Search PubMed⌕ Search

Biomedical subjects

Z L Lu

Publications and source records attributed to Z L Lu.

At least 37 records · Page 2Linked to original sources

The mechanism of isoluminant chromatic motion perception.

An isoluminant chromatic display is a color display in which the component colors have been so carefully equated in luminance that they stimulate only color-sensitive perceptual mechanisms and not luminance-sensitive mechanisms. The nature of the mechanism by which isoluminant chromatic motion is perceived is an important issue because color and motion processing historically have been associated with different neural pathways. Here we show that isoluminant chromatic motion (i) fails a pedestal test, (ii) has a temporal tuning function that declines to half-amplitude at 3-6 Hz, and (iii) is perceived equally well when the entire motion sequence is presented monocularly (entire motion sequence to one eye) versus interocularly (the frames of motion sequence alternate between eyes so that neither eye individually could perceive motion). These three characteristics indicate that chromatic motion is detected by the third-order motion system. Based on this theory, it was possible to take a moving isoluminant red-green grating and, by simply increasing the chromatic contrast of the green component, to generate the full gamut of motion percepts, from compelling smooth motion to motion standstill. The perception of motion standstill when the third-order mechanism is nullified indicates that there is no other motion computation available for purely chromatic motion. It follows that isoluminant chromatic motion is not computed by specialized chromatic motion mechanisms within a color pathway but by the third-order motion system at a brain level where binocular inputs of form, color, depth, and texture are simultaneously available and where selective attention can exert a major influence.

Calibration↗

The conformational switch in 7-transmembrane receptors: the muscarinic receptor paradigm.

The rhodopsin-like superfamily of 7-transmembrane receptors is the largest class of signalling molecules in the mammalian genome. Recently, a combination of mutagenesis, biophysical and modelling studies have suggested a credible model for the alpha-carbon backbone in the transmembrane region of the 7-transmembrane receptors, and have started to reveal the structural basis of the conformational switch from the inactive to the active state. A key feature may be the replacement of a network of radial constraints, centred on transmembrane helix three, which stabilise the inactive ground state of the receptor by a new set of axial interactions which help to stabilise the activated state. Transmembrane helix three may act as a rotary switch in the activation mechanism.

Binding Sites↗

The functional topography of transmembrane domain 3 of the M1 muscarinic acetylcholine receptor, revealed by scanning mutagenesis.

Alanine-scanning mutagenesis has been applied to residues 100-121 in transmembrane domain 3 of the M1 muscarinic acetylcholine receptor. This study complements a previous investigation of the triad Asp122-Arg123-Tyr124 (Lu, Z-L., Curtis, C. A., Jones, P. G., Pavia, J., and Hulme, E. C. (1997) Mol. Pharmacol. 51, 234-241). The results demonstrate the alpha-helical secondary structure of the domain and suggest its orientation with respect to the other transmembrane domains. The C-terminal part of the helix appears to be largely buried within the receptor structure. On its surface, there is a patch of three residues, Val113, Leu116, and Ser120, which may form intramolecular contacts that help to stabilize the inactive ground state of the receptor. Mutagenic disruption of these increased agonist affinity and signaling efficacy. In two cases (L116A and S120A), this led to constitutive activation of the receptor. Parallel to the helix axis and spanning the whole transmembrane region, a distinct strip of residues on one face of transmembrane domain 3 forms intermolecular (acetylcholine-receptor, receptor-G protein) or intrareceptor bonds that contribute to the activated state. The binding of acetylcholine may destabilize the first set of contacts while favoring the formation of the second.

Acetylcholine↗

Mechanisms of perceptual learning.

Systematic measurements of perceptual learning were performed in the presence of external or stimulus noise. In the new external noise method (Dosher, B, & Lu, Z.-L. (1997). Investigative Ophthalmology and Visual Science, 38, S687; Lu, Z.-L., & Dosher, B. (1998). Vision Research, 38, 1183-1198), increasing amounts of external noise (white Gaussian random noise) is added to the visual stimulus in order to identify mechanisms of perceptual learning. Performance improved (threshold contrast was reduced) over days of practice on a peripheral orientation discrimination task--labelling Gabor patches as tilted slightly to the right or left. Practice improvements were largely specific to the trained quadrant of the display. Performance improved at all levels of external noise. The external noise method and perceptual template model (PTM) of the observer identifies the mechanism(s) of performance improvements as due to stimulus enhancement, external noise exclusion, or internal noise suppression. The external noise method was further extended by measuring thresholds at two threshold performance levels, allowing identification of mixtures in the PTM model. Perceptual learning over 8-10 days improved the filtering or exclusion of external noise by a factor of two or more, and improved suppression of additive internal noise--equivalent to stimulus enhancement--by 50% or more. Coupled improvements in external noise exclusion and stimulus enhancement in the PTM model may reflect channel weighting. Perceptual learning may not reflect neural plasticity at the level of basic visual channels, nor cognitive adjustments of strategy, but rather plasticity at an intermediate level of weighting inputs to decision.

