Olfactory sniffing signals consciousness in unresponsive patients with brain injuries.

After severe brain injury, it can be difficult to determine the state of consciousness of a patient, to determine whether the patient is unresponsive or perhaps minimally conscious1, and to predict whether they will recover. These diagnoses and prognoses are crucial, as they determine therapeutic strategies such as pain management, and can underlie end-of-life decisions2,3. Nevertheless, there is an error rate of up to 40% in determining the state of consciousness in patients with brain injuries4,5. Olfaction relies on brain structures that are involved in the basic mechanisms of arousal6, and we therefore hypothesized that it may serve as a biomarker for consciousness7. Here we use a non-verbal non-task-dependent measure known as the sniff response8-11 to determine consciousness in patients with brain injuries. By measuring odorant-dependent sniffing, we gain a sensitive measure of olfactory function10-15. We measured the sniff response repeatedly over time in patients with severe brain injuries and found that sniff responses significantly discriminated between unresponsive and minimally conscious states at the group level. Notably, at the single-patient level, if an unresponsive patient had a sniff response, this assured future regaining of consciousness. In addition, olfactory sniff responses were associated with long-term survival rates. These results highlight the importance of olfaction in human brain function, and provide an accessible tool that signals consciousness and recovery in patients with brain injuries.

Breathwork-induced psychedelic experiences modulate neural dynamics.

Breathwork is an understudied school of practices involving intentional respiratory modulation to induce an altered state of consciousness (ASC). We simultaneously investigate the phenomenological and neural dynamics of breathwork by combining Temporal Experience Tracing, a quantitative methodology that preserves the temporal dynamics of subjective experience, with low-density portable EEG devices. Fourteen novice participants completed a course of up to 28 breathwork sessions-of 20, 40, or 60 min-in 28 days, yielding a neurophenomenological dataset of 301 breathwork sessions. Using hypothesis-driven and data-driven approaches, we found that "psychedelic-like" subjective experiences were associated with increased neural Lempel-Ziv complexity during breathwork. Exploratory analyses showed that the aperiodic exponent of the power spectral density-but not oscillatory alpha power-yielded similar neurophenomenological associations. Non-linear neural features, like complexity and the aperiodic exponent, neurally map both a multidimensional data-driven composite of positive experiences, and hypothesis-driven aspects of psychedelic-like experience states such as high bliss.

Decreasing Alertness Modulates Perceptual Decision-Making.

The ability to make decisions based on external information, prior knowledge, and evidence is a crucial aspect of cognition and may determine the success and survival of an organism. Despite extensive work on decision-making mechanisms/models, understanding the effects of alertness on neural and cognitive processes remain limited. Here we use EEG and behavioral modeling to characterize cognitive and neural dynamics of perceptual decision-making in awake/low alertness periods in humans (14 male, 18 female) and characterize the compensatory mechanisms as alertness decreases. Well-rested human participants, changing between full-wakefulness and low alertness, performed an auditory tone-localization task, and its behavioral dynamics were quantified with psychophysics, signal detection theory, and drift-diffusion modeling, revealing slower reaction times, inattention to the left side of space, and a lower rate of evidence accumulation in periods of low alertness. Unconstrained multivariate pattern analysis (decoding) showed a ∼280 ms delayed onset driven by low alertness of the neural signatures differentiating between left and right decision, with a spatial reconfiguration from centroparietal to lateral frontal regions 150-360 ms. To understand the neural compensatory mechanisms with decreasing alertness, we connected the evidence-accumulation behavioral parameter to the neural activity, showing in the early periods (125-325 ms) a shift in the associated patterns from right parietal regions in awake, to right frontoparietal during low alertness. This change in the neurobehavioral dynamics for central accumulation-related cognitive processes defines a clear reconfiguration of the brain networks' regions and dynamics needed for the implementation of decision-making, revealing mechanisms of resilience of cognition when challenged by decreased alertness.SIGNIFICANCE STATEMENT Most living organisms make multiple daily decisions, and these require a degree of evidence from both the environment and the internal milieu. Such decisions are usually studied under sequential sampling models and involve making a behavioral choice based on sensory encoding, central accumulation, and motor implementation processes. Since there is little research on how decreasing alertness affects such cognitive processes, this study has looked at the cognitive and neural dynamics of perceptual decision-making in people while fully awake and in drowsy periods. Using computational modeling of behavior and neural dynamics on human participants performing an auditory tone-localization task, we reveal how low alertness modulates evidence accumulation-related processes and its corresponding compensatory neural signatures.

