Summary: Researchers tested a new MRI correction method, called the traveling-subject (TS) approach, to resolve inconsistencies in ADHD brain imaging results. By scanning the same healthy subjects across multiple MRI machines, they identified and corrected for measurement biases, producing more reliable data.
The study revealed that children with ADHD show reduced gray matter volume in frontotemporal regions, areas important for decision-making and emotion regulation. This method could pave the way for early diagnosis and more personalized interventions for ADHD.
Key Facts
- TS Method Advantage: Unlike traditional ComBat correction, TS reduces MRI bias without erasing biological variation.
- Brain Findings: Children with ADHD had smaller frontotemporal brain volumes, key to cognition and emotional control.
- Clinical Potential: TS-corrected MRI data could serve as neuroimaging biomarkers for early and individualized ADHD treatment.
Source: University of Fukui
Over five percent of children and adolescents are diagnosed with attention deficit/hyperactivity disorder (ADHD) globally. This condition is characterized by a short attention span, hyperactivity or impulsive behavior that is age-inappropriate, making it difficult for patients to navigate interpersonal relationships, the formal education system, and social life.
Researchers have used brain imaging analyses such as magnetic resonance imaging (MRI) to understand the neurological basis of ADHD. Understanding brain structure abnormalities that lead to ADHD-related pathologies is crucial for designing early assessment and intervention systems, especially for children.
Although multiple studies have used MRI to understand ADHD in children, the results have been inconclusive. While some brain imaging studies have shown decreased gray matter volume (GMV) in children with ADHD, others have either reported no change or an increase in GMV compared to subjects without ADHD.
These conflicting results are mostly due to small sample sizes, differences in MRI machines used, or the variation among the subjects recruited. Previous studies have accounted for the bias caused by different MRI machines using a method called ComBat harmonization, which controls for site and MRI differences in large samples.
However, ComBat overcorrects sampling bias, which may include biological characteristics of the sample; therefore, it may not be able to accurately correct the MRI differences.
The traveling-subject (TS) method is a new correction approach to account for variations in measurements across MRI machines for the same subject. In this method, measurement biases can be controlled for the same participants using MRI scans from multiple institutions, facilitating the collection of more accurate datasets.
In this collaborative study, Assistant Professor Qiulu Shou and Associate Professor Yoshifumi Mizuno from the University of Fukui, Japan, Professor Yoshiyuki Hirano from Chiba University, Japan, and Professor Kuriko Kagitani-Shimono at The University of Osaka, Japan, validated the TS method in an independent dataset. T
heir findings were published in Molecular Psychiatry on August 8, 2025.
Dr. Shou introduces the methodological framework of the study: “MRI data of 14 TS, 178 typically developing (TD) children, and 116 children with ADHD were collected from multiple sites, and the TS method and ComBat were used to correct for measurement bias.”
Fourteen healthy subjects underwent MRI scans on four different machines over a three-month period to extract measurement biases across these machines. This was then applied to an independent dataset of children from the Child Developmental MRI (CDM) database.
The CDM database was jointly established by the University of Fukui, The University of Osaka, and Chiba University, with the goal of collecting brain imaging data from over 1,000 child participants for research on neurodevelopmental disorders such as ADHD. GMV was then estimated and compared between the two groups of children in the study.
The research team calculated measurement and sampling biases among TS-corrected, ComBat-corrected, and raw data.
The results showed that compared to raw data, the TS method significantly reduced measurement bias while maintaining sampling bias. In contrast, ComBat effectively reduced measurement bias and significantly decreased sampling bias.
“TS-corrected data showed decreased brain volumes in the frontotemporal regions in the ADHD group compared to the TD group,” explains Dr. Mizuno while discussing their findings.
“Patients with ADHD displayed smaller volumes in those regions of the brain that are crucial for cognitive functions, such as information processing and emotional control, which are often affected in these patients,” adds Dr. Shou.
Furthermore, if TS-harmonized multi-site MRI data on specific brain structure patterns can be associated with ADHD, they can then be used as neuroimaging biomarkers for accurate and early ADHD diagnosis, treatment, and treatment outcome monitoring, leading to effective personalized therapeutic strategies.
“By applying the TS harmonization method to correct for site-related biases in multi-site MRI data, this study aims to identify brain structure characteristics in children with ADHD.
“These identified characteristics could facilitate earlier diagnosis and more precise, individualized interventions. In the long term, this approach may improve the quality of life for affected children and reduce the risk of secondary psychiatric disorders,” concludes Dr. Shou.
Funding information
This work was funded by the:
- Japan Society for the Promotion of Science (JSPS) (KAKENHI; grant numbers: 24K16647, 24K21453, 21K02380, 23K12814, 23H00949, 22H01090, 23K02956, 23K07004, and 24K21493)
- Kawano Masanori Memorial Public Interest Incorporated Foundation for Promotion of Pediatrics
- The Mother and Child Health Foundation
- The Japan-U.S. Brain Research Cooperative Program
- University of Fukui, Japan
- The Taiju Life Social Welfare Foundation
- The Collaborative Research Program of the Collaborative Research Network for Asian Children with Developmental Disorders: MEXT Policy Initiative
About this neuroimaging and ADHD research news
Author: Yuuka Kawamoto
Source: University of Fukui
Contact: Yuuka Kawamoto – University of Fukui
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Brain structure characteristics in children with attention-deficit/hyperactivity disorder elucidated using traveling-subject harmonization” by Qiulu Shou et al. Molecular Psychiatry
Abstract
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 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.
