This thesis describes a set of experiments investigating the impact of the higher-order aberrations of the eye on contrast sensitivity. The principal aim is to investigate if asymmetric blur induced by the aberrations of the eye can produce orientation selective effects. Orientation in contrast sensitivity testing has been largely ignored as it has been thought that the oblique effect, the preference for vertical and horizontal stimuli over obliques, was entirely neural in origin. Studies measuring the oblique effect were conducted using diffraction-limited pupils yet in larger pupils the higher order aberrations have an increasing impact on visual performance. These aberrations can be circularly asymmetric and so this raises the possibility that they may influence orientation selectivity when the pupil is large. The second aim of the study is to investigate orientation selective contrast sensitivity in refractive surgery patients.

Natural images contain statistical regularities that the human visual system is adapted to. Images that contain excess contrast energy at mid-range spatial frequencies are particularly aversive and can cause a variety of adverse effects including seizures, headaches and illusions. Some individuals experience more pattern-induced discomfort and illusions than others. However, the physiological mechanisms associated with the discomfort are unknown. Several well-known visual illusions appear to be caused by weak accommodation to the target. Individuals who experience pattern-induced discomfort and illusions show a weaker accommodative response suggesting that there may be a relationship between accommodation and discomfort. The aversion to chromatic and achromatic grating patterns that were either static or moving was investigated. Both sets of patterns varied in how epileptogenic they were. It was found that discomfort was not dependent on the epileptogenic properties of the pattern. Ocular accommodation to the patterns was then measured to see if the parameters of the patterns that induced discomfort produced a weaker accommodative response. There was no effect of the pattern on accommodation, suggesting that the discomfort is not caused by problems in accommodating to the pattern., Migraineurs and patients with photosensitive epilepsy show a heightened cortical response to uncomfortable grating patterns, suggesting that the discomfort might be cortical in origin. The haemodynamic and electrophysiological responses to the grating patterns were measured. The uncomfortable patterns produced a large change in the haemodynamic response, and a larger decrease in alpha power than the less uncomfortable patterns, both of which suggest that the discomfort is associated with an increase in cortical excitability I Page 1 Abstract Natural images contain statistical regularities that the human visual system is adapted to. Images that contain excess contrast energy at mid-range spatial frequencies are particularly aversive and can cause a variety of adverse effects including seizures, headaches and illusions. Some individuals experience more pattern-induced discomfort and illusions than others. However, the physiological mechanisms associated with the discomfort are unknown. Several well-known visual illusions appear to be caused by weak accommodation to the target. Individuals who experience pattern-induced discomfort and illusions show a weaker accommodative response suggesting that there may be a relationship between accommodation and discomfort. The aversion to chromatic and achromatic grating patterns that were either static or moving was investigated. Both sets of patterns varied in how epileptogenic they were. It was found that discomfort was not dependent on the epileptogenic properties of the pattern. Ocular accommodation to the patterns was then measured to see if the parameters of the patterns that induced discomfort produced a weaker accommodative response. There was no effect of the pattern on accommodation, suggesting that the discomfort is not caused by problems in accommodating to the pattern., Migraineurs and patients with photosensitive epilepsy show a heightened cortical response to uncomfortable grating patterns, suggesting that the discomfort might be cortical in origin. The haemodynamic and electrophysiological responses to the grating patterns were measured. The uncomfortable patterns produced a large change in the haemodynamic response, and a larger decrease in alpha power than the less uncomfortable patterns, both of which suggest that the discomfort is associated with an increase in cortical excitability. The discomfort may be a homeostatic warning that the cortex is showing a heightened response to the images. Increased neural firing comes at a metabolic cost, and so the discomfort may signal that prolonged exposure to the stimulus will produce a greater demand on the body's food and oxygen.

