Nature reviews. Neuroscience
April 20, 2016
Christof Koch, Marcello Massimini, Melanie Boly et al.
1,654 citations
The neural correlates of consciousness—the minimum neural mechanisms sufficient for any one specific conscious percept—are primarily localized to a posterior cortical hot zone that includes sensory areas, rather than to a fronto-parietal network involved in task monitoring and reporting. Some candidate neurophysiological markers of consciousness have proved illusory, while measures of differentiation and integration of neural activity offer more promising quantitative indices of consciousness.
Science
September 29, 2005
Marcello Massimini, Fabio Ferrarelli, Reto Huber et al.
1,603 citations
During non-rapid eye movement sleep, the brain's response to a direct cortical stimulus is stronger but fails to propagate beyond the stimulation site, unlike during quiet wakefulness when the activation spreads to distant connected areas. This breakdown in cortical effective connectivity may explain why consciousness fades during certain sleep stages despite ongoing brain activity.
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.
Journal of Neuroscience
October 4, 2017
Melanie Boly, Marcello Massimini, Naotsugu Tsuchiya et al.
591 citations
The role of the frontal cortex in consciousness is debated. This Perspective critically reviews clinical and neuroimaging evidence for the involvement of the front versus the back of the cortex in specifying conscious contents and discusses promising research avenues.
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.
Cognitive Neuroscience
July 1, 2010
Marcello Massimini, Fabio Ferrarelli, Michael J. Murphy et al.
205 citations
During the first REM sleep episode of the night, transcranial magnetic stimulation (TMS) triggered widespread and differentiated patterns of cortical activation on electroencephalography (EEG), similar to those observed during wakefulness. In contrast, during NREM sleep, cortical activations became more local and stereotypical, indicating impaired intracortical dialogue. These findings suggest that TMS combined with high-density EEG can probe the internal dialogue of the thalamocortical system, potentially offering a method to assess brain function in patients who are unable to move or communicate.
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.
Trends in Neurosciences
December 10, 2019
Tim Bayne, Anil K. Seth, Marcello Massimini
146 citations
Consciousness might persist in brain tissue that is fully causally isolated from the body and environment, forming an 'island of awareness'—a conscious state neither shaped by sensory input nor able to produce motor output. This opinion paper examines three potential cases: ex cranio brains (brains kept alive outside the body), the disconnected hemisphere after hemispherotomy surgery, and cerebral organoids (lab-grown brain tissue). The authors discuss methods for detecting consciousness in such disconnected brains, noting that current detection tools rely on sensory or motor interaction and may not apply. They argue that discovering islands of awareness would have profound ethical and legal implications and would challenge theories holding that consciousness requires embodiment or interaction with the world.
Annals of the New York Academy of Sciences
May 1, 2008
Giulio Tononi, Marcello Massimini
135 citations
Consciousness fades during deep NREM sleep early in the night even though cortical neurons remain active and receive sensory inputs. According to integrated information theory, what matters for consciousness is not firing rates or synchronization but the brain's ability to integrate information—having a large repertoire of available states that cannot be decomposed into independent subsystems. Experiments using transcranial magnetic stimulation and high-density electroencephalography (TMS/hd-EEG) in humans tested this prediction. The sleeping brain, though active and reactive, loses its ability to enter states that are both integrated and differentiated; it either breaks into causally independent modules, responding with short local activation, or produces an explosive, aspecific slow wave.
Nature Communications
February 25, 2022
Minji Lee, Leandro Sanz, Alice Barra et al.
120 citations
A deep-learning-based explainable consciousness indicator (ECI) uses EEG responses to transcranial magnetic stimulation and resting-state EEG to separately quantify arousal and awareness. Tested during sleep (n=6), general anesthesia (n=16), and severe brain injury (n=34), ECI distinguishes states such as ketamine-induced anesthesia and rapid eye movement sleep, which combine low arousal with high awareness. Parietal brain regions are most relevant for these measurements. The indicator offers a way to disentangle the two components of consciousness across physiological, pharmacological, and pathological conditions.
Neuron
May 15, 2024
Johan F Storm, P Christiaan Klink, Jaan Aru et al.
108 citations
Consciousness may be explained by multiple, partly compatible theories rather than a single winner. A group of scientists representing different theories argue that various accounts often address different aspects or mechanistic levels of conscious experience, so they do not necessarily contradict each other. Instead, several theories may converge on fundamental neuronal mechanisms and be complementary, allowing multiple perspectives to simultaneously advance understanding. The authors advocate for unifying, integration-oriented approaches that combine valuable elements from diverse theories, an approach that has so far been largely neglected.
PLoS ONE
May 13, 2015
Melanie Boly, Shuntaro Sasai, Olivia Gosseries et al.
