Brain structure characteristics in children with attention-deficit/hyperactivity disorder elucidated using traveling-subject harmonization

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Abstract

Background Brain imaging studies for attention-deficit/hyperactivity disorder (ADHD) have not always yielded consistent findings, potentially owing to measurement bias in magnetic resonance imaging (MRI) scanners. This study aimed to elucidate the structural brain characteristics in children with ADHD by addressing measurement bias in multi-site MRI data using the traveling-subject (TS) method. Methods The MRI data of 14 traveling subjects, 181 typical development (TD), and 117 ADHD children were collected from multiple sites. The TS method and ComBat were used to correct for measurement bias. Gray matter volumes were estimated using FreeSurfer, and the ADHD and TD groups were compared using mixed-effect models. Results Compared to raw data and ComBat-corrected data, the TS method significantly reduced measurement bias while maintaining sampling bias. The results from the TS-corrected data showed that the brain volume of the ADHD group was significantly smaller than that of the TD group in the bilateral middle temporal cortex, bilateral orbitofrontal cortex, right inferior frontal gyrus, right middle frontal gyrus, left inferior temporal gyrus, left precuneus cortex, and bilateral insular cortex. Brain regions that showed significant differences differed across the TS method, ComBat, and raw data. In contrast, notably significant volumetric reductions in the right middle temporal gyrus of ADHD patients were consistently observed across all methods. Conclusions The TS method effectively reduces measurement bias across MRI scanners, which may affect the findings of a multi-site study. The right middle temporal gyrus showed significant differences in all methods, suggesting it is a crucial region for ADHD.

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