Early developmental emergence of human amygdala-prefrontal connectivity after maternal deprivation

Proc Natl Acad Sci U S A. 2013 Sep 24;110(39):15638-43. doi: 10.1073/pnas.1307893110. Epub 2013 Sep 9.


Under typical conditions, medial prefrontal cortex (mPFC) connections with the amygdala are immature during childhood and become adult-like during adolescence. Rodent models show that maternal deprivation accelerates this development, prompting examination of human amygdala-mPFC phenotypes following maternal deprivation. Previously institutionalized youths, who experienced early maternal deprivation, exhibited atypical amygdala-mPFC connectivity. Specifically, unlike the immature connectivity (positive amygdala-mPFC coupling) of comparison children, children with a history of early adversity evidenced mature connectivity (negative amygdala-mPFC coupling) and thus, resembled the adolescent phenotype. This connectivity pattern was mediated by the hormone cortisol, suggesting that stress-induced modifications of the hypothalamic-pituitary-adrenal axis shape amygdala-mPFC circuitry. Despite being age-atypical, negative amygdala-mPFC coupling conferred some degree of reduced anxiety, although anxiety was still significantly higher in the previously institutionalized group. These findings suggest that accelerated amygdala-mPFC development is an ontogenetic adaptation in response to early adversity.

Keywords: emotion regulation; fMRI; neurodevelopment; stress.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Amygdala / growth & development*
  • Amygdala / physiopathology*
  • Anxiety, Separation / physiopathology
  • Child, Preschool
  • Humans
  • Hydrocortisone / metabolism
  • Institutionalization
  • Magnetic Resonance Imaging
  • Maternal Deprivation*
  • Nerve Net / growth & development*
  • Nerve Net / physiopathology*
  • Phenotype
  • Prefrontal Cortex / growth & development*
  • Prefrontal Cortex / physiopathology


  • Hydrocortisone