Disrupted brain connectivity in children treated with therapeutic hypothermia for neonatal encephalopathy

Arthur P C Spencer, Jonathan C W Brooks, Naoki Masuda, Hollie Byrne, Richard Lee-Kelland, Sally Jary, Marianne Thoresen, James Tonks, Marc Goodfellow, Frances M Cowan, Ela Chakkarapani*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

1 Citation (Scopus)
12 Downloads (Pure)

Abstract

Therapeutic hypothermia following neonatal encephalopathy due to birth asphyxia reduces death and cerebral palsy. However, school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal encephalopathy still have reduced performance on cognitive and motor tests, attention difficulties, slower reaction times and reduced visuo-spatial processing abilities compared to typically developing controls. We acquired diffusion-weighted imaging data from school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal encephalopathy at birth, and a matched control group. Voxelwise analysis (33 cases, 36 controls) confirmed reduced fractional anisotropy in widespread areas of white matter in cases, particularly in the fornix, corpus callosum, anterior and posterior limbs of the internal capsule bilaterally and cingulum bilaterally. In structural brain networks constructed using probabilistic tractography (22 cases, 32 controls), graph-theoretic measures of strength, local and global efficiency, clustering coefficient and characteristic path length were found to correlate with IQ in cases but not controls. Network-based statistic analysis implicated brain regions involved in visuo-spatial processing and attention, aligning with previous behavioural findings. These included the precuneus, thalamus, left superior parietal gyrus and left inferior temporal gyrus. Our findings demonstrate that, despite the manifest successes of therapeutic hypothermia, brain development is impaired in these children.

Original languageEnglish
Article number102582
Number of pages14
JournalNeuroImage: Clinical
Volume30
Early online date10 Feb 2021
DOIs
Publication statusE-pub ahead of print - 10 Feb 2021

Bibliographical note

Funding Information:
This work was supported by the Baily Thomas Charitable Fund ( TRUST/VC/AC/SG4681-7596 ), David Telling Charitable Trust, as well as Sparks (05/BTL/01 and 14/BTL/01) and the Moulton Foundation. AS is supported by the Wellcome Trust (WT220070/Z/20/Z). JB is supported by the UK Medical Research Council (MR/N026969/1). MG is supported by the EPSRC (EP/N014391/1) and by a Wellcome Trust Institutional Strategic Support Award (WT105618MA).

Publisher Copyright:
© 2021 The Authors

Keywords

  • Neonatal encephalopathy
  • Therapeutic hypothermia
  • White matter
  • Structural connectivity
  • Brain networks
  • Diffusion-weighted imaging

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