| Summary: | Background: Preterm birth is associated with a marked increase in the risk of later neurodevelopmental impairment. With the incidence rising, novel tools are needed to provide an improved understanding of the underlying pathology and better prognostic information. Functional Magnetic Resonance Imaging (fMRI) with Blood Oxygen Level Dependent (BOLD) contrast has the potential to add greatly to the knowledge gained through traditional MRI techniques. However, it has been rarely used with neonatal subjects due to difficulties in application and inconsistent results. Central to this is uncertainity regarding the effects of early brain development on the Haemodynamic Response Function (HRF), knowledge of which is fundamental to fMRI methodology and analysis. Hypotheses: (1) Well localised and positive BOLD functional responses can be identified in the neonatal brain. (2) The morphology of the neonatal HRF differs significantly during early human development. (3) The application of an age-appropriate HRF will improve the identification of functional responses in neonatal fMRI studies. Methods: To test these hypotheses, a systematic fMRI study of neonatal subjects was carried out using a custom made somatosensory stimulus, and an adapted study design and analysis pipeline. The neonatal HRF was then characterised using an event related study design. The potential future application of the findings was then tested in a series of small experiments. Results: Well localised and positive BOLD functional responses were identified in neonatal subjects, with a maturational tendency towards an increasingly complex pattern of activation. A positive amplitude HRF was identified in neonatal subjects, with a maturational trend of a decreasing time-to-peak and increasing positive peak amplitude. Application of the empirical HRF significantly improved the precision of analysis in further fMRI studies. Conclusions: fMRI can be used to study functional activity in the neonatal brain, and may provide vital new information about both development and pathology.
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