Strengthening of top-down frontal cognitive control networks underlying the development of inhibitory control: a functional magnetic resonance imaging effective connectivity study

Abstract

The ability to voluntarily inhibit responses to task-irrelevant stimuli, which is a fundamental component of cognitive control, has a protracted development through adolescence. Previous human developmental imaging studies have found immaturities in localized brain activity in children and adolescents. However, little is known about how these regions integrate with age to form the distributed networks known to support cognitive control. In the present study, we used Granger causality analysis to characterize developmental changes in effective connectivity underlying inhibitory control (antisaccade task) compared with reflexive responses (prosaccade task) in human participants. By childhood, few top-down connectivities were evident with increased parietal interconnectivity. By adolescence, connections from prefrontal cortex increased and parietal interconnectivity decreased. From adolescence to adulthood, there was evidence of increased number and strength of frontal connections to cortical regions as well as subcortical regions. Together, results suggest that developmental improvements in inhibitory control may be supported by age-related enhancements in top-down effective connectivity between frontal, oculomotor, and subcortical regions.

Figure 1.

Regions selected as ROIs. Both left- and right-hemisphere regions are placed on the right hemisphere to aid with visualization, and coordinates of each ROI are listed in Table 1. Twenty-six regions known to be involved in oculomotor control/response inhibition (Luna et al., 2001) and general cognitive control processes (Dosenbach et al., 2006, 2007) were selected. These regions can be sorted into different functional subgroups based on published literatures and their anatomical locations. We specified ROIs that comprised the oculomotor circuitry, including the SEF, bilateral FEF, bilateral IPreCS, bilateral IPS, bilateral SPC, and bilateral SMG (Luna et al., 1998, 2001; Berman et al., 1999; Merriam et al., 2001). We also identified several cognitive control regions in the frontal cortex associated with task control (Müri et al., 1998; Dosenbach et al., 2006, 2007), attentional processes (Corbetta and Shulman, 2002; Bressler et al., 2008), working memory (Curtis and D'Esposito, 2003), and response inhibition (Aron et al., 2004), including the right MFG, right IFG, and bilateral insula. The ACC was included because of its association with monitoring the consequences of actions or conflicts between motor responses (Paus et al., 1993; Carter et al., 1998; Braver et al., 2001; Rushworth et al., 2004). Subcortical regions included bilateral putamen (denoted as BG for basal ganglia), bilateral dorsal medial thalamus (TH), the SC, and the cerebellum (Cere), and these are also known to be involved in the inhibitory control of saccades (Sweeney et al., 1996; Müri et al., 1998; Luna et al., 2001). Abbreviations apply to all figures.

Figure 2.

The results of effective connectivity analysis for both the AS and PS tasks, separated by age group and task (A, adults; B, adolescents; C, children). Both left- and right-hemisphere connections are placed on the right hemisphere to aid with visualization. Arrows connecting two ROIs represent significant effective connectivity from one ROI to another. Only significant connections (FDR < 0.05) are displayed. For the AS task, across age groups we observed dominant influencing connectivity from frontal regions to parietal regions and subcortical regions. Connections were also evident from parietal regions to subcortical regions. The PS connectivity profile lacked connections seen in AS from the right frontal cortex to parietal and subcortical regions.

Figure 3.

The results of contrasting effective connectivity between task conditions separated by age group. Both left- and right-hemisphere connections are placed on the right hemisphere to aid with visualization. These are connections in which effective connectivity strengths were significantly greater or more asymmetric for AS compared with PS (FDR < 0.05). These connections are likely involved in active inhibitory control processes. For all age groups, no connections showed greater effective connectivity strength for PS compared with AS.

Figure 4.

Developmental patterns of effective connectivity underlying inhibitory control. These are connections in which effective connectivity strengths were significantly different across age groups (children, adolescents, adults). Both left- and right-hemisphere connections are placed on the right hemisphere to aid with visualization. Connections are grouped into two overarching developmental patterns: developmental increase and developmental decrease. Left shows connections that showed developmental increase in effective connectivity strengths (adults significantly greater than adolescents and/or adolescents significantly greater than children). Right shows connections that showed developmental decrease in effective connectivity strengths (children significantly greater than adolescents and/or adolescents significantly greater than adults). Solid lines with arrows represent developmental increasing connections, and dashed lines with arrows represent developmental decreasing connections. Connections from frontal to parietal and subcortical regions increased with age, whereas connections within the parietal cortex decreased with age. A, Adults; C, children; T, adolescents.

Figure 5.

Box plots of developmental changes in effective connectivity. These are connections in which effective connectivity strengths were significantly different across age groups (also see Fig. 4). For every box plot, the dependent measure (y-axis) is the effective connectivity strength (difference of influencing strength, DOI) of the AS task. A shows connections that showed developmental increase in effective connectivity strengths (adults significantly greater than adolescents and/or adolescents significantly greater than children). B shows connections that showed developmental decrease in effective connectivity strengths (children significantly greater than adolescents and/or adolescents significantly greater than adults). L, Left; R, right.

Figure 6.

Developmental patterns of functional connectivity associated with the AS task. Connections are grouped into two overarching developmental patterns: developmental increase and developmental decrease. Both left- and right-hemisphere connections are placed on the right hemisphere to aid with visualization. Left shows connections that showed developmental increases in functional connectivity (adults significantly greater than adolescents and/or adolescents significantly greater than children). Right shows connections that showed developmental decreases in functional connectivity (children significantly greater than adolescents and/or adolescents significantly greater than adults). Solid lines represent developmental increasing connections, and dashed lines represent developmental decreasing connections. Functional connectivity between distant regions increased with age, whereas functional connectivity within the frontal and parietal cortex decreased with age. A, Adults; C, children; T, adolescents.