Assessing mismatch negativity (MMN) and P3b within-individual sensitivity - A comparison between the local-global paradigm and two specialized oddball sequences.

Mismatch negativity (MMN) and P3b are well known for their clinical utility. There exists no gold standard, however, for acquiring them as EEG markers of consciousness in clinical settings. This may explain why the within-individual sensitivity of MMN/P3b paradigms is often quite poor and why seemingly identical EEG markers can behave differently across Disorders of consciousness (DoC) studies. Here, we compare two traditional paradigms for MMN or P3b assessment with the recently more popular local-global paradigm that promises to assess MMN and P3b orthogonally within one oddball sequence. All three paradigms were administered to healthy participants (N = 15) with concurrent EEG. A clear MMN and local effect were found for 15/15 participants. The P3b and global effect were found for 14/15 and 13/15 participants, respectively. There were no systematic differences between the global effect and P3b. Indeed, P3b amplitude was highly correlated across paradigms. The local effect differed clearly from the MMN, however. It occurred earlier than MMN and was followed by a much more prominent P3a. The peak latencies and amplitudes were also not correlated across paradigms. Caution should therefore be exercised when comparing the local effect and MMN across studies. We conclude that the within-individual MMN sensitivity is adequate for both the local-global and a dedicated MMN paradigm. The within-individual sensitivity of P3b was lower than expected for both the local-global and a dedicated P3b paradigm, which may explain the often-low sensitivity of P3b paradigms in patients with DoC.

Unconsciousness or unresponsiveness in akinetic mutism? Insights from a multimodal longitudinal exploration.

The clinical assessment of patients with disorders of consciousness (DoC) relies on the observation of behavioural responses to standardised sensory stimulation. However, several medical comorbidities may directly impair the production of reproducible and appropriate responses, thus reducing the sensitivity of behaviour-based diagnoses. One such comorbidity is akinetic mutism (AM), a rare neurological syndrome characterised by the inability to initiate volitional motor responses, sometimes associated with clinical presentations that overlap with those of DoC. In this paper, we describe the case of a patient with large bilateral mesial frontal lesions, showing prolonged behavioural unresponsiveness and severe disorganisation of electroencephalographic (EEG) background, compatible with a vegetative state/unresponsive wakefulness syndrome (VS/UWS). By applying an unprecedented multimodal battery of advanced imaging and electrophysiology-based techniques (AIE) encompassing spontaneous EEG, evoked potentials, event-related potentials, transcranial magnetic stimulation combined with EEG and structural and functional MRI, we provide the following: (i) a demonstration of the preservation of consciousness despite unresponsiveness in the context of AM, (ii) a plausible neurophysiological explanation for behavioural unresponsiveness and its subsequent recovery during rehabilitation stay and (iii) novel insights into the relationships between DoC, AM and parkinsonism. The present case offers proof-of-principle evidence supporting the clinical utility of a multimodal hierarchical workflow that combines AIEs to detect covert signs of consciousness in unresponsive patients.

Dissociations between spontaneous electroencephalographic features and the perturbational complexity index in the minimally conscious state.

The analysis of spontaneous electroencephalogram (EEG) is a cornerstone in the assessment of patients with disorders of consciousness (DoC). Although preserved EEG patterns are highly suggestive of consciousness even in unresponsive patients, moderately or severely abnormal patterns are difficult to interpret. Indeed, growing evidence shows that consciousness can be present despite either large delta or reduced alpha activity in spontaneous EEG. Quantifying the complexity of EEG responses to direct cortical perturbations (perturbational complexity index [PCI]) may complement the observational approach and provide a reliable assessment of consciousness even when spontaneous EEG features are inconclusive. To seek empirical evidence of this hypothesis, we compared PCI with EEG spectral measures in the same population of minimally conscious state (MCS) patients (n = 40) hospitalized in rehabilitation facilities. We found a remarkable variability in spontaneous EEG features across MCS patients as compared with healthy controls: in particular, a pattern of predominant delta and highly reduced alpha power-more often observed in vegetative state/unresponsive wakefulness syndrome (VS/UWS) patients-was found in a non-negligible number of MCS patients. Conversely, PCI values invariably fell above an externally validated empirical cutoff for consciousness in all MCS patients, consistent with the presence of clearly discernible, albeit fleeting, behavioural signs of awareness. These results confirm that, in some MCS patients, spontaneous EEG rhythms may be inconclusive about the actual capacity for consciousness and suggest that a perturbational approach can effectively compensate for this pitfall with practical implications for the individual patient's stratification and tailored rehabilitation.

