Sensory development in the newborn infant: modulation by early life experience and the impact of brain injury

Neurological examination in newborn infants is challenging and novel methods of evaluating how multiple sensory systems are affected are needed to compliment developmental care interventions and treatments in the neonatal intensive care (NICU) setting. Infants who are born prematurely and those who are born with a perinatal complication are most vulnerable to debilitating neurocognitive dysfunction. Even though in some cases the problems may arise from clearly identifiable brain lesions routinely captured by brain ultrasound, more subtle changes in brain development may not be identified until school age. Bedside neuroimaging techniques such as the recording of evoked potentials (EP) can provide information regarding the functional integrity of sensory pathways, yet due to the technical challenges of performing them and interpretational issues, they are not widely used in neonatal care. In this thesis, electroencephalography (EEG) was recorded in infants born between 27 – 42 weeks gestational age (GA) and evoked responses to different types of sensory stimulation were analysed using advanced data driven analysis techniques. The spatial and temporal aspects of evoked activity in response to visual, tactile, and noxious stimulation in healthy term infants were characterised, and morphological templates were constructed for each stimulus modality. These templates were designed such that they could be projected onto data collected in independent infant cohorts to evaluate the early maturation of visual and somatosensory processing in prematurely-born infants and to establish how brain activity is altered by brain damage and hypothermia. Using this data-driven analytical approach, the normative development of stimulus evoked activity was studied longitudinally in infants between 28-36 weeks post menstrual age (PMA). This study demonstrated the refinement of the spatial organisation of the stimulus-evoked activity with age and show how the developmental trajectory of these responses differs with the stimulus modality. Comparisons with cross sectional data recorded from a near-term control group of prematurely-born infants shows how specific components of the tactile and visual evoked response are altered by premature exposure to the ex-utero environment. In addition, similar methods were applied to a cohort of infants with neonatal hypoxic ischaemic encephalopathy (HIE) which were compared to a healthy term control group. Tactile and noxious stimulation in infants with HIE evokes significantly reduced magnitude EP responses compared with healthy term infants. This thesis demonstrates how novel methods of evoked potential analysis can be used to evaluate evoked brain activity in newborn infants to address clinically relevant questions across various infant cohorts. In this thesis, I show how normal ex-utero sensory development is potentially affected by early exposure to the ex-utero environment. This supports the importance of developmental care interventions in the NICU. I also show the significant impact of neonatal HIE on somatosensory processing, highlighting the important effects of sedation on the interpretation of evoked potentials in this cohort of infants.