Multimodal prediction of residual consciousness in the intensive care unit: the CONNECT-ME study.

Functional MRI (fMRI) and EEG may reveal residual consciousness in patients with disorders of consciousness (DoC), as reflected by a rapidly expanding literature on chronic DoC. However, acute DoC is rarely investigated, although identifying residual consciousness is key to clinical decision-making in the intensive care unit (ICU). Therefore, the objective of the prospective, observational, tertiary centre cohort, diagnostic phase IIb study 'Consciousness in neurocritical care cohort study using EEG and fMRI' (CONNECT-ME, NCT02644265) was to assess the accuracy of fMRI and EEG to identify residual consciousness in acute DoC in the ICU. Between April 2016 and November 2020, 87 acute DoC patients with traumatic or non-traumatic brain injury were examined with repeated clinical assessments, fMRI and EEG. Resting-state EEG and EEG with external stimulations were evaluated by visual analysis, spectral band analysis and a Support Vector Machine (SVM) consciousness classifier. In addition, within- and between-network resting-state connectivity for canonical resting-state fMRI networks was assessed. Next, we used EEG and fMRI data at study enrolment in two different machine-learning algorithms (Random Forest and SVM with a linear kernel) to distinguish patients in a minimally conscious state or better (≥MCS) from those in coma or unresponsive wakefulness state (≤UWS) at time of study enrolment and at ICU discharge (or before death). Prediction performances were assessed with area under the curve (AUC). Of 87 DoC patients (mean age, 50.0 ± 18 years, 43% female), 51 (59%) were ≤UWS and 36 (41%) were ≥ MCS at study enrolment. Thirty-one (36%) patients died in the ICU, including 28 who had life-sustaining therapy withdrawn. EEG and fMRI predicted consciousness levels at study enrolment and ICU discharge, with maximum AUCs of 0.79 (95% CI 0.77-0.80) and 0.71 (95% CI 0.77-0.80), respectively. Models based on combined EEG and fMRI features predicted consciousness levels at study enrolment and ICU discharge with maximum AUCs of 0.78 (95% CI 0.71-0.86) and 0.83 (95% CI 0.75-0.89), respectively, with improved positive predictive value and sensitivity. Overall, both machine-learning algorithms (SVM and Random Forest) performed equally well. In conclusion, we suggest that acute DoC prediction models in the ICU be based on a combination of fMRI and EEG features, regardless of the machine-learning algorithm used.

Resting-State EEG Signature of Early Consciousness Recovery in Comatose Patients with Traumatic Brain Injury.

BACKGROUND: Resting-state electroencephalography (rsEEG) is usually obtained to assess seizures in comatose patients with traumatic brain injury (TBI). We aim to investigate rsEEG measures and their prediction of early recovery of consciousness in patients with TBI. METHODS: This is a retrospective study of comatose patients with TBI who were admitted to a trauma center (October 2013 to January 2022). Demographics, basic clinical data, imaging characteristics, and EEGs were collected. We calculated the following using 10-min rsEEGs: power spectral density, permutation entropy (complexity measure), weighted symbolic mutual information (wSMI, global information sharing measure), Kolmogorov complexity (Kolcom, complexity measure), and heart-evoked potentials (the averaged EEG signal relative to the corresponding QRS complex on electrocardiography). We evaluated the prediction of consciousness recovery before hospital discharge using clinical, imaging, and rsEEG data via a support vector machine. RESULTS: We studied 113 of 134 (84%) patients with rsEEGs. A total of 73 (65%) patients recovered consciousness before discharge. Patients who recovered consciousness were younger (40 vs. 50 years, p = 0.01). Patients who recovered also had higher Kolcom (U = 1688, p = 0.01), increased beta power (U = 1,652 p = 0.003) with higher variability across channels (U = 1534, p = 0.034) and epochs (U = 1711, p = 0.004), lower delta power (U = 981, p = 0.04), and higher connectivity across time and channels as measured by wSMI in the theta band (U = 1636, p = 0.026; U = 1639, p = 0.024) than those who did not recover. The area under the receiver operating characteristic curve for rsEEG was higher than that for clinical data (using age, motor response, pupil reactivity) and higher than that for the Marshall computed tomography classification (0.69 vs. 0.66 vs. 0.56, respectively; p < 0.001). CONCLUSIONS: We describe the rsEEG signature in recovery of consciousness prior to discharge in comatose patients with TBI. rsEEG measures performed modestly better than the clinical and imaging data in predicting recovery.

Multimodal Prediction of 3- and 12-Month Outcomes in ICU Patients with Acute Disorders of Consciousness.

