Abstract
Background
Enriched language exposure may benefit infants in the neonatal intensive care unit. We hypothesized that changes in neonatal electroencephalogram (EEG) coherence during sleep, in response to maternal voice exposure, predict language development.
Methods
Convalescent neonates underwent 12-h polysomnography. A recording of the mother’s voice was randomized to continuous playback in the first or second 6 h. We calculated the imaginary coherence (ICOH—a measure of functional connectivity) between EEG leads. Spearman correlations were computed between ICOH and 18-month Bayley-III language scores.
Results
Thirty-five neonates were included (N = 18 33-to-<35 weeks gestation; N = 17 ≥ 35 weeks). Predictive value of ICOH during neonatal non-rapid eye movement (NREM) sleep was left lateralized, and varied with gestational age and voice playback. ICOH in the left-hemispheric (C3-Cz; T3-Cz) channels across multiple EEG frequency bands was associated with 18-month language scores (rho = −0.34 to −0.48). The association was driven by neonates born at 33–34 weeks gestation, and a trend suggested a possible effect of maternal voice at some EEG frequencies. Right hemisphere ICOH (C4-Cz; T4-Cz) was not associated with language outcome.
Conclusions
Left-hemispheric EEG functional connectivity during neonatal NREM sleep shows early signs of physiologic asymmetry that may predict language development. We speculate that sleep analyses could have unique prognostic value.
Impact
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During neonatal NREM sleep, EEG functional connectivity predicts future language development.
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Left temporal and central EEG coherence—specifically the imaginary component of coherence—is predictive, whereas the same analysis from the right hemisphere is not.
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These results appear to vary according to the infant’s gestational age, and a trend suggests they may be enhanced by measuring functional connectivity during exposure to the mother’s voice.
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These findings identify early evidence of physiologic differentiation within the cerebral hemispheres and raise the possibility that neonatal NREM sleep has a role to play in language development.
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Acknowledgements
The authors deeply appreciate the infants and parents for their interest in research and enthusiasm for this work. They also thank the clinical research coordinators and sleep technologists, whose tireless attention to detail and care for each of the participating infants was integral to this study. This study was supported by NIH and the Michigan Institute for Clinical and Health Research (R21HD083409; UL1TR002240).
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R.A.S. conceptualized and designed the study, acquired and analyzed the data, drafted the initial manuscript, and approved the final version for submission. R.D.C. assisted with study design and interpretation of the results, critically reviewed the manuscript for important intellectual content, and approved the final version for submission. J.D.E.B. assisted with study design and interpretation of the results, critically reviewed the manuscript for important intellectual content, and approved the final version for submission. F.H interpreted the research polysomnograms, assisted with interpretation of the data, critically reviewed the manuscript for important intellectual content, and approved the final version for submission. M.D.C. assisted with interpretation of the data, critically reviewed the manuscript for important intellectual content, and approved the final version for submission. J.W.B. analyzed the data, assisted with interpretation of the data, critically reviewed the manuscript for important intellectual content, and approved the final version for submission.
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R.A.S’ research is supported by grants from NIH, PCORI, the Pediatric Epilepsy Research Foundation, and the University of Michigan. She serves as a consultant for the Epilepsy Study Consortium and as an Associate Editor for Neurology. She receives royalties from UpToDate for authorship of topics related to neonatal seizures. R.D.C. has had financial relationships with the American Academy of Sleep Medicine, the Associated Professional Sleep Societies, UpToDate, and Cambridge University Press; has been a member of the boards for the International Pediatric Sleep Association and the not-for-profit Sweet Dreamzzz; is a member of an advisory board for the not-for-profit Pajama Program; receives research support from the NIH; is named in patents and copyrighted material, owned by the University of Michigan, that concern identification and treatment of sleep disorders; and has received royalties from Zansors. J.D.E.B. receives grant funding from NIH. F.H. has previously served as a consultant for Biogen, and has received research funding from Jazz pharmaceuticals. M.D.C. has nothing to disclose. J.W.B. receives grant funding from NIH and is named in patents, owned by Michigan Technological University and the University of Michigan, that concern identification and treatment of sleep disorders.
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A parent of every infant provided written informed consent to participate in the study.
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Shellhaas, R.A., Chervin, R.D., Barks, J.D.E. et al. Lateralized neonatal EEG coherence during sleep predicts language outcome. Pediatr Res 91, 962–969 (2022). https://doi.org/10.1038/s41390-021-01554-y
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DOI: https://doi.org/10.1038/s41390-021-01554-y
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