Despite advances in perinatal care over the past decades, extremely low birth weight (ELBW: birth weight <1000gm; age at birth ~ < 30 wks) infants are at high risk for cerebral palsy (CP), developmental delay, and sensory-motor deficits in infancy and learning disabilities, dyslexia, and hyperactivity-inattention syndromes at school age. Risk factors for these poor outcomes include abnormalities on head ultrasound exam (HUS), chronic lung disease (CLD), weight and age at birth, intrauterine growth restriction (IUGR), sepsis, chorioamnionitis, necrotizing enterocolitis, use of postnatal steroids, and sex. The most striking association with CP and adverse mental development is an abnormal HUS with evidence of intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), and ventriculomegaly. However, recent clinical research has demonstrated that adverse outcome can occur in ELBW infants with a normal HUS. Magnetic Resonance Imaging (MRI) at term equivalent age shows that ELBW infants have diffuse white matter injury and regionally reduced brain tissue volumes that correlate with adverse neurodevelopmental outcome. These findings point to a gap in our diagnostic techniques for a more readily available and sensitive means to identify, early on, subtle cerebral abnormalities that presage abnormal clinical outcomes later in life. Based on our preliminary research, we propose that measures of electrocortical synchrony derived from analyses of high density (128-lead) EEG from ELBW infants can identify both the location and extent of altered cortical function that is related to perinatal risk factors for adverse neurodevelopmental outcome. Quantitative computations of EEG waveform synchrony at various spatial scales are acknowledged measures of regional neural functional connectivity. At the smallest scales (< cm), that of the cortical columns, cortical synchrony is quantified by EEG spectral power. At cm and larger scales, functional connectivity between brain regions is measured by the synchrony of EEG waveforms between two regions as quantified by methods such as the coherence algorithm. In our preliminary analyses, ELBW and healthy full term (HFT) control infants, at term post conceptual age (PCA), did not have differences in regional EEG power but the ELBW infants had altered regional coherence values reflecting changes in functional electrocortical connectivity. The locations of decreased functional connectivity paralleled regions of abnormality in brain structure observed in MRI studies conducted by other investigators. Of equal interest, in analyses of the NICHD CHIME data base, we found a significant correlation between the EEG interhemispheric coherence of ELBW infants at term equivalent age and their Bayley Mental Development Index (MDI) at one year thus linking EEG functional connectivity to outcome. To provide new knowledge for understanding the causes of electrocortical dysfunction in ELBW infants we propose to examine associations between regional cortical function and perinatal factors known to increase risk for adverse outcome. Our approach is to collect high density EEG from ELBW infants, stratified by risk, and from a control group of healthy term infants. Our long-term goal is to determine if measures of altered EEG synchrony will be sensitive and specific predictors of the neurodevelopmental outcome of ELBW infants. We will test this hypothesis in future studies using results from the present study as pilot data. Extremely low birth weight premature infants are at risk for adverse neurodevelopmental outcome even when there are no apparent brain injuries. Our new method, using noninvasive measurements of infant brain electricity, has the potential to provide new methods of care for these infants. ? ? ?
| Grieve, Philip G; Isler, Joseph R; Izraelit, Asya et al. (2008) EEG functional connectivity in term age extremely low birth weight infants. Clin Neurophysiol 119:2712-20 |
