Abstract

Previous structural imaging studies have revealed gray matter volume abnormalities to reflect the etiology of attention deficit hyperactivity disorder (ADHD), however, which are confounded by age, medication and comorbidity and also ignore the core feature of brain structure in the executive impairments of ADHD. In the present study, we explored gray matter volume abnormalities in male children and adolescents with ADHD who were drug-naive and without comorbidities, and tried to connect structural data and behavioral executive dysfunction to provide more information regarding the brain–behavior relationships in ADHD. Seventy-two male subjects (37 patients and 35 controls) underwent three-dimensional high-resolution structural magnetic resonance imaging and executive function assessments, including the Stroop Color–Word Test and Wisconsin Card Sorting Test (WCST). Voxel-based morphometry with diffeomorphic anatomical registration through exponentiated Lie algebra was used to identify gray matter volume differences between the ADHD and controls. Correlation analyses were performed to identify neuroanatomical deficits that were associated with executive dysfunctions. Significantly reduced gray matter volumes were identified in the right orbitofrontal cortex, right primary motor/premotor cortex, left anterior cingulate cortex and left posterior midcingulate cortex of ADHD patients compared with controls (P<0.05, corrected for family-wise errors). In patients group, the gray matter volumes of the right orbitofrontal cortex and left posterior midcingulate cortex were positively correlated with the completed categories on the WCST, and the gray matter volume of the left posterior midcingulate cortex was negatively correlated with the total and non-perseverative errors on the WCST (P<0.05). The present findings show gray matter volume reductions in motor regions as well as the orbitofrontal and cingulate cortex; this evidence supports theories that suggest frontal abnormalities in children and adolescents with ADHD at early illness stage. The correlations between structural abnormalities and executive dysfunction suggest that neuroanatomical substrate deficits are implicated in the pathophysiology of ADHD.

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