Alzheimer's disease Part 2: visual changes

This article describes the pathological changes that have been observed in different parts of the visual system in Alzheimer's disease as well as the visual symptoms which may result from these changes.

Sun and sky:does human vision assume a mixture of point and diffuse illumination when interpreting shape-from-shading?

People readily perceive smooth luminance variations as being due to the shading produced by undulations of a 3-D surface (shape-from-shading). In doing so, the visual system must simultaneously estimate the shape of the surface and the nature of the illumination. Remarkably, shape-from-shading operates even when both these properties are unknown and neither can be estimated directly from the image. In such circumstances humans are thought to adopt a default illumination model. A widely held view is that the default illuminant is a point source located above the observer's head. However, some have argued instead that the default illuminant is a diffuse source. We now present evidence that humans may adopt a flexible illumination model that includes both diffuse and point source elements. Our model estimates a direction for the point source and then weights the contribution of this source according to a bias function. For most people the preferred illuminant direction is overhead with a strong diffuse component.

The influence of age on the pattern and flash visual evoked field

We have investigated the effect of ageing on the visual system using the relatively new technique of magentoencephalography (MEG). This technique measures the magnetic signals produced by the visual system using a SQUID magnetometer. The magnetic visual evoked field (VEF) was measured over the occipital cortex to pattern and flash stimuli in 86 normal subjects aged 15 - 86 years. Factors that influenced subject defocussing or defixating the stimulus or selective attention were controlled as far as possible. The latency of the major positive component to the pattern reversal stimulus (P100M) increased with age particularly after the age of 55 years while the amplitude of the P100M decreased over the life span. The latency of the major flash component (P2M) increased much more slowly with age, while its amplitude decreased in only a proportion of elderly subjects. Changes in the P100M with age may reflect senile changes in the eye and optic nerve, e.g. senile miosis or degenerative changes in the retina. The P2M may be more susceptible to senile changes in the retina. The data suggest that the spatial frequency channels deteriorate more rapidly with age than the luminance channels and that MEG may be an effective method of studying ageing in the visual system.

Topography of visual evoked magnetic responses to pattern shift, pattern onset and flash stimuli

Different visual stimuli may activate separate channels in the visual system and produce magnetic responses from the human bran which originate from distinct regions of the visual cortex. To test this hypothesis, we have investigated the distribution of visual evoked magnetic responses to three distinct visual stimuli over the occipital region of the scalp with a DC-SQUID second-order gradiometer in an ubshielded environment. Patterned stimuli were presented full field and to the right half field, while a flash stimulus was presented full field only, in five normal subjects. Magnetic responses were recorded from 20 to 42 positions over the occipital scalp. Topographic maps were prepared of the major positive component within the first 150ms to the three stimuli, i.e., the P100m (pattern shift), C11m (pattern onset) and P2m (flash). For the pattern shift stimulus the data suggested the source of the P100m was close to the midline with the current directed towards the medial surface. The data for the pattern onset C11m suggested a source at a similar depth but with the current directed away from the midline towards the lateral surface. The flash P2m appeared to originate closer to the surface of the occipital pole than both the patterned stimuli. Hence the pattern shift (which may represent movement), and the pattern onset C11m (representing contrast and contour) appear to originate in similar areas of brain but to represent different asepcts of cortical processing. By contrast, the flash P2m (representing luminance change) appears to originate in a distinct area of visual cortex closer to the occipital pole.

Magnetoencephalography:technical improvements in image co-registration and studies of visual cortical oscillations

