Presented at the Neonatal Society 2014 Autumn Meeting.
Kimpton JA1, Allievi AG2, Counsell SJ1, Burdet E2, Edwards AD1,2,3, Arichi T1,2
1 Centre for the Developing Brain, King’s College London, St Thomas’ Hospital, London, UK
2 Department of Bioengineering, Imperial College London, South Kensington Campus, UK
3 The Neonatal Intensive Care Unit, St Thomas’ Hospital, London, UK
Background: Functional neural networks rapidly mature during the preterm period. Resting state fMRI studies show that this process is characterised by marked increases in long-range (and in particular interhemispheric) connectivity 1. At the end point of this period, the specificity of functional connectivity increases, resulting in an adult-like distribution at term equivalent age. However, the maturation of functional connectivity within task-evoked responses is unknown. We hypothesised that, as seen at rest, interhemispheric functional connectivity during a simple motor task initially increases during the preterm period but then decreases as connections become increasingly specific at full term.
Methods: The work was carried out with ethical approval (REC ref: 12/LO/1247) and supported by MRC funding. 62 neonatal subjects between 30+2 to 43+2 weeks post-menstrual age (PMA) were studied. Neonates were excluded if they had focal brain pathology, congenital malformations or if there were severe image artefacts, leaving a study population of 48 infants. fMRI data were obtained with a 3-T Philips MRI system and an EPI sequence lasting 6.5 minutes. Chloral hydrate sedation was administered to neonates >37 weeks PMA. Passive motor stimulation (right wrist extension/flexion) was elicited using a fully automated fMRI-compatible robotic interface and a simple block paradigm 2. fMRI data was analysed using FSL (www.fmrib.ox.ac.uk/fsl) and MATLAB. Functional connectivity was assessed by calculating the partial correlation coefficient (normalised using the Fisher’s z transformation) between the mean BOLD signal time-series within anatomically defined left and right peri-rolandic regions (figure (a)).
Results: The z-transformed partial correlation coefficient between the anatomically defined right (figure (a), red) and left (figure (a) blue) peri-rolandic regions was seen to rapidly increase during the preterm period until approximately 36 weeks PMA. It then steadily decreases towards term equivalent age leading to an inverted U-shape relationship (figure (b)).
Conclusion: The late pre-term period is associated with a significant increase in interhemispheric functional connectivity. This may be driven by the rapid growth of cortico-cortical connections through the corpus callosum. Whilst connectivity appears to decrease at term equivalent age, this may be due to increasing spatial specificity of the functional response during task activity.
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1. Doria et al., 2010. PNAS, 16:20015-20.
2. Allievi et al. 2013. Annals of Biomedical Engineering; 41(6): 1181-92.