The mechanisms involved in the cause and progression of chronic neurodegenerative diseases are still unclear. The ubiquitin proteasome system (UPS) plays an essential role in the maintenance of intracellular protein homeostasis by degrading unwanted proteins. The accumulation of ubiquitinated proteins is a hallmark of major neurodegenerative diseases, including Alzheimer’s and Parkinson’s diseases. In most cases, these diseases are also associated with changes in cytoskeletal proteins and microtubule stability. We previously reported decreased levels of microtubule destabilizing protein stathmin (STMN) following 26S proteasome dysfunction in mouse cortical neurons; associated with neurodegeneration and the formation of intraneuronal protein inclusions in surviving neurons. This suggested a role for the 26S proteasome in maintaining the neuronal cytoskeleton. This thesis investigates the levels and localisation of cytoskeletal proteins in mouse cortical neurons following 26S proteasome dysfunction (Psmc1fl/fl;CaMKIIα-Cre). This study provides new insights into the role of the UPS in maintain cytoskeletal proteins that may be important in neurodegenerative disease. We found an early increase in neurofilaments following 26S proteasome dysfunction; before obvious changes in microtubule stability. An increased free/polymerised tubulin ratio was evident at later stages indicative of microtubule instability in Psmc1fl/fl;CaMKIIα-Cre mice. In addition, we found decreased levels of microtubule proteins, microtubule-associated proteins and detyrosinated-tubulin; with increased tyrosinated-tubulin following 26S proteasome dysfunction. These changes are contrary to decreased STMN expression observed in Psmc1fl/fl;CaMKIIα-Cre mice. We suggest that decreasing STMN may be part of a negative feedback loop to stabilize MT following 26S proteasome dysfunction. STMN is known to be a downstream target of p53, p27 and the PI3K/Akt pathway. We found expression of p53 was increased in the cortex following 26S proteasome dysfunction, correlating with decreased phosphorylated-Akt expression at an early stage and may effect STMN expression. However, we did not observe any significant differences in pro- and anti-apoptotic proteins of the Bcl-2 family between control and Psmc1fl/fl;CaMKIIα-Cre mice, which may also by effected by p53 and phosphorylated-Akt. Immunohistochemical studies revealed changes in cortical neuron morphology accompanied 26S proteasome dysfunction. Cortical thickness was significantly decreased; associated with less neurons in the layers III and V. However, nuclear size of cortical neurons was increased, as well as the length and arborisation of their apical dendrites. Taken together, our novel data contributes to our understanding of molecular and cellular events underlying neurodegeneration and suggest that control of microtubule changes may help to slow or restore pathology of neurons.

Older adults with dementia are at increased risk of becoming incapable of making their own decisions and may therefore benefit from planning for care at the end-of-life. Advance care planning (ACP) is a complex, multifaceted process by which people can express their wishes about care at the end-of-life in case they become incompetent to make decisions for themselves. However, we have little understanding of the ACP process among people with dementia and their families. This study addressed three questions: 1) when and how to cognitively impaired older adults and their families receive information about ACP; 2) in which aspects of the ACP process do families of cognitively impaired older adults engage, and why (and does this fit within the framework of the transtheoretical model of behaviour change [TTM]); and 3) how ACP relates to the way in which family members perceive the quality of death of their loved one. 22 family members of deceased older adults with dementia were interviewed and data was analyzed using interpretive description qualitative methods. Participants reported that information about ACP is provided in a haphazard and often incomplete manner, leading to difficulty engaging in the ACP process. Older adults were in various stages of readiness to engage in ACP behaviours, with most only engaging in a subset of ACP behaviours. Although ACP was viewed as beneficial by participants, several barriers were identified that prevented people with dementia from dying in a way that was aligned with previously-expressed wishes. Implications for the practice of clinical neuropsychology and implications for policy on ACP are discussed. / Graduate

