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Biomedical subjects

G Mather

Publications and source records attributed to G Mather.

At least 19 recordsLinked to original sources
PubMed1999

Second-order processing of four-stroke apparent motion.

In four-stroke apparent motion displays, pattern elements oscillate between two adjacent positions and synchronously reverse in contrast, but appear to move unidirectionally. For example, if rightward shifts preserve contrast but leftward shifts reverse contrast, consistent rightward motion is seen. In conventional first-order displays, elements reverse in luminance contrast (e.g. light elements become dark, and vice-versa). The resulting perception can be explained by responses in elementary motion detectors turned to spatio-temporal orientation. Second-order motion displays contain texture-defined elements, and there is some evidence that they excite second-order motion detectors that extract spatio-temporal orientation following the application of a non-linear 'texture-grabbing' transform by the visual system. We generated a variety of second-order four-stroke displays, containing texture-contrast reversals instead of luminance contrast reversals, and used their effectiveness as a diagnostic test for the presence of various forms of non-linear transform in the second-order motion system. Displays containing only forward or only reversed phi motion sequences were also tested. Displays defined by variation in luminance, contrast, orientation, and size were effective. Displays defined by variation in motion, dynamism, and stereo were partially or wholly ineffective. Results obtained with contrast-reversing and four-stroke displays indicate that only relatively simple non-linear transforms (involving spatial filtering and rectification) are available during second-order energy-based motion analysis.

Contrast Sensitivity↗
PubMed1999

Characterization of the in vitro biotransformation of the HIV-1 reverse transcriptase inhibitor nevirapine by human hepatic cytochromes P-450.

Nevirapine (NVP), a non-nucleoside inhibitor of HIV-1 reverse transcriptase, is concomitantly administered to patients with a variety of medications. To assess the potential for its involvement in drug interactions, cytochrome P-450 (CYP) reaction phenotyping of NVP to its four oxidative metabolites, 2-, 3-, 8-, and 12-hydroxyNVP, was performed. The NVP metabolite formation rates by characterized human hepatic microsomes were best correlated with probe activities for either CYP3A4 (2- and 12-hydroxyNVP) or CYP2B6 (3-and 8-hydroxyNVP). In studies with cDNA-expressed human hepatic CYPs, 2- and 3-hydroxyNVP were exclusively formed by CYP3A and CYP2B6, respectively. Multiple cDNA-expressed CYPs produced 8- and 12-hydroxyNVP, although they were produced predominantly by CYP2D6 and CYP3A4, respectively. Antibody to CYP3A4 inhibited the rates of 2-, 8-, and 12-hydroxyNVP formation by human hepatic microsomes, whereas antibody to CYP2B6 inhibited the formation of 3- and 8-hydroxyNVP. Studies using the CYP3A4 inhibitors ketoconazole, troleandomycin, and erythromycin suggested a role for CYP3A4 in the formation of 2-, 8-, and 12-hydroxyNVP. These inhibitors were less effective or ineffective against the biotransformation of NVP to 3-hydroxyNVP. Quinidine very weakly inhibited only 8-hydroxyNVP formation. NVP itself was an inhibitor of only CYP3A4 at concentrations that were well above those of therapeutic relevance (K(i) = 270 microM). Collectively, these data indicate that NVP is principally metabolized by CYP3A4 and CYP2B6 and that it has little potential to be involved in inhibitory drug interactions.

Antibodies↗
PubMed1999

In vitro evaluation of potential drug interactions with levetiracetam, a new antiepileptic agent.

Levetiracetam and its carboxylic metabolite (AcL) were tested for their potential inhibitory effect on 11 different drug metabolizing enzyme activities using human liver microsomes. The following specific assays were investigated: testosterone 6beta-hydroxylation [cytochrome P-450 3A4 (CYP3A4)], coumarin hydroxylation (CYP2A6), (R)-warfarin hydroxylation (CYP1A2), (S)-mephenytoin hydroxylation (CYP2C19), p-nitrophenol hydroxylation (CYP2E1) tolbutamide hydroxylation (CYP2C9), dextromethorphan O-demethylation (CYP2D6), epoxide hydrolase and UDP-glucuronyltransferase (UGT) toward paracetamol (UGT1*6), ethinyloestradiol (UGT1*1), p-nitrophenol (UGT(pl 6.2)), and valproic acid. None of these activities were affected by levetiracetam or AcL added at concentrations up to 1 mM. Additionally, primary cultures of rat hepatocytes were used to assess a potential inducing effect of levetiracetam on CYPs. Phenobarbital (2 mM), beta-naphtoflavone (40 microM), dexamethasone (1 microM), and phenytoin (up to 300 microM) were tested as positive controls. When added to cells for 48 h, all the positive controls increased 7-ethoxycoumarin O-deethylase activity demonstrating the inducibility of CYPs in the present culture conditions. By contrast, levetiracetam did not affect the activity up to 1 mM. The highest levetiracetam concentrations examined in the above in vitro studies are well in excess of those measured in the plasma of patients receiving therapeutic doses. It is thus concluded that levetiracetam is unlikely to produce pharmacokinetic interactions through inhibition of CYPs, UGTs, and epoxide hydrolase. Furthermore, based on the in vitro assays with rat hepatocytes, it could be speculated that levetiracetam does not act as a CYP inducer.

