Regulating Pathological Neural Connectivity in Posttraumatic Stress Disorder

Informations projet

PTSD Neurofeedback

N° de convention de subvention: 897709

DOI

10.3030/897709

Projet clôturé le 31 Août 2020

Date de signature de la CE 28 Février 2020

Date de début 15 Mars 2020

Date de fin 14 Mars 2022

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 174 167,04

Contribution de l’UE

€ 174 167,04

Coordonné par

UNIVERSITAT WIEN
Austria

Periodic Reporting for period 1 - PTSD Neurofeedback (Regulating Pathological Neural Connectivity in Posttraumatic Stress Disorder)

Période du rapport: 2020-03-15 au 2022-03-14

Résumé du contexte et des objectifs généraux du projet

The advent of functional magnetic resonance imaging (fMRI) has provided unprecedented insights into specific brain networks that underlie psychological illness; however, these advances are not fully incorporated into current therapeutic approaches. Here, we implement state-of-the-art fMRI as a therapeutic tool in patients with posttraumatic stress disorder (PTSD). This method involves using real-time fMRI and neurofeedback of brain signals in order to teach patients with PTSD to self-regulate pathological neural networks that are associated with their symptoms. Indeed, there is an urgent societal need for the development and rigorous testing of novel and efficacious personalized treatment interventions for PTSD. In response to this demand, the current innovation involves conducting a randomized clinical trial (RCT) that regulates abnormal neural connectivity patterns in patients with PTSD with the aim to reduce symptoms. It is clear that PTSD can be difficult to treat, and that current therapies are not always effective for all patients. Importantly, there is growing evidence to suggest that neurofeedback represents a novel adjunctive treatment in a wide range of other psychiatric disorders. The result of such scientific efforts could lead to a frontline, non-invasive, personalized treatment for PTSD. Taken together, the proposed innovation is both timely and in line with current European research trends and societal needs to decrease the economic resources required to support mental health treatment. The primary research objective is to investigate clinical symptom improvement among PTSD patients as a function of neurofeedback treatment. The secondary research objective is to examine the underlying neural mechanisms that mediate network regulation during neurofeedback, and in relation, examine how specific symptoms and individual differences predict regulation success with machine learning computations. Taken together, the goal of the current action is to develop a connectivity-based neurofeedback treatment protocol for PTSD and elucidate the key factors and symptoms that mediate such treatment success.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

Ethics approval for the current research innovation was obtained at the University of Vienna. The applicant then received extensive connectivity-based neurofeedback training from the host supervisor and his international team of experts. The applicant also received valuable clinical training from Prof. Brigitte Lueger-Schuster within the department at the University of Vienna. Data-management plans were implemented, and community outreach activates were planned before pandemic lockdowns were enforced. Recruitment strategies were also defined with clinical collaborators in order to effectively recruit individuals diagnosed with PTSD.

Subsequently, the neuroimaging protocol was successfully piloted offline at the University of Vienna. This involved i) developing the neurofeedback experimental interface, ii) coding scripts for the presentation of stimuli, iii) optimizing fMRI scanner parameters for real-time neurofeedback/imaging, iv) troubleshooting in-house neurofeedback software at the fMRI scanner, and v) meeting regularly with the developers of the neurofeedback software that are part of the host-supervisors team.

One of the main objectives of this granting opportunity is to position applicants on a track towards obtaining professorship at a leading research-driven university post completion. Demonstrating the catalytic effect of this funding action, within the 5th month of funding, the applicant received a Professor position at McMaster University in the Department of Psychiatry and Neuroscience.

Moving forward, this current research innovation will be conducted as a multi-site collaboration between the Andrew Nicholson (Professor, McMaster University) and the host supervisor (Professor, University of Vienna), where new ethics has already been submitted. Formally, the applicant now holds a senior research fellow affiliation with the University of Vienna and funding for the current action was terminated in the 5th month of funding. Importantly, the neuroimaging protocol that was piloted at the University of Vienna will now be implemented both in Canada and in Austria and is now being set up at both sites. Scanning will commence as soon as COVID-related restrictions have been lifted at the scanner sites.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

We expect the proposed innovation will lead to clinical meaningful reductions in PTSD symptoms in the experimental group after the neurofeedback intervention and at the 1-week follow-up. Additionally, we predict that machine learning computations will allow us to identify highly relevant symptomatic and demographic features that can predict neurofeedback learning success and response to treatment. We also predict plastic changes within intrinsic connectivity networks during the resting-state in PTSD patients from the experimental group, with increased connectivity to emotion regulation areas. The knowledge gained from the current research innovation will significantly benefit the following impact zones: clinical practice and public policy, the scientific knowledge base, and the current European societal environment and economy. As the proposed research action has direct clinical significance, it will greatly inform novel treatment interventions for PTSD that are rooted in the normalization of pathological neural-circuits maintaining the disorder. Hence, the current proposal has the potential to greatly reduce the economic and psychological illness burden of PTSD.

Critically, several related projects were also conducted during the funding period that extended beyond the state-of-the-art innovation, and involve:
1) Publishing a connectivity-based real-time fMRI neurofeedback study with the host supervisor in healthy individuals in "Human Brain Mapping".
2) Conducting a machine learning analysis with the host supervisor in order to identify predictors of real-time fMRI neurofeedback success, currently under review in "NeuroImage".
3) Publishing a clinical trial protocol for a novel psychological intervention for refugee populations in Austria experiencing PTSD symptoms, published in "Trials". Here, the applicant worked with collaborator Prof. Brigitte Lueger-Schuster at the University of Vienna to develop this protocol.
4) Several machine learning projects were conducted with the host supervisor examining perceived health and fear during the COVID-19 lockdown. This yielded two papers that are currently under review in "PLoS One" and the "Journal of Social and Personal Relationships".
5) The applicant formed a multi-site collaboration between the host-supervisor’s lab in Austria, and Dr. Ruth Lanius’ lab in Canada. Here, we conducted a real-time fMRI neurofeedback study in individuals with PTSD and healthy controls, regulating the posterior-cingulate cortex. This paper has been prepared and will be submitted to "NeuroImage: Clinical".
6) The applicant utilized skills developed in the host supervisor’s lab concerning dynamic causal modelling (DCM) to publish a study showing abnormal directed connectivity in patients with PTSD during trauma provocation. This resulted in a senior author publication in "NeuroImage: Clinical".

Figure 1: Neurofeedback target models