EEG Microstate Comparative Model for Improving the Assessment of Prolonged Disorders of Consciousness: A Pilot Study

Background: Accurate assessment of prolonged disorders of consciousness (pDOC) is a critical clinical challenge. Misdiagnosis in pDOC can occur in up to 40% of cases, highlighting the need for more objective and reproducible biomarkers to support neurophysiological scales, thereby improving diagnosis and guiding therapeutic and prognostic decisions. Electroencephalography (EEG) microstate analysis is a promising, non-invasive method for tracking large-scale brain dynamics, but research in pDOC has predominantly relied on a canonical 4-class model. This methodological constraint may limit the ability to capture the full complexity of neural alterations present in these patients. Objective: This pilot study aimed to offer an objective method for assessing consciousness, complementing and enhancing the existing approaches established in the literature. The classical 4-class and an extended 7-class microstate model were compared to determine which more accurately characterizes the complexity of resting-state brain dynamics across different levels of consciousness in pDOC patients and healthy controls (HCs). Methods: Retrospective resting-state EEG (rsEEG) data from a cohort of pDOC patients and HC subjects were analyzed. Microstate analysis was performed using both 4-class and 7-class templates. The models were evaluated and compared based on three criteria: spatial correspondence with canonical maps (shared variance), the number of significant intra-group correlations between temporal features (Spearman test), and their ability to discriminate between the pDOC and HC groups (Wilcoxon test). Results: The 7-class microstate model provided a more accurate description of brain activity for most participants, with a greater number of microstate classes exceeding the 50% shared variance threshold compared to the 4-class model. In the pDOC group, both the 4-class and 7-class models showed a mean shared variance <50% in class D, which is associated with executive functioning across both templates. For the HC group, a prevalence of classes B and D emerged in both models, indicating higher engagement of executive functions. Furthermore, the 7-class model allowed for a group-specific analysis, which demonstrated that microstates A and F were consistently shared among 86% of pDOC patients. This suggests the potential preservation of specific intrinsic brain networks, particularly the sensory and default networks, even in the presence of severely impaired consciousness. Moreover, the 7-class model yielded a higher number of significant correlations within both groups and identified a broader set of temporal features that were significantly different between pDOC patients and HCs. These results highlight the enhanced sensitivity of the 7-class model in distinguishing subtle brain dynamics and improving the diagnostic capability for pDOC. Conclusions: The 7-class microstate model provides a more fine-grained and sensitive characterization of brain activity in both pDOC patients and healthy individuals. It demonstrated better performance in capturing individual brain dynamics, identifying shared network patterns, and discriminating between clinical populations. These findings suggest that the extended 7-class model holds greater potential for clinical utility and could lead to the development of more robust biomarkers for assessing consciousness.