Resting-State Functional MRI and Clinical Outcomes After Acute Disorders of Consciousness

BACKGROUND AND OBJECTIVES: Accurate assessment and prognostication of patients with acute disorders of consciousness (DoC) after severe brain injury remain a substantial clinical challenge. Resting-state fMRI (rs-fMRI) measures spontaneous, temporally correlated brain activity in the absence of external stimulation and provides objective insight into the integrity of large-scale neural networks that support brain function. Emerging evidence suggests that assessing neural integrity using rs-fMRI may improve outcome prediction in patients with acute DoC. This review summarizes the current evidence of rs-fMRI as an assessment tool during the acute phase of severe brain injury. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic literature search using MEDLINE and Embase databases from January 2006 to March 2026. Eligible studies included peer-reviewed empirical investigations of adult patients with acute DoC (<28 days postinjury) that examined associations between rs-fMRI measures and clinical outcomes. The systematic review protocol was registered in the PROSPERO International Prospective Register of Systematic Reviews (CRD420251085923). RESULTS: Of 396 studies screened, 30 met eligibility criteria. Across these studies, a total of 800 patients (mean age = 48, 69% male) were scanned at a weighted average of 9.31 days after intensive care unit admission. Ten studies included patients exclusively with traumatic brain injury, 8 with cardiac arrest, 2 with encephalopathy, and 10 included mixed etiologies. The most frequently assessed resting-state networks were the default mode (n = 20) and executive control networks (n = 11), followed by visual (n = 6), salience (n = 6), sensorimotor (n = 6), and auditory (n = 5) networks. Across studies, significant associations between rs-fMRI measures and outcome were consistently reported, despite heterogeneity in methodology. The most commonly reported patient outcomes were functional or neurologic status, assessed at hospital discharge or between 3 and 12 months postinjury. DISCUSSION: Current evidence consistently demonstrates that rs-fMRI acquired during the acute phase of brain injury is associated with neurologic and functional outcomes in patients with DoC. In addition, rs-fMRI may help identify patients more likely to recover consciousness and achieve favorable functional outcomes by characterizing the integrity of large-scale brain networks. However, substantial heterogeneity and small sample sizes limit comparability across studies. Standardized acquisition and analysis frameworks, along with larger prospective studies, are needed to validate the clinical utility of rs-fMRI and support translation into an assessment tool after brain injury.