Combining model free and modelbased biomarkers for the consciousness diagnosis

Project summary

Studying the brain mechanisms behind consciousness is a major challenge for neuroscience and medicine. Yet so far, there is no such thing as a unique biomarker that can precisely define the state of consciousness of a patient with disorders of consciousness (DOC). All the biomarkers proposed so far are theory-based but empirically defined (MFB; model-free biomarkers): the thresholds that separate categories are set in a data-driven way. Overall, researchers have focused on separating patients’ categories, sometimes disregarding the heterogeneity of the DOC patients’ population. This is the reason why, nowadays, our current knowledge on the brain mechanisms sustaining global states of consciousness is limited. In this project, we propose a novel approach using model-based biomarkers (MBB). This new family of biomarkers will complement the existing MFB and will provide novel quantitative diagnosis tools. In addition, these new tools will also advance our understating of the underlying causal mechanisms of consciousness. The modeling of the structural and functional connectivity will be combined with novel, systematic perturbational approaches that have already provided new insights into the human brain’s ability to integrate and segregate information over time. We will develop computational whole-brain models based on single-patient neuroimaging data. We will extract MBB from the adjusted model parameters and from in-silico simulations. We will test the utility of these biomarkers for the diagnosis of patients with chronic DOC. Then, we will contrast the MBB with a set of previously developed MFB. Finally, we will analyze the diagnostic and prognostic capacity of these biomarkers in DOC patients in an acute stage, as well as evaluate these biomarkers in the frame of therapeutic intervention efficacy (using pharmacology and non-invasive brain stimulation). This project will be carried on by a consortium of two research teams’ leaders in DOC and two computational neuroscience teams. The main goal of this proposal is to obtain a multi-centric validated set of biomarkers for the diagnosis, prognosis and therapeutic responsiveness of post-comatose and DOC patients in both chronic and acute stages. Clinically, our results may point to the specific reason to include each patient within a diagnostic group, hence setting the basis for future developments of specific interventions and treatments.

Partnering Organisations

Key facts

Time frame: 17.03.2022 - 31.03.2023

Origin: FLAG-ERA JTC 2021

Funding: French National Research Agency (ANR), Agencia Estatal de Investigación (AEI), Fonds de la Recherche Scientifique (FNRS), Unitatea Executiva pentru finantarea invatamantului superior, a cercetarii, dezvoltarii si inovarii (UEFISCDI)