Diffusion tensor imaging provides new clues in adults with ADHD (Commentary on Konrad et al.)

Magnetic resonance imaging has provided an increasing number of methods for examining the structure and function of the human brain. Among these, Diffusion Tensor Imaging (DTI), first described by Basser et al. (1994), has filled an important niche in structural brain imaging. By quantifying the diffusivity of water molecules within white matter tracts, investigators can obtain indices of their microstructural integrity. Most dramatically, by taking advantage of the rotational invariance of DTI, researchers can perform tractography, i.e. constructing 3D models of the principal white matter tracts (Assaf & Pasternak, 2008). Despite the esthetic beauty of many such figures, the workhorse measures of DTI remain the voxel-wise indices of fractional anisotropy and mean diffusivity (White et al., 2008). In this current issue of EJN, Konrad et al. (2010) used DTI to examine white matter in a substantial sample (n = 37) of never-medicated adults with Attention-Deficit ⁄ Hyperactivity Disorder (ADHD). ADHD, which is characterized by behavioural symptoms of inattention, impulsivity and hyperactivity (American Psychiatric Association, 2000), is increasingly recognized as a disorder that affects individuals throughout the lifespan (Biederman et al., 2007). As expected (Casey et al., 2007; Makris et al., 2008), Konrad et al. (2010) found that patients with ADHD have reduced white matter fractional anisotropy in the right anterior cingulate bundle, and both reduced white matter fractional anisotropy and increased mean diffusivity in bilateral inferior frontoccipital fasciculus. The novel findings of DTI abnormalities in the inferior frontoccipital fasciculus highlight the role of the orbitofrontal cortex in adult ADHD, complementing previous anatomic results (Hesslinger et al., 2002; Makris et al., 2007). Furthermore, DTI indices correlated in the expected directions with objective measures of attention (TOVA ADHD score), impulsivity (TOVA commission errors) and total ADHD symptomatology (Brown Attention Deficit Disorder Scale). In contrast, Konrad et al. (2010) also found increased white matter fractional anisotropy in bilateral temporal inferior frontoccipital fasciculus and in the uncinate fasciculus in the ADHD group. They speculate that these results may indicate fewer crossing fibers in the patients with ADHD, as white matter fractional anisotropy measures are highly sensitive to such crossings or to the splaying of white matter tracts as they terminate in gray matter structures. The authors are to be congratulated on their rigorous standards for inclusion in the study which allow them to exclude the possibility of confounding by medication effects or from comorbidity. The cost of such rigor was an extended recruitment period, and the use of earlier albeit adequate DTI methods. The authors also acknowledge that their results would not have survived correction for multiple comparisons, and point out that the only prior voxel-wise DTI study in ADHD (Ashtari et al., 2005) also reported uncorrected statistical values. Publication of tentative results is necessary early in the development of any literature but such results must be interpreted with caution pending definitive replications appropriately corrected for multiple comparisons. Otherwise, differentiating false positives from true results will remain a challenge to the field (Rossi, 1990). We look forward to the continued advances of diffusion-based approaches (Hagmann et al., 2007) in parallel with the recent emergence of functional connectivity methods that appear to be particularly amenable to large-scale data aggregation (Biswal et al., 2010). These techniques join the multiplicity of magnetic resonance methods that can now be brought to bear on clinical questions, i.e. standard volumetric analyses, cortical thickness measures, magnetic resonance spectroscopy and traditional task-based functional neuroimaging methods. Thus, one may reasonably conclude that we are now embarking on the true Decade of the Brain.