Recovery of consciousness is mediated by a network of discrete metastable activity states

Abstract

It is not clear how, after a large perturbation, the brain explores the vast space of potential neuronal activity states to recover those compatible with consciousness. Here, we analyze recovery from pharmacologically induced coma to show that neuronal activity en route to consciousness is confined to a low-dimensional subspace. In this subspace, neuronal activity forms discrete metastable states persistent on the scale of minutes. The network of transitions that links these metastable states is structured such that some states form hubs that connect groups of otherwise disconnected states. Although many paths through the network are possible, to ultimately enter the activity state compatible with consciousness, the brain must first pass through these hubs in an orderly fashion. This organization of metastable states, along with dramatic dimensionality reduction, significantly simplifies the task of sampling the parameter space to recover the state consistent with wakefulness on a physiologically relevant timescale.anesthesia | state transitions | spectral analysis | emergence T he brain exhibits a remarkable ability to recover normal function associated with wakefulness, even after large perturbations to its activity. Two well-known examples of this are anesthesia and brain injury (1, 2). How the brain recovers from large perturbations currently is unknown. Given the number of neurons involved, the potential space of activity is huge. Thus, it is not clear how the brain samples the vast parameter space to discover patterns of activity that are consistent with consciousness after a large perturbation.The simplest possibility for the recovery of consciousness (ROC) is that, driven by noise inherent in many aspects of neuronal activity (3), the brain performs a random walk through the parameter space until it eventually enters the region that is consistent with consciousness. An alternative possibility is that although the motion through the parameter space is not random, the trajectory nonetheless is smooth. Lastly, it is possible that en route to ROC, the brain passes through a set of discrete metastable states-that is, a series of jumps between long-lived activity configurations.The utility of metastable intermediates to the problem of ROC is well illustrated by analogy with protein folding. Levinthal's paradox (4) refers to the implausibility of a denatured protein recovering its native fold conformation by random walk alone, as the time required to randomly explore the conformational space will rapidly exceed the age of the universe, even for a small number of residues. (ii), a "small-world" structure, in which most states are connected only locally whereas a few central hub states connect widely, allowing rapid long-distance travel through the network; and (iii) a lattice structure, in which all states have approximately the same connectivity, allowing multiple routes to ROC.In this report, we demonstrate that in rats under isoflurane anesthesia, ROC occurs after the brain traverses a series of metastable in...

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