Multimodal MRI reveals three-tiered pathological co-alterations in prolonged disorders of consciousness: structural disconnection, network disintegration, and regional hyperconnectivity

Background Clinical diagnosis of prolonged disorders of consciousness (pDoC) relies primarily on behavioral scales, which lack sensitivity to covert cerebral cognitive activity and carry a risk of misdiagnosis. Few studies integrate structural and functional brain abnormalities to explore pDoC. The objective of this study was to employ resting-state functional magnetic resonance imaging (rs-fMRI) with diffusion tensor imaging (DTI) to delineate multimodal neuroimaging abnormalities in pDoC, clarify its neural mechanisms, and identify potential neuroimaging biomarkers. Methods Eighteen patients with pDoC and 20 healthy controls (HCs) underwent rs-fMRI and DTI acquisition. Key metrics included fractional anisotropy (FA), amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), and functional connectivity (FC). Correlations between these metrics and Coma Recovery Scale-Revised (CRS-R) scores were analyzed. Results Compared with HCs, pDoC patients exhibited reduced FA in the left anterior corona radiata (ACR-L) ( p < 0.05), altered ALFF/fALFF/ReHo in prefrontal, cerebellar, and limbic regions, and disrupted FC within higher-order cortical networks. CRS-R scores positively correlated with ACR-L FA and prefrontal ReHo, and negatively correlated with cerebellar and limbic hyperactivity ( p < 0.05). Conclusion Patients with pDoC demonstrate three simultaneous tiers of pathological co-alterations: extensive white matter structural disruption with peak significance in ACR-L; disintegration of higher-order cortical networks; patterns of hyperactivity and hyperconnectivity in the cerebellum, limbic system, and angular gyrus. Our findings provide a framework for understanding the pathophysiological mechanisms underlying consciousness impairment in pDoC. The neuroimaging biomarkers found in this study facilitate objective pDoC assessment and prognostic evaluation.