M.A. / With the advances achieved in medical technology in recent years, society is increasingly faced with the issue of determining how fit individuals are for reintegration in society following the event of traumatic brain injury. Together with Neurology and it's diagnostic capabilities, many other disciplines such as Neuropsychology, Physiotherapy and Occupational Therapy, to name but a few, have placed strong emphasis on the rehabilitation of individuals with brain damage, with a view to reintegrate them into society. Besides the physical rehabilitation which aims at normalizing the individual's physical health, issues such as psychological ,cognitive and social functioning have been the focus of a great body of research in recent years. Whereas in the past the prognosis for many such patients in respect of returning to a normal life style were discouraging, health workers are now more optimistic in most cases regarding the individuals' probability to achieve a higher level of functioning after recovery. In this context, the individuals' ability to function in society, their ability to be integrated into the family and working environment and competence to be active and valued members of society have thus become the new aims which the therapeutic team together with the patient strive to achieve. With this in mind, rehabilitation teams now place greater emphasis and effort on optimizing recovery in the areas of cognitive and emotional competence. Amongst these issues, the individuals' competence to make moral judgements and socially adequate decisions in everyday living is of the utmost importance. This impacts on their ability to abide by social rules and norms which will determine their competence and desirability as active members in the family, social and working environments. This is the main focus of the present study. The issue of moral judgement and behaviour is central to this discussion, and a delineation of what defines morality and moral judgement is mandatory. Contributions to this analysis were found in the writings of the various authors and schools of thought presented here, and each of them has dealt with the theme of morality, moral behaviour and judgement from a different theoretical perspective. Theorists such as Lawrence Kohlberg made a major contribution to the understanding of the development of moral judgement through his stage theory, which forms one of the cornerstones of the present study. The site and the severity of the brain injury is paramount to the prognosis for rehabilitation. The frontal lobes have been described as the structures responsible for the widest range of symptoms and seen as the seat of intellect, responsible for deviations in moral and emotional functioning. An overview of the frontal lobes and associated cognitive functions as well as behaviors observed as a result of injury to these structures is presented. The existential-phenomenological system of inquiry has been described by its proponents as the most adequate to investigate phenomena relating to human behaviour, when an understanding of the subjective experience of the individuals involved is desired. For this reason this methodology is used in the present study to facilitate a qualitative analysis of the experience of brain injury particularly in respect of possible alterations in moral judgement and behaviour following the accident. The present investigation is based on interviews with three subjects and their primary caretakers, who answered questions regarding moral dilemmas. These dilemmas aim at tapping the individual's underlying reasoning processes when faced with the decision of what is right and wrong. The analysis and integration of the data obtained through these interviews reveals a complex cluster of alterations in thought and behaviour, much in line with those expected from patients suffering traumatic injury of the frontal lobes. Although different behaviours were revealed by each participant in this study, they were generally in line with the alterations described in the literature resulting from injury to the described brain areas. The value of this study lies in projecting a clearer picture of the experience of brain injury from the point of view of the victims as well as the close family members. Furthermore, analysis of data obtained in this investigation highlights certain typical behaviors and responses observed in individuals with such brain injuries, as described in the literature presented here.

M.A. (Clinical Psychology) / The purpose of this study was to assess the differential and relative effects of cortical immaturity and non-cortical immaturity in specific learning disabled children on the development of maladaptive behavior. For this purpose twenty specific learning disabled children were selected according to certain criteria. This group was divided into a group of children with specific learning disabilities with cortical immaturity, and a group with specific learning disabilities without cortical immaturity. Acontrol group consisting of ten children without any learning disabilities was also selected. The three groups thus obtained were assessed on indices of aggression, withdrawal, class- and learning problems, and personal and social efficacy. The results indicated that specific learning disabled children manifested more maladaptive behavior than non-specific learning disabled children. Concerning the differential effect of cortical immaturity and noncortical immaturity in specific learning disabled children on the development of maladaptive behavior there were no meaningful differences. The recommendation was made that future studies should control contaminating variables among which socio-economic class differences and parental child rearing practices.