Discrimination, Psychological↗

Characterizing human perceptual inefficiencies with equivalent internal noise.

A widely used method for characterizing and comparing inefficiencies in perceptual processes is the method of equivalent internal noise--the amount of random internal noise necessary to produce the degree of inefficiency exhibited by the perceptual system in processing [J. Opt. Soc. Am. 46, 634 (1956)]. One normally estimates the amount of equivalent internal noise by systematically increasing the amount of external noise added to the signal stimulus and observing how threshold--signal stimulus energy required for an observer to maintain a given performance level--depends on the amount of external noise. In a variety of perceptual tasks, a simple noisy linear amplifier model [D. Pelli, Ph.D. dissertation (University of Cambridge, Cambridge, UK 1981)] has been utilized to estimate the equivalent internal noise Ninternal by fitting of the relation between threshold contrast c tau and external noise N(ext) at a single (d') performance level: c tau 2 =(d'/beta)2(N(ext)2 + Ninternal2). This model makes a strong prediction: Independent of observer and external noise contrast, the ratio between two thresholds at each external noise level is equal to the ratio of the two corresponding d' values. To our knowledge, this potential test for the internal consistency of the model had never been examined previously. In this study we estimated threshold ratios between multiple performance levels at various external noise contrasts in two different experiments: Gabor orientation identification, and Gabor detection. We found that, in both identification and detection, the observed threshold ratios between different performance levels departed substantially from the d' ratio predicted by the simple noisy linear amplifier model. An elaborated perceptual template model [Vision Res. 38, 1183 (1998)] with nonlinear transducer functions and multiplicative noise in addition to the additive noise in the simple linear amplifier model leads to a substantially better description of the data and suggests a reinterpretation of earlier results that relied on the simple noisy linear amplifier model. The relationship of our model and method to other recent parallel and independent developments [J. Opt. Soc. Am. A 14, 2406 (1997)] is discussed.

Artifacts↗

Second-order reversed phi.

In a first-order reversed-phi motion stimulus (Anstis, 1970), the black-white contrast of successive frames is reversed, and the direction of apparent motion may, under some conditions, appear to be reversed. It is demonstrated here that, for many classes of stimuli, this reversal is a mathematical property of the stimuli themselves, and the real problem is in perceiving forward motion, which involves the second- or third-order motion systems or both. Three classes of novel second-order reversed-phi stimuli (contrast, spatial frequency, and flicker modulation) that are invisible to first-order motion analysis were constructed. In these stimuli, the salient stimulus features move in the forward (feature displacement) direction, but the second-order motion energy model predicts motion in the reversed direction. In peripheral vision, for all stimulus types and all temporal frequencies, all the observers saw only the reversed-phi direction of motion. In central vision, the observers also perceived reversed motion at temporal frequencies above about 4 Hz, but they perceived movement in the forward direction at lower temporal frequencies. Since all of these stimuli are invisible to first-order motion, these results indicate that the second-order reversed-phi stimuli activate two subsequent competing motion mechanisms, both of which involve an initial stage of texture grabbing (spatiotemporal filtering, followed by fullwave rectification). The second-order motion system then applies a Reichardt detector (or equivalently, motion energy analysis) directly to this signal and arrives at the reversed-phi direction. The third-order system marks the location of features that differ from the background (the figure) in a salience map and computes motion in the forward direction from the changes in the spatiotemporal location of these marks. The second-order system's report of reversed movement dominates in peripheral vision and in central vision at higher temporal frequencies, because it has better spatial and temporal resolution than the third-order system, which has a cutoff frequency of 3-4 Hz (Lu & Sperling, 1995b). In central vision, below 3-4 Hz, the third-order system's report of resolvable forward movement of something salient (the figure) dominates the second-order system's report of texture contrast movement.

Adult↗

Brain-wave recognition of sentences.

