Functional connectivity between cognitive control regions is sensitive to familial risk for ADHD

Abstract

Familial risk for attention-deficit hyperactivity disorder (ADHD) has been associated with changes in brain activity related to cognitive control. However, it is not clear whether changes in activation are the primary deficit or whether they are related to impaired communication between regions involved in this ability. We investigated whether (1) functional connectivity between regions involved in cognitive control was affected by familial risk and (2) changes were specific to these regions. Correlational seed analyses were used to investigate temporal covariance between cognitive control and motor regions in two independent samples of typically developing controls, subjects with ADHD and their unaffected siblings. In both samples, correlation coefficients between cognitive control regions were greater for typically developing controls than for subjects with ADHD, with intermediate values for unaffected siblings. Within the motor network, unaffected siblings showed correlations similar to typically developing children. There were no differences in activity between the brain regions involved. These data show that functional connectivity between cognitive control regions is sensitive to familial risk for ADHD. Results suggest that changes in connectivity associated with cognitive control may be suitable as an intermediate phenotype for future studies.

Figure 1

Seed points selected from whole group analyses. Seed regions were taken from a whole group one‐sample t‐test at P = 0.0001, extent 10 voxels (corresponding to P = 0.05 corrected at the cluster level) for each sample. For each seed region, the peak activity was used to define 10 mm spheres (yellow circles). The graphs show BOLD activity level in the seed regions from individual subjects (healthy controls—blue; unaffected siblings—green; and subjects with ADHD—red). Boxes represent the interquartile range (difference between first and third quartiles. Legend: ACG, anterior cingulate gyrus; BOLD, blood oxygenation level dependent; rIFG, right inferior frontal gyrus; MTC, motor cortex.

Figure 2

Group differences in functional connectivity. Functional connectivity between ACG and CB is decreased for subjects with ADHD (red) compared with typically developing controls (blue). Correlation coefficients for unaffected siblings (green) are intermediate (A and B). Functional connectivity between motor cortex and striatum is decreased for subjects with ADHD (red), but not for their unaffected siblings (green) (C). There are no differences between groups in the BOLD response in any of the regions (small graphs). Boxes represent the interquartile range, dashed lines connect means. * P < 0.05.

Figure 3

When connectivity between regions is disturbed, one consequence could be delay in the simultaneous activation of regions. As the delay becomes greater, the correlation coefficient decreases (B) and large shift could even lead to negative correlation coefficients (C). r = correlation coefficient.