Optometry and Vision Sciences - Theses
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ItemReceptive field analysis in cat primary visual cortex( 2019)Characterising receptive fields (RFs) in the primary visual cortex (V1) is central to understanding how neurons and neural circuits process visual information. The goal of this thesis is to systemically compare the two most robust RF characterisation techniques available. The best performing technique will then be used to correlate spatial RFs to two fundamental neuronal properties in V1: cell classification (using extracellular spike identification); and contrast adaptation. I recorded (extracellularly) and estimated the RFs of anaesthetised cat V1 neurons in response to white-Gaussian noise (WGN) using 32-channel array probes. Single units were characterised using the generalised quadratic model (GQM), which is based on prior knowledge and assumptions about cortical processing, and the nonlinear input model (NIM), which is a more physiologically based parametric modelling framework. Qualitatively, the variability between the two models increased as the number of required filters increased. I also compared the performance of the two models quantitatively and found that it is better to use the more parametric framework of the NIM for RF characterisation than the GQM, though those advantages depend somewhat on the availability of spiking data. In the next part of my thesis, I extracted the extracellular spikes of V1 neurons and correlated their shapes to their spatial RFs extracted using the NIM. Extracellular spike waveforms from recordings in V1 have traditionally consisted of negative first phases. I identified these spike types in my data, but I show that there are also distinct classes of spikes with positive first phases. The RFs and spiking characteristics of these different spike waveform types were examined, and I found that the negative spiking units showed characteristics typical of cortical cells (i.e. simple and complex cell types) and the positive first phase spiking units showed characteristics typical of thalamic cells, which provide the input to cortex. To further investigate this theory, I recorded from V1 before and after cortical silencing, and found that only positive first phase spikes remained. This provides strong evidence in support of the theory that the positive first phase spikes are derived from the thalamic input fibres to the cortex. For the final part of the project I recovered the RFs (using NIM) of neurons during adaptation to drifting gratings (i.e. contrast adaptation). There were no consistent changes in the spatial RFs following contrast adaptation for either simple or complex cells. I also observed that the responses to WGN images of adapted units were significantly slower than the control units (i.e. response latency was increased). However, there were several limitations that arose from this project, which are discussed in detail. The results of my work have demonstrated three aspects of V1 processing: (1) the NIM is better than the GQM for RF characterisation; (2) some extracellular positive first phase spiking units may correspond to recordings from thalamic axons projecting to V1; and (3) contrast adaptation has no effect on the spatial RFs, but it does have an effect on the temporal RFs of cortical V1 neurons.
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ItemReversibility of IOP-induced retinal ganglion cell injury in mice( 2019)It is commonly believed that high eye pressure induced retinal ganglion cell injury is irreversible in glaucoma, however current studies suggest otherwise. This thesis developed a glaucoma model in mice to demonstrate that retinal ganglion cells can recover their activity, but only if intervention occurs early. The functional recovery of retinal ganglion cells is associated with changes to the purinergic pathway.
