Infants' neural sensitivity to social interactions varies by income and infant-directed speech.

Social interactions are essential for infant brain development, yet we know little about how infant functional connectivity differs between social and nonsocial contexts, or how sensitivity to differences between contexts might be related to early distal and proximal environmental factors. We compared 12-month-old infants' intrahemispheric electroencephalographic (EEG) coherence between a social and a nonsocial condition, then examined whether differences between conditions varied as a function of family economic strain and two maternal behaviors at 6 months, positive affect and infant-directed speech. We found lower EEG coherence from the frontal region to the central, parietal, temporal, and occipital regions during the social condition, but only for infants from higher-income families and infants whose mothers used higher proportions of infant-directed speech. In contrast, there were no differences between social and nonsocial conditions for infants from economically strained families or infants whose mothers used lower proportions of infant-directed speech. This study demonstrates that neural organization differs between a nonsocial baseline and a social interaction, but said differentiation is not present for infants from less privileged backgrounds. Our results underscore the importance of examining brain activity during species-typical contexts to understand the role of environmental factors in brain development.

Family nurture intervention increases term age forebrain EEG activity: A multicenter replication trial.

OBJECTIVE: This trial (RCT-2) sought to replicate the EEG findings of a randomized controlled trial of Family Nurture Intervention in the NICU (FNI-NICU) (RCT-1) comparing infants receiving standard care (SC) with infants receiving SC plus FNI . METHODS: RCT-2 (NCT02710474) was conducted at two NICUs. Subjects were randomly assigned to receive SC or FNI during their NICU stay. The primary outcome was EEG power in the frontal polar region at 39-41 weeks gestational age (GA). Sixty preterm infants (26-34 weeks GA; 33 SC, 27 FNI) were assessed. FNI-NICU consisted of repeated calming sessions (∼4 times/week) facilitated by Nurture Specialists during which mothers engaged in emotional expression during clothed or skin-to-skin holding, vocal soothing, and eye contact. EEGs were collected from 128 leads. EEG power was computed using Fast Fourier Transforms. RESULTS: RCT-2 replicated RCT-1 results; FNI-NICU led to significantly increased frontal polar power at frequencies > 12 Hz. Effects were spatially more widespread than in RCT-1, with substantial effect sizes (∼0.50) in frontal and parietal regions. CONCLUSIONS: RCT-2 results provide further evidence that FNI-NICU increases term age brain activity. SIGNIFICANCE: FNI-NICU is designed to facilitate autonomic emotional connection and coregulation between mothers and infants in the NICU resulting in profound effects on early brain development.

Family nurture intervention alters relationships between preterm infant EEG delta brush characteristics and term age EEG power.

OBJECTIVE: Family Nurture Intervention (FNI) facilitates mother/infant emotional connection, improves neurodevelopmental outcomes and increases electroencephalogram (EEG) power at term age. Here we explored whether delta brushes (DB), early EEG bursts that shape brain development, are altered by FNI and mediate later effects of FNI on EEG. METHODS: We assessed DB characteristics in EEG data from a randomized controlled trial comparing infants with standard care (SC, n = 31) versus SC + FNI (n = 33) at ~35 and ~40 weeks GA. RESULTS: Compared to SC infants, FNI infant DB amplitude increased more from ~35 to ~40 weeks, and FNI infants had longer duration DBs. DB parameters (rate, amplitude, brush frequency) at ~35 weeks were correlated with power at ~40 weeks, but only in SC infants. FNI effects on DB parameters do not mediate FNI effects on EEG power or coherence at term. CONCLUSIONS: DBs are related to subsequent brain activity and FNI alters DB parameters. However, FNI's effects on electrocortical activity at term age are not dependent on its earlier effects on DBs. SIGNIFICANCE: While early DBs can have important effects on later brain activity in preterm infants, facilitating emotional connection with FNI may allow brain maturation to be less dependent on early bursts.

