Models of the neural basis of visually guided behavior suggest that the mammalian brain has two independent visual systems: one involved in pattern vision, and the other involved in orienting to visual stimuli. Orienting was measured in this series of studies by examining both the thirsty rat's ability to disrupt licking in response to the presentation of visual and auditory displays and the animal's head and postural responses to the displays. Habituation of orienting behavior with repeated presentation of a display, and dishabituation to the subsequent introduction of changes in it were also examined. The effect on this behavior of variously sized cortical and subcortical lesions of the visual system and the influence of extrinsic and intrinsic variables were assessed. The investigation revealed that lesions of the superior colliculus do not result in visual agnosia or the inability to perform the appropriate motor responses involved in orienting; rather, while the orienting response is available in the behavioral repertoire of the lesioned animal, it is not always emitted in response to the visual displays that the intact animals treat as less salient. The superior colliculus lesioned animals do orient to and localize visual displays which are more salient for the intact animal. Further, the deficit in orienting to the "less" salient stimulus displays can be reduced or eliminated by changing the degree of water deprivation prior to testing and they are capable of using this display as a signal of shock. Lesions restricted to a very small portion of the lateral edges of the deep layers of the superior colliculus and the dorsal tegmentum had the same consequences as superior colliculus lesions, while lesions which included only the superficial layers of the superior colliculus did not. Lesions of the striate and extrastriate cortex did not significantly affect orienting behavior. Rats with lesions of the superficial or deep layers of the superior colliculus and rats with lesions including area 7 of cortex as well as the striate and extrastriate cortex, did,however, habituate more quickly than intact animals to the repeated presentation of the visual displays, and generally did not dishabituate in response to the changes in the visual displays. These findings suggest a relationship-between the cortex, the superficial layers, and the deep layers of the superior colliculus and the ability of animals to shift attention within a stimulus modality. The deep layers of the superior colliculus may also be important for shifts of attention between stimulus modalities (Jane, Levey, & Carlson, 1972). Overall, these results were discussed with regard to a possible modulating role of the superior-colliculus and cortex in orienting behavior and in terms of the parameters of orienting which must be taken into account in the development of an adequate model of the neural basis of orienting behavior. / Arts, Faculty of / Psychology, Department of / Graduate

Spatially structured bursts of propagating neural activity revealed in cortical slice experiments and in vivo tantalise many scientists on their possible functional mechanisms. Theoretical studies suggest waves with complex firing patterns afford a great capacity for the transmission of information across the brain. This thesis develops a framework for analysing the dynamics of such waves within spiking neuronal networks. We seek to investigate important questions concerning how the wave’s spatiotemporal voltage properties, propagation speed and spike time interval distributions depend on the underlying network structure and the intrinsic features of the neurons that make up the network. These are often difficult to extract with biophysically detailed network models. We therefore analyse simplified spiking networks of synaptically connected neurons, capable of supporting a rich repertoire of propagating activity, yet, amenable to mathematical analysis. Useful information is then obtained on the dynamics of waves found in this network in relation to the model’s parameters. These results can be compared to the findings obtained from more detailed computational studies and experimental observations. Numerical simulations in discrete networks of integrate-and-fire neurons reveal localised bumps that can wander diffusively across the network. These wandering bumps are seen to evolve into persistent synchronous coherent propagating structures, where neurons fire multiple times as the wave envelope passes over. We call these structures multiple-spike waves. An intrinsic feature of the neuron, describing how quickly neurons process synaptic current, is shown to be an important determinant in the emergent network activity. Waves with different number of spiking events co-exist across most parameter regimes, and with lateral-inhibition synaptic connectivity structure, can exhibit large variability in wave speed that has not been reported in studies of networks with purely excitatory connectivity. As a result, we investigate the interaction dynamics of multiple-spike waves on a large spatial domain. Here we find that multiple-spikes waves can merge to form a composite system, with greater complexity in the firing patterns, increasing the wave’s information content. Mathematical progress is made by studying a partial integro-differential equation that is equivalent to the discrete network as the number of neurons tends to infinity. We develop a method of solving the wave speed of the multiple spike waves and its set of spike-times, which then allows us to construct the network’s exact voltage and synaptic profiles and formulate a non-local eigenvalue problem to compute asymptotic stability. This is achieved by considering general perturbations around the wave’s firing times. An in-depth numerical study on the multiple-spike wave’s bifurcation structure is performed, uncovering various mechanisms behind propagation failure and how the wave’s dynamics depend on the network’s system parameters. The analysis of waves with a large number of spikes poses interesting questions regarding the existence of stationary bump solutions in the continuum limit. Uncertainty quantification is performed on waves, revealing how different types of uncertainty in system parameters influence the wave solutions statistical properties. This allows for predictions of the spatial regions of the waves profile most vulnerable to destabilisation. We finally analyse synaptically generated waves in a similar spiking network of Morris-Lecar neurons, where we find interesting transitions from single to double spike waves. Also, similar to what was seen in the integrate-and-fire network, the wave’s dynamics at the network level is strongly influenced by the neuron’s intrinsic features.

