How Premature Birth Alters Early Brain Network Development
Babies born prematurely show a relative preservation of core brain connections but have reduced connectivity in local pathways compared to babies born closer to their due dates.
Source
Early development of structural networks and the impact of prematurity on brain connectivity
Study at a glance
- Design
- Cohort — Neonatal diffusion MRI tractography and neurite-density mapping by gestational age at birth
- N
- N=65 · 8 infants scanned twice; birth GA 24+2 to 41+1 weeks; scanned ≤46 weeks PMA
- Population
- Preterm and term neonates undergoing high-resolution diffusion MRI
- Outcome
- Age- and prematurity-related change in structural-network neurite density and fractional anisotropy
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How Premature Birth Alters Early Brain Network Development
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8 subjects were scanned twice
Of those, 8 subjects were scanned twice (median 6 +6 , range 3 +3 −8 +5 weeks after the first scan).
What was the primary objective of this study regarding structural brain networks prior to term-equivalent age?
In this study we used high angular resolution multi-shell dMRI to assess connectivity between brain regions using connectivity metrics obtained from the diffusion tensor (fractional anisotropy, FA) as well as streamline measures obtained using constrained spherical deconvolution (CSD) with the spherical-deconvolution informed filtering of tractograms (SIFT) algorithm (, ) and NODDI model characteristics: neurite density index (NDI) and orientation dispersion index (ODI).
What they did
The researchers scanned 65 neonates using high-resolution diffusion magnetic resonance imaging, with 8 subjects scanned twice. The infants' gestational age at birth ranged from 24 +2 to 41 +1 weeks, and post-menstrual age at scanning ranged from 25 +3 to 45 +6 weeks. The team mapped structural brain networks using advanced tractography and estimated tissue microstructure using modeling techniques.
What they found
With increasing age, infants showed a widespread increase in neurite density and fractional anisotropy across most brain connections, particularly between deep grey matter and central cortical regions. However, infants born more prematurely had significantly lower neurite density and fractional anisotropy values in local, short-range connections, while their highly central core connections remained relatively preserved. This imbalance resulted in an apparent increase in normalized neurite density-weighted global efficiency in preterm infants, driven specifically by the loss of local connection strength rather than an actual improvement in network architecture.
The limits
What it doesn't show
This study is primarily correlational and cannot prove that premature birth directly causes the observed structural abnormalities, as confounding clinical factors like respiratory distress or medical treatments could also play a role. The sample size of 65 neonates is relatively small, and because the infants were scanned during sleep or under mild sedation at term-equivalent age, potential long-term functional and behavioral outcomes could not be directly measured at this stage. Additionally, the study does not show how these early structural network alterations adapt or resolve as these children grow older.
Key terms
- Diffusion MRI (dMRI)
- An imaging technique that maps the diffusion of water molecules to visualize the structural pathways and white matter tracts of the brain.
- Neurite Orientation Dispersion and Density Imaging (NODDI)
- An advanced diffusion MRI modeling technique that estimates the density and spatial orientation of axons and dendrites in brain tissue.
- Fractional Anisotropy (FA)
- A measure derived from diffusion tensor imaging that reflects the directivity of water diffusion, often used as an index of white matter integrity.
- Neurite Density Index (NDI)
- A microstructural metric representing the volume fraction of tissue occupied by axons and dendrites, providing a more specific measure of tissue maturity than traditional anisotropy.
- Global Efficiency
- A graph theory metric that reflects how easily information can be integrated and shared across a whole network based on the shortest paths between nodes.
- Core Connections
- Highly central, heavily trafficked pathways in a network that act as major hubs to facilitate rapid communication across the entire brain.
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Quiz yourself
What was the primary objective of this study regarding structural brain networks prior to term-equivalent age?
Common questions
Why did the researchers focus on local connections instead of just the main core pathways?
While core connections are vital for overall brain communication, local connections support specific, specialized tasks like language, emotional regulation, and attention. Understanding how prematurity selectively damages these local circuits helps explain why preterm children often experience specific cognitive and behavioral difficulties later in life despite overall brain development.
What is the advantage of using NODDI over standard Diffusion Tensor Imaging (DTI)?
Traditional DTI measures like fractional anisotropy (FA) can be influenced by multiple factors, such as crossing fibers or water content, making them less specific. NODDI separates these factors to measure biological properties like neurite density and fiber orientation directly, providing a clearer picture of how brain tissue is actually maturing.
Why did premature babies show an 'increase' in global efficiency if their brains were less developed?
This counterintuitive finding is an artifact of the mathematical normalization process. Because premature babies lost connectivity strength specifically in their local (non-core) connections while keeping their strong core connections intact, the relative mathematical weight of their core connections artificially inflated, making the network appear globally efficient even though it was actually damaged.
Were the infants sedated during the MRI scans?
Most infants, including term controls and preterm infants scanned before their due dates, were imaged during natural sleep without sedation. However, preterm infants scanned at their term-equivalent age were given a mild oral sedative, chloral hydrate, to prevent motion during the scan.
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