The work presented in this thesis is divided into two distinct sections. In the first, the functional neuroimaging technique of Magnetoencephalography (MEG) is described and a new technique is introduced for accurate combination of MEG and MRI co-ordinate systems. In the second part of this thesis, MEG and the analysis technique of SAM are used to investigate responses of the visual system in the context of functional specialisation within the visual cortex. In chapter one, the sources of MEG signals are described, followed by a brief description of the necessary instrumentation for accurate MEG recordings. This chapter is concluded by introducing the forward and inverse problems of MEG, techniques to solve the inverse problem, and a comparison of MEG with other neuroimaging techniques. Chapter two provides an important contribution to the field of research with MEG. Firstly, it is described how MEG and MRI co-ordinate systems are combined for localisation and visualisation of activated brain regions. A previously used co-registration methods is then described, and a new technique is introduced. In a series of experiments, it is demonstrated that using fixed fiducial points provides a considerable improvement in the accuracy and reliability of co-registration. Chapter three introduces the visual system starting from the retina and ending with the higher visual rates. The functions of the magnocellular and the parvocellular pathways are described and it is shown how the parallel visual pathways remain segregated throughout the visual system. The structural and functional organisation of the visual cortex is then described. Chapter four presents strong evidence in favour of the link between conscious experience and synchronised brain activity. The spatiotemporal responses of the visual cortex are measured in response to specific gratings. It is shown that stimuli that induce visual discomfort and visual illusions share their physical properties with those that induce highly synchronised gamma frequency oscillations in the primary visual cortex. Finally chapter five is concerned with localization of colour in the visual cortex. In this first ever use of Synthetic Aperture Magnetometry to investigate colour processing in the visual cortex, it is shown that in response to isoluminant chromatic gratings, the highest magnitude of cortical activity arise from area V2.

Edge coding in human vision: a psychophysical and computational investigation

This thesis presents a study of how edges are detected and encoded by the human visual system. The study begins with theoretical work on the development of a model of edge processing, and includes psychophysical experiments on humans, and computer simulations of these experiments, using the model. The first chapter reviews the literature on edge processing in biological and machine vision, and introduces the mathematical foundations of this area of research. The second chapter gives a formal presentation of a model of edge perception that detects edges and characterizes their blur, contrast and orientation, using Gaussian derivative templates. This model has previously been shown to accurately predict human performance in blur matching tasks with several different types of edge profile. The model provides veridical estimates of the blur and contrast of edges that have a Gaussian integral profile. Since blur and contrast are independent parameters of Gaussian edges, the model predicts that varying one parameter should not affect perception of the other. Psychophysical experiments showed that this prediction is incorrect: reducing the contrast makes an edge look sharper; increasing the blur reduces the perceived contrast. Both of these effects can be explained by introducing a smoothed threshold to one of the processing stages of the model. It is shown that, with this modification,the model can predict the perceived contrast and blur of a number of edge profiles that differ markedly from the ideal Gaussian edge profiles on which the templates are based. With only a few exceptions, the results from all the experiments on blur and contrast perception can be explained reasonably well using one set of parameters for each subject. In the few cases where the model fails, possible extensions to the model are discussed.

Effects of pixel noise and stimulus structure on visual detection performance

This thesis consisted of two major parts, one determining the masking characteristics of pixel noise and the other investigating the properties of the detection filter employed by the visual system. The theoretical cut-off frequency of white pixel noise can be defined from the size of the noise pixel. The empirical cut-off frequency, i.e. the largest size of noise pixels that mimics the effect of white noise in detection, was determined by measuring contrast energy thresholds for grating stimuli in the presence of spatial noise consisting of noise pixels of various sizes and shapes. The critical i.e. minimum number of noise pixels per grating cycle needed to mimic the effect of white noise in detection was found to decrease with the bandwidth of the stimulus. The shape of the noise pixels did not have any effect on the whiteness of pixel noise as long as there was at least the minimum number of noise pixels in all spatial dimensions. Furthermore, the masking power of white pixel noise is best described when the spectral density is calculated by taking into account all the dimensions of noise pixels, i.e. width, height, and duration, even when there is random luminance only in one of these dimensions. The properties of the detection mechanism employed by the visual system were studied by measuring contrast energy thresholds for complex spatial patterns as a function of area in the presence of white pixel noise. Human detection efficiency was obtained by comparing human performance with an ideal detector. The stimuli consisted of band-pass filtered symbols, uniform and patched gratings, and point stimuli with randomised phase spectra. In agreement with the existing literature, the detection performance was found to decline with the increasing amount of detail and contour in the stimulus. A measure of image complexity was developed and successfully applied to the data. The accuracy of the detection mechanism seems to depend on the spatial structure of the stimulus and the spatial spread of contrast energy.

