Optometry and Vision Sciences - Theses
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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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ItemPerceptual suppression mechanisms in healthy ageing( 2017)Healthy ageing alters contextual spatial interactions such as centre surround contrast suppression and spatial suppression of motion discrimination. However, the exact neural mechanisms that underlie age related changes to contextual spatial interactions are still elusive. The body of work reported in this thesis explored the perceptual mechanisms behind altered contextual spatial interactions in younger and older adults using psychophysical and neuroimaging methods. Experiment 1 investigated the strength of foveal centre surround contrast suppression under intraocular and interocular viewing for two stimulus durations (40 ms and 200 ms) in younger and older adults. Foveal intraocular center surround contrast suppression decreased with longer stimulus duration whereas interocular surround suppression did not, suggesting contributions from separate mechanisms to these forms of suppression. In addition, intraocular center surround contrast suppression was increased in older adults compared to younger adults; however, interocular suppression was similar in both groups. Experiment 2 studied the effect of orientation of the surround grating in relation to the orientation of the centre grating (surround orientation effect) on centre surround contrast suppression under intraocular and interocular viewing in younger and older adults. Interocular and intraocular centre surround contrast suppression showed different surround orientation effect, and older adults demonstrated unaltered levels of surround orientation effect compared to younger adults under both intraocular and interocular viewing. Experiment 3 measured Gamma Aminobutyric Acid (GABA, the principal inhibitory neurotransmitter of the adult brain) levels in visual cortex of younger and older adults using magnetic resonance spectroscopy. Visual cortical GABA levels were increased in older adults compared to younger adults. In addition, visual cortical Glx (combined estimate of glutamate - the principal excitatory neurotransmitter, and glutamine) levels were reduced in older adults compared to younger adults. Neither GABA levels nor Glx levels in visual cortex correlated with foveal centre surround contrast suppression. The final experiment of this thesis (Experiment 4) investigated the relationship between visual cortical GABA levels and performance on two visual tasks that are hypothesised to be mediated, at least in part, by GABAergic inhibition: spatial suppression of motion discrimination and binocular rivalry. Both younger and adults participated in this experiment as well. Increased visual cortical GABA levels were associated with prolonged binocular rivalry percept durations and reduced spatial suppression of motion discrimination. The experimental frameworks used in the thesis were based on our modern understanding of cortical circuits that are implicated in mediating centre surround contrast suppression, and a neuroimaging technique that could potentially link physiology with behaviour. The novel findings reported in thesis answered some of the important questions related to perceptual surround suppression in younger and older adults. The current findings suggested that healthy ageing differentially affects distinct forms of suppression arising at various levels of the visual pathway, and challenged prior assumptions regarding age related changes to GABA levels within the visual cortex and its association with centre surround contrast suppression and spatial suppression of motion discrimination.
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ItemIncorporating spatial information into visual field testing algorithms( 2017)Current clinical perimetric thresholding algorithms are susceptible to high test-retest variability in areas of low vision and require long periods of patient concentration. A possible approach to addressing these limitations is exploiting spatial information in the visual field to inform the choice of stimulus location and intensity. This thesis aimed develop new perimetric algorithms using this approach, in an attempt to reduce test times and test-retest variability. The first experiment described in this thesis aimed to develop an algorithm that uses a heuristic approach to incorporate spatial information (Chapter 3). The new algorithm — SWeLZ (Spatially Weighted Liklelihoods in ZEST) — is a Bayesian procedure that uses modified likelihood functions to update information at multiple locations after each stimulus presentation. Computer simulations showed that SWeLZ achieved a