold pressor response of the frostbite subjects at 260 m, 26°C and a very significant increase at 260 m, 6.8°C as compared to non-frostbite subjects. The subjects who recovered from high altitude pulmonary oedema did not show significant differences as compared with the control subjects. The results suggest certain basic physiological differences in regulation of supply of blood to the extremities under condition of general and local cold exposure.     

Prediction of body density using A-mode ultrasonoscope in Japanese physical education major college students

The purpose of the present study was to examine the distribution of subcutaneous fat and to derive several equations to predict body density (BD) using an amplitude modulation type of ultrasonoscope (A-mode ultrasonoscope, FUKUDA FT-100). Subjects were 188 male physical education major college students ranging in age from 18 to 24 years. Fifty subjects who were randomly selected out of the 188 subjects were measured for BD by the underwater weighing technique and were used to derive the equation for estimating the BD. Four points (scapular, triceps, suprailiac, and thigh) of subcutaneous fat which had been commonly selected, height, and weight were measured. The four measurements of fat for the 188 subjects indicated rather small means and small standard deviations respectively. Furthermore, histograms of those measurements tended to show a significant skewness for low values and deviated from the normal probability curve (p less than 0.01). Regarding the means, they were almost all the same except for suprailiac measurements. Suprailiac measurements showed more large values and were distributed rather more widely than the other measurements. Derivations of the multiple regression equations from anthropometric measurements were made using the Wherry-Doolittle test selection method (Clarke & Clarke, 1972). Four measurements (triceps, suprailiac, height, and weight) were selected by the Wherry-Doolittle method.     

Assessment of selected haemostatic parameters in obese patients

BACKGROUND: Epidemiologic data show significantly higher frequency of thromboembolic incidents in obesity than in normal weight persons. Disorders of haemostasis seem to play a crucial role in their development. In the literature there are only few papers assessing coagulation and fibrynolitic parameters in obese subjects. AIM OF THE STUDY: Assessment of protein C (PC), antithrombin (AT) and alpha2 antiplasmin (alpha2AP) activity and thrombomodulin (TM) concentration in the blood plasma of obese person (BMI > 30 kg/m(2)). MATERIALS AND METHODS: The study involved 32 patients (22 women and 10 men, mean age 39.7 +/- 15.3 years) and 20 healthy volunteers matched correctly according to sex and age who constituted a control group. In the examined subjects activity of PC, AT, alpha2 AP were assessed by means of the colorimetric methods and TM concentration in the blood plasma using ELISA method. RESULTS: No statistically significant differences in activities of PC, AT, alpha2 AP and TM concentrations between the patients and the control group were found. However the tendency to higher activities of PC and concentrations of TM were noticed in the obese patients. Assessing tested parameters according to sex, statistically significant differences were found in AT activity between the male patients and healthy men. Statistically lower values, but still in the normal range, were found in the obese men. Comparing the groups of women, significantly lower concentrations of TM were found in the obese ones. CONCLUSIONS: It seems that changed values of PC, AT, alpha2 AP activities are not responsible for increased risk of thromboembolic events in obese persons. Increased TM concentration in obese, may indirectly indicate endothelium damage.