Profiling Neural Correlates of Consciousness based on Brain Biological Ontologies

2475 

Abstract Submission 

Arianna Sala¹, Naji Alnagger¹, Simona Abagnale², Baris Kaan¹, Michiel Meys¹, Zhixin Wang¹, Marjorie Bardiau¹, Simon Eickhoff³, Daniel Martins⁴, Marco Tettamanti⁵, steven laureys¹, Olivia Gosseries¹, Aurore Thibaut¹, Jitka Annen¹

¹University of Liege, Liege, Belgium, ²University of Campania Luigi Vanvitelli, Naples, Italy, ³Institute for Systems Neuroscience, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany, ⁴King's College London, London, United Kingdom, ⁵University of Milano-Bicocca, Milano, Milano

Arianna Sala  
University of Liege
Liege, Belgium

Naji Alnagger  
University of Liege
Liege, Belgium

Simona Abagnale  
University of Campania Luigi Vanvitelli
Naples, Italy

Baris Kaan  
University of Liege
Liege, Belgium

Michiel Meys  
University of Liege
Liege, Belgium

Zhixin Wang  
University of Liege
Liege, Belgium

Marjorie Bardiau  
University of Liege
Liege, Belgium

Simon Eickhoff  
Institute for Systems Neuroscience, Medical Faculty, Heinrich-Heine University Düsseldorf
Düsseldorf, Germany

Daniel Martins  
King's College London
London, United Kingdom

Marco Tettamanti  
University of Milano-Bicocca
Milano, Milano

steven laureys  
University of Liege
Liege, Belgium

Olivia Gosseries  
University of Liege
Liege, Belgium

Aurore Thibaut  
University of Liege
Liege, Belgium

Jitka Annen  
University of Liege
Liege, Belgium

Studying the neural correlates of consciousness, i.e. the neural system whose state is causally linked with whether a subject is conscious or not (Chalmers, 1998), is non-trivial. Despite 25 years of neuroscientific research, the topography of the neural correlates of consciousness remains currently debated (Seth & Bayne, 2022) and even less is known about the biological (e.g. molecular, microstructural) characteristics of the neural systems underlying consciousness. One way to study the neural correlates of consciousness is by comparing states of (un)consciousness, e.g. contrasting control subjects with patients with disorders of consciousness (DoC) after severe brain injury, reducing or nullifying awareness despite the presence of arousal.
The present meta-analysis aims to shed light on the micro (molecular, microstructural) and macro (functional, evolutionary) biological ontologies of the neural correlates of consciousness, based on a quantitative synthesis of the existing evidence on brain structural, functional and molecular alterations in DoC.

In June 2023, we used MEDLINE via Ovid, and Scopus and Embase via Elsevier databases to search for resting-state MRI and PET studies, published from 2000 to 2023, and involving predominantly adults (≥16 years old) with prolonged DoC (≥28 days) and either a clinical diagnosis of DoC (unresponsive wakefulness syndrome or minimally conscious state) based on a validated behavioural scale (Schnakers et al., 2020). At least two referees (among AS, BK, NA, SA, JA) independently screened abstracts and full texts of selected studies and extracted coordinates of whole-brain, voxel-based comparisons performed between DoC patients and controls. Coordinate-based meta-analysis was performed via activation likelihood estimation. The resulting statistical maps of voxel-wise likelihoods were compared to the topography of 24 molecular, microstructural, functional and evolutionary biological ontologies, using standard settings in the neuromaps toolbox. All maps included were surface-type maps, i.e. including cortical areas only. Spatial correlations were deemed significant at p<0.05 Bonferroni-corrected for multiple comparison within map-type. The full protocol, including search strategy using controlled vocabulary and keyword terms, is available on PROSPERO (CRD42022327151).

As of June 2023, of the resulting 2798 MRI and PET studies, 24 studies including 35 experiments (4 structural, 13 functional and 18 molecular) met criteria for inclusion, for a total of 665 patients (338 UWS; 327 MCS) and 351 controls (Fig. 1).
Likelihood of consciousness-related alterations distributed following molecular, functional and evolutionary brain biological ontologies (Fig.2). No significant association was found with microstructural ontologies (T1w/T2w ratio and thickness).
In details, likelihood of consciousness-related alterations spatially distributed following:
- the degree of cerebral blood flow, with areas with higher cerebral blood flow most likely to be altered in disorders of consciousness
- a unimodal-transmodal brain functional hierarchy, with higher-order associative areas (as opposed to sensory ones) most likely to be altered in disorders of consciousness
- an evolutionary and allometric hierarchy, with areas that expanded the most in the evolution from macaque to human and that expand the most in the development from childhood to adulthood, most likely to be altered in disorders of consciousness

This meta-analysis provides the most extensive evidence to date on biological features of neural systems related to consciousness, where high-order cortical areas, that evolved the most in recent evolution and expand the most during development, and requiring higher cerebral perfusion, are most likely to be associated with the ability to express consciousness. Our findings should be independently confirmed based on evidence in other ordinary and non-ordinary states of consciousness (e.g. sleep, anesthesia).

Higher Cognitive Functions Other ²

Consciousness and Awareness ¹

CHEMOARCHITECTURE

Consciousness

Cortex

FUNCTIONAL MRI

Meta- Analysis

MRI

Positron Emission Tomography (PET)