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ItemEmpathy during childhood; an investigation of associations with anxiety and depressive symptoms, and brain structure and functionBray, Katherine Olivia ( 2021)This thesis investigated the associations between empathy and internalising (i.e., depressive and anxiety) symptoms, and the underlying structural, and functional connectivity neural correlates of empathy in late childhood. Background: Empathy refers to the understanding and sharing of others’ emotions, is a multidimensional construct, and includes cognitive and affective components. Empathy is important for social functioning, and alterations in empathy have been demonstrated in many developmental/psychiatric disorders. Studies in adults have demonstrated that both cognitive and affective empathy are associated with internalising symptoms. Studies in adults have also examined the neural underpinnings of empathy, implicating two major functional brain networks: the Default Mode Network (DMN) has been implicated in cognitive empathy, while the Salience Network (SN) has been implicated in affective empathy. These findings have mostly resulted from investigating brain activity during empathy tasks (i.e., in functional Magnetic Resonance Imaging [fMRI] studies). Less research has examined the associations between trait empathy, and brain structure or intrinsic functional connectivity. Few studies have investigated these associations between empathy and either internalising symptoms or the neural correlates in young people, particularly children. Investigating associations between empathy, mental health, and brain structure and function during childhood is beneficial to begin to build a comprehensive picture of the development of empathy components and the neural correlates of empathy across the lifespan. Based on previous research in adults and preliminary work in children, we hypothesised that higher levels of empathic distress and lower levels of cognitive empathy would be associated with higher depressive and anxiety symptoms (particularly social anxiety symptoms). We also hypothesised that children’s cognitive and affective empathy would be associated with individual differences in brain structure and function within areas related to the DMN and the SN, respectively. Methods: Participants were 9- and 10-year-old children, a subset from the second wave of the Families and Childhood Transitions Study (FACTS), a longitudinal, community-based cohort study. Sample size across the empirical chapters of the thesis differed depending on measures completed and quality of brain images (study 1 n =127, study 2 n = 125, study 3 n = 112). Self-report measures of empathy (cognitive empathy, affective empathy: affective sharing, empathic concern, empathic distress) and internalising (anxiety and depressive) symptoms were administered, as well as a task-based measure of cognitive empathy. To investigate associations between empathy and internalising symptoms (study 1), canonical correlation analysis (CCA), a multivariate technique, was employed. Participants underwent MRI of the brain where T1-weighted structural images and resting-state functional sequences were collected. Grey matter volume, cortical thickness (study 2), seed-to-whole-brain and dual regression resting-state functional connectivity (study 3) were examined. Results: Study 1: CCA demonstrated that components of affective empathy, specifically affective sharing and empathic distress, were associated with internalising (particularly social anxiety) symptoms. Cognitive empathy was not associated with internalising symptoms. Study 2: In region of interest analyses, individual differences in affective and cognitive empathy were related to grey matter volume in the insula and the precuneus. Although these associations were of similar strength to those found in previous research, they did not survive correction for multiple comparisons. While no associations were detected between grey matter volume and empathy in exploratory whole-brain analysis, associations were found between empathic concern and cortical thickness in the right precentral gyrus. Study 3: Seed-to-whole-brain resting-state functional connectivity analyses demonstrated that both affective sharing and empathic distress were associated with decreased connectivity between key hubs of the DMN (precuneus and temporal parietal junction) and other widespread areas in the brain. Analyses of resting-state networks demonstrated that cognitive empathy was associated with both increased and decreased connectivity between dorsal and lateral regions of the DMN and regions outside of the DMN, including the pre- and postcentral gyrus, and the cerebellum. Affective empathy was associated with increased connectivity between the anterior SN and the pre- and postcentral gyrus. These relationships did not survive strict correction for multiple comparisons. Conclusions: Findings suggested that children who share others’ emotions strongly are more likely to experience anxiety, particularly of a social nature. This study also provided preliminary evidence that individual differences in self-reported empathy in children may be related to certain aspects of brain structure and functional connectivity. Overall, we observed less clear dissociations between the neural correlates of affective versus cognitive empathy, and more widely spread involvement from other brain areas. This potentially indicates reduced maturation and specialisation of the systems underlying affective versus cognitive empathy in this age group. However, more research is required to demonstrate reproducibility of the findings. More research investigating the mental health associations and neurobiological correlates of empathy in children is needed, particularly of a longitudinal nature, to track these changes across development. One limitation of our study is that the majority of our findings were based around self-report measures of empathy, which may not accurately reflect empathic ability.