Brain Microstructure and Metabolite Maturation and Capacity for Self-Regulation

Post by Stephanie Williams

What's the science?

During development, brain regions undergo changes in architecture and metabolite concentrations. It’s not always clear how these structural changes are related to the corresponding changes at the level of behavior. One aspect of cognition, self-regulation capacity, or the ability to monitor and control thoughts, emotions, and actions, is known to develop rapidly during development. This week in the Journal of Neuroscience, Nelson and colleagues use voxel-wise analysis of diffusion tensor imaging and Multiplanar Chemical Shift Imaging (MPCSI) data to characterize maturation in microstructure and metabolites across the brain, and their relationship to self-regulatory capacity.

How did they do it?

The authors investigated microstructure and metabolite maturation-related changes in the context of self-regulation capacity and general executive function in grade school-age racial and ethnic minority youth. To assess self-regulation capacity, the authors used data from a battery of cognitive assessments designed to probe attention, memory, executive functions, fine motor dexterity and visual-integration of the enrolled youth (~300 participants). The authors also examined white matter integrity and myelination with 1) diffusion imaging and- 2) multi-planar chemical shift imaging (~200 participants). Diffusion imaging shows how water is able to move through tracts in the brain as a function of its position. Multi-planar chemical shift imaging (MPCSI) offers high spatial resolution map of metabolite concentrations in the brain. The authors were interested in two measures from the diffusion data: 1) Fractional Anisotropy and 2) Apparent Diffusion Coefficient. Higher Fractional Anisotropy values in an area typically indicate greater structural integrity of the white matter tracts. They also analyzed several different brain metabolites with MPCSI, including N-acetyl-L-aspartate (NAA), which measures the density of viable neurons, Ch, which measures membrane turnover, and Glx, which measures energy metabolism, and Cr, which measures metabolic activity. The authors analyzed how cerebral microstructure and metabolite concentrations changed with age in a brain network that is known to support self-regulation, called the cortico-striato-thalamo-cortical loops (CSTC).

What did they find?

From the diffusion imaging analysis, the authors found that fractional anisotropy values were positively correlated with age in deep white matter bundles and in superficial cortical white matter in prefrontal and parietal cortex. These findings suggest that age is positively correlated with white matter maturation. Fractional Anisotropy was also positively correlated with age in several grey matter areas, including the anterior and posterior cingulate cortices, superficial grey matter, lenticular nucleus, caudate, thalamus, midbrain, medial occipital cortex, and cerebellum. Apparent Diffusion Coefficient, in contrast, was inversely correlated with age in several white matter and grey matter regions. The authors conclude from the strong positive correlation between age and higher Fractional Anisotropy values, along with the inverse correlations of age with Apparent Diffusion Coefficient values, that cellular maturation reduces diffusion in the radial direction of the fibre bundles. The authors hypothesize that age-related increases in myelination or axon packing density could be responsible for these changes. From their analysis on maturation-related metabolites, the authors found that NAA concentration was correlated with age in the dorsolateral PFC and inversely correlated with age in parietal white matter. NAA is involved in energy metabolism and higher NAA concentrations likely reflect increased energy metabolism. Age-related increases in NAA in grey matter regions, therefore, indicate structural or functional growth in those regions. Conversely, age-related decreases in NAA indicate pruning in those regions (parieto-occipital cortices). Importantly, the authors found evidence that the age-related microstructure changes were not accompanied by age-related alterations in white matter metabolite concentrations. They offer two possible explanations for this finding: 1) the transient changes in metabolite concentrations could have evaded detection by their statistical analysis, or 2) microstructure changes during development may not actually require significant metabolic changes, because myelin within white matter likely undergoes reorganization, rather than new synthesis, in these regions during pre-adolescence.


Together, these findings suggest that the improvements in executive functioning and self-regulatory ability in youth during maturation are supported by white matter maturation in frontal regions and subcortical projections, as well as simultaneous pruning in posterior regions.

What's the impact?

By combining these imaging modalities, the authors were able to pinpoint specific maturational changes in microstructure and metabolites that mediate performance improvements during the transition from late childhood to early adolescence. The authors also established normative values for microstructure and metabolite concentrations during this development period, which will allow future research to investigate aberrant development trajectories 


Nelson, M, et al. Maturation of Brain Microstructure and Metabolism Associates with Increased Capacity for Self-Regulation during the Transition from Childhood to Adolescence. The Journal of Neuroscience (2019). Access the original scientific publication here.