This thesis reports the results of five novel studies that used eye movement patterns to elucidate the role of shape information content of object shape representation in human visual perception. In Experiments 1, and 2 eye movements were recorded while observers either actively memorised or passively viewed different sets of novel objects, and during a subsequent recognition memory task. ..• -'", ••. Fixation data were contrasted against different models of shape mralyses based on surface curvature bounding vs. internal contour and low level image visual saliency. The results showed a preference for fixation at regions of internal local features (either concave or/and convex) during both active memorisation and passive viewing of object shape. This pattern changed during the recognition phase where there was a fixation preference towards regions containing concave surface curvature minima. It is proposed that the preference of fixation at regions of concavity reflect the operation of a depth-sensitive view interpolation process that is constrained by key points encoding regions of concave curvature minima. Experiments 3 and 4 examined the extent to which fixation-based local shape analysis patterns are influenced by the perceptual expertise of the observer and the level of stimulus classification required by the task. These studies were based on the paradigm developed by Wong, Palmeri & Gauthier (2009) in which observers are extensively trained to categorize sets of novel objects (Ziggerins) at either a basic or subordinate level of classification. The effects of training were measured by comparing performance between a pre- and post-test sequential shape matching task that required either basic- or subordinate-level judgements. In addition, we also recorded fixation patterns during the pre- and post-tests.

The aim of this thesis was to investigate if haemodynamic function in response to both simple and complex visual stimulation could be quantified using functional near infrared spectroscopy (fNIRS). Event-related potentials (ERPs) were used in conjunction with fNIRS in order to study the nature of neuro-vascular correlates underlying visual processing. Cortical mapping of haemodynamic function in response to simple visual stimulation using reversing checkerboards over the occipital and parieto- . . occipital cortices showed that locations only overlying V1, with the exception of those on the midline, elicited the biggest activation. Neuro-vascular correlates of responses to static random dot stereograms revealed that haemodynamic activity was possibly representative of responses to pattern- onset/global aspects of the stimulus. In general, change in haemodynamic activity was strongly correlated with that of neural activation. Changes in vascular function in response to radial motion and dynamic stereograms, when the effect due to a pattern onset was eliminated, at occipital and parieto-occipital cortices showed that fNIRS was able to detect haemodynamic activation as a result of motion and stereopsis respectively. Finally, investigation of a new complex stimulus encompassing the properties of motion, depth and luminance over parieto-occipital cortices showed that changes in haemoglobin concentration were only representative of the 'global' form of the stimulus. In contrary to ERP results, no motion adaptation effects were observed within the haemodynamic response. The work presented in this thesis has shown how simple and complex visual stimulation over a large proportion of human visual cortex affects absolute concentrations of haemoglobin chromophores and are good indicators of absolute oxygen consumption by the brain. Furthermore, the technique can be used to study the physiological nature of neurovascular coupling in both normal and compromised visual functioning in the future by modifying experimental paradigms presented in this thesis, and with improved probe design. 11.

Magnetoencephalography (MEG), functional magnetic resonance imaging (fMRI) and behavioural experiments were used to investigate the neural processes underlying global form perception in human vision. The main findings from normally-sighted observers were: 1) sensitivity to horizontal structure was less than for radial or rotational structure; 2) the neural response to global structure was a reduction in cortical oscillatory power (10-30 Hz) within a network of extrastriate areas, including V4 and V3a; 3) the extend of reduced cortical power was least for horizontal patters; 4) V1 was not identified as a region of peak activity with either MEG or fMRI. The main findings with the strabismic amblyope were: 1) sensitivity for detection of radial, rotational, and horizontal structure was reduced when viewed with the amblyopic- relative to the fellow- eye; 2) cortical power changes within V4 to the presentation of rotational Glass patterns were less when viewed with the amblyopic- compared with the fellow- eye. The main conclusions are: 1) a network of extrastriate cortical areas are involved in the analysis of global form, with the most prominent change in neural activity being a reduction in oscillatory power within the 10-30 Hz band; 2) in strabismic amblyopia, the neuronal assembly associated with form perception in extrastriate cortex may be dysfunctional, the nature of this dysfunction may be a change in the normal temporal pattern of neuronal discharges; 3) MEG, fMRI and behavioural measures support the notion that different neural processes underlie the perception of horizontal as opposed to radial or rotational structure.

