Resting gamma power during the postnatal critical period for GABAergic system development is modulated by infant diet and sex.

Gamma band activity (30-50 Hz) plays an essential role in brain development and function, but neither the early postnatal development nor subject and environmental factors influencing this development have been reported. We documented the development of resting gamma power using high density EEG recordings obtained each month from postnatal month 2 to 6 in 518 healthy infants who were breast-fed (170; 85 boys), fed milk formula (186; 97 boys), or fed soy formula (162; 90 boys). Gamma power was determined for 44 sites distributed over major brain regions and analyses were adjusted for background variables relevant to neurodevelopment. The results show gamma power follows a gradually increasing function across this time period that varies in topographic magnitude and is differentially influenced by subject and environmental variables-among which gestation, head circumference, and infant diet-sex interactions figure most prominently. Relationships between gamma power and standardized measures of infant behavioral development appear to be emerging but are in flux during this time. Since this postnatal period is considered critical in the development of the GABAergic system underlying the generation of gamma activity, the observed findings may reflect organizational changes that will influence the future development of gamma-related behavioral and neurocognitive functions.

Cesarean Delivery Impacts Infant Brain Development.

BACKGROUND AND PURPOSE: The cesarean delivery rate has increased globally in the past few decades. Neurodevelopmental outcomes associated with cesarean delivery are still unclear. This study investigated whether cesarean delivery has any effect on the brain development of offspring. MATERIALS AND METHODS: A total of 306 healthy children were studied retrospectively. We included 3 cohorts: 2-week-old neonates (cohort 1, n = 32/11 for vaginal delivery/cesarean delivery) and 8-year-old children (cohort 2, n = 37/23 for vaginal delivery/cesarean delivery) studied at Arkansas Children's Hospital, and a longitudinal cohort of 3-month to 5-year-old children (cohort 3, n = 164/39 for vaginal delivery/cesarean delivery) studied independently at Brown University. Diffusion tensor imaging, myelin water fraction imaging, voxel-based morphometry, and/or resting-state fMRI data were analyzed to evaluate white matter integrity, myelination, gray matter volume, and/or functional connectivity, respectively. RESULTS: While not all MR imaging techniques were shared across the institutions/cohorts, post hoc analyses showed similar results of potential effects of cesarean delivery. The cesarean delivery group in cohort 1 showed significantly lower white matter development in widespread brain regions and significantly lower functional connectivity in the brain default mode network, controlled for a number of potential confounders. No group differences were found in cohort 2 in white matter integrity or gray matter volume. Cohort 3 had significantly different trajectories of white matter myelination between groups, with those born by cesarean delivery having reduced myelin in infancy but normalizing with age. CONCLUSIONS: Cesarean delivery may influence infant brain development. The impact may be transient because similar effects were not observed in older children. Further prospective and longitudinal studies may be needed to confirm these novel findings.

Brain activation to high-calorie food images in healthy normal weight and obese children: a fMRI study.

BACKGROUND: Understanding how normal weight and obese young children process high-calorie food stimuli may provide information relevant to the neurobiology of eating behavior contributing to childhood obesity. In this study, we used fMRI to evaluate whether brain activation to high-calorie food images differs between normal weight and obese young children. METHODS: Brain activation maps in response to high-calorie food images and non-food images for 22 healthy, 8-10-years-old children (N = 11/11 for normal weight/obese respectively) were generated and compared between groups. RESULTS: When comparing brain activation differences in response to viewing high-calorie food versus non-food images between normal weight and obese children, group differences were observed in areas related to memory and cognitive control. Specifically, normal weight children showed higher activation of posterior parahippocampal gyri (PPHG) and dorsomedial prefrontal cortex (DMPFC). Further ROI analyses indicated higher activation strength (Z scores) in the right PPHG (p = 0.01) and higher activation strength (p < 0.001) as well as a larger activation area (p = 0.02) in the DMPFC in normal weight than obese children. CONCLUSIONS: Normal weight and obese children process high-calorie food stimuli differently even from a young age. Normal weight children exhibit increased brain activation in regions associated with memory and cognitive control when viewing high-calorie food images.

Environmental Forces that Shape Early Development: What We Know and Still Need to Know.