Animals↗
PubMed1998

Evidence for global motion interactions between first-order and second-order stimuli.

Recent research indicates that the early stages of visual-motion analysis involve two parallel neural pathways, one conveying information from luminance-defined (first-order) image features, the other conveying information from texture-defined (second-order) features. It is still not clear whether these two pathways converge during later stages of global motion integration. According to one account they remain segregated, and feed separate global analyses. In the alternative account, all responses feed a common stage of global analysis. Two perceptual phenomena are universally held to result from interactions between detector responses during global motion integration--direction repulsion and motion capture. We conducted two psychophysical experiments on these phenomena to test for segregation of first-order and second-order responses during integration. Stimuli contained two components, either two random-block patterns transparently drifting in different directions (repulsion measurements), or a drifting square-wave grating superimposed on an incoherent random-block pattern (capture measurements). Repulsion and capture effects were measured when both stimulus components were the same order, and when one component was first order and the other was second order. Both effects were obtained for all combinations of first-order and second-order patterns. Repulsion effects were stronger with first-order inducing patterns, and capture effects were stronger with second-order inducers. The presence of perceptual interactions regardless of stimulus order strongly suggests that responses in first-order and second-order pathways interact during global motion analysis.

Computer Graphics↗
PubMed1997

Order-specific and non-specific motion responses in the human visual system.

A series of experiments measured direction discrimination in two-frame random block kinematograms. Blocks were presented against a uniform grey background, and were filled either with uniform grey (darker or brighter than the background; first-order blocks) or with random microtexture (isoluminant with the background; second-order blocks). Experiment 1 found that when blocks maintained their order from frame to frame, performance declined from near-perfect to chance levels as block displacement increased. When blocks switched order between frames, performance was generally worse (65-75% correct at best), but still above chance levels. Results from control experiments established that it is important to remove intensity cues in second-order patterns using a psychophysical technique, and that above-chance responses with order-switching patterns persisted, even when such intensity cues were removed or randomised. The last experiment measured the effects of block density manipulation. First-order and second-order patterns showed the same decline in Dmax performance as pattern density increased, and results from patterns containing a mixture of first- and second-order blocks could be predicted from performance obtained with each set of blocks presented separately, except at very low densities. It is concluded that both order-specific and non-specific responses are available during motion analysis, but order-specific responses tend to predominate.

Humans↗
PubMed1997

The use of image blur as a depth cue.

Images of three-dimensional scenes inevitably contain regions that are spatially blurred by differing amounts, owing to depth-of-focus limitations in the imaging apparatus. Recent perceptual data indicate that this blur variation acts as an effective cue to depth: if one image region contains sharply focused texture, and another contains blurred texture, then the two regions may be perceived at different depths, even in the absence of other depth cues. Calculations based on the optical properties of the human eye have shown that variation in blur as a function of depth follows the same course as variation in binocular disparity with depth. Computational modelling has shown that the effect of blur on single-step edges is very similar to its effect on random fractal patterns, because the two stimuli have similar Fourier amplitude spectra. Blur discrimination thresholds for the two stimuli were also very similar, and could be predicted by a model based on high-spatial-frequency discrimination. A comparison of blur discrimination thresholds with the range of binocular stereopsis indicates that blur and disparity cues cover different distance ranges: stereopsis is most effective for distances relatively close to fixation, while blur information should be more effective for larger distances.

Contrast Sensitivity↗
PubMed1996

Elemental sulfur toxicosis in a flock of sheep.

Two thousand Panama X Rambouillet ewes from a flock of 2,200 developed signs of acute toxicosis after being moved to a field that had been sprayed 16 hours earlier with elemental sulfur. Acute signs were lethargy, abdominal discomfort, and prostration. Two hundred six (10%) of the affected ewes died within 24 hours. Polioencephalomalacia that was unresponsive to thiamine treatment developed in another 40 (2%) of the ewes; 28 (70%) of the ewes with polioencephalomalacia recovered. Sulfur is converted to hydrogen sulfide in the rumen. Signs of sulfur toxicosis are a result of absorption of hydrogen sulfide and interaction with the cytochrome system and hemoglobin. Sulfide is detoxified in the RBC and by the liver.

