White Matter Patterns Underlie ADHD Heterogeneity

Investigators have deciphered white matter patterns and how they impact the cognitive and behavioral trajectory of patients with attention deficit/hyperactivity disorder (ADHD).

A team, led by Xuan Bu, Department of Radiology, Huaxi MR Research Center, West China Hospital of Sichuan University, identified associations between white matter and a broad set of clinical features across pediatric patients with and without ADHD.

White Matter

The integrity of white matter microstructure is known to play a role in the neural mechanism of ADHD presentations. However, the link between specific behavioral dimensions and white matter microstructure are not entirely understood.

“White matter undergoes profound changes throughout childhood and adolescence, playing a fundamental role for the development of the normal cognition and behavior,” the authors wrote. “In recent years, diffusion tensor imaging (DTI) is an effective tool for investigating the microstructural properties of white matter. Developmental changes in diffusion measures reflect the maturation processes, such as myelination, increased axonal size and axonal packing, all of which coincide with emerging cognitive abilities and behavior.”

The Study

In the study, the investigators used a data-drive multivariate approach among a population of 130 pediatric patients, 62 of which were diagnosed with ADHD. The remaining 68 participants did not have ADHD but were matched based on age and sex.

The team employed regularized generalized canonical correlation analysis to characterize the associations between white matter and a comprehensive set of clinical measures covering 3 domains, including symptoms, cognition, and behavior.

The investigators used Conners' Parent Rating Scale (CPRS) to characterize ADHD symptom based on parental reports and Child Behavior Checklist (CBCL) to assess comprehensive behavior problems.

They then applied linear discriminant analysis to integrate the identified associations to further explore potential developmental effects.

Results

Each domain had a delineated 2 brain-behavioral dimensional association resulting in 6 multivariate patterns of white matter microstructural alterations linked to hyperactivity—impulsivity and mild affected, executive functions and working memory, and externalizing behavior and social withdrawal, respectively.

While executive function and externalizing behavior share similar white matter patterns, the other dimensions linked to a specific pattern of white matter microstructural alterations.

In addition, multivariate dimensional association scores resulted in an overall increase and normalization with age in the ADHD. This remained stable in controls.

“We found multivariate neurobehavioral associations exist across ADHD and controls, which suggested that multiple white matter patterns underlie ADHD heterogeneity and provided neural bases for more precise diagnosis and individualized treatment,” the authors wrote.

Limitations

There were several limitations associated with the study. For example, the generalizability of the study needs to be examined in larger samples with independent datasets.

Another limitation is because development and alterations of different brain tissue types may not occur separately, integrating different imaging modalities should be considered to better understand the interplay among variations of grey matter, white matter microstructure, and functional activity.

Other limitations were from the interpretation of DTI results because underestimating FA in crossing, diverging, or converging fibers, potential head motion, microstructural alterations presented before or after the disorder. The final limitation was due to the structure of the study.

The study, “Multivariate associations between behavioral dimensions and white matter across children and adolescents with and without attention-deficit/hyperactivity disorder,” was published online in the Journal of Child Psychology and Psychiatry.