comparable level of error to ZEST across all levels of sensitivity. SWeLZ was able to detect both glaucomatous and non-glaucomatous localised visual field loss. The number of presentations was reduced by 25% for SWeLZ relative to ZEST for normal visual fields. This reduction in test time was not found for visual fields with areas of visual field loss. The second experiment described in this thesis aimed to develop an algorithm that uses a Markov Random Field representation of the visual field to drive stimulus placement (Chapter 4). The newly developed algorithm—BART (Bayesian Adaptive Random Test) — uses local conditional probability distributions to describe likely sensitivity values. Many variants of the procedure were explored. BART was set to terminate in the same number of presentations as ZEST. BART achieved a similar level or error to ZEST for simulations when simulated with a reliable responder, but tended to overestimate visual sensitivity values in areas of absolute visual field loss, when simulated with a typical false positive responder. As is common in algorithm development, the newly developed algorithms were tested using computer simulation, which allows many tests to be run in a relatively short period of time. The final experiment described in this thesis aimed to explore the assumptions underpinning simulated responses (Chapter 5). Frequency of seeing curves were measured at three locations in the visual field for 16 observers with glaucoma, using both a forced choice and a yes-no procedure. The relationship found between sensitivity and frequency of seeing curve upper asymptote found in yes-no experiments disappeared when observers were forced to choose. This finding suggests that observers preferentially allocate attention towards locations with higher sensitivity. These experiments confirm previous findings that areas of moderate-to-severe visual field loss are associated with high test variability and reduced maximum response rates when measured with white-on-white standard automated perimetry. Given the small amount of information gleaned from testing these locations, it may be prudent to focus testing power elsewhere, such as on spatial extent of defects rather than defect depth.
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ItemIntegration of auditory and visual temporal rate in aging( 2017)This thesis investigated how aging affects the integration of visual flicker (the temporal modulation of luminance) with auditory flutter (the temporal modulation of sound amplitude) to produce a unified audiovisual percept of temporal modulation rate. A group of younger and older adults judged the temporal rate of an auditory and/or visual stimulus oscillating at 10 Hz. Whichever sensory modality discriminates temporal rate more precisely, contributes more to the audiovisual percept. Consequently, the first experiment explored how aging affected the precision of auditory temporal rate discrimination relative to vision. Auditory temporal rate discrimination in older adults was degraded by an age-related impairment in sensitivity to auditory amplitude modulation. In subsequent audiovisual experiments, auditory modulation depth was individually tailored to equate flutter and flicker temporal rate discrimination thresholds to normalise for this age-related sensory loss. When auditory and visual rates were conflicting, partial integration distorted perceived rate such that the auditory or visual rate subjectively equivalent to a reference was nonveridical. Distortions in perceived rate were unaffected by older age, indicating that the ability to integrate conflicting auditory and visual rates is preserved in aging. However, younger adults’ heightened sensitivity to auditory amplitude modulation was sufficient to increase the influence of audition on perceived rate when the modulation depth of auditory flutter was the same as the average older adult. Therefore, the age-related impairment in auditory rate discriminability is expected to increase visual influence on audiovisual rate perception in older adults. When auditory and visual rates are identical, temporal rate discrimination thresholds improved in line with statistically optimal integration in younger but not older adults. This indicates an age-related impairment in integration, which will be further compounded by the age-related decline in auditory temporal rate discriminability under natural conditions. These findings indicate that older adults will perceive audiovisual temporal rate differently to younger adults. These age-related changes in audiovisual rate perception will be the complex product of the age-related interaction between rate congruence and integration ability, and the age-related decline in auditory temporal rate discrimination.
