Three dimensional eye movement analysis during off vertical axis rotation in human subjects

Three dimensional analysis of eye movements during OVAR was performed in 37 healthy human subjects using the computerized image recognition technique developed by us. The modulation component of eye movement was observed in all three components (horizontal, vertical and torsional), whereas the bias component was only clearly seen in the horizontal eye movement. The phase lag of the torsional component was quite consistent with a small variation between each subject with respect to the head position. The phase of vertical eye movement was, however, less consistent compared to that of the horizontal and torsional eye movements. From these results, in human subjects, there should be some differences in the dynamic function of the otolith system compared to that observed in monkeys.     

A new method for estimating the axis of rotation and the center of rotation.

A new method is presented for estimating the parameters of two different models of a joint. The two models are: (1) A rotational joint with a fixed axis of rotation, also referred to as a hinge joint and (2) a ball and socket model, corresponding to a spherical joint. Given the motion of a set of markers, it is shown how the parameters can be estimated, utilizing the whole data set. The parameters are estimated from motion data by minimizing two objective functions. The method does not assume a rigid body motion, but only that each marker rotates around the same fixed axis of rotation or center of rotation. Simulation results indicate that in situations where the rigid body assumption is valid and when measurement noise is present, the proposed method is inferior to methods that utilize the rigid body assumption. However, when there are large skin movement artefacts, simulation results show the proposed method to be more robust.     

The effect of radish plant rotation around a vertical axis on leaf morphology and lipid composition

The effects of radish (Raphanus sativus L. var. radicula D.C., cv. Rozovo-krasnyi s belym konchikom) plant clockwise rotation (2 rpm) around the vertical axis during their growth on growth parameters and also on the composition and content of polar lipids (PL) and neutral lipids (NL) in plant leaves and fatty acids included in them were studied. Rotation in the plane of the Earth’s magnetic field horizontal component did not affect the number of leaves but declined their total mass by 25%. However, a reduction of the root mass was observed only at elevated temperature. Rotation reduced the ratio of PL to NL by 1.5–2.0 times as compared with control, decreasing the content of such PL as glycoand phospholipids and increasing the content of NL, triacylglycerols and free sterols. Among glycolipids, the content of monogalactosyldiacylglycerols and digalactosyldiacylglycerols was reduced in comparison with stationary control, and among phospholipids the content of phosphatidylcholin was reduced by ∼50%. The ratio of phospholipids to sterols was reduced more than by 30%, indirectly indicating the decreased fluidity of the lipid bilayer of membranes; the ratio PL/NL was reduced as well, indicating an acceleration of age-dependent changes in the rotated plants. Rotation increased the content of linolenic acid and reduced the contents of oleic and erucic acids, thus increasing the index of fatty acid desaturation. We concluded that radish plant clockwise rotation around the vertical axis is an unfavorable factor inducing the appearance of the signs of premature senescence.     

A model of Alexander's law of vestibular nystagmus

The observation that the amplitude of vestibular nystagmus grows as gaze is increased in the direction of the nystagmus fast phase and diminished with gaze in the opposite direction is known as Alexander's law. We have developed an analog computer model to simulate Alexander's law in nystagmus secondary to dysfunction of a semicircular canal. The model utilizes relevant brainstem anatomy and physiology and includes gaze modulation of vestibular signals and push-pull integration to create eye positition commands. When simulating normally functioning semicircular canals, the model produced no nystagmus. When simulating total impairment of the canal on one side with gaze directed maximally in the opposite direction, the model produced a large amplitude nystagmus with linear slow phases directed toward the affected side. As gaze was changed from far contralateral to ipsilateral, the nystagmus gradually diminished to zero. When simulating partial impairment of one canal, the nystagmus was smaller in amplitude and absent in ipsilateral gaze.     

Robust estimation of dominant axis of rotation

A simple method is developed for robustly estimating a fixed dominant axis of rotation (AoR) of anatomical joints from surface marker data. Previous approaches which assume a model of circular marker trajectories use plane fitting to estimate the direction of the AoR. However, when there is limited joint range of motion and rotation due to a second degree of freedom, minimizing only the planar error can give poor estimates of the AoR direction. Optimizing a cost function which includes the error component within a plane, instead of only the component orthogonal to a plane, leads to improved estimates of the AoR direction for joints which exhibit additional rotational motion from a second degree of freedom. Results from synthetic data validation show the ranges of motion where the new method has lower estimation error compared to plane-fitting techniques. Estimates of the flexion-extension AoR from empirical motion capture data of the knee and index finger joints were also more anatomically plausible.     