Sensory Target Detection at Local and Global Timescales Reveals a Hierarchy of Supramodal Dynamics in the Human Cortex.

To ensure survival in a dynamic environment, the human neocortex monitors input streams from different sensory organs for important sensory events. Which principles govern whether different senses share common or modality-specific brain networks for sensory target detection? We examined whether complex targets evoke sustained supramodal activity while simple targets rely on modality-specific networks with short-lived supramodal contributions. In a series of hierarchical multisensory target detection studies (n = 77, of either sex) using EEG, we applied a temporal cross-decoding approach to dissociate supramodal and modality-specific cortical dynamics elicited by rule-based global and feature-based local sensory deviations within and between the visual, somatosensory, and auditory modality. Our data show that each sense implements a cortical hierarchy orchestrating supramodal target detection responses, which operate at local and global timescales in successive processing stages. Across different sensory modalities, simple feature-based sensory deviations presented in temporal vicinity to a monotonous input stream triggered a mismatch negativity-like local signal which decayed quickly and early, whereas complex rule-based targets tracked across time evoked a P3b-like global neural response which generalized across a late time window. Converging results from temporal cross-modality decoding analyses across different datasets, we reveal that global neural responses are sustained in a supramodal higher-order network, whereas local neural responses canonically thought to rely on modality-specific regions evolve into short-lived supramodal activity. Together, our findings demonstrate that cortical organization largely follows a gradient in which short-lived modality-specific as well as supramodal processes dominate local responses, whereas higher-order processes encode temporally extended abstract supramodal information fed forward from modality-specific cortices.SIGNIFICANCE STATEMENT Each sense supports a cortical hierarchy of processes tracking deviant sensory events at multiple timescales. Conflicting evidence produced a lively debate around which of these processes are supramodal. Here, we manipulated the temporal complexity of auditory, tactile, and visual targets to determine whether cortical local and global ERP responses to sensory targets share cortical dynamics between the senses. Using temporal cross-decoding, we found that temporally complex targets elicit a supramodal sustained response. Conversely, local responses to temporally confined targets typically considered modality-specific rely on early short-lived supramodal activation. Our finding provides evidence for a supramodal gradient supporting sensory target detection in the cortex, with implications for multiple fields in which these responses are studied (e.g., predictive coding, consciousness, and attention).

Can neural correlates of encoding explain the context dependence of reward-enhanced memory?

Selective encoding can be studied by manipulating how valuable it is for participants to remember specific stimuli, for instance, by varying the monetary reward participants receive for recalling a particular stimulus in a subsequent memory test. It would be reasonable for participants to strategically attend more to high-reward items compared to low-reward items in mixed list contexts, but to attend both types of items equally in pure list contexts, where all items are of equal value. Reward-enhanced memory may be driven by automatic dopaminergic interactions between reward circuitry and the hippocampus and thus be insensitive to list context; or it may be driven by meta-cognitive strategies, and thus context-dependent. We contrasted these alternatives by manipulating list composition and tracked selective encoding through multiple EEG measures of attention and rehearsal. Behavioral results were context-dependent, such that recall of high-reward items was increased only in mixed lists. This result and aspects of the recall dynamics confirm predictions of the eCMR (emotional Context Maintenance and Retrieval) model. The power of ssVEPs was lower for high-reward items regardless of list composition, suggesting decreased visual processing of high-reward stimuli and that ssVEPs may index the modulation of context-to-item associations predicted by eCMR. By contrast, reward modulated the amplitude of Late Positive Potential and Frontal Slow Wave only in mixed lists. Taken together, the results provide evidence that reward-enhanced memory is caused by an interplay between strategic processes applied when high- and low-reward items compete for cognitive resources during encoding and context-dependent mechanisms operating during recall.