Animals↗
PubMed1996

Image blur as a pictorial depth cue.

A range of cues are already known to mediate depth perception in pictures and have been exploited by artists in drawings and paintings. Modern images are commonly generated by photographic or video equipment, and these images contain a depth cue that cannot be found in artistic depictions of natural scenes: different image regions are often blurred by different amounts, because of depth of focus limitations. Demonstrations presented here show that this selective image blur also acts as a pictorial depth cue, even when other pictorial cues are removed. Experimental data indicate that the degree of blur at borders between blurred and sharp image regions is used by the visual system to establish the depth ordering of different regions. Selective image blur is thus a potentially useful addition to computer-generated and cartoon images to enhance the impression of depth they convey. It may well also contribute to depth perception in natural retinal images, because the depth of focus of the human eye is limited.

Computer Graphics↗
PubMed1995

Temporal filtering enhances direction discrimination in random-dot patterns.

In conventional presentations of random-dot kinematograms, two frames of random dots are presented in temporal sequence, separated by a blank inter-stimulus interval, and a coherent offset in spatial position is added to dots in one frame relative to dots in the other frame. Direction discrimination performance is limited temporally to inter-stimulus intervals below about 100 msec (Tmax). Experiments are described in which temporal smoothing was applied to the onset and offset of each frame in the kinematogram. Tmax was found to increase in proportion with the time constant of the temporal smoothing function. An explanation based on contrast-dependent responses in simple motion detectors cannot accommodate the results. Instead, the increase in Tmax with temporal smoothing, and analogous increase in spatial limit (Dmax) with spatial blurring, can be related to the spatiotemporal frequency content of the stimulus. Random-dot kinematograms can be viewed as continuously drifting patterns that have been discretely sampled at regular spatiotemporal intervals. Sampling introduces artefacts (alias signals), which become more intrusive as sampling rate declines (i.e. inter-stimulus interval or spatial displacement increases) and consequently limit discrimination performance. Temporal smoothing or spatial blurring extends performance because it removes alias signals generated by high spatiotemporal frequencies in the pattern. Computational modelling to estimate the Fourier energy available in random-dot kinematograms confirmed that the sampling account can predict the proportional increase in Tmax and Dmax limits as filter time or space constant increases.

Contrast Sensitivity↗
PubMed1995

Motion detection in interleaved random dot patterns: evidence for a rectifying nonlinearity preceding motion analysis.

Three experiments examined direction discrimination in temporally interleaved random dot patterns. The stimulus consisted of two or more uncorrelated random patterns presented in a repeating temporal sequence, so that each pattern appeared only once every n frames, separated by uncorrelated patterns. Each pattern shifted either leftward or rightward at each re-appearance (all patterns shifted in the same direction in any one presentation). Subjects could specify shift direction correctly even when eight different patterns were interleaved, provided that the duration of each frame was brief. An explanation based on responses in first-order motion energy detectors tuned to low spatiotemporal frequencies (effectively summating the interleaved patterns over time) was tested using a stimulus in which each pattern inverted in contrast mid-way through each frame. Contrary to predictions based on temporal summation, performance with contrast-inverting patterns was only slightly lower than with non-inverting patterns. An alternative explanation was examined, based on responses in motion detectors that full-wave rectify image contrast before extracting motion energy. Computed responses from such detectors successfully predicted psychophysical performance with interleaved random patterns. Implications for models of motion analysis are discussed.

Discrimination, Psychological↗
PubMed1995

Second-order texture contrast resolves ambiguous apparent motion.

When a black and a white square on a grey surround exchange places, it was previously shown that on a dark surround it is the white square, and on a light surround it is the black square, that is seen in apparent motion (AM). Thus the higher-contrast square carries the AM. We now show that the same is true for second-order AM of texture-defined squares. Squares were defined by four different textures: by anisotropy (horizontal versus vertical random dashes), by alpha numeric letters, by hash marks, or by dot size. The result was that the square that differed more from the surround in texture properties carried the second-order AM. Judgments of texture salience revealed a high correlation between salience and apparent motion. In a third experiment, crossover AM between dissimilar textures was investigated, and it was found that the more salient textures carried the AM. Results cannot be explained by the concept of "texture activity', but instead indicate that the system extracts a measure of "texture contrast' prior to analysis of salience and apparent motion.