Electrical and magnetic brain waves of two subjects were recorded for the purpose of recognizing which one of 12 sentences or seven words auditorily presented was processed. The analysis consisted of averaging over trials to create prototypes and test samples, to each of which a Fourier transform was applied, followed by filtering and an inverse transformation to the time domain. The filters used were optimal predictive filters, selected for each subject. A still further improvement was obtained by taking differences between recordings of two electrodes to obtain bipolar pairs that then were used for the same analysis. Recognition rates, based on a least-squares criterion, varied, but the best were above 90%. The first words of prototypes of sentences also were cut and pasted to test, at least partially, the invariance of a word's brain wave in different sentence contexts. The best result was above 80% correct recognition. Test samples made up only of individual trials also were analyzed. The best result was 134 correct of 288 (47%), which is promising, given that the expected recognition number by chance is just 24 (or 8.3%). The work reported in this paper extends our earlier work on brain-wave recognition of words only. The recognition rates reported here further strengthen the case that recordings of electric brain waves of words or sentences, together with extensive mathematical and statistical analysis, can be the basis of new developments in our understanding of brain processing of language.

Adult↗

Perceptual learning reflects external noise filtering and internal noise reduction through channel reweighting.

To investigate the nature of plasticity in the adult visual system, perceptual learning was measured in a peripheral orientation discrimination task with systematically varying amounts of external (environmental) noise. The signal contrasts required to achieve threshold were reduced by a factor or two or more after training at all levels of external noise. The strong quantitative regularities revealed by this novel paradigm ruled out changes in multiplicative internal noise, changes in transducer nonlinearites, and simple attentional tradeoffs. Instead, the regularities specify the mechanisms of perceptual learning at the behavioral level as a combination of external noise exclusion and stimulus enhancement via additive internal noise reduction. The findings also constrain the neural architecture of perceptual learning. Plasticity in the weights between basic visual channels and decision is sufficient to account for perceptual learning without requiring the retuning of visual mechanisms.

Adult↗

External noise distinguishes attention mechanisms.

We developed and tested a powerful method for identifying and characterizing the effect of attention on performance in visual tasks as due to signal enhancement, distractor exclusion, or internal noise suppression. Based on a noisy Perceptual Template Model (PTM) of a human observer, the method adds increasing amounts of external noise (white gaussian random noise) to the visual stimulus and observes the effect on performance of a perceptual task for attended and unattended stimuli. The three mechanisms of attention yield three "signature" patterns of performance. The general framework for characterizing the mechanisms of attention is used here to investigate the attentional mechanisms in a concurrent location-cued orientation discrimination task. Test stimuli--Gabor patches tilted slightly to the right or left--always appeared on both the left and the right of fixation, and varied independently. Observers were cued on each trial to attend to the left, the right, or evenly to both stimuli, and decide the direction of tilt of both test stimuli. For eight levels of added external noise and three attention conditions (attended, unattended, and equal), subjects' contrast threshold levels were determined. At low levels of external noise, attention affected threshold contrast: threshold contrasts for non-attended stimuli were systematically higher than for equal attention stimuli, which were, in turn, higher than for attended stimuli. Specifically, when the rms contrast of the external noise is below 10%, there is a consistent 17% elevation of contrast threshold from attended to unattended condition across all three subjects. For higher levels of external noise, attention conditions did not affect threshold contrast values at all. These strong results are characteristic of a signal enhancement, or equivalently, an internal additive noise reduction mechanism of attention.

Attention↗

Brain wave recognition of words.

Electrical and magnetic brain waves of seven subjects under three experimental conditions were recorded for the purpose of recognizing which one of seven words was processed. The analysis consisted of averaging over trials to create prototypes and test samples, to both of which Fourier transforms were applied, followed by filtering and an inverse transformation to the time domain. The filters used were optimal predictive filters, selected for each subject and condition. Recognition rates, based on a least-squares criterion, varied widely, but all but one of 24 were significantly different from chance. The two best were above 90%. These results show that brain waves carry substantial information about the word being processed under experimental conditions of conscious awareness.

Brain↗

Structure detection: a statistically certified unsupervised learning procedure.