Ketamine and sleep modulate neural complexity dynamics in cats.

There is increasing evidence that the level of consciousness can be captured by neural informational complexity: for instance, complexity, as measured by the Lempel Ziv (LZ) compression algorithm, decreases during anaesthesia and non-rapid eye movement (NREM) sleep in humans and rats, when compared with LZ in awake and REM sleep. In contrast, LZ is higher in humans under the effect of psychedelics, including subanaesthetic doses of ketamine. However, it is both unclear how this result would be modulated by varying ketamine doses, and whether it would extend to other species. Here, we studied LZ with and without auditory stimulation during wakefulness and different sleep stages in five cats implanted with intracranial electrodes, as well as under subanaesthetic doses of ketamine (5, 10, and 15 mg/kg i.m.). In line with previous results, LZ was lowest in NREM sleep, but similar in REM and wakefulness. Furthermore, we found an inverted U-shaped curve following different levels of ketamine doses in a subset of electrodes, primarily in prefrontal cortex. However, it is worth noting that the variability in the ketamine dose-response curve across cats and cortices was larger than that in the sleep-stage data, highlighting the differential local dynamics created by two different ways of modulating conscious state. These results replicate previous findings, both in humans and other species, demonstrating that neural complexity is highly sensitive to capture state changes between wake and sleep stages while adding a local cortical description. Finally, this study describes the differential effects of ketamine doses, replicating a rise in complexity for low doses, and further fall as doses approach anaesthetic levels in a differential manner depending on the cortex.

Exploring electrophysiological markers of auditory predictive processes and pathological ageing in adults with Down's syndrome.

Down's syndrome is associated with pathological ageing and a propensity for early-onset Alzheimer's disease. The early symptoms of dementia in people with Down's syndrome may reflect frontal lobe vulnerability to amyloid deposition. Auditory predictive processes rely on the bilateral auditory cortices with the recruitment of frontal cortices and appear to be impaired in pathologies characterized by compromised frontal lobe. Hence, auditory predictive processes were investigated to assess Down's syndrome pathology and its relationship with pathological ageing. An auditory electroencephalography (EEG) global-local paradigm was presented to the participants, in which oddball stimuli could either violate local or higher level global rules. We characterised predictive processes in individuals with Down's syndrome and their relationship with pathological ageing, with a focus on the EEG event-related potential called Mismatch Negativity (MMN) and the P300. In Down's syndrome, we also evaluated the EEG components as predictor of cognitive decline 1 year later. We found that predictive processes of detection of auditory violations are overall preserved in Down's syndrome but also that the amplitude of the MMN to local deviancies decreases with age. However, the 1-year follow-up of Down's syndrome found that none of the ERPs measures predicted subsequent cognitive decline. The present study provides a novel characterization of electrophysiological markers of local and global predictive processes in Down's syndrome.

Cambridge Psycholinguistic Inventory of Christian Beliefs: A registered report of construct validity, internal consistency and test-retest reliability.

