Basal ganglia surface morphology and the effects of stimulant medications in youth with attention deficit hyperactivity disorder

Abstract

Objective: Disturbances in the basal ganglia portions of cortico-striato-thalamo-cortical circuits likely contribute to the symptoms of attention deficit hyperactivity disorder (ADHD). The authors examined the morphologic features of the basal ganglia nuclei (caudate, putamen, and globus pallidus) in children with ADHD.

Method: A total of 104 individuals (combined-type ADHD patients: N=47; healthy comparison subjects: N=57), aged 7 to 18 years, were examined in a cross-sectional case-control study using anatomical magnetic resonance imaging. Conventional volumes and the surface morphology for the basal ganglia were measured.

Results: Overall volumes were significantly smaller only in the putamen. Analysis of the morphological surfaces revealed significant inward deformations in each of the three nuclei, localized primarily in portions of these nuclei that are components of limbic, associative, and sensorimotor pathways in the cortico-striato-thalamo-cortical circuits in which these nuclei reside. The more prominent these inward deformations were in the patient group, the more severe the ADHD symptoms. Surface analyses also demonstrated significant outward deformations of all basal ganglia nuclei in the ADHD children treated with stimulants compared with those ADHD youth who were untreated. These stimulant-associated enlargements were in locations similar to the reduced volumes detected in the ADHD group relative to the comparison group. The outward deformations associated with stimulant medications attenuated the statistical effects of the primary group comparisons.

Conclusions: These findings potentially represent evidence of anatomical dysregulation in the circuitry of the basal ganglia in children with ADHD and suggest that stimulants may normalize morphological features of the basal ganglia in children with the disorder.

Figure 1. Main Effects of Diagnosis on Surface Morphologic Features

The right and left caudate, putamen, and globus pallidus are displayed in rotational views and in their dorsal and ventral perspectives. Anterior (A), posterior (P), lateral (L) and medial (M) views of each nucleus are shown. The curved arrow at the top of each column indicates the direction of rotation. The color bar at the bottom indicates the significance value for group comparisons at each point on the surface. Green values represent statistically non-significant differences (P ≥ 0.05) of the surface of the basal ganglia nuclei between groups. Yellow and red values (P<0.0001) represent outward deformations of the surfaces, or local volume increases, whereas blue and purple represent inward deformations of the surfaces, or local volume reductions (P<0.0001). Gaussian Random Field (GRF)-corrected maps are shown for each nucleus.

Figure 2. Main effects of Stimulants on Surface Morphologic Features

For ease of comparison, GRF-corrected images are displayed in anterior, posterior, lateral, and medial views, whereas the GRF-uncorrected images are displayed in lateral and medial views only. The color bar at the bottom indicates the color coding for P values associated with either the diagnosis term (column A and C) or the stimulant term (column B). A. Main effect of diagnosis in youth with ADHD off stimulants compared to controls. B. Main effect of stimulant use in youth with ADHD taking stimulants compared to those with ADHD not taking stimulants. The outward deformations in the basal ganglia of youth treated with stimulants compared to those untreated approximately align with the inward deformations detected in the overall main effects of diagnosis (Fig. 1). C. Main effect of diagnosis in youth with ADHD on stimulants compared to controls. The statistical attenuation of the main effects of diagnosis, indicated by a less significant inward deformations on the surface of the basal ganglia in the youth on stimulants (C) versus those off stimulants (A) compared to controls, suggests that a major component of the overall main effects of diagnosis (Fig. 1) was attenuated by the effects of stimulant medications on the morphological features of the basal ganglia. Abbreviations are as described in Figure 1.

Figure 3. Correlations of Symptom Severity with Surface Features of the Basal Ganglia in Youth with ADHD

Correlation of surface measures with total ADHD symptom severity. The color bar depicts the P-value for the partial Pearson correlation coefficient, r, with the p-value ranging from P<0.0001 in red (highly significant positive correlation) to P<0.0001 in purple (highly significant inverse correlations).