Orbitofrontal and Medial Frontal Gray Matter Volumes Are Associated With Hyperactivity Traits in 2548 Nonclinical...

Attention-deficit/hyperactivity disorder (ADHD) traits vary continuously across the general population, yet whether the frontal structural correlates established in clinical ADHD extend to trait variation in nonclinical adults is unknown. Based on meta-analytic evidence, we hypothesized that orbitofrontal gray matter volumes would be negatively associated with hyperactivity traits in 2548 nonclinical Japanese adults (1488 males, 1060 females; aged 23-76 years) who underwent structural MRI and completed the Adult ADHD Self-Report Scale. Regional gray matter volumes of 61 bilateral-averaged regions were tested against inattention, hyperactive motor, and hyperactive verbal trait subscales using partial correlations controlling for age and sex, with false discovery rate (FDR) correction. Five associations survived correction, all linking smaller orbital or medial frontal volumes to higher hyperactivity: medial frontal cortex with hyperactive motor and hyperactive verbal traits, and anterior orbital gyrus, lateral orbital gyrus, and orbital inferior frontal gyrus with hyperactive verbal traits (r = -0.070 to -0.078). The effect sizes were within the range reported for clinical ADHD by the ENIGMA consortium, and secondary analyses found no evidence that bilateral averaging concealed an additional hemisphere-specific association. The findings were robust across sensitivity and permutation analyses. Inattention showed no FDR-significant associations, with Bayesian and equivalence analyses supporting near-null effects at the benchmarked magnitude for most regions. Brain volumes did not improve individual-level prediction of trait scores. These findings identify small orbitofrontal and medial frontal volume associations with hyperactivity along the adult ADHD trait continuum and provide a foundational nonclinical baseline for clinical and transdiagnostic studies of ADHD traits.