Melbourne School of Psychological Sciences - Theses
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ItemCerebello-cortical and fronto-parietal contributions to working memory function in children born extremely preterm: a diffusion MRI study( 2016)Survivors of extremely preterm birth (<28 weeks’ gestation) and/or extremely low birth weight (<1000 grams) have elevated rates of working memory impairment compared with term-born peers. This impairment may be a core deficit underlying problems experienced by these children in other areas of cognitive, behavioural and academic functioning. Extremely preterm survivors are also at risk of white matter injury and cerebellar injury as a result of neurological disruptions associated with preterm birth. However, it is not yet known whether this injury and developmental disruption to cerebellar white matter connections underlies the working memory deficits seen in this population. It is also unclear whether working memory deficits may be ameliorated through intensive working memory training, and whether white matter microstructural plasticity underlies training gains in working memory capacity. This thesis aimed to examine whether variability in the maturity and microstructural organisation of white matter pathways associated with working memory were related to working memory ability in a group of 7-year-old extremely preterm children. It also aimed to evaluate whether working memory capacity and white matter microstructure were capable of change (functional and neuroplastic change, respectively), in response to the most widely evaluated adaptive working memory training intervention, Cogmed. Sixty participants were recruited from a large cohort of 7-year-old extremely preterm children born in Victoria, Australia. Two white matter pathways in the brain were investigated using probabilistic tractography with diffusion-weighted MRI; the superior longitudinal fasciculus (SLF), a monosynaptic fronto-parietal white matter tract well-recognised for its involvement in working memory function, and the cerebello-thalamo-prefrontal (CTP) pathway, a polysynaptic efferent cerebellar white matter pathway hypothesised to be involved in working memory function. The CTP pathway was further divided into two monosynaptic components; the cerebello-thalamic tract (CT), and the thalamo-prefrontal tract (TP). The diffusion-weighted MRI measures of fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity were used to assess white matter microstructure. The Cogmed working memory training intervention (5-7 weeks) was administered using a double-blinded, placebo-controlled, randomised control trial. In the adaptive Cogmed intervention, activities became more complex with increasing proficiency of the participant, thereby challenging working memory capacity. In the placebo Cogmed intervention, activities remained at a fixed, low level of difficulty. Working memory capacity and white matter microstructure were assessed at baseline and two-weeks post-intervention using gold-standard measures. The study found that, prior to the intervention, immaturity of microstructural connectivity in cerebello-thalamo-prefrontal and fronto-parietal white matter pathways was related to lower working memory performance. Following the intervention, no significant difference in working memory performance or microstructural white matter maturity was noted in children who undertook adaptive versus placebo training. The novel finding of this thesis is that early disruption to the microstructural development of cerebello-cortical white matter pathways (as a result of extremely preterm birth) may represent a potential neurobiological mechanism underlying working memory dysfunction in this population. Evaluation of these tracts in the perinatal period therefore has the potential to identify children at risk of developing working memory deficits later in life, so that close surveillance or early interventions may be applied. However, Cogmed adaptive (versus placebo) working memory training does not appear to be an effective intervention in improving working memory capacity for school-age extremely preterm children.
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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.