title: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Washington University in St. Louis. Electronic address: rogersc@psychiatry.wustl.edu.
authors.forename: Cynthia E
authors.initials: CE
authors.lastname: Rogers
authors.affiliation: Washington University in St. Louis.
authors.forename: Chad M
authors.initials: CM
authors.lastname: Sylvester
authors.affiliation: Washington University in St. Louis.
authors.forename: Carrie
authors.initials: C
authors.lastname: Mintz
authors.affiliation: Washington University in St. Louis.
authors.forename: Jeanette K
authors.initials: JK
authors.lastname: Kenley
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University in St. Louis.
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Shimony
authors.affiliation: Washington University in St. Louis; Mallinckrodt Institute of Radiology, Washington University in St. Louis; Program in Neuroscience at Washington University in St. Louis.
authors.forename: Deanna M
authors.initials: DM
authors.lastname: Barch
authors.affiliation: Washington University in St. Louis; Mallinckrodt Institute of Radiology, Washington University in St. Louis.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Smyser
mesh_terms: D000679:Amygdala / Q000000981:diagnostic imaging / Q000502:physiology* / Q000503:physiopathology; D001007:Anxiety / Q000000981:diagnostic imaging / Q000503:physiopathology*; D063132:Connectome; D003863:Depression / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007223:Infant; D018730:Infant Behavior / Q000502:physiology*; D007231:Infant, Newborn / Q000502:physiology*; D007234:Infant, Premature / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D000066553:Problem Behavior
keywords: amygdala; functional connectivity; infant; internalizing