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ItemThe effects of task-induced stress and mental workload on visual performance and eye movement behaviour in nystagmus and controls( 2016)Background and aims: During daily activities, individuals may experience stress when a visual task is combined with an irrelevant mental task (e.g. conversing). Clinical examinations of patients with infantile nystagmus syndrome (INS) may elicit subjective reports of worsened nystagmus under internal states such as stress. Although the negative effects of stress on visual function have been widely studied in healthy subjects, few studies are available for patients with INS. Previous findings have demonstrated that INS is influenced by task conditions (i.e. visual demand and internal states such as stress); however, these studies limited their methodologies to only the null or central gaze position. Gaze position, solely, can affect visual function in INS and can affect INS parameters such as foveation time. By acknowledging that gaze position can affect INS, one gaze position (e.g. central) may not be enough to measure the changes in INS arising from task variations. Here, we hypothesised that a task-induced change from baseline in INS parameters at the null position would differ from task-induced changes at the gaze position away from the null. Patients with INS may also complain of being slow to see. Target acquisition time and the following visual processing time can affect the total period taken to react to a visual object. Surgical improvement in foveation has resulted in a reduction in both target acquisition time and visual recognition time. A few studies have reported that stress exacerbates nystagmus by increasing its intensity and reducing foveation time. Since tenotomy has been reported to decrease target acquisition time in INS, there was a possibility that changes in INS parameters under internal states such as stress affected target acquisition time. Thus, our second hypothesis stated that the effects of stress on visual timing would differ between control and INS subjects. The objective was to measure the extent to which saccades, target acquisition and visual processing times are affected by cognitively induced stress in INS subjects in comparison to the control group. Methods: To test our first hypothesis, we conducted a visual acuity experiment. We varied task conditions by manipulating levels of mental load and visual demand, thus inducing varying stress levels. Participants with idiopathic INS were required to determine the direction of Tumbling-E targets, which varied in size and contrast, using a staircase procedure across ±25° gaze positions, with 5° steps from the centre. To test our second hypothesis, we conducted a saccade experiment, which required INS and control subjects to respond to the direction of horizontal E targets presented randomly at the post-saccade position, set at ±25° with 5° step, away from the centre. Visual task performance was measured by subjects’ reaction time and their response accuracy to the direction of the post-saccade target. Each of the above tasks was performed under two conditions: alone (low mental load) and with mental arithmetic and time restriction (induced high mental load). Perceived workload across these task conditions was assessed via changes in heart rate as well as other physiological measurements such as skin conductance level, and subjective ratings. The subjects’ eye movements and visual task performance were recorded across varying task conditions. Results: The induction of the mental arithmetic task and time restriction increased mental workload. For both visual acuity and saccade experiments, the metrics of task performance worsened under high mental load. For the visual acuity experiment, there was a significant interaction between mental load and gaze position for foveation time and task performance. Interaction effects were interpreted as follows; during high visual demand, the change in foveation time due to mental load was greater at the null than away from it. Similarly, the increase in last optotype size from the low to high mental load condition was more pronounced at the null than away from it. During both low and high mental load, saccade latency, target acquisition time, and visual recognition time were longer in the INS group in comparison to controls. For both control and INS subjects, saccade latency and target acquisition time increased with high mental load. The LATER model (Linear Approach to Threshold with Ergodic Rate), implemented to analyse saccade latency in the control group, highlighted that the rate of rise in saccade decision signal decreased during high mental load. Visual recognition time increased with high mental load only in the INS group. The effects of mental load on the gain of prosaccades and target acquisition time varied between INS and control subjects. Discussion: We suggested that the extent to which foveation duration contributes to visual function varies across both task conditions and gaze positions. We agreed with the notion that an extended foveation time does not guarantee an improvement in visual task performance in INS. Previous studies have highlighted that INS subjects are late in detecting a new target, which can result in a delay in target acquisition. Consistent with the literature, our study concluded that difficulty in the accurate programming of eye movements used to acquire a new target can also delay target acquisition time. Our results suggest that a further increase in target acquisition time with stress worsens the phenomenon of being slow to see in INS. We concluded that an increase in saccade latency with high mental load is due to a reduction in the capacity of information processing resources in both individuals with and without INS. However, visual recognition time in INS is multifactorial and can show additional increases under stress (e.g. driving) when compared to normal subjects. We have suggested that the efficacy of visual processing further decreases with effort to see in INS. Conclusion: Possible main and interaction effects of task condition and gaze position on foveation time can lead to an overestimation of visual function in INS. Accuracy and speed of the subjects’ response to visual targets should be measured with a mental load resembling real world conditions. The results can be useful in relation to work safety and clinical assessment of INS, especially in terms of treatment outcomes.
