Optometry and Vision Sciences - Theses
Permanent URI for this collection
Search Results
1 - 10 of 18
-
ItemAudiovisual synchrony perception in older adults( 2015)The purpose of this project was to examine differences in the behavioural and neural measures of audiovisual synchrony perception between younger and older adults. To accurately perceive events in the natural scene, the human perceptual system needs to combine related and segregate unrelated auditory and visual stimuli. The amount of temporal asynchrony is one of the key properties that define whether an auditory and a visual stimulus are related, and whether they should be perceived as originating from the same event. As older adults experience reduced visual contrast and hearing sensitivities, this project investigated audiovisual synchrony perception in older adults after scaling stimulus levels to individual detection thresholds. It was also investigated if older adults are able to realign their perception of audiovisual synchrony after adapting to asynchrony - an ability that is potentially important for correctly perceiving audiovisual pairs across distance. Additionally, this project investigated the impact of older age on the underlying neural time course for audiovisual synchrony perception. The results from this project demonstrated that older adults were less sensitive to audiovisual asynchrony even after scaling the stimuli to their own detection thresholds for visual contrast and sound intensity. Older adults also adapted less to sound-lag asynchrony adaptation as compared to the younger adults. In addition, older adults showed additional neural activity in the frontal and parietal regions in order to form perceptual decisions for audiovisual synchrony. The findings from this project could imply that older adults find it more difficult to correctly perceive related audiovisual events in a natural scene, particularly for distant events. The additional involvement of the frontal and parietal areas in older adults may indicate that they may compensate by recruiting extra neural resources to perform the same perceptual task as younger observers. This project also considered some future work that are required to understand the real-life implications of older age on audiovisual synchrony perception like the effect of spatial clutter (i.e. in crowds) and the effect of rapid adaptation. As a whole, the findings from this project added knowledge to the body of work of ageing on audiovisual synchrony perception.
-
ItemUsing structural information to improve perimetry test procedures( 2015)Existing literature on perimetry suggests that current perimetric test procedures suffer from two major limitations; 1) test-retest variability and 2) sampling density. In this thesis, I aimed to improve perimetric testing by leveraging information about an individual’s retinal structure. Current perimetric test procedures are designed to be applicable for a widespread population and are not based on individual information about a given patient. Optical Coherence Tomography (OCT) provides us with some ready information about an individual’s RNFL thickness which might be useful for perimetric testing. This thesis explores ways to incorporate information gained from OCT into perimetric test procedures. In Experiment 1, an individual’s RNFL thickness information is used to bias the prior of a Bayesian perimetric test procedure. Experiment 2 studies the limitations of the relationship between Retinal Nerve Fiber Layer (RNFL) thickness, as measured by OCT data, and perimetric thresholds. In Experiment 3, an individual’s RNFL thickness information is used to customise visual field test locations. The results of this thesis suggest that an individual’s RNFL thickness information can be used to improve the accuracy, precision and test duration of perimetric testing (Experiment 1). The strength of the structure-function relationship in glaucoma can be better revealed improve by relating both measures using customised optic nerve head sectors rather than choosing fixed optic nerve head sector boundaries (Experiment 2). This thesis also shows that customising visual field locations based on the individual’s RNFL thickness improves the chances of detecting abnormal visual field locations (Experiment 3).