BACKGROUND: In intensive care unit (ICU) patients with coma and other disorders of consciousness (DoC), outcome prediction is key to decision-making regarding prognostication, neurorehabilitation, and management of family expectations. Current prediction algorithms are largely based on chronic DoC, whereas multimodal data from acute DoC are scarce. Therefore, the Consciousness in Neurocritical Care Cohort Study Using Electroencephalography and Functional Magnetic Resonance Imaging (i.e. CONNECT-ME; ClinicalTrials.gov identifier: NCT02644265) investigates ICU patients with acute DoC due to traumatic and nontraumatic brain injuries, using electroencephalography (EEG) (resting-state and passive paradigms), functional magnetic resonance imaging (fMRI) (resting-state) and systematic clinical examinations. METHODS: We previously presented results for a subset of patients (n = 87) concerning prediction of consciousness levels in the ICU. Now we report 3- and 12-month outcomes in an extended cohort (n = 123). Favorable outcome was defined as a modified Rankin Scale score ≤ 3, a cerebral performance category score ≤ 2, and a Glasgow Outcome Scale Extended score ≥ 4. EEG features included visual grading, automated spectral categorization, and support vector machine consciousness classifier. fMRI features included functional connectivity measures from six resting-state networks. Random forest and support vector machine were applied to EEG and fMRI features to predict outcomes. Here, random forest results are presented as areas under the curve (AUC) of receiver operating characteristic curves or accuracy. Cox proportional regression with in-hospital death as a competing risk was used to assess independent clinical predictors of time to favorable outcome. RESULTS: Between April 2016 and July 2021, we enrolled 123 patients (mean age 51 years, 42% women). Of 82 (66%) ICU survivors, 3- and 12-month outcomes were available for 79 (96%) and 77 (94%), respectively. EEG features predicted both 3-month (AUC 0.79 [95% confidence interval (CI) 0.77-0.82]) and 12-month (AUC 0.74 [95% CI 0.71-0.77]) outcomes. fMRI features appeared to predict 3-month outcome (accuracy 0.69-0.78) both alone and when combined with some EEG features (accuracies 0.73-0.84) but not 12-month outcome (larger sample sizes needed). Independent clinical predictors of time to favorable outcome were younger age (hazard ratio [HR] 1.04 [95% CI 1.02-1.06]), traumatic brain injury (HR 1.94 [95% CI 1.04-3.61]), command-following abilities at admission (HR 2.70 [95% CI 1.40-5.23]), initial brain imaging without severe pathological findings (HR 2.42 [95% CI 1.12-5.22]), improving consciousness in the ICU (HR 5.76 [95% CI 2.41-15.51]), and favorable visual-graded EEG (HR 2.47 [95% CI 1.46-4.19]). CONCLUSIONS: Our results indicate that EEG and fMRI features and readily available clinical data predict short-term outcome of patients with acute DoC and that EEG also predicts 12-month outcome after ICU discharge.

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).

What lies underneath: Precise classification of brain states using time-dependent topological structure of dynamics.

The self-organising global dynamics underlying brain states emerge from complex recursive nonlinear interactions between interconnected brain regions. Until now, most efforts of capturing the causal mechanistic generating principles have supposed underlying stationarity, being unable to describe the non-stationarity of brain dynamics, i.e. time-dependent changes. Here, we present a novel framework able to characterise brain states with high specificity, precisely by modelling the time-dependent dynamics. Through describing a topological structure associated to the brain state at each moment in time (its attractor or 'information structure'), we are able to classify different brain states by using the statistics across time of these structures hitherto hidden in the neuroimaging dynamics. Proving the strong potential of this framework, we were able to classify resting-state BOLD fMRI signals from two classes of post-comatose patients (minimally conscious state and unresponsive wakefulness syndrome) compared with healthy controls with very high precision.

Predicting the loss of responsiveness when falling asleep in humans.

Falling asleep is a dynamical process that is poorly defined. The period preceding sleep, characterized by the progressive alteration of behavioral responses to the environment, which may last several minutes, has no electrophysiological definition, and is embedded in the first stage of sleep (N1). We aimed at better characterizing this drowsiness period looking for neurophysiological predictors of responsiveness using electro and magneto-encephalography. Healthy participants were recorded when falling asleep, while they were presented with continuous auditory stimulations and asked to respond to deviant sounds. We analysed brain responses to sounds and markers of ongoing activity, such as information and connectivity measures, in relation to rapid fluctuations of brain rhythms observed at sleep onset and participants' capabilities to respond. Results reveal a drowsiness period distinct from wakefulness and sleep, from alpha rhythms to the first sleep spindles, characterized by diverse and transient brain states that come on and off at the scale of a few seconds and closely reflects, mainly through neural processes in alpha and theta bands, decreasing probabilities to be responsive to external stimuli. Results also show that the global P300 was only present in responsive trials, regardless of vigilance states. A better consideration of the drowsiness period through a formalized classification and its specific brain markers such as described here should lead to significant advances in vigilance assessment in the future, in medicine and ecological environments.