We present a class of structure detection procedures (SDPs) that can extract the characteristic structures in an arbitrary population of images. An SDP adaptively augments the power of a novel, statistical, structure test to reject the null hypothesis that a randomly chosen image is devoid of structure. The core of the structure test consists of an orthonormal basis B of receptive fields that is refined into an increasingly sensitive detector of characteristic image structures. Adaptive refinement is accomplished as follows: for each image x in a random training sequence, B is updated by a planar rotation that decreases the p-value of a statistical structure test for x. This image-by-image refinement procedure is very efficient, obeying time and space constraints similar to those that limit processes of perceptual organization in real organisms. SDPs' capabilities are demonstrated in three test populations: natural images, faulty random number generators, and artificial images composed of mixtures of basis functions. (1) An SDP succeeds in rejecting the null hypothesis that the UNIX random number generator rand() is truly random. (2) When images are composed by adding arbitrary pairs of orthogonal component images, an SDP extracts the components. (3) For a large set of natural image patches, an SDP yields a basis B1 that detects structure with p-value < 0.005 in 88% of a new set of patches. B1's elements resemble the receptive fields of V1 simple cells. (4) Of special interest are biconvergent SDPs that derive in parallel a basis B, as well as a pointwise transformation f, specifically sensitized to evaluate the response values that result from applying B to images in the target population. A biconvergent SDP applied to natural image patches yields a basis B2 similar to B1, as well as a pointwise transformation f with vastly heightened sensitivity to extreme response values. We conjecture that sensory neurons have evolved cooperatively to maximize their collective power to reject the null hypothesis that their input is devoid of structure, thereby evolving receptive fields that efficiently represent characteristic input structures.

Form Perception↗

Study of human occipital alpha rhythm: the alphon hypothesis and alpha suppression.

Alpha rhythm of the parieto-occipital area is comprised of a parade of short-lived cortical excitations (alphons), each of which exhibits oscillations having a stable period within the alpha bandwidth. Strong alpha rhythm is produced by alphons extending over a larger cortical area, although an enhanced cortical current density may also contribute. Local suppression of alpha rhythm indicates when specific cortical areas become engaged in sensory or cognitive functions. Examples are provided for mental imagery, visual memory, auditory memory, and silent rhythming.

Alpha Rhythm↗

The role of the aspartate-arginine-tyrosine triad in the m1 muscarinic receptor: mutations of aspartate 122 and tyrosine 124 decrease receptor expression but do not abolish signaling.

An Asp-Arg-Tyr triad occurs in a majority of rhodopsin-like G protein-coupled receptors. The fully conserved Arg is critical for G protein activation, but the function of the flanking residues is not well understood. We expressed in COS-7 cells m1 muscarinic receptors that were mutated at Asp122 and Tyr124. Most mutations at either position strongly attenuated or prevented the expression of binding sites for the antagonist [3H]N-methylscopolamine. However, sites that were expressed displayed unaltered affinity for the antagonist. Receptor protein, visualized with a carboxyl-terminally directed antibody, was reduced but never completely abolished. The effects of these mutations were partially reversed by the deletion of 129 amino acids from the third intracellular loop of the receptor. In several cases, comparison of immunocytochemistry with binding measurements suggested the presence of substantial amounts of inactive, presumably misfolded, receptor protein. Some of the variants that bound [3H]N-methylscopolamine underwent small changes in their affinities for acetylcholine. All retained nearly normal abilities to mediate an acetylcholine-induced phosphoinositide response. We propose that Asp122 and Tyr124 make intramolecular contacts whose integrity is important for efficient receptor folding but that they do not participate directly in signaling. The role of these residues is completely distinct from that of Arg123, whose mutation abolishes signaling without diminishing receptor expression.

Acetylcholine↗

Determination of benflumetol in human plasma by reversed-phase high-performance liquid chromatography with ultraviolet detection.

A reversed-phase high-performance liquid chromatographic method for the determination of benflumetol in human plasma is described. Benflumetol in plasma samples was extracted with a glacial acetic acid-ethyl acetate (1:100, v/v) mixture at pH 4.0. Chromatography was performed on a Spherisorb C18 column using a methanol-water-glacial acetic acid-diethyl amine (93:6:1:0.03, v/v) mixture as the mobile phase and UV-VIS detection at 335 nm. The identity and purity of the benflumetol peak were carefully examined, and the internal standard method was applied for its quantitation. The absolute recovery of benflumetol in spiked plasma samples was 92.91% over the concentration range 5-4000 ng/ml. The recovery of internal standard "8212" at a concentration of 300 ng/ml in spiked plasma was 84.85%. The detection limit of benflumetol was 11.8 ng/ml. Plasma concentration-time profiles in healthy volunteer adults were measured after a single-dose oral administration of 500 mg of benflumetol. The assay procedures were within the quality control limits.

