Diffusion tensor imaging uncovers several keys to ADHD

The disruption of dopamine transportation in brain white matter may be the underlying reason that children suffer from attention-deficit/hyperactivity disorder, or ADHD. In addition, MR diffusion tensor imaging suggests that drug therapy repairs the damaged fiber bundles indicated in ADHD pathology.

The results of two decades of imaging ADHD with structural and functional MRI indicate involvement of the right frontal lobe and the cerebellum. Most of these studies, however, are macroscopic in nature, measuring whole-brain volumetric differences - specifically, in white matter.

Researchers have for the first time used diffusion tensor imaging (DTI) to examine white-matter fibers in children with ADHD. Their results may indicate the underlying mechanism for the previous volumetric findings.

Mansar Ashtari, Ph.D., and colleagues at North Shore-Long Island Jewish Health System used 25-direction DTI to image 18 patients with a diagnosis of ADHD and 15 normal controls.

DTI measures water motion between axons in white matter. Normal myelination of fiber bundles helps restrict water flow to one direction, also called anisotropy. Damaged fibers allow water to flow with less restriction, or isotropically. DTI assigns anisotropic values to fiber bundles, reflecting the integrity of axonal myelination, Ashtari said.

The most significant areas of difference between ADHD patients and controls as measured by their fractional anisotropy were the right pre-motor, anterior limb of the right internal capsule, right cerebral peduncles, left middle cerebellar peduncle, left cerebellum, and left parietooccipital area.

An unexpected finding was brain stem involvement in the ADHD patients. When Ashtari connected the all the areas affected, she was surprised to find they formed a known circuit called the cortocopontocerebellar.

Because of the involvement of the brain stem, which produces dopamine, Ashtari hypothesized that perhaps a disruption in the cortocopontocerebellar circuit would cause deficits of dopamine to multiple brain regions areas known to control attention and motor activities.

In another study, Ashtari and colleagues found that children who have been treated with stimulants have fewer areas of fractional anisotropy abnormalities than drug-naïve ADHD patients.

Researchers used DTI to image 10 children on stimulants and 10 children with ADHD not on drug therapy. Each group was matched with its own respective normal controls.

Compared with the patient on stimulants, the drug-naive cohort showed many more areas with lower fractional anisotropy, including the right midbrain, orbitofrontal, frontostriatal, cerebellum, bilateral temporal, cingulate, and bilateral optic radiation fiber bundles.

Fewer areas of fractional anisotropy abnormalities were present in the medicated group. These areas were limited to the bilateral pons and the bilateral prefrontal fiber bundles.

Other researchers have previously shown white-matter volume normalization in medicated ADHD patients. The white-matter microstructural abnormalities that can be detected by DTI may form the basis for macroscopic findings in volume reduction of white matter, Ashtari said.

While these findings are promising, they are preliminary, she said.

"I don't want people to run and medicate their children," Ashtari said.

For a more conclusive study, drug-naive ADHD patients would be medicated, followed over time, and then imaged again.