Integrity of the default mode network (DMN) is believed to be essential for human consciousness. However, the effects of acute severe traumatic brain injury (TBI) on DMN functional connectivity are poorly understood. Furthermore, the temporal dynamics of DMN reemergence during recovery of consciousness have not been studied longitudinally in patients with acute severe TBI. We performed resting-state functional magnetic resonance imaging (rs-fMRI) to measure DMN connectivity in 17 patients admitted to the intensive care unit (ICU) with acute severe TBI and in 16 healthy control subjects. Eight patients returned for follow-up rs-fMRI and behavioral assessment six months post-injury. At each time point, we analyzed DMN connectivity by measuring intra-network correlations (i.e. positive correlations between DMN nodes) and inter-network anticorrelations (i.e. negative correlations between the DMN and other resting-state networks). All patients were comatose upon arrival to the ICU and had a disorder of consciousness (DoC) at the time of acute rs-fMRI (9.2 ± 4.6 days post-injury): 2 coma, 4 unresponsive wakefulness syndrome, 7 minimally conscious state, and 4 post-traumatic confusional state. We found that, while DMN anticorrelations were absent in patients with acute DoC, patients who recovered from coma to a minimally conscious or confusional state while in the ICU showed partially preserved DMN correlations. Patients who remained in coma or unresponsive wakefulness syndrome in the ICU showed no DMN correlations. All eight patients assessed longitudinally recovered beyond the confusional state by 6 months post-injury and showed normal DMN correlations and anticorrelations, indistinguishable from those of healthy subjects. Collectively, these findings suggest that recovery of consciousness after acute severe TBI is associated with partial preservation of DMN correlations in the ICU, followed by long-term normalization of DMN correlations and anticorrelations. Both intra-network DMN correlations and inter-network DMN anticorrelations may be necessary for full recovery of consciousness after acute severe TBI.

Many patients with severe coronavirus disease 2019 (COVID-19) remain unresponsive after surviving critical illness. Although several structural brain abnormalities have been described, their impact on brain function and implications for prognosis are unknown. Functional neuroimaging, which has prognostic significance, has yet to be explored in this population. Here we describe a patient with severe COVID-19 who, despite prolonged unresponsiveness and structural brain abnormalities, demonstrated intact functional network connectivity, and weeks later recovered the ability to follow commands. When prognosticating for survivors of severe COVID-19, clinicians should consider that brain networks may remain functionally intact despite structural injury and prolonged unresponsiveness.

doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. We thank the members of the Patient and Family Advisory Board of the Massachusetts General Hospital Laboratory for NeuroImaging of Coma and Consciousness for their feedback and insights regarding the ethical conduct of this clinical trial. We also thank Dr. David A. Schoenfeld for helpful statistical consultation.