Scale-Free Functional Connectivity of the Brain Is Maintained in Anesthetized Healthy Participants but Not in Patients with Unresponsive Wakefulness Syndrome

Xiaolin Liu, B. Douglas Ward, Jeffrey R. Binder, Shi-Jiang Li, Anthony G. Hudetz

Loss of consciousness in anesthetized healthy participants and in patients with unresponsive wakefulness syndrome (UWS) is associated with substantial alterations of functional connectivity across large-scale brain networks. Yet, a prominent distinction between the two cases is that after anesthesia, brain connectivity and consciousness are spontaneously restored, whereas in patients with UWS this restoration fails to occur, but why? A possible explanation is that the self-organizing capability of the brain is compromised in patients with UWS but not in healthy participants undergoing anesthesia. According to the theory of self-organized criticality, many natural complex systems, including the brain, evolve spontaneously to a critical state wherein system behaviors display spatial and/or temporal scale-invariant characteristics. Here we tested the hypothesis that the scale-free property of brain network organization is in fact fundamentally different between anesthetized healthy participants and UWS patients. We introduced a novel, computationally efficient approach to determine anatomical-functional parcellation of the whole-brain network at increasingly finer spatial scales. We found that in healthy participants, scale-free distributions of node size and node degree were present across wakefulness, propofol sedation, and recovery, despite significant propofol-induced functional connectivity changes. In patients with UWS, the scale-free distribution of node degree was absent, reflecting a fundamental difference between the two groups in adaptive reconfiguration of functional interaction between network components. The maintenance of scale-invariance across propofol sedation in healthy participants suggests the presence of persistent, on-going self-organizing processes to a critical state--a capacity that is compromised in patients with UWS.