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.

Exploration of Theta Burst-Induced Modulation of Transcranial Magnetic Stimulation-Evoked Potentials Over the Motor Cortex.

OBJECTIVES: This study investigates the way theta burst stimulation (TBS) applied to the motor cortex (M1) affects TMS-evoked potentials (TEPs). There have been few direct comparisons of continuous TBS (cTBS) and intermittent TBS (iTBS), and there is a lack of consensus from existing literature on the induced effects. We performed an exploratory trial to assess the effect of M1-cTBS and M1-iTBS on TEP components. MATERIALS AND METHODS: In a cross-over design, 15 participants each completed three experimental sessions with ≥one week in between sessions. The effect of a single TBS train administered over M1 was investigated using TEPs recorded at the same location, 20 to 30 minutes before and in the first 10 minutes after the intervention. In each session, a different type of TBS (cTBS, iTBS, or active control cTBS) was administered in a single-blinded randomized order. For six different TEP components (N15, P30, N45, P60, N100, and P180), amplitude was compared before and after the intervention using cluster-based permutation (CBP) analysis. RESULTS: We were unable to identify a significant modulation of any of the six predefined M1 TEP components after a single train of TBS. When waiving statistical correction for multiple testing in view of the exploratory nature of the study, the CBP analysis supports a reduction of the P180 amplitude after iTBS (p = 0.015), whereas no effect was observed after cTBS or in the active control condition. The reduction occurred in ten of 15 subjects, showing intersubject variability. CONCLUSIONS: The observed decrease in the P180 amplitude after iTBS may suggest a neuromodulatory effect of iTBS. Despite methodologic issues related to our study and the potential sensory contamination within this latency range of the TEP, we believe that our finding deserves further investigation in hypothesis-driven trials of adequate power and proper design, focusing on disentanglement between TEPs and peripherally evoked potentials, in addition to indicating reproducibility across sessions and subjects. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT05206162.

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.

Neocortical and medial temporal seizures have distinct impacts on brain responsiveness.

Focal epileptic seizures are characterized by abnormal neuronal discharges that can spread to other cortical areas and interfere with brain activity, thereby altering the patient's experience and behavior. The origin of these pathological neuronal discharges encompasses various mechanisms that converge toward similar clinical manifestations. Recent studies have suggested that medial temporal lobe (MTL) and neocortical (NC) seizures are often underpinned by two characteristic onset patterns, which, respectively, affect and spare synaptic transmission in cortical slices. However, these synaptic alterations and their effects have never been confirmed or studied in intact human brains. To fill this gap, we here evaluate whether responsiveness of MTL and NC are differentially affected by focal seizures, using a unique data set of cortico-cortical evoked potentials (CCEPs) collected during seizures triggered by single-pulse electrical stimulation (SPES). We find that responsiveness is abruptly reduced by the onset of MTL seizures, despite increased spontaneous activity, whereas it is preserved in the case of NC seizures. The present results provide an extreme example of dissociation between responsiveness and activity and show that brain networks are diversely affected by the onset of MTL and NC seizures, thus extending at the whole brain level the evidence of synaptic alteration found in vitro.

Electrophysiological findings in migraine may reflect abnormal synaptic plasticity mechanisms: A narrative review.

