Neonatal Amygdala Functional Connectivity at Rest in Healthy and Preterm Infants and Early Internalizing Symptoms

Abstract

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.

Social brain circuitry and social cognition in infants born preterm

“…Similar results have been found with PT-born individuals later in life: at 36 months of age, PT-born children show relatively weaker connectivity between resting state networks including the DMN [157]. One recent study also examined functional connectivity in the amygdala of 65 FT (birth GA > 36 weeks) and 57 PT (birth GA < 30 weeks) infants imaged at TEA [158]. Here, functional connectivity patterns in the PT and FT groups were similar to those of older children and adults, though prematurity was associated with reduced magnitude of activation.…”

Shyness and Trajectories of Functional Network Connectivity Over Early Adolescence

“…Along these lines, Rogers et al. () related rs‐fc of the amygdala at birth to symptoms of behavioral inhibition at age 2 years, while Roy et al. () examined amygdala rs‐fc in adults who had been classified as inhibited or noninhibited during early childhood.…”

“…Rogers et al. () reported a positive relation between behavioral inhibition and rs‐fc between the amygdala and part of the mPFC (which may have been within the DMN), while Roy et al. () reported a negative association between behavioral inhibition and a similar amygdala–mPFC connection.…”

“…Additional consistently described brain differences in children with high versus low shyness include increased activity in the amygdala to emotionally evocative faces (Pérez‐Edgar et al., ; Schwartz, Wright, Shin, Kagan, & Rauch, ); alterations in activity in the nucleus accumbens, striatum, and other subcortical areas during reward processing (Guyer et al., , ); and structural and functional alterations in brain regions involved in directing attention and cognitive control, such as the FPN, SN, and VAN networks described earlier (Guyer et al., ; Jarcho, Fox, Pine, Etkin, et al., ; Jarcho, Fox, Pine, Leibenluft, et al., ; Sylvester et al., ). Cross‐sectional studies using rs‐fc have indicated that shyness or behavioral inhibition is associated with variation of connectivity of the amygdala as well as regions within the DMN, SN, FPN, VAN, and somatosensory networks (Clauss, Benningfield, Rao, & Blackford, ; Rogers et al., ; Roy et al., ; Sylvester et al., ; Taber‐Thomas, Morales, Hillary, & Pérez‐Edgar, ). Together, these cross‐sectional data suggest that shyness is marked by alterations in connectivity both in brain systems involved in self‐directed processing (e.g., the DMN) and externally focused processing (e.g., the FPN).…”

White matter maturation in the neonatal brain is predictive of school age cognitive capacities in children born very preterm

“…In support of this postulate, white matter disorders in both children and adults have been related to diminished cognitive performance and executive functioning deficits, while language remains relatively intact . Similarly, behavioural correlates may originate in specific structures as well …”