Understanding health requires more than knowledge of the genome. Environmental factors regulate gene function through epigenetics. Collectively, environmental exposures have been called the "exposome." Caregivers are instrumental in shaping exposures in a child's initial years. Maternal dietary patterns, physical activity, degree of weight gain, and body composition while pregnant will influence not only fetal growth, but also the infant's metabolic response to nutrients and energy. Maternal over- or underweight, excess caloric intake, nutrient imbalances, glucose dysregulation, and presence of chronic inflammatory states have been shown to establish risk for many later chronic diseases. During the period from birth to age 3 y, when the infant's metabolic rate is high and synaptogenesis and myelination of the brain are occurring extremely rapidly, the infant is especially prone to damaging effects from nutrient imbalances. During this period, the infant changes from a purely milk-based diet to one including a wide variety of foods. The process, timing, quality, and ultimate dietary pattern acquired are a direct outcome of the caregiver-infant feeding relationship, with potentially lifelong consequences. More research on how meal time interactions shape food acceptance is needed to avoid eating patterns that augment existing disease risk. Traditional clinical trials in nutrition, meant to isolate single factors for study, are inadequate to study the highly interconnected realm of environment-gene interactions in early life. Novel technologies are being used to gather broad exposure data on disparate populations, employing pioneering statistical approaches and correlations applied specifically to the individual, based on their genetic make-up and unique environmental experiences.

Gestational Age at Birth and Brain White Matter Development in Term-Born Infants and Children.

BACKGROUND AND PURPOSE: Studies on infants and children born preterm have shown that adequate gestational length is critical for brain white matter development. Less is known regarding how variations in gestational age at birth in term infants and children affect white matter development, which was evaluated in this study. MATERIALS AND METHODS: Using DTI tract-based spatial statistics methods, we evaluated white matter microstructures in 2 groups of term-born (≥37 weeks of gestation) healthy subjects: 2-week-old infants (n = 44) and 8-year-old children (n = 63). DTI parameters including fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were calculated by voxelwise and ROI methods and were correlated with gestational age at birth, with potential confounding factors such as postnatal age and sex controlled. RESULTS: Fractional anisotropy values, which are markers for white matter microstructural integrity, positively correlated (P < .05, corrected) with gestational age at birth in most major white matter tracts/regions for the term infants. Mean diffusivity values, which are measures of water diffusivities in the brain, and axial and radial diffusivity values, which are markers for axonal growth and myelination, respectively, negatively correlated (P < .05, corrected) with gestational age at birth in all major white matter tracts/regions excluding the body and splenium of the corpus callosum for the term infants. No significant correlations with gestational age were observed for any tracts/regions for the term-born 8-year-old children. CONCLUSIONS: Our results indicate that longer gestation during the normal term period is associated with significantly greater infant white matter development (as reflected by higher fractional anisotropy and lower mean diffusivity, axial diffusivity, and radial diffusivity values); however, similar associations were not observable in later childhood.

Infant Diet-Related Changes in Syllable Processing Between 4 and 5 Months: Implications for Developing Native Language Sensitivity.

Since maturational processes triggering increased attunement to native language features in early infancy are sensitive to dietary factors, infant-diet related differences in brain processing of native-language speech stimuli might indicate variations in the onset of this tuning process. We measured cortical responses (ERPs) to syllables in 4 and 5 month old infants fed breast milk, milk formula, or soy formula and found syllable discrimination (P350) and syntactic-related functions (P600) but not syllable perception (P170) varied by diet, but not gender or background measures. The results suggest breastfed and formula-fed infants differ in onset of this critical period in speech perception.

Differences in brain functional connectivity at resting state in neonates born to healthy obese or normal-weight mothers.