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ItemThe effect of aging on spatial visual process outside the fovea( 2018)Studies have repeatedly shown that physiological aging impacts contextual spatial vision in central vision. Some visual functions are different between foveal and non-foveal vision and we have limited understanding of parafoveal contextual vision in aging. My thesis addressed how healthy aging influences spatial vision in non-foveal areas. Tasks involved in Experiment 1 were visual crowding and surround suppression of contrast detection. In the literature, these functions are often poorly differentiated The experiments described in this thesis investigated the consequences of healthy aging on visual crowding and surround suppression of contrast detection and determined whether such tasks were related to visuospatial attention as measured by visual search. Surround suppression of contrast detection increased in healthy older adults whereas visual crowding was relatively unchanged, supporting the existing evidence that crowding and suppression are distinct phenomena. Older adults showed longer reaction times for visual search, but visual search was not predicted by performance in either the crowding or surround suppression task in either age group. Although attention is considered important mechanistically for both visual search and visual crowding, the results did not reveal a role for attention in the magnitude of crowding. Since visual crowding relatively remained unchanged in older adults, Experiment 2 and 3 continued to explore surround suppression of contrast detection. Contrast detection, however, does not change across the visual field in a globally equivalent fashion, instead there are orientation biases that depend on eccentricity. The effect of surround on these anisotropies are unknown. Experiment 2 investigated if there are aspects related to stimulus orientation of surround suppression of contrast detection at different eccentricities and the role of centre-surround orientation using psychophysical methods. The results indicated that suppression is increased for horizontal centre-surround stimuli at 6ᵒ eccentricity while radial stimulus showed increased suppression at 15ᵒ eccentricity. Suppression was greater for a horizontal centre than for a vertical centre regardless of its surround orientation (parallel or orthogonal) at 6ᵒ and a radial centre was more susceptible for suppression than a tangential centre only for parallel surround condition at 15ᵒ. Experiment 3 determined if biases of suppression strength according to stimulus orientation and retinal eccentricity are observed in older adults. Orientation anisotropy of surround suppression changed from a horizontal bias to a radial bias moving from 6ᵒ to 15ᵒ in older groups indicating similar eccentricity dependency of orientation biases of surround suppression of contrast detection in both young and older adults. The experiments described in this thesis broadened our understanding of how aging effects non-foveal spatial vision. Advanced understanding of the effects of healthy aging in non-foveal vision is not only important for better understand of fundamental aspects of visual perception, but also for developing remediation strategies in diseases such as Age-Related Macular Disease (AMD).
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ItemLocal microvascular reactivity in the regulation of retinal blood flow( 2018)Although a well-regulated blood supply is important for healthy neural function, the mechanism by which this occurs is still disputed; some studies charge this physiological response solely to the muscular arterioles, whilst others suggest capillaries are involved if not the principal co-ordinators. As this debate arises mostly from animal data, this thesis aims to determine whether the human inner retinal microvasculature, visualised in vivo using flood-illumination adaptive optics imaging, plays a role in modifying blood supply to meet metabolic demand.
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ItemA structural and functional profile of high myopia as a function of eye size( 2018)The prevalence of myopia and its associated sight threatening pathology is anticipated to increase, making high myopia a global health concern, especially in our ageing population. Although pathological sequelae and visual dysfunction have been attributed to excessive elongation in the highly myopic eye, a link between axial elongation and visual dysfunction in the absence of significant pathology is less well described. Furthermore, emmetropia and high myopia are variably defined, and in most instances, defined according to refractive error and not eye size. This thesis was designed to define and distinguish emmetropic and highly myopic eyes with regard to axial length and vitreous chamber depth and to apply these definitions to studies exploring the impact of ocular expansion on visual function and ocular structure. The first experiment (Chapter 2) used meta-analysis to predict the axial length (23.47 ± 0.07 mm) and vitreous chamber depth (16.12 ± 0.14 mm) of an emmetropic eye. Based on gender matched studies, male eyes not selected for refractive error were found to be larger with respect to both axial length (+0.52 ± 0.04 mm) and vitreous chamber depth (+0.40 ± 0.04 mm) relative to female eyes. Male emmetropic eyes displayed longer vitreous chamber depths (+0.47 ± 0.15 mm) relative to female emmetropic eyes, but axial lengths of emmetropic eyes did not vary with gender. Linear and non-linear meta-regressions predicted minimum dimensions of -5, -6 and -8 Dioptre (D) eyes, with a – 5 D high myope characterised by an axial length and vitreous chamber depth of at least 24.66 and 16.94 mm, respectively. Refractive errors of -5, -6 and -8 D were selected as they have previously been used to define high myopia in other studies, and were the refractive error groupings investigated in Chapters 3 and 4 of this thesis. Systematic review showed that vitreous chamber depth is presented less frequently than axial length in published literature. This may reflect instrumentation used to perform biometry and suggests that vitreous chamber elongation is mostly assumed but not demonstrated by researchers. In