Community Research and Development Information Service - CORDIS

Periodic Report Summary 2 - BRAINTRAIN (Taking imaging into the therapeutic domain: Self-regulation of brain systems for mental disorders)

Project Context and Objectives:

Advances in neuroimaging have led to a better knowledge of both mental dysfunction and potential compensatory mechanisms in patients. Major nodes of disordered neural networks are in deep regions of the brain, which makes them difficult to access by electroencephalography or transcranial stimulation. Neuroimaging techniques are therefore essential for the development of non-invasive neuromodulation techniques for mental and behavioural disorders.

Real-time functional magnetic resonance imaging (fMRI) uses magnetic resonance imaging to measure brain activity, by detecting associated changes in blood flow which increases with neuronal activation. fMRI can be used for on-line-monitoring of brain function as well as for selfmodulation of neural processes via interactive training. With the neurofeedback (NF) procedure, patients learn control over brain activity using real-time signals from their own brain.

BRAINTRAIN is based on this idea that real-time functional neuroimaging can be used to train patients to regulate their own brain activity via NF training and thus modulate the brain networks of mental disorder, restore function, improve symptoms and promote resilience. The BRAINTRAIN project brings together the core groups that have been instrumental in the development of methods for real-time functional imaging and fMRI-based NF and have led the initial clinical applications in neuropsychiatric disorders.

BRAINTRAIN objectives

BRAINTRAIN will improve and adapt the methods of real-time fMRI NF for clinical use, including the combination with EEG and the development of standardised procedures for the mapping of brain networks that can be targeted with NF. Its core component will be the exploration of the efficacy of fMRI-NF in selected mental and neurodevelopmental disorders that involve motivational, emotional and social neural systems targetable with this technique and pose major public health problems because of their prevalence and hitherto limited treatment options. They are characterised by dysfunctional motivational drives (particularly addiction and binge eating disorder), social communication abilities (particularly autism-spectrum disorder) and emotional regulation (particularly anxiety disorders, including post-traumatic stress disorder), which all have well-established correlates in functional imaging. The development and evaluation of fMRI-NF protocols for these disorders is thus particularly promising on both neurobiological and clinical grounds.
BRAINTRAIN has three main components:
• the development and refinement of methods for the real-time analysis and feedback of fMRI data and combination with other imaging modalities (WP2)
• the adaptation of fMRI mapping techniques to localise disease-relevant networks and development of protocols for their self-regulation through NF (WP3)
• and the assessment of feasibility and clinical effects in several mental disorders that are characterised by dysfunctional brain systems for motivation, emotion regulation and social communication and by important therapeutic gaps (autism spectrum disorders, alcohol addiction,
post-traumatic stress disorder, childhood anxiety disorders, binge-eating disorder) (WP4).

