Melbourne School of Psychological Sciences - Theses
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ItemCognitive and psychosocial functioning in genetic generalised epilepsy( 2017)Genetic generalised epilepsies (GGE) are a common, but under-studied cluster of epileptic syndromes of predominantly child and adolescent onset. The primary syndromes of GGE are childhood absence epilepsy (CAE), juvenile absence epilepsy(JAE), juvenile myoclonic epilepsy (JME), and genetic generalised epilepsy with generalised tonic-clonic seizures only (GTSCO). Important questions remain regarding: the degree of cognitive and psychopathological comorbidity, particularly in adults and in syndromes other than JME; effects of the disease on cognitive function; and psychopathology and psychosocial wellbeing in these patient groups. This thesis aimed to provide a detailed and quantitative description of cognitive function and psychopathology in GGE, assess the impact of contributing factors including subclinical epileptiform discharges on cognitive and psychopathology outcomes, and to evaluate the relationship between psychopathology and cognition. Methods employed include narrative systematic review, quantitative meta-analysis, and prospective assessment of cognitive and psychosocial functioning of a relatively large sample of people with GGE. Results indicated mild to moderately large reductions across most cognitive factors relative to that of healthy control participants and age-based normative data, with a relative weakness in long-term retrieval and memory function. Short-term memory function was not reduced relative to age-based normative data. Overall cognitive ability and memory function was negatively associated with total duration of epileptiform discharges during a 24-hour period. Approximately 50% of the sample reported elevated symptoms on a measure of psychopathology spanning six symptom types, with depression and anxiety the most common amongst these. Collectively, these findings highlight the need for increased awareness, screening and the provision of services for psychological comorbidities for people with GGE.
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ItemNeural correlates of attention in the context of prematurity( 2014)This study aimed to examine attention outcomes in a high-risk very preterm (VPT; <30 weeks’ gestational age) and/or very low birth weight (VLBW; <1250 g) children at 7 years, and to assess whether brain abnormality measured by neonatal magnetic resonance imaging (MRI) can predict later adverse outcome within this domain. It also aimed to investigate whether the attention difficulties observed at 7 years were associated with abnormalities in the key white matter pathways associated with attention. A cohort of 198/224 VPT/VLBW children and 70/77 term controls were examined. Neonatal MRI scans performed at term-equivalent age were assessed for white matter, cortical grey matter, deep grey matter, and cerebellar abnormalities. Standardised neuropsychological tests of attention and MRI scans were conducted at 7 years. Diffusion tractography analyses were performed on the key white matter tracts associated with attention (the superior longitudinal fasciculi, the cingulum bundles, and the reticular activating system). At 7 years of age, the VPT/VLBW group performed significantly worse than term controls on all attention outcomes. Associations between higher neonatal brain abnormality scores and adverse attention performances at 7 years were found in the VPT group; in particular, white matter and deep grey matter abnormalities were reasonable predictors of long-term attention outcomes. Findings at 7 years also revealed altered microstructural organisation and reduced tract volume within the proposed attention tracts in the VPT children compared with the term controls and also that, such alterations were related to the adverse attention outcomes in VPT children. Attention is a significant area of concern in VPT/VLBW children. This is the first study to show that neonatal brain pathology may be used to predict, in conjunction with other known risk factors, which children may be at risk of later adverse attention outcomes. This study also highlights the importance of white matter tract integrity for the development of attention abilities in VPT children.
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ItemThe neuroendocrine system following preterm birth and its effects on cognitive and brain development at age 7( 2012)Preterm birth is associated with a well-defined pattern of neurodevelopmental impairments which include a range of cognitive deficits, as well as structural brain abnormalities. Further, preterm infants are known to have a transiently altered neuroendocrine system during the first weeks of postnatal life. Although recent studies have focused on characterising long-term neurobehavioural deficits, few have examined potential mechanisms that may, at least partly, explain these poorer outcomes. This study aimed to address this shortcoming by focusing on the postnatal neuroendocrine system and its association with neurodevelopmental outcomes at age 7 in a group of children born very preterm. Postnatal concentrations of three hormones, free thyroxine, cortisol, and growth hormone, were examined using both direct hypothesis testing and exploratory hypothesis-generating approaches. Three direct hypotheses were proposed following review of the literature. Firstly, it was hypothesised that lower postnatal free thyroxine concentrations would be associated with poorer performances on measures of intellect, attention, and visuoperceptual abilities, as well as reductions in grey and white matter volumes at age 7 in children born very preterm. Secondly, it was hypothesised that higher postnatal cortisol concentrations would be associated with poorer performances on tasks of new learning and memory and volumetric reductions in the hippocampi at age 7 in children born very preterm. The final hypothesis predicted that elevated postnatal growth hormone concentrations would be related to deficits in attention and executive functioning and reductions in the prefrontal brain volumes at age 7 in children born very preterm. The current study investigated 83 children born very preterm (gestational age <30 weeks and/or birth weight <1250g), born between June 2002 and December 2003 in Melbourne, Victoria. During the neonatal period, hormone analysis was conducted over eight time points during the first 42 days of life (cord, Day 1, Day 4, Day 7, Day 14, Day 21, Day 28, and Day 42) to characterise the hormone profiles associated with preterm birth. At age 7, the children participated in a cognitive assessment and an MRI scan. A broad neuropsychological battery that assessed six domains of cognition, namely intellect, language, visuoperceptual reasoning, memory, attention and executive functioning, and processing speed, was used to characterise the cognitive profiles of this group of children. MRI imaging analysis was conducted using Freesurfer (v 5.1.0) to obtain cortical and subcortical brain volumes. The results did not confirm the direct hypotheses, although some interesting and novel findings arose. Firstly, elevated free thyroxine concentrations were related to poorer processing speed performances. A similar relationship was observed with elevated cortisol concentrations and decrements in processing speed. Lastly, elevated cortisol concentrations were related to volumetric reductions in subcortical regions, particularly the basal ganglia. Possible explanations for these findings were reviewed, though more research is required to confirm these relationships. Using a critical illness theory of endocrinology, it was concluded that the hormone profile exhibited by this cohort of children born very preterm during the early postnatal period, namely low concentrations of free thyroxine, and elevated concentrations of cortisol and growth hormone, reflected a transient reaction to acute critical illness. Moreover, given the adaptive nature of this acute illness phase, it was concluded that this postnatal hormone profile did not explain the diffuse nature of the neurodevelopmental impairments common to the preterm population.