Integrated information in the EEG of preterm infants increases with family nurture intervention, age, and conscious state.

A putative quantifier of consciousness, integrated information, was applied to preterm infant EEG data after novel pre-processing. Integrated information had a non-random structure as a function of the time lag over which it was computed. For most lags, it increased with age in early life, but even more so in infants exposed to Family Nurture Intervention (FNI), providing further evidence that FNI advances brain maturation in preterm infants. Also, it discriminated between conscious states (awake, REM sleep, NREM sleep), providing empirical support for the Integrated Information Theory of Consciousness in human infants.

Family nurture intervention in preterm infants increases early development of cortical activity and independence of regional power trajectories.

AIM: Premature delivery and maternal separation during hospitalisation increase infant neurodevelopmental risk. Previously, a randomised controlled trial of Family Nurture Intervention (FNI) in the neonatal intensive care unit demonstrated improvement across multiple mother and infant domains including increased electroencephalographic (EEG) power in the frontal polar region at term age. New aims were to quantify developmental changes in EEG power in all brain regions and frequencies and correlate developmental changes in EEG power among regions. METHODS: EEG (128 electrodes) was obtained at 34-44 weeks postmenstrual age from preterm infants born 26-34 weeks. Forty-four infants were treated with Standard Care and 53 with FNI. EEG power was computed in 10 frequency bands (1-48 Hz) in 10 brain regions and in active and quiet sleep. RESULTS: Percent change/week in EEG power was increased in FNI in 132/200 tests (p < 0.05), 117 tests passed a 5% False Discovery Rate threshold. In addition, FNI demonstrated greater regional independence in those developmental rates of change. CONCLUSION: This study strengthens the conclusion that FNI promotes cerebral cortical development of preterm infants. The findings indicate that developmental changes in EEG may provide biomarkers for risk in preterm infants as well as proximal markers of effects of FNI.

Maternal cortisol slope at 6 months predicts infant cortisol slope and EEG power at 12 months.

Physiological stress systems and the brain rapidly develop through infancy. While the roles of caregiving and environmental factors have been studied, implications of maternal physiological stress are unclear. We assessed maternal and infant diurnal cortisol when infants were 6 and 12 months. We measured 12-month infant electroencephalography (EEG) 6-9 Hz power during a social interaction. Steeper 6-month maternal slope predicted steeper 12-month infant slope controlling for 6-month infant slope and breastfeeding. Steeper 6-month maternal slope predicted lower 6-9 Hz power. Six-month maternal area under the cuve (AUCg) was unrelated to 12-month infant AUCg and 6-9 Hz power. Psychosocial, caregiving, and breastfeeding variables did not explain results. At 6 months, maternal and infant slopes correlated, as did maternal and infant AUCg. Twelve-month maternal and infant cortisol were unrelated. Results indicate maternal slope is an informative predictor of infant physiology and suggest the importance of maternal physiological stress in this developmental period.

A Within-subjects Experimental Protocol to Assess the Effects of Social Input on Infant EEG.

Despite the importance of social interactions for infant brain development, little research has assessed functional neural activation while infants socially interact. Electroencephalography (EEG) power is an advantageous technique to assess infant functional neural activation. However, many studies record infant EEG only during one baseline condition. This protocol describes a paradigm that is designed to comprehensively assess infant EEG activity in both social and nonsocial contexts as well as tease apart how different types of social inputs differentially relate to infant EEG. The within-subjects paradigm includes four controlled conditions. In the nonsocial condition, infants view objects on computer screens. The joint attention condition involves an experimenter directing the infant's attention to pictures. The joint attention condition includes three types of social input: language, face-to-face interaction, and the presence of joint attention. Differences in infant EEG between the nonsocial and joint attention conditions could be due to any of these three types of input. Therefore, two additional conditions (one with language input while the experimenter is hidden behind a screen and one with face-to-face interaction) were included to assess the driving contextual factors in patterns of infant neural activation. Representative results demonstrate that infant EEG power varied by condition, both overall and differentially by brain region, supporting the functional nature of infant EEG power. This technique is advantageous in that it includes conditions that are clearly social or nonsocial and allows for examination of how specific types of social input relate to EEG power. This paradigm can be used to assess how individual differences in age, affect, socioeconomic status, and parent-infant interaction quality relate to the development of the social brain. Based on the demonstrated functional nature of infant EEG power, future studies should consider the role of EEG recording context and design conditions that are clearly social or nonsocial.