BRAINTRAIN will also explore the potential transfer of (laboratory-based) imaging feedback training into everyday settings through ambulatory and assistive technologies such as electroencephalography (EEG) and gaming (WP5). BRAINTRAIN will engage with potential users of these technologies (healthcare professionals and providers, medical instrument and software manufacturers, patient and carer associations) through several workshops, liaise with regulatory authorities and disseminate findings to the academic and user communities in WP6.
Project Results:
The consortium is well established and collaborates efficiently. The governing structure and IAB work well. The management tools are well known and used, and updated regularly. The reporting procedures are well known, and the first reporting has been completed without major difficulties. The requested amendments have been submitted and approved of according to the procedures.
In WP2, a toolbox for optimizing fMRI sequences with respect to BOLD sensitivity in user specified brain areas based on simulations and on field maps was developed; general recommendations for the use of optimized real-time (rt) fMRI protocols were released; an optimized 3D-Multiecho EPI-Sequence was installed; the stimulus/feedback software “BrainStim” has been modified to work directly with the neurofeedback (NF) software in rt; a 3D EPI reconstruction with parallel image reconstruction was implemented and Gadgetron and optimized image reconstruction algorithms were installed; the rt- fMRI NF toolbox has been completed; a new rt-EEG analysis software has been developed and the rt-fMRI software has been optimized; a theoretical analysis of the transfer function in directly coupled NF and ultra-fast acquisition methods speed to achieve transfer functions with a sufficient bandwidth were explored.
WP3 is now terminated. The following has been achieved for the period: using fMRI we have defined functional paradigms to delineate specific processes, aiming to use them for NF outcome measurements or target localizers. This include empathy related processes in the human brain using a unique paradigm that was developed by TAU to differentiate between mentalization and embodiment; reward related processes using a monetary naturalistic game; ecological paradigm for an interpersonal anger provocation and regulation using two-person interactions and a modified ultimatum game; a self-control process relevant for NF training in obese people; a paradigm for a central cognitive control process. In addition, two new context specific interface scenarios were tested using specific neural targets in fMRI-NF for ADHD and PTSD.
In WP4 all the clinical trials have started and are ongoing, with generally good recruitment rates. All ethical approvals were obtained (incl. for amendments). The trials have been registered on public repositories. The protocol of the CU trial has been published in the journal Trials. The trials database is working and being used by all teams. Work on the statistical analysis plans is ongoing. The teams are also conducting quality control analyses on their imaging/electrophysiology data. Patient recruitment is being monitored in monthly meetings with SEWTU, and we had two meetings of the Trials Steering Committee in the period.
In WP5, the brain networks supporting the interpretation of biological facial expressions were studied. Additionally, a NF paradigm was designed to optimise the feedback strategy. An analysis of the EEG signal acquired during fMRI experiments showed correlations between both signals, providing relevant information concerning fMRI to EEG transfer. We are studying the feasibility of an EEG-based NF version of the protocol. An EEG-based BCI coupled with VR was developed to train goal oriented behaviour to social vs. non-social target objects in autism. An adapted version of a social cueing training system is under validation by a clinical trial. Several virtual reality paradigms were developed to study the functional nature of social impairments in ASD, leading to the definition and prototypical development of a serious game for job interview simulation.
Lastly, all partners made good use of the communication tools, and have regularly disseminated the project. All are aware of and understand the IP aspects. The BPC is active, and a preliminary version of the exploitation plan has been produced. The AGMs were characterised by lively exchanges and fostered an excellent collaborative atmosphere, and were augmented by two open workshops.
Potential Impact:
The ultimate goals of BRAINTRAIN are to:
• Develop new or optimize existing imaging technologies
• Validate their application as a therapeutic tool for mental and behavioural disorders by integrating imaging data with complementary knowledge from bioinformatics and clinical data
• Facilitate the diagnosis of mental disorders at the pre-symptomatic stage or early during development
• Better measure disease progression
• Develop transfer technologies for fMRI-NF through EEG and serious games.

The BRAINTRAIN consortium is creating new technologies because no standardised solutions for clinical fMRI-based NF are available to date. The scope of BRAINTRAIN includes mental disorders affecting a third of the EU’s population, and its technological developments can support the application of fMRI-NR to an even wider range of psychiatric and neurological disorders. Potential markets include:
• Scanner manufacturers wanting to incorporate clinical NF protocols in their clinical hard-/software packages
• Healthcare providers (private and public) wanting to offer NF as part/ add-on to existing in- or outpatient treatments for mental disorders and as part of personalized medicine schemes in psychiatry
• Governments wanting to implement NF training to promote resilience/ prevent PTSD in service personnel; end-users (patients) purchasing NF as treatment option (similar to private psychotherapy etc.) Education –the real-life version may be integrated as enhancement programs in schools to help deal with affective and cognitive disturbances.

BRAINTRAIN addresses the needs of an international market. MRI technology for diagnostic purposes is ubiquitous in industrialised countries, with increasing uptake in developing countries and huge expansion potential there. BRAINTRAIN consortium is the first one to complement this with a strategy to develop fully integrated (standardised, across platform, ready to use, manual-guided) solutions for therapeutic functional MRI and with integrated transfer technologies. Given clinical success of the proposed interventions (even in only some of the investigated disorders), this could lead to a huge demand of these tools from current and new customers of MRI systems and from manufacturers of such devices (to integrate into turnkey solutions).

The economic impact could thus be expected in the following key domains:
• Sales of products developed as part of BRAINTRAIN, especially an increase in the target market for MR systems if clinical use is added.
• Licensing of IP developed in BRAINTRAIN or other collaboration with industrial partners outside the consortium (e.g. scanner and EEG hardware manufacturers), leading to increased sales and efficiency gains for these partners.
• Standardisation and harmonisation of real-time imaging procedures, with considerable time gain, error, downtime and cost reduction.

Moreover BRAINTRAIN will provide data for preliminary health economics calculations about potential cost savings in treatment and non-treatment costs (such as facilitating return to work, reducing long-term disability), which will be conducted in collaboration with the Welsh Health Economics Support Service.
BRAINTRAIN will reduce health care costs, ultimately benefiting patients and society as a whole.
In the case of ASD, the real life transfer paradigms, and in particular the use of serious games will strongly reduce the need of the physical presence of a therapist thereby reducing costs. Also, the increased level of social autonomy will also contribute to the reduction of social care expenses.
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United Kingdom


Life Sciences
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