Recent studies have shown associations between maternal obesity at pre- or early pregnancy and long-term neurodevelopment in children, suggesting in utero effects of maternal obesity on offspring brain development. In this study, we examined whether brain functional connectivity to the prefrontal lobe network is different in newborns from normal-weight or obese mothers. Thirty-four full-term healthy infants from uncomplicated pregnancies were included, with 18 born to normal-weight and 16 born to obese mothers. Two weeks after delivery, the infants underwent an magnetic resonance imaging (MRI) examination during natural sleep, which included structural imaging and resting-state functional MRI (fMRI) scans. Independent component analysis was used to identify the prefrontal lobe network, and dual regression was used to compare functional connectivity between groups. Infants born to normal-weight mothers had higher recruiting (P<0.05, corrected) of dorsal anterior cingulate cortex regions to the prefrontal network after adjusting for maternal intelligence quotient, gestational weight gain and infant postmenstrual age, gender, birth weight/length, head circumference and neonatal diet. The functional connectivity strength in dorsal anterior cingulate cortex negatively correlated (P<0.05) with maternal fat mass percentage measured at early pregnancy. This preliminary study indicates that exposure to maternal obesity in utero may be associated with changes in resting-state functional connectivity in the newborn offspring's brain.

Voxel-Based Morphometry and fMRI Revealed Differences in Brain Gray Matter in Breastfed and Milk Formula-Fed Children.

BACKGROUND AND PURPOSE: Infant diets may have significant impact on brain development in children. The aim of this study was to evaluate brain gray matter structure and function in 8-year-old children who were predominantly breastfed or fed cow's milk formula as infants. MATERIALS AND METHODS: Forty-two healthy children (breastfed: n = 22, 10 boys and 12 girls; cow's milk formula: n = 20, 10 boys and 10 girls) were studied by using structural MR imaging (3D T1-weighted imaging) and blood oxygen level-dependent fMRI (while performing tasks involving visual perception and language functions). They were also administered standardized tests evaluating intelligence (Reynolds Intellectual Assessment Scales) and language skills (Clinical Evaluation of Language Fundamentals). RESULTS: Total brain gray matter volume did not differ between the breastfed and cow's milk formula groups. However, breastfed children had significantly higher (P < .05, corrected) regional gray matter volume measured by voxel-based morphometry in the left inferior temporal lobe and left superior parietal lobe compared with cow's milk formula-fed children. Breastfed children showed significantly more brain activation in the right frontal and left/right temporal lobes on fMRI when processing the perception task and in the left temporal/occipital lobe when processing the visual language task than cow's milk formula-fed children. The imaging findings were associated with significantly better performance for breastfed than cow's milk formula-fed children on both tasks. CONCLUSIONS: Our findings indicated greater regional gray matter development and better regional gray matter function in breastfed than cow's milk formula-fed children at 8 years of age and suggested that infant diets may have long-term influences on brain development in children.

Brain gray and white matter differences in healthy normal weight and obese children.

PURPOSE: To compare brain gray and white matter development in healthy normal weight and obese children. METHODS: Twenty-four healthy 8- to 10-year-old children whose body mass index was either <75(th) percentile (normal weight) or >95(th) percentile (obese) completed an MRI examination which included T1-weighted three-dimensional structural imaging and diffusion tensor imaging (DTI). Voxel-based morphometry was used to compare the regional gray and white matter between the normal weight and obese children, and tract-based spatial statistics was used to compare the water diffusion parameters in the white matter between groups. RESULTS: Compared with normal weight children, obese children had significant (P < 0.05, family wise error corrected) regional gray matter reduction in the right middle temporal gyrus, left and right thalami, left superior parietal gyrus, left pre/postcentral gyri, and left cerebellum. Obese children also had higher white matter (P < 0.05, corrected) in multiple regions in the brain and higher DTI measured fractional anisotropy (FA) values (P < 0.05, corrected) in part of the left brain association and projection fibers. There was no difference in mean diffusivity at P < 0.05, corrected. DTI eigenvalues suggested that the FA differences were likely from decreased radial diffusivity (P < 0.1, corrected) and there was no change in axial diffusivity (corrected P > 0.35 for all voxels). CONCLUSION: Our results indicated that obese but otherwise healthy children have different regional gray and white matter development in the brain and differences in white matter microstructures compared with healthy normal weight children.

Infant diet, gender and the development of vagal tone stability during the first two years of life.