Acetic Acid↗

The value of Tc-99m MIBI SPECT during isosorbide dinitrate infusion in assessment of viable myocardium in patients with myocardial infarction.

Tc-99m MIBI myocardial SPECT has shown promise for evaluation of coronary artery disease. But its role in predicting myocardial viability is still under investigation. The purpose of this study was to evaluate the value of Tc-99m MIBI myocardial SPECT during isosorbide dinitrate (ISDN) infusion in the assessment of myocardial viability. Thirty-seven patients with previous myocardial infarction (the infarct age ranged from < or = 30 days to 900 days) were studied, of them 13 patients had Tc-99m MIBI studies before and after coronary artery bypass grafting (CABG). The results showed that out of 134 segments with hypoperfusion at resting SPECT, 56 segments (41.8%) had an increase in Tc-99m MIBI uptake during ISDN infusion. Among them, 17 segments (30.4%) were normalized, 6 segments (10.7%) were significantly improved and 33 segments (58.9%) were improved. The degree of improvement in perfusion was related to the age of the myocardial infarction. In 13 patients with CABG, of 31 segments with improvement in perfusion post CABG, 25 segments (80.6%) showed perfusion improvement during ISDN infusion, and of 28 segments with improved wall motion post CABG, 23 segments (82.1%) showed improvement in perfusion during ISDN infusion. Tc-99m MIBI SPECT during ISDN infusion may therefore be a useful approach for assessing myocardial viability.

Adult↗

Second-order illusions: Mach bands, Chevreul, and Craik--O'Brien--Cornsweet.

Mach bands, which normally occur at the edges of ramp modulations of luminance, are demonstrated to occur in fullwave stimuli that have ramp modulations of contrast while maintaining constant expected luminance. [The fullwave stimuli are random textures that (1) have a ramp contrast modulation that is exposed by fullwave rectification (e.g. absolute value or square) or by halfwave rectification but (2) have a uniform expected luminance throughout, so the modulation remains hidden without rectification.] Two different textures were used: random pixels and 'Mexican hats'. Stimuli were presented dynamically, with a new instantiation of the texture every 67 msec (this enhances the magnitude of the illusion). Both fullwave Mach-band stimuli exhibit perceptual Mach bands that are decreases or increases in apparent texture contrast with no concomitant change in apparent brightness. The perceived contrast bands in fullwave Mach stimuli and the brightness bands in a conventional luminance Mach-band stimulus have approximately the same magnitude. Chevreul (staircase) illusions in luminance and in fullwave patterns also are found to have approximately similar magnitudes, as do luminance and fullwave Craik--O'Brien--Cornsweet illusions. None of these illusions can be perceived with halfwave textures. These results indicate that second-order (texture) illusions result from fullwave, not halfwave, rectification and involve spatial interactions that are remarkably similar to those in first-order (luminance) processing.

Contrast Sensitivity↗

Contrast gain control in first- and second-order motion perception.

A novel pedestal-plus-test paradigm is used to determine the nonlinear gain-control properties of the first-order (luminance) and the second-order (texture-contrast) motion systems, that is, how these systems' responses to motion stimuli are reduced by pedestals and other masking stimuli. Motion-direction thresholds were measured for test stimuli consisting of drifting luminance and texture-contrast-modulation stimuli superimposed on pedestals of various amplitudes. (A pedestal is a static sine-wave grating of the same type and same spatial frequency as the moving test grating.) It was found that first-order motion-direction thresholds are unaffected by small pedestals, but at pedestal contrasts above 1-2% (5-10 x pedestal threshold), motion thresholds increase proportionally to pedestal amplitude (a Weber law). For first-order stimuli, pedestal masking is specific to the spatial frequency of the test. On the other hand, motion-direction thresholds for texture-contrast stimuli are independent of pedestal amplitude (no gain control whatever) throughout the accessible pedestal amplitude range (from 0 to 40%). However, when baseline carrier contrast increases (with constant pedestal modulation amplitude), motion thresholds increase, showing that gain control in second-order motion is determined not by the modulator (as in first-order motion) but by the carrier. Note that baseline contrast of the carrier is inherently independent of spatial frequency of the modulator. The drastically different gain-control properties of the two motion systems and prior observations of motion masking and motion saturation are all encompassed in a functional theory. The stimulus inputs to both first- and second-order motion process are normalized by feedforward, shunting gain control. The different properties arise because the modulator is used to control the first-order gain and the carrier is used to control the second-order gain.

Contrast Sensitivity↗