BACKGROUND: The cyclical brain disorder of sensory processing accompanying migraine phases lacks an explanatory unified theory. METHODS: We searched Pubmed for non-invasive neurophysiological studies on migraine and related conditions using transcranial magnetic stimulation, electroencephalography, visual and somatosensory evoked potentials. We summarized the literature, reviewed methods, and proposed a unified theory for the pathophysiology of electrophysiological abnormalities underlying migraine recurrence. RESULTS: All electrophysiological modalities have determined specific changes in brain dynamics across the different phases of the migraine cycle. Transcranial magnetic stimulation studies show unbalanced recruitment of inhibitory and excitatory circuits, more consistently in aura, which ultimately results in a substantially distorted response to neuromodulation protocols. Electroencephalography investigations highlight a steady pattern of reduced alpha and increased slow rhythms, largely located in posterior brain regions, which tends to normalize closer to the attacks. Finally, non-painful evoked potentials suggest dysfunctions in habituation mechanisms of sensory cortices that revert during ictal phases. CONCLUSION: Electrophysiology shows dynamic and recurrent functional alterations within the brainstem-thalamus-cortex loop varies continuously and recurrently in migraineurs. Given the central role of these structures in the selection, elaboration, and learning of sensory information, these functional alterations suggest chronic, probably genetically determined dysfunctions of the synaptic short- and long-term learning mechanisms.

Depth of sedation with dexmedetomidine increases transcranial magnetic stimulation-evoked potential amplitude non-linearly.

BACKGROUND: Cortical excitability is higher in unconsciousness than in wakefulness, but it is unclear how this relates to anaesthesia. We investigated cortical excitability in response to dexmedetomidine, the effects of which are not fully known. METHODS: We recorded transcranial magnetic stimulation (TMS) and EEG in frontal and parietal cortex of 20 healthy subjects undergoing dexmedetomidine sedation in four conditions (baseline, light sedation, deep sedation, recovery). We used the first component (0-30 ms) of the TMS-evoked potential (TEP) to measure cortical excitability (amplitude), slope, and positive and negative peak latencies (collectively, TEP indices). We used generalised linear mixed models to test the effect of condition, brain region, and responsiveness on TEP indices. RESULTS: Compared with baseline, amplitude in the frontal cortex increased by 6.52 µV (P<0.001) in light sedation, 4.55 µV (P=0.003) in deep sedation, and 5.03 µV (P<0.001) in recovery. Amplitude did not change in the parietal cortex. Compared with baseline, slope increased in all conditions (P<0.02) in the frontal but not parietal cortex. The frontal cortex showed 5.73 µV higher amplitude (P<0.001), 0.63 µV ms-1 higher slope (P<0.001), and 2.2 ms shorter negative peak latency (P=0.001) than parietal areas. Interactions between dexmedetomidine and region had effects over amplitude (P=0.004) and slope (P=0.009), with both being higher in light sedation, deep sedation, and recovery compared with baseline. CONCLUSIONS: Transcranial magnetic stimulation-evoked potential amplitude changes non-linearly as a function of depth of sedation by dexmedetomidine, with a region-specific paradoxical increase. Future research should investigate other anaesthetics to elucidate the link between cortical excitability and depth of sedation.

Measuring Consciousness in the Intensive Care Unit.

Early reemergence of consciousness predicts long-term functional recovery for patients with severe brain injury. However, tools to reliably detect consciousness in the intensive care unit are lacking. Transcranial magnetic stimulation electroencephalography has the potential to detect consciousness in the intensive care unit, predict recovery, and prevent premature withdrawal of life-sustaining therapy.

Measures of differentiation and integration: One step closer to consciousness.

Interpreting empirical measures of integration and differentiation as indices of cortical performance and memory consolidation during wakefulness rather than consciousness per se is inconsistent with the literature. Recent studies show that these theory-inspired measures can dissociate from such processes and reliably index the brain's capacity for experience. We consider this as a positive trend in consciousness research.

Neural correlates of consciousness: progress and problems.

There have been a number of advances in the search for the neural correlates of consciousness--the minimum neural mechanisms sufficient for any one specific conscious percept. In this Review, we describe recent findings showing that the anatomical neural correlates of consciousness 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. We also discuss some candidate neurophysiological markers of consciousness that have proved illusory, and measures of differentiation and integration of neural activity that offer more promising quantitative indices of consciousness.

