Decreased frontostriatal microstructural organization in attention deficit/hyperactivity disorder

Abstract

Frontostriatal brain areas have been implicated in the neurobiology of attention deficit/hyperactivity disorder (ADHD), but little work has directly addressed the white matter connections between these regions. The present study investigates the microstructural organization and myelination of frontostriatal white matter in children with ADHD and controls. Diffusion tensor imaging and magnetization transfer imaging scans were acquired in 30 children with ADHD and 34 controls. A study specific volume of interest (VOI) of frontostriatal white matter was created using a tractography based statistical group map. Fractional anisotropy (FA, indexing microstructural organization) and magnetization transfer ratio (MTR, indexing macromolecular content, myelin in particular) were computed for the frontostriatal VOI and for total cerebral white matter. Exploratory analyses were conducted investigating the effect of stimulant use on these measures. Frontostriatal FA but not MTR was decreased in ADHD compared with controls. There were no differences in FA or MTR for total cerebral white matter. Frontostriatal FA correlated negatively with teacher-rated attention problems in controls but not children with ADHD. The duration of stimulant use did not affect the main results. Changes in frontostriatal connectivity in ADHD appear to be related to changes in microstructural organization rather than myelination per se. A correlation with attention problems for controls suggests that frontostriatal organization is relevant to ADHD-related behaviors.

Figure 1

The contribution to VOI is similar between groups, independent of the probability per voxel. On the X‐axis, bins are presented of probability of contribution to a voxel, the Y‐axis shows the voxel count per bin.

Figure 2

Frontostriatal tract selection and definition of the study specific volume of interest. (A) Individual frontostriatal tracts were defined in model space, using two regions of interest (striatum and prefrontal cortex); (B) A cumulative group map of individual binary frontostriatal maps was created; (C) The frontostriatal volume of interest in model space as defined by all voxels that include frontostriatal fibers in 60% or more of the individuals in the sample; (D) 3D rendering of the frontostriatal tracts (turquoise) and the frontostriatal VOI (red) for one subject in native space. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Figure 3

Frontostriatal microstructural organization is reduced in ADHD but myelination is not. The smaller insets show the results for the exploratory analyses on the short versus long medication treatment groups. ADHD: attention deficit/hyperactivity disorder (ADHD‐short: relatively short methylphenidate treatment; ADHD‐long: long duration of methylphenidate treatment); FA: fractional anisotropy; MTR: magnetization transfer ratio.

Figure 4

Frontostriatal microstructural organization is related to teacher‐rated attention problems for typically developing children but not for children with ADHD. Linear regression for typically developing children (solid black line) and for children with ADHD (dashed gray line). ADHD: attention deficit/hyperactivity disorder; FA: fractional anisotropy; TRF: teacher report form.