-
ItemReceptive field properties and dynamics in mammalian primary visual cortex( 2015)The functional properties and structure of receptive fields in primary visual cortical (V1) neurons represent how visual information is processed in the mammalian neocortex. Cortical receptive fields are diverse and highly dynamic to accommodate the constantly changing visual environment. The mechanisms behind the organisation of different types of receptive fields are still highly debated after David Hubel and Torsten Wiesel first described the fundamental properties of cortical receptive fields half a century ago. These pivotal discoveries were conducted in the classic animal models of vision research: cats and monkeys. In recent years, fuelled by the opportunities for genetic and molecular manipulation, mice have rapidly become a major model for studying cortical visual processing. It is essential to recognise the similarities and differences between mouse V1 and that of the well-established animal models. A major goal in this thesis is to compare the receptive field properties of mouse V1 (area 17) and cat V1 (area 17 and 18). Cortical neurons are largely composed of excitatory pyramidal cells and GABAergic inhibitory cells. Compared to excitatory neurons, the receptive field properties of inhibitory neurons are poorly understood due to the difficulty in identifying the diverse inhibitory subpopulations. In Chapter 4, by separating inhibitory and excitatory neurons based on their spike waveform shapes, I was able to examine the inhibitory receptive fields in both mouse and cat V1 and demonstrate differences in orientation selectivity and response linearity between these cell types in two species. In addition, I was also able to show that inhibitory cells were significantly over-represented in layer 1 of cat V1 and were less sensitive to low contrasts, as a population, compared to excitatory cells. Based on receptive field structures and response properties, V1 neurons are classified into simple cells and complex cells. Simple cells are thought to have spatially segregated ON and OFF subfields and are thus highly selective for the spatial phases of oriented edges. Complex cells have intermingled ON and OFF subfields and are largely phase-insensitive. Recent evidence reveals that some complex cells in cat and monkey V1 show increased phase sensitivity in their spiking activity as stimulus contrast is reduced, which suggests a shift towards a simple-like receptive field at low contrasts. By employing drifting sine-wave gratings (Chapter 5) and contrast-reversing gratings as visual stimuli (Chapter 6), I demonstrated the same effect in mouse V1 neurons. Furthermore, through intracellular recording I also observed contrast-dependent phase-sensitivity in the subthreshold membrane potentials of the cells as well as their spiking responses. This confirmed that the contrast-driven effect was a result of altered synaptic inputs and not the non-linear transformation from membrane potential to spike output.
-
ItemInvestigating the neurobiological and cognitive features of anorexia nervosa( 2015)Objective: Anorexia nervosa (AN) is a serious psychiatric condition characterised by significantly low body weight, a fear of weight gain and a disturbance in the experience of one’s own body weight or shape. The 12-month prevalence of AN is approximately 0.4% among females, and approximately one-tenth of that among males. AN is associated with exceptionally high morbidity rates, and a mortality rate among the highest of any psychiatric illness. AN is also associated with exceptionally high relapse rates. A major contributing factor for the high rates of morbidity and mortality experienced by these individuals is that the factors involved in the genesis and maintenance of the illness remain unclear, resulting in a hindrance in the improvement of current treatments or the development of new and more effective treatments. Though a number of treatment modalities have emerging evidence for efficacy, many patients remain under- or unresponsive. Thus, gaining a better understanding of the factors involved in the illness has the potential to lead to the development of more effective treatments in the future. Therefore, the aim of this thesis was to investigate the neurobiological and cognitive features of AN through a range of cognitive assessments, eyetracking tasks and functional neuroimaging measures. Method: Twenty-six right-handed female participants with AN and 27 healthy controls, matched for age, gender and premorbid intelligence participated in the study. Participants were required to attend three test sessions within a one week period that involved the completion of a variety of tasks. Included among these tasks were a cognitive battery, basic saccade tasks (prosaccade/antisaccade/no-go, memory-guided and self-paced saccade tasks), an emotional face processing task, a body size estimation task, a resting state functional magnetic resonance imaging (fMRI) scan, and a fixation task. Results: Participants with AN were found to demonstrate differences in performance on a variety of measures, relative to controls. AN participants showed a trend for poorer performance on a working memory task component of the cognitive battery which required the manipulation of visuospatial information. AN participants also displayed shorter prosaccade latencies and an increased rate of inhibitory errors on the memory-guided saccade task, but no significant difference in antisaccade, no-go or self-paced saccade performance. AN participants also demonstrated intact emotion identification of others, and relatedly, no significant difference in blood oxygen level dependent (BOLD) activity to face stimuli depicting different emotions. BOLD activity was however found to significantly differ to participants’ own faces, with AN participants displaying increased activity in the right inferior and middle temporal gyri, and right lingual gyrus. AN participants also avoided fixating on salient features of their own face and showed hyperscanning behaviours to images of their own face, emotional face stimuli and biological motion stimuli. The estimation of body size of biological motion stimuli was, however, not found to differ between groups. Findings of the resting state analysis indicated reduced functional connectivity within the sensorimotor and visual network in AN, but no significant group difference in default mode network connectivity. Finally, AN participants were found to make saccadic intrusions, specifically square wave jerks (SWJs), at a greater rate than healthy controls during fixation. The rate of SWJs also negatively correlated with state anxiety in AN, but not in controls. Discussion: The findings of the study indicate distinctive eye movement differences and visuospatial processing deficits in individuals with AN. The findings are discussed in terms of their overlap with reported findings in anxiety disorders, and the potential brain areas contributing to these results. Specifically, the potential role of the superior colliculus and gamma-aminobutyric acid (GABA) in AN are implicated through a number of findings. Furthermore, the negative correlation between SWJ rate and state anxiety classified groups with very high accuracy and was identified as a distinctive biomarker for AN. The clinical implications of these findings are discussed, as are the potential directions for treatment focus.