Vital signs and their cross-correlation in sepsis and NEC: a study of 1,065 very-low-birth-weight infants in two NICUs.

BACKGROUND: Subtle changes in vital signs and their interactions occur in preterm infants prior to overt deterioration from late-onset septicemia (LOS) or necrotizing enterocolitis (NEC). Optimizing predictive algorithms may lead to earlier treatment. METHODS: For 1,065 very-low-birth-weight (VLBW) infants in two neonatal intensive care units (NICUs), mean, SD, and cross-correlation of respiratory rate, heart rate (HR), and oxygen saturation (SpO2) were analyzed hourly (131 infant-years' data). Cross-correlation (cotrending) between two vital signs was measured allowing a lag of ± 30 s. Cases of LOS and NEC were identified retrospectively (n = 186) and vital sign models were evaluated for ability to predict illness diagnosed in the ensuing 24 h. RESULTS: The best single illness predictor within and between institutions was cross-correlation of HR-SpO2. The best combined model (mean SpO2, SDHR, and cross-correlation of HR-SpO2,) trained at one site with ROC area 0.695 had external ROC area of 0.754 at the other site, and provided additive value to an established HR characteristics index for illness prediction (Net Reclassification Improvement: 0.205; 95% confidence interval (CI): 0.113, 0.328). CONCLUSION: Despite minor inter-institutional differences in vital sign patterns of VLBW infants, cross-correlation of HR-SpO2 and a 3-variable vital sign model performed well at both centers for preclinical detection of sepsis or NEC.

Variation in infant EEG power across social and nonsocial contexts.

To understand the infant social brain, it is critical to observe functional neural activation during social interaction. Yet many infant electroencephalography (EEG) studies on socioemotional development have recorded neural activity only during a baseline state. This study investigated how infant EEG power (4-6Hz and 6-9Hz) varies across social and nonsocial contexts. EEG was recorded in 12-month-olds across controlled conditions to disentangle the neural bases of social interactions. Four conditions-nonsocial, joint attention, language-only, and social engagement-were designed to tease apart how different environmental inputs relate to infant EEG power. We analyzed EEG power in frontal, central, temporal, and parietal regions. During the joint attention condition compared with the other conditions, 4-6Hz frontal, central, and parietal power was lowest, indexing greater neural activation. There was lower 4-6Hz and 6-9Hz power in the temporal region in both the joint attention and social engagement conditions compared with the nonsocial condition. In 6-9Hz, the pattern was consistent with 4-6Hz findings for the frontal region such that 6-9Hz frontal power was lower, indexing greater neural activation, in the joint attention condition compared with the nonsocial condition. There were no differences between conditions in central and parietal regions in 6-9Hz. Findings highlight the methodological importance of recording functional brain activity in multiple controlled contexts to explicate the neural bases of the infant social brain.

Electroencephalographic activity of preterm infants is increased by Family Nurture Intervention: a randomized controlled trial in the NICU.

