Periodic Reporting for period 4 - STIPED (Transcranial brain stimulation as innovative therapy for chronic pediatric neuropsychiatric disorder – STIPED)
Reporting period: 2021-07-01 to 2022-06-30
Chronic pediatric neuropsychiatric disorders (CPND), e.g. attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are highly prevalent, severely affecting patients, families, and society. Available treatment options exist but insufficiently improve associated behavioral impairments. Thus, new technological approaches targeting underlying mechanisms are required. STIPED aims at studying safety, dose-response relation, mechanisms, and treatment effects of transcranial direct-current stimulation (tDCS) in underage CPND patients. TDCS is an innovative non-invasive neuromodulation technique applying low-amplitude direct currents to the brain via surface electrodes on the scalp. During the last 5 and a half years, STIPED focused on the following objectives:
-Testing tDCS effects on neurocognitive and behavioral impairments and studying tolerability in under-age patients with ADHD/ASD (WP4, WP5, WP9)
-Identifying attitudes and intentions towards tDCS in patients, parents, health care providers, and teachers and investigating individual benefit-risk-ratios from an ethical perspective (WP2)
-Improving tDCS effects through personalized application (WP3, WP6) by determining its influence on brain development
-Flexible integration of tDCS into clinical routine with a pipeline for home application (WP8)
-Establishing biomarkers to disentangle individuals’ phenotypic heterogeneity and identify biologically homogeneous subgroups/strata of patients expected to respond well to tDCS (WP6, WP7)
-Establishing a comprehensive framework to disseminate and utilize STIPED outcomes and technology (WP10)
STIPED performed were five randomized, double-blind sham-controlled clinical trials in which young ADHD and ASD patients as well as healthy individuals were included. These trials each targeted a specific brain region involved in ADHD or ASD. Additionally, innovative technological progress was made in the form of an easy-to-use, home-based tDCS system that can be remotely supervised and applied by caregivers.
-Testing tDCS effects on neurocognitive and behavioral impairments and studying tolerability in under-age patients with ADHD/ASD (WP4, WP5, WP9)
-Identifying attitudes and intentions towards tDCS in patients, parents, health care providers, and teachers and investigating individual benefit-risk-ratios from an ethical perspective (WP2)
-Improving tDCS effects through personalized application (WP3, WP6) by determining its influence on brain development
-Flexible integration of tDCS into clinical routine with a pipeline for home application (WP8)
-Establishing biomarkers to disentangle individuals’ phenotypic heterogeneity and identify biologically homogeneous subgroups/strata of patients expected to respond well to tDCS (WP6, WP7)
-Establishing a comprehensive framework to disseminate and utilize STIPED outcomes and technology (WP10)
STIPED performed were five randomized, double-blind sham-controlled clinical trials in which young ADHD and ASD patients as well as healthy individuals were included. These trials each targeted a specific brain region involved in ADHD or ASD. Additionally, innovative technological progress was made in the form of an easy-to-use, home-based tDCS system that can be remotely supervised and applied by caregivers.
In 66 months STIPED achieved the following:
WP2: Semi-structure interviews were performed with young healthy and ADHD subjects and their parents. The interviews revealed high acceptance of tDCS. Next to financial incentives, main motives to participate were curiosity and the possibility to help develop treatments for children affected by neurological disorders. Additionally, WP2 provided positive internal ethics support at each stage of the project.
WP3:The data analysis for part 1 of this study was completed. The study demonstrates limited but clear transfer effects of tDCS targeting left Dorsolateral Prefrontal Cortex (DLPFC) and right Inferior Frontal Gyrus (IFG) in children and adolescents. Because of pandemic, the recruitment for part 2 of OptiStim, which focused on the personalized stimulation, was finished in March 2022. The data analysis will be completed till the end of 2022. The automated pipeline generating finite element head meshes from Magnetic Resonance Imaging (MRI) data and producing an individual model of electrical field distribution with suggestions concerning electrode montages and current intensity for individual stimulation was completed and tested in healthy subjects and patients.
WP4:Data processing for the EStimADHD study was finished, the data analysis of ADHDStimHome study is ongoing. Recruitment was significantly affected by COVID-19 pandemic. tDCS was well tolerated. EStimADHD first results: the montage used to target the rIFG seems to be promising to alter ADHD related neuropsychological impairments and to positively affect ADHD symptom load. ADHDStimHome first results: study shows a high participant satisfaction with support, as well as with a guideline-compliant user training. Recommendations for application of tDCS at home were developed.
WP5:Recruitment for StimAT finished in October 2021. The trial was also affected by COVID-19-related closures of recruitment sites and responsible authorities. tDCS was well tolerated in ASD patients. The data analysis is ongoing.
WP6:Using an unsupervised clustering approach, Starlab demonstrated that it is possible to stratify subjects based on their Electroencephalogram (EEG) profile before anodal tDCS intervention: members of particular clusters demonstrated a significant improvement in symptom severity following tDCS. Using measures of neuroanatomy, University of Frankfurt revealed inter-individual differences in response to tDCS, which are mediated by neuroanatomical differences in several large-scale neuro-cognitive networks that also include brain areas outside the stimulated regions. Measures of surface area were more closely related to the individuals’ response to tDCS than measures of cortical thickness.
WP7:UC has published substantial work on connectivity analyses and is already processing and analysing EEG and fMRI datasets. The first results regarding fMRI showed some features that seem to distinguish functional connectivity between groups (HC, ADHD, and ASD). Concerning EEG analysis, specific EEG patterns were identified to demonstrate tDCS effects in ADHD and ASD.
