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Combining model free and model-based biomarkers for the consciousness diagnosis

Combining model free and model-based biomarkers for the consciousness diagnosis

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

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.


 from 31-December-2021 to 30-December-2024

Jacobo Sitt 

Gustavo Deco
Olivia Gosseries
Raul C. Muresan