Postnatal nutrition influences neurodevelopment, but it is not known whether the development of individual differences in physiologic measures is related to variations in early postnatal diet. To address this issue we studied the stability of vagal tone (V)--an index of individual differences in parasympathetic heart rate control-by measuring resting V quarterly during infancy and again at 2 years in 146 breast-fed (BF), 143 milk formula-fed (MF), and 137 soy formula-fed (SF) infants. Stability of V across infancy was more consistently significant for BF than formula-fed infants. Stability was similar for boys and girls in BF and SF groups but was generally higher in boys than girls in the MF group. Significant stability between infancy and 2 years emerged later in SF than other groups and later in boys than girls. Stability generally peaked between 6 and 9 months-a time when postnatal vagal myelination slows and which may represent a pivotal stage in the development of V stability. These findings indicate that infant diet and gender are important modulators of the early development of autonomic state control.

Sex-specific association between infant diet and white matter integrity in 8-y-old children.

BACKGROUND: The American Academy of Pediatrics recommends breastfeeding, which is well known to promote cognitive and behavioral development. The evidence for why this occurs is not well understood. METHODS: Fifty-six 7.5- to 8.5-y-old healthy children were breastfed (BF; n = 22, 10 males) or formula-fed (FF; n = 34, 16 males) as infants. All children were administered: the Reynolds Intellectual Assessment Scale (RIAS); the Clinical Evaluation of Language Fundamentals (CELF-4) tests; and magnetic resonance imaging of the brain. Diffusion tensor imaging (DTI) measured fractional anisotropy (FA) values were correlated with RIAS and CELF-4 scores. RESULTS: DTI tract-based spatial statistics (TBSS) analyses showed multiple white matter regions in the left hemisphere with significantly higher FA (P < 0.05, corrected) values in BF than FF males, but no significant group differences in females. Males who were exclusively BF for at least 1 y appeared to have the greatest differences in FA. Mean FA values positively correlated with composite scores of RIAS (P = 0.03) and CELF-4 (P = 0.02). CONCLUSION: Breastfeeding during infancy was associated with better white matter development at 8 y of age in boys. A similar association was not observed in girls.

Infant diet, gender and the normative development of vagal tone and heart period during the first two years of life.

Relationships between early postnatal diet and the development of cardiac regulation were studied using resting vagal tone and heart period measures obtained quarterly during infancy and at 2years in 158 breast-fed, 159 milk formula-fed, and 148 soy formula-fed infants. Both measures increased across time for all groups. Heart period was greater in boys than in girls-particularly in soy-fed infants. Higher vagal tone in girls than in boys was not strongly influenced by diet. At 1 and 2years measures differed among boys (soy-fed>breast-fed) but not among girls. Earlier slowing in breast-fed than in formula-fed infants in the rate of increase in vagal tone during infancy suggests that the timing of this developmental shift is sensitive to early infant diet. Finally, the findings do not indicate atypical development of cardiac activity in soy-fed infants that might be associated with estrogenic compounds in this formula.

Developmental status of 1-year-old infants fed breast milk, cow's milk formula, or soy formula.

BACKGROUND AND OBJECTIVE: Although soy formula has been reported to support normal development, concerns exist regarding potential adverse developmental effects of phytochemicals associated with soy protein. This study characterized developmental status (mental, motor, and language) of breastfed (BF), milk-based formula-fed (MF), or soy protein-based formula-fed (SF) infants during the first year of life. METHODS: Healthy infants (N = 391) were assessed longitudinally at ages 3, 6, 9, and 12 months. Development was evaluated by using the Bayley Scales of Infant Development and the Preschool Language Scale-3. Mixed effects models were used while adjusting for socioeconomic status, mother's age and IQ, gestational age, gender, birth weight, head circumference, race, age, and diet history. RESULTS: No differences were found between formula-fed infants (MF versus SF). BF infants scored slightly higher than formula-fed infants on the Mental Developmental Index (MDI) score at ages 6 and 12 months (P < .05). Infants who were breastfed also had higher Psychomotor Development Index scores than SF infants at age 6 months and slightly higher Preschool Language Scale-3 scores than MF infants at ages 3 and 6 months (P < .05). In addition, BF infants had a lower probability to score within the lower MDI quartile compared with MF infants and a higher likelihood to score within the upper quartile for the MDI and Psychomotor Development Index compared with SF infants. CONCLUSIONS: This unique study showed that all scores on developmental testing were within established normal ranges and that MF and SF groups did not differ significantly. Furthermore, this study demonstrated a slight advantage of BF infants on cognitive development compared with formula-fed infants.

