Functional Connectivity in Term Neonates With Hypoxic-Ischemic Encephalopathy Undergoing Therapeutic Hypothermia

Background: We investigated whether therapeutic hypothermia and rewarming impact functional connectivity using electroencephalography (EEG) as a measure in neonates with hypoxic-ischemic encephalopathy. We hypothesized that EEG coherence and voltage correlations would be lower and phase lag greater in infants with hypoxic-ischemic encephalopathy than control subjects and that functional connectivity would evolve during therapeutic hypothermia with the greatest improvement occurring during rewarming. Methods: This study was a retrospective study of 14 term neonates (greater than 37 weeks) with moderate hypoxic-ischemic encephalopathy who underwent therapeutic hypothermia and rewarming. Continuous EEG and video monitoring was conducted for 96 hours during therapeutic hypothermia and rewarming. The primary quantitative EEG measures of functional connectivity were coherence, phase lag, and voltage correlations. These EEG parameters were compared with a cohort of normal agematched neonates. Results: Neonates with hypoxic-ischemic encephalopathy had marked decreases in power, coherences, and voltage correlation and increases in phase lag when compared with control neonates. However, there were no significant changes in these measures between therapeutic hypothermia and rewarming. Conclusions: Neonates with hypoxic-ischemic encephalopathy demonstrate significant abnormalities in functional connectivity compared with control subjects. These abnormalities persist through therapeutic hypothermia and rewarming and are not altered after rewarming. Although hypoxic-ischemic encephalopathy is associated with impaired functional brain connectivity, there is no evidence, using quantitative EEG measures, that therapeutic hypothermia or rewarming either improves or exacerbates these abnormalities in connectivity. (C) 2019 Elsevier Inc. All rights reserved.