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ItemTemporal disintegration: a phenomenological and neurophysiological investigation( 2017)The primary aim of this PhD research programme was to explore the neurophysiological correlates of temporal disintegration. This phenomenon is typified by disturbing anomalies in the normal flow and experience of time, and is a significant co-morbidity in a variety psychiatric illnesses. The research focused on the application of sub-second and supra-second psychophysical methods as well as neuroimaging to explore neural correlates of temporal disintegration. Experiments were conducted with two cohorts: patients with bipolar disorder, and healthy participants who were administered the dissociative agent ketamine. The bipolar disorder study utilised a longitudinal, repeated measures design. The ketamine experiments were randomised, double blind studies with placebo controls. Three main types of measurements were used in the studies. Firstly, questionnaires were administered which measured mood states, dissociative states and temporal disintegration. Secondly, behavioural responses to visual stimuli were measured in two temporal domains: sub-second perceptual ordering, and supra-second perceived duration judgement. Thirdly, during performance of the sub-second task, neuroimaging was conducted: fMRI for participants given ketamine and EEG for patients with bipolar disorder. The sub-second method was adapted from the temporal order judgement task of Morrone et al. [2005]. Participants reported the order of two briefly flashed stimuli presented close to the time that they made an eye movement. In this task, the stimuli may appear to be inverted in temporal order, especially when eye movements coincide with the flashed stimuli. The supra-second method was adapted from the colour-time task of Coull et al. [2004]. It involved judging the relative duration of two successive stimuli that cycled through a range of colours over time. In the bipolar disorder patients, a strong association was found between measures of mood, dissociative symptoms and the phenomenon of temporal dissociation. For the supra-second task, we found lower mood scores (measured by the Bipolar Depression Rating Scale) were associated with a greater number of errors in the time condition than the colour condition. For the sub-second psychophysical tests, the proportion of inverted temporal judgements increased in association with manic symptoms (11% increase for each point increase in Young Mania Rating Scale, p<0.05). Manual reaction times in 2AFC responses to temporal judgements were lengthened by ketamine and in inverted judgements. The fMRI results showed increased BOLD signal for inverted trials bilaterally in the insular/claustral regions and in the anterior cingulate cortex (p<0.001). In inverted trials, temporal disintegration as measured by the Temporal Integration Inventory was correlated with the activity of the left temporoparietal junction (Kendall’s τ = 0.48, p < 0.01). Together, these findings indicate that there is a significant linkage between mood and dissociative states and the phenomenon of temporal disintegration. They also reveal that both sub-second and supra- second timing performance are altered by ketamine induced dissociation and with mood changes in bipolar disorder. The findings provide support for an integrated functional network involved in sub-second temporal processing which includes the claustrum and temporoparietal junctions. These insights are important in that they can inform our understanding of the determinants of temporal disintegration and may also provide insights into the underlying pathology of bipolar disorder.