such cases, the role of posterior segment elongation in the development of structural and/or functional sequelae is hypothetical. The second experiment (Chapter 3) contrasted luminance and S-cone pathway spatial processing of axial high myopes ( -8 D) and emmetropes using psychophysical tools. Luminance and S-cone pathways were both probed to discriminate between pathway selective and non-selective visual dysfunction, given the known redundancy of neuronal elements comprising the S-cone pathway and reports of altered colour vision in high myopia. High spatial frequency loss and increased critical area indicated increased separation of neural elements. Critical area enlargement was consistent with a non-uniform posterior pole model of ocular expansion. Models previously reported in the literature have included non-uniform, posterior pole and global expansion. However, unlike the wrok presented here, these studies did not assess visual function with regards to vitreous chamber depth. Reduced contrast sensitivity for spatial summation tasks in the presence of retained sensitivity at lower spatial frequencies suggested non-selective post-receptoral dysfunction due to ocular enlargement and either normal or enhanced photoreceptor sensitivity. The third experiment (Chapter 4) utilised readily available clinical tools, customised automated perimetry and optical coherence tomography, to investigate structure-function relationships in enlarged highly myopic eyes ( -5 D). Generalised choroidal thinning for the central 4 mm and localised retinal thinning confined to the central ±1 mm were evident for high myopes. Although overall visual sensitivity decreased with increasing eye size, regional relationships between sensitivity and structural thickness or eye size were not evident. However, the nasal region appeared predominantly thinner with ocular enlargement suggesting that it may be more susceptible to visual dysfunction in longer eyes. The finding of marked nasal thinning of the ocular structural layers has been reported previously and is consistent with choroidal watershed zones predominantly affecting the nasal posterior pole. This reduced blood supply could underpin structural and functional changes in eyes demonstrating posterior pole expansion. The findings support that vitreous chamber elongation causes high myopia, visual dysfunction, and generalised choroidal and localised retinal thinning. Psychophysical and available clinical tools supported non-uniform ocular expansion in high myopia, with the nasal region predominantly thinned and potentially at risk of visual dysfunction. Although meta-analysis is not a novel tool, its application to defining emmetropia and high myopes with regards to axial length and vitreous chamber depth is novel, and has application in subsequent research and clinical settings.
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ItemOrigins of feature selectivity in the visual system of two mammalian species( 2018)Visual information is transmitted from the retina to the primary visual cortex (V1) through the lateral geniculate nucleus (LGN). At each stage along this visual pathway, the receptive field properties of neurons are transformed, with sharp feature selectivity originating for the first time in the primary visual cortex. In this thesis, I studied the mechanism underlying the generation of the full range of, as well as the sharpening of, two such feature selectivities - the orientation and spatial frequency tuning of neurons- along the visual pathways of tree shrews and macaques. Undertaking this study in two species helps us examine the mechanisms that may be conserved during evolution. In experiment 1 (chapter 4), I used the differences in spatial scale between the geniculate inputs and the V1 spiking outputs in the optical imaging of intrinsic signals to examine the differences in the preferred orientations of the inputs and outputs in V1 of anaesthetized macaques. I determined that the majority of inputs were tuned to the radial orientation (the orientation of the line joining a point on the visual field to the centre of gaze, or fovea in the macaque). A bias for the radial orientation is already evident in the retina. I suggest that the full range of orientation preferences observed in the outputs are generated from a limited number of broadly tuned channels. In experiment 2 (chapter 5), I explored the mechanism underlying the sharpening of orientation tuning from layer 4 to layer 2/3 in tree shrew V1. I found that the orientation selectivity of layer 2/3 is generated from sharpening the broad biases observed in layer 4 of the cortex. It is likely that intracortical inhibitory connections play a bigger role in sharpening feature selectivity in the tree shrews (and by extension in macaques) compared to cats, where most such studies are undertaken. In experiment 3 (chapter 6), I found that neurons in the visual layers of the superior colliculus (SC), which form part of an alternate pathway to the visual cortices, and those in the LGN and layer 4 of V1 show similar orientation and spatial frequency tuning. Hence, it is likely that neurons in these two pathways inherit their feature selectivity from biases established in the retina. In experiment 4 (chapter 7), I found that unlike the macaques, simple cells in the tree shrew V1 act more as Fourier analysers; i.e., they deconstruct the visual scene into their spatial frequency components. I conclude that the tree shrew has several spatial frequency tuning channels in V1 in comparison. Together, my results suggest that sharp feature selectivity observed in the primary visual cortex may be generated from broad biases that are present sub-cortically. Further, in tree shrews and macaques, where sharpening of feature selectivity occurs from layer 4 to layer 2/3, intracortical mechanisms, such as cross-orientation inhibition also play an important role in elaborating feature selectivity. The full range of orientation and spatial frequency preferences in the cortex may be generated from a limited number of broadly tuned channels in both the macaques and tree shrews. These results indicate that sub-cortical biases play an important role in elaborating feature selectivity within the primary visual cortex.
