9 December 2011. In the first study of coordinated anatomical changes across development, a team of researchers headed by Jay Giedd of the National Institute of Mental Health in Bethesda, Maryland, reports that functionally connected brain regions mature in a correlated manner. Published in the December 8 issue of Neuron, the study used magnetic resonance imaging (MRI) to track cortical thickness (CT) in a large cohort of individuals between the ages of nine and 22.
Since schizophrenia is thought to be a neurodevelopmental disorder that involves dysfunction of multiple brain circuits, understanding the basics of how these circuits mature is an important avenue of research. Unlike previous imaging studies that have examined single cortical regions in isolation, the new study quantifies how the relationships among brain regions change across development. In the largest and longest longitudinal brain maturation study to date, the authors identify several aspects of cortical development that may provide insight into the abnormal developmental trajectory of the brain in schizophrenia, which is marked by thinner than usual CT (see SRF related news story).
Rates of change
Based on 376 scans gathered from 108 study participants who had been imaged every two years, first author Armin Raznahan and colleagues found most cortical areas thinned with age. However, when they looked at how the rates of CT change were coordinated across the brain, they found high correlations among some brain regions but not others. For example, the rates of CT change in higher-order frontal and temporal association cortex exhibited the strongest correlations with the rates of CT change across the rest of the cortex, and formed the most spatially extensive set of correlations with other cortical regions. Lower-order primary visual and sensorimotor cortices, on the other hand, exhibited the weakest and least distributed correlations with the rest of the cortex. Given that both the frontal and temporal lobes are implicated in schizophrenia, these results suggest that a perturbation of connectivity early in life may result in a disruption of coordinated brain development, eventually producing a distributed network of neuroanatomical alterations later in life.
The authors also demonstrated that cortical regions within the default-mode network, a group of brain regions that are active while an individual is awake but not cognitively engaged (Fox et al., 2005), exhibit very high correlations in rate of CT change with each other. Interestingly, the default-mode network exhibits hyperactivity as well as altered connectivity in schizophrenia (see SRF related news story). Additionally, highly correlated rates of CT change were also found within a second set of distributed cortical regions, the task positive network, known to be active during mental tasks (Fox et al., 2005). These data suggest that both functionally and anatomically connected regions exhibit coordinated patterns of development during brain maturation.
On male and female
The researchers also found sexual dimorphism in left frontopolar cortex rates of CT change, which replicates prior data from the same group using a different method of analysis (Raznahan et al., 2010), and in this region, maturational coupling with other brain areas. Female subjects exhibited significantly higher correlations of frontopolar cortical rates of CT change over time with bilateral dorsolateral prefrontal cortex and right ventrolateral prefrontal cortex than males did, implicating the frontopolar cortex as a region of interest in the study of sex differences. These prefrontal regions are strongly implicated in cognitive control and decision-making (Badre and Wagner, 2004), and the sex differences identified in their maturation may underlie the sex differences in cognitive control, risk-taking, and motivation that are well documented (Christakou et al., 2009; Steinberg, 2010).
The coordinated patterns of maturation found in this study might depend on the inherent connectivity among the brain regions involved. For example, one plausible explanation for the greater maturational coupling of higher-order regions is that they require more widespread integration with the rest of the cortex in order to carry out the more integrated cognitive processes they underlie. Perhaps not surprisingly, cortical regions that exhibit structural and functional interconnectivity also display highly correlated rates of maturation. Finally, sexually dimorphic rates of maturation in the prefrontal cortex, and in its coupling with other regions, provide interesting clues about the neural circuitry underlying sex differences in cognitive control and adolescent behavior. The integrative approach to exploring cortical maturation utilized in this study will be a useful tool for further investigation of both the normal and perturbed developing brain.—Allison A. Curley.
Raznahan A, Lerch JP, Lee N, Greenstein D, Wallace GL, Stockman M, Clasen L, Shaw PW, Giedd JN. Patterns of Coordinated Anatomical Change in Human Cortical Development: A Longitudinal Neuroimaging Study of Maturational Coupling. Neuron. 2011 Dec 8;72(5):873-84. Abstract