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

J Am Acad Child Adolesc Psychiatry. 2017 Feb;56(2):157-166. doi: 10.1016/j.jaac.2016.11.005. Epub 2016 Nov 25.


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. Voxelwise 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, although magnitudes were decreased in VPT infants. Neonatal amygdala rs-FC predicted internalizing symptoms at age 2 years 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.

Keywords: amygdala; functional connectivity; infant; internalizing.

MeSH terms

  • Amygdala / diagnostic imaging
  • Amygdala / physiology*
  • Amygdala / physiopathology
  • Anxiety / diagnostic imaging
  • Anxiety / physiopathology*
  • Connectome*
  • Depression / diagnostic imaging
  • Depression / physiopathology*
  • Female
  • Humans
  • Infant
  • Infant Behavior / physiology*
  • Infant, Newborn / physiology*
  • Infant, Premature / physiology*
  • Magnetic Resonance Imaging
  • Male
  • Problem Behavior*