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.

Cortical morphology as a shared neurobiological substrate of attention-deficit/hyperactivity symptoms and executive functioning: a population-based pediatric neuroimaging study

“…Another potential explanation could be that these previous studies were performed in clinical populations, in whom symptoms are usually more severe and in whom there is a greater chance of referral bias. In line with the results of previous clinical studies, 38 we found attention-deficit/ hyperactivity symptoms to be associated with a thinner Both determinant (CBCL/NEPSY) and outcome (gyrification) were residualized for age during assessment/scanning. Analyses adjusted for child sex, nationality, gestational age at birth, birth weight, psychostimulant use, IQ, maternal education, drinking during pregnancy, smoking during pregnancy and household income.…”

“…Furthermore, we were able to correct for many confounding factors, including the use of psychostimulant medication. As psychostimulant use may alter brain structure 38 and influences cognitive functioning, 39,40 this is a very important potentially confounding factor to take into account. Although our ability to correct for many confounding factors may be considered a strength, it may have also led to some overcorrecting and attenuation of effects.…”

Real‐time fMRI neurofeedback in adolescents with attention deficit hyperactivity disorder

“…A meta‐analysis of 11 rtfMRI‐NF studies using 9 different ROIs, showed that, besides the trained ROIs, participants co‐activated a cognitive control network of bilateral fronto‐insular, striato‐thalamic and parieto‐temporal regions presumably mediating self‐regulation per se, independently of the self‐regulated region [Emmert et al, 2016]. These are key areas of ADHD underactivation [Cortese et al, 2012; Hart et al, 2012, 2013; Norman et al, 2016; Rubia, 2011, 2017; Rubia et al, 1999, 2005, 2014a] and overlap with regions of increased inhibition‐related activation after EEG‐ and EMG‐NF in ADHD [Baumeister et al, 2016], suggesting that fMRI‐NF induced neural self‐regulation may benefit ADHD children, independently of the target ROI. This would be in line with findings of comparable parent‐rated clinical ADHD improvements with different self‐regulation methods including near‐infrared spectroscopy (NIRS)‐NF, EMG‐NF, or EEG‐NF [Marx et al, 2014].…”

“…5B, Table 5). It is thus possible that the active group benefitted from trained rIFG‐striato‐insular activation increase, while the control group benefitted from trained activation increase in posterior visual‐spatial attention regions, which are connected to lPHG [Aminoff et al, 2013], and both of which are relevant to ADHD [Hart et al, 2012, 2013; Norman et al, 2016; Rubia, 2011, 2017; Rubia et al, 2014a]. Hence, both common and group‐specific underlying processes could have accounted for their clinical improvements.…”

“…The faster learning may be due to brain baroreceptors informing on blood flow but not on electrical activity [Dworkin, 1988; Thibault et al, 2016], and/or superior signal/contrast to noise ratio and superior spatial localization specificity of the fMRI signal. Furthermore, EEG‐NF cannot modulate activation in key underfunctioning regions in ADHD found in fMRI meta‐analyses, such as right inferior frontal gyrus (rIFG) or basal ganglia [Hart et al, 2013; Norman et al, 2016; Rubia, 2011, 2017; Rubia et al, 1999, 2005, 2008, 2014a]. rIFG in particular is a key hub region mediating functions that are compromised in ADHD like attention, inhibition, and timing [Hugdahl et al, 2015; Kim, 2014; Radua et al, 2014], and its activation correlates with behavioral impulsiveness [Rubia et al, 1999, 2005].…”