Lateral frontoparietal effective connectivity differentiates and predicts state of consciousness in a cohort of patients with traumatic disorders of consciousness

PLoS One. 2024 Jul 5;19(7):e0298110. doi: 10.1371/journal.pone.0298110. eCollection 2024.

Abstract

Neuroimaging studies have suggested an important role for the default mode network (DMN) in disorders of consciousness (DoC). However, the extent to which DMN connectivity can discriminate DoC states-unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS)-is less evident. Particularly, it is unclear whether effective DMN connectivity, as measured indirectly with dynamic causal modelling (DCM) of resting EEG can disentangle UWS from healthy controls and from patients considered conscious (MCS+). Crucially, this extends to UWS patients with potentially "covert" awareness (minimally conscious star, MCS*) indexed by voluntary brain activity in conjunction with partially preserved frontoparietal metabolism as measured with positron emission tomography (PET+ diagnosis; in contrast to PET- diagnosis with complete frontoparietal hypometabolism). Here, we address this gap by using DCM of EEG data acquired from patients with traumatic brain injury in 11 UWS (6 PET- and 5 PET+) and in 12 MCS+ (11 PET+ and 1 PET-), alongside with 11 healthy controls. We provide evidence for a key difference in left frontoparietal connectivity when contrasting UWS PET- with MCS+ patients and healthy controls. Next, in a leave-one-subject-out cross-validation, we tested the classification performance of the DCM models demonstrating that connectivity between medial prefrontal and left parietal sources reliably discriminates UWS PET- from MCS+ patients and controls. Finally, we illustrate that these models generalize to an unseen dataset: models trained to discriminate UWS PET- from MCS+ and controls, classify MCS* patients as conscious subjects with high posterior probability (pp > .92). These results identify specific alterations in the DMN after severe brain injury and highlight the clinical utility of EEG-based effective connectivity for identifying patients with potential covert awareness.

MeSH terms

  • Adult
  • Brain Injuries, Traumatic / diagnostic imaging
  • Brain Injuries, Traumatic / physiopathology
  • Case-Control Studies
  • Cohort Studies
  • Consciousness Disorders* / diagnostic imaging
  • Consciousness Disorders* / physiopathology
  • Consciousness* / physiology
  • Electroencephalography* / methods
  • Female
  • Frontal Lobe / diagnostic imaging
  • Frontal Lobe / physiopathology
  • Humans
  • Male
  • Middle Aged
  • Nerve Net / diagnostic imaging
  • Nerve Net / physiopathology
  • Parietal Lobe* / diagnostic imaging
  • Parietal Lobe* / physiopathology
  • Persistent Vegetative State / diagnostic imaging
  • Persistent Vegetative State / physiopathology
  • Positron-Emission Tomography
  • Young Adult

Grants and funding

The study was further supported by the University and University Hospital of Liège, the Belgian National Funds for Scientific Research (FRS-FNRS), the FNRS MIS project (F.4521.23), the FNRS PDR project (T.0134.21), the ERA-Net FLAG-ERA JTC2021 project ModelDXConsciousness (Human Brain Project Partnering Project, R.8005.21), MSCA Staff-Exchange project DOC-BOX (HORIZON-MSCA-2022-101131344), the fund Generet, the King Baudouin Foundation, the Télévie Foundation, the European Space Agency (ESA) and the Belgian Federal Science Policy Office (BELSPO) in the framework of the PRODEX Programme, the BIAL Foundation, the Mind Science Foundation, the European Commission, and the Fondation Leon Fredericq. SL is supported by the National Natural Science Foundation of China (Grant no. 81920108023), European Foundation of Biomedical Research FERB Onlus, fund Generet of King Baudouin Foundation, Mind Care International Foundation. SL is Chairholder of the Canada Excellence Research Chair in Integrative Neuroscience for Sustainable Mental Health, Laval University, CERVO Brain Research Centre, Quebec, Canada and Research Director at the National Fund for Scientific Research, Belgium. JA is postdoctoral fellow funded (1265522N) by the Fund for Scientific Research-Flanders (FWO). SC is supported by a UKRI EPSRC grant (grant no. EP/P033199/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.