Developmental changes in the organization of functional connections between the basal ganglia and cerebral cortex

Abstract

The basal ganglia (BG) comprise a set of subcortical nuclei with sensorimotor, cognitive, and limbic subdivisions, indicative of functional organization. BG dysfunction in several developmental disorders suggests the importance of the healthy maturation of these structures. However, few studies have investigated the development of BG functional organization. Using resting-state functional connectivity MRI (rs-fcMRI), we compared human child and adult functional connectivity of the BG with rs-fcMRI-defined cortical systems. Because children move more than adults, customized preprocessing, including volume censoring, was used to minimize motion-induced rs-fcMRI artifact. Our results demonstrated functional organization in the adult BG consistent with subdivisions previously identified in anatomical tracing studies. Group comparisons revealed a developmental shift in bilateral posterior putamen/pallidum clusters from preferential connectivity with the somatomotor "face" system in childhood to preferential connectivity with control/attention systems (frontoparietal, ventral attention) in adulthood. This shift was due to a decline in the functional connectivity of these clusters with the somatomotor face system over development, and no change with control/attention systems. Applying multivariate pattern analysis, we were able to reliably classify individuals as children or adults based on BG-cortical system functional connectivity. Interrogation of the features driving this classification revealed, in addition to the somatomotor face system, contributions by the orbitofrontal, auditory, and somatomotor hand systems. These results demonstrate that BG-cortical functional connectivity evolves over development, and may lend insight into developmental disorders that involve BG dysfunction, particularly those involving motor systems (e.g., Tourette syndrome).

Keywords: basal ganglia; development; functional connectivity; resting state.

Figure 1.

A, Voxels included in the basal ganglia mask are indicated in white with a black boundary; slices are shown in the transverse plane (image left is anatomical left), z-coordinate is in the top left corner. B, Eleven cortical systems from Power et al. (2011).

Figure 2.

Partial correlation maps for each cortical system in the adult group (n = 120). Purple, blue, and green lines displayed across the cortex on the left correspond to the transverse slices (in the z-plane) shown here. Slices were chosen that best represent the peak partial correlation values between basal ganglia voxels and each cortical system. Significant partial correlations are defined as those with a z-score >2.3 (p < 0.01). Image left is anatomical left.

Figure 3.

Children differ significantly from adults. A, Partial correlations for the somatomotor face system in adults and children; z-score scale is 2.3–8, as in Figure 2. B, Voxels with a significant difference in partial correlations between children and each adult cohort; colored orange to correspond with the somatomotor face system. C, Correlation between age and mean partial correlation coefficient within the voxels colored in B. *Significance. D, Frequency histogram showing the number of voxels labeled differently (in winner-take-all assignment) across 100,000 random assignments of data in two groups composed of children and adults (blue). The number of voxels labeled differently between the 60 children and the two original adults cohorts shown by the red stars.

Figure 4.

A, Whole-brain functional connectivity of left hemisphere putamen/pallidum seed (MNI coordinates: −26, −11, −1) in children (n = 60) and each adult cohort (n = 60 each). Positive correlations are displayed in warm colors. B, Comparisons of each adult cohort to the cohort of children. Stronger correlations in children than adults are displayed in warm colors; stronger correlations in adults than children are displayed in cool colors.

Figure 5.

Winner-take-all maps in adults and children, displaying functional connectivity between the basal ganglia and functionally defined cortical systems. Each basal ganglia voxel is colored according to the cortical system it most correlates with (color key at the bottom). On the left, slices shown in the transverse plane (image left is anatomical left), z = −7 to z = 22 (top left corner). On the right, 3-D renderings displayed in lateral, dorsal, ventral, and medial views. Superior (S) direction is shown with a blue arrow; anterior (A) and posterior (P) directions are shown with a green arrow; and medial (M) and lateral (L) directions are shown with a red arrow.

Figure 6.

A, Reliability of winner assignments in adults and children. Arrows highlight the regions with high reliability in children, but not adults. B, Δr value between the “winning” system and the system with the second highest correlation in adults and children. Slices shown in the transverse plane (image left is anatomical left), z = −6 to z = 15 (top left corner).

Figure 7.

A, B, Distribution of consensus features (percentage of all consensus features) by cortical system for classifier 1 (children and adult cohort 1) and classifier 2 (children and adult cohort 2) identified by the SVM based on BG–cortical system functional connectivity (A) and by the SVM that excluded BG voxels that showed a developmental difference in the univariate analyses (B; i.e., orange voxels in Fig. 3B).