Cognitive Neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) and Its Clinical Translation.

Katya Rubia

doi:10.3389/fnhum.2018.00100

Abstract

This review focuses on the cognitive neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) based on functional magnetic resonance imaging (fMRI) studies and on recent clinically relevant applications such as fMRI-based diagnostic classification or neuromodulation therapies targeting fMRI deficits with neurofeedback (NF) or brain stimulation. Meta-analyses of fMRI studies of executive functions (EFs) show that ADHD patients have cognitive-domain dissociated complex multisystem impairments in several right and left hemispheric dorsal, ventral and medial fronto-cingulo-striato-thalamic and fronto-parieto-cerebellar networks that mediate cognitive control, attention, timing and working memory (WM). There is furthermore emerging evidence for abnormalities in orbital and ventromedial prefrontal and limbic areas that mediate motivation and emotion control. In addition, poor deactivation of the default mode network (DMN) suggests an abnormal interrelationship between hypo-engaged task-positive and poorly “switched off” hyper-engaged task-negative networks, both of which are related to impaired cognition. Translational cognitive neuroscience in ADHD is still in its infancy. Pattern recognition analyses have attempted to provide diagnostic classification of ADHD using fMRI data with respectable classification accuracies of over 80%. Necessary replication studies, however, are still outstanding. Brain stimulation has been tested in heterogeneously designed, small numbered proof of concept studies targeting key frontal functional impairments in ADHD. Transcranial direct current stimulation (tDCS) appears to be promising to improve ADHD symptoms and cognitive functions based on some studies, but larger clinical trials of repeated stimulation with and without cognitive training are needed to test clinical efficacy and potential costs on non-targeted functions. Only three studies have piloted NF of fMRI-based frontal dysfunctions in ADHD using fMRI or near-infrared spectroscopy, with the two larger ones finding some improvements in cognition and symptoms, which, however, were not superior to the active control conditions, suggesting potential placebo effects. Neurotherapeutics seems attractive for ADHD due to their safety and potential longer-term neuroplastic effects, which drugs cannot offer. However, they need to be thoroughly tested for short- and longer-term clinical and cognitive efficacy and their potential for individualized treatment.

Highlights

Attention Deficit Hyperactivity Disorder (ADHD) is characterized by symptoms of age-inappropriate inattention, hyperactivity and impulsivity (American Psychiatric Association, 2000)
An older large meta-analysis that included 55 whole-brain functional magnetic resonance imaging (fMRI) studies of a range of executive functions (EFs), attention, reward and emotion processing tasks in 16 adult and 39 pediatric studies, found reduced activation in 741 ADHD patients relative to 801 controls in different functional brain systems, including the bilateral ventral attention system (IFC, basal ganglia) and predominantly right hemispheric fronto-temporo-parietal cognitive control networks, including dorsolateral prefrontal cortex (DLPFC)/inferior prefrontal cortex (IFC), basal ganglia, thalamus, anterior cingulate cortex (ACC) and supplementary motor area (SMA) (Cortese et al, 2012), which overlap with the findings of the above reviewed task-domain specific meta-analyses (Hart et al, 2012, 2013; McCarthy et al, 2014; Lei et al, 2015; Norman et al, 2016)
The findings suggest that Transcranial direct current stimulation (tDCS) over different prefrontal regions may be necessary to improve the range of cognitive functions that are impaired in ADHD