Background: Healthy cognitive ageing entails a number of neurobiological processes which may contribute to optimal functioning and quality of life in ageing. While the full extent of the underlying mechanisms of healthy ageing are yet to be described, there is an important interplay between brain structure, function, and genetic makeup that determines ageing trajectories. Notably, the Apolipoprotein E (APOE) gene has been established in the Alzheimer’s disease (AD) literature to impact brain structure and function, and may also show congruent effects in healthy older adults, although findings in this population are much less consistent. Structural Magnetic Resonance Imaging (MRI), Diffusion Tensor Imaging (DTI), and neuropsychological measures present as useful, non-invasive tools to investigate the impact of APOE allele status on grey matter structure, white matter integrity, and cognitive functioning, respectively. Few studies have used these measures together to describe healthy ageing, and findings are mixed (e.g., no differences seen, different suggested regions of difference, etc.). The current study aims to describe the impact of APOE genotype on brain structure and function in healthy older adults using multimodal methods. Method: Data were obtained from the Alzheimer’s Disease Initiative phase 3 (ADNI3) database. Baseline MRI, DTI and cognitive composite scores for memory (ADNI-Mem) and EF (ADNI-EF) were acquired from 116 healthy controls. Participants were grouped according to APOE allele presence (APOE-ε2+ N= 17, APOE-ε3ε3 N= 64, APOE-ε4+ N=35). Voxel-based morphometry (VBM) and tract based spatial statistics (TBSS) were used to compare grey matter volume (GMV) and white matter integrity respectively between APOE-ε2+ and APOE-ε3ε3 controls, and again between APOE-ε4+ and APOE-ε3ε3 controls. Multivariate analysis of covariance (MANCOVA) was used to examine the effects of APOE polymorphism on memory and EF across all APOE groups with covariates of age, sex, and education, and cognitive scores were correlated (Pearson r) with imaging metrics within groups. Results: No significant differences were seen across groups or within-groups in MRI metrics or cognitive performance (p>0.05, corrected for multiple comparisons). Non-significant trend-level results suggested 1) Increased fractional anisotropy (FA) and GMV was present in APOE-ε2+ compared to APOE-ε3ε3. 2) Increased mean diffusivity (MD) and decreased GMV was present in APOE-ε4+ compared to APOE-ε3ε3 (p<0.2, corrected for multiple comparisons). Non-significant moderate effect sizes were seen for a positive trend between GMV and EF (r= 0.36, p= 0.18) in APOE-ε2+ and a negative trend between MD and EF in APOE-ε4+ (r= -0.33, p= 0.05). Conclusions: APOE polymorphisms do not appear to impact brain structure and function differently in healthy ageing. Trend-level findings align with reports from previous research, although results remain mixed. Overall, this study suggests neurostructural and functional differences across APOE genotype are not present in cognitively healthy older adults, and future studies should aim to clarify APOE mechanisms in healthy ageing with the addition of other variables (e.g., imaging, cognitive, & lifestyle factors), longitudinal design, and in a larger sample. / Graduate / 2022-08-17

