Brain Metastability in the Human Neonate

The flexibility and adaptability of the brain are supported by metastable dynamics, i.e. rapid transitions between transiently stable neural configurations. These dynamics rely on the interplay between large-scale functional integration and local segregation, supported by underlying structural infrastructure and the balance between excitatory-inhibitory (E-I) neurotransmission. Despite its relevance for cognitive flexibility, the ontogeny of metastability remains poorly characterised. At birth, humans are altricial and the brain’s structural and functional infrastructure is still developing. This thesis investigates whether resting neonatal brain activity exhibits changes in metastable dynamics as a reflection of ongoing development, and examines the maturation of their supporting functional systems during the full-term period (37–45 weeks corrected gestational age). Metastability can be assessed through spatiotemporal patterning of brain activity; an example transient state is the EEG-derived microstate. Chapter 3 examines the reliability of neonatal EEG microstate analysis across two London sites, highlighting methodological sensitivities and lays the foundation for improving cross-site standardisation. Chapter 4 compares neonatal and adult microstates across sleep and wakefulness. While neonates and adults share common spatial microstate configurations, neonates display slower dynamics, a reduced repertoire of transition patterns, and minimal state-dependent modulation, suggesting developmental immaturity in metastable dynamics. Chapter 5 explores the functional systems that may support metastability, examining the associations at rest between periodic and aperiodic EEG activity, MRS-derived neurotransmitter concentrations, and fMRI BOLD fluctuations. The absence of consistent associations at this stage may reflect the immaturity of the developing functional systems underlying metastability. Taken together, these findings suggest that: (i) EEG microstates offer a promising tool for studying neonatal brain metastability; (ii) neonatal metastability is immature compared to adults; and (iii) such immaturity may reflect ongoing maturation in homeostatic regulation and in the coordination between functional activity and neurochemical signalling systems.