Contrast matching and discrimation in human vision

The aim of this work was to investigate human contrast perception at various contrast levels ranging from detection threshold to suprathreshold levels by using psychophysical techniques. The work consists of two major parts. The first part deals with contrast matching, and the second part deals with contrast discrimination. Contrast matching technique was used to determine when the perceived contrasts of different stimuli were equal. The effects of spatial frequency, stimulus area, image complexity and chromatic contrast on contrast detection thresholds and matches were studied. These factors influenced detection thresholds and perceived contrast at low contrast levels. However, at suprathreshold contrast levels perceived contrast became directly proportional to the physical contrast of the stimulus and almost independent of factors affecting detection thresholds. Contrast discrimination was studied by measuring contrast increment thresholds which indicate the smallest detectable contrast difference. The effects of stimulus area, external spatial image noise and retinal illuminance were studied. The above factors affected contrast detection thresholds and increment thresholds measured at low contrast levels. At high contrast levels, contrast increment thresholds became very similar so that the effect of these factors decreased. Human contrast perception was modelled by regarding the visual system as a simple image processing system. A visual signal is first low-pass filtered by the ocular optics. This is followed by spatial high-pass filtering by the neural visual pathways, and addition of internal neural noise. Detection is mediated by a local matched filter which is a weighted replica of the stimulus whose sampling efficiency decreases with increasing stimulus area and complexity. According to the model, the signals to be compared in a contrast matching task are first transferred through the early image processing stages mentioned above. Then they are filtered by a restoring transfer function which compensates for the low-level filtering and limited spatial integration at high contrast levels. Perceived contrasts of the stimuli are equal when the restored responses to the stimuli are equal. According to the model, the signals to be discriminated in a contrast discrimination task first go through the early image processing stages, after which signal dependent noise is added to the matched filter responses. The decision made by the human brain is based on the comparison between the responses of the matched filters to the stimuli, and the accuracy of the decision is limited by pre- and post-filter noises. The model for human contrast perception could accurately describe the results of contrast matching and discrimination in various conditions.

The chromatic visual evoked response as an indication of visual development

In an endeavour to provide further insight into the maturation of the cortical visual system in human infants, chromatic transient pattern reversal visual evoked potentials to red/green stimuli, were studied in a group of normal full term infants between the ages of 1 and 14 weeks post term in both cross sectional and longitudinal studies. In order to produce stimuli in which luminance cues had been eliminated with an aim to eliciting a chromatic response, preliminary studies of isoluminance determination in adults and infants were undertaken using behavioural and electrophysiological techniques. The results showed close similarity between the isoluminant ratio for adults and infants and all values were close to photometric isoluminance. Pattern reversal VEPs were recorded to stimuli of a range of red/green luminance ratios and an achromatic checkerboard. No transient VEP could be elicited with an isoluminant chromatic pattern reversal stimulus from any infant less than 7 weeks post term and similarly, all infants more than 7 weeks post term showed clear chromatic VEPs. The chromatic response first appeared at that age as a major positive component (P1) of long latency. This was delayed and reduced in comparison to the achromatic response. As the infant grew older, the latency of the P1 component decreased with the appearance of N1 and N by the 10th week post term. This finding was consistent throughout all infants assessed. In a behavioural study, no infant less than 7 weeks post term demonstrated clear discrimination of the chromatic stimulus, while those infants older than 7 weeks could do so. These findings are reviewed with respect to current neural models of visual development.

The visually evoked magnetic response (VEMR) to a pattern onset/offset stimulus

This study characterizes the visually evoked magnetic response (VEMR) to pattern onset/offset stimuli, using a single channel BTi magnetometer. The influence of stimulus parameters and recording protocols on the VEMR is studied with inferences drawn about the nature of cortical processing, its origins and optimal recording strategies. Fundamental characteristics are examined, such as the behaviour of successive averaged and unaveraged responses; the effects of environmental shielding; averaging; inter- and intrasubject variability and equipment specificity. The effects of varying check size, field size, contrast and refractive error on latency, amplitude and topographic distribution are also presented. Latency and amplitude trends are consistent with previous VEP findings and known anatomical properties of the visual system. Topographic results are consistent with the activity of sources organised according to the cruciform model of striate cortex. A striate origin for the VEMR is also suggested by the results to quarter, octant and annulus field stimuli. Similarities in the behaviour and origins of the sources contributing to the CIIm and CIIIm onset peaks are presented for a number of stimulus conditions. This would be consistent with differing processing event in the same, or similar neuronal populations. Focal field stimuli produce less predictable responses than full or half fields, attributable to a reduced signal to noise ratio and an increased sensitivity to variations in cortical morphology. Problems with waveform peak identification are encountered for full field stimuli that can only be resolved by the careful choice of stimulus parameters, comparisons with half field responses or with reference to the topographic distribution of each waveform peak. An anatomical study of occipital lobe morphology revealed large inter- and intrasubject variation in calcarine fissure shape and striate cortex distribution. An appreciation of such variability is important for VEMR interpretation, due to the technique's sensitivity to source depth and orientation, and it is used to explain the experimental results obtained.