OBJECTIVE: To assess the impact of Family Nurture Intervention (FNI) on electroencephalogram (EEG) activity in preterm infants (26-34 weeks gestation). METHODS: Two groups were tested in a single, level IV neonatal intensive care unit (NICU; standard care or standard care plus FNI) using a randomized controlled trial design. The intervention consists of sessions designed to achieve mutual calm and promote communication of affect between infants and their mothers throughout the NICU stay. EEG recordings were obtained from 134 infants during sleep at ∼35 and ∼40 weeks postmenstrual age (PMA). Regional brain activity (power) was computed for 10 frequency bands between 1 and 48 Hz in each of 125 electrodes. RESULTS: Near to term age, compared to standard care infants, FNI infants showed robust increases in EEG power in the frontal polar region at frequencies 10 to 48 Hz (20% to 36% with p-values <0.0004). Effects were significant in both quiet and active sleep, regardless of gender, singleton-twin status, gestational age (26-30 or 30-35 weeks) or birth weight (<1500 or >1500 g). CONCLUSION: FNI leads to increased frontal brain activity during sleep, which other investigators find predictive of better neurobehavioral outcomes. SIGNIFICANCE: FNI may be a practicable means of improving outcomes in preterm infants.

Toward an electrocortical biomarker of cognition for newborn infants.

The event-related potential (ERP) effect of mismatch negativity (MMN) was the first electrophysiological probe to evaluate cognitive processing (change detection) in newborn infants. Initial studies of MMN predicted clinical utility for this measure in identification of infants at risk for developmental cognitive deficits. These predictions have not been realized. We hypothesized that in sleeping newborn infants, measures derived from wavelet assessment of power in the MMN paradigm would be more robust markers of the brain's response to stimulus change than the ERP-derived MMN. Consistent with this premise, we found increased power in response to unpredictable and infrequent tones compared to frequent tones. These increases were present at multiple locations on the scalp over a range of latencies and frequencies and occurred even in the absence of an ERP-derived MMN. There were two predominant effects. First, theta band power was elevated at middle and late latencies (200 to 600 ms), suggesting that neocortical theta rhythms that subserve working memory in adults are present at birth. Second, late latency (500 ms) increased power to the unpredictable and infrequent tones was observed in the beta and gamma bands, suggesting that oscillations involved in adult cognition are also present in the neonate. These findings support the expectation that frequency dependent measures, such as wavelet power, will improve the prospects for a clinically useful test of cortical function early in the postnatal period.

Anesthetic-specific electroencephalographic patterns during emergence from sevoflurane and isoflurane in infants and children.

BACKGROUND: Devices that monitor the depth of anesthesia are increasingly used to titrate sedation and avoid awareness during anesthesia. Many of these monitors are based upon electroencephalography (EEG) collected from large adult reference populations and not pediatric populations (Anesthesiology, 86, 1997, 836; Journal of Anaesthesia, 92, 2004, 393; Anesthesiology, 99, 2003, 34). We hypothesized that EEG patterns in children would be different from those previously reported in adults and that they would show anesthetic-specific characteristics. METHODS: This prospective observational study was approved by the Institutional Review Board, and informed written consent was obtained. Patients were randomized to receive maintenance anesthesia with isoflurane or sevoflurane. EEG data collection included at least 10 min at steady-state maintenance anesthesia. The EEG was recorded continuously through emergence until after extubation. A mixed model procedure was performed on global and regional power by pooled data analysis and by analyzing each anesthetic group separately. Statistical significance was defined as P < 0.05. RESULTS: Thirty-seven children completed the study (ages 22 days-3.6 years). Isoflurane and sevoflurane had different effects on global and regional EEG power during emergence from anesthesia, and frontal predominance patterns were significantly different between these two anesthetic agents. CONCLUSIONS: The principal finding of the present study was that there are anesthetic-specific and concentration-dependent EEG effects in children. Depth-of-anesthesia monitors that utilize algorithms based on the EEGs of adult reference populations therefore may not be appropriate for use in children.

EEG functional connectivity in term age extremely low birth weight infants.

