Science Translational Medicine
August 14, 2013
Adenauer G. Casali, Olivia Gosseries, Mario Rosanova et al.
1,299 citations
A new index called the perturbational complexity index (PCI) can objectively measure a person's level of consciousness without requiring them to respond or interact. PCI works by using transcranial magnetic stimulation to briefly perturb the cortex and then measuring the algorithmic complexity of the resulting brain activity patterns. The index was tested on healthy individuals during wakefulness, dreaming, nonrapid eye movement sleep, and under sedation with midazolam, xenon, and propofol, as well as on patients who had emerged from coma. PCI reliably distinguished conscious from unconscious states in single individuals across all conditions, including vegetative state, minimally conscious state, and locked-in syndrome.
Annals of Neurology
September 22, 2016
Silvia Casarotto, Angela Comanducci, Mario Rosanova et al.
504 citations
A brain-based measure called the Perturbational Complexity Index (PCI) can reliably distinguish conscious from unconscious individuals, even when they cannot speak or move. The index was first validated in 150 healthy and brain-injured people who could report their conscious state, achieving perfect accuracy in separating conscious from unconscious conditions. Applied to 81 noncommunicative patients, PCI correctly identified 94.7% of those in a minimally conscious state and revealed that 9 of 43 patients diagnosed as vegetative had PCI values overlapping with conscious individuals. These findings suggest that some behaviorally unresponsive patients may retain hidden conscious capacity.
NeuroImage
January 11, 2019
Michele Colombo, Martino Napolitani, Melanie Boly et al.
359 citations
During anesthesia, people may still be conscious even though they do not respond. A marker of consciousness based on the decay rate of the power spectral density (PSD) of resting EEG—measured by the spectral exponent β—was tested in healthy participants under xenon, propofol, or ketamine anesthesia (n=5 per group). Delayed reports indicated whether consciousness was present or absent. Xenon and propofol, which abolish consciousness, caused a steeper PSD decay (more negative β) compared to wakefulness. Ketamine, which preserves consciousness, showed a PSD decay similar to wakefulness overall but a flattening in high frequencies (20–40 Hz). The spectral exponent correlated strongly with the Perturbational Complexity Index (PCI), supporting its use as a marker of consciousness.
The International Journal of Neuropsychopharmacology
June 7, 2012
Wallace C. Duncan, Simone Sarasso, Fabio Ferrarelli et al.
253 citations
A single infusion of the NMDA receptor antagonist ketamine rapidly reduces depressive symptoms in patients with treatment-resistant major depressive disorder. In 30 patients, ketamine increased electroencephalogram slow wave activity during early non-REM sleep and raised plasma levels of brain-derived neurotrophic factor. The occurrence of high amplitude slow waves and their slope also increased, indicating enhanced synaptic strength. Changes in BDNF levels correlated with changes in EEG parameters, but only in patients who responded to ketamine. This suggests that enhanced synaptic plasticity, reflected by increased slow wave activity and BDNF, is part of the mechanism behind ketamine's rapid antidepressant effects.
Neuroscience of Consciousness
January 1, 2021
Simone Sarasso, Adenauer G. Casali, Silvia Casarotto et al.
183 citations
A growing body of empirical studies has identified complexity-related measures as reliable markers of consciousness across conditions including sleep, anesthesia, hallucinatory states, coma, and related disorders. These measures were proposed independently by researchers working within different frameworks and using diverse methods. This paper systematically reviews that literature, identifies a common denominator among the measures, and traces it to theoretical principles and predictions made over 20 years ago. The authors highlight a consistent trajectory across two decades of consciousness research and offer a provisional taxonomy of the existing work. They argue that this convergence provides a solid foundation for designing future experiments and advancing the field.
Clinical EEG and Neuroscience
January 1, 2014
Simone Sarasso, Mario Rosanova, Adenauer G. Casali et al.
