Individualized Gray Matter Deviations in Children with ADHD: Insights from Structural MRI Modeling

Abstract Background Attention-Deficit/Hyperactivity Disorder (ADHD) affects approximately 7.6% of children globally and exhibits heterogeneous cognitive and behavioral manifestations. Conventional group-level MRI analyses often obscure individual variability in brain structure, limiting understanding of personalized neuroanatomical profiles. Objective This study quantified individualized gray matter volume (GMV) deviations in children with ADHD using age- and sex-matched normative structural MRI references. Methods Structural MRI data from 31 children with ADHD (16 males, 15 females; ages 7–15) and 413 typically developing controls (TDC; ages 7–22) were analyzed. Voxel-based morphometry extracted regional GMV across prefrontal cortex, striatal nuclei, and cerebellar vermis. Individual deviations were calculated as z-scores relative to normative distributions and categorized as typical, mild, moderate, strong, and extreme. Results Lateral and orbital prefrontal regions exhibited the highest deviations: for females, the Lateral Orbital Gyrus (LOrG) showed 33.3% mild-to-strong deviations and 13.3% extreme deviations, while the Opercular Inferior Frontal Gyrus (OpIFG) had 73.3% mild-to-strong deviations. In males, the LOrG showed 31.2% moderate, 6.2% strong, and 18.8% extreme deviations. Striatal nuclei exhibited mixed patterns: female caudate volumes were typical in 33.3% of participants, moderate-to-extreme deviations occurred in 46.7%; male putamen was typical in 31.2%, with 37.5% showing strong or extreme deviations. Cerebellar vermis values were mostly typical (50–60%) with occasional mild-to-strong deviations. Medial and superior frontal regions remained largely typical (40–73%). Conclusion Children with ADHD display heterogeneous and region-specific GMV deviations, most pronounced in lateral and orbital prefrontal cortex and select striatal regions. Individualized z-score profiling captures variability obscured in group averages, supporting personalized neuroanatomical assessment for understanding ADHD and guiding targeted treatment.