The current study examined the WAIS-IV and how the changes to the test may impact the measure's usefulness in neuropsychological evaluations. It was hypothesized that the WAIS-IV would be a significantly better predictor of performance on the neuropsychological measures of the Category Test, Finger Tapping Test, Trail Making Test, and Wisconsin Card Sorting Test over the WAIS-III. The mixed clinical sample came from an archival database of volunteer research participants and individuals clinically referred to a university outpatient facility. A total of 91 participants were administered the WAIS-III and WAIS-IV as part of a larger neuropsychological battery. The results of the current study found that both the WAIS-III and the WAIS-IV were able to account for a significant amount of the variance in performance on the neuropsychological measures, with the exception of the FTT dominant and non-dominant hands, where only the WAIS-IV was able to significantly account for the variance in performance on the measures. Using the Alf and Graf (1999) model, there were no significant R2 differences between the WAIS-III subtests and WAIS-IV at the .01 significance level. Thus, the WAIS-IV did not provide a better model for predicting performance on any of the neuropsychological measures. It should be noted that the small sample size of the current study may have inflated the R2, particularly in the WAIS-III models, which could have masked greater R2 differences between the two models. While the publishers endeavored to make the WAIS-IV a better measure of processing speed, working memory, and fluid reasoning, these goals were largely unmet. The analyses of the WAIS-IV working memory subtests, showed that the sequencing component added to the Digit Span subtest did not add to the relationship with neuropsychological measures with working memory components. The analyses of the WAIS-IV processing speed subtests showed that the Coding subtest of the WAIS-IV was a better measure of processing speed than the WAIS-III version, but this was not found for the PSI as a whole. Changes to Symbol Search did not show any improvement in the relationship to neuropsychological measures. One interesting finding was that the new subtest of Visual Puzzles does appear to add to the relationship with neuropsychological measures over the other subtests of the WAIS-IV. Visual Puzzles was consistently the highest correlated PRI subtest with the neuropsychological measures, with the exception of the WCST. The subtest appears to assess a wide range of abilities outside of the spatial reasoning skills purported by the test publishers. Specifically, the subtest was correlated with measures of processing speed, executive skills, and motor speed/reaction time. Thus, clinicians should use caution and examine all possible options when evaluating poor performance on this new subtest. Since none of the WAIS-IV models were able to significantly predict performance on any of the neuropsychological measures over the WAIS-III models, it would appear that the WAIS-IV as a whole is not a better neuropsychological measure than its predecessor. Despite being the gold standard for intellectual assessment, the WAIS-IV appears to add little to clinical utility over the WAIS-III outside of shorter administrative time. Clinicians are advised to continue using neuropsychological measures to assess processing speed, working memory, and higher order cognitive skills in conjunction with the WAIS.

Current models of face perception suggest independent processing of identity and expression, though this distinction is still unclear. Using converging methods of psychophysics and functional magnetic resonance imaging (fMRI) in healthy and patient populations we assessed the relationship between these two perceptual processes. First, using perceptual aftereffects, we explored the neural representations underlying identity and expression. The expression aftereffect only partially transferred across different identities, suggesting adaptation within identity-invariant and identity-dependent expression representations. Contrarily, the identity aftereffect fully transferred across different expressions. This asymmetry cannot be explained through low-level adaptation. The identity-dependent component of the expression aftereffect relies on adaptation to a coherent expression, not low-level features, in the adapting face. Thus adaptation generating the expression aftereffect must occur within high-level representations of facial expression. Second, using fMRI adaptation, we examined identity and expression sensitivity in healthy controls. The fusiform face area and posterior superior temporal sulcus showed sensitivity for both identity and expression changes. Independent sensitivity for identity and expression changes was observed in the precuneus and middle superior temporal sulcus respectively. Finally, we explored identity and expression perception in a neuropsychological population. Selective identity impairments were associated with inferior occipitotemporal damage, not necessarily affecting the occipital or fusiform face areas. Impaired expression perception was associated with superior temporal sulcus damage, and also with deficits in the integration of identity and expression. In summary, psychophysics, neuroimaging and neuropsychological methods all provide converging evidence for the independent processing of identity and expression within the face network. However, these same methods also supply converging evidence for a partial dependence of these two perceptual processes: in the expression aftereffect, the functional sensitivities of the FFA and pSTS, and identity deficits observed in a patient with primarily impaired expression perception and a spared inferotemporal cortex. Thus, future models of face perception must incorporate representations or regions which independently process identity or expression as well as those which are involved in the perception of both identity and expression. / Medicine, Faculty of / Graduate

