Brain Growth and Atrophy: Relationships between Gray Matter Thinning and Cortical Surface Morphology During Normal Development and Aging

7th International Conference on Functional Mapping of the Human Brain, Brighton, England, June 2001.

Introduction:
In a recent study of brain maturation between adolescence and adulthood, we observed a highly consistent inverse relationship between cortical thinning and radial expansion of the brain primarily in dorsal frontal regions (1). Specifically, we found that regions of greatest brain growth spatially and temporally corresponded to regions of greatest cortical thinning. These findings lead us to speculate we might see an opposite relationship between brain surface extent and gray matter thinning during normal aging when degenerative processes (i.e., atrophy) are more prominent.

Methods:
We studied a group of 25 normally developing children and adolescents (mean age 11.1 years) and another group of 20 middle aged adults (mean age 48.2 years) using high-resolution MRI. Image data sets were linearly transformed into standard space and tissue segmented, and sulcal boundaries were drawn on the surface renderings of each individual's brain. Elastic deformation maps were used to encode gyral patterns and drive each individual's cortical anatomy into a group average (i.e., young, old). Gray matter density at each point on the cortical surface was estimated for each individual (2) as was radial expansion/contraction, quantified by creating a measure of the distance from the center (DFC) of the brain to each cortical surface point. Statistical maps of correlations between DFC and gray matter density at each cortical surface point were created for the younger and older groups. Differences between the statistical maps for each group were evaluated.

Results:
Relationships between DFC and gray matter density were strongly negative over vast areas of dorsal frontal and parietal cortex in the children and adolescents, such that greater brain surface expansion (i.e. growth) was related to lower gray matter density. A drastic alteration in this pattern was observed in the older group where positive relationships between DFC and gray matter density were observed in dorsolateral prefrontal cortex bilaterally. Specifically, in these regions shrinkage or contraction of the cortical surface was associated with thinning of the cortex. Negative relationships between DFC and gray matter density were also observed in this group, but only in the lateral, posterior temporo-parietal junction. Notably, this was the only region that showed small positive correlations between DFC and gray matter density in the younger group.

Discussion:
As predicted cortical thinning is associated with shrinkage or contraction of the cortical surface, at least in dorsolateral prefrontal regions, probably as a result of normal atrophic processes. This is a reversal of the pattern observed much earlier in life where progressive cellular maturational events, such as increased myelination, result in the appearance of thinning gray matter with concomitant brain surface expansion (i.e., growth). These results suggest that the changes observed during adolescence are a distinct process that is inverse to the atrophic change observed during normal aging.

References. [1] E. R. Sowell, P.M. Thompson, K.D. Tessner, and A. W. Toga [submitted], [2]: P. M. Thompson et al., Cereb Cortex 11, 1-16 (2001).

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