While religious beliefs are typically studied using questionnaires, there are no standardized tools available for cognitive psychology and neuroscience studies of religious cognition. Here we present the first such tool-the Cambridge Psycholinguistic Inventory of Christian Beliefs (CPICB)-which consists of audio-recorded items of religious beliefs as well as items of three control conditions: moral beliefs, abstract scientific knowledge and empirical everyday life knowledge. The CPICB is designed in such a way that the ultimate meaning of each sentence is revealed only by its final critical word, which enables the precise measurement of reaction times and/or latencies of neurophysiological responses. Each statement comes in a pair of Agree/Disagree versions of critical words, which allows for experimental contrasting between belief and disbelief conditions. Psycholinguistic and psychoacoustic matching between Agree/Disagree versions of sentences, as well as across different categories of the CPICB items (Religious, Moral, Scientific, Everyday), enables rigorous control of low-level psycholinguistic and psychoacoustic features while testing higher-level beliefs. In the exploratory Study 1 (N = 20), we developed and tested a preliminary version of the CPICB that had 480 items. After selecting 400 items that yielded the most consistent responses, we carried out a confirmatory test-retest Study 2 (N = 40). Preregistered data analyses confirmed excellent construct validity, internal consistency and test-retest reliability of the CPICB religious belief statements. We conclude that the CPICB is suitable for studying Christian beliefs in an experimental setting involving behavioural and neuroimaging paradigms, and provide Open Access to the inventory items, fostering further development of the experimental research of religiosity.

Decreased Alertness Reconfigures Cognitive Control Networks.

Humans' remarkable capacity to flexibly adapt their behavior based on rapid situational changes is termed cognitive control. Intuitively, cognitive control is thought to be affected by the state of alertness; for example, when drowsy, we feel less capable of adequately implementing effortful cognitive tasks. Although scientific investigations have focused on the effects of sleep deprivation and circadian time, little is known about how natural daily fluctuations in alertness in the regular awake state affect cognitive control. Here we combined a conflict task in the auditory domain with EEG neurodynamics to test how neural and behavioral markers of conflict processing are affected by fluctuations in alertness. Using a novel computational method, we segregated alert and drowsy trials from two testing sessions and observed that, although participants (both sexes) were generally sluggish, the typical conflict effect reflected in slower responses to conflicting information compared with nonconflicting information, as well as the moderating effect of previous conflict (conflict adaptation), were still intact. However, the typical neural markers of cognitive control-local midfrontal theta-band power changes-that participants show during full alertness were no longer noticeable when alertness decreased. Instead, when drowsy, we found an increase in long-range information sharing (connectivity) between brain regions in the same frequency band. These results show the resilience of the human cognitive control system when affected by internal fluctuations of alertness and suggest that there are neural compensatory mechanisms at play in response to physiological pressure during diminished alertness.SIGNIFICANCE STATEMENT The normal variability in alertness we experience in daily tasks is rarely taken into account in cognitive neuroscience. Here we studied neurobehavioral dynamics of cognitive control with decreasing alertness. We used the classic Simon task where participants hear the word "left" or "right" in the right or left ear, eliciting slower responses when the word and the side are incongruent-the conflict effect. Participants performed the task both while fully awake and while getting drowsy, allowing for the characterization of alertness modulating cognitive control. The changes in the neural signatures of conflict from local theta oscillations to a long-distance distributed theta network suggest a reconfiguration of the underlying neural processes subserving cognitive control when affected by alertness fluctuations.

Attentional modulation of neural dynamics in tactile perception of complex regional pain syndrome patients.

Body perceptual disturbances are an increasingly acknowledged set of symptoms and possible clinical markers of complex regional pain syndrome (CRPS), but the neurophysiological and neurocognitive changes that underlie them are still far from being clear. We adopted a multivariate and neurodynamical approach to the analysis of EEG modulations evoked by touch to highlight differences between patients and healthy controls, between affected and unaffected side of the body, and between "passive" (i.e., no task demands and equiprobable digit stimulation) and "active" tactile processing (i.e., where a digit discrimination task was administered and spatial probability manipulated). When correct identifications are considered, an early reduction in cortical decodability (28-56 ms) distinguishes CRPS patients from healthy volunteers. However, when error trials are included in the classifier's training, there is an unexpected increased decodability in the CRPS group compared with healthy volunteers (280-320 ms). These group differences in neural processing seemed to be driven by the affected rather than the unaffected side. We corroborated these findings with several exploratory analyses of neural representation dynamics and behavioural modelling, highlighting the need for single participant analyses. Although several limitations impacted the robustness and generalizability of these comparisons, the proposed analytical approach yielded promising insights (as well as possible biomarkers based on neural dynamics) into the relatively unexplored alterations of tactile decision-making and attentional control mechanisms in chronic CRPS.