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ItemThe role of oral long chain omega-3 supplements for treating dry eye disease( 2017)Dry eye disease (DED) is a highly prevalent multifactorial eye condition. While traditional therapies, such as ocular lubricants, provide symptomatic relief for dry eye sufferers, they do not treat the inflammatory overlay found in DED. Omega-3 (ω-3) essential fatty acid (EFA) supplements show promise as a potential treatment for DED. The major aim of this thesis was to compare the efficacy of two forms of long chain ω-3 EFAs, stored primarily as either triacylglycerides (fish oil) or as phospholipids (krill oil), for treating DED. In this regard, a randomised, placebo-controlled, double-masked, three-arm, parallel- group clinical trial was conducted. Sixty participants with clinically significant DED-related symptoms were enrolled for a three-month study. In addition this thesis aimed to determine the effects of elevated tear osmolarity on central corneal thickness (CCT) and corneal reflectivity. In a cross-sectional study involving 38 participants with hyperosmolar tears and 10 age-similar controls with normo-osmolar tears, anterior-segment optical coherence tomography (OCT) was used to detect subtle corneal microstructural changes that occur in association with tear hyperosmolarity. This study aimed to examine the effects of elevated tear osmolarity on central corneal thickness (CCT); and to measure the effects of elevated tear osmolarity and corneal reflectivity. Central corneal thickness (CCT) of participants with severely hyperosmolar tears (defined as eyes in the upper quartile for tear hyperosmolarity, 539.1 ± 7.4 µm) was found to be less than those with mildly hyperosmolar tears (defined as hyperosmolar eyes in the lower quartile for tear hyperosmolarity, 622.7±5.8 µm, p<0.0001) and control eyes (583.1 ± 15.0 µm, p = 0.02). Central corneal reflectivity (45.1 ± 0.3 versus 48.1 ± 0.6 greyscale units, p = 0.02) was relatively lower and peak tear film reflectivity higher (by 4.8% ± 3.5%, p = 0.04) in eyes with hyperosmolar tears than eyes having normo-osmolar tears. In order to test the relative efficacy of two forms of long-chain ω-3 EFA supplements over a three month intervention period, a randomised, placebo-controlled, double-masked, three-arm, parallel-group clinical trial was conducted. Sixty participants with clinically significant DED-related symptoms (Ocular Surface Disease Index Score (OSDI) score of 18-64) and tear hyperosmolarity (≥ 316 mOsmol/L) were randomly allocated (1:1:1) to one of three groups: triacylglyceride ω-3 EFAs (1000 mg/day eicosapentaenoic acid, EPA + 500 mg/day docosahexaenoic acid, DHA), phospholipid ω-3 EFAs (945 mg/day EPA, + 510 mg/day DHA) or placebo (1500 mg/day of olive oil). Primary outcome measures were: mean change in tear osmolarity and OSDI score from baseline (Day 1) to Day 90. Secondary outcomes included: mean change in key clinical signs of DED (ocular surface staining, ocular redness, meibomian gland integrity, anterior blepharitis, tear stability, tear production and tear volume). Fifty-four participants completed the study. Tear osmolarity was significantly reduced from baseline in both the triacylglyceride (fish oil) [n = 19, -19.8 ± 4.5 mOsmol/L, p < 0.001] and phospholipid (krill oil) [n = 18, -18.6 ± 4 mOsmol/L, p < 0.001] groups at Day 90. Only the krill oil group showed a significant reduction in OSDI symptom score [-61.4% ± 5.2%, p = 0.009] relative to the placebo group [n = 17, -32.4% ± 9.6%] at Day 90. Secondary outcome measures of ocular redness, meibomian gland capping, tear stability and corneal staining, were all significantly improved with long-chain ω-3 EFA treatment at Day 90 compared to baseline. There were no significant inter-group difference in tear production, tear volume, corneal thickness, corneal transparency, peak tear film reflectivity or Symptom Assessment in Dry Eye (SANDE) questionnaire scores relative to baseline. These two studies give insight into both the corneal micro-structural changes that occur in association with tear hyperosmolarity and provide evidence that moderate daily doses of long-chain ω-3 EFA supplements, in either predominantly triacylglyceride or phospholipid form, significantly reduce key clinical signs and symptoms of DED, compared to placebo over a three-month treatment period.
