Review
Neuroimaging Studies of Normal Brain Development and Their Relevance for Understanding Childhood Neuropsychiatric Disorders

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Abstract

Objective

To review the maturational events that occur during prenatal and postnatal brain development and to present neuroimaging findings from studies of healthy individuals that identify the trajectories of normal brain development.

Method

Histological and postmortem findings of early brain development are presented, followed by a discussion of anatomical, diffusion tensor, proton spectroscopy, and functional imaging findings from studies of healthy individuals, with special emphasis on longitudinal data.

Results

Early brain development occurs through a sequence of major events, beginning with the formation of the neural tube and ending with myelination. Brain development at a macroscopic level typically proceeds first in sensorimotor areas, spreading subsequently and progressively into dorsal and parietal, superior temporal, and dorsolateral prefrontal cortices throughout later childhood and adolescence. These patterns of anatomical development parallel increasing activity in frontal cortices that subserves the development of higher-order cognitive functions during late childhood and adolescence. Disturbances in these developmental patterns seem to be involved centrally in the pathogenesis of various childhood psychiatric disorders including childhood-onset schizophrenia, attention-deficit/hyperactivity disorder, developmental dyslexia, Tourette's syndrome, and bipolar disorder.

Conclusions

Advances in imaging techniques have enhanced our understanding of normal developmental trajectories in the brain, which may improve insight into the abnormal patterns of development in various childhood psychiatric disorders.

Section snippets

Imaging the Major Events of Early Brain Development

Much of what we know about fetal and early postnatal brain development has been extrapolated either from histological studies in rodents or from sparse postmortem and imaging data in human and nonhuman primates. Practical and ethical concerns, as well as methodological limitations, have constrained studies of early development in both humans and primates.1, 2 Because imaging data in the developing fetus, infant, and young child are so sparse, we review briefly what is known about the cellular

Anatomical MRI Studies in Children and Adolescents

The first anatomical MRI studies of healthy brain development used techniques to measure regional brain volumes that first divide the brain into anatomical regions having presumably differing functional characteristics (e.g., the frontal and parietal lobes, or the hippocampus and amygdala) and then correlated the volumes of those regions with age. Findings from these cross-sectional studies revealed that volumes of cortical and subcortical gray matter decreased from childhood to adulthood when

Sex Differences in Anatomical Maturation of the Brain

Interest in identifying differences in brain development between the sexes has been generated primarily by widely documented differences between males and females in cognitive abilities, including a male advantage for spatial abilities67 and a female advantage for verbal skills.68 Females, however, tend to have smaller bodies, and the scaling relation between body size and brain size (i.e., people with larger bodies tend to have larger heads and brains) accounts, at least in part, for their

Diffusion Tensor Imaging of Normal Brain Development

Diffusion tensor imaging (DTI) is an MRI modality that provides information about the direction and integrity of neural fiber tracks in the brain in vivo by characterizing the three-dimensional diffusion of water molecules. Because myelin and cell membranes tend to restrict the diffusion of water, water molecules tend to diffuse along the longitudinal axis of myelinated axons. Thus, by describing mathematically the diffusion of water molecules, investigators can track the direction of bundles

Magnetic Resonance Spectroscopy Studies of Normal Brain Development

Magnetic resonance spectroscopy (MRS) is an MRI modality that derives signal not only from protons in water but also from protons in molecules such as creatine, N-acetylaspartate (NAA), choline (Cho), and glutamate (Glu).79 Proton MRS studies have reported age-related increases in levels of NAA, which begin at low levels around birth and then increase rapidly during the first 2 years of life, becoming less pronounced thereafter.98, 99 In addition, findings from a study of 15 healthy children

Functional MRI Studies of Cognitive Development

Functional MRI (fMRI) permits exploration of structure-function relations across development, allowing identification of where, when, and how cognitive abilities develop in relation to the maturation of anatomical brain systems. Cognitive processes such as language, executive functioning, and emotion regulation are most likely to elicit differences in patterns of brain activations in children compared with adults because association cortices in the brain that are critically important for these

Discussion

Noninvasive imaging techniques now permit investigation of the anatomical and functional maturation of the healthy brain. Understanding healthy developmental trajectories of brain structure and function is of crucial importance for the generation of hypotheses regarding the neural bases of developmentally based psychopathologies. Longitudinal anatomical MRI studies of healthy children have shown that brain maturation typically proceeds in a back-to-front wave, occurring first dorsally, then

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    This work was supported in part by NIMH grants K02-74677, K01-MH077652, T32 MH16434, and MH068318, by National Institute on Drug Abuse grant DA017820, by a grant from the National Alliance for Research on Schizophrenia and Depression, and by funding from the Sackler Institute for Developmental Psychobiology, Columbia University.

    Portions of this article were presented at the 2007 research forum The Future of Neuroimaging: Relevance for Child Psychiatry at the American Academy of Child and Adolescent Psychiatry, Boston, MA, October 2007.

    This article is the subject of an editorial by Dr. Ellen Leibenluft in this issue.

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