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 (CSTC) circuits likely contribute to the symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD). This study examines the morphologic features of the basal ganglia nuclei (caudate, putamen, and globus pallidus) in children with ADHD. Design We examined 104 individuals (47 with combined-type ADHD and 57 controls) aged 7 to 18 years, in a cross-sectional case-control study using anatomical magnetic resonance imaging. We measured conventional volumes and the surface morphology for the basal ganglia. 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 that were localized primarily in portions of these nuclei that are components of limbic, associative, and sensorimotor pathways in the CSTC circuits in which these nuclei reside. The more prominent these inward deformations were in the patient group, the more severe were their ADHD symptoms. Surface analyses also demonstrated significant outward deformations of all basal ganglia nuclei in the ADHD children treated with stimulants compared to those with ADHD who were untreated. These stimulant-associated enlargements were in locations similar to the reduced volumes detected in the ADHD group relative to controls. The outward deformations associated with stimulant medications attenuated the statistical effects of the primary group comparisons. Conclusion These findings potentially represent evidence of anatomical dysregulation in the circuitry of the basal ganglia of children with ADHD and suggest that stimulants may “normalize” morphological features of the basal ganglia in children with ADHD.

Long-Term Oral Methylphenidate Treatment in Adolescent and Adult Rats: Differential Effects on Brain Morphology and Function

“…The effects of methylphenidate on striatal morphology echo clinical observations of medication-induced normalization of inward caudate nuclei deformations (Sobel et al, 2010). These findings are in line with a recent meta-analysis (Nakao et al, 2011) that indicated that in ADHD, and in terms of medication effects, the most prominent and replicable structural abnormalities occur in the basal ganglia.…”

“…Similarly, childhood psychostimulant medication was found to normalize ADHD-related reductions of anterior cingulate cortex volume, whereas caudate nuclei volumes remained markedly reduced regardless of medication history (Semrud-Clikeman et al, 2006). Yet, the shapes of the caudate nuclei of untreated patients showed inward deformations that appeared normalized after psychostimulant treatment (Sobel et al, 2010). Longitudinal measurements of cerebral cortex thickness indicated that ADHD-associated excess cortical thinning during adolescence could be moderated by psychostimulant treatment (Shaw et al, 2009).…”

ADHD: Volumetry, Motor, and Oculomotor Functions

“…Among medication-naïve participants, there were volume reductions in putamen that were primarily driven by inward deformations of structures, including those nuclei within the putamen that are components of limbic, sensorimotor, and associative pathways. In contrast, those treated with stimulants had outward deviations of putamen nuclei, suggesting that stimulants may affect, and perhaps facilitate, development of basal ganglia morphology in ADHD (Sobel et al 2010) in a manner that serves to ameliorate ADHD-related deficits in executive and motor control. Admittedly, comparison of treated versus nontreated children with ADHD is complicated, in part because it is possible that groups may have differed in some systematic way before onset of treatment.…”

Reward processing in male adults with childhood ADHD—a comparison between drug-naïve and methylphenidate-treated subjects

“…A 5-year longitudinal study found smaller total white matter volume in unmedicated compared with medicated ADHD children (Castellanos et al 2002). More normative volumes in several brain areas, i.e., the inferior frontal cortex (Shaw et al 2009), cerebellum (Bledsoe et al 2009), basal ganglia (Sobel et al 2010), and anterior cingulate cortex have been found in chronically treated compared with unmedicated children. Pliszka et al (2006) reported more pronounced differences in the anterior cingulate cortex and ventrolateral prefrontal cortex during an inhibition task in drug-naïve ADHD compared with healthy children, but direct comparisons between drug-naïve subjects and subjects with a history of psychostimulant treatment revealed no differences.…”