Newer, Later-Maturing Areas Show More Genetic Effects with Age
• Science Update
Evolutionarily older areas of the human brain that mature earliest follow a simple, straight-line growth pattern. In contrast, newer areas that support our uniquely human capacities, such as thinking and language, mature latest and show the most complex growth pattern, NIMH researchers say. In keeping with their relatively recent evolution, newer areas are composed of more complex layers of cells and show stronger genetic influence later in development compared with evolutionarily older areas.
The researchers studied the thickening and thinning of the cortex, or outer mantle, in children and teens as they grew up. By revealing the ages at which each brain area reaches its peak thickness, the imaging studies have produced dramatic time-lapse movies of the brain maturing and maps pinpointing sites of high heritability during development.
Two research teams led by Philip Shaw, M.D., and Rhoshel Lenroot, M.D., of the NIMH Child Psychiatry Branch reported their magnetic resonance imaging (MRI) findings in the April 2, 2008 issue of the Journal of Neuroscience and online November 27, 2007 in Human Brain Mapping.
Shaw and colleagues followed brain development in 375 youth, scanning each at least twice and measuring the thickness at 40,000 cortex points. Overall, as seen in an earlier NIMH MRI brain maturation study, they observed a spurt of cortex growth in childhood, followed by pruning as the brain is streamlined for efficiency during adolescence. But the much finer resolution of the new approach allowed them to see the different growth trajectories that linked the course of development to the brain's evolutionary history (see graphic and movie below).
The complexity of an area's growth pattern, in turn, mirrored the complexity of its cellular architecture. Relating the new MRI findings to tissues described in brain atlases confirmed that early maturing and evolutionarily older areas are composed of just a few layers, while later maturing younger areas contain as many as six laminations.
Movie of the human brain maturing. Older, earlier maturing brain areas show a straight-line growth pattern (darker shade of red). Newer areas near the top front of the brain that mature last show the most complex growth trajectory (last areas to turn pink).
Source Philip Shaw, M.D., NIMH Child Psychiatry Branch.
Complexity of Growth Mirrors Evolutionary Age
Newer, more uniquely human brain areas (red) follow a more complex trajectory as they mature, compared to the evolutionarily oldest brain areas (blue), which follow a simple straight line pattern through development. Transitional areas (green) show an intermediate pattern of complexity. The index of maturation is the age at which an area reaches its peak thickness.
In the first MRI study to show how genes and the environment have different effects on maturation, Lenroot and colleagues scanned 600 youth, including twins.
They found that genes are relatively more influential in shaping cortex thickness earlier in brain areas which develop first.
By contrast, differences in later-maturing regions initially appear more related to environmental influences, but become increasingly determined by genetic factors with time. These more uniquely human areas are responsible for thinking, speech, sociality and language. Genetic differences exerted more effects in these newer regions, perhaps due to more genetic variation -- a "remnant" of rapid genetic changes that accompanied human divergence from other primates, suggest the researchers. Variation in the genes influencing older regions would have had more time to winnow through natural selection, they speculate.
"Knowing when during development regions most clearly show the influence of genetic factors may be useful for studies attempting to relate specific genes to behaviors in studies of mental illnesses," said Lenroot.
The phase during which the cortex thickens appears to reflect a 'critical period' during which experience exerts more influence, according to the researchers. Regions supporting simpler functions mature early and have a shorter critical period, perhaps related to stronger genetic influence during early development. Regions which support very complex functions are likely more open to being molded by the environment for a more extensive period earlier in development -- and thus have a longer window to reach peak cortical thickness.
Genes Influence Newer Areas Most During Late Teens
Heritability of brain areas at different ages. The brighter the color, the more heritable the area. Higher-order functions in the front of the brain (right) are most influenced by genetics during late teens.
Shaw P, Kabani NJ, Lerch JP, Eckstrand K, Lenroot R, Gogtay N, Greenstein D, Clasen L, Evans A, Rapoport JL, Giedd JN, Wise SP . Neurodevelopmental trajectories of the human cerebral cortex. J Neurosci. 2008 Apr 2;28(14):3586-94.PMID: 18385317
Lenroot RK, Schmitt JE, Ordaz SJ, Wallace GL, Neale MC, Lerch JP, Kendler KS, Evans AC, Giedd JN . Differences in genetic and environmental influences on the human cerebral cortex associated with development during childhood and adolescence. Hum Brain Mapp. 2007 Nov 27; [Epub ahead of print] PMID: 18041741