Australian researchers have applied a new analytical method for brain imaging in the study of children with attention deficit hyperactivity disorder (ADHD), offering better insight into how their brains diverge from those of children without the disorder.

The researchers focused on differences in white matter, made up of long nerve cells protected by fatty, insulating myelin, which helps the nerves relay signals faster. "We have been able to model the many different directions in which white matter pathways go in the brain and obtain more specific measures relating to their organization," Ian Fuelscher, a senior lecturer in the Cognitive Neuroscience unit of the School of Psychology at Deakin University and lead author of the study, published March 3 in Cortex, told The Academic Times. 

"Our key finding is that children with a history of ADHD may have altered white matter organization — possibly indicating a reduced ability to relay information — along communication pathways that are important for cognition and movement relative to children without a history of ADHD," Fuelscher said. 

The research was made possible by fixel-based analysis. Fixels represent individual populations of fibers inside voxels, the 3D pixels that form the building blocks of brain imaging. Fixel-based analysis is an alternative to fractional anisotropy, which pinpoints white matter by measuring the movement of water molecules in the brain. Unlike fractional anisotropy, which generates an average for every voxel, fixel-based analysis can detect where white matter fibers cross each other in a voxel. Like railways, highways, and surface streets in a bustling city, they cross each other frequently.

"Research has shown that up to 90% of white matter voxels contain crossing fibers," Fuelscher said. "That is, most voxels contain several fiber populations that run in distinct directions." 

Fuelscher explained that this makes it hard to interpret fractional anisotropy scores. While a lower score could mean that there are fewer white matter fibers in a voxel, it could also mean that there is less myelin insulating each fiber. 

In the paper, the authors highlighted ambiguous findings on white matter in the corpus callosum, which connects the left and right hemispheres of the brain. With a little help from fixel-based analysis, the researchers steered clear of these issues.

The team looked at magnetic resonance imaging (MRI) of 144 children between the ages of 9 and 11. Seventy-six children had a history of ADHD; 68 did not. The team found that white matter fibers were less dense in several regions of the brains of children with ADHD, which could mean that white matter connectivity is lower in those areas. In one region involved in motor control — the left frontopontine tract — higher symptom severity correlated with lower fiber density. In other words, children with more severe ADHD had less dense white matter in that area.

"The findings help to understand what and where the brain changes are that may give rise to the presentation of ADHD symptoms," Fuelscher explained. "For example, the structural organization of tracts that connect to the supplementary motor area may help explain some of the motor difficulties commonly observed in ADHD. These difficulties include excessive motor overflow (unintentional movements that accompany voluntary movements) and impaired response inhibition (the ability to inhibit a planned movement). However, further work with behavioral and clinical data is essential before we can draw firm conclusions about the clinical relevance of our findings."

Interestingly, although some study participants were medicated at the time of imaging, that treatment did not alter their white matter profiles. "This study was not designed to investigate the effects of medication," Fuelscher noted.

"Our analysis method is well placed to model the many different directions in which white matter pathways go in the brain and allows us to obtain more specific measures relating to their organization," he said. "However, many of the brain's communication pathways funnel together along substantial proportions of their length, and we can't always be certain which pathway is involved."

Fuelscher hopes others can replicate the research team's findings. He also wants to understand why and how the white matter differences that he observed develop over time. "This knowledge will provide valuable insight into whether the observed brain differences between children with and without ADHD represent specific brain abnormalities characteristic of ADHD or a delay of normal development," he explained, adding that his field needs more large longitudinal datasets to track children with and without ADHD over time. The cohort in this study came from the Children's Attention Project.

Yet even as brain imaging and computational modeling continue to improve, Fuelscher does not think clinicians will use magnetic resonance imaging to diagnose ADHD anytime soon.

"Rather than using MRI as a diagnostic tool, for now the value of this technique is that it can assist researchers in examining the effect that pharmacological and/or nonpharmacological treatments for ADHD have on the brain, including the brain's white matter," he explained. "This knowledge is important for the design of targeted and effective treatments for children with ADHD."

The paper, "White matter tract signatures of fiber density and morphology in ADHD," published March 3 in Cortex, was authored by Ian Fuelscher and Christian Hyde, Deakin University; Vicki Anderson, Murdoch Children's Research Institute and the Royal Children's Hospital; and Timothy J. Silk, Deakin University and the Murdoch Children's Research Institute.