Integrated information theory: from consciousness to its physical substrate.

In this Opinion article, we discuss how integrated information theory accounts for several aspects of the relationship between consciousness and the brain. Integrated information theory starts from the essential properties of phenomenal experience, from which it derives the requirements for the physical substrate of consciousness. It argues that the physical substrate of consciousness must be a maximum of intrinsic cause-effect power and provides a means to determine, in principle, the quality and quantity of experience. The theory leads to some counterintuitive predictions and can be used to develop new tools for assessing consciousness in non-communicative patients.

Local sleep-like cortical reactivity in the awake brain after focal injury.

The functional consequences of focal brain injury are thought to be contingent on neuronal alterations extending beyond the area of structural damage. This phenomenon, also known as diaschisis, has clinical and metabolic correlates but lacks a clear electrophysiological counterpart, except for the long-standing evidence of a relative EEG slowing over the injured hemisphere. Here, we aim at testing whether this EEG slowing is linked to the pathological intrusion of sleep-like cortical dynamics within an awake brain. We used a combination of transcranial magnetic stimulation and electroencephalography (TMS/EEG) to study cortical reactivity in a cohort of 30 conscious awake patients with chronic focal and multifocal brain injuries of ischaemic, haemorrhagic and traumatic aetiology. We found that different patterns of cortical reactivity typically associated with different brain states (coma, sleep, wakefulness) can coexist within the same brain. Specifically, we detected the occurrence of prominent sleep-like TMS-evoked slow waves and off-periods-reflecting transient suppressions of neuronal activity-in the area surrounding focal cortical injuries. These perilesional sleep-like responses were associated with a local disruption of signal complexity whereas complex responses typical of the awake brain were present when stimulating the contralesional hemisphere. These results shed light on the electrophysiological properties of the tissue surrounding focal brain injuries in humans. Perilesional sleep-like off-periods can disrupt network activity but are potentially reversible, thus representing a principled read-out for the neurophysiological assessment of stroke patients, as well as an interesting target for rehabilitation.

Mechanisms Underlying Disorders of Consciousness: Bridging Gaps to Move Toward an Integrated Translational Science.

AIM: In order to successfully detect, classify, prognosticate, and develop targeted therapies for patients with disorders of consciousness (DOC), it is crucial to improve our mechanistic understanding of how severe brain injuries result in these disorders. METHODS: To address this need, the Curing Coma Campaign convened a Mechanisms Sub-Group of the Coma Science Work Group (CSWG), aiming to identify the most pressing knowledge gaps and the most promising approaches to bridge them. RESULTS: We identified a key conceptual gap in the need to differentiate the neural mechanisms of consciousness per se, from those underpinning connectedness to the environment and behavioral responsiveness. Further, we characterised three fundamental gaps in DOC research: (1) a lack of mechanistic integration between structural brain damage and abnormal brain function in DOC; (2) a lack of translational bridges between micro- and macro-scale neural phenomena; and (3) an incomplete exploration of possible synergies between data-driven and theory-driven approaches. CONCLUSION: In this white paper, we discuss research priorities that would enable us to begin to close these knowledge gaps. We propose that a fundamental step towards this goal will be to combine translational, multi-scale, and multimodal data, with new biomarkers, theory-driven approaches, and computational models, to produce an integrated account of neural mechanisms in DOC. Importantly, we envision that reciprocal interaction between domains will establish a "virtuous cycle," leading towards a critical vantage point of integrated knowledge that will enable the advancement of the scientific understanding of DOC and consequently, an improvement of clinical practice.

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.

Bistability, Causality, and Complexity in Cortical Networks: An In Vitro Perturbational Study.

