Mapping the development of the basal ganglia in children with attention-deficit/hyperactivity disorder

Abstract

Objective: The basal ganglia are implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD), but little is known of their development in the disorder. Here, we mapped basal ganglia development from childhood into late adolescence using methods that define surface morphology with an exquisite level of spatial resolution.

Method: Surface morphology of the basal ganglia was defined from neuroanatomic magnetic resonance images acquired in 270 youth with DSM-IV-defined ADHD and 270 age- and sex-matched typically developing controls; 220 individuals were scanned at least twice. Using linear mixed model regression, we mapped developmental trajectories from age 4 through 19 years at approximately 7,500 surface vertices in the striatum and globus pallidus.

Results: In the ventral striatal surfaces, there was a diagnostic difference in developmental trajectories (t = 5.6, p < .0001). Here, the typically developing group showed surface area expansion with age (estimated rate of increase of 0.54 mm(2) per year, standard error [SE] 0.29 mm(2) per year), whereas the ADHD group showed progressive contraction (decrease of 1.75 mm(2) per year, SE 0.28 mm(2) per year). The ADHD group also showed significant, fixed surface area reductions in dorsal striatal regions, which were detected in childhood at study entry and persisted into adolescence. There was no significant association between history of psychostimulant treatment and developmental trajectories.

Conclusions: Progressive, atypical contraction of the ventral striatal surfaces characterizes ADHD, localizing to regions pivotal in reward processing. This contrasts with fixed, nonprogressive contraction of dorsal striatal surfaces in regions that support executive function and motor planning.

Keywords: attention-deficit/hyperactivity disorder; basal ganglia; development; neuroimaging; ventral striatum.

Figure 1:

Regions where the group with attention-deficit/hyperactivity disorder (ADHD) showed a significant reduction in surface area at study entry, following adjustment for multiple comparisons. Note: A) R lateral view; B) L lateral view; c) Inferior (ventral) view.

Figure 2:

Developmental trajectories (estimates with 95% CI) for the striatal and globus pallidus volumes and total surface areas. Note: There were no significant differences in the shapes of the curves. The group with attention-deficit/hyperactivity disorder (ADHD) is shown in red and typically developing in blue.

Figure 3:

Regions where there was a significant difference in trajectories following adjustment for multiple comparison (overall slope difference in this region, t=5.6, p<0.0001) and a graph showing the trajectories of surface area change for this region, with 95% CI). Note: ADHD = attention-deficit/hyperactivity disorder.

Figure 4:

The emergence of significant group differences in surface area in the ventral striatal region from ages 8 to 18. Note: This is derived from the linear mixed model regression by re-centering age from age 8 to 18 and illustrates the progression of ventral striatal contraction in attention-deficit/hyperactivity disorder (ADHD).