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ItemThe influence of playing video games as an attention rehabilitation technique in patients with traumatic brain injury( 2016)Introduction: Video game playing has been suggested to modify various aspects of visual attention in healthy adults. Moreover, it has been tried as a training regimen to improve less than normal cognitive and perceptual abilities in groups such as the elderly and individuals with amblyopia and dyslexia. However, so far there is little evidence regarding possible game related modifications on overt allocation of visual attention (i.e. saccadic eye movements). Therefore, our first aim was to investigate whether or not observed benefits of gaming on covert allocation of attention can be related to any modifications in eye movement behaviour. Then, the influence of video game training as a possible attention rehabilitation technique in patients with traumatic brain injury (TBI) was examined. Methods: Three experiments were conducted to address these aims. In experiment one, saccadic eye movement characteristics of 33 gamers and 18 non-gamers were compared using four simple saccade paradigms along with two attentional measures. In experiment two, 40 healthy non-gamers were allocated to play either an action video game (Call of Duty: Modern Warfare 2) or a control card game for 10 hours to investigate the causal influence of gaming on saccadic eye movements in five visual search paradigms. In experiment three, four patients with history of traumatic brain injury were trained on the game Call of Duty and their eye movement characteristics and attentional abilities were assessed using a single case experimental design. Results: Except for a shorter antisaccade latency in video gamers, there were not any significant differences between gamers and non-gamers in their eye movement characteristics as tested with simple paradigms. However, gamers tended to be more impulsive, as measured with a continuous performance test. In the second experiment, non-gamers who were trained on an action game did not show any significant modification of their eye movement behaviour while performing visual search tasks. However the vertical distribution of their fixations became narrower in the game-related search task, suggesting that they only learned the likely distribution of targets important in the game. A few significant improvements were observed in each patient with TBI as a result of the action game training, including shorter memory-guided saccade latency and faster search time in patient 1, shorter antisaccade latency and higher rate of self-paced saccade generation in patient 2, more accurate prosaccade gain, higher rate of self-paced saccade generation and faster search time in patient 3 and faster search time and shorter fixation duration in patient 4. Discussion: The findings generally suggest no eye movement modifications as a result of video gaming in neurologically intact people obtained both in cross-sectional and game training experiments. This finding might be related to already optimal eye movement functioning, as we normally move our eyes 2-3 times a second, therefore experiences such as video games cannot further enhance this function. A few improvements were observed after action game training in each patient with TBI in this exploratory study. The differences seen in the patients may reflect differences in underlying pathology. However to propose this technique for attention rehabilitation, more evidence, perhaps using custom made video games adaptable to patients’ needs, is required.
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ItemImproving adaptive optics image quality in high powered eyes( 2016)Adaptive optics (AO) retinal imaging has been widely used for high resolution in vivo imaging studies in the human eye over the last two decades. More recently, this technology has been applied to image the retina of small animals such as rodents. Small animal eyes offer many advantages for the scientific study of retinal diseases, and theoretically have potential for superior image quality compared to human eyes. Unfortunately, to date AO image quality in practice is inferior to state-of-the-art image quality obtained from the human eye, and the cause of these limitations has not been fully understood. This work aimed to investigate and address the limitations to AO image quality in rodent eyes, and explore novel techniques in adaptive optics correction and image processing to overcome these limitations. The first experiment used optical modelling to test several commonly made assumptions in human AO imaging. These assumptions were found to be inappropriate for extrapolation to rodent eyes, due to their very high power and dioptric thickness of the retina. Specifically, results showed that AO image quality for the human eye is robust against positioning errors of the AO corrector and to differences in imaging depth and wavelength compared to the wavefront beacon. On the other hand, image quality for the rat eye declined sharply with each of these manipulations. The second experiment used a purpose-built flood-illumination AO ophthalmoscope designed for rat eyes to validate the modelling results from the first experiment, using physical model eyes of varying optical power. It was found that in general, AO image quality from the lower powered (60 D) model eye was much less susceptible to manipulations similar to those described in the first experiment, compared to the higher powered (220 D) model eye, thus confirming the optical modelling results. The same optical system was then used to account for these limitations as much as possible, while imaging adult pigmented Long-Evans rats. However the images obtained showed only modest improvement compared to the pilot experiment. It is argued that this occurred primarily due to intra-ocular scatter and the challenging wavefront sensing step in the rat eye which are exacerbated in our flood illumination setup. The third and fourth experiments explored two novel techniques, HiLo imaging and non-sensing AO, to address problems with intra-ocular scatter and wavefront sensing respectively. Both experiments resulted in noticeable improvements in AO image quality from the rat eye. In conclusion, with almost twice the numerical aperture, retinal image resolution for rodent eyes is potentially far better than the human eye, provided aberrations can be corrected with AO. This thesis explored the limitations to AO image quality in rodent eyes, as well as practical methods to improve image quality by addressing these limitations. Although the final flood-illumination AO image quality from the rat eye was still inferior compared to scanning AO modalities, the findings from this thesis could be used to improve the AO image quality for all imaging modalities for both human and rat eyes.