Measuring the spatiotemporal complexity of cortical responses to direct perturbations provides a reliable index of the brain's capacity for consciousness in humans under both physiological and pathological conditions. Upon loss of consciousness, the complex pattern of causal interactions observed during wakefulness collapses into a stereotypical slow wave, suggesting that cortical bistability may play a role. Bistability is mainly expressed in the form of slow oscillations, a default pattern of activity that emerges from cortical networks in conditions of functional or anatomical disconnection. Here, we employ an in vitro model to understand the relationship between bistability and complexity in cortical circuits. We adapted the perturbational complexity index applied in humans to electrically stimulated cortical slices under different neuromodulatory conditions. At this microscale level, we demonstrate that perturbational complexity can be effectively modulated by pharmacological reduction of bistability and, albeit to a lesser extent, by enhancement of excitability, providing mechanistic insights into the macroscale measurements performed in humans.

Are the Neural Correlates of Consciousness in the Front or in the Back of the Cerebral Cortex? Clinical and Neuroimaging Evidence.

The role of the frontal cortex in consciousness remains a matter of debate. In this Perspective, we will critically review the clinical and neuroimaging evidence for the involvement of the front versus the back of the cortex in specifying conscious contents and discuss promising research avenues.Dual Perspectives Companion Paper: Should a Few Null Findings Falsify Prefrontal Theories of Conscious Perception?, by Brian Odegaard, Robert T. Knight, and Hakwan Lau.

Consciousness Regained: Disentangling Mechanisms, Brain Systems, and Behavioral Responses.

How consciousness (experience) arises from and relates to material brain processes (the "mind-body problem") has been pondered by thinkers for centuries, and is regarded as among the deepest unsolved problems in science, with wide-ranging theoretical, clinical, and ethical implications. Until the last few decades, this was largely seen as a philosophical topic, but not widely accepted in mainstream neuroscience. Since the 1980s, however, novel methods and theoretical advances have yielded remarkable results, opening up the field for scientific and clinical progress. Since a seminal paper by Crick and Koch (1998) claimed that a science of consciousness should first search for its neural correlates (NCC), a variety of correlates have been suggested, including both content-specific NCCs, determining particular phenomenal components within an experience, and the full NCC, the neural substrates supporting entire conscious experiences. In this review, we present recent progress on theoretical, experimental, and clinical issues. Specifically, we (1) review methodological advances that are important for dissociating conscious experience from related enabling and executive functions, (2) suggest how critically reconsidering the role of the frontal cortex may further delineate NCCs, (3) advocate the need for general, objective, brain-based measures of the capacity for consciousness that are independent of sensory processing and executive functions, and (4) show how animal studies can reveal population and network phenomena of relevance for understanding mechanisms of consciousness.

Human fronto-parietal response scattering subserves vigilance at night.

Lack of sleep has a considerable impact on vigilance: we perform worse, we make more errors, particularly at night, when we should be sleeping. Measures of brain functional connectivity suggest that decrease in vigilance during sleep loss is associated with an impaired cross-talk within the fronto-parietal cortex. However, fronto-parietal effective connectivity, which is more closely related to the causal cross-talk between brain regions, remains unexplored during prolonged wakefulness. In addition, no study has simultaneously investigated brain effective connectivity and wake-related changes in vigilance, preventing the concurrent incorporation of the two aspects. Here, we used electroencephalography (EEG) to record responses evoked by Transcranial Magnetic Stimulation (TMS) applied over the frontal lobe in 23 healthy young men (18-30 yr.), while they simultaneously performed a vigilance task, during 8 sessions spread over 29 h of sustained wakefulness. We assessed Response Scattering (ReSc), an estimate of effective connectivity, as the propagation of TMS-evoked EEG responses over the fronto-parietal cortex. Results disclose a significant change in fronto-parietal ReSc with time spent awake. When focusing on the night-time period, when one should be sleeping, participants with lower fronto-parietal ReSc performed worse on the vigilance task. Conversely, no association was detected during the well-rested, daytime period. Night-time fronto-parietal ReSc also correlated with objective EEG measures of sleepiness and alertness. These changes were not accompanied by variations in fronto-parietal response complexity. These results suggest that decreased brain response propagation within the fronto-parietal cortex is associated to increased vigilance failure during night-time prolonged wakefulness. This study reveals a novel facet of the detrimental effect on brain function of extended night-time waking hours, which is increasingly common in our societies.