Melbourne School of Psychological Sciences - Theses
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ItemVolumetric Analysis of the Entorhinal and Transentorhinal Cortices in the Early Detection of Alzheimer’s Disease( 2024-02)Diagnosing Alzheimer’s disease (AD) early in the disease process can be challenging. Incorporating biomarkers into the diagnostic evaluation for AD has been recommended to increase diagnostic accuracy. Structural magnetic resonance imaging (MRI) is a particularly appealing biomarker because it is a widely available and noninvasive procedure. In view of the early pathological involvement of the entorhinal and transentorhinal cortices in the disease process, MRI-based volume measurements of these regions are promising candidate markers for early AD. Whilst significant advances have been achieved in automated segmentation of brain MRI in recent years, the entorhinal and transentorhinal cortices have been shown to be particularly challenging regions for automated segmentation. The current dissertation sought to examine the role of entorhinal and transentorhinal cortical MRI volumetric analysis to enhance the early detection of AD. Chapter 2 presented a systematic review and meta-analysis of studies comparing automated and manual regional brain volume measurements across healthy controls (HCs), individuals with amnestic mild cognitive impairment (aMCI), and individuals with AD dementia. There was no significant difference in automatic and manual volume measurements for the hippocampus, lateral ventricles, and parahippocampal gyrus. There was, however, significant heterogeneity in the effect estimates across the studies. Chapter 3 comprised an investigation into the effect of MRI scan orientation on the reliability of entorhinal and transentorhinal cortical volume measurement in order to establish a standard protocol for segmentation for subsequent Chapters. Aligning MRI scans to a common orientation improved the reliability of entorhinal and transentorhinal cortical volume measurement. Chapter 4 described an independent validation of a recently developed automated segmentation method, Automatic Segmentation of Hippocampal Subfields-T1 (ASHS-T1), for the measurement of entorhinal and transentorhinal cortical volumes in HCs, individuals with aMCI, and individuals with AD dementia. Despite differences between the volumes obtained from ASHS-T1 and those obtained from manual segmentation, ASHS-T1 was sensitive to AD-related entorhinal and transentorhinal cortical atrophy. Chapter 5 contained an examination of the contribution of selected mesial temporal lobe volumes obtained from ASHS-T1 alongside test scores derived from comprehensive neuropsychological assessment to aid identification of individuals with aMCI and individuals with AD dementia in a memory clinic cohort. Volumes of the entorhinal cortex, transentorhinal cortex, and hippocampus performed no better than chance and offered no utility over and above valid and reliable neuropsychological measures for identifying individuals with AD. Chapter 6 introduced a novel, deep learning-based automated segmentation method, TransEntorhinal Segmentation by Deep Learning (TES-DL), to segment the entorhinal and transentorhinal cortices. Despite suboptimal segmentation accuracy, TES-DL showed mostly medium to large effect sizes for the differences in entorhinal and transentorhinal cortical volumes between HC, aMCI, and AD groups in two AD cohorts. Taken together, the findings from the current dissertation highlight the difficulty of accurate automated segmentation of the entorhinal and transentorhinal cortices and challenge the clinical utility of the volumes of these regions in the early detection of AD. Importantly, whilst advances in automated neuroimaging methods promise exciting new possibilities, it is essential that these methods are thoroughly validated prior to widespread clinical application.
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ItemLongitudinal prospective study of self-esteem and psycho-social function after childhood traumatic brain injury: delineating the contribution of injury, environmental, and individual factors( 2023-07)Background: Traumatic brain injury (TBI) is a significant public health burden that is a key contributor to lifelong disability. Such injuries can disrupt brain networks undergoing maturation during childhood and derail their ongoing development, contributing to profound changes in functioning. Sustaining a childhood TBI may also influence how individuals perceive themselves i.e., their self-esteem; however, current evidence base is weakened by retrospective, cross-sectional designs, and recruitment of heterogeneous samples. The overall aim of this prospective, longitudinal investigation was to examine the impact of paediatric TBI on self-esteem across childhood/adolescence and into young adulthood, and identify factors that contribute to individual variation in self-esteem. Method: The original study comprised 112 children and adolescents with mild-severe TBI (Anderson et al., 2013). For comparison, 43 typically developing controls matched on age, sex, and socioeconomic status were included. Participating families, both children and their parents, completed assessments at an outpatient clinic or at home at 6- and 12-months post-injury. At the 13-year follow-up time point, 29 young adults with childhood TBI and 10 typically developing controls were recruited from the existing cohort. Consenting participants completed questionnaires online. Results: As documented in three published and one submitted manuscript (chapters 6-9), findings revealed that some aspects of self-esteem may be especially vulnerable to deterioration following TBI. Specifically, perceived competence in both academic and behavioural domains was found to be significantly lower amongst children and adolescents with TBI, relative to typically developing controls. Individual variance in longitudinal self-esteem outcomes was documented in relation to injury factors (TBI severity, injury age, presence of frontal lobe pathology), environmental variables (parent mental health, family function, peer relations), and individual characteristics (social isolation, emotional wellbeing). For young adult survivors of childhood TBI, low self-esteem was endorsed by a sizeable proportion (approximately 20% or 1 in 5 TBI participants). Conclusions: Evidence for links between self-esteem and a multitude of injury, environmental, and individual factors accord with both developmental and brain-injury specific theoretical frameworks, and caution against exclusive reliance on injury-related variables when determining consequences of childhood TBI, especially in the context of self-esteem. While injury severity had some influence, environmental, and individual factors consistently made the largest and most significant contribution to global and domain-specific self-esteem. Collectively, results from the present investigation underscore the importance of routine and ongoing screening of non-injury, potentially modifiable risk factors, which likely represent useful targets for clinical interventions and rehabilitation programs seeking to optimise self-esteem in the short- and long-term following childhood TBI.
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ItemPersistent post concussive symptoms in children: a neuroimaging approach( 2021)Persisting post-concussion symptoms (PPCS) refer to a collection of concussion symptoms (such as headache, dizziness, mood changes) that persist after the normal recovery period. In children, almost 30% of cases of concussion still have symptoms three months after injury, leading to poorer emotional wellbeing, school absences and a lower overall quality of life. It remains unclear as to what causes PPCS in children and how clinicians should diagnose the condition, however early intervention is known to be beneficial. This thesis sought to utilise novel neuroimaging techniques to gain a better understanding of the aetiology of PPCS in children and to provide clinical recommendations as to the use of neuroimaging for its diagnosis. Firstly, a systematic review and methodological critique conducted on existing neuroimaging research into concussion and mild traumatic brain injury was conducted to identify novel neuroimaging modalities which required further study. The literature was found to suffer from methodological heterogeneity, small sample sizes, and wide neuroimaging acquisition timeframes, however three novel neuroimaging modalities were highlighted as possible targets for investigation: diffusion weighted imaging (DWI), susceptibility weighted imaging (SWI), and resting state functional magnetic resonance imaging (rs-fMRI). Following on from the systematic review, the thesis investigated the aetiology of PPCS across two studies. As part of a larger study into concussion recovery, 45 children underwent neuroimaging at a two-week timepoint to assess whether there was an observable difference between children who recover normally and those who were predicted to have delayed recovery as per the Post-Concussion Symptom Inventory. No evidence of a difference was found between the groups for DWI, SWI, and rs-fMRI, with Bayesian analysis showing that there was no difference between the two groups on DWI. It was concluded neuroimaging is unlikely to successfully differentiate between normally recovering children and those who are likely to develop PPCS, given current technological constraints. In addition, it is likely that the aetiological factors of PPCS are more psychological in nature rather than arising from purely biological processes post-concussion.