OBJECTIVE: The hypothesis is tested that electrocortical functional connectivity (quantified by coherence) of extremely low birth weight (ELBW) infants, measured at term post-menstrual age, has regional differences from that of full term infants. METHODS: 128 lead EEG data were collected during sleep from 8 ELBW infants with normal head ultrasound exams and 8 typically developing full term infants. Regional spectral power and coherence were calculated. RESULTS: No significant regional differences in EEG power were found between infant groups. However, compared to term infants, ELBW infants had significantly reduced interhemispheric coherence (in frontal polar and parietal regions) and intrahemispheric coherence (between frontal polar and parieto-occipital regions) in the 1-12Hz band but increased interhemispheric coherence between occipital regions in the 24-50Hz band. CONCLUSIONS: ELBW infants at term post-menstrual age manifest regional differences in EEG functional connectivity as compared to term infants. SIGNIFICANCE: Distinctive spatial patterns of electrocortical synchrony are found in ELBW infants. These regional patterns may presage regional alterations in the structure of the cortex.

Cross-frequency phase coupling of brain rhythms during the orienting response.

A critical function of the brain's orienting response is to evaluate novel environmental events in order to prepare for potential behavioral action. Here, measures of synchronization (power, coherence) and nonlinear cross-frequency phase coupling (m:n phase locking measured with bicoherence and cross-bicoherence) were computed on 62-channel electroencephalographic (EEG) data during a paradigm in which unexpected, highly-deviant, novel sounds were randomly intermixed with frequent standard and infrequent target tones. Low frequency resolution analyses showed no significant changes in phase coupling for any stimulus type, though significant changes in power and synchrony did occur. High frequency resolution analyses, on the other hand, showed significant differences in phase coupling, but only for novel sounds compared to standard tones. Novel sounds elicited increased power and coherence in the delta band together with m:n phase locking (bicoherence) of delta:theta (1:3) and delta:alpha (1:4) rhythms in widespread fronto-central, right parietal, temporal, and occipital regions. Cross-bicoherence revealed that globally synchronized delta oscillations were phase coupled to theta oscillations in central regions and to alpha oscillations in right parietal and posterior regions. These results suggest that globally synchronized low frequency oscillations with phase coupling to more localized higher frequency oscillations provide a neural mechanism for the orienting response.

Frequency domain analyses of neonatal flash VEP.

A battery of frequency-dependent measures was made for high-density electroencephalographic recording measured in response to a flash stimulus in 12 normal term infants within 2 d of birth. Significant changes recorded in posterior electrodes in the same time window as the visual evoked potential (VEP) included increased local synchrony at approximately 40 Hz, increased power at approximately 16 Hz, the emergence of nonlinear coupling of lower (approximately 2 Hz) and higher frequency oscillations, and phase locking over a wide range of frequencies. This research provides evidence of neural synchrony and nonlinear coupling in response to a simple visual stimulus. These mechanisms are functional in early development. It is proposed that the frequency domain metrics of this study may augment current diagnostic measures of cortical function at birth.

Electrocortical functional connectivity in infancy: response to body tilt.

To test the hypothesis that infant cortical regions activated by a head-up tilt also exhibit increased functional electrocortical connectivity, prone sleeping newborn and 2- to 4-month-old infants were tilted head-up to 30 degrees. Electroencephalogram (EEG) data were collected with 128 electrodes and coherence calculated to quantify electrocortical synchrony. Local coherence, defined as the average of coherence measurements between the EEG at each electrode site and neighboring sites (approximately 1 cm electrode spacing), was found in activated cortical regions that had previously shown increased high-frequency power with tilt. Long-distance coherence was computed between the regions. Newborn infants had significant increases in local coherence in the activated left frontal, right frontal-temporal, and occipital cortical regions; long-distance coherence increased between the right frontal-temporal and occipital regions. In contrast, infants at 2 to 4 months old, the age of maximum risk for sudden infant death syndrome, had no significant changes in coherence. Newborn and 2- to 4-month-old infants thus have different electrocortical responses to a classic cardiovascular challenge.

High-density electroencephalogram monitoring in the neonate.

