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Transcranial brain stimulation as innovative therapy for chronic pediatric neuropsychiatric disorder – STIPED

Periodic Reporting for period 2 - STIPED (Transcranial brain stimulation as innovative therapy for chronic pediatric neuropsychiatric disorder – STIPED)

Reporting period: 2018-07-01 to 2019-12-31

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 the associated behavioral impairments. Thus, new technological approaches targeting the underlying mechanisms are required. STIPED aims at studying safety, dynamic 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 involving low-amplitude direct currents to the brain via surface electrodes on the scalp. It has a favorable safety-feasibility profile, offers a convincing placebo, is bilaterally applicable, portable, and inexpensive. For this end, STIPED has the following objectives:
-Proving tDCS effects on neurocognitive (working memory, behavioral control, social cognition) and behavioral (attention, impulsivity, hyperactivity, social withdrawal) impairments and studying tolerability of tDCS in underage patients with ADHD/ASD (WP4, WP5, WP9)
-Identifying attitudes, intentions, and reservations 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 optimal, personalized application (WP3, WP6) by determining its influence on brain development
-A flexible integration of tDCS into clinical routine with a pipeline for tDCS 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)
In period 1(M1-M36), STIPED achieved the following:
Data collection of a semi-structure interview study with participants/parents is completed for OptiStim – WP3 and ongoing for EStim – WP4. The online survey was designed for parents of children with ADHD in Germany and approved by the ethics committee of the Kiel University. A publication of ethical mapping and recommendations for tDCS research with pediatric ADHD population is finalized. The team of the WP2 provided positive internal ethics support, contributed to the preparation of documents to regional, national, and international ethics committees, provided additional ethics advices for current potential ethical challenges during recruitment (all randomized clinical trials).
The patients recruitment is nearly completed (trials OptiStimPFC, OptiStimIFG, OptiStimAtemp) and the first data analysis is initiated. The automated pipeline generating finite element head meshes from structural MRI data, which is required to calculate E-field distribution and generate files for optimizations per subject’s individual model, is completed. A sub-pipeline for automatic generation of finite element meshes is developed by RegionH, based on new volume segmentation method to process T1 and T2w MRIs per subject; optimizations were created by NE with its proprietary optimization algorithm, Stimweaver (Ruffini et al., 2014), to create standard multichannel optimized montages targeting areas of interest per experimental group (left dorsolateral prefrontal cortex (lDLPFC), right inferior frontal gyrus (rIFG), temporal parietal junction (TPJ)). The multichannel optimized montage was compared with the bipolar montage. A case report on epileptic seizure (SAE) in the context of OptiStim study and a preliminary study were published.
Study protocol was finalized and approved by German National Authorities. The recruitment center in Kiel at UKSH was closed in 2018 due to appointment of Coordinator, Prof. Siniatchkin, as head of Department of Child and Adolescent Psychiatry (EvKB, Bielefeld). EVKB (2019) and CU (2020) were included as new study sites. Recruitment will be carried out until end of summer 2020. No SAEs so far. The study protocol for home-based tDCS intervention was finalized and submitted to German National Authorities); study protocol and investigator’s brochure was forwarded to all partners. EvKB and NE developed a training for home application of tDCS.
All primary and secondary outcome measures were completed. Neurocognitive training tasks were implemented. Study was initiated at GU and EvKB. Ethics committees and regulatory authorities have approved the StimAT study in Portugal and France. Patients recruitment was started.
An automated pipeline for preprocessing and generation of surface-based cortical meshes with FreeSurfer software was developed. Monitoring of MRI data quality was done. A novel EEG biomarker was proposed based on echo-state networks detecting changes in non-stationary dynamics and chaotic synchronization between EEG time-series. Non-supervised machine learning methods to automatically predict responses to tDCS (Starlab) were developed.
Novel analytical frameworks modelling individuals’ response to tDCS were tested and optimized.
A pipeline for tDCS home application was developed. A wearable, wireless EEG-tDCS stimulator for home/non-clinical environments was constructed. A simple, fail-safe electrode-positioning headset was designed. Home software to supervise tDCS home therapy, including EEG metrics of ADHD characterization (WP6) was developed and validated.
A protocols for data monitoring and randomization was developed and established, electronic case report forms per clinical trial were tested.
Promotion (website, social media, press release, project newsletter, project flyers) and participation in international scientific and local communication event.
The STIPED project has an important impact for the scientific community, the society, and the EU. Beside improvement of treatment quality for ADHD/ASD, the project will achieve the following aims:
- Improving service and increasing confidence in compliance support system for disease/patient management
- Reducing health care costs of CPND
- Opening a new market for a clinical target group
- Distributing stimulation devices in clinics and outpatient departments
- Increasing European competitiveness concerning new innovative treatment techniques
The project raises the awareness about neuromodulation in the paediatric population. Its achievements will be open source, providing access to scientific developments to the (non-)scientific society and medical institutions. This will increase treatment effectiveness reduce direct (disorder-related) and indirect (secondary disabilities, academic underachievement) costs of CPND. As tDCS is applied during early development, the project 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.