brainlife.io: a decentralized and open-source cloud platform to support neuroscience research.

Neuroscience is advancing standardization and tool development to support rigor and transparency. Consequently, data pipeline complexity has increased, hindering FAIR (findable, accessible, interoperable and reusable) access. brainlife.io was developed to democratize neuroimaging research. The platform provides data standardization, management, visualization and processing and automatically tracks the provenance history of thousands of data objects. Here, brainlife.io is described and evaluated for validity, reliability, reproducibility, replicability and scientific utility using four data modalities and 3,200 participants.

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.

Limited usefulness of neurocognitive functioning indices as predictive markers for treatment response to methylphenidate or neurofeedback@home in children and adolescents with ADHD.

Introduction: Earlier studies exploring the value of executive functioning (EF) indices for assessing treatment effectiveness and predicting treatment response in attention-deficit/hyperactivity disorder (ADHD) mainly focused on pharmacological treatment options and revealed rather heterogeneous results. Envisioning the long-term goal of personalized treatment selection and intervention planning, this study comparing methylphenidate treatment (MPH) and a home-based neurofeedback intervention (NF@Home) aimed to expand previous findings by assessing objective as well as subjectively reported EF indices and by analyzing their value as treatment and predictive markers. Methods: Children and adolescents (n = 146 in the per protocol sample) aged 7-13 years with a formal diagnosis of an inattentive or combined presentation of ADHD were examined. We explored the EF performance profile using the Conners Continuous Performance Task (CPT) and the BRIEF self-report questionnaire within our prospective, multicenter, randomized, reference drug-controlled NEWROFEED study with sites in five European countries (France, Spain, Switzerland, Germany, and Belgium). As primary outcome for treatment response, the clinician-rated ADHD Rating Scale-IV was used. Patients participating in this non-inferiority trial were randomized to either NF@home (34-40 sessions of TBR or SMR NF depending on the pre-assessed individual alpha peak frequency) or MPH treatment (ratio: 3:2). Within a mixed-effects model framework, analyses of change were calculated to explore the predictive value of neurocognitive indices for ADHD symptom-related treatment response. Results: For a variety of neurocognitive indices, we found a significant pre-post change during treatment, mainly in the MPH group. However, the results of the current study reveal a rather limited prognostic value of neurocognitive indices for treatment response to either NF@Home or MPH treatment. Some significant effects emerged for parent-ratings only. Discussion: Current findings indicate a potential value of self-report (BRIEF global score) and some objectively measured neurocognitive indices (CPT commission errors and hit reaction time variability) as treatment markers (of change) for MPH. However, we found a rather limited prognostic value with regard to predicting treatment response not (yet) allowing recommendation for clinical use. Baseline symptom severity was revealed as the most relevant predictor, replicating robust findings from previous studies.

brainlife.io: A decentralized and open source cloud platform to support neuroscience research.

Neuroscience research has expanded dramatically over the past 30 years by advancing standardization and tool development to support rigor and transparency. Consequently, the complexity of the data pipeline has also increased, hindering access to FAIR data analysis to portions of the worldwide research community. brainlife.io was developed to reduce these burdens and democratize modern neuroscience research across institutions and career levels. Using community software and hardware infrastructure, the platform provides open-source data standardization, management, visualization, and processing and simplifies the data pipeline. brainlife.io automatically tracks the provenance history of thousands of data objects, supporting simplicity, efficiency, and transparency in neuroscience research. Here brainlife.io's technology and data services are described and evaluated for validity, reliability, reproducibility, replicability, and scientific utility. Using data from 4 modalities and 3,200 participants, we demonstrate that brainlife.io's services produce outputs that adhere to best practices in modern neuroscience research.

Clinical and Experimental Factors Influencing the Efficacy of Neurofeedback in ADHD: A Meta-Analysis.

Meta-analyses have been extensively used to evaluate the efficacy of neurofeedback (NFB) treatment for Attention Deficit/Hyperactivity Disorder (ADHD) in children and adolescents. However, each meta-analysis published in the past decade has contradicted the methods and results from the previous one, thus making it difficult to determine a consensus of opinion on the effectiveness of NFB. This works brings continuity to the field by extending and discussing the last and much controversial meta-analysis by Cortese et al. (1). The extension comprises an update of that work including the latest control trials, which have since been published and, most importantly, offers a novel methodology. Specifically, NFB literature is characterized by a high technical and methodological heterogeneity, which partly explains the current lack of consensus on the efficacy of NFB. This work takes advantage of this by performing a Systematic Analysis of Biases (SAOB) in studies included in the previous meta-analysis. Our extended meta-analysis (k = 16 studies) confirmed the previously obtained results of effect sizes in favor of NFB efficacy as being significant when clinical scales of ADHD are rated by parents (non-blind, p-value = 0.0014), but not when they are rated by teachers (probably blind, p-value = 0.27). The effect size is significant according to both raters for the subset of studies meeting the definition of "standard NFB protocols" (parents' p-value = 0.0054; teachers' p-value = 0.043, k = 4). Following this, the SAOB performed on k = 33 trials identified three main factors that have an impact on NFB efficacy: first, a more intensive treatment, but not treatment duration, is associated with higher efficacy; second, teachers report a lower improvement compared to parents; third, using high-quality EEG equipment improves the effectiveness of the NFB treatment. The identification of biases relating to an appropriate technical implementation of NFB certainly supports the efficacy of NFB as an intervention. The data presented also suggest that the probably blind assessment of teachers may not be considered a good proxy for blind assessments, therefore stressing the need for studies with placebo-controlled intervention as well as carefully reported neuromarker changes in relation to clinical response.

Is there a cluster of high theta-beta ratio patients in attention deficit hyperactivity disorder?

OBJECTIVE: It has been suggested that there exists a subgroup of ADHD patients that have a high theta-beta ratio (TBR). The aim of this study was to analyze the distribution of TBR values in ADHD patients and validate the presence of a high-TBR cluster using objective metrics. METHODS: The TBR was extracted from eyes-open resting state EEG recordings of 363 ADHD patients, aged 5-21 years. The TBR distribution was estimated with three Bayesian Gaussian Mixture Models (BGMMs) with one, two, and three components, respectively. The pairwise comparison of BGMMs was carried out with deviance tests to identify the number of components that best represented the data. RESULTS: The two-component BGMM modeled the TBR values significantly better than the one-component BGMM (p-value = 0.005). No significant difference was observed between the two-component and three-component BGMM (p-value = 0.850). CONCLUSION: These results suggest that there exist indeed two TBR clusters within the ADHD population. SIGNIFICANCE: This work offers a global framework to understanding values found in the literature and suggest guidelines on how to compute theta-beta ratio values. Moreover, using objective data-driven method we confirm the existence of a high theta-beta ratio cluster.