-
ItemWireless visual electrophysiology in conscious rats for preclinical drug testing( 2014)Aim: To develop a montage to measure electroretinogram (ERG) and visual evoked response without anaesthesia and apply to detect central penetrance for drug testing. Material and methods: Anaesthetised works were firstly undertaken to determine optimal electrode placements (3-month-old male Long-Evans rats, n = 6). Telemetry transmitters were implanted in rats (3-month-old male Long-Evans rats, n = 8), from which ERG and VEP in conscious rats are recorded. Using the telemetry montage, we investigated the effect commonly used laboratory anaesthetics (intramuscular ketamine:xylazine or inhalant isoflurane) has on visual electrophysiology. To test for central penetrance, rats (3-month-old male Long-Evans rats, n=8 each group) were implanted with telemetry transmitter and administered with either isoguvacine or muscimol. Both drugs are GABAa agonists, with the difference being muscimol readily crosses the blood-neural-barriers whereas isoguvacine does not. Therefore systemic administration of isoguvacine should return different ERG and VEP changes to local administration but the signal changes should be similar between local and systemic muscimol injections. The results of this experiment are compared to that of anaesthetised (3-month-old male Long-Evans rats, n=5 each group), conventional recordings to investigate anaesthesia confounds. Results: We show, for first time, wireless ERGs and VEPs are recordable in conscious rodents. Furthermore, the data indicates that the signals are stable for at least four weeks but commonly used laboratory anaesthesia alters waveform profiles. The GABAa agonists experiment suggests that the telemetry system is capable of detecting drug penetrance, however, the presence of anaesthesia confounds findings. Conclusion: We show that current conventional recording are confounded by anaesthesia and this novel system can potentially be used to detect drug penetrance. Moreover this system demonstrates potential for longitudinal studies, paving the way for neurodegenerative studies such as glaucoma in the future.
-
ItemCustomized, automated stimulus location choice to improve visual field procedures( 2014)It is well accepted in the literature that test-retest variability is a key limitation in current automated perimetric procedures, especially with moderate to advanced visual field loss. This obfuscates the ability to discriminate between true progression of the visual field and measurement noise. Studies have shown that sampling the visual field at a greater spatial resolution not only reduces global measures of test-retest variability, but can also describe the spatial extent of scotomata with more accuracy and detect scotomata otherwise missed in conventional perimetry. However, to date there has been no automated application of these principles, and previous approaches which have employed high resolution sampling have sacrificed test duration in order to measure more locations than standard stimulus distribution patterns. The primary objective of this thesis was to address each of these problems by developing a novel, automated, perimetric approach which customises test location choice based on spatial information and observer response during the examination. It was not only important that new procedures did not increase test times compared to current procedures, but also are computationally feasible to implement. The experimentation reported in this thesis concentrated on computer simulation (Experiments 1 to 3) in order to develop and tune these new procedures before testing their performance on human observers (Experiment 4). The outcome measures were precision of threshold estimates (test-retest variability), accuracy (absolute error) and efficiency (number of presentations). It was discovered that one of the developed approaches, Gradient-Oriented Automated Natural Neighbour Approach (GOANNA), improved accuracy and precision in areas surrounding scotoma borders without increasing test duration compared to current procedures (Chapter 3, Experiment 2). This led to further exploration of GOANNA, whereby it was demonstrated (through computer simulation) that the improvement in scotoma characterisation seen in Experiment 2 gave rise to earlier and more accurate detection of glaucomatous progression. It was assumed that the assumptions made in the simulation studies hold true for real data. This thesis lends support to previous findings that implementing high resolution grids is beneficial in glaucomatous progression detection, and that the conventional 6° rectangular grid of fixed locations may not be the most suitable stimulus arrangement for characterising and monitoring all visual field defects. It also reports on initial approaches that didn’t work, which may be useful for future investigators in this field of research. Most importantly, it provides a novel, principled, automated approach of locally increasing sampling spatial resolution without having to sacrifice efficiency.