M.A. (Counselling Psychology) / Gray proposed two psycho-neurobiological systems, namely the behavioural approach system (BAS) and the behavioural inhibition system (BIS) which are respectively related to positive affectivity and negative affectivity. The literature does not currently indicate any specific positive emotional traits related to the BAS scale with certainty, although happiness, elation and hope have been suggested as possibilities. Curiosity, empathy and hope were chosen as positive emotional traits to study in relation to the BAS, as these positive emotional traits can each be related to the three factors of the BAS, namely drive, fun seeking and reward responsiveness. Fredrickson’s broaden-and-build theory explains that each emotion evokes a thought-action tendency and when positive emotions are experienced, the types of possible behavioural responses are broadened. It is expected that this broadened response repertoire should be detected in the behavioural approach system, which is responsible for organising behaviour in response to stimuli that signal rewards or no punishment. Fredrickson’s broaden-and-build theory is thus a useful framework to utilise in the conceptualisation of the study. The purpose of the study was to determine the extent to which curiosity, empathy and hope act as predictors for the variance in the BAS. The sample consisted of 130 first year mathematics students at the University of Johannesburg. Psychometric instruments utilised for the study included Carver and White’s BIS/BAS scales, the Curiosity and Exploration Inventory (CEI), the short form of the Empathy Quotient (EQ-short) and the Adult Dispositional Hope Scale. A standard multiple regression was conducted to investigate the nature of the relationships between the BAS and curiosity, empathy and hope. The results indicate the total variance in the BAS levels explained by curiosity, empathy and hope simultaneously was 16.8 percent. Hope made the largest unique contribution by accounting for 6.8 percent of the variance in the total BAS scores while curiosity also made a statistically significant contribution by accounting for 3.2 percent of the variance in the total BAS scores. Empathy did not make a statistically significant unique contribution to the variance in the total BAS scores. Future studies of this nature should consider a larger sample size. The prefrontal cortex was identified as a neural counterpart that might be related to Fredrickson’s broaden-and-build theory of positive emotions, but future research could explore this further.

Diet plays a pivotal role in preventing, managing, and reducing the risk of weight gain, diabetes and heart disease. Increasing pressure is directed towards food manufacturers to offer healthier options. The challenge is to develop products which are both nutritious and accepted by the consumer. Oral sensitivity, and therefore product perception, varies greatly amongst individuals, and likely affects food choice. Taste phenotype and genotype are frequently proposed as markers for overall oral sensitivity. This thesis performs fundamental research to further current understanding of the impact of taste phenotype and genotype on the response to oral stimuli. The effect of 6-n-propylthiouracil (PROP) taster status (PTS), fungiform papillae density, TAS2R38 and gustin rs2274333 genotype on the perceived intensity of prototypical tastants and metallic stimuli is explored. Experiments were first conducted to develop oral stimuli for use in the subsequent fMRI studies, which interestingly identified that some metallic stimuli may have a gustatory component. Perceptually, few or no differences were identified across taste phenotypes or genotypes. Interestingly, functional Magnetic Resonance Imaging (fMRI) identified variation in cortical processing that was associated with PTS. PROP intensity ratings were found to correlate with cortical activation in the anterior insula, an area of the brain thought to be the primary gustatory cortex, in response to sweet and metallic stimuli, but not for sour, salt, bitter or umami stimuli. These limited differences observed may have been due to the occurrence of a concentration effect, where the increased gustatory sensitivity frequently associated with PROP tasters compared to PROP non-tasters was lost when administering strong supra-threshold stimuli used in the current study. These findings are of interest to food manufacturers and health professionals as they could indicate that taste phenotype and genotype has less impact on product perception, and therefore food choice, than previously proposed. Thermal taster status (TTS) refers to a new taste phenotype in which individuals perceive phantom tastes when the tongue is thermally stimulated, whilst thermal non-tasters (TnTs) only perceive temperature. In this thesis, variation in the phantom tastes reported by thermal tasters (TTs) are explored, and for the first time the temporal phantom taste response is measured. Different categories of temporal taste responses are identified, and interestingly it is shown that phantom tastes are perceived at variable temperature ranges across both TTs and taste qualities. Importantly, the onset of sweet taste was found to occur as the temperature increased between 22-35°C, supporting the hypothesis that the TRPM5 may be involved in sweet phantom taste responses. This is the first study to assess the brain’s response when thermally stimulating the tongue of TTs to elicit a phantom taste response. Interestingly, when using fMRI it is shown that at the time when TTs perceive a phantom taste, cortical activation is induced in the anterior insula, which is thought to be the primary gustatory cortex. This indicates that thermal stimulation may activate temperature sensitive gustatory nerve fibres in TTs, and supports the hypothesis of cross wiring between gustatory and trigeminal nerves. When comparing the cortical response to thermal stimulation of the tongue across TTs and TnTs, greater activation is observed in oral somatosensory areas of the brain in TTs compared to TnTs. These findings show cortical processing differs across thermal taste phenotype, and supports evidence that thermal taster status may be a marker for oral sensitivity. This original research provides a valuable contribution towards understanding the effect of taste phenotype and genotype on perception of prototypical taste, metallic, and thermal stimuli. The novel multidisciplinary approach of utilising sensory evaluation and fMRI techniques has provided valuable insights into the impact of taste phenotype on gustatory responses, and has suggested possible mechanisms that may be involved in thermal taste phenotype.