Contrast sensitivity for complex and random gratings

This thesis studied the effect of (i) the number of grating components and (ii) parameter randomisation on root-mean-square (r.m.s.) contrast sensitivity and spatial integration. The effectiveness of spatial integration without external spatial noise depended on the number of equally spaced orientation components in the sum of gratings. The critical area marking the saturation of spatial integration was found to decrease when the number of components increased from 1 to 5-6 but increased again at 8-16 components. The critical area behaved similarly as a function of the number of grating components when stimuli consisted of 3, 6 or 16 components with different orientations and/or phases embedded in spatial noise. Spatial integration seemed to depend on the global Fourier structure of the stimulus. Spatial integration was similar for sums of two vertical cosine or sine gratings with various Michelson contrasts in noise. The critical area for a grating sum was found to be a sum of logarithmic critical areas for the component gratings weighted by their relative Michelson contrasts. The human visual system was modelled as a simple image processor where the visual stimuli is first low-pass filtered by the optical modulation transfer function of the human eye and secondly high-pass filtered, up to the spatial cut-off frequency determined by the lowest neural sampling density, by the neural modulation transfer function of the visual pathways. The internal noise is then added before signal interpretation occurs in the brain. The detection is mediated by a local spatially windowed matched filter. The model was extended to include complex stimuli and its applicability to the data was found to be successful. The shape of spatial integration function was similar for non-randomised and randomised simple and complex gratings. However, orientation and/or phase randomised reduced r.m.s contrast sensitivity by a factor of 2. The effect of parameter randomisation on spatial integration was modelled under the assumption that human observers change the observer strategy from cross-correlation (i.e., a matched filter) to auto-correlation detection when uncertainty is introduced to the task. The model described the data accurately.

Electrophysiological studies of the visual pathways in Alzheimer's and Parkinson's disease

It is known that parallel pathways exist within the visual system. These have been described as magnocellular and parvocellular as a result of the layered organisation of the lateral geniculate nucleus and extend from the retina to the cortex. Dopamine (DA) and acetylcholine (ACH) are neurotransmitters that are present in the visual pathway. DA is present in the retina and is associated with the interplexiform cells and horizontal cells. ACH is also present in the retina and is associated with displaced amacrine cells; it is also present in the superior colliculus. DA is found to be significantly depleted in the brain of Parkinson's disease (PD) patients and ACH in Alzheimer's disease (AD) patients. For this reason these diseases were used to assess the function of DA and ACH in the electrophysiology of the visual pathway. Experiments were conducted on young normals to design stimuli that would preferentially activate the magnocellular or parvocellular pathway. These stimuli were then used to evoke visual evoked potentials (VEP) in patients with PD and AD, in order to assess the function of DA and ACH in the visual pathway. Electroretinograms (ERGs) were also measured in PD patients to assess the role of DA in the retina. In addition, peripheral ACH function was assessed by measuring VEPs, ERGs and contrast sensitivity (CS) in young normals following the topical instillation of hyoscine hydrobromide (an anticholinergic drug). The results indicate that the magnocellular pathway can be divided into two: a cholinergic tectal-association area pathway carrying luminance information, and a non-cholinergic geniculo-cortical pathway carrying spatial information. It was also found that depletion of DA had very little effect on the VEPs or ERGs, confirming a general regulatory function for this neurotransmitter.

