A disruption of normal brain development during early stages of life has been associated with higher male vulnerability expressed by male preponderance among affected individuals and/or more severe impairments in males for developmental disorders. Although this phenomenon is frequently acknowledged by the scientific community, its neurophysiological underpinnings remain largely unclear. In this thesis I investigate male vulnerability in very preterm children and individuals with Autism Spectrum Disorder (ASD). Both clinical child populations entail early developmental adversity leading to behavioural and cognitive alterations, believed to be elicited, in part, by disrupted communication between brain areas. Therefore, I examine resting state whole-brain connectivity and its developmental changes in these clinical populations using fMRI and MEG and test the hypothesis of sex-specific connectivity differences between males and females resulting in male disadvantage. In the first study I investigate sex differences in interhemispheric homotopic connectivity and its developmental trajectories in participants with ASD as well as in typically developing individuals. Our findings demonstrate differences in developmental trajectories rather than connectivity. Both females and males with ASD deviate from typical female trajectories while expressing similar developmental trajectories to typical males. In the second study I examine local connectivity and its age-related changes using a similar cohort of participants. Group and sex differences are observed in both local connectivity and its developmental trajectories. Females with ASD are characterised by more robust alterations. Lastly, in the third study I test the hypothesis that male vulnerability in very preterm children can be detected as more pronounced alterations in inter-regional connectivity in boys compared to girls. Our results confirm this hypothesis suggesting that connectivity alterations might contribute to male disadvantage reflected in long-term behavioural and cognitive outcome. Overall, this thesis highlights that disruptions in brain connectivity and/or its developmental trajectories differ between males and females with altered early development supporting the existence of female protective features preventing females from developing pathological outcome.
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Thesis advisor: Doesburg, Sam
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