Frontoparietal Structural Connectivity in Childhood Predicts Development of Functional Connectivity and Reasoning Ability: A Large-Scale Longitudinal Investigation

Abstract

Prior research points to a positive concurrent relationship between reasoning ability and both frontoparietal structural connectivity (SC) as measured by diffusion tensor imaging (Tamnes et al., 2010) and frontoparietal functional connectivity (FC) as measured by fMRI (Cocchi et al., 2014). Further, recent research demonstrates a link between reasoning ability and FC of two brain regions in particular: rostrolateral prefrontal cortex (RLPFC) and the inferior parietal lobe (IPL) (Wendelken et al., 2016). Here, we sought to investigate the concurrent and dynamic, lead-lag relationships among frontoparietal SC, FC, and reasoning ability in humans. To this end, we combined three longitudinal developmental datasets with behavioral and neuroimaging data from 523 male and female participants between 6 and 22 years of age. Cross-sectionally, reasoning ability was most strongly related to FC between RLPFC and IPL in adolescents and adults, but to frontoparietal SC in children. Longitudinal analysis revealed that RLPFC-IPL SC, but not FC, was a positive predictor of future changes in reasoning ability. Moreover, we found that RLPFC-IPL SC at one time point positively predicted future changes in RLPFC-IPL FC, whereas, in contrast, FC did not predict future changes in SC. Our results demonstrate the importance of strong white matter connectivity between RLPFC and IPL during middle childhood for the subsequent development of both robust FC and good reasoning ability.SIGNIFICANCE STATEMENT The human capacity for reasoning develops substantially during childhood and has a profound impact on achievement in school and in cognitively challenging careers. Reasoning ability depends on communication between lateral prefrontal and parietal cortices. Therefore, to understand how this capacity develops, we examined the dynamic relationships over time among white matter tracts connecting frontoparietal cortices (i.e., structural connectivity, SC), coordinated frontoparietal activation (functional connectivity, FC), and reasoning ability in a large longitudinal sample of subjects 6-22 years of age. We found that greater frontoparietal SC in childhood predicts future increases in both FC and reasoning ability, demonstrating the importance of white matter development during childhood for subsequent brain and cognitive functioning.

Keywords: fMRI; functional connectivity; longitudinal; reasoning; structural connectivity.

Figure 1.

ROIs, including RLPFC, DLPFC, IPL, and SPL. Smaller circles indicate the extent of the 5 mm spheres uses for FC analysis and larger circles indicate the extent of the 12 mm spheres used as targets for probabilistic tractography.

Figure 2.

White matter tracts, obtained via probabilistic tractography, including frontoparietal tracts from RLPFC or DLPFC to IPL (red) or SPL (blue) (A); bilateral prefrontal tracts between left and right DLPFC (blue) and between left and right RLPFC (yellow) (B); and bilateral parietal tracts between left and right IPL (blue) and between left and right SPL (yellow) (C). End-point masks (12 mm spheres) are indicated with white circles. Purple (A) and green (B, C) indicate overlap between tracts.

Figure 3.

Scatter plot of the relationship between age and matrix reasoning. Gray lines indicate longitudinal data. The fit line was calculated using the cumulative distribution function (pnorm in R). Optimal parameters μ = 6 and σ = 3.5, extracted from the data, indicate maximal change at age 6 (i.e., at the beginning of the examined age range).

Figure 4.

Scatter plot of the relationship between average frontoparietal SC (FA) and reasoning ability (matrix reasoning score). Lines between data points indicate longitudinal data. The fit line is linear.

Figure 5.

A, Scatter plot of RLPFC–IPL SC (FA) versus age with a nonlinear (pnorm) fit line. B, Scatter plot of RLPFC–IPL FC versus age with a nonlinear (pnorm) fit line.

Figure 6.

Scatter plot of the relationship between SC and FC for the RLPFC–IPL connection with a linear fit line. Lines between data points indicate longitudinal data.

Figure 7.

A, Predictors of RLPFC–IPL FC change. B, Predictors of RLPFC–IPL SC change. Shaded boxes indicate factors that survived stepwise regression. Solid lines indicate factors that survived both stepwise regression and correction for study site (with at least marginal significance).

Figure 8.

Predictors of change in reasoning ability (R), in younger participants (6–11 years old; A), and older participants (12–22 years old; B). Shaded boxes indicate factors that survived stepwise regression. Solid lines indicate factors that survived both stepwise regression and correction for study site (with at least marginal significance).