Neuroimaging and neurotherapeutics for Attention Deficit Hyperactivity Disorder (ADHD)

This paper reviews the functional magnetic resonance imaging (fMRI) literature of Attention Deficit Hyperactivity Disorder (ADHD) of the past three decades and the modern neurotherapies that have used these biomarkers as targets for treatment. Meta-analyses of task-based fMRI studies have shown functional abnormalities in different domain-dependent frontal, striatal, parietal, and cerebellar regions in ADHD. Resting state fMRI studies confirm abnormalities in different fronto-striato-parietal cognitive control, dorsal and ventral attention networks. The frontal parts of these networks have been targeted by neurotherapeutics. Only three small-numbered studies so far have applied functional near infrared spectroscopy (NIRS) and fMRI-Neurofeedback to ADHD. Studies have mostly shown feasibility and some promising effects on clinical, cognitive or imaging measures which invite further testing in larger samples. Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) or inferior frontal cortex (IFC) has not shown promising effects so far on improving cognition or symptoms. Eighteen studies tested the effects of single or multi-session transcranial direct current stimulation (tDCS) of mostly left DLPFC on mostly cognitive functions with fewer studies targeting right DLPFC or IFC. Our meta-analysis of tDCS studies shows relatively small effects of improvement of cognitive function while insufficient studies have tested clinical efficacy. A proof of concept study of trigeminal nerve stimulation (TNS) showed promising medium size effects for improving clinical symptoms but requires replication in larger samples. In conclusion, neurotherapies are attractive due to minimal side effects and potential longer-term effects on brain plasticity which drugs cannot offer; however, they are still in their infancy. They require systematic testing of optimal protocols in large samples, including optimal site of stimulation/neurofeedback, optimal frequency of treatment sessions, or optimal stimulation amplitude. Importantly, they will need to show potential for individualised treatment by providing understanding of treatment response prediction.