Japanese researchers develop advanced brain imaging technique to improve early diagnosis and intervention
Over five percent of children worldwide live with attention deficit/hyperactivity disorder (ADHD), a condition marked by inattention, impulsivity, and hyperactivity that is out of step with developmental expectations. These symptoms often disrupt education, social interactions, and family life, making ADHD one of the most common and challenging neurodevelopmental disorders to manage.
For years, scientists have turned to magnetic resonance imaging (MRI) to uncover the neurological roots of ADHD. However, the results have often been conflicting: some studies reported reduced gray matter volume (GMV) in children with ADHD, others found no difference, and some even showed increases.
Now, a team of researchers in Japan believes they have found a way to cut through the noise. Their new study, published in Molecular Psychiatry on August 8, 2025, introduces a correction method that could provide clearer insights into how ADHD shapes the developing brain.
Why Previous Results Have Been Inconclusive
One of the biggest challenges in ADHD brain research is that MRI scans are often collected at different sites using different machines. Variations in MRI equipment, combined with small sample sizes, make it hard to tell whether differences in brain structure are real or just technical artifacts.
Traditionally, researchers have used a correction tool called ComBat harmonization to minimize these site-related differences. While effective at reducing machine bias, ComBat can sometimes “overcorrect,” stripping away not just technical differences but also genuine biological variations linked to ADHD.
The New Traveling-Subject (TS) Method
To solve this problem, scientists at the University of Fukui, Chiba University, and The University of Osaka tested a new approach: the traveling-subject (TS) method.
Here’s how it works: the same group of healthy volunteers undergoes MRI scans at multiple sites using different machines. By comparing scans of the same people across different machines, researchers can directly measure and correct for machine-related biases without losing the underlying biological signals.
In this study, 14 healthy subjects underwent MRI scans on four different machines over three months. These “reference scans” were then used to correct a much larger dataset: MRI scans from 178 typically developing children and 116 children with ADHD, all collected through the Child Developmental MRI (CDM) database a major resource with data from more than 1,000 children.
Key Findings
After applying the TS method, the researchers observed a consistent pattern:
- Children with ADHD had smaller gray matter volumes in the frontotemporal regions compared to their typically developing peers.
- These brain regions are linked to cognitive functions, information processing, and emotional control areas frequently affected in ADHD.
- Compared to ComBat, the TS method reduced measurement bias while preserving biological differences, offering a clearer picture of the disorder.
As Associate Professor Yoshifumi Mizuno explained:
“Patients with ADHD displayed smaller volumes in brain regions crucial for cognitive and emotional control, helping us better understand the neurological roots of their symptoms.”
Toward Early Diagnosis and Personalized Care
The implications of this research are significant. If validated across larger and more diverse populations, TS-harmonized MRI data could serve as a biomarker for ADHD. This means doctors might one day use brain scans not just to study ADHD but to:
- Diagnose it earlier and more accurately
- Monitor treatment outcomes
- Tailor interventions to each child’s unique brain profile
Dr. Qiulu Shou, lead author of the study, highlighted the long-term vision:
“By applying TS harmonization, we can identify brain structure characteristics in children with ADHD. This opens the door to earlier diagnosis, more precise interventions, and ultimately, a better quality of life.”
Why It Matters
ADHD has long been diagnosed based on behavioral assessments, which, while effective, are subjective and can vary across cultures and clinical settings. A reliable biological marker — like TS-corrected MRI signatures could transform ADHD care by adding an objective dimension to diagnosis.
Moreover, earlier and more personalized treatment could reduce the risk of secondary psychiatric disorders, such as depression and anxiety, that often develop when ADHD is left untreated.
