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.

Modulation of long-range neural synchrony reflects temporal limitations of visual attention in humans

Because of attentional limitations, the human visual system can process for awareness and response only a fraction of the input received. Lesion and functional imaging studies have identified frontal, temporal, and parietal areas as playing a major role in the attentional control of visual processing, but very little is known about how these areas interact to form a dynamic attentional network. We hypothesized that the network communicates by means of neural phase synchronization, and we used magnetoencephalography to study transient long-range interarea phase coupling in a well studied attentionally taxing dual-target task (attentional blink). Our results reveal that communication within the fronto-parieto-temporal attentional network proceeds via transient long-range phase synchronization in the beta band. Changes in synchronization reflect changes in the attentional demands of the task and are directly related to behavioral performance. Thus, we show how attentional limitations arise from the way in which the subsystems of the attentional network interact. The human brain faces an inestimable task of reducing a potentially overloading amount of input into a manageable flow of information that reflects both the current needs of the organism and the external demands placed on it. This task is accomplished via a ubiquitous construct known as “attention,” whose mechanism, although well characterized behaviorally, is far from understood at the neurophysiological level. Whereas attempts to identify particular neural structures involved in the operation of attention have met with considerable success (1-5) and have resulted in the identification of frontal, parietal, and temporal regions, far less is known about the interaction among these structures in a way that can account for the task-dependent successes and failures of attention. The goal of the present research was, thus, to unravel the means by which the subsystems making up the human attentional network communicate and to relate the temporal dynamics of their communication to observed attentional limitations in humans. A prime candidate for communication among distributed systems in the human brain is neural synchronization (for review, see ref. 6). Indeed, a number of studies provide converging evidence that long-range interarea communication is related to synchronized oscillatory activity (refs. 7-14; for review, see ref. 15). To determine whether neural synchronization plays a role in attentional control, we placed humans in an attentionally demanding task and used magnetoencephalography (MEG) to track interarea communication by means of neural synchronization. In particular, we presented 10 healthy subjects with two visual target letters embedded in streams of 13 distractor letters, appearing at a rate of seven per second. The targets were separated in time by a single distractor. This condition leads to the “attentional blink” (AB), a well studied dual-task phenomenon showing the reduced ability to report the second of two targets when an interval <500 ms separates them (16-18). Importantly, the AB does not prevent perceptual processing of missed target stimuli but only their conscious report (19), demonstrating the attentional nature of this effect and making it a good candidate for the purpose of our investigation. Although numerous studies have investigated factors, e.g., stimulus and timing parameters, that manipulate the magnitude of a particular AB outcome, few have sought to characterize the neural state under which “standard” AB parameters produce an inability to report the second target on some trials but not others. We hypothesized that the different attentional states leading to different behavioral outcomes (second target reported correctly or not) are characterized by specific patterns of transient long-range synchronization between brain areas involved in target processing. Showing the hypothesized correspondence between states of neural synchronization and human behavior in an attentional task entails two demonstrations. First, it needs to be demonstrated that cortical areas that are suspected to be involved in visual-attention tasks, and the AB in particular, interact by means of neural synchronization. This demonstration is particularly important because previous brain-imaging studies (e.g., ref. 5) only showed that the respective areas are active within a rather large time window in the same task and not that they are concurrently active and actually create an interactive network. Second, it needs to be demonstrated that the pattern of neural synchronization is sensitive to the behavioral outcome; specifically, the ability to correctly identify the second of two rapidly succeeding visual targets

Binocular contrast vision at and above threshold

A fundamental problem for any visual system with binocular overlap is the combination of information from the two eyes. Electrophysiology shows that binocular integration of luminance contrast occurs early in visual cortex, but a specific systems architecture has not been established for human vision. Here, we address this by performing binocular summation and monocular, binocular, and dichoptic masking experiments for horizontal 1 cycle per degree test and masking gratings. These data reject three previously published proposals, each of which predict too little binocular summation and insufficient dichoptic facilitation. However, a simple development of one of the rejected models (the twin summation model) and a completely new model (the two-stage model) provide very good fits to the data. Two features common to both models are gently accelerating (almost linear) contrast transduction prior to binocular summation and suppressive ocular interactions that contribute to contrast gain control. With all model parameters fixed, both models correctly predict (1) systematic variation in psychometric slopes, (2) dichoptic contrast matching, and (3) high levels of binocular summation for various levels of binocular pedestal contrast. A review of evidence from elsewhere leads us to favor the two-stage model. © 2006 ARVO.