Eating breakfast enhances the efficiency of neural networks engaged during mental arithmetic in school-aged children.

To determine the influence of a morning meal on complex mental functions in children (8-11 y), time-frequency analyses were applied to electroencephalographic (EEG) activity recorded while children solved simple addition problems after an overnight fast and again after having either eaten or skipped breakfast. Power of low frequency EEG activity [2 Hertz (Hz) bands in the 2-12 Hz range] was determined from recordings over frontal and parietal brain regions associated with mathematical thinking during mental calculation of correctly answered problems. Analyses were adjusted for background variables known to influence or reflect the development of mathematical skills, i.e., age and measures of math competence and math fluency. Relative to fed children, those who continued to fast showed greater power increases in upper theta (6-8 Hz) and both alpha bands (8-10 Hz; 10-12 Hz) across sites. Increased theta suggests greater demands on working memory. Increased alpha may facilitate task-essential activity by suppressing non-task-essential activity. Fasting children also had greater delta (2-4 Hz) and greater lower-theta (4-6 Hz) power in left frontal recordings-indicating a region-specific emphasis on both working memory for mental calculation (theta) and activation of processes that suppress interfering activity (delta). Fed children also showed a significant increase in correct responses while children who continued to fast did not. Taken together the findings suggest that neural network activity involved in processing numerical information is functionally enhanced and performance is improved in children who have eaten breakfast, whereas greater mental effort is required for this mathematical thinking in children who skip breakfast.

Effects of diet on early stage cortical perception and discrimination of syllables differing in voice-onset time: a longitudinal ERP study in 3 and 6 month old infants.

The influence of diet on cortical processing of syllables was examined at 3 and 6 months in 239 infants who were breastfed or fed milk or soy-based formula. Event-related potentials to syllables differing in voice-onset-time were recorded from placements overlying brain areas specialized for language processing. P1 component amplitude and latency measures indicated that at both ages infants in all groups could extract and discriminate categorical information from syllables. Between-syllable amplitude differences-present across groups-were generally greater for SF infants. Responses peaked earlier over left hemisphere speech-perception than speech-production areas. Encoding was faster in BF than formula-fed infants. The results show that in preverbal infants: (1) discrimination of phonetic information occurs in early stages of cortical processing; (2) areas overlying brain regions of speech perception are activated earlier than those involved in speech production; and (3) these processes are differentially modulated by infant diet and environmental factors.

Diet and gender influences on processing and discrimination of speech sounds in 3- and 6-month-old infants: a developmental ERP study.

Early post-natal nutrition influences later development, but there are no studies comparing brain function in healthy infants as a function of dietary intake even though the major infant diets differ significantly in nutrient composition. We studied brain responses (event-related potentials; ERPs) to speech sounds for infants who were fed either breast milk (BF), milk-based formula (MF), or soy formula (SF) during the first 6 months of life. Two syllables presented in an oddball paradigm elicited a late positive wave (P350) from temporal and frontal brain regions involved in language processes. All groups showed significantly greater response amplitudes to the infrequent syllable across sites at 3 months and frontally at 6 months, but significant discrimination at temporal sites was only observed at 6 months in BF infants. Decreases in response amplitudes from 3 to 6 months were greater for the frequently presented syllable, most prominent in BF infants, and greater in females than males. The results indicate greater syllable discrimination in BF than formula-fed infants, but whether this can be attributed to dietary influences alone remains unclear. Feeding method and background factor differences between breastfed and formula-fed infants may also contribute to the observed differences. The general absence of differences between formula-fed groups is notable and suggests that milk-based formula and soy formula equally support brain development and function during the first post-natal 6 months. Finally, the results indicate gender differences in the development of neural and temporal processes involved in sensory discrimination, and suggest that at 6 months these processes are better developed in females.

Cortical responses to speech sounds in 3- and 6-month-old infants fed breast milk, milk formula, or soy formula.

