Neonatal Functional Connectivity Research Articles

Differences in Neonatal Functional Connectivity Related to Sensory Overresponsivity in Toddlers

Differences in Neonatal Functional Connectivity Related to Sensory Overresponsivity in Toddlers

Maternal prenatal social disadvantage and neonatal functional connectivity: Associations with psychopathology symptoms at age 12 months.

Recent research has reported effects of socioeconomic status on neurobehavioral development as early as infancy, including positive associations between income and brain structure, functional connectivity, and behavior later in childhood (Ramphal, Whalen, et al., 2020; Triplett et al., 2022). This study extends this literature by investigating the relation of maternal prenatal social disadvantage (PSD) to neonatal amygdala and hippocampus functional connectivity and whether socioeconomic-related alterations in functional connectivity subsequently predict behavior at age 12 months in a large, socioeconomically diverse sample (N = 261 mother-infant dyads). PSD was assessed across gestation; neonatal magnetic resonance imaging was completed within the first weeks of life; and infant internalizing and externalizing symptoms were evaluated using the Infant-Toddler Social and Emotional Assessment at age 12 months. The results showed that PSD was significantly related to neonatal right amygdala and left hippocampus functional connectivity with prefrontal and motor-related regions. Social disadvantage-related right amygdala and left hippocampus functional connectivity with these regions was subsequently related to infant externalizing and internalizing symptoms at age 12 months. Building off an emerging literature exploring prenatal impacts on neonatal functional connectivity, this study further emphasizes the important role of the maternal environment during gestation on infant brain function and its relationship with externalizing and internalizing behavior in the first years of life. The results suggest that the prenatal socioeconomic environment may be a promising target for interventions aimed at improving infant neurobehavioral outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Neonatal brain dynamic functional connectivity in term and preterm infants and its association with early childhood neurodevelopment

Brain dynamic functional connectivity characterises transient connections between brain regions. Features of brain dynamics have been linked to emotion and cognition in adult individuals, and atypical patterns have been associated with neurodevelopmental conditions such as autism. Although reliable functional brain networks have been consistently identified in neonates, little is known about the early development of dynamic functional connectivity. In this study we characterise dynamic functional connectivity with functional magnetic resonance imaging (fMRI) in the first few weeks of postnatal life in term-born (n = 324) and preterm-born (n = 66) individuals. We show that a dynamic landscape of brain connectivity is already established by the time of birth in the human brain, characterised by six transient states of neonatal functional connectivity with changing dynamics through the neonatal period. The pattern of dynamic connectivity is atypical in preterm-born infants, and associated with atypical social, sensory, and repetitive behaviours measured by the Quantitative Checklist for Autism in Toddlers (Q-CHAT) scores at 18 months of age.

The Effects of Prenatal Exposure to Neighborhood Crime on Neonatal Functional Connectivity

BackgroundMaternal exposure to adversity during pregnancy has been found to affect infant brain development; however, the specific effect of prenatal crime exposure on neonatal brain connectivity remains unclear. Based on existing research, we hypothesized that living in a high-crime neighborhood during pregnancy would affect neonatal frontolimbic connectivity over and above other individual- and neighborhood-level adversity and that these associations would be mediated by maternal psychosocial stress. MethodsParticipants included 399 pregnant women, recruited as part of the eLABE (Early Life Adversity, Biological Embedding, and Risk for Developmental Precursors of Mental Disorders) study. In the neonatal period, 319 healthy, nonsedated infants were scanned using resting-state functional magnetic resonance imaging (repetition time = 800 ms; echo time = 37 ms; voxel size = 2.0 × 2.0 × 2.0 mm3; multiband = 8) on a Prisma 3T scanner and had at least 10 minutes of high-quality data. Crime data at the block group level were obtained from Applied Geographic Solution. Linear regressions and mediation models tested associations between crime, frontolimbic connectivity, and psychosocial stress. ResultsLiving in a neighborhood with high property crime during pregnancy was related to weaker neonatal functional connectivity between the thalamus–anterior default mode network (aDMN) (β = −0.15, 95% CI = −0.25 to −0.04, p = .008). Similarly, high neighborhood violent crime was related to weaker functional connectivity between the thalamus-aDMN (β = −0.16, 95% CI = −0.29 to −0.04, p = .01) and amygdala-hippocampus (β = −0.16, 95% CI = −0.29 to −0.03, p = .02), controlling for other types of adversity. Psychosocial stress partially mediated relationships between the thalamus-aDMN and both violent and property crime. ConclusionsThese findings suggest that prenatal exposure to crime is associated with weaker neonatal limbic and frontal functional brain connections, providing another reason for targeted public policy interventions to reduce crime.