Natural images dominate in binocular rivalry

Ecological approaches to perception have demonstrated that information encoding by the visual system is informed by the natural environment, both in terms of simple image attributes like luminance and contrast, and more complex relationships corresponding to Gestalt principles of perceptual organization. Here, we ask if this optimization biases perception of visual inputs that are perceptually bistable. Using the binocular rivalry paradigm, we designed stimuli that varied in either their spatiotemporal amplitude spectra or their phase spectra. We found that noise stimuli with “natural” amplitude spectra (i.e., amplitude content proportional to 1/f, where f is spatial or temporal frequency) dominate over those with any other systematic spectral slope, along both spatial and temporal dimensions. This could not be explained by perceived contrast measurements, and occurred even though all stimuli had equal energy. Calculating the effective contrast following attenuation by a model contrast sensitivity function suggested that the strong contrast dependency of rivalry provides the mechanism by which binocular vision is optimized for viewing natural images. We also compared rivalry between natural and phase-scrambled images and found a strong preference for natural phase spectra that could not be accounted for by observer biases in a control task. We propose that this phase specificity relates to contour information, and arises either from the activity of V1 complex cells, or from later visual areas, consistent with recent neuroimaging and single-cell work. Our findings demonstrate that human vision integrates information across space, time, and phase to select the input most likely to hold behavioral relevance.

Interocular suppression and contrast gain control in human vision

The human visual system combines contrast information from the two eyes to produce a single cyclopean representation of the external world. This task requires both summation of congruent images and inhibition of incongruent images across the eyes. These processes were explored psychophysically using narrowband sinusoidal grating stimuli. Initial experiments focussed on binocular interactions within a single detecting mechanism, using contrast discrimination and contrast matching tasks. Consistent with previous findings, dichoptic presentation produced greater masking than monocular or binocular presentation. Four computational models were compared, two of which performed well on all data sets. Suppression between mechanisms was then investigated, using orthogonal and oblique stimuli. Two distinct suppressive pathways were identified, corresponding to monocular and dichoptic presentation. Both pathways impact prior to binocular summation of signals, and differ in their strengths, tuning, and response to adaptation, consistent with recent single-cell findings in cat. Strikingly, the magnitude of dichoptic masking was found to be spatiotemporally scale invariant, whereas monocular masking was dependent on stimulus speed. Interocular suppression was further explored using a novel manipulation, whereby stimuli were presented in dichoptic antiphase. Consistent with the predictions of a computational model, this produced weaker masking than in-phase presentation. This allowed the bandwidths of suppression to be measured without the complicating factor of additive combination of mask and test. Finally, contrast vision in strabismic amblyopia was investigated. Although amblyopes are generally believed to have impaired binocular vision, binocular summation was shown to be intact when stimuli were normalized for interocular sensitivity differences. An alternative account of amblyopia was developed, in which signals in the affected eye are subject to attenuation and additive noise prior to binocular combination.

Blur adaptation explained by a norm-based model of contrast adaptation

Adapting to blurred images makes in-focus images look too sharp, and vice-versa (Webster et al, 2002 Nature Neuroscience 5 839 - 840). We asked how such blur adaptation is related to contrast adaptation. Georgeson (1985 Spatial Vision 1 103 - 112) found that grating contrast adaptation followed a subtractive rule: perceived (matched) contrast of a grating was fairly well predicted by subtracting some fraction k(~0.3) of the adapting contrast from the test contrast. Here we apply that rule to the responses of a set of spatial filters at different scales and orientations. Blur is encoded by the pattern of filter response magnitudes over scale. We tested two versions - the 'norm model' and 'fatigue model' - against blur-matching data obtained after adaptation to sharpened, in-focus or blurred images. In the fatigue model, filter responses are simply reduced by exposure to the adapter. In the norm model, (a) the visual system is pre-adapted to a focused world and (b) discrepancy between observed and expected responses to the experimental adapter leads to additional reduction (or enhancement) of filter responses during experimental adaptation. The two models are closely related, but only the norm model gave a satisfactory account of results across the four experiments analysed, with one free parameter k. This model implies that the visual system is pre-adapted to focused images, that adapting to in-focus or blank images produces no change in adaptation, and that adapting to sharpened or blurred images changes the state of adaptation, leading to changes in perceived blur or sharpness.