-
ItemA novel rat model of ocular hypertension induced by a circumlimbal suture( 2014)The aim of the thesis is to develop a rat model of non-inflammatory, chronic ocular hypertension that produces glaucomatous optic neuropathy. Oculo-pression with circumlimbal suture produces a mild chronic ocular hypertension for over 15 weeks that gives rise to a preferential ganglion cell dysfunction, nerve fibre layer thinning and ganglion cell loss. These changes can be reversed by cutting the suture to produce IOP lowering. The model can be used to explore factors that lead to irreversible changes in glaucoma.
-
ItemContrast processing in ageing and early glaucoma( 2014)A natural visual experience commonly requires an ability to differentiate objects of supra-threshold contrast (contrast discrimination) and to adjust to changes in contrast (contrast adaptation). While the loss of contrast sensitivity with glaucoma has been well documented in the literature, the effect of glaucoma on supra-threshold contrast processing is less studied. This thesis investigated the effects of early glaucoma on contrast discrimination and rapid contrast adaptation. Additionally, alterations in retinal and cortical responses to supra-threshold contrast stimuli with glaucoma were investigated using electrophysiology techniques. As age is a risk factor for glaucoma, this thesis also considered the effects of normal ageing on contrast processing. The results of this thesis suggest that glaucoma can result in supra-threshold contrast deficits, with patients having early glaucoma demonstrating a reduction in rapid contrast adaptation and poorer contrast discrimination. As ageing did not alter rapid contrast adaptation, the assessment of contrast adaptation might be a useful functional tool in early glaucoma, although further studies are required to develop this. Further studies are also required to consider the implications of supra-threshold contrast deficits with glaucoma on natural vision. The smaller cortical deficits relative to retinal deficits revealed with electrophysiological recordings suggest that post-retinal abnormalities are minimal in patients with early glaucoma. Hence, there is a possibility that the supra-threshold contrast deficits seen in early glaucoma in this thesis may mainly arise from retinal abnormalities. There is also the possibility that post-retinal compensation resulted in minimal cortical deficits in patients with early glaucoma. Further experiments involving patients with more advanced glaucoma may help to elucidate post-retinal contrast processing mechanisms with glaucoma. In older adults, elevated cortical responses in the presence of reduced retinal responses suggest the possibility of age-related reduction in cortical inhibition. Altogether, the results of this thesis provide further understanding of the mechanisms underlying supra-threshold contrast deficits in early glaucoma and ageing.
-
ItemVision anomalies in migraine( 2013)The aim of this thesis was to investigate visual responses of people with migraine in between attacks, in order to infer possible mechanism/s underlying migraine pathophysiology. The proposed neural abnormality in migraine is cortical hyperexcitability. To measure neural activity in the visual cortex, previous studies have measured the cortical evoked response to patterned visual stimulation; however, these have yielded inconsistent results. This raises the possibility that mechanisms other than cortical hyperexcitability might contribute to vision anomalies in migraine. In this thesis, people with migraine (with and without aura) were compared to non-headache control participants. By measuring the cortical and retinal evoked responses simultaneously, Experiment 1 aimed to determine whether abnormalities in the cortical evoked response could be explained by dysfunction occurring earlier in the visual pathway. People with migraine showed reduced cortical responses but normal retinal function, indicating that the cortical deficits were unlikely to be a result of retinal dysfunction. The purpose of Experiment 2 was to consider whether loss of visual field sensitivity in people with migraine was related to abnormal cortical and/or retinal function. Performance was compared between two visits: less than and more than seven days after a migraine. Migraine sufferers showed repeatable deficits in the cortical evoked response that were not worse in the days immediately after migraine, implying stability of the cortical deficit. In contrast, Experiment 2 found further reductions in sensitivity in the days immediately after a migraine attack, confirming previous reports. Some individuals showed monocular and/or localised visual field defects that were worse after an attack, suggesting that these might be retinal effects of migraine. The final experiment explored the balance between inhibition and excitation, one of the competing theories underlying cortical hyperexcitability in migraine. Using a perceptual centre-surround task to assess inhibition and excitation simultaneously, Experiment 3 found increased suppression in people with migraine, indicating increased inhibition, for stimuli of lower centre contrast. The contrast-dependent changes in perception were associated with abnormal contrast gain, as demonstrated by increased cortical evoked responses at low contrast and decreased responses at high contrast. Thus, Experiment 3 provided further evidence for cortical hyperexcitability leading to abnormal visual perception in between migraine attacks. However, cortical hyperexcitability cannot account for all vision anomalies in migraine. Rather, there is also the potential for adverse sequelae of migraine, possibly outside of the brain, in otherwise healthy and asymptomatic individuals (Experiments 1 and 2). This thesis has implications for the use of non-invasive, clinical tests of visual function in clinical and research settings. People with migraine, on average, showed abnormal visual responses, even when asymptomatic and tested more than a few days after a migraine. This result reinforces previous suggestions that regular migraine sufferers should be excluded from normative databases. Additionally, there was considerable inter-individual variability in the visual responses, demonstrating that only a subset of individuals with migraine fall outside the range of normal visual performance. Further investigation of these particular individuals is potentially more informative regarding the pathophysiological processes of this debilitating condition.