Escalating rates of aggression in South African schools, particularly in the Western Cape, are disconcerting. The early childhood through adolescent years is therefore an important platform for investigations to inform strategies to reduce and prevent aggressive behaviour. Studies conducted outside of South Africa have identified numerous correlates of aggressive behaviour; investigation in South Africa has, however, been sparse. The role of empathy, in specific, has been limited to one prior investigation. Furthermore, while empathy is considered an important construct in explanations of aggressive behaviour internationally, theoretical and methodological issues have undermined findings to date. Our understanding of the relationship between empathy and aggressive behaviour needs refining. I investigated the role of empathy, while simultaneously investigating the role of several known correlates of empathy and aggressive behaviour in typically developing young adolescents (N = 160, ages 11-13; Study 1) and children (N = 76, ages 6-8; Study 2) living in the Western Cape of South Africa. To improve on previous investigations, I employed a framework informed by both neurobiological and behavioural approaches. I conceptualised empathy as comprising affective and cognitive components, as well as a self-regulation component concerned with regulation of affective states. Employing a contextual approach, I argued that the interaction between these empathy components along with multiple contextual factors would provide a more nuanced understanding of the relationship between empathy and aggressive behaviour. I used hierarchical regression and structural equation models to investigate the correlates of aggressive behaviour. Empathy was significantly correlated with Aggressive Behaviour in young adolescents, but not in children. Furthermore, as expected, contextual factors were also significantly correlated with Aggressive Behaviour: Household Income, Parenting Style, and Parent Empathy were correlated with Aggressive Behaviour in young adolescents, while among the measures taken only Parenting Style was correlated with Aggressive Behaviour in children. Future investigations should, as in the current dissertation, work towards articulating the complex web of relationships between correlates of aggressive behaviour and their changes across development.

This experiment tested three hypotheses regarding right cerebral involvement in hostility and physiological arousal. First, replication of previous research indicating heightened physiological responding to stress among high hostile individuals was attempted. Second, high hostile individuals were predicted to an increased tendency toward right hemisphere dominance following exposure to a stressor. Third, high hostile individuals were expected to maintain their physiological arousal and shift in cerebral laterality longer than the low-hostile comparison group. Low- and high-hostile participants (25 males per group, drawn from the undergraduate Psychology pool) were identified using the Cook-Medley Hostility Scale (CMHS). Physiological measures (SBP, DBP, HR) were recorded at baseline, as were results from a dichotic listening procedure. Participants were then administered the cold-pressor procedure, and physiological recordings were taken again. Dichotic listening procedures were then administered 3 consecutive times to monitor for shifts in cerebral laterality. After the final dichotic listening procedure, physiological measures were taken once again to determine recovery rates. Results did not support the a priori hypotheses. Specifically, low-hostile individuals were consistently higher on the physiological measures when compared to the high-hostiles. The predicted maintenance of increased physiological arousal was also not supported by the data. Neuropsychological measures also failed to differentiate between the groups, and failed to demonstrate the predicted shift in cerebral laterality. / Master of Science

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Using the Limited Capacity Model of hostility (Walters & Harrison, 2006; Williamson & Harrison, 2005; Williamson, Harrison, & Walters, 2007) as a guide, the stress response of individuals with a variable and dysregulated fuel supply to their brain (diabetes) was examined subsequent to lateralized fluency-stress. This theoretical "capacity" model of hostility was applied to a relatively unknown population of high hostile-diabetics. Given the associations between hostility and diabetes, it was argued that a very robust stress response would be evident, as measured as by peripheral glucose and QEEG magnitudes, as a result of modest regulatory capacity subsequent to right frontal lobe stress. Moreover, it was expected that high hostile-diabetics would show diminished performance on neuropsychological indicants of right frontal functions. / Ph. D.