This thesis is concerned with the investigation of the nature of adaptation and aftereffects in the human visual system. We extend previous research first by specifically investigating the temporal aspect of these processes. The technique we develop and present here offers a method of measuring the temporal dynamics of visual aftereffects which captures how the aftereffect is varying in both strength and duration. In the first experimental chapter we present data following the application of this technique to the Depth After Effect. We then go on to apply this technique to the investigation of the Motion After Effect and in particular look at the temporal dynamics of this effect using different stimuli during adaptation. The results of this form the second and third experimental chapter of this thesis. Having addressed aspects of the nature of visual aftereffects to both motion and disparity, we then present an experiment looking at adaptation to both motion and disparity, and the effect this has on an ambiguous stimuli, that of a transparent surface. We found that observers' biases for which direction of motion moved in front was influenced in a manner mostly consistent with a depth-contingent motion aftereffect following adaptation. These results emphasize the critical role of neural structures sensitive to both motion and binocular disparity in the perception of motion transparency. In summary, this thesis addresses the nature of visual aftereffects and also presents a method of measuring how they vary with time.

Humans inspect the environment around them by selecting a sequence of locations to fixate which will provide information about the scene. How are these locations chosen? The saliency map model suggests that points in the scene are represented topographically and that the likelihood of them being fixated depends on low-level feature contrast. This model makes specific predictions about the way people will move their eyes when looking at natural scenes, although there are few experimental tests of these predictions. The experiments described in this thesis show effects of visual saliency on the likelihood and the speed at which objects are fixated. Experiment 1 shows that the potency of salient objects is moderated by the task being performed. When the task does not constrain the regions of interest, as in a general encoding situation, the saliency model performs better than chance estimates (Experiments 2 and 3). There are also sequential patterns of eye movements in this task - scanpaths - that the model does not reproduce. In visual search, participants can saccade to a target object, and this is quicker, in some cases, if the target is more salient (Experiments 4-7). A salient distractor impedes search more than a non-salient one (Experiments 8 and 9). The context of the scene also has an effect on search, and features of the layout, in particular the horizon, may cause an asymmetry in saccade direction (Experiment 10). Findings from research with a visual agnosia patient are consistent with the idea that scene understanding and saliency combine in guiding the eyes (Experiment 11). These experiments support a framework that incorporates a task-driven prior, gist and the relevance of each region to the task, in addition to bottom-up saliency. Thus saliency is just one part of the way in which people move their eyes.

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From the airport security guard monitoring luggage to the rushed commuter looking for their car keys, visual search is one of the most common requirements of our visual system. Despite its ubiquity, many aspects of visual search remain unaccounted for by computational models. Difficulty arises when trying to account for any internal biases of an observer undertaking a search task or trying to decompose an image of a natural scene into relevant fundamental properties. Previous studies have attempted to understand visual search by using highly simplified stimuli, such as discrete search arrays. Although these studies have been useful, the extent to which the search of discrete search arrays can represent the search of more naturalistic stimuli is subject to debate. The experiments described in this thesis used as stimuli images of natural scenes and attempted to address two key objectives. The first was to determine which image properties influenced the detectability of a target. Features investigated included chroma, entropy, contrast, edge contrast and luminance. The proportion of variance in detection ability accounted for by each feature was estimated and the features were ranked in order of importance to detection. The second objective was to develop a method for guiding human fixations by modifying image features while observers were engaged in a search task. To this end, images were modified using the image-processing method unsharp masking. To assess the effect of the image modification on fixations, eye movements were monitored using an eye-tracker. Another subject addressed in the thesis was the classification of fixations from eye movement data. There exists no standard method for achieving this classification. Existing methods have employed thresholds for speed, acceleration, duration and stability of point-of-gaze to classify fixations, but these thresholds have no commonly accepted values. Presented in this thesis is an automatic nonparametric method for classifying fixations, which extracts fixations without requiring any input parameters from the experimenter. The method was tested against independent classifications by three experts. The accurate estimation of Kullback-Leibler Divergence, an information theoretic quantity which can be used to compare probability distributions, was also addressed in this thesis since the quantity was used to compare fixation distributions. Different methods for the estimation of Kullback-Leibler divergence were tested using artificial data and it was shown than a method for estimating the quantity directly from input data outperformed methods which required binning of data or kernel density estimation to estimate underlying distributions.