A burst-feedback model of fast-phase burst generation during nystagmus

 Vestibular and optokinetic nystagmus are characterized by alternating slow-phase eye rotations that stabilize the retinal image, and fast-phase eye rotations that reset eye position. Nystagmus is coordinated in the brainstem by burst neurons that fire an intense, temporally circumscribed burst that terminates the slow phase and drives the fast phase. This paper demonstrates that such a burst can be generated during nystagmus using a simple neural network model containing only known brainstem neurons and their interconnections. These include the feedback connections of the burst neuron (burst feedback). The burst neuron excites itself directly, and disinhibits itself by inhibiting the pause neuron (positive feedback). It also inhibits itself by inhibiting the vestibular neuron (negative feedback). The burst neuron begins to fire after its inhibitory bias is overcome by excitation from the vestibular neuron, and burst neuron positive feedback then produces an intense burst with an abrupt onset. The burst causes the vestibular and pause neurons to pause. The benefit of the pause neuron loop is that it contributes to burst neuron positive feedback when it is needed at burst onset, but that contribution is eliminated when the pause neuron pauses and opens the loop. The burst can then terminate, with an offset duration proportional to burst amplitude, under the control of burst neuron self-excitation and inhibitory bias. Model neuron behavior is comparable to that of real brainstem neurons. Synchronized bursts can be produced over the population of burst neurons in a distributed version of the network. Variability in connection weights in the distributed network results in variability in prelude activity among burst neurons that is similar to the spread in lead observed for real burst neurons during nystagmus. Received: 11 April 1996 / Accepted in revised form: 6 August 1996     

Phase-linking and the perceived motion during off-vertical axis rotation

Human off-vertical axis rotation (OVAR) in the dark typically produces perceived motion about a cone, the amplitude of which changes as a function of frequency. This perception is commonly attributed to the fact that both the OVAR and the conical motion have a gravity vector that rotates about the subject. Little-known, however, is that this rotating-gravity explanation for perceived conical motion is inconsistent with basic observations about self-motion perception: (a) that the perceived vertical moves toward alignment with the gravito-inertial acceleration (GIA) and (b) that perceived translation arises from perceived linear acceleration, as derived from the portion of the GIA not associated with gravity. Mathematically proved in this article is the fact that during OVAR these properties imply mismatched phase of perceived tilt and translation, in contrast to the common perception of matched phases which correspond to conical motion with pivot at the bottom. This result demonstrates that an additional perceptual rule is required to explain perception in OVAR. This study investigates, both analytically and computationally, the phase relationship between tilt and translation at different stimulus rates—slow (45°/s) and fast (180°/s), and the three-dimensional shape of predicted perceived motion, under different sets of hypotheses about self-motion perception. We propose that for human motion perception, there is a phase-linking of tilt and translation movements to construct a perception of one’s overall motion path. Alternative hypotheses to achieve the phase match were tested with three-dimensional computational models, comparing the output with published experimental reports. The best fit with experimental data was the hypothesis that the phase of perceived translation was linked to perceived tilt, while the perceived tilt was determined by the GIA. This hypothesis successfully predicted the bottom-pivot cone commonly reported and a reduced sense of tilt during fast OVAR. Similar considerations apply to the hilltop illusion often reported during horizontal linear oscillation. Known response properties of central neurons are consistent with this ability to phase-link translation with tilt. In addition, the competing “standard” model was mathematically proved to be unable to predict the bottom-pivot cone regardless of the values used for parameters in the model.     

