¹King's College London, Institute of Psychiatry, Psychology & Neuroscience, London, United Kingdom, ²King's College London, Child & Adolescent Psychiatry, London, United Kingdom, ³University of Southampton, School of Psychology, Southampton, United Kingdom

Background: Stimulant medications are effective for ADHD. However, they have side effects, unknown longer-term effects, poor adherence and are not preferred by children and their parents. Brain modulation has been suggested as a promising non-drug treatment alternative for ADHD as it can target the brain differences established over the last 3 decades of our fMRI studies with minimal and transient side effects.

Aims & Objectives: We conducted several RCTs of novel neurotherapies for ADHD aimed to modify ADHD relevant brain activation differences with the aim to imrpove associated clinical behaviours and cognitive performance. We conducted two RCTs of fMRI-Neurofeedback of right inferior frontal cortex in children and adolescents with ADHD, two RCTs of transcranial direct current stimulation (tDCS) in children and adults with ADHD, targeting right inferior and dorsolateral prefrontal cortex, respectively, and a large multicenter RCT of trigeminal nerve stimulation (TNS) in children and adolescents with ADHD.

Method: TNS received clearance by the FDA as the only device-based non-drug treatment for ADHD based on a pilot RCT that found improvement of ADHD symptoms with medium effect size in 62 children with ADHD. However, a limitation was a very weak placebo condition with no stimulation in the control group. We conducted a confirmatory multi-centre, double-blind, randomized, and rigorously sham-controlled, phase 2b RCT investigating short and longer-term efficacy (6 months) of real vs sham eTNS in 150 children with ADHD. Bilateral stimulation of V1 trigeminal nerve branches - thought to innervate the brainstem and from there in a bottom-up manner other frontal and thalamic regions -was provided through battery powered electrodes applied to participants’ forehead every night for 8 hours for 4 weeks with sham eTNS providing 30s stimulation every hour only. We tested improvement in a wide range of ADHD-relevant clinical and cognitive measures, as well as in objective measures of hyperactivity and arousal and mechanistic effects in fMRI.

Results: fMRI-NF training showed relevant changes in right and left inferior frontal cortex, but this did not translate into clinical or cognitive benefits (Alegria et al., 2017, Lam et al., 2022). tDCS shows no effects in children and adults after 14/15 sessions (Westwood et al., 2023), but large clinical benefits in attention in adults with ADHD after 28 sessions (Leffa et al., 2022). The TNS trial was overall successful, with over 93% adherence, compliance and retention, excellent safety and successful blinding. However, TNS showed no clinical or cognitive effects for ADHD children after 4 weeks or 6 months (Conti et al., 2026).

Discussion & Conclusions: While tDCS shows efficacy for the treatment of attention symptom in adults with ADHD, fMRI-NF and TNS do not seem to be promising treatments for children with ADHD. Our findings show the importance of controlling for the "neuroenchantment" effect, which is particularly high with brain technologies which participants expect to normalise the brain differences which are underlying their atypical behaviours. They also highlight the importance of conducting large rigorous trials so that families and clinicians don’t waste their time and money on non-effective treatments for ADHD and researchers can focus on those that work.