Normal development of brain circuits

Abstract

Spanning functions from the simplest reflex arc to complex cognitive processes, neural circuits have diverse functional roles. In the cerebral cortex, functional domains such as visual processing, attention, memory, and cognitive control rely on the development of distinct yet interconnected sets of anatomically distributed cortical and subcortical regions. The developmental organization of these circuits is a remarkably complex process that is influenced by genetic predispositions, environmental events, and neuroplastic responses to experiential demand that modulates connectivity and communication among neurons, within individual brain regions and circuits, and across neural pathways. Recent advances in neuroimaging and computational neurobiology, together with traditional investigational approaches such as histological studies and cellular and molecular biology, have been invaluable in improving our understanding of these developmental processes in humans in both health and illness. To contextualize the developmental origins of a wide array of neuropsychiatric illnesses, this review describes the development and maturation of neural circuits from the first synapse through critical periods of vulnerability and opportunity to the emergent capacity for cognitive and behavioral regulation, and finally the dynamic interplay across levels of circuit organization and developmental epochs.

Figure 1

Timeline of major events in brain development. This diagram represents brain development beginning with neurolation, and proceeding with neuronal migration, synaptogenesis, pruning, myelination, and cortical thinning. Reproduced with permission and modified from Giedd (1999) (Copyright 1999) American Psychiatric Association.

Figure 2

The embryonic layers of the developing human neocortex. (a) Schematic illustration of the development of the layers in the human neocortex. (b) Histochemical section of the human fetal brain at GA 16 weeks stained with cresyl violet to show cortical lamination. (a) Reproduced with permission from Bystron et al (2008) (Copyright 2008) Nature Publishing Group; (b) reproduced with permission from Kostović et al (2002) (Copyright 2002) Oxford University Press.

Figure 3

The diversity of neurons within cortical laminae. Reconstructed coronal view of the different cell types that are represented in mature cortical layers I–VI. Cells were colored for ease of viewing, as follows: axons, bright blue or bright yellow; dendrites; dark blue or dark yellow. L, cortical layer; wm, white matter; b, basket cells; db, double bouquet cell; p, pyramidal cells; ss, spiny stellate cells. Scale bar, 300 μm. Reproduced with permission from Binzegger et al (2004) (Copyright 2004) Society for Neuroscience.

Figure 4

Schematic of the connections between layers 3 and 6 neurons of the cerebral cortex in adults. This diagram represents a summary of data from paired intracellular recordings and dye filling of connected neurons from the visual cortex of adult rats and cats. Triangles, excitatory neurons; circles, inhibitory interneurons. Clearly, many more types of interlaminar connections remain to be described in detail. Reproduced with permission from (Thomson and Bannister, 2003) (Copyright 2003) Oxford University Press.

Figure 5

Brain myelination across development. Top panels: T1-weighted axial MRI images acquired longitudinally from one child, showing age-related increase in brain size and white matter intensity. Bottom panels: DTI images of white matter tractography in a cross-sectional comparison showing of age-related increase in the organization of corpus callosum white matter. Each panel represents one subject. Color scale represents fractional anisotropy; higher values correlate with greater organization of fibers tracks. Panels are labeled with age of participants at the time of scan. A, anterior; L left. Reproduced with permission from Gilmore et al (2006) (Copyright 2006) American Psychiatric Association.

Figure 6

Gray matter maturation across development. Right lateral and top views of the brain showing the dynamic sequence of temporal changes in gray matter volume over the cortical surface. The images represent modeled data from 52 anatomical MRI scans from 13 individuals 4–21 years of age, each scanned four times at approximately 2-year intervals. Color scale represents gray matter units of volume. Reproduced with permission from Gogtay et al (2004) (Copyright 2004) National Academy of Sciences, USA.

Figure 7

Development of neural circuits for cognitive control. Images represent brain activation in a cross-sectional developmental fMRI of the Stroop task. (a) Voxel-wise correlations of age with Stroop activations are represented in transaxial slices positioned superiorly to inferiorly (left to right). (b) Group composite t-maps for the fMRI signal change associated with the naming of colors in incongruent compared with congruent stimuli for children and adults. Increases in signal during the incongruent relative to congruent are coded in yellow, and decreases are coded in purple or blue. Right frontostriatal (ILPFC and Lent) increases in activity associated with incongruent stimuli came on line progressively with age. Thus, increasing activity in frontostriatal circuits with age supports the developmental improvements in cognitive control in healthy individuals. PCC, posterior cingulate cortex; ACC, anterior cingulate cortex; VACC, ventral anterior cingulate cortex; STG, superior temporal gyrus; Lnuc, lenticular nucleus; LPFC, lateral prefrontal cortex; MPFC, mesial prefrontal cortex; IFG, inferior frontal gyrus (Marsh et al, 2006) (Copyright 2006) John Wiley and Sons.