Imaging the ADHD brain: disorder-specificity, medication effects and clinical translation

Abstract

A plethora of magnetic resonance imaging studies have shown that ADHD is characterized by multiple functional and structural neural network abnormalities beyond the classical fronto-striatal model, including fronto-parieto-temporal, fronto-cerebellar and even fronto-limbic networks. There is evidence for a maturational delay in brain structure development which likely extends to brain function and structural and functional connectivity, but this needs corroboration by longitudinal imaging studies. Dysfunction of the ventrolateral prefrontal cortex seems to be more pronounced relative to other pediatric disorders and is also the most consistent target of acute psychostimulant medication. Future studies are likely to focus on using neuroimaging for clinical translation such as for individual diagnostic and prognostic classification and as a neurotherapy to reverse brain function abnormalities.

Keywords::

• atomoxetine
• attention deficit hyperactivity disorder
• autism spectrum disorder
• bipolar disorder
• conduct disorder
• diffusion tensor imaging
• functional magnetic resonance imaging
• methylphenidate
• MRI
• obsessive-compulsive disorder
• psychostimulants

Acknowledgements

We thank Joaquim Radua for help with one of the Figures.

Financial & competing interests disclosure

KR has received research support from Lilly Pharmaceuticals and speaker’s honoraria from Lilly, Medice and Novartis. KR received support from the National Institute of Health Research (NIHR) Biomedical Research Centre (BRC) for Mental Health at South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, Kings College London and Lilly Pharmaceuticals. Dr Helen Brinson received post-doctoral support from Action Medical Research. Ms Alegria was supported by an Institute of Psychiatry PhD excellence award. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Attention deficit hyperactivity disorder (ADHD) is characterized by a delay in brain structure maturation which possibly extends to brain function and structural and functional connectivity.

• ADHD is most prominently associated with the dysmorphology, dysfunction and underconnectivity of multiple fronto-striatal, fronto-parietal and fronto-cerebellar networks that mediate ‘cool’ executive functions.

• Executive function deficits appear to be associated with both poor activation of task-relevant fronto-striato-cerebellar systems and with poor deactivation of the default mode network.

• There is evidence that inferior prefrontal activation deficits may be more pronounced in ADHD relative to other childhood disorders such as conduct, obsessive–compulsive and bipolar disorder.

• A meta-analysis shows that acute stimulant medication most consistently increases the activation of the right inferior frontal cortex and the striatum in ADHD which it also normalizes in their underfunctioning relative to controls.

• Meta-regression analyses and retrospective comparisons between medicated and nonmedicated ADHD patients showed that long-term stimulant medication appears to be associated with abnormally high dopamine transporter levels, but with more normal brain structure, which need to be corroborated in longitudinal prospective studies.

• Future studies will focus on using neuroimaging for clinical translation, for example, to predict individual diagnostic or prognostic classification or as a neurotherapy to remediate the brain function abnormalities via neurofeedback or neurostimulation.

Notes