Lag in maturation of the brain's intrinsic functional architecture in attention-deficit/hyperactivity disorder

Proc Natl Acad Sci U S A. 2014 Sep 30;111(39):14259-64. doi: 10.1073/pnas.1407787111. Epub 2014 Sep 15.

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood, and there is great interest in understanding its neurobiological basis. A prominent neurodevelopmental hypothesis proposes that ADHD involves a lag in brain maturation. Previous work has found support for this hypothesis, but examinations have been limited to structural features of the brain (e.g., gray matter volume or cortical thickness). More recently, a growing body of work demonstrates that the brain is functionally organized into a number of large-scale networks, and the connections within and between these networks exhibit characteristic patterns of maturation. In this study, we investigated whether individuals with ADHD (age 7.2-21.8 y) exhibit a lag in maturation of the brain's developing functional architecture. Using connectomic methods applied to a large, multisite dataset of resting state scans, we quantified the effect of maturation and the effect of ADHD at more than 400,000 connections throughout the cortex. We found significant and specific maturational lag in connections within default mode network (DMN) and in DMN interconnections with two task positive networks (TPNs): frontoparietal network and ventral attention network. In particular, lag was observed within the midline core of the DMN, as well as in DMN connections with right lateralized prefrontal regions (in frontoparietal network) and anterior insula (in ventral attention network). Current models of the pathophysiology of attention dysfunction in ADHD emphasize altered DMN-TPN interactions. Our finding of maturational lag specifically in connections within and between these networks suggests a developmental etiology for the deficits proposed in these models.

Keywords: connectomics; default network; resting state.

Publication types

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

MeSH terms

  • Adolescent
  • Attention Deficit Disorder with Hyperactivity / pathology*
  • Attention Deficit Disorder with Hyperactivity / physiopathology
  • Brain / growth & development*
  • Brain / pathology*
  • Brain / physiopathology
  • Cerebral Cortex / growth & development
  • Cerebral Cortex / pathology
  • Cerebral Cortex / physiopathology
  • Child
  • Connectome
  • Female
  • Functional Neuroimaging
  • Gyrus Cinguli / growth & development
  • Gyrus Cinguli / pathology
  • Gyrus Cinguli / physiopathology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Models, Neurological
  • Nerve Net / growth & development
  • Nerve Net / pathology
  • Nerve Net / physiopathology
  • Prefrontal Cortex / growth & development
  • Prefrontal Cortex / pathology
  • Prefrontal Cortex / physiopathology
  • Young Adult