Blurred edges look faint, and faint edges look sharp:The effect of a gradient threshold in a multi-scale edge coding model

A multi-scale model of edge coding based on normalized Gaussian derivative filters successfully predicts perceived scale (blur) for a wide variety of edge profiles [Georgeson, M. A., May, K. A., Freeman, T. C. A., & Hesse, G. S. (in press). From filters to features: Scale-space analysis of edge and blur coding in human vision. Journal of Vision]. Our model spatially differentiates the luminance profile, half-wave rectifies the 1st derivative, and then differentiates twice more, to give the 3rd derivative of all regions with a positive gradient. This process is implemented by a set of Gaussian derivative filters with a range of scales. Peaks in the inverted normalized 3rd derivative across space and scale indicate the positions and scales of the edges. The edge contrast can be estimated from the height of the peak. The model provides a veridical estimate of the scale and contrast of edges that have a Gaussian integral profile. Therefore, since scale and contrast are independent stimulus parameters, the model predicts that the perceived value of either of these parameters should be unaffected by changes in the other. This prediction was found to be incorrect: reducing the contrast of an edge made it look sharper, and increasing its scale led to a decrease in the perceived contrast. Our model can account for these effects when the simple half-wave rectifier after the 1st derivative is replaced by a smoothed threshold function described by two parameters. For each subject, one pair of parameters provided a satisfactory fit to the data from all the experiments presented here and in the accompanying paper [May, K. A. & Georgeson, M. A. (2007). Added luminance ramp alters perceived edge blur and contrast: A critical test for derivative-based models of edge coding. Vision Research, 47, 1721-1731]. Thus, when we allow for the visual system's insensitivity to very shallow luminance gradients, our multi-scale model can be extended to edge coding over a wide range of contrasts and blurs. © 2007 Elsevier Ltd. All rights reserved.

The role of texture in shape from shading: are humans biased towards seeing relief textures?

When a textured surface is modulated in depth and illuminated, the level of illumination varies across the surface, producing coarse-scale luminance modulations (LM) and amplitude modulation (AM) of the fine-scale texture. If the surface has an albedo texture (reflectance variation) then the LM and AM components are always in-phase, but if the surface has a relief texture the phase relation between LM and AM varies with the direction and nature of the illuminant. We showed observers sinusoidal luminance and amplitude modulations of a binary noise texture, in various phase relationships, in a paired-comparisons design. In the first experiment, the combinations under test were presented in different temporal intervals. Observers indicated which interval contained the more depthy stimulus. LM and AM in-phase were seen as more depthy than LM alone which was in turn more depthy than LM and AM in anti-phase, but the differences were weak. In the second experiment the combinations under test were presented in a single interval on opposite obliques of a plaid pattern. Observers were asked to indicate the more depthy oblique. Observers produced the same depth rankings as before, but now the effects were more robust and significant. Intermediate LM/AM phase relationships were also tested: phase differences less than 90 deg were seen as more depthy than LM-only, while those greater than 90 deg were seen as less depthy. We conjecture that the visual system construes phase offsets between LM and AM as indicating relief texture and thus perceives these combinations as depthy even when their phase relationship is other than zero. However, when different LM/AM pairs are combined in a plaid, the signals on the obliques are unlikely to indicate corrugations of the same texture, and in this case the out-of-phase pairing is seen as flat. [Supported by the Engineering and Physical Sciences Research Council (EPSRC)].