164 citations
Consciousness requires both functional integration and differentiation in the brain, a property termed brain complexity. Transcranial Magnetic Stimulation combined with electroencephalography (TMS/EEG) can quantify this complexity. Studies consistently show that the complexity of the cortical response to TMS collapses during loss of consciousness in deep sleep, anesthesia, and vegetative state after severe brain injury. Complexity recovers when consciousness returns during wakefulness, dreaming, the minimally conscious state, or locked-in syndrome. This approach may help understand the pathophysiology of disorders of consciousness and requires careful methodological attention.
Neuroscience of Consciousness
January 27, 2017
Michael Schartner, Andrea Pigorini, Steve A. Gibbs et al.
158 citations
During non-rapid eye movement (NREM) sleep, neural dynamical complexity—measured by Lempel-Ziv complexity, amplitude coalition entropy, and synchrony coalition entropy—decreased substantially across broadly distributed brain regions in ten epilepsy patients. This decrease partially reversed during late-night NREM sleep and returned to wakeful rest levels during rapid eye movement (REM) sleep. Local brain regions mirrored this global pattern. The frontal lobe showed elevated signal complexity. These changes were not solely due to spectral power differences. The findings suggest that level of consciousness correlates with neural dynamical complexity.
iScience
May 19, 2023
Andres Ort, John W Smallridge, Simone Sarasso et al.
47 citations
Classical psychedelic drugs like psilocybin induce profound changes in consciousness, including heightened sensory-emotional awareness and arousal, accompanied by increased spontaneous EEG signal diversity. By combining Transcranial Magnetic Stimulation (TMS) with EEG, this work shows that psilocybin creates a state of increased chaotic brain activity, which is not due to altered complexity in causal interactions between brain regions. The study also maps regional effects of psilocybin on TMS-evoked activity, identifying changes in frontal brain structures that may relate to the phenomenology of psychedelic experiences.
Current biology : CB
June 9, 2025
Davide Albertini, Maria Del Vecchio, Ivana Sartori et al.
9 citations
Conscious perception of simple touch depends on sustained neural activity in higher-order somatosensory regions, specifically the posterior perisylvian areas. Using human intracortical recordings, tonic responses in these regions showed all-or-nothing patterns at the sensory threshold, remained unchanged whether or not participants reported the stimulus, and most clearly distinguished perceived from non-perceived stimuli. These dynamics may serve as an organizational principle of somatosensory awareness.
PLoS biology
October 1, 2025
Michele Angelo Colombo, Jacopo Favaro, Ezequiel Mikulan et al.
7 citations
After hemispherotomy surgery for epilepsy, which disconnects an entire brain hemisphere, the isolated cortex shows brainwave patterns typical of deep sleep or anesthesia, not wakefulness. In 10 pediatric patients, EEG recordings revealed prominent slow oscillations and a steeper spectral decay in the disconnected hemisphere, while the connected hemisphere maintained normal waking patterns. These sleep-like patterns persisted years after surgery, suggesting the isolated cortex likely lacks awareness.
Eur J Neurosci
November 18, 2024
Athina Tzovara, Thomas Andrillon, Katrin H. Preller et al.
Consciousness research has two main approaches: studying the global state of being conscious (e.g., during sleep, anesthesia, or brain injury) and studying the specific contents of consciousness (e.g., perceiving a particular stimulus). This special issue collects 12 articles that investigate mechanisms and measures of consciousness. Key findings include that during sevoflurane anesthesia in mice, neural complexity in the somatosensory cortex diminishes while firing rates and long-range connections decrease in deep cortical layers. Other work shows that during anesthesia, word judgments can be preserved while working memory is impaired. Auditory EEG responses during sleep have complexity and spectral slope modulated by sleep stages.
bioRxiv Preprint Server
December 9, 2025
Tomas Berjaga-Buisan, Juan Manuel Monti, Martina Cortada et al.
preprint
A non-invasive framework using generative whole-brain models of non-equilibrium dynamics reveals that violations of the Fluctuation-Dissipation Theorem (FDT) in spontaneous brain signals are reduced in unresponsive disorders of consciousness and anesthesia compared to conscious states, mirroring patterns seen with the Perturbational Complexity Index (PCI). This links PCI to fundamental physics principles and offers new objective, model-based tools for assessing consciousness loss and recovery.