Brain structural and functional connectivity and associated outcomes in children without cerebral palsy treated with therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)


Perturbations to healthy brain structure and function, for example caused by brain injury, result in impairments to cognitive, motor and behavioural outcomes. Children without severe disability who were treated with therapeutic hypothermia (TH) for neonatal hypoxic-ischaemic encephalopathy (HIE) have impaired outcomes at early school-age. The underlying differences in brain structure and function which cause these impairments must be understood in order to inform research into treatment or therapeutic intervention. This thesis comprises five journal articles and one preprint presenting neuroimaging findings from the “CoolMRI” study – a study of early school age children treated with TH for neonatal HIE – in addition to methodological developments to aid the study of human brain structure and function. Four chapters focus on structural connectivity, as follows. Spencer et al. (2022a) presents an age specific atlas of white matter tracts in children aged 6–8 years, and demonstrates the need for an age-matched atlas when studying white matter pathways in children. Spencer et al. (2021b) demonstrates alterations to structural brain networks, constructed from diffusion-weighted imaging data using tractography, in cooled children compared to controls, and demonstrates associations with cognitive outcome. This network neuroscience approach is then used in Spencer et al. (2021a) to highlight associations between structural connectivity and motor outcome in cooled children. Spencer et al. (2023) investigates mammillary body abnormalities, cognitive outcomes, and diffusivity in the mammillothalamic tract and fornix in cooled children. The subsequent two chapters focus on functional connectivity analysis of resting-state fMRI data. Spencer and Goodfellow (2022) introduces a novel development to the dynamic functional connectivity analysis methodology, evaluating the use of dimensionality reduction prior to clustering windowed functional connectivity data into brain states. Spencer et al. (2022b) (preprint) then investigates functional connectivity in the CoolMRI cohort, incorporating the methods introduced in the preceding chapter in addition to static functional connectivity analyses.
Date of Award9 May 2023
Original languageEnglish
Awarding Institution
  • The University of Bristol
SupervisorElavazhagan Chakkarapani (Supervisor), Jonathan C W Brooks (Supervisor) & Marc Goodfellow (Supervisor)

Cite this