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ItemEye movements in neurocognitive disorders and frontotemporal dementia( 2016)Introduction/Objective: Frontotemporal dementia (FTD) is a young onset heterogeneous neurodegenerative condition which presents with changes to behaviour and language and causes degeneration of a number of cortical regions, particularly the frontal and temporal lobes. Onset of the disease is often insidious, and a wide variety of presentations can be seen clinically. Signs and symptoms can be difficult to quantify early in the disease and there is a large overlap with a range of other diagnoses. Neuropsychological testing can often under-represent the deficit seen behaviourally by collateral observers and return a non-specific profile. Vision is a dominant sense and the brain pathways and networks used for eye movements are widespread and well-documented. Therefore the aim of this thesis was to characterise eye movements in frontotemporal dementia across a hierarchical range of movements and to investigate if eye movements could be linked to neuropsychological deficits occurring in the disease. Method: FTD and control participants were recruited to examine eye movement changes in the disease. A hierarchical battery of eye movements were examined beginning with the simplest movements, saccades, which require only a short pathway through the brainstem, and progressed to examining scan paths in more complex tasks including facial emotion recognition, visual search and driving, thus recruiting additional cortical regions and networks. These tasks were selected as FTD patients are reported to have difficulty correctly undertaking them. Saccadic eye movements included horizontal and vertical reflexive saccades, which were then built upon by examining higher-order saccades including antisaccades, self-paced, predictive and memory-guided saccades. Results were examined with regard to eye movement characteristics reported in the literature for other neurocognitive conditions including parkinson’s-plus disorders, schizophrenia and Alzheimer’s disease. Results: A total of 28 FTD variant and 25 controls were recruited to participate. Not all participants undertook all tasks. Some participants were unable to undertake specific tasks either due to complexity or in the case of the driving task because they had never held a licence. In addition some participants had to stop partway through a task due to simulator sickness. Within the FTD group insufficient semantic dementia and progressive non-fluent aphasia patient participants were able to be recruited and so their data is presented in each task as pilot data. There was also a reduction in data due to some trials being excluded for poor tracking. Saccadic eye movements revealed an increased latency across all basic movements. Scan paths to emotional faces from the Ekman Pictures of Facial Affect series revealed a reduced gaze time to the right eye for both implicit and explicit face viewing but otherwise resembled those of controls. Eye movements whilst driving revealed gaze times not significantly different to any area of interest other than to pedestrians, which elicited less gaze time from bvFTD participants. Eye movements during visual search revealed an increased reaction time intercept but a similar processing time per item to control participants. Scan paths to all tasks were qualitatively normal. Discussion: Eye movements were analysed across a hierarchical range of movements, starting with simple eye movement circuitry and progressively incorporating more brain regions and networks. Stimuli were selected to specifically target tasks known to produce errors in FTD. Our study revealed bvFTD patients display eye movement changes sharing two prominent features: a psychomotor slowing and a disruption of salience, possibly due to changes in their assignment of mind. Psychomotor slowing has been evidenced in both saccade and visual search tasks as patients were able to correctly undertake the task but at a significantly slower pace, seen in increased reaction times and increased latencies. The alterations in salience noted including reduced gaze time to the right eye and a lack of gaze time to pedestrians whilst maintaining qualitatively normal scan paths and gaze durations to other areas of interest, leads to the conclusion that social cues are detected but not processed and interpreted correctly. Qualitatively normal scan paths are in stark contrast to those seen in a number of overlapping neurocognitive diseases including schizophrenia and Alzheimer’s disease, which have been reported in the literature to lead to hypo-scanning and disorganised scan paths respectively. Our study did not differentiate different pathological groups; however there were a wide range of responses in each task which may reflect different underlying pathologies, this finding warrants future studies examining saccadic paradigms other than reflexive and antisaccades. Scan paths, such as to faces, may be able to be utilised diagnostically in conjunction with other examinations to differentiate between bvFTD and other degenerative groups. Performance on the driving simulator task suggests potential for a driving task to be developed to examine safety to drive.