Open Access

Dragana Manasova, Laouen Mayal Louan Belloli, Martin Justinus Rosenfelder, Lina Willacker, Emilia Fló Rama, Chiara Valota, Bertrand Hermann, Brigitte Charlotte Kaufmann, Alice Pirastru, Chiara Camilla Derchi, Theresa Raiser, Melanie Valente, Aude Sangare, Başak Türker, Nadya Pyatigorskaya, Benoît Béranger, Michele Colombo, Esteban Munoz-Musat, Anira Escrichs, Tiziana Atzori, Francesca Baglio, Constantin Lapa, Ansgar Berlis, Kristina Krüger, Tina Luther, Vincent Perlbarg, Gustavo Deco, Yonathan Sanz-Perl, Enzo Tagliazucchi, Louis Puybasset, Benjamin Rohaut, Lionel Naccache, Angela Comanducci, Anat Arzi, Mario Rosanova, Andreas Bender, Jacobo Diego Sitt

• Severely brain-injured patients may enter a spectrum of conditions collectively known as disorders of consciousness. This spectrum includes clinical conditions such as unresponsive wakefulness syndrome or minimally conscious state, where the behavioural assessment of consciousness can often be deceptive. To bridge this dissociation, neuroimaging techniques are employed to identify the residual brain functions. Each neuroimaging modality imperfectly captures distinct aspects of brain preservation—functional, anatomical, or both. In this study, we adopt a comprehensive approach by integrating the neurophysiology and neuroimaging modalities available from the standard and advanced clinical assessments through interpretable machine learning. The electrophysiological modalities included high-density EEG (resting state and task), whereas neuroimaging modalities included anatomical and resting-state functional MRI, diffusion MRI and 18F-fluorodeoxyglucose PET. Our investigation reveals thatSeverely brain-injured patients may enter a spectrum of conditions collectively known as disorders of consciousness. This spectrum includes clinical conditions such as unresponsive wakefulness syndrome or minimally conscious state, where the behavioural assessment of consciousness can often be deceptive. To bridge this dissociation, neuroimaging techniques are employed to identify the residual brain functions. Each neuroimaging modality imperfectly captures distinct aspects of brain preservation—functional, anatomical, or both. In this study, we adopt a comprehensive approach by integrating the neurophysiology and neuroimaging modalities available from the standard and advanced clinical assessments through interpretable machine learning. The electrophysiological modalities included high-density EEG (resting state and task), whereas neuroimaging modalities included anatomical and resting-state functional MRI, diffusion MRI and 18F-fluorodeoxyglucose PET. Our investigation reveals that specific modalities, such as functional assessments, provide comprehensive insights into the currently evaluated state of consciousness, the diagnosis of the patients. Conversely, structural modalities offer valuable information about the patient's evolution within the consciousness spectrum. We validate the proposed analysis with data coming from other centres with different acquisition parameters. Importantly, we demonstrate that model performance improves with an increase in the number of modalities. We observe a higher inter-modality disagreement for minimally conscious state patients and those patients who improve. Lastly, we observe a difference in feature importances between diagnosis and prognosis, with an interaction between modality and anatomical structures: some subcortical markers tend to contribute more to prognosis, while other cortical markers are more informative for diagnosis. This integrative multimodal and machine learning methodology presents a promising avenue for a more nuanced understanding of disorders of consciousness, contributing to enhanced diagnostic precision, prognostic capabilities and the personalization of rehabilitative strategies in clinical practice.…