Perceiving edge blur: Gaussian-derivative filtering and a rectifying nonlinearity

We studied the visual mechanisms that encode edge blur in images. Our previous work suggested that the visual system spatially differentiates the luminance profile twice to create the `signature' of the edge, and then evaluates the spatial scale of this signature profile by applying Gaussian derivative templates of different sizes. The scale of the best-fitting template indicates the blur of the edge. In blur-matching experiments, a staircase procedure was used to adjust the blur of a comparison edge (40% contrast, 0.3 s duration) until it appeared to match the blur of test edges at different contrasts (5% - 40%) and blurs (6 - 32 min of arc). Results showed that lower-contrast edges looked progressively sharper. We also added a linear luminance gradient to blurred test edges. When the added gradient was of opposite polarity to the edge gradient, it made the edge look progressively sharper. Both effects can be explained quantitatively by the action of a half-wave rectifying nonlinearity that sits between the first and second (linear) differentiating stages. This rectifier was introduced to account for a range of other effects on perceived blur (Barbieri-Hesse and Georgeson, 2002 Perception 31 Supplement, 54), but it readily predicts the influence of the negative ramp. The effect of contrast arises because the rectifier has a threshold: it not only suppresses negative values but also small positive values. At low contrasts, more of the gradient profile falls below threshold and its effective spatial scale shrinks in size, leading to perceived sharpening.

Perceiving edge blur: linear filtering and a rectifying nonlinearity

We studied the visual mechanisms that encode edge blur in images. Our previous work suggested that the visual system spatially differentiates the luminance profile twice to create the 'signature' of the edge, and then evaluates the spatial scale of this signature profile by applying Gaussian derivative templates of different sizes. The scale of the best-fitting template indicates the blur of the edge. In blur-matching experiments, a staircase procedure was used to adjust the blur of a comparison edge (40% contrast, 0.3 s duration) until it appeared to match the blur of test edges at different contrasts (5% - 40%) and blurs (6 - 32 min of arc). Results showed that lower-contrast edges looked progressively sharper.We also added a linear luminance gradient to blurred test edges. When the added gradient was of opposite polarity to the edge gradient, it made the edge look progressively sharper. Both effects can be explained quantitatively by the action of a half-wave rectifying nonlinearity that sits between the first and second (linear) differentiating stages. This rectifier was introduced to account for a range of other effects on perceived blur (Barbieri-Hesse and Georgeson, 2002 Perception 31 Supplement, 54), but it readily predicts the influence of the negative ramp. The effect of contrast arises because the rectifier has a threshold: it not only suppresses negative values but also small positive values. At low contrasts, more of the gradient profile falls below threshold and its effective spatial scale shrinks in size, leading to perceived sharpening.

Seeing edge blur: receptive fields as multiscale neural templates

Edge blur is an important perceptual cue, but how does the visual system encode the degree of blur at edges? Blur could be measured by the width of the luminance gradient profile, peak ^ trough separation in the 2nd derivative profile, or the ratio of 1st-to-3rd derivative magnitudes. In template models, the system would store a set of templates of different sizes and find which one best fits the `signature' of the edge. The signature could be the luminance profile itself, or one of its spatial derivatives. I tested these possibilities in blur-matching experiments. In a 2AFC staircase procedure, observers adjusted the blur of Gaussian edges (30% contrast) to match the perceived blur of various non-Gaussian test edges. In experiment 1, test stimuli were mixtures of 2 Gaussian edges (eg 10 and 30 min of arc blur) at the same location, while in experiment 2, test stimuli were formed from a blurred edge sharpened to different extents by a compressive transformation. Predictions of the various models were tested against the blur-matching data, but only one model was strongly supported. This was the template model, in which the input signature is the 2nd derivative of the luminance profile, and the templates are applied to this signature at the zero-crossings. The templates are Gaussian derivative receptive fields that covary in width and length to form a self-similar set (ie same shape, different sizes). This naturally predicts that shorter edges should look sharper. As edge length gets shorter, responses of longer templates drop more than shorter ones, and so the response distribution shifts towards shorter (smaller) templates, signalling a sharper edge. The data confirmed this, including the scale-invariance implied by self-similarity, and a good fit was obtained from templates with a length-to-width ratio of about 1. The simultaneous analysis of edge blur and edge location may offer a new solution to the multiscale problem in edge detection.

