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Cerebral Cortex Advance Access originally published online on July 24, 2008
Cerebral Cortex 2009 19(3):640-657; doi:10.1093/cercor/bhn117
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© The Author 2008. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Development of Anterior Cingulate Functional Connectivity from Late Childhood to Early Adulthood

A.M. Clare Kelly1, Adriana Di Martino1,2, Lucina Q. Uddin1, Zarrar Shehzad1, Dylan G. Gee1, Philip T. Reiss3, Daniel S. Margulies1,4, F. Xavier Castellanos1,5 and Michael P. Milham1

1 Phyllis Green and Randolph Cowen Institute for Pediatric Neuroscience at the NYU Child Study Center, New York, NY, USA, 2 Division of Child and Adolescent Neuropsychiatry, Department of Neuroscience, University of Cagliari, Italy, 3 NYU Child Study Center, Division of Biostatistics, New York, NY, USA, 4 Berlin School of Mind and Brain, Humboldt Universität, Berlin, Germany, 5 Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA

Address correspondence to Michael P. Milham, MD, PhD, Phyllis Green and Randolph Cowen Institute for Pediatric Neuroscience, NYU Child Study Center, New York, NY 10016, USA. Email: Michael.Milham{at}nyumc.org.

Human cerebral development is remarkably protracted. Although microstructural processes of neuronal maturation remain accessible only to morphometric post-mortem studies, neuroimaging tools permit the examination of macrostructural aspects of brain development. The analysis of resting-state functional connectivity (FC) offers novel possibilities for the investigation of cerebral development. Using seed-based FC methods, we examined the development of 5 functionally distinct cingulate-based intrinsic connectivity networks (ICNs) in children (n = 14, 10.6 ± 1.5 years), adolescents (n = 12, 15.4 ± 1.2) and young adults (n=14, 22.4 ± 1.2). Children demonstrated a more diffuse pattern of correlation with voxels proximal to the seed region of interest (ROI) ("local FC"), whereas adults exhibited more focal patterns of FC, as well as a greater number of significantly correlated voxels at long distances from the seed ROI. Adolescents exhibited intermediate patterns of FC. Consistent with evidence for different maturational time courses, ICNs associated with social and emotional functions exhibited the greatest developmental effects. Our findings demonstrate the utility of FC for the study of developing functional organization. Moreover, given that ICNs are thought to have an anatomical basis in neuronal connectivity, measures of FC may provide a quantitative index of brain maturation in healthy subjects and those with neurodevelopmental disorders.

Key Words: anterior cingulate • BA 25 • development • functional connectivity • self-regulation


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