Transcranial direct current stimulation and the theta beta ratio in the context of the attention deficit hyperactivity disorder and pediatric neuropsychiatry.

Background: Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental condition worldwide. Transcranial direct current stimulation (tDCS) is a potential novel treatment option for ADHD. tDCS is widely used in adults, but disproportionately understudied in children. This thesis aimed to investigate the safety, tolerability, and acceptability of tDCS via a systematic review, a randomized, double-blind, placebo-controlled trial (RCT) in children and adults, and a qualitative acceptability study. Finally, tDCS treatment of ADHD could be optimized by using electroencephalography (EEG) and targeting a biomarker such as the theta-beta ratio (TBR). Since TBR remains controversial we aimed to test its validity. Methods: In the first study, a systematic review of tDCS safety in youth was conducted focusing on adverse effects and cognitive/neuroimaging/neuropsychiatric outcomes. In the second study, 60 participants (30 children aged 6-17 and 30 adults 18-45) received 10 minutes of tDCS twice, separated by a 1-hour interval. The stimulation amperage (sham, 0.5mA, 1mA, and 2mA), and anode/cathode locations were randomized. The researcher conducting the outcome measures (at all 6 time points) and the participant were blinded to the amperage. In the third study, parents of 14 children who participated in the second study were interviewed regarding the acceptability/desirability/feasibility of tDCS compared to medication for their child. The fourth study used EEG and derived statistical and machine learning models to test the validity of TBR thresholds in a sample of healthy controls evaluated for ADHD (n=189). Results: There were no serious adverse events reported across 1067 sessions in 156 children from 12 studies nor did any participants report any serious adverse effects in the randomized controlled trial. Moreover, children tolerated tDCS in a similar manner as adults. Parents find tDCS safe and acceptable and prefer it as an alternative to stimulant medication. The lack of side effects was important for acceptability. TBR thresholds appear to be unrelated to ADHD. Conclusion: tDCS is safe, tolerable, and acceptable to use in pediatric neuropsychiatry and there is a demand for clinically available tDCS especially in patients who are medication-resistant. The TBR threshold lacks clinical relevance and needs to be reconsidered in ADHD.