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ItemInvestigating the functional influence of perceptual stabilisation mechanisms of small eye movements( 2018)Even when we stare intently at an object, our eyes are in constant motion due to small, involuntary eye movements. Despite this, we do not perceive a jittery world as the visual system is able to compensate for the motion that arises and construct a stable visual percept. The thesis explores the need for such compensatory mechanisms by combining phenomenology and psychophysics to determine whether perceptual stabilisation mechanisms can have a measurable influence on visual function..
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ItemCharacterising the ocular phenotype in a murine model of Alzheimer’s disease( 2018)This thesis shows that amyloid beta found in the brain is also present in the retina of a murine model of Alzheimer’s disease. By applying non-invasive retinal techniques, we show that neuronal structural and functional changes occur early in this model and that these are associated with vascular dysfunction. Such retinal hallmarks differentiate Alzheimer's changes from healthy ageing mice and provide evidence that the retina is a viable biomarker for dementia.
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ItemElectrophysiological and behavioural studies of top-down mechanisms of attention( 2018)Most modern skills, like driving a car, playing video games or reading a book, are relatively recent occurrences in human history and have presumably no specific hard-wired neural pathways. Instead, they piggyback on neural mechanisms that the brain evolved for other purposes, such as object recognition or visual attention. To take one specific example, reading is fundamental to function in modern daily life. It has been claimed that visuo-spatial attention is essential for selecting and binding strings of letters to identify words. In spite of half a century of extensive research on the mechanisms underlying visual processing, it is not well understood how cognitive abilities such as visual attention are related to reading. This thesis aimed to study not only the mutual interaction between reading and attention, but also first shed more light on the underlying neural mechanisms of visuospatial attention by investigating attention in one of our closest primate relatives. Study of electrical properties of several neurons surrounding an implanted microelectrode – known as extracellular recording – has been a robust method for basic understanding of how the nervous system works. However, performing this method in humans is unethical and as a result, electrophysiologists rely on recordings from animal brains, especially from the monkey as a species closely related to humans. Therefore, to understand further the neural mechanisms of top-down attention, I analysed electrophysiological neural signals which were recorded from macaques whilst they performed an attention-demanding task. I found two different parallel synchronized activities between posterior parietal and middle temporal cortices, one in the high- frequency range (high gamma) for feature discrimination and one in the low-frequency range (beta, low gamma) for attentional modulation. These results suggest that one process extracts and retains feature information, which is then used by a second process for top- down modulation of spatial attention. Although several theories have been suggested to explain how such oscillations in the neural activities reflect our performances in a particular cognitive function such as visual attention, the link between electrophysiology and psychophysics has not been fully studied. For the third experimental chapter, a slightly different version of the attention task was used from the one that earlier monkeys were trained on whilst collecting the data used for the first and second experiments. I found that reported oscillations in the neural activities in experiments one and two appear in the animal’s behaviour in a much lower frequency range: between 6 to 15 Hz. This rhythmicity in attention resembles fluctuations in the sampling of the external world by the visual system. It has been proposed that rhythmic allocation of attention is involved in the mechanisms of reading scripts. As such, languages with different scripts may therefore modulate attention differently. Using psychophysical tests, I found that visual attention is allocated asymmetrically depending on an individual’s habitual direction of reading. The results showed that efficiency of visuo-spatial attention mechanisms of left-to-right readers (such as English readers) and right-to-left readers (such as Farsi readers) were biased towards the right and left visual fields, respectively. On the other hand, bidirectional readers (fluent in both English and Farsi) were equally sensitive in the two hemifields. Search ability was not only found to be influenced by the habitual direction of reading, but such an influence could be modulated by even relatively short periods of reading. The improved visual attention was not accompanied by changes is oculomotor parameters i.e., fixation duration or saccade length. These findings provide evidence that the allocation of top-down attention in the visual field as measured by visual search ability can be influenced by the reading habit. The principle of rhythmic modulation of brain processes appears to underpin both visual attention as seen in common visual tasks as well as high level cognitive functions such as reading. The basic understanding of how complex, relatively modern, human functions are built upon processes inherited from evolution is likely to yield insights into the cause of many common ailments that affect human behaviour and indicate ways of managing them.