Controversy exists about the safety of soy formula, with the main concern relating to potential estrogenic effects of soy protein. Since estrogens influence early brain development, we compared behavioral development and cortical responses (event-related potentials; ERPs) to speech sounds in infants fed either breast milk or formula (milk- or soy-based). Across-groups ERP measures were generally similar and behavioral measures were within normal ranges, suggesting no important influences of soy formula on behavioral development and brain function during the study period. Analyses relating ERP and behavioral measures revealed diet- and gender-specific emphases that may reflect differences in developmental trajectories of brain-behavior relationships.

A longitudinal study of differences in electroencephalographic activity among breastfed, milk formula-fed, and soy formula-fed infants during the first year of life.

BACKGROUND: The extent to which adequate nutrition from infant diets differentially influence developmental outcomes in healthy infants has not been determined. AIM: To compare the effects of the major infant diets on the development of brain electrical activity during infancy. STUDY DESIGN: Scalp EEG signals (124 sites) recorded from the same infants during quiet wakefulness at 3, 6, 9, and 12months. SUBJECTS: Healthy, full-term infants (40/group; gender matched) either breastfed (BF) or fed milk formula (MF) or soy formula (SF) through the first 6months. OUTCOME MEASURES: Power spectral values for frequencies in the 0.1-30Hz range. RESULTS: Significant diet-related differences were present across frequency bands and included effects that were time- [peaks in 0.1-3Hz at 6 (MF,SF) and 9months (BF); 3-6Hz at 6months (MF, SF>BF); increases in 6-9Hz from 3 to 6months (MF>BF) and from 6 to 9months (MF>SF)] and gender-related (9-12Hz and 12-30Hz: at 9months BF>MF, SF boys, and MF>SF girls). CONCLUSIONS: The development of brain electrical activity during infancy differs between those who are breastfed compared with those fed either milk or soy formula, but is generally similar for formula-fed groups. These variations in EEG activity reflect diet-related influences on the development of brain structure and function that could put infants on different neurodevelopmental trajectories along which cognitive and brain function development will proceed.

Early infant diet and the omega 3 fatty acid DHA: effects on resting cardiovascular activity and behavioral development during the first half-year of life.

This investigation evaluated variations in resting heart rate (HR) measures during the first half year of life in healthy, full-term infants who were either breast-fed (BF), or fed formula with (milk-based: MF; soy-based: SF) or without (soy-based: SF(-)) commercially supplemented DHA (decosahexaenoic acid). In infants fed the DHA-deficient diet, higher HR and lower values for heart rate variability measures were observed, indicating decreased parasympathetic tone in this group. These effects, appearing at 4 months and continuing for the remainder of the study period, are consistent with suggestions that the 3-5-month postnatal interval may be an important period in the development of cardiovascular regulation. The absence of these effects in SF infants receiving the DHA-supplemented formula suggests that neither soy protein nor the associated phytochemicals in soy formula contribute to these effects to any appreciable extent. In general, the results do not indicate differences in any of the study variables attributable to soy formula per se.

No difference indicated in electroencephalographic power spectral analysis in 3- and 6-month-old infants fed soy- or milk-based formula.

Increasing concern has been recently raised on the possible effects of soy-derived phyto-oestrogens on the development of cognitive functions in infants. However, limited studies have been conducted to date, and no data have been made available for determining whether infant soy formula can affect normal development of the human brain. We compared electroencephalographic (EEG) spectral power derived from high-density recordings of infants fed milk-based or soy formula (46 fed milk-based formula and 39 fed soy formula) at 3 and 6 months of age. The spectral parameters included absolute power, relative power and spectral edge frequency (SEF) at 85%, 90% and 95% levels. The frequency domain contained four bands (0.1-3, 3-6, 6-9 and 9-12 Hz). EEG signals were collected from eight brain areas in each hemisphere. The results showed that the highest spectral power was mainly distributed in the low-frequency bands and was predominant in the frontal and anterior temporal areas. None of the spectral variables significantly differed between the soy- and milk-fed infants (anova, all P > 0.2). However, significant effects were indicated on the SEFs for factors of sex, age and brain area (all P < 0.01). Hemispheric differences in the absolute and relative power were also indicated. Our results suggest that the EEG power spectral development of soy-fed infants does not differ from that of infants fed milk-based formula. In addition, EEG spectral development appears more advanced in female than in male infants at 6 months.