Association of Maternal Prepregnancy Body Mass Index With Fetal Growth and Neonatal Thalamic Brain Connectivity Among Adolescent and Young Women

Higher maternal prepregnancy body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is associated with adverse long-term outcomes for offspring, including obesity, poorer cognitive and social abilities, and increased risk of psychiatric disorders. Less clear is whether higher maternal BMI disrupts fetal growth and brain development. To investigate the association of maternal prepregnancy BMI with fetal growth and neonatal functional connectivity. This prospective longitudinal cohort study was conducted from 2012 to 2017. Participants included nulliparous pregnant adolescent and young adult women, aged 14 to 19 years who were recruited in the second trimester through Columbia University Irving Medical Center and Weill Cornell Medical College. Women received routine prenatal care and had no major health problems at the time of recruitment. Data were analyzed from January 2018 to March 2020. Maternal prepregnancy BMI. The main outcomes were fetal growth, measured as estimated fetal weight, and neonatal functional connectivity, measured using magnetic resonance imaging. Prepregnancy BMI and fetal ultrasonographic measurements were obtained from electronic health record review. Resting-state brain imaging data were acquired in infants within the first month of postnatal life. Functional connectivity was measured using intrinsic functional distribution and seed-based methods. Among 129 women recruited, 105 had ultrasonographic data from at least 2 points and were included in analyses. The mean (SD) age at delivery was 17.82 (1.31) years. Maternal prepregnancy BMI was positively associated with the slope of estimated fetal weight (β = 0.668; 95% CI, 0.163 to 1.175; P = .01) but not with fetal head circumference (β = -0.004; 95% CI, -0.024 to 0.016; P = .70). In a subsample of 45 infants with magnetic resonance imaging data, maternal prepregnancy BMI was positively correlated with global connectivity in the left thalamus. Using this thalamic region as a seed, higher maternal BMI was associated with greater local thalamic (both hemispheres) and lower frontothalamic connectivity. These results suggest that maternal prepregnancy BMI was associated with the development of regulation of body weight and thalamic functional brain connectivity in offspring even during fetal development.

Neonatal brain connectivity outliers identify over forty percent of IQ outliers at 4years of age.

BackgroundDefining reliable brain markers for the prediction of abnormal behavioral outcomes remains an urgent but extremely challenging task in neuroscience research. This is particularly important for infant studies given the most dramatic brain and behavioral growth during infancy.MethodsIn this study, we proposed a novel prediction scheme through abstracting individual newborn's whole‐brain functional connectivity pattern to three outlier measures (Triple O) and tested the hypothesis that neonates identified as “brain outliers” based on Triple O were more likely to develop as IQ outliers at 4 years of age. Without need for training with behavioral data, Triple O represents a novel proof‐of‐concept approach to predict later IQ outcomes based on neonatal brain data.ResultsTriple O correctly identified 42.1% true IQ outliers among a mixed cohort of 175 newborns with different term, twin, and maternal disorder statuses. Triple O also reached a high level of specificity (96.2%) and overall accuracy (90.3%). Further incorporating a demographic information indicator, the enhanced Triple O+ could further differentiate between high and low 4YR IQ outliers. Validation tests against seven independent reference samples revealed highly consistent results and a minimum sample size of ~50 for robust performance.ConclusionsConsidering that postnatal brain growth and various environmental factors likely also contribute to 4YR IQ, the fact that Triple O, based purely on neonatal functional connectivity data, could identify >40% of 4YR IQ outliers is striking. Together with the very high level of specificity, each outlier predicted by Triple O represents a meaningful risk but future efforts are needed to explore ways to identify the rest of outliers. Overall, with no need for training, a high level of robustness, and a minimal requirement on sample size, the proposed Triple O approach demonstrates great potential to predict later outlying IQ performances using neonatal functional connectivity data.