A random walk model of fast-phase timing during optokinetic nystagmus

 Most vertebrate animals produce optokinetic nystagmus in response to rotation of their visual surround. Nystagmus consists of an alternation of slow-phase eye rotations, which follow the surround, and fast-phase eye rotations, which quickly reset eye position. The time intervals between fast phases vary stochastically, even during optokinetic nystagmus produced by constant velocity rotation of a uniform surround. The inter-fast-phase interval distribution has a long tail, and intervals that are long relative to the mode become even more likely as constant surround velocity is decreased. This paper provides insight into fast-phase timing by showing that the process of fast-phase generation during constant velocity optokinetic nystagmus is analogous to a random walk with drift toward a threshold. Neurophysiologically, the output of vestibular nucleus neurons, which drive the slow phase, would approximate a random walk with drift because they integrate the noisy, constant surround velocity signal they receive from the visual system. Burst neurons, which fire a burst to drive the fast phase and reset the slow phase, are brought to threshold by the vestibular nucleus neurons. Such a nystagmic process produces stochastically varying inter-fast-phase intervals, and long intervals emerge naturally because, as drift rate (related to surround velocity) decreases, it becomes more likely that any random walk can meander for a long time before it crosses the threshold. The theoretical probability density function of the first threshold crossing times of random walks with drift is known to be that of an inverse Gaussian distribution. This probability density function describes well the distributions of the intervals between fast phases that were either determined experimentally, or simulated using a neurophysiologically plausible neural network model of fast-phase generation, during constant velocity optokinetic nystagmus. Received: 1 June 1995/Accepted in revised form: 15 February 1996     

A common model for cytokine receptor activation: combined scissor-like rotation and self-rotation of receptor dimer induced by class I cytokine

The precise mechanism by which the binding of a class I cytokine to the extracellular domain of its corresponding receptor transmits a signal through the cell membrane remains unclear. Receptor activation involves a cytokine-receptor complex with a 1∶2 stoichiometry. Previously we used our transient-complex theory to calculate the rate constant of the initial cytokine-receptor binding to form a 1∶1 complex. Here we computed the binding pathway leading to the 1∶2 activation complex. Three cytokine systems (growth hormone, erythropoietin, and prolactin) were studied, and the focus was on the binding of the extracellular domain of the second receptor molecule after forming the 1∶1 complex. According to the transient-complex theory, translational and rotation diffusion of the binding entities bring them together to form a transient complex, which has near-native relative separation and orientation but not the short-range specific native interactions. Subsequently conformational rearrangement leads to the formation of the native complex. We found that the changes in relative orientations between the two receptor molecules from the transient complex to the 1∶2 native complex are similar for the three cytokine-receptor systems. We thus propose a common model for receptor activation by class I cytokines, involving combined scissor-like rotation and self-rotation of the two receptor molecules. Both types of rotations seem essential: the scissor-like rotation separates the intracellular domains of the two receptor molecules to make room for the associated Janus kinase molecules, while the self-rotation allows them to orient properly for transphosphorylation. This activation model explains a host of experimental observations. The transient-complex based approach presented here may provide a strategy for designing antagonists and prove useful for elucidating activation mechanisms of other receptors.     

A new model of depression induced by psychogenenic stress

A new depression model has been obtained, based on use of stressors of the psychogenic nature. The laboratory rats in a special stress-camera turned out to be unable to induce the bilateral reaction of active avoidance, with subsequently led to formation of depression in the animals. Analysis of the tests sensitive to depression--a forceful swimming and a hanging by tail as well as of dynamics of the animals' body mass and of the behavior on the whole confirms development of their depression. This model has turned out to be sensitive to a selective inhibitor of the serotonin reuptake--fluoxetine; this also indicates our obtained model to be a model of depression.     

A role for the strained phenylalanine ring rotation induced by substrate binding to cytochrome CYP102A1

X-ray crystal structures of CYP102A1 (P450BM-3) have shown that PHE87 rotates upon substrate binding and is in contact with the heme cofactor. Analysis of substrate binding data combined with DFT calculations suggest that the ring is rotated into an unfavorable interaction with the heme and this could drive active site rearrangement.     

A new model of depression induced by psychogenic stress

A new model of depression based on use of stressors of the psychogenic nature has been created. It turned out that laboratory rats in a special stress-camera were unable to elaborate bilateral reaction of active avoidance, which later on led to formation of their depression-like state. Development of such their state was confirmed by analysis of tests sensitive to depression: forced swimming and tail suspension, dynamics of the animal body mass and their behavior on the whole. This model has turned out to be sensitive to a selective inhibitor of the serotonin uptake??fluoxetine, which also confirms that our obtained model is the model of depression.