-
ItemThalamocortical transformation of visual signals: role of geniculate orientation biases and intracortical circuits in orientation selectivity of striate cortical neurons( 2013)One of the fundamental questions in our understanding of the visual system is posed by various neurons along the afferent visual pathway, from eye to the brain, which differ in their response properties. While the neurons in the retina and the lateral geniculate nucleus (LGN) of cats and most mammals respond reasonably to diffuse patches of light, most primary visual cortical neurons (striate cortex) respond only to elongated stimuli of particular orientation. Hubel and Wiesel’s Nobel prize winning discovery of this orientation selective property of striate cortical neurons has opened up an enormous field for investigation. They proposed that striate cortical orientation selectivity arises from excitatory convergence of several non-oriented LGN afferents whose receptive fields are arranged along the long axis of the striate cell’s receptive field. The emergence of orientation-tuned responses among these striate cortical neurons from relatively poorly tuned thalamic neurons has been a topic that courted an intense debate. This comes from the findings of alternative models of orientation selectivity that have shown that the excitatory input from the LGN is almost circular, that the major excitatory drive comes from within the cortex and intracortical inhibition may have a role in the generation of orientation selectivity. These models claimed that inhibitory circuits within the visual cortex are required to sharpen the broadly tuned input from the LGN. One such model, called anisotropic LGN-driven recurrent model (ALD-R model), suggests an alternative scheme that exploits the orientation biases present in the responses of subcortical neurons, with the intracortical inhibitory and excitatory networks sharpening this broadly tuned subcortical inputs at the cortical level. Several experiments were designed in this study to test the predictions of the ALD-R model, including the role played by geniculate orientation biases and non-specific inhibition in the orientation tuning of cat striate cortical neurons. Firstly, the contribution of broadly tuned inhibition on geniculate orientation biases was tested using a novel electrical stimulation protocol within the LGN. The effect of this LGN electrical stimulation was also studied in the topographically corresponding striate cortical region. Our results showed that the non-specific inhibition brought about by electrical stimulation within the LGN resulted in significant sharpening of the LGN orientation biases as well as a mild broadening of the orientation selectivity of neurons in the corresponding striate cortical region. The effect of non-specific inhibition generated by this electrical stimulation paradigm was also compared with pharmacologically induced inhibition on geniculate relay cells and the results were comparable. These findings add support to the ALD-R model, where even non-specific inhibition acting on geniculate orientation biases could lead to sharper orientation tuning similar to those seen among striate cortical neurons. The dependence of striate cortical orientation preferences on LGN orientation biases was tested in the second experiment, where simultaneous paired extracellular recordings were performed from a geniculate cell and a cortical cell, which had overlapping receptive fields. The rationale behind this study is that a geniculocortical pair with matched orientation preferences would show higher coherence than a pair that has near orthogonal orientation preferences. The degree of coherence between the spikes from each neuronal pair was compared with the differences in optimal orientations exhibited by each geniculocortical pair. The results support the prediction of ALD-R model that orientation preferences of LGN neurons can predict the orientation preferences of striate neurons that they purportedly project to. The next experiment tested whether contrast invariance of orientation tuning, a property that is often pointed out as a drawback of Hubel and Wiesel’s model, is a subcortical property that gets transferred to striate cortical neurons. Extracellular responses of LGN neurons for varying stimulus contrasts were studied and their orientation sensitivities for the high and low contrast stimuli were compared. The results show that cat LGN neurons exhibit contrast invariance of orientation tuning and striate neurons could acquire this property from the geniculate excitatory inputs. Together, the results of the above studies substantiate the claims of ALD-R model where broad orientation selectivities present in geniculate inputs predict striate cortical orientation tuning and also other properties such as contrast invariance. The contribution of intracortical inhibition, especially those that are broadly tuned or non-specific is pivotal for the generation of orientation selectivity of striate cortical neurons.