Premature Birth Can Alter Neural Connectivity

Premature birth can alter the connectivity between key areas of the brain, according to a new study led by King’s College London. The findings should help researchers to better understand why premature birth is linked to a greater risk of neurodevelopmental problems, including autistic spectrum disorders and attention deficit disorders.

The NIHR-funded study, published in the journal PNAS, used functional magnetic resonance imaging (fMRI) to look at specific connections in the brains of 66 infants, 47 of whom were born before 33 weeks and were therefore at high risk of neurological impairment, and 19 born at term. The brain connections investigated were between the thalamus and the cortex, connections which develop rapidly during the period a preterm infant is cared for on a neonatal unit.

Researchers found that those born in the normal window of birth (37-42 weeks) showed a remarkably similar structure to adults in these brain regions, strengthening existing evidence that the brain’s network of connections is quite mature at the time of birth.

However, infants born prematurely (before 33 weeks gestation) were found to have less connectivity between areas of the thalamus and particular areas of the brain’s cortex known to support higher cognitive functions, but greater connectivity between the thalamus and an area of primary sensory cortex which is involved in processing signals from the face, lips, jaw, tongue, and throat.

The greater the extent of prematurity, the more marked were the differences in the pattern of brain connectivity.

This shows brain scans taken from the study.
The greater the extent of prematurity, the more marked were the differences in the pattern of brain connectivity. Image adapted from the KCL press release.

The authors suggest that the stronger connections involving face and lips in babies born preterm may reflect their early exposure to breastfeeding and bottlefeeding, while the reduced connectivity in other brain regions may be linked to the higher incidence of difficulties seen in later childhood.

Dr Hilary Toulmin, first author from the Centre for the Developing Brain at King’s College London, said: ‘The next stage of our work will be to understand how these findings relate to the learning, concentration and social difficulties which many of these children experience as they grow older.’

Professor David Edwards, senior author from the Centre for the Developing Brain at King’s College London, said: ‘The ability of modern science to image the connections in the brain would have been inconceivable just a few years ago, but we are now able to observe brain development in babies as they grow, and this is likely to produce remarkable benefits for medicine.’

About this neurology research

Funding: This paper summaries independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-0707-10154) and the Medical Research Council (MRC) Strategic Grant ‘Pre-term Brain Injury’.

Source: Kings College London
Image Source: The image is adapted from the Kings College London press release
Original Research: Full open access research (PDF) for “Specialization and integration of functional thalamocortical connectivity in the human infant” by Hilary Toulmin, Christian F. Beckmann, Jonathan O’Muircheartaigh, Gareth Ball, Pumza Nongena, Antonios Makropoulos, Ashraf Ederies, Serena J. Counsell, Nigel Kennea, Tomoki Arichi, Nora Tusor, Mary A. Rutherford, Denis Azzopardi, Nuria Gonzalez-Cinca, Joseph V. Hajnal, and A. David Edwards in PNAS. Published online May 4 2015 doi:10.1073/pnas.1422638112


Abstract

Specialization and integration of functional thalamocortical connectivity in the human infant

Connections between the thalamus and cortex develop rapidly before birth, and aberrant cerebral maturation during this period may underlie a number of neurodevelopmental disorders. To define functional thalamocortical connectivity at the normal time of birth, we used functional MRI (fMRI) to measure blood oxygen level-dependent (BOLD) signals in 66 infants, 47 of whom were at high risk of neurocognitive impairment because of birth before 33 wk of gestation and 19 of whom were term infants. We segmented the thalamus based on correlation with functionally defined cortical components using independent component analysis (ICA) and seed-based correlations. After parcellating the cortex using ICA and segmenting the thalamus based on dominant connections with cortical parcellations, we observed a near-facsimile of the adult functional parcellation. Additional analysis revealed that BOLD signal in heteromodal association cortex typically had more widespread and overlapping thalamic representations than primary sensory cortex. Notably, more extreme prematurity was associated with increased functional connectivity between thalamus and lateral primary sensory cortex but reduced connectivity between thalamus and cortex in the prefrontal, insular and anterior cingulate regions. This work suggests that, in early infancy, functional integration through thalamocortical connections depends on significant functional overlap in the topographic organization of the thalamus and that the experience of premature extrauterine life modulates network development, altering the maturation of networks thought to support salience, executive, integrative, and cognitive functions.

“Specialization and integration of functional thalamocortical connectivity in the human infant” by Hilary Toulmin, Christian F. Beckmann, Jonathan O’Muircheartaigh, Gareth Ball, Pumza Nongena, Antonios Makropoulos, Ashraf Ederies, Serena J. Counsell, Nigel Kennea, Tomoki Arichi, Nora Tusor, Mary A. Rutherford, Denis Azzopardi, Nuria Gonzalez-Cinca, Joseph V. Hajnal, and A. David Edwards in PNAS. Published online May 4 2015 doi:10.1073/pnas.1422638112

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