Maternal Adiposity Influences Neonatal Brain Functional Connectivity.

The neural mechanisms associated with obesity have been extensively studied, but the impact of maternal obesity on fetal and neonatal brain development remains poorly understood. In this study of full-term neonates, we aimed to detect potential neonatal functional connectivity alterations associated with maternal adiposity, quantified via body-mass-index (BMI) and body-fat-mass (BFM) percentage, based on seed-based and graph theoretical analysis using resting-state fMRI data. Our results revealed significant neonatal functional connectivity alterations in all four functional domains that are implicated in adult obesity: sensory cue processing, reward processing, cognitive control, and motor control. Moreover, some of the detected areas showing regional functional connectivity alterations also showed global degree and efficiency differences. These findings provide important clues to the potential neural basis for cognitive and mental health development in offspring of obese mothers and may lead to the derivation of imaging-based biomarkers for the early identification of risks for timely intervention.

Maternal Immune Activation During the Third Trimester Is Associated with Neonatal Functional Connectivity of the Salience Network and Fetal to Toddler Behavior.

Prenatal maternal immune activation (MIA) is associated with altered brain development and risk of psychiatric disorders in offspring. Translational human studies of MIA are few in number. Alterations of the salience network have been implicated in the pathogenesis of the same psychiatric disorders associated with MIA. If MIA is pathogenic, then associated abnormalities in the salience network should be detectable in neonates immediately after birth. We tested the hypothesis that third trimester MIA of adolescent women who are at risk for high stress and inflammation is associated with the strength of functional connectivity in the salience network of their neonate. Thirty-six women underwent blood draws to measure interleukin-6 (IL-6) and C-reactive protein (CRP) and electrocardiograms to measure fetal heart rate variability (FHRV) at 34-37 weeks gestation. Resting-state imaging data were acquired in the infants at 40-44 weeks postmenstrual age (PMA). Functional connectivity was measured from seeds placed in the anterior cingulate cortex and insula. Measures of cognitive development were obtained at 14 months PMA using the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). Both sexes were studied. Regions in which the strength of the salience network correlated with maternal IL-6 or CRP levels included the medial prefrontal cortex, temporoparietal junction, and basal ganglia. Maternal CRP level correlated inversely with FHRV acquired at the same gestational age. Maternal CRP and IL-6 levels correlated positively with measures of cognitive development on the BSID-III. These results suggest that MIA is associated with short- and long-term influences on offspring brain and behavior.SIGNIFICANCE STATEMENT Preclinical studies in rodents and nonhuman primates and epidemiological studies in humans suggest that maternal immune activation (MIA) alters the development of brain circuitry and associated behaviors, placing offspring at risk for psychiatric illness. Consistent with preclinical findings, we show that maternal third trimester interleukin-6 and C-reactive protein levels are associated with neonatal functional connectivity and with both fetal and toddler behavior. MIA-related functional connectivity was localized to the salience, default mode, and frontoparietal networks, which have been implicated in the pathogenesis of psychiatric disorders. Our results suggest that MIA alters functional connectivity in the neonatal brain, that those alterations have consequences for cognition, and that these findings may provide pathogenetic links between preclinical and epidemiological studies associating MIA with psychiatric risk in offspring.

Cortical Functional Connectivity Evident After Birth and Behavioral Inhibition at Age 2.