Neural Dynamics of Associative Learning during Human Sleep.

Recent evidence indicates that humans can learn entirely new information during sleep. To elucidate the neural dynamics underlying sleep-learning, we investigated brain activity during auditory-olfactory discriminatory associative learning in human sleep. We found that learning-related delta and sigma neural changes are involved in early acquisition stages, when new associations are being formed. In contrast, learning-related theta activity emerged in later stages of the learning process, after tone-odor associations were already established. These findings suggest that learning new associations during sleep is signaled by a dynamic interplay between slow-waves, sigma, and theta activity.

Sedation Modulates Frontotemporal Predictive Coding Circuits and the Double Surprise Acceleration Effect.

Two important theories in cognitive neuroscience are predictive coding (PC) and the global workspace (GW) theory. A key research task is to understand how these two theories relate to one another, and particularly, how the brain transitions from a predictive early state to the eventual engagement of a brain-scale state (the GW). To address this question, we present a source-localization of EEG responses evoked by the local-global task-an experimental paradigm that engages a predictive hierarchy, which encompasses the GW. The results of our source reconstruction suggest three phases of processing. The first phase involves the sensory (here auditory) regions of the superior temporal lobe and predicts sensory regularities over a short timeframe (as per the local effect). The third phase is brain-scale, involving inferior frontal, as well as inferior and superior parietal regions, consistent with a global neuronal workspace (GNW; as per the global effect). Crucially, our analysis suggests that there is an intermediate (second) phase, involving modulatory interactions between inferior frontal and superior temporal regions. Furthermore, sedation with propofol reduces modulatory interactions in the second phase. This selective effect is consistent with a PC explanation of sedation, with propofol acting on descending predictions of the precision of prediction errors; thereby constraining access to the GNW.

Dissociable Neural Information Dynamics of Perceptual Integration and Differentiation during Bistable Perception.

At any given moment, we experience a perceptual scene as a single whole and yet we may distinguish a variety of objects within it. This phenomenon instantiates two properties of conscious perception: integration and differentiation. Integration is the property of experiencing a collection of objects as a unitary percept and differentiation is the property of experiencing these objects as distinct from each other. Here, we evaluated the neural information dynamics underlying integration and differentiation of perceptual contents during bistable perception. Participants listened to a sequence of tones (auditory bistable stimuli) experienced either as a single stream (perceptual integration) or as two parallel streams (perceptual differentiation) of sounds. We computed neurophysiological indices of information integration and information differentiation with electroencephalographic and intracranial recordings. When perceptual alternations were endogenously driven, the integrated percept was associated with an increase in neural information integration and a decrease in neural differentiation across frontoparietal regions, whereas the opposite pattern was observed for the differentiated percept. However, when perception was exogenously driven by a change in the sound stream (no bistability), neural oscillatory power distinguished between percepts but information measures did not. We demonstrate that perceptual integration and differentiation can be mapped to theoretically motivated neural information signatures, suggesting a direct relationship between phenomenology and neurophysiology.

Time to Face Language: Embodied Mechanisms Underpin the Inception of Face-Related Meanings in the Human Brain.

In construing meaning, the brain recruits multimodal (conceptual) systems and embodied (modality-specific) mechanisms. Yet, no consensus exists on how crucial the latter are for the inception of semantic distinctions. To address this issue, we combined electroencephalographic (EEG) and intracranial EEG (iEEG) to examine when nouns denoting facial body parts (FBPs) and nonFBPs are discriminated in face-processing and multimodal networks. First, FBP words increased N170 amplitude (a hallmark of early facial processing). Second, they triggered fast (~100 ms) activity boosts within the face-processing network, alongside later (~275 ms) effects in multimodal circuits. Third, iEEG recordings from face-processing hubs allowed decoding ~80% of items before 200 ms, while classification based on multimodal-network activity only surpassed ~70% after 250 ms. Finally, EEG and iEEG connectivity between both networks proved greater in early (0-200 ms) than later (200-400 ms) windows. Collectively, our findings indicate that, at least for some lexico-semantic categories, meaning is construed through fast reenactments of modality-specific experience.

