Development and aging of cortical thickness correspond to genetic organization patterns

Abstract

There is a growing realization that early life influences have lasting impact on brain function and structure. Recent research has demonstrated that genetic relationships in adults can be used to parcellate the cortex into regions of maximal shared genetic influence, and a major hypothesis is that genetically programmed neurodevelopmental events cause a lasting impact on the organization of the cerebral cortex observable decades later. Here we tested how developmental and lifespan changes in cortical thickness fit the underlying genetic organizational principles of cortical thickness in a longitudinal sample of 974 participants between 4.1 and 88.5 y of age with a total of 1,633 scans, including 773 scans from children below 12 y. Genetic clustering of cortical thickness was based on an independent dataset of 406 adult twins. Developmental and adult age-related changes in cortical thickness followed closely the genetic organization of the cerebral cortex, with change rates varying as a function of genetic similarity between regions. Cortical regions with overlapping genetic architecture showed correlated developmental and adult age change trajectories and vice versa for regions with low genetic overlap. Thus, effects of genes on regional variations in cortical thickness in middle age can be traced to regional differences in neurodevelopmental change rates and extrapolated to further adult aging-related cortical thinning. This finding suggests that genetic factors contribute to cortical changes through life and calls for a lifespan perspective in research aimed at identifying the genetic and environmental determinants of cortical development and aging.here is a growing realization that events during development impact brain and cognition throughout the entire lifespan (1). For instance, the major portion of the relationship between cortical thickness and IQ in old age can be explained by childhood IQ (2), and genotype may explain a substantial part of the lifetime stability in intelligence (3). Effects of genes on the organization of the cortex have been shown in adults (4-6), but it is unknown whether and how regional differences in cortical development correspond to these regional genetic subdivisions.Although consensus has not been reached for the exact trajectories, cortical thickness as measured by MRI appears to decrease in childhood (7-12). The exact foundation for this thinning is not known, as MRI provides merely representations of the underlying neurobiology, and available histological data cannot with certainty be used to guide interpretations of MRI results. Although speculative, apparent thickness decrease may be grounded in factors such as synaptic pruning and intracortical myelination, although the link between established synaptic processes (13-15) and cortical thickness has not been empirically confirmed. After childhood, cortical thinning continues throughout the remainder of the lifespan, speculated to reflect neuronal shrinkage and reductions in number of spines and synapses (16), although sim...

Neurodevelopmental origins of lifespan changes in brain and cognition

“…This finding fits with the notion that GCA is supported by distributed brain networks (44,45). Using genetically defined cortical clusters (6,35), there was evidence that especially prefrontal and medial and posterolateral temporal clusters related more strongly to GCA. Most previous studies have focused on cortical volume or thickness, but the present results correspond with previously reported findings on areacognition relationships (24) in a sample not overlapping with the current developmental cohort wherein the region was currently identified.…”

“…Previous research has shown that the cortex can be divided into regions of maximum shared genetic variance, and these regions can further be organized into superordinate clusters based on genetic similarity. As described above, we have recently shown that developmental and adult age-related changes in cortical thickness follow this genetic organization of the cerebral cortex (6). The most fundamental genetic influence on cortical surface area goes along an anterior-posterior axis (35).…”

“…Much focus has been on age-specific mechanisms of neural foundations of cognition and their change (3,4). In contrast, neurodevelopmental origins of functional variation in older age are now increasingly being acknowledged (5)(6)(7)(8), but identification of how early factors may impact human brain and cognition throughout the lifespan has remained challenging.…”

“…It has even been shown that childhood GCA can account for GCA-cortical thickness associations in old age (12). Cortical thickness is known to decrease with age monotonously from relatively early childhood through the entire lifespan (6,13,14). This thinning, albeit continuous, signifies different neurobiological events at different stages of life (15,16), and does not have a stable functional correlate at different ages; opposite relationships between cognitive ability and cortical thickness have been identified in development and aging (17,18).…”

“…This thinning, albeit continuous, signifies different neurobiological events at different stages of life (15,16), and does not have a stable functional correlate at different ages; opposite relationships between cognitive ability and cortical thickness have been identified in development and aging (17,18). We recently showed that genetic factors contribute to apparent cortical thickness changes through life, calling for a lifespan perspective in research aimed at identifying the genetic and environmental determinants of cortical development and aging (6). Cortical surface area, which is the other component of cortical volume, is genetically (19), phylogenetically, and ontogentically (20) distinct from cortical thickness.…”