69 citations
A meaningful sequence of stimuli, like movie frames, triggers varied experiences, while meaningless stimuli, like TV noise, produce a uniform experience despite physical differences. The differentiation of cortical responses, measured by Lempel-Ziv complexity of functional MRI images, reflects the overall meaningfulness of a stimulus set rather than differences among stimuli. Brain activity patterns showed highest differentiation during a movie, intermediate for a temporally scrambled movie, and minimal for spatially scrambled TV noise, even though overall cortical activation was strong and widespread in all conditions. Meaningfulness also correlated with higher information integration among cortical regions. This approach can assess stimulus meaningfulness without identifying relevant features or neural locations.
Scientific Reports
August 5, 2016
Jaakko O. Nieminen, Olivia Gosseries, Marcello Massimini et al.
60 citations
During non-rapid eye movement (NREM) sleep, the brain's response to transcranial magnetic stimulation (TMS) differs depending on whether the person is conscious (dreaming) or not. When subjects reported no conscious experience upon awakening, TMS evoked a larger negative deflection and a shorter phase-locked response compared to when they reported a dream. The amplitude of the negative deflection—a hallmark of neuronal bistability—was inversely correlated with the length of the dream report. These findings suggest that variations in the level of consciousness within the same physiological state are associated with changes in underlying cortical bistability.
bioRxiv Preprint Server
March 19, 2017
Melanie Boly, Marcello Massimini, Naotsugu Tsychiya et al.
56 citations
preprint
The role of the frontal cortex in consciousness is debated. This perspective critically reviews clinical and neuroimaging evidence on whether the front or back of the cortex specifies conscious contents, and discusses promising research avenues. The authors argue that current evidence does not clearly support a primary role for the frontal cortex in generating conscious experience, pointing instead to posterior regions as more directly involved. They suggest that future research should focus on distinguishing neural correlates of consciousness from prerequisites and consequences.
Progress in brain research
January 1, 2009
Melanie Boly, Marcello Massimini, Giulio Tononi
50 citations
Assessing consciousness in noncommunicative brain-damaged patients is challenging because behavioral responses are limited by motor impairment and cognitive dysfunctions. Recent studies have compared brain activity in comatose, vegetative state, sleep, anesthesia, and epileptic seizure conditions, but no consensus on the brain mechanisms generating consciousness has emerged. The authors argue that combining theoretical approaches with experimental procedures is necessary for a coherent explanation of consciousness loss across these conditions. They review current theories, emphasizing the Integrated Information Theory of Consciousness (IITC), which predicts reduced consciousness in certain states. While technical and conceptual issues limit its clinical applicability, some predictions are testable with available imaging techniques.
Brain Injury
August 1, 2014
Martino Napolitani, Olivier Bodart, Paola Canali et al.
44 citations
Transcranial magnetic stimulation combined with high-density electroencephalography (TMS-hdEEG) offers advantages over other brain imaging techniques for assessing consciousness. A key requirement for consciousness is the brain's capacity to rapidly integrate information across specialized cortical areas. TMS-EEG stimulates any cortical area and records immediate electrical responses, successfully measuring changes in brain complexity under physiological, pharmacological, and pathological conditions. This technique reliably discriminates between conscious and unconscious patients at the single subject level, though further validation as a clinical tool is needed.
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.
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.
bioRxiv Preprint Server
April 18, 2023
Martin Breyton, Jan Fousek, Giovanni Rabuffo et al.
preprint
Consciousness depends on the brain's ability to produce complex, variable patterns of activity after a perturbation, but measuring this directly is difficult. Using a whole-brain model, researchers found that such complexity only arises when spontaneous brain activity is highly fluid—meaning functional networks reorganize extensively. This fluid regime can be captured by a small set of dynamical systems metrics, which predict the effects of consciousness-altering drugs like Xenon, Propofol, and Ketamine. These predictions were validated in 15 subjects at different consciousness levels, showing agreement with established perturbational complexity measures but using a simpler, more accessible paradigm. The findings point to complexity properties underlying consciousness.
The Journal of neuroscience : the official journal of the Society for Neuroscience
November 8, 2017
Johan F Storm, Melanie Boly, Adenauer G Casali et al.
The mind-body problem—how consciousness arises from brain processes—has long been considered a philosophical puzzle but is now being tackled empirically. This review describes progress since Crick and Koch (1998) proposed searching for the neural correlates of consciousness (NCC). It covers content-specific NCCs, which link particular brain activity to specific experiences, and the full NCC, which supports entire conscious states. The authors discuss methodological advances for isolating conscious experience from enabling functions, suggest that reconsidering the frontal cortex's role may refine NCCs, advocate for objective brain-based measures of consciousness independent of sensory or executive processes, and show how animal studies reveal network phenomena relevant to consciousness mechanisms.