Multimodal imaging of the self-regulating developing brain

Abstract

Self-regulation refers to the ability to control behavior, cognition, and emotions, and self-regulation failure is related to a range of neuropsychiatric problems. It is poorly understood how structural maturation of the brain brings about the gradual improvement in self-regulation during childhood. In a large-scale multicenter effort, 735 children (4-21 y) underwent structural MRI for quantification of cortical thickness and surface area and diffusion tensor imaging for quantification of the quality of major fiber connections. Brain development was related to a standardized measure of cognitive control (the flanker task from the National Institutes of Health Toolbox), a critical component of self-regulation. Ability to inhibit responses and impose cognitive control increased rapidly during preteen years. Surface area of the anterior cingulate cortex accounted for a significant proportion of the variance in cognitive performance. This finding is intriguing, because characteristics of the anterior cingulum are shown to be related to impulse, attention, and executive problems in neurodevelopmental disorders, indicating a neural foundation for self-regulation abilities along a continuum from normality to pathology. The relationship was strongest in the younger children. Properties of large-fiber connections added to the picture by explaining additional variance in cognitive control. Although cognitive control was related to surface area of the anterior cingulate independently of basic processes of mental speed, the relationship between white matter quality and cognitive control could be fully accounted for by speed. The results underscore the need for integration of different aspects of brain maturation to understand the foundations of cognitive development.

Conflict of interest statement

Conflict of interest statement: A.M.D. is a founder of and holds equity interest in CorTechs Labs, La Jolla, CA and serves on its scientific advisory board. The terms of this arrangement have been reviewed and approved by the University of California, San Diego, in accordance with its conflict of interest policies.

Figures

Fig. 1.

Cognitive performance and age. RT in z scores, corrected for sex, site, and GAF, plotted as a function of age for congruent (Left) and incongruent (Center) stimuli as well as the cognitive conflict effects operationalized as the percentage of slowing of RT for incongruent relative to congruent stimuli (Right). The red lines represent the smoothing spline function, with the harshness of the smoothing parameter chosen to minimize Bayesian information Criteria (BIC) (40).

Fig. 2.

Cortical surface area and cognitive conflict. Relationship between incongruent RT and local cortical surface area in the participants 12 y or younger corrected for age, sex, scanner, GAF, and congruent RT. The analyses were unbiased, with no anatomical constraints imposed. The effect was corrected for multiple comparisons by z Monte Carlo simulations and thresholded at P < 0.05.

Fig. 3.

Age relationships. (Upper) Correlations between incongruent RT and area of the right caudal anterior cingulate (Left), FA (Center), and ADC (Right) in forceps major. Correlations were calculated in 5-y age bins, with a moving time window of 1 y and the results smoothed (smoothing spline). P values are from the nonsmoothed correlations. Age, sex, scanner, and GAF were regressed out from all variables in addition to RT from the congruent condition for the area correlations. (Lower) Relationships between age and the imaging variables residualized for GAF, scanner, and sex. The age trajectory is estimated with smoothing spline (see above). Age did not correlate with right caudal anterior cingulate surface area (Pearson r = 0.06, P = 0.10), whereas the correlations for FA and ADC were significant (Spearman ρ = 0.25, P < 0.10−10 and Spearman ρ = −0.08, P < 0.05, respectively).

Fig. 4.

Probabilistic tractography. Selected tracts in individual participants of different ages. These tracts were all significantly related to incongruent RT at P < 0.05 (ADC: corpus callosum and superior longitudinal fasciculus; FA: corpus callosum and inferior longitudinal fasciculus), but only forceps major survived Bonferroni corrections (ADC and FA).