The development and stability analysis of a nonlinear growth model for microorganisms

A nonlinear dynamic model of microbial growth is established based on the theories of the diffusion response of thermodynamics and the chemotactic response of biology. Except for the two traditional variables, i.e. the density of bacteria and the concentration of attractant, the pH value, a crucial influencing factor to the microbial growth, is also considered in this model. The pH effect on the microbial growth is taken as a Gaussian function G0e-(f- fc)2/G1, where G0, G1 and fc are constants, f represents the pH value and fc represents the critical pH value that best fits for microbial growth. To study the effects of the reproduction rate of the bacteria and the pH value on the stability of the system, three parameters a, G0 and G1 are studied in detail, where a denotes the reproduction rate of the bacteria, G0 denotes the impacting intensity of the pH value to microbial growth and G1 denotes the bacterial adaptability to the pH value. When the effect of the pH value of the solution which microorganisms live in is ignored in the governing equations of the model, the microbial system is more stable with larger a. When the effect of the bacterial chemotaxis is ignored, the microbial system is more stable with the larger G1 and more unstable with the larger G0 for f0 > fc. However, the stability of the microbial system is almost unaffected by the variation G0 and G1 and it is always stable for f0 < fc under the assumed conditions in this paper. In the whole system model, it is more unstable with larger G1 and more stable with larger G0 for f0 < fc. The system is more stable with larger G1 and more unstable with larger G0 for f0 > fc. However, the system is more unstable with larger a for f0 < fc and the stability of the system is almost unaffected by a for f0 > fc. The results obtained in this study provide a biophysical insight into the understanding of the growth and stability behavior of microorganisms.

Paradoxical psychometric functions ("swan functions") are explained by dilution masking in four stimulus dimensions

The visual system dissects the retinal image into millions of local analyses along numerous visual dimensions. However, our perceptions of the world are not fragmentary, so further processes must be involved in stitching it all back together. Simply summing up the responses would not work because this would convey an increase in image contrast with an increase in the number of mechanisms stimulated. Here, we consider a generic model of signal combination and counter-suppression designed to address this problem. The model is derived and tested for simple stimulus pairings (e.g. A + B), but is readily extended over multiple analysers. The model can account for nonlinear contrast transduction, dilution masking, and signal combination at threshold and above. It also predicts nonmonotonic psychometric functions where sensitivity to signal A in the presence of pedestal B first declines with increasing signal strength (paradoxically dropping below 50% correct in two-interval forced choice), but then rises back up again, producing a contour that follows the wings and neck of a swan. We looked for and found these "swan" functions in four different stimulus dimensions (ocularity, space, orientation, and time), providing some support for our proposal.

Design and validity of a miniaturized open-field aberrometer

PURPOSE: To validate a new miniaturised, open-field wavefront device which has been developed with the capacity to be attached to an ophthalmic surgical microscope or slit-lamp. SETTING: Solihull Hospital and Aston University, Birmingham, UK DESIGN: Comparative non-interventional study. METHODS: The dynamic range of the Aston Aberrometer was assessed using a calibrated model eye. The validity of the Aston Aberrometer was compared to a conventional desk mounted Shack-Hartmann aberrometer (Topcon KR1W) by measuring the refractive error and higher order aberrations of 75 dilated eyes with both instruments in random order. The Aston Aberrometer measurements were repeated five times to assess intra-session repeatability. Data was converted to vector form for analysis. RESULTS: The Aston Aberrometer had a large dynamic range of at least +21.0 D to -25.0 D. It gave similar measurements to a conventional aberrometer for mean spherical equivalent (mean difference ± 95% confidence interval: 0.02 ± 0.49D; correlation: r=0.995, p<0.001), astigmatic components (J0: 0.02 ± 0.15D; r=0.977, p<0.001; J45: 0.03 ± 0.28; r=0.666, p<0.001) and higher order aberrations RMS (0.02 ± 0.20D; r=0.620, p<0.001). Intraclass correlation coefficient assessments of intra-sessional repeatability for the Aston Aberrometer were excellent (spherical equivalent =1.000, p<0.001; astigmatic components J0 =0.998, p<0.001, J45=0.980, p<0.01; higher order aberrations RMS =0.961, p<0.001). CONCLUSIONS: The Aston Aberrometer gives valid and repeatable measures of refractive error and higher order aberrations over a large range. As it is able to measure continuously, it can provide direct feedback to surgeons during intraocular lens implantations and corneal surgery as to the optical status of the visual system.