Criticality of resting-state EEG predicts perturbational complexity and level of consciousness during anesthesia.

Consciousness has been proposed to be supported by electrophysiological patterns poised at criticality, a dynamical regime which exhibits adaptive computational properties, maximally complex patterns and divergent sensitivity to perturbation. Here, we investigated dynamical properties of the resting-state electroencephalogram of healthy subjects undergoing general anesthesia with propofol, xenon or ketamine. We then studied the relation of these dynamic properties with the perturbational complexity index (PCI), which has shown remarkably high sensitivity in detecting consciousness independent of behavior. All participants were unresponsive under anesthesia, while consciousness was retained only during ketamine anesthesia (in the form of vivid dreams)., enabling an experimental dissociation between unresponsiveness and unconsciousness. We estimated (i) avalanche criticality, (ii) chaoticity, and (iii) criticality-related measures, and found that states of unconsciousness were characterized by a distancing from both the edge of activity propagation and the edge of chaos. We were then able to predict individual subjects' PCI (i.e., PCImax) with a mean absolute error below 7%. Our results establish a firm link between the PCI and criticality and provide further evidence for the role of criticality in the emergence of consciousness.

The maturation of aperiodic EEG activity across development reveals a progressive differentiation of wakefulness from sleep.

During development, the brain undergoes radical structural and functional changes following a posterior-to-anterior gradient, associated with profound changes of cortical electrical activity during both wakefulness and sleep. However, a systematic assessment of the developmental effects on aperiodic EEG activity maturation across vigilance states is lacking, particularly regarding its topographical aspects. Here, in a population of 160 healthy infants, children and teenagers (from 2 to 17 years, 10 subjects for each year), we investigated the development of aperiodic EEG activity in wakefulness and sleep. Specifically, we parameterized the shape of the aperiodic background of the EEG Power Spectral Density (PSD) by means of the spectral exponent and offset; the exponent reflects the rate of exponential decay of power over increasing frequencies and the offset reflects an estimate of the y-intercept of the PSD. We found that sleep and development caused the EEG-PSD to rotate over opposite directions: during wakefulness the PSD showed a flatter decay and reduced offset over development, while during sleep it showed a steeper decay and a higher offset as sleep becomes deeper. During deep sleep (N2, N3) only the spectral offset decreased over age, indexing a broad-band voltage reduction. As a result, the difference between values in deep sleep and those in both light sleep (N1) and wakefulness increased with age, suggesting a progressive differentiation of wakefulness from sleep EEG activity, most prominent over the frontal regions, the latest to complete maturation. Notably, the broad-band spectral exponent values during deep sleep stages were entirely separated from wakefulness values, consistently across developmental ages and in line with previous findings in adults. Concerning topographical development, the location showing the steepest PSD decay and largest offset shifted from posterior to anterior regions with age. This shift, particularly evident during deep sleep, paralleled the migration of sleep slow wave activity and was consistent with neuroanatomical and cognitive development. Overall, aperiodic EEG activity distinguishes wakefulness from sleep regardless of age; while, during development, it reveals a postero-anterior topographical maturation and a progressive differentiation of wakefulness from sleep. Our study could help to interpret changes due to pathological conditions and may elucidate the neurophysiological processes underlying the development of wakefulness and sleep.

Beyond alpha power: EEG spatial and spectral gradients robustly stratify disorders of consciousness.

Neurophysiological markers can overcome the limitations of behavioural assessments of Disorders of Consciousness (DoC). EEG alpha power emerged as a promising marker for DoC, although long-standing literature reported alpha power being sustained during anesthetic-induced unconsciousness, and reduced during dreaming and hallucinations. We hypothesized that EEG power suppression caused by severe anoxia could explain this conflict. Accordingly, we split DoC patients (n = 87) in postanoxic and non-postanoxic cohorts. Alpha power was suppressed only in severe postanoxia but failed to discriminate un/consciousness in other aetiologies. Furthermore, it did not generalize to an independent reference dataset (n = 65) of neurotypical, neurological, and anesthesia conditions. We then investigated EEG spatio-spectral gradients, reflecting anteriorization and slowing, as alternative markers. In non-postanoxic DoC, these features, combined in a bivariate model, reliably stratified patients and indexed consciousness, even in unresponsive patients identified as conscious by an independent neural marker (the Perturbational Complexity Index). Crucially, this model optimally generalized to the reference dataset. Overall, alpha power does not index consciousness; rather, its suppression entails diffuse cortical damage, in postanoxic patients. As an alternative, EEG spatio-spectral gradients, reflecting distinct pathophysiological mechanisms, jointly provide a robust, parsimonious, and generalizable marker of consciousness, whose clinical application may guide rehabilitation efforts.

The spectral exponent of the resting EEG indexes the presence of consciousness during unresponsiveness induced by propofol, xenon, and ketamine.

Despite the absence of responsiveness during anesthesia, conscious experience may persist. However, reliable, easily acquirable and interpretable neurophysiological markers of the presence of consciousness in unresponsive states are still missing. A promising marker is based on the decay-rate of the power spectral density (PSD) of the resting EEG. We acquired resting electroencephalogram (EEG) in three groups of healthy participants (n = 5 each), before and during anesthesia induced by either xenon, propofol or ketamine. Dosage of each anesthetic agent was tailored to yield unresponsiveness (Ramsay score = 6). Delayed subjective reports assessed whether conscious experience was present ('Conscious report') or absent/inaccessible to recall ('No Report'). We estimated the decay of the PSD of the resting EEG-after removing oscillatory peaks-via the spectral exponent ß, for a broad band (1-40 Hz) and narrower sub-bands (1-20 Hz, 20-40 Hz). Within-subject anesthetic changes in ß were assessed. Furthermore, based on ß, 'Conscious report' states were discriminated against 'no report' states. Finally, we evaluated the correlation of the resting spectral exponent with a recently proposed index of consciousness, the Perturbational Complexity Index (PCI), derived from a previous TMS-EEG study. The spectral exponent of the resting EEG discriminated states in which consciousness was present (wakefulness, ketamine) from states where consciousness was reduced or abolished (xenon, propofol). Loss of consciousness substantially decreased the (negative) broad-band spectral exponent in each subject undergoing xenon or propofol anesthesia-indexing an overall steeper PSD decay. Conversely, ketamine displayed an overall PSD decay similar to that of wakefulness-consistent with the preservation of consciousness-yet it showed a flattening of the decay in the high-frequencies (20-40 Hz)-consistent with its specific mechanism of action. The spectral exponent was highly correlated to PCI, corroborating its interpretation as a marker of the presence of consciousness. A steeper PSD of the resting EEG reliably indexed unconsciousness in anesthesia, beyond sheer unresponsiveness.