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ItemAn investigation of spatial receptive fields of complex cells in the primary visual cortex( 2017)One of the main concerns of visual neuroscience is to understand how information is processed by the neural circuits in the visual system. Since the historic experiments of Hubel and Wiesel, many more aspects of visual information processing in the brain have been discovered using experimental approaches. However, a lot of computations underlying such processing remain unclear or even unknown. In the retina and the lateral geniculate nucleus, the basic computations have been identified by measuring the responses of neurons to simple visual stimuli such as gratings and oriented bars. However, in higher areas of the visual pathway, e.g. the cortical visual areas, many neurons (including complex cells) cannot be characterised entirely based on their responses to simple stimuli. The complex cells in the visual cortex do not exhibit linear receptive field properties. Hence, the failure of linear receptive field models to describe the behaviour of such neurons leads neuroscientists to seek more plausible quantitative models. Efficient coding is a computational hypothesis about sensory systems. Recently developed models based on the efficient coding hypothesis were able to capture certain properties of complex cells in the primary visual cortex. The Independent feature Subspace Analysis (ISA) model and the covariance model are such examples of these models. The ISA model employs the notion of the energy model in describing the responses of complex cells, whereas the covariance model is based on a recent speculation that complex cells tend to encode the second-order statistical dependencies of the visual input. In this thesis, the parametric technique of the generalised quadratic model (GQM) in conjunction with white Gaussian noise stimulation is used to identify the spatial receptive fields of complex cells in cat primary visual cortex. The validity of the identified receptive field filters are verified by measuring their performance in predicting the responses to test stimuli using correlation coefficients. The findings suggest that a majority of the complex cells in cat primary visual cortex are best described using a linear and one or more quadratic receptive field filters, which are classified as mixed complex cells. We observed that some complex cells exhibit linear as well as quadratic dependencies on an identified filter of their receptive fields. This often introduces a significant shift in the feature-contrast responses of these cells, which results in violations of the polarity invariance property of complex cells. Lastly, a quantitative comparison is performed between the experiment and theory using statistical analysis of the population of the cells' receptive fields identified by experiment and those predicted by the efficient coding models. For this, motivated by the experimental findings for complex cells, a modification of the ISA model that incorporates a linear term is introduced. The simulated model receptive fields of the modified ISA and the covariance model are then used to draw comparison to the experimental data. While the modified ISA and the covariance models are comparable in predicting the complex cell receptive fields characteristics in the primary visual cortex, the latter shows more capable in explaining the observed intra-receptive field inhomogeneity of complex cells, including differences in orientation preference and ratio spatial frequency for the receptive field filters of the same cell. However, the major discrepancies between theory and experiment lie in the orientation bandwidth and spatial frequency bandwidth of the receptive field filters, where the population of the predicted model receptive field filters demonstrate much narrower bandwidths. These findings, thereby, suggest the sub-optimality of the experimental receptive field filters in terms of the efficiency of the code.
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