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Maturation of Interhemispheric Functional Connectivity During a Passive Wrist Motor Task in the Preterm Period

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)).

Maturation of Interhemispheric Functional Connectivity During a Passive Wrist Motor Task in the Preterm Period

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.

Corresponding author: tomoki.arichi@kcl.ac.uk

References
1. Doria et al., 2010. PNAS, 16:20015-20.
2. Allievi et al. 2013. Annals of Biomedical Engineering; 41(6): 1181-92.

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