Neurotherapeutics for Attention Deficit Hyperactivity Disorder (ADHD): a Review

Abstract

This review focuses on the evidence for neurotherapeutics for Attention Deficit Hyperactivity Disorder (ADHD). EEG-Neurofeedback has been tested for about 45 years with latest meta-analyses of randomised controlled trials (RCT) showing small/medium effects compared to non-active controls only. Three small studies piloted neurofeedback of frontal activations in ADHD using functional magnetic resonance imaging or near-infrared spectroscopy, finding no superior effects over control conditions. Brain stimulation has been applied to ADHD using mostly repetitive transcranial magnetic and direct current stimulation (rTMS/tDCS). rTMS has shown mostly negative findings on improving cognition or symptoms. Meta-analyses of tDCS studies targeting mostly dorsolateral prefrontal cortex show small effects on cognitive improvements with only two out of three studies showing clinical improvements. Trigeminal nerve stimulation has shown to improve ADHD symptoms with medium effect in one RCT. Modern neurotherapeutics are attractive due to their relative safety and potential neuroplastic effects. However, they need to be thoroughly tested for clinical and cognitive efficacy across settings and beyond core symptoms and for their potential for individualised treatment.

Transcranial Random Noise Stimulation combined with Cognitive Training for Treating ADHD: A Randomized, Sham-Controlled Clinical Trial

“…[37], [58]-[60]. In contrast, studies involving tDCS + CT in paediatric ADHD samples have not shown consistent results in reducing ADHD symptoms, and recent meta-analyses concluded that there is limited evidence of improvements in clinical symptoms [21], [23], [61]. However, these effects are strongly dependent on stimulation parameters [22], and future studies should examine the parameters that could yield bene cial effects using tDCS.…”

“…We further examined, for the rst time in ADHD, the effects of stimulation on resting-state (RS) neural activity. Abnormal RS-EEG oscillations have been documented in paediatric ADHD (e.g., [21], [32], [33]), potentially indicating a disorder of arousal [34] and unfocused states [35], [36]. It has been suggested that tRNS may improve the capacity for sustained attention in individuals with suboptimal cortical arousal, as indexed by reduction in theta/beta ratio [26] and may lead to alterations in the amplitude of neural markers related to attention and preparatory activity [37].…”

Optimizing spatial specificity and signal quality in fNIRS: an overview of potential challenges and possible options for improving the reliability of real-time applications

“…On the other hand, NFB focuses more on selfregulation of brain activity by providing feedback through sensory cues with the overall goal of improving cognitive functions or alleviating symptoms (Marzbani et al, 2016;Sitaram et al, 2017;Kohl et al, 2020;Soekadar et al, 2021). Accordingly, NFB is more commonly used in clinical settings, and research on this topic includes conditions such as ADHD (e.g., Hudak et al, 2018;Rubia et al, 2021), anxiety (e.g., Kimmig et al, 2019;Linhartová et al, 2019;Lipp and Cohen Kadosh, 2020), depression (e.g., Trambaiolli et al, 2021;González Méndez et al, 2022), stroke (e.g., Rieke et al, 2020;Sanders et al, 2022), and Parkinson's disease (e.g., Subramanian et al, 2011Subramanian et al, , 2016Mehler, 2022). Because of the methodological overlap, BCI and NFB probably cannot be considered as completely independent methods.…”