Contrast masking in strabismic amblyopia: attenuation, noise, interocular suppression and binocular summation

To investigate amblyopic contrast vision at threshold and above we performed pedestal-masking (contrastdiscrimination) experiments with a group of eight strabismic amblyopes using horizontal sinusoidal gratings (mainly 3 c/deg) in monocular, binocular and dichoptic configurations balanced across eye (i.e. five conditions). With some exceptions in some observers, the four main results were as follows. (1) For the monocular and dichoptic conditions, sensitivity was less in the amblyopic eye than in the good eye at all mask contrasts. (2) Binocular and monocular dipper functions superimposed in the good eye. (3) Monocular masking functions had a normal dipper shape in the good eye, but facilitation was diminished in the amblyopic eye. (4) A less consistent result was normal facilitation in dichoptic masking when testing the good eye, but a loss of this when testing the amblyopic eye. This pattern of amblyopic results was replicated in a normal observer by placing a neutral density filter in front of one eye. The two-stage model of binocular contrast gain control [Meese, T.S., Georgeson, M.A. & Baker, D.H. (2006). Binocular contrast vision at and above threshold. Journal of Vision 6, 1224--1243.] was `lesioned' in several ways to assess the form of the amblyopic deficit. The most successful model involves attenuation of signal and an increase in noise in the amblyopic eye, and intact stages of interocular suppression and binocular summation. This implies a behavioural influence from monocular noise in the amblyopic visual system as well as in normal observers with an ND filter over one eye.

Human sensitivity to phase perturbations in natural images:A statistical framework

Fourier-phase information is important in determining the appearance of natural scenes, but the structure of natural-image phase spectra is highly complex and difficult to relate directly to human perceptual processes. This problem is addressed by extending previous investigations of human visual sensitivity to the randomisation and quantisation of Fourier phase in natural images. The salience of the image changes induced by these physical processes is shown to depend critically on the nature of the original phase spectrum of each image, and the processes of randomisation and quantisation are shown to be perceptually equivalent provided that they shift image phase components by the same average amount. These results are explained by assuming that the visual system is sensitive to those phase-domain image changes which also alter certain global higher-order image statistics. This assumption may be used to place constraints on the likely nature of cortical processing: mechanisms which correlate the outputs of a bank of relative-phase-sensitive units are found to be consistent with the patterns of sensitivity reported here.

Independent detectors for expansion and rotation, and for orthogonal components of deformation

It is well known that optic flow - the smooth transformation of the retinal image experienced by a moving observer - contains valuable information about the three-dimensional layout of the environment. From psychophysical and neurophysiological experiments, specialised mechanisms responsive to components of optic flow (sometimes called complex motion) such as expansion and rotation have been inferred. However, it remains unclear (a) whether the visual system has mechanisms for processing the component of deformation and (b) whether there are multiple mechanisms that function independently from each other. Here, we investigate these issues using random-dot patterns and a forced-choice subthreshold summation technique. In experiment 1, we manipulated the size of a test region that was permitted to contain signal and found substantial spatial summation for signal components of translation, expansion, rotation, and deformation embedded in noise. In experiment 2, little or no summation was found for the superposition of orthogonal pairs of complex motion patterns (eg expansion and rotation), consistent with probability summation between pairs of independent detectors. Our results suggest that optic-flow components are detected by mechanisms that are specialised for particular patterns of complex motion.

Broad direction bandwidths for complex motion mechanisms

Growing evidence from psychophysics and single-unit recordings suggests specialised mechanisms in the primate visual system for the detection of complex motion patterns such as expansion and rotation. Here we used a subthreshold summation technique to determine the direction tuning functions of the detecting mechanisms. We measured thresholds for discriminating noise and signal + noise for pairs of superimposed complex motion patterns (signal A and B) carried by random-dot stimuli in a circular 5° field. For expansion, rotation, deformation and translation we found broad tuning functions approximated by cos(d), where d is the difference in dot directions for signal A and B. These data were well described by models in which either: (a) cardinal mechanisms had direction bandwidths (half-widths) of around 60° or (b) the number of mechanisms was increased and their half-width was reduced to about 40°. When d = 180° we found summation to be greater than probability summation for expansion, rotation and translation, consistent with the idea that mechanisms for these stimuli are constructed from subunits responsive to relative motion. For deformation, however, we found sensitivity declined when d = 180°, suggesting antagonistic input from directional subunits in the deformation mechanism. This is a necessary property for a mechanism whose job is to extract the deformation component from the optic flow field. © 2001 Elsevier Science Ltd.