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

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 addre...

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Published in:Molecular psychiatry Vol. 30; no. 12; p. 5873
Main Authors: Shou, Qiulu, Yamashita, Masatoshi, Hirano, Yoshiyuki, Yao, Akiko, Li, Min, Wang, Yide, Kato, Yoko, Yoshida, Tokiko, Matsumoto, Koji, Tsujikawa, Tetsuya, Okazawa, Hidehiko, Tomoda, Akemi, Kagitani-Shimono, Kuriko, Mizuno, Yoshifumi
Format: Journal Article
Language:English
Published: England 01.12.2025
Subjects:
Adolescent
Attention Deficit Disorder with Hyperactivity - diagnostic imaging
Attention Deficit Disorder with Hyperactivity - pathology
Brain - diagnostic imaging
Brain - pathology
Child
Female
Gray Matter - diagnostic imaging
Gray Matter - pathology
Humans
Image Processing, Computer-Assisted - methods
Magnetic Resonance Imaging - methods
Male
Organ Size
ISSN:1476-5578, 1476-5578
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Abstract 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 harmonization method, traveling-subject (TS) approach. The MRI data of 14 traveling subjects, 178 typically developing (TD) children, and 116 children with ADHD 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. Compared to raw data, the TS method significantly reduced measurement bias while maintaining sampling bias. In contrast, ComBat effectively reduced measurement bias but also significantly decreased sampling bias. TS-corrected data showed decreased brain volumes in the frontotemporal regions in the ADHD group compared to the TD group. Specifically, significant volumetric reductions were found in the right middle temporal gyrus in children with ADHD (TS-corrected data: β = -0.255, FDR [family discovery rate] p = 0.001). These results demonstrate that the TS method effectively reduces measurement bias across MRI scanners, ensuring reliable findings in multi-site studies. The observed frontotemporal volume reductions in ADHD, especially in the right middle temporal gyrus, highlight the reliability of findings obtained with TS correction.
AbstractList 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 harmonization method, traveling-subject (TS) approach. The MRI data of 14 traveling subjects, 178 typically developing (TD) children, and 116 children with ADHD 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. Compared to raw data, the TS method significantly reduced measurement bias while maintaining sampling bias. In contrast, ComBat effectively reduced measurement bias but also significantly decreased sampling bias. TS-corrected data showed decreased brain volumes in the frontotemporal regions in the ADHD group compared to the TD group. Specifically, significant volumetric reductions were found in the right middle temporal gyrus in children with ADHD (TS-corrected data: β = -0.255, FDR [family discovery rate] p = 0.001). These results demonstrate that the TS method effectively reduces measurement bias across MRI scanners, ensuring reliable findings in multi-site studies. The observed frontotemporal volume reductions in ADHD, especially in the right middle temporal gyrus, highlight the reliability of findings obtained with TS correction.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 harmonization method, traveling-subject (TS) approach. The MRI data of 14 traveling subjects, 178 typically developing (TD) children, and 116 children with ADHD 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. Compared to raw data, the TS method significantly reduced measurement bias while maintaining sampling bias. In contrast, ComBat effectively reduced measurement bias but also significantly decreased sampling bias. TS-corrected data showed decreased brain volumes in the frontotemporal regions in the ADHD group compared to the TD group. Specifically, significant volumetric reductions were found in the right middle temporal gyrus in children with ADHD (TS-corrected data: β = -0.255, FDR [family discovery rate] p = 0.001). These results demonstrate that the TS method effectively reduces measurement bias across MRI scanners, ensuring reliable findings in multi-site studies. The observed frontotemporal volume reductions in ADHD, especially in the right middle temporal gyrus, highlight the reliability of findings obtained with TS correction.
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 harmonization method, traveling-subject (TS) approach. The MRI data of 14 traveling subjects, 178 typically developing (TD) children, and 116 children with ADHD 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. Compared to raw data, the TS method significantly reduced measurement bias while maintaining sampling bias. In contrast, ComBat effectively reduced measurement bias but also significantly decreased sampling bias. TS-corrected data showed decreased brain volumes in the frontotemporal regions in the ADHD group compared to the TD group. Specifically, significant volumetric reductions were found in the right middle temporal gyrus in children with ADHD (TS-corrected data: β = -0.255, FDR [family discovery rate] p = 0.001). These results demonstrate that the TS method effectively reduces measurement bias across MRI scanners, ensuring reliable findings in multi-site studies. The observed frontotemporal volume reductions in ADHD, especially in the right middle temporal gyrus, highlight the reliability of findings obtained with TS correction.
Author Wang, Yide
Tsujikawa, Tetsuya
Li, Min
Yao, Akiko
Hirano, Yoshiyuki
Yoshida, Tokiko
Kagitani-Shimono, Kuriko
Mizuno, Yoshifumi
Kato, Yoko
Shou, Qiulu
Yamashita, Masatoshi
Tomoda, Akemi
Matsumoto, Koji
Okazawa, Hidehiko
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  organization: United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Osaka, Japan
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  surname: Mizuno
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  email: mizunoy@u-fukui.ac.jp, mizunoy@u-fukui.ac.jp, mizunoy@u-fukui.ac.jp
  organization: Department of Child and Adolescent Psychological Medicine, University of Fukui Hospital, Fukui, Japan. mizunoy@u-fukui.ac.jp
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Snippet Brain imaging studies for attention-deficit/hyperactivity disorder (ADHD) have not always yielded consistent findings, potentially owing to measurement bias in...
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SubjectTerms Adolescent
Attention Deficit Disorder with Hyperactivity - diagnostic imaging
Attention Deficit Disorder with Hyperactivity - pathology
Brain - diagnostic imaging
Brain - pathology
Child
Female
Gray Matter - diagnostic imaging
Gray Matter - pathology
Humans
Image Processing, Computer-Assisted - methods
Magnetic Resonance Imaging - methods
Male
Organ Size
Title Brain structure characteristics in children with attention-deficit/hyperactivity disorder elucidated using traveling-subject harmonization
URI https://www.ncbi.nlm.nih.gov/pubmed/40781545
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