Objective Alterations in the normal developmental trajectory of amygdala resting state-functional connectivity (rs-FC) have been associated with atypical emotional processes and psychopathology. Little is known, however, regarding amygdala rs-FC at birth or its relevance to outcomes. This study examined amygdala rs-FC in healthy, full-term (FT) infants and in very preterm (VPT) infants and tested whether variability of neonatal amygdala rs-FC predicted internalizing symptoms at age 2 years. Method Resting state-fMRI data were obtained shortly after birth from 65 FT infants (gestational age [GA] ≥36 weeks) and 57 VPT infants (GA <30 weeks) at term-equivalent. Voxel-wise correlation analyses were performed using individual-specific bilateral amygdala regions of interest. Total internalizing symptoms and the behavioral inhibition, depression/withdrawal, general anxiety, and separation distress subdomains were assessed in a subset (n=44) at age 2 years using the Infant Toddler Social Emotional Assessment. Results In FT and VPT infants, the amygdala demonstrated positive correlations with subcortical and limbic structures and negative correlations with cortical regions, though magnitudes were decreased in VPT infants. Neonatal amygdala rs-FC predicted internalizing symptoms at age 2 with regional specificity consistent with known pathophysiology in older populations: connectivity with the anterior insula related to depressive symptoms, with the dorsal anterior cingulate related to generalized anxiety, and with the medial prefrontal cortex related to behavioral inhibition. Conclusion Amygdala rs-FC is well-established in neonates. Variability in regional neonatal amygdala rs-FC predicted internalizing symptoms at 2 years, suggesting that risk for internalizing symptoms may be established in neonatal amygdala functional connectivity patterns.

Background: This study examines relationships between neonatal white and gray matter microstructure and neurodevelopment in very preterm infants (VPT; ≤30 weeks gestation) with high-grade brain injury (BI). Methods: Term-equivalent diffusion tensor magnetic resonance imaging (DTI) data were obtained in 32 VPT infants with high-grade BI spanning grade III/IV intraventricular hemorrhage, post-hemorrhagic hydrocephalus (PHH), and cystic periventricular leukomalacia (BI group); 69 VPT infants without high-grade injury (VPT group); and 55 term-born infants. The Bayley-III assessed neurodevelopmental outcomes at age 2-years. Results: BI infants had lower fractional anisotropy (FA) in the posterior limb of the internal capsule (PLIC), cingulum, and corpus callosum; and higher mean diffusivity (MD) in the optic radiations and cingulum than VPT infants. PHH was associated with higher MD in the optic radiations and left PLIC; and higher FA in the right caudate. For BI infants, higher MD in the right optic radiation and lower FA in the right cingulum, PLIC, and corpus callosum were related to motor impairments. Conclusions: BI infants demonstrated altered white and gray matter microstructure in regions affected by injury in a manner dependent upon injury type. PHH infants demonstrated the greatest impairments. Aberrant white matter microstructure was related to motor impairment in BI infants.

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.

Low childhood socioeconomic status (SES) predisposes individuals to altered trajectories of brain development and increased rates of mental illness. Brain connectivity at birth is associated with psychiatric outcomes. We sought to investigate whether SES at birth is associated with neonatal brain connectivity and if these differences account for socioeconomic disparities in infant symptoms at age 2 years that are predictive of psychopathology. Resting state functional MRI was performed on 75 full-term and 37 term-equivalent preterm newborns (n = 112). SES was characterized by insurance type, the Area Deprivation Index, and a composite score. Seed-based voxelwise linear regression related SES to whole-brain functional connectivity of five brain regions representing functional networks implicated in psychiatric illnesses and affected by socioeconomic disadvantage: striatum, medial prefrontal cortex (mPFC), ventrolateral prefrontal cortex (vlPFC), and dorsal anterior cingulate cortex. Lower SES was associated with differences in striatum and vlPFC connectivity. Striatum connectivity with frontopolar and medial PFC mediated the relationship between SES and behavioral inhibition at age 2 measured by the Infant-Toddler Social Emotional Assessment (n = 46). Striatum-frontopolar connectivity mediated the relationship between SES and externalizing symptoms. These results, convergent across three SES metrics, suggest that neurodevelopmental trajectories linking SES and mental illness may begin as early as birth.

Polyphenol-rich pomegranate juice has been shown to have benefit as a neuroprotectant in animal models of neonatal hypoxic-ischemia. No published studies have investigated maternal polyphenol administration as a potential neuroprotectant in at-risk newborns, such as those with intrauterine growth restriction (IUGR). This was a randomized, placebo-controlled, double-blind pilot study to investigate the impact of maternal pomegranate juice intake in pregnancies with IUGR, on newborn brain structure and function at term-equivalent age (TEA). Mothers with IUGR at 24–34 weeks’ gestation were recruited from Barnes-Jewish Hospital obstetrical clinic. Consented mothers were randomized to treatment (8 oz. pomegranate juice) or placebo (8 oz. polyphenol-free juice) and continued to take juice daily from enrollment until delivery (mean 20.1 and 27.1 days, respectively). Infants underwent brain MRI at TEA (36–41 weeks’ gestation). Brain measures were compared between groups including: brain injury score, brain metrics, brain volumes, diffusion tensor imaging and resting state functional connectivity. Statistical analyses were undertaken as modified intention-to-treat (including randomized participants who received their allocated intervention and whose infants received brain MRI) and per-protocol (including participants who strictly adhered to the protocol, based on metabolite status). Seventy-seven mothers were randomized to treatment (n = 40) or placebo (n = 37). Of these, 28 and 27 infants, respectively, underwent term-equivalent MRI. There were no group differences in brain injury, metrics or volumes. However, treatment subjects displayed reduced diffusivity within the anterior and posterior limbs of the internal capsule compared with placebo. Resting state functional connectivity demonstrated increased correlation and covariance within several networks in treatment subjects, with alterations most apparent in the visual network in per-protocol analyses. Direct effects on health were not found. In conclusion, maternal pomegranate juice intake in pregnancies with known IUGR was associated with altered white matter organization and functional connectivity in the infant brain, suggesting differences in brain structure and function following in utero pomegranate juice exposure, warranting continued investigation. Clinical trial registration. NCT00788866 , registered November 11, 2008, initial participant enrollment August 21, 2012.