Le récepteur MerTK est impliqué dans la phagocytose des segments externes des photorécepteurs (SEP) par l'épithélium pigmentaire rétinien (EPR), fonction cruciale pour la survie des photorécepteurs et la vision. Dans la rétine, ces deux tissus sont en contact permanent et la phagocytose ne survient qu'une fois par jour, cette fonction nécessite donc d'être contrôlée précisément. Le pic de phagocytose est lié à l'activation intracellulaire de MerTK via l'intégrine αvβ5. Ce projet a eu pour but d'étudier les mécanismes extracellulaires régulant la fonction de MerTK au cours de cette phagocytose.Nous avons montré que MerTK est clivé à la surface des cellules d'EPR in vivo avant et après le pic de phagocytose. Ceci permettrait d'éviter une phagocytose trop prononcée des SEP.Nous avons démontré le rôle opposé des ligands de MerTK, spécifique à l'EPR. Gas6 semble inhibiteur, il stimule le clivage de MerTK et inhibe la phagocytose in vitro, et son expression in vivo est faible au moment du pic de phagocytose. Au contraire, Protéine S, dont l'expression augmente in vivo au moment du pic, inhibe le clivage de MerTK et stimule la phagocytose in vitro, et pourrait ainsi potentialiser cette fonction.Parmi les protéases étudiées, l'inhibition d'ADAM17 in vitro engendre une diminution du clivage de MerTK corrélée à une augmentation de sa biodisponibilité à la surface cellulaire et de son activité. Cependant, cet effet n'étant pas total, l'implication d'une autre protéase n'est pas exclue.Ainsi, mes travaux de Doctorat permettent de mieux comprendre la régulation complexe de l'activité de MerTK dans la phagocytose rétinienne, essentielle pour le rythme circadien de cette fonction. / The MerTK receptor is involved in the daily phagocytosis of photoreceptor outer segments (POS) by the retinal pigment epithelium (RPE), an indispensable process for photoreceptors survival and vision. In the retina, the contact between POS and RPE is permanent, and POS phagocytosis occurs once a day, requiring a precise control of this function. The phagocytic peak is initiated by activation of MerTK via the αvβ5 integrin receptor. This project aimed at studying extracellular mechanisms that control MerTK function during POS phagocytosis. We have shown that MerTK can be cleaved from the RPE cell surface in vivo before and just after the phagocytic peak. This process might avoid an excess of POS phagocytosis. We have also shown the opposite role of MerTK ligands, specific to RPE cells. Gas6 appears to act as an inhibitor as it stimulates MerTK cleavage and inhibits POS phagocytosis in vitro. Moreover, in vivo, Gas6 expression is weak at peak phagocytosis time. In contrast, Protein S, which in vivo expression increases at the time of the phagocytic peak, inhibits MerTK cleavage and stimulates POS phagocytosis in vitro, and thus might potentiate phagocytosis. Among the protease candidates we studied, in vitro inhibition of ADAM17 results in decreased MerTK cleavage associated with the increase of full-length receptors available at cell surface and of MerTK activation. However, as cleavage still occurs in these conditions, we cannot exclude the implication of another protease. Taken together, my PhD data allows us to better understand the complex regulation of MerTK activity during retinal phagocytosis, which is essential for the circadian rhythm of this function.