Feasibility of EEG Phase-Amplitude Coupling to Stratify Encephalopathy Severity in Neonatal HIE Using Short Time Window

Abstract

Goal: It is challenging to clinically discern the severity of neonatal hypoxic ischemic encephalopathy (HIE) within hours after birth in time for therapeutic decision-making for hypothermia. The goal of this study was to determine the shortest duration of EEG based PAC index to provide real-time guidance for clinical decision-making for neonates with HIE.

Methods: Neonates were recruited from a single-center Level III NICU between 2017-2019. A time-dependent, PAC-frequency-averaged index, tPAC_m, was calculated to characterize intrinsic coupling between the amplitudes of 12-30 Hz and the phases of 1-2 Hz oscillation from 6-hr EEG data at electrode P3 during the first day of life, using different sizes of moving windows including 10 s, 20 s, 1 min, 2 min, 5 min, 10 min, 20 min, 30 min, 60 min and 120 min. Time-dependent receiver operating characteristic (ROC) curves were generated to examine the performance of accurate window tPAC_m as a neurophysiologic biomarker.

Results: A total of 33 neonates (No-HIE, n=15 and moderate/severe HIE, n=18)  were enrolled. Mixed effects models demonstrated that tPAC_m between the two groups were significantly different with window time segments of 3 -120 min. By observing the estimates of group differences in tPAC_m across different window sizes, we found 20 min was the shortest window size to optimally distinguish the two groups (p<0.001). Time-varying ROC showed significant average area-under-the-curve of 0.82.

Conclusion: We demonstrate the feasibility of using tPAC_m with a 20min EEG time window to differentiate the severity of HIE and facilitate earlier diagnosis and treatment initiation.

Note:
Funding Information: Dr. Lina Chalak is funded by NIH Grant R01NS102617.

Declaration of Interests: Authors have no conflict of interest to report.

Ethics Approval Statement: This study was approved by the institutional review board at the University of Texas Southwestern Medical Center. The parent of each neonate signed a written informed consent prior to enrollment.

Keywords: Neonatal Hypoxic Ischemic Encephalopathy, Time-Dependent Phase Amplitude Coupling, EEG, Hypoxic Ischemic Encephalopathy biomarkers, mixed effects models