Anisotropy↗
PubMed1994

Motion discrimination in two-frame sequences with differing spatial frequency content.

We measured the upper threshold for directional motion discrimination (Dmax) in two-frame random binary luminance patterns (random dot kinematograms) in which either one or both frames was spatially low-pass filtered by convolution with a Gaussian filter. When both frames were low-pass filtered, Dmax increased as a function of the standard deviation of the Gaussian blurring function, in agreement with previous findings. However, when only one of the two frames was blurred, Dmax showed little change with blurring space constants below about 20 min arc, and at larger space constants motion discrimination became impossible. We take this as evidence against the proposal that Dmax is preferentially determined by motion signals from high spatial frequencies; and as evidence for the alternative that Dmax depends upon the mean spatial interval between features in the pattern after a single stage of spatial frequency pre-filtering. The breakdown in motion discrimination for space constants above about 20 min arc can be predicted from the computed effects of blurring upon the correlation between features (zero-bounded regions) in the broad-band and spatially filtered patterns. At values of blur where motion discrimination began to collapse there was a temporal order asymmetry; discrimination was easier when the low-pass pattern preceded the broadband pattern than when the broadband pattern appeared first. We propose that the temporally sustained high spatial frequency signal in the broadband pattern is delayed relative to the more transient low frequency signal; or alternatively, that the inhibitory surround of the spatial prefilter is switched in after a delay relative to the excitatory centre. The processing-delay interpretation was tested and confirmed in a second experiment by manipulating the frame duration.

Discrimination, Psychological↗
PubMed1993

Recognition of animal locomotion from dynamic point-light displays.

To date, studies of biological motion have been restricted to displays of humans filmed (or synthesised by computer) with lights attached at the major joints. Observers can readily extract meaning from such displays. There have been no studies to assess the generality of this ability by assessing observers' accuracy in identifying various animals solely on the basis of biological motion. An experiment is reported for which biological-motion displays were created from the stop-action photographs taken by Muybridge in the last century. Naive observers could reliably identify the animals involved when biological-motion displays were animated, but not when they were given static views of dot positions. Thus the ability to interpret biological motion is general and is not restricted to human movements.

Adult↗
PubMed1992

Low-level visual processing of biological motion.

Biological motion displays depict a moving human figure by means of just a few isolated points of light attached to the major joints of the body. Naive observers readily interpret the moving pattern of dots as representing a human figure, despite the complete absence of form cues. This paper reports a series of experiments which investigated the visual processes underlying the phenomenon. Results suggest that (i) the effect relies upon responses in low-level motion-detecting processes, which operate over short temporal and spatial intervals and respond to local modulations in image intensity; and (ii) the effect does not involve hierarchical visual analysis of motion components, nor does it require the presence of dots which move in rigid relation to each other. Instead, movements of the extremities are crucial. Data are inconsistent with current theoretical treatments.

Humans↗
PubMed1991

Polarity specific adaptation to motion in the human visual system.

Three experiments investigated polarity specific adaptation to movement. Experiment 1 tested for temporal polarity specific adaptation, using counterphase sawtooth gratings as adapting and test stimuli. Each counterphase grating contained oppositely moving sawtooth components, and was thus balanced for direction, but both components of the adapting grating created only one polarity of luminance change over time, whereas the components of the test grating presented different signs. After adaptation, only the test component containing the unadapted temporal change was visible. A second experiment, using an analogous procedure, found evidence for spatial polarity specific adaptation. Experimental results can be explained by motion detectors which preserve information about spatial and temporal polarity. A third experiment found that spatial and temporal polarity specific adaptation differ in their dependence on temporal frequency.

Adaptation, Ocular↗
PubMed1991

The spacing illusion: a spatial aperture problem?

A geometrical illusion in which the horizontal spacing between adjacent parallel lines in a row is underestimated when the lines are tilted away from vertical in a chevron configuration was investigated in two experiments. The perceived spacing was found to decrease as the tilt angle increased, consistent with the idea that separation judgements are influenced by the normal spacing between lines ie at right angles to the line orientation. It is proposed that this illusion reveals an analogue in spatial perception to the well-known aperture problem in motion perception. In establishing the separation of nearby or overlapping shapes in an image, the visual system cannot only rely upon the normal separation of contours belonging to each shape (as would be visible through small spatial apertures or receptive fields), since this varies with contour orientation. The system is therefore faced with a spatial aperture problem. The spacing illusion may arise because information usually available to solve the problem is absent in the illusion figure, or it may reflect a bias in favour of the orthogonal, which is adopted in the face of the ambiguity.

Adult↗