Introduction: The cognitive benefits of physical activity and sport on executive function are of interest to researchers, especially considering the subsequent interventions that could be implemented. However, researchers frequently use different approaches to conceptualize and measure executive function, often using only a few computerized tasks. My Master’s thesis, therefore, aims to investigate the associations between executive function and physical activity and sport through two different studies to obtain a robust evaluation of executive function: 1) A quantitative study examining physical activity, sport and concussion history in university students and their effect on executive function, and 2) A qualitative study exploring the executive functions engaged during a game from elite university athletes’ experiences. Methods: Quantitative Study. Canadian university students (n=247) completed an online study with nine computerized executive function tasks and a behavioural self-report of executive function, as well as questions assessing weekly physical activity, athletic status, and concussion history. Structural equation modelling and linear regression were conducted to predict executive function based on age, sex, physical activity, athletic status and concussion history. Qualitative study. Canadian university athletes (n=19) participated in semi-structured interviews via Zoom to determine the executive functions engaged during a game. Thematic analysis was used to analyze the interview transcripts. Results: Quantitative Study. The three-factor model of executive function had an overall good fit: χ2 = 66.38, df = 51, p = 0.07, CFI = 0.95, TLI = 0.93, RMSEA = 0.04 [90% CI: 0.00–0.06], SRMR = 0.05. No direct relationship was found between the factors and age, physical activity, concussion history, or athletic status. Sex was significantly related to inhibition, b = 0.52, p = 0.02, such that males had greater inhibition. Physical activity (b = 0.09, p < .01), concussion history (b = 3.29, p < .05) and athletic status (b = -4.01, p < .05) were found to be significant predictors in the regression predicting self-reported executive functioning. Qualitative study. Three themes were generated: 1) Engaging in pre-play or pre-game planning, organization and decision making, 2) Engaging in mid-play problem solving and purposive action and 3) Engaging in post-play or post-game information processing, emotional control and effective performance. Conclusions: The quantitative study found that physical activity, athletic status and concussion history were predictive of subjective but not objective executive function. The qualitative study determined that athletes engage many executive functions that are dependent on the timing of both the play and the game (pre-, mid- or post-). Real-life behavioural manifestations of executive functioning are more challenging to assess and measure but may be better predicted by and relate to life factors such as physical activity and sport participation. The results of my thesis provide support for future research to utilize and develop more unique and ecologically valid methods of measuring EF in the field of physical activity and sport. / Graduate

Cognition in schizophrenia (SCZ) has been reported to be heterogeneous. Some have ascribed this to the existence of cognitive subtypes, while others have attributed heterogeneity to the types of assessments used and the implications of various research designs. In absence of a uniform standardized battery, The MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) Consensus Cognitive Battery (MCCB) was developed to measure the effects of pharmacological treatment. Other neuropsychological tasks such as the Attention Network Test (ANT), Change Localization (CL), and Stop Signal Task (SST) have also been heavily researched in this population. The overall aim of this dissertation is to assess not only the participant performance on these tasks, but also the test-rest reliability of these assessments in a relatively short retest interval (14±2 days) in a Healthy Volunteer (HV) and SCZ group. In addition, the relationship between Continuous Performance Test-Identical Pairs (CPT-IP), an attention task (ANT), and working memory task (CL) was explored to examine the potential working memory (WM) component of CPT-IP. Lastly, to better understand the heterogeneity of cognition observed in SCZ, Intraindividual Variability (IIV) in performance of SST was compared in relation to other tasks. The results indicated that the MCCB has fair to excellent test-retest reliability in both groups with minimal practice effect (PE) in SCZ. Most interesting, two distinct cognitive profiles were observed: cognitively-normal and below-normal. The 4-digit condition of CPT-IP was found to be the most difficult in both groups. The primary metrics of CPT-IP lacked an association with the three primary domains of ANT in HV and SCZ. No relationship was observed between WM and CPT-IP in HV, primarily due to CL’s ceiling effect, while in SCZ, moderate to strong associations in these tasks were observed. Lastly, little to no relationship was observed between IIV and MCC domain scores in HV and SCZ. The HV group demonstrated some relationship between IIV and domains of ANT. The SCZ group failed to show similar relationships primarily due to larger inter-individual variability. Taken together, the findings of this dissertation suggest the potential for cognitive heterogeneity unrelated to PE and reliability of tasks. / 2021-10-07T00:00:00Z