WP8:Pipeline for tDCS home application was developed. A wireless EEG-tDCS stimulator for home/non-clinical environments was constructed. A fail-safe electrode-positioning headset was designed. Home software to supervise tDCS at home, incl. EEG metrics of ADHD characterization (WP6) was developed and validated.
WP9:Data monitoring was finished, data analysis plans for all five clinical trials were developed, first statistical data analyses with primary and secondary outcome measures were conducted.
WP10:This WP focused on promotion (website, social media, press release, project newsletter, project flyers) of the STIPED consortium. New results of STIPED were presented during national and international scientific meetings. Finally, a first international meeting on non-invasive brain stimulation in children and adolescents took place in Barcelona at the end of Mai 2022.
WP2: Semi-structure interviews were performed with young healthy and ADHD subjects and their parents. The interviews revealed high acceptance of tDCS. Next to financial incentives, main motives to participate were curiosity and the possibility to help develop treatments for children affected by neurological disorders. Additionally, WP2 provided positive internal ethics support at each stage of the project.
WP3:The data analysis for part 1 of this study was completed. The study demonstrates limited but clear transfer effects of tDCS targeting left Dorsolateral Prefrontal Cortex (DLPFC) and right Inferior Frontal Gyrus (IFG) in children and adolescents. Because of pandemic, the recruitment for part 2 of OptiStim, which focused on the personalized stimulation, was finished in March 2022. The data analysis will be completed till the end of 2022. The automated pipeline generating finite element head meshes from Magnetic Resonance Imaging (MRI) data and producing an individual model of electrical field distribution with suggestions concerning electrode montages and current intensity for individual stimulation was completed and tested in healthy subjects and patients.
WP4:Data processing for the EStimADHD study was finished, the data analysis of ADHDStimHome study is ongoing. Recruitment was significantly affected by COVID-19 pandemic. tDCS was well tolerated. EStimADHD first results: the montage used to target the rIFG seems to be promising to alter ADHD related neuropsychological impairments and to positively affect ADHD symptom load. ADHDStimHome first results: study shows a high participant satisfaction with support, as well as with a guideline-compliant user training. Recommendations for application of tDCS at home were developed.
WP5:Recruitment for StimAT finished in October 2021. The trial was also affected by COVID-19-related closures of recruitment sites and responsible authorities. tDCS was well tolerated in ASD patients. The data analysis is ongoing.
WP6:Using an unsupervised clustering approach, Starlab demonstrated that it is possible to stratify subjects based on their Electroencephalogram (EEG) profile before anodal tDCS intervention: members of particular clusters demonstrated a significant improvement in symptom severity following tDCS. Using measures of neuroanatomy, University of Frankfurt revealed inter-individual differences in response to tDCS, which are mediated by neuroanatomical differences in several large-scale neuro-cognitive networks that also include brain areas outside the stimulated regions. Measures of surface area were more closely related to the individuals’ response to tDCS than measures of cortical thickness.
WP7:UC has published substantial work on connectivity analyses and is already processing and analysing EEG and fMRI datasets. The first results regarding fMRI showed some features that seem to distinguish functional connectivity between groups (HC, ADHD, and ASD). Concerning EEG analysis, specific EEG patterns were identified to demonstrate tDCS effects in ADHD and ASD.
WP8:Pipeline for tDCS home application was developed. A wireless EEG-tDCS stimulator for home/non-clinical environments was constructed. A fail-safe electrode-positioning headset was designed. Home software to supervise tDCS at home, incl. EEG metrics of ADHD characterization (WP6) was developed and validated.
WP9:Data monitoring was finished, data analysis plans for all five clinical trials were developed, first statistical data analyses with primary and secondary outcome measures were conducted.
WP10:This WP focused on promotion (website, social media, press release, project newsletter, project flyers) of the STIPED consortium. New results of STIPED were presented during national and international scientific meetings. Finally, a first international meeting on non-invasive brain stimulation in children and adolescents took place in Barcelona at the end of Mai 2022.
STIPED has an important impact for the scientific community, society, and EU. Beside improvement of treatment quality for ADHD/ASD, the project achieved the following aims:
- Improving service and increasing confidence in support system for patient management
- Increasing European competitiveness concerning new innovative treatment techniques
- Opening a new market for clinical target group
These achievements are the preconditions to realize the next goals:
- Reduce health care costs of Chronic Paediatric Neuropsychiatric Disorders (CPND)
- Distribute stimulation devices in clinics and outpatient departments
STIPED raises awareness about neuromodulation in paediatric population. Achievements are open source, providing access to the (non-)scientific society and medical institutions. This may increase treatment effectiveness, reduce direct (disorder-related) and indirect (secondary disabilities, academic underachievement) costs of CPND. As tDCS is applied during early development, STIPED contributes to prevention of future disabilities and improves employment and social integration of affected individuals. Therefore, STIPED provides an important contribution to the mental health in Europe.
- Improving service and increasing confidence in support system for patient management
- Increasing European competitiveness concerning new innovative treatment techniques
- Opening a new market for clinical target group
These achievements are the preconditions to realize the next goals:
- Reduce health care costs of Chronic Paediatric Neuropsychiatric Disorders (CPND)
- Distribute stimulation devices in clinics and outpatient departments
STIPED raises awareness about neuromodulation in paediatric population. Achievements are open source, providing access to the (non-)scientific society and medical institutions. This may increase treatment effectiveness, reduce direct (disorder-related) and indirect (secondary disabilities, academic underachievement) costs of CPND. As tDCS is applied during early development, STIPED contributes to prevention of future disabilities and improves employment and social integration of affected individuals. Therefore, STIPED provides an important contribution to the mental health in Europe.