The infant temperament behavioral inhibition is a potent risk factor for development of an anxiety disorder. It is difficult to predict risk for behavioral inhibition at birth, however, and the neural underpinnings are poorly understood. The authors hypothesized that neonatal functional connectivity of the ventral attention network is related to behavioral inhibition at age 2 years beyond sociodemographic and familial factors. This hypothesis is supported by the ventral attention network's role in attention to novelty, a key feature of behavioral inhibition. Using a longitudinal design (N=45), the authors measured functional connectivity using MRI in neonates and behavioral inhibition at age 2 using the Infant-Toddler Social and Emotional Assessment. Whole-brain connectivity maps were computed for regions from the ventral attention, default mode, and salience networks. Regression analyses related these maps to behavioral inhibition at age 2, covarying for sex, social risk, and motion during scanning. Decreased neonatal functional connectivity of three connections was associated with increased behavioral inhibition at age 2. One connection (between the right ventrolateral prefrontal cortex and the right temporal-parietal junction) included the ventral attention network seed, and two connections (between the medial prefrontal cortex and both the right superior parietal lobule and the left lateral occipital cortex) included the default mode network seed. Neonatal functional connectivity of the ventral attention and default mode networks is associated with behavioral inhibition at age 2. These results inform the developmental neurobiology of behavioral inhibition and anxiety disorders and may aid in early risk assessment and intervention.

Machine-learning to characterise neonatal functional connectivity in the preterm brain

Brain development is adversely affected by preterm birth. Magnetic resonance image analysis has revealed a complex fusion of structural alterations across all tissue compartments that are apparent by term-equivalent age, persistent into adolescence and adulthood, and associated with wide-ranging neurodevelopment disorders. Although functional MRI has revealed the relatively advanced organisational state of the neonatal brain, the full extent and nature of functional disruptions following preterm birth remain unclear.In this study, we apply machine-learning methods to compare whole-brain functional connectivity in preterm infants at term-equivalent age and healthy term-born neonates in order to test the hypothesis that preterm birth results in specific alterations to functional connectivity by term-equivalent age.Functional connectivity networks were estimated in 105 preterm infants and 26 term controls using group-independent component analysis and a graphical lasso model. A random forest–based feature selection method was used to identify discriminative edges within each network and a nonlinear support vector machine was used to classify subjects based on functional connectivity alone.We achieved 80% cross-validated classification accuracy informed by a small set of discriminative edges. These edges connected a number of functional nodes in subcortical and cortical grey matter, and most were stronger in term neonates compared to those born preterm. Half of the discriminative edges connected one or more nodes within the basal ganglia.These results demonstrate that functional connectivity in the preterm brain is significantly altered by term-equivalent age, confirming previous reports of altered connectivity between subcortical structures and higher-level association cortex following preterm birth.

The Neonatal Connectome During Preterm Brain Development.

The human connectome is the result of an elaborate developmental trajectory. Acquiring diffusion-weighted imaging and resting-state fMRI, we studied connectome formation during the preterm phase of macroscopic connectome genesis. In total, 27 neonates were scanned at week 30 and/or week 40 gestational age (GA). Examining the architecture of the neonatal anatomical brain network revealed a clear presence of a small-world modular organization before term birth. Analysis of neonatal functional connectivity (FC) showed the early formation of resting-state networks, suggesting that functional networks are present in the preterm brain, albeit being in an immature state. Moreover, structural and FC patterns of the neonatal brain network showed strong overlap with connectome architecture of the adult brain (85 and 81%, respectively). Analysis of brain development between week 30 and week 40 GA revealed clear developmental effects in neonatal connectome architecture, including a significant increase in white matter microstructure (P < 0.01), small-world topology (P < 0.01) and interhemispheric FC (P < 0.01). Computational analysis further showed that developmental changes involved an increase in integration capacity of the connectivity network as a whole. Taken together, we conclude that hallmark organizational structures of the human connectome are present before term birth and subject to early development.