Personalized at-home neurofeedback compared to long-acting methylphenidate in children with ADHD: NEWROFEED, a European randomized noninferiority trial.

BACKGROUND: Neurofeedback is considered a promising intervention for the treatment of attention-deficit hyperactivity disorder (ADHD). NEWROFEED is a prospective, multicentre, randomized (3:2), reference drug-controlled trial in children with ADHD aged between 7 and 13 years. The main objective of NEWROFEED was to demonstrate the noninferiority of personalized at-home neurofeedback (NF) training versus methylphenidate in the treatment of children with ADHD. METHODS: The NF group (n = 111) underwent eight visits and two treatment phases of 16 to 20 at-home sessions with down-training of the theta/beta ratio (TBR) for children with high TBR and enhancing the sensorimotor rhythm (SMR) for the others. The control group (n = 67) received optimally titrated long-acting methylphenidate. The primary endpoint was the change between baseline and endpoint in the Clinician ADHD-RS-IV total score in the per-protocol population (90 NF/59 controls). TRIAL REGISTRATION: US National Institute of Health, ClinicalTrials.gov #NCT02778360. RESULTS: Our study failed to demonstrate noninferiority of NF versus methylphenidate (mean between-group difference 8.09 90% CI [8.09; 10.56]). However, both treatment groups showed significant pre-post improvements in core ADHD symptoms and in a broader range of problems. Reduction in the Clinician ADHD-RS-IV total score between baseline and final visit (D90) was 26.7% (SMD = 0.89) in the NF and 46.9% (SMD = 2.03) in the control group. NF effects increased whereas those of methylphenidate were stable between intermediate and final visit. CONCLUSIONS: Based on clinicians' reports, the effects of at-home NF were inferior to those of methylphenidate as a stand-alone treatment.

Personalized at-home neurofeedback compared with long-acting methylphenidate in an european non-inferiority randomized trial in children with ADHD.

BACKGROUND: Neurofeedback (NF) has gained increasing interest among non-pharmacological treatments for Attention Deficit Hyperactivity Disorder (ADHD). NF training aims to enhance self-regulation of brain activities. The goal of the NEWROFEED study is to assess the efficacy of a new personalized NF training device, using two different protocols according to each child's electroencephalographic pattern, and designed for use at home. This study is a non-inferiority trial comparing NF to methylphenidate. METHODS: The study is a prospective, multicentre, randomized, reference drug-controlled trial. One hundred seventy-nine children with ADHD, aged 7 to 13 years will be recruited in 13 clinical centres from 5 European countries. Subjects will be randomized to two groups: NF group (Neurofeedback Training Group) and MPH group (Methylphenidate group). Outcome measures include clinicians, parents and teachers' assessments, attention measures and quantitative EEG (qEEG). Patients undergo eight visits over a three-month period: pre-inclusion visit, inclusion visit, 4 "discovery" (NF group) or titration visits (MPH group), an intermediate and a final visit. Patients will be randomized to either the MPH or NF group. Children in the NF group will undergo either an SMR or a Theta/Beta training protocol according to their baselineTheta/Beta Ratio obtained from the qEEG. DISCUSSION: This is the first non-inferiority study between a personalized NF device and pharmacological treatment. Innovative aspects of Mensia Koala™ include the personalization of the training protocol according to initial qEEG characteristics (SMR or Theta/Beta training protocols) and an improved accessibility of NF due to the opportunity to train at home with monitoring by the clinician through a dedicated web portal. TRIAL REGISTRATION: NCT02778360 . Date registration (retrospectively registered): 5-12-2016. Registered May 19, 2016.

Alpha-phase synchrony EEG training for multi-resistant chronic low back pain patients: an open-label pilot study.

PURPOSE: Chronic low back pain (cLBP) affects a quarter of a population during its lifetime. The most severe cases include patients not responding to interventions such as 5-week-long in-hospital multi-disciplinary protocols. This document reports on a pilot study offering an alpha-phase synchronization (APS) brain rehabilitation intervention to a population of n = 16 multi-resistant cLBP patients. METHODS: The intervention consists of 20 sessions of highly controlled electroencephalography (EEG) APS operant conditioning (neurofeedback) paradigm delivered in the form of visual feedback. Visual analogue scale for pain, Dallas, Hamilton, and HAD were measured before, after, at 6-month and 12-month follow-up. Full-scalp EEG data were analyzed to study significant changes in the brain's electrical activity. RESULTS: The intervention showed a great and lasting response of most measured clinical scales. The clinical improvement was lasting beyond the 6-month follow-up endpoints. The EEG data confirm that patients did control (intra-session trends) and learned to better control (intersession trends) their APS neuromarker resulting in (nonsignificant) baseline changes in their resting state activity. Last and most significantly, the alpha-phase concentration (APC) neuromarker, specific to phase rather than amplitude, was found to correlate significantly with the reduction in clinical symptoms in a typical dose-response effect. CONCLUSION: This first experiment highlights the role of the APC neuromarker in relation to the nucleus accumbens activity and its role on nociception and the chronicity of pain. This study suggests APC rehabilitation could be used clinically for the most severe cases of cLBP. Its excellent safety profile and availability as a home-use intervention makes it a potentially disruptive tool in the context of nonsteroidal anti-inflammatory drugs and opioid abuses. These slides can be retrieved under Electronic Supplementary Material.