Neonatal infant EEG bursts are altered by prenatal maternal depression and serotonin selective reuptake inhibitor use.

OBJECTIVE: Increasingly, serotonin selective reuptake inhibitor (SSRI) medications are prescribed in pregnancy. These medications pass freely into the developing fetus but little is known about their effect on brain development in humans. In this study we determine if prenatal maternal depression and SSRI medication change the EEG infant delta brush bursts which are an early marker of normal brain maturation. METHODS: We measured delta brush bursts from the term infants of three groups of mothers (controls (N = 52), depressed untreated (N = 15), and those taking serotonin SSRI medication (N = 10). High density EEGs were obtained during sleep at an average age of 44 weeks post conceptional age. We measured the rate of occurrence, brush amplitude, oscillation frequency and duration of the bursts. RESULTS: Compared to infants of control mothers, the parameters of delta brush bursts of the offspring of depressed and SSRI-using mothers are significantly altered: burst amplitude is decreased; the oscillation frequency increased, and the duration increased (SSRI only). These significant differences were found during both sleep states. CONCLUSIONS: Electrocortical bursting activity (i.e. delta brushes) is known to play an important role in early central nervous system (CNS) synaptic formation and function. SIGNIFICANCE: Maternal depression or SSRI use may alter brain function in their offspring.

Newborn electroencephalographic correlates of maternal prenatal depressive symptoms.

Maternal perinatal depression exerts pervasive effects on the developing brain, as evidenced by electroencephalographic (EEG) patterns that differ between children of women who do and do not meet DSM or ICD diagnostic criteria. However, little research has examined if the same EEG pattern of right-frontal alpha asymmetry exists in newborns and thus originates in utero independent of postnatal influences, and if depressive symptoms are associated with this neural signature. Utilizing 125-lead EEG (n=18), this study considered clinician-rated maternal prenatal depressive symptoms in relation to newborn EEG. Maternal depressive symptomatology was associated with greater relative right-frontal alpha asymmetry during quiet sleep. These results suggest that even subclinical levels of maternal depression may influence infant brain development, and further support the role of the prenatal environment in shaping children's future neurobehavioral trajectories.

Family Nurture Intervention in preterm infants alters frontal cortical functional connectivity assessed by EEG coherence.

AIM: To assess the impact of Family Nurture Intervention (FNI) on cortical function in preterm infants at term age. METHODS: Family Nurture Intervention is a NICU-based intervention designed to establish emotional connection between mothers and preterm infants. Infants born at 26-34 weeks postmenstrual age (PMA) were divided into two groups, standard care (SC, N = 49) and FNI (FNI, N = 56). Infants had EEG recordings of ~one hour duration with 124 lead nets between 37 and 44 weeks PMA. Coherence was measured between all pairs of electrodes in ten frequency bands. Data were summarised both within and between 12 regions during two sleep states (active, quiet). RESULTS: Coherence levels were negatively correlated with PMA age in both groups. As compared to SC infants, FNI infants showed significantly lower levels of EEG coherence (1-18 Hz) largely within and between frontal regions. CONCLUSION: Coherence in FNI infants was decreased in regions where we previously found robust increases in EEG power. As coherence decreases with age, results suggest that FNI may accelerate brain maturation particularly in frontal brain regions, which have been shown in research by others to be involved in regulation of attention, cognition and emotion regulation; domains deficient in preterm infants.

Fetal cerebrovascular resistance and neonatal EEG predict 18-month neurodevelopmental outcome in infants with congenital heart disease.

OBJECTIVES: The purpose of this study was to investigate early markers of risk for neurobehavioral compromise in survivors with congenital heart disease (CHD). METHODS: Pregnant women in whom a fetal CHD had been diagnosed before 24 weeks' gestational age (GA) were enrolled in this prospective pilot study for serial Doppler ultrasound assessment of the fetal middle cerebral artery (MCA) and umbilical arteries. The cerebral-to-placental resistance ratio (CPR) and MCA pulsatility index (PI) Z-scores for GA were calculated. After birth, subjects underwent high-density (128-lead) electroencephalography (EEG), and beta frequency (12-24 Hz) band EEG power, a measure of local neural synchrony, was analyzed. Neurodevelopment was assessed at 18 months with the Bayley Scales of Infant Development (BSID)-III. RESULTS: Thirteen subjects were enrolled: four with hypoplastic left heart syndrome (HLHS), four with transposition of the great arteries (TGA) and five with tetralogy of Fallot (TOF). Compared with subjects with normal CPR, those with CPR < 1 (n = 7) had lower mean BSID cognitive scores (91.4 ± 4.8 vs. 99.2 ± 3.8, P = 0.008). Fetal MCA-PI Z-score also correlated with BSID cognitive score (r = 0.589, P = 0.03) as did neonatal EEG left frontal polar (r = 0.58, P = 0.037) and left frontal (r = 0.77, P = 0.002) beta power. Furthermore, fetal Doppler measures were associated with EEG power: fetuses with CPR < 1 had lower left frontal polar (t = 2.36, P = 0.038) and left frontal (t = 2.85, P = 0.016) beta power as newborns than did fetuses with normal CPR, and fetal MCA-PI Z-score correlated with neonatal EEG left frontal polar (r = 0.596, P = 0.04) and left frontal (r = 0.598, P = 0.04) beta power. CONCLUSION: In fetuses with HLHS, TGA and TOF, abnormal cerebrovascular resistance predicts decreased neonatal EEG left frontal beta power and lower 18-month cognitive development scores.