Early diagnosis of neurologic conditions is crucial for successful early intervention; therefore, minimally invasive diagnostic procedures are invaluable during the neonatal period. The clinical usefulness of one such technique, the electroencephalogram (EEG), is well documented. However, the advent of high-density recording systems has extended its application. High-density EEG recording uses a significantly increased number of recordings sites: 128 to 256 electrodes compared with 10 to 30 in standard recording systems. This report describes the benefits of using more electrode sites and highlights the use of related procedures for the assessment of neural integrity across sensory modalities.

Local coherence oscillations in the EEG during development in the fetal baboon.

OBJECTIVE: To test the hypothesis that local coherence in extra-dural EEG recordings, a direct measure of synchronous cortical network activity, oscillates with the same periodicity as EEG power cycling and follows a similar developmental trajectory. METHODS: Local coherence was derived from continuous EEG recordings from closely spaced (1 cm) chronically implanted extra-dural electrodes over the right hemisphere in five fetal baboons (Papio sp.). A ratio of high to low frequency EEG band power (14-18 Hz to 4-7 Hz), was used to characterize EEG power cycling. RESULTS: Data were obtained within a developmental window (137-151 days; term approximately 175 days) during which fetal EEG power cycling becomes increasingly well-organized. During this period ultradian oscillations in local coherence with periods of approximately 1h developed in parallel with EEG power cycling of approximately the same periods. However, the cross-correlation and phase relationship between local coherence and power oscillations were variable. CONCLUSIONS: These findings suggest that cycles in cortical synchrony develop in parallel with fetal power cycles, but are not tightly coupled to them. SIGNIFICANCE: Coherence provides a direct measure of cortical network dynamics not possible with univariate EEG measures such as spectral power. Reported here are the first measurements of local coherence in the developing fetal brain. Local coherence is studied with the long-term goal of monitoring the development of cortical network activity.

Topographic localization of electrocortical activation in newborn and two- to four-month-old infants in response to head-up tilting.

AIMS: (1) To confirm that head-up tilting causes sustained increases in the heart rate (HR) of newborn infants but not during the period of maximum vulnerability to SIDS at 2-4 mo of age, and (2) to determine whether electrocortical activation (changes in high-frequency EEG power) also shows topographic and age-dependent effects of tilting. METHODS: HR and electrocortical activity were recorded in 15 newborn and 12 2- to 4-mo-old infants during head-up tilting. Infants were tilted, three times, to a 30 degrees head-up position. Electrocortical activity was acquired using a 128-lead EEG system. Changes in HR and high-frequency (12-50 Hz) power in the electrocortical signal were computed from the flat to the head-up position. RESULTS: Newborn infants had significant increases in HR and robust increases in high-frequency power in the left frontal, right frontal-temporal, and occipital regions following head-up tilt. At 2 to 4 mo of age, HR did not change significantly and tilt-related increases in high-frequency power were smaller. CONCLUSION: The patterns of HR change and electrocortical activation with tilting of newborn infants are different from infants at the age of highest risk for SIDS.

Quantitative analysis of spatial sampling error in the infant and adult electroencephalogram.

The purpose of this report was to determine the required number of electrodes to record the infant and adult electroencephalogram (EEG) with a specified amount of spatial sampling error. We first developed mathematical theory that governs the spatial sampling of EEG data distributed on a spherical approximation to the scalp. We then used a concentric sphere model of current flow in the head to simulate realistic EEG data. Quantitative spatial sampling error was calculated for the simulated EEG, with additive measurement noise, for 64, 128, and 256 electrodes equally spaced over the surface of the sphere corresponding to the coverage of the human scalp by commercially available "geodesic" electrode arrays. We found the sampling error for the infant to be larger than that for the adult. For example, a sampling error of less than 10% for the adult was obtained with a 64-electrode array but a 256-electrode array was needed for the infant to achieve the same level of error. With the addition of measurement noise, with power 10 times less than that of the EEG, the sampling error increased to 25% for both the infant and adult, for these numbers of electrodes. These results show that accurate measurement of the spatial properties of the infant EEG requires more electrodes than for the adult.