Melbourne School of Psychological Sciences - Theses
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ItemNeuropsychology and functional brain organisation of working memory in children and adolescents with agenesis of the corpus callosum( 2017)Background: The corpus callosum is the largest brain white matter pathway. Its main function is to coordinate and transfer information between the two hemispheres, thus contributing to higher cognitive functions including working memory (WM). Developmental absence of the corpus callosum, or Agenesis of the Corpus Callosum (AgCC), is one of the most common brain malformations but its consequences on neurobehavioural functioning and functional brain organisation in school-age children are not well understood. Aims: The goal of the current work was: 1) To describe the impact of AgCC on neurobehavioural functioning, including WM functions, in school-age children; and investigate the role of age, social, and neurological factors that might underlie neurobehavioural outcomes in children with AgCC; 2) To investigate the functional brain organisation of WM in school-age children with AgCC using functional magnetic resonance imaging (fMRI). Methods: 28 children diagnosed with AgCC based on MRI and a control sample of 16 typically developing children, aged 8 to 17 years, completed a neurobehavioural assessment and brain imaging with anatomical T1 sequences and an fMRI task (AgCC, n=9; controls, n=16) tapping WM processes, i.e., encoding, maintenance and retrieval. Parents and teachers completed questionnaires to evaluate executive, behavioural and social functions. Results: In our cohort, ~50% experienced general intellectual, academic, executive, social and/or behavioural difficulties and ~20% reached a level comparable to typically developing children. Social risk was found to have an important impact on variability in functional outcomes. Additional brain anomalies or complete AgCC were associated with lower mathematics performance and poorer executive functioning. fMRI findings showed that globally similar brain regions were recruited in the AgCC and the control groups during the WM task, despite significant disparity in brain development, i.e., bilateral occipito-frontal activations during verbal encoding, and bilateral fronto-parietal executive control network during retrieval. However, there were notable differences in activations between groups that might reflect different susceptibility to concurrent tasks during WM, subsequent to different degrees of hemispheric lateralisation during the task. Conclusion: This work constitutes the first comprehensive report of cognitive, executive, behavioural and social consequences of AgCC in school-age children, and provides a first step towards a better understanding of functional brain networks underlying higher cognitive functions in children with AgCC.
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ItemA longitudinal study of attention and inhibitory control in 6- to 11-year-old children( 2017)Attention and inhibitory control are important cognitive abilities. Attention consists of three components: activation, selection, and control. The activation of attention involves alertness, the maintenance of response readiness, and sustained attention. The selection of attention involves reflexive and voluntary shifts of attention to a specific location or point in time, and the breaking and reorienting of attention. The control of attention involves resolution of conflict, such as that induced by distractors, and inhibitory control. There is a lack of longitudinal data on the development of these aspects of attention in typically developing children, so their developmental trajectories remain unclear. The aim of this thesis was to map the developmental trajectories of alerting, sustained attention, orienting, reorienting, conflict resolution and inhibitory control. Participants involved in this research were 114 children aged 6, 8, or 10 years at study onset, referred to as the 6-7, 8-9, and 10-11 groups. Children performed three attention tasks, three times at 6-monthly intervals. The Attention Network Task (ANT) measures alerting, orienting, reorienting, and conflict resolution. The Random Sustained Attention to Response Task (SART) and the Fixed SART measure sustained attention and response inhibition; they require frequent responding with infrequent inhibition to a No-Go target. Intra-individual variability of response time (RT) during the SART was analysed with a Fast Fourier Transform and an ex-Gaussian model of RT data. Results indicate that each component of attention followed a different rate of development. In terms of activation, there was ongoing maturation throughout the study. The functioning of the alerting network, as measured by the ANT, improved over the year in all children. There was, however, little difference in alerting score between the two youngest groups, suggesting greater maturation of alerting after 9 years of age than before. Findings for sustained attention were task-dependent: during the arousing Random SART, there were few differences in performance between the two older groups, but during the unengaging Fixed SART, the 8-9 group mostly performed at an intermediate level compared with the other groups. The 8-9 group exhibited greater momentary fluctuations in response time and made more very long responses than the 10-11 group on both SARTs, indicating more momentary lapses in attention. The 6-7 group performed less well than the older groups on most measures on both SARTs. The selection of attention - the orienting and reorienting networks as measured by the ANT - showed no developmental changes during the study. Control of attention - conflict resolution and response inhibition as measured by the ANT and Random SART - was relatively stable from 7 and 8 years respectively. This thesis proposes that between 6 and 7 years is an important period for the development of attention and response inhibition. There may be some level of developmental stability between 8 and 11 years on unpredictable engaging tasks. The ability to self-sustain attention and arousal on an unarousing unengaging task, however, appears to follow a protracted maturation throughout childhood.
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ItemDepression and immunity in adolescents: early precursors to disease?( 2012)Inflammation and immune dysfunction have been proposed to be mechanisms relevant to clinical depression. However, research on this topic is limited by the paucity of lifespan and longitudinal studies, making it difficult to address causality. This project aimed to examine inflammatory and depressive measures in adolescents from the community using both cross-sectional and prospective longitudinal designs. Experiment 1 was a cross-sectional, two-group study of 13 clinically depressed adolescents aged 13-18 years (11 females), and 13 age- and sex-matched healthy controls, both recruited from the community. Sixteen cytokines were measured in saliva and serum. Depressed adolescents displayed significantly elevated levels of C-reactive protein (CRP), Haptoglobin, Serum Amyloid P (SAP), and Alpha-2-macroglobulin (A2M) in saliva compared to controls, but not in serum, or for any other cytokine. Depressed adolescents also did not display a higher ratio of T helper cell 1- to T helper cell 2-type cytokines compared to controls. Experiment 2 was a prospective study of 67 adolescents (27 females) followed from 12-18 years of age and recruited from the community. Self-report depressive symptoms measured by the Center for Epidemiological Studies Depression Scale (CES-D) and Axis-I psychopathology measured by The Schedule for Affective Disorder and Schizophrenia for School-age Children (KSADS) were measured at four phases, and four salivary acute-phase proteins (CRP, Haptoglobin, SAP, and A2M) were measured at Phase II. Temperamental negative emotionality (NEM) was also assessed at age 12. Results showed that elevated CRP was significantly correlated with elevated CES-D scores cross-sectionally, but no inflammatory markers predicted the onset of a depressive illness or an increase in depressive symptoms over time. There was a significant Sex x CRP interaction effect on CES-D measured at Phase I, II, and IV, with a relationship between CRP and CES-D only apparent for females. Examining only females demonstrated significant associations between CRP and CES-D at all four phases, including CES-D measured two years prior to inflammation, suggesting that for females, depressive symptoms may precede elevated levels of CRP, however, further longitudinal research is required that measures inflammation at more than one time point. At Phase II, there were significant interactions of NEM temperament x CRP on CES-D, with a relationship between CRP and CES-D only for those with a high NEM score. Post-hoc analyses showed that body mass index (BMI) was also a significant moderator of the relationship between CRP and CES-D at Phase II, with a stronger association for participants with a higher BMI score. Measures of early-life stress and childhood trauma were not associated with inflammatory markers. These results suggest that salivary CRP is a marker of adolescent depression, but levels of this inflammatory marker do not predict the development of depressive illness. The results, along with other research, suggest that depressive symptoms may be a risk factor for chronic inflammation and associated medical diseases, especially for females. Furthermore, obesity may be another consequence of depression which can lead to this observed elevated inflammation. Finally, sex hormones should be considered in models of depression, obesity, and inflammation.