Developmental profiles of infant EEG: overlap with transient cortical circuits.

OBJECTIVE: To quantify spectral power in frequency specific bands and commonly observed types of bursting activities in the EEG during early human development. METHODS: An extensive archive of EEG data from human infants from 35 to 52 weeks postmenstrual age obtained in a prior multi-center study was analyzed using power spectrum analyses and a high frequency burst detection algorithm. RESULTS: Low frequency power increased with age; however, high frequency power decreased from 35 to 45 weeks. This unexpected decrease was largely attributable to a rapid decline in the number of high frequency bursts. CONCLUSIONS: The decline in high frequency bursting activity overlaps with a developmental shift in GABA's actions on neurons from depolarizing to hyperpolarizing and the dissolution of the gap junction circuitry of the cortical subplate. SIGNIFICANCE: We postulate that quantitative characterization of features of the EEG unique to early development provide indices for tracking changes in specific neurophysiologic mechanisms that are critical for normal development of brain function.

Reduced functional connectivity in visual evoked potentials in children with autism spectrum disorder.

OBJECTIVE: An analysis of EEG synchrony between homologous early visual areas tested the hypothesis that interhemispheric functional connectivity during visual stimulation is reduced in children with autism compared to controls. METHODS: EEG power and coherence within and between two homologous regions of the occipital cortex were measured during long latency flash visual evoked potentials. Measures were compared between two groups of children (5.5-8.5years), one with autism spectrum disorders and the other with typical development. RESULTS: In and below the theta band, interhemispheric synchrony was reduced in autistic subjects compared to typical controls by as much as 50%. Above the theta band interhemispheric synchrony in autistic children became indistinguishable from what would occur for uncorrelated cortical activity. Interhemispheric synchrony in autistic subjects was decreased in spite of bilaterally increased power. Wavelet power showed autistic children had a more rapid initial response to stimulation, a slower recovery, and more modulation at longer latencies. CONCLUSIONS: Results suggest that the sensory cortices of autistic children are hypersensitive to stimulation with concurrent diminished functional connectivity between hemispheres. SIGNIFICANCE: Simultaneously increased intrahemispheric power and decreased interhemispheric synchronization of elementalvisual information suggests either that power increases cause poor interhemispheric connectivity or that processes, such as thalamocortical regulation, impact power and coherence independently.

Behavioral states in the fetal baboon.

This study was designed to characterize behavioral states in the fetal baboon. Automated methods were developed and validated to recognize behavioral states based on relationships among three physiologic variables (EEG patterns, eye movements, heart period variability). Data included twelve 16-h records from 3 chronically instrumented fetal baboons at 0.8-0.9 of term. Randomly generated control records were used to differentiate occurrences of state from chance association of the variables. For 41.2 +/- 4.6% (mean +/- S.E.) of the time, the physiologic variables were synchronous and formed cycles of state with a mean duration of 34.4 min. Components of these cycles had mean +/- S.E. durations of 7.2 +/- 0.3 min for state 1FB (the analogue of quiet sleep in the human infant and state 1F in the human fetus), 20.7 +/- 1.2 min for the state 2FB (the analogue of active sleep in the human infant and state 2F in the human fetus), and 3.6 +/- 0.2 min for state transitions. For 24.6 +/- 2.4% of the time, the state variables exhibited coincidental, state-like agreements, that were not part of state cycles. Finally, for 34.3 +/- 2.7% of the time, there was no systematic agreement among the three variables. These data provide convincing evidence that organized behavioral states are present in the fetal baboon as early as 0.8 of term gestation.

A quantitative method for classification of EEG in the fetal baboon.

Electroencephalographic (EEG) activity is used as a primary indicator of sleep states in adults and infants of many species and in the ovine fetus. We recently reported that the baboon fetus exhibits visually discernable patterns of EEG activity. One pattern of activity, characterized by the intermittent presence of repetitive bursts of high-voltage EEG, is indistinguishable from trace alternant (TA). TA is a distinctive pattern of EEG activity found only during early stages of development in primates. TA is the predominant pattern of EEG activity during quiet sleep in human infants < 2 mo of age. The focus of this study was to derive quantitative parameters that would discriminate TA from other activity and then to develop a method for automated categorization of EEG patterns. Results demonstrate that several parameters derived from frequency-domain analyses are related to visually coded EEG states. Among these parameters, high-frequency power (12-24 Hz) and spectral-edge frequency are good discriminators of EEG patterns. This paper describes a new parameter, EEG ratio, computed as spectral power in the rectified EEG within a band that corresponds to the frequency of bursts of activity during TA (0.03-0.20 Hz) divided by power in the 12- to 24-Hz band. This new composite parameter of EEG activity provides a markedly better correlate of visually coded EEG than any of the individual parameters tested. Using cluster analysis, we devised a method for objective minute-by-minute dichotomization of EEG ratio. The method produces results that agree with visual coding of EEG activity 87.1% of the time.(ABSTRACT TRUNCATED AT 250 WORDS)