Novel evidence on the effect of tramadol on self-paced high-intensity cycling.

The use of tramadol is a controversial topic in cycling. In order to provide novel evidence on this issue, we tested 29 participants in a pre-loaded cycling time trial (TT; a 20-min TT preceded by 40-min of constant work-rate at 60% of the VO2max) after ingesting 100 mg of tramadol (vs placebo and paracetamol (1.5 g)). Participants performed the Psychomotor Vigilance Task (PVT) at rest and a Sustained Attention to Response Task (SART) during the 60 min of exercise. Oscillatory electroencephalography (EEG) activity was measured throughout the exercise. The results showed higher mean power output during the 20-min TT in the tramadol vs. paracetamol condition, but no reliable difference was reported between tramadol and placebo (nor paracetamol vs. placebo). Tramadol resulted in faster responses in the PVT and higher heart rate during exercise. The main effect of substance was reliable in the SART during the 40-min constant workload (no during the 20-min TT), with slower reaction time, but better accuracy for tramadol and paracetamol than for placebo. This study supports the increased behavioural and neural efficiency at rest for tramadol but not the proposed ergogenic or cognitive (harmful) effect of tramadol (vs. placebo) during self-paced high-intensity cycling.

Alertness fluctuations when performing a task modulate cortical evoked responses to transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) has been widely used in human cognitive neuroscience to examine the causal role of distinct cortical areas in perceptual, cognitive and motor functions. However, it is widely acknowledged that the effects of focal cortical stimulation can vary substantially between participants and even from trial to trial within individuals. Recent work from resting state functional magnetic resonance imaging (fMRI) studies has suggested that spontaneous fluctuations in alertness over a testing session can modulate the neural dynamics of cortical processing, even when participants remain awake and responsive to the task at hand. Here we investigated the extent to which spontaneous fluctuations in alertness during wake-to-sleep transition can account for the variability in neurophysiological responses to TMS. We combined single-pulse TMS with neural recording via electroencephalography (EEG) to quantify changes in motor and cortical reactivity with fluctuating levels of alertness defined objectively on the basis of ongoing brain activity. We observed rapid, non-linear changes in TMS-evoked responses with decreasing levels of alertness, even while participants remained responsive in the behavioural task. Specifically, we found that the amplitude of motor evoked potentials peaked during periods of EEG flattening, whereas TMS-evoked potentials increased and remained stable during EEG flattening and the subsequent occurrence of theta ripples that indicate the onset of NREM stage 1 sleep. Our findings suggest a rapid and complex reorganization of active neural networks in response to spontaneous fluctuations of alertness over relatively short periods of behavioural testing during wake-to-sleep transition.

Transient Topographical Dynamics of the Electroencephalogram Predict Brain Connectivity and Behavioural Responsiveness During Drowsiness.

As we fall sleep, our brain traverses a series of gradual changes at physiological, behavioural and cognitive levels, which are not yet fully understood. The loss of responsiveness is a critical event in the transition from wakefulness to sleep. Here we seek to understand the electrophysiological signatures that reflect the loss of capacity to respond to external stimuli during drowsiness using two complementary methods: spectral connectivity and EEG microstates. Furthermore, we integrate these two methods for the first time by investigating the connectivity patterns captured during individual microstate lifetimes. While participants performed an auditory semantic classification task, we allowed them to become drowsy and unresponsive. As they stopped responding to the stimuli, we report the breakdown of alpha networks and the emergence of theta connectivity. Further, we show that the temporal dynamics of all canonical EEG microstates slow down during unresponsiveness. We identify a specific microstate (D) whose occurrence and duration are prominently increased during this period. Employing machine learning, we show that the temporal properties of microstate D, particularly its prolonged duration, predicts the response likelihood to individual stimuli. Finally, we find a novel relationship between microstates and brain networks as we show that microstate D uniquely indexes significantly stronger theta connectivity during unresponsiveness. Our findings demonstrate that the transition to unconsciousness is not linear, but rather consists of an interplay between transient brain networks reflecting different degrees of sleep depth.

Neural Encoding of Attended Continuous Speech under Different Types of Interference.

We examined how attention modulates the neural encoding of continuous speech under different types of interference. In an EEG experiment, participants attended to a narrative in English while ignoring a competing stream in the other ear. Four different types of interference were presented to the unattended ear: a different English narrative, a narrative in a language unknown to the listener (Spanish), a well-matched nonlinguistic acoustic interference (Musical Rain), and no interference. Neural encoding of attended and unattended signals was assessed by calculating cross-correlations between their respective envelopes and the EEG recordings. Findings revealed more robust neural encoding for the attended envelopes compared with the ignored ones. Critically, however, the type of the interfering stream significantly modulated this process, with the fully intelligible distractor (English) causing the strongest encoding of both attended and unattended streams and latest dissociation between them and nonintelligible distractors causing weaker encoding and early dissociation between attended and unattended streams. The results were consistent over the time course of the spoken narrative. These findings suggest that attended and unattended information can be differentiated at different depths of processing analysis, with the locus of selective attention determined by the nature of the competing stream. They provide strong support to flexible accounts of auditory selective attention.

Tracking wakefulness as it fades: Micro-measures of alertness.

A major problem in psychology and physiology experiments is drowsiness: around a third of participants show decreased wakefulness despite being instructed to stay alert. In some non-visual experiments participants keep their eyes closed throughout the task, thus promoting the occurrence of such periods of varying alertness. These wakefulness changes contribute to systematic noise in data and measures of interest. To account for this omnipresent problem in data acquisition we defined criteria and code to allow researchers to detect and control for varying alertness in electroencephalography (EEG) experiments under eyes-closed settings. We first revise a visual-scoring method developed for detection and characterization of the sleep-onset process, and adapt the same for detection of alertness levels. Furthermore, we show the major issues preventing the practical use of this method, and overcome these issues by developing an automated method (micro-measures algorithm) based on frequency and sleep graphoelements, which are capable of detecting micro variations in alertness. The validity of the micro-measures algorithm was verified by training and testing using a dataset where participants are known to fall asleep. In addition, we tested generalisability by independent validation on another dataset. The methods developed constitute a unique tool to assess micro variations in levels of alertness and control trial-by-trial retrospectively or prospectively in every experiment performed with EEG in cognitive neuroscience under eyes-closed settings.

Intracranial high-γ connectivity distinguishes wakefulness from sleep.

Neural synchrony in the γ-band is considered a fundamental process in cortical computation and communication and it has also been proposed as a crucial correlate of consciousness. However, the latter claim remains inconclusive, mainly due to methodological limitations, such as the spectral constraints of scalp-level electroencephalographic recordings or volume-conduction confounds. Here, we circumvented these caveats by comparing γ-band connectivity between two global states of consciousness via intracranial electroencephalography (iEEG), which provides the most reliable measurements of high-frequency activity in the human brain. Non-REM Sleep recordings were compared to passive-wakefulness recordings of the same duration in three subjects with surgically implanted electrodes. Signals were analyzed through the weighted Phase Lag Index connectivity measure and relevant graph theory metrics. We found that connectivity in the high-γ range (90-120 Hz), as well as relevant graph theory properties, were higher during wakefulness than during sleep and discriminated between conditions better than any other canonical frequency band. Our results constitute the first report of iEEG differences between wakefulness and sleep in the high-γ range at both local and distant sites, highlighting the utility of this technique in the search for the neural correlates of global states of consciousness.