Habituation of auditory startle reflex is a new sign of minimally conscious state.

Neurological examination of non-communicating patients relies on a few decisive items that enable the crucial distinction between vegetative state (VS)-also coined unresponsive wakefulness syndrome (UWS)-and minimally conscious state. Over the past 10 years, this distinction has proven its diagnostic value as well as its important prognostic value on consciousness recovery. However, clinicians are currently limited by three factors: (i) the current behavioural repertoire of minimally conscious state items is limited and restricted to a few cognitive domains in the goldstandard revised version of the Coma Recovery Scale; (ii) a proportion of ∼15-20% clinically VS/UWS patients are actually in a richer state than VS/UWS as evidenced by functional brain imaging; and (iii) the neurophysiological and cognitive interpretation of each minimally conscious state item is still unclear and debated. In the current study we demonstrate that habituation of the auditory startle reflex (hASR) tested at bedside constitutes a novel, simple and powerful behavioural sign that can accurately distinguish minimally conscious state from VS/UWS. In addition to enlarging the minimally conscious state items repertoire, and therefore decreasing the low sensitivity of current behavioural measures, we also provide an original and rigorous description of the neurophysiological basis of hASR through a combination of functional (high density EEG and 18F-fluorodeoxyglucose PET imaging) and structural (diffusion tensor imaging MRI) measures. We show that preservation of hASR is associated with the functional and structural integrity of a brain-scale fronto-parietal network, including prefrontal regions related to control of action and inhibition, and meso-parietal areas associated with minimally conscious and conscious states. Lastly, we show that hASR predicts 6-month improvement of consciousness. Taken together, our results show that hASR is a cortically-mediated behaviour, and suggest that it could be a new clinical item to clearly and accurately identify non-communicating patients who are in the minimally conscious state.

Robust EEG-based cross-site and cross-protocol classification of states of consciousness.

Determining the state of consciousness in patients with disorders of consciousness is a challenging practical and theoretical problem. Recent findings suggest that multiple markers of brain activity extracted from the EEG may index the state of consciousness in the human brain. Furthermore, machine learning has been found to optimize their capacity to discriminate different states of consciousness in clinical practice. However, it is unknown how dependable these EEG markers are in the face of signal variability because of different EEG configurations, EEG protocols and subpopulations from different centres encountered in practice. In this study we analysed 327 recordings of patients with disorders of consciousness (148 unresponsive wakefulness syndrome and 179 minimally conscious state) and 66 healthy controls obtained in two independent research centres (Paris Pitié-Salpêtrière and Liège). We first show that a non-parametric classifier based on ensembles of decision trees provides robust out-of-sample performance on unseen data with a predictive area under the curve (AUC) of ~0.77 that was only marginally affected when using alternative EEG configurations (different numbers and positions of sensors, numbers of epochs, average AUC = 0.750 ± 0.014). In a second step, we observed that classifiers based on multiple as well as single EEG features generalize to recordings obtained from different patient cohorts, EEG protocols and different centres. However, the multivariate model always performed best with a predictive AUC of 0.73 for generalization from Paris 1 to Paris 2 datasets, and an AUC of 0.78 from Paris to Liège datasets. Using simulations, we subsequently demonstrate that multivariate pattern classification has a decisive performance advantage over univariate classification as the stability of EEG features decreases, as different EEG configurations are used for feature-extraction or as noise is added. Moreover, we show that the generalization performance from Paris to Liège remains stable even if up to 20% of the diagnostic labels are randomly flipped. Finally, consistent with recent literature, analysis of the learned decision rules of our classifier suggested that markers related to dynamic fluctuations in theta and alpha frequency bands carried independent information and were most influential. Our findings demonstrate that EEG markers of consciousness can be reliably, economically and automatically identified with machine learning in various clinical and acquisition contexts.

Brain-heart interactions reveal consciousness in noncommunicating patients.

OBJECTIVE: We here aimed at characterizing heart-brain interactions in patients with disorders of consciousness. We tested how this information impacts data-driven classification between unresponsive and minimally conscious patients. METHODS: A cohort of 127 patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS; n = 70) and minimally conscious state (MCS; n = 57) were presented with the local-global auditory oddball paradigm, which distinguishes 2 levels of processing: short-term deviation of local auditory regularities and global long-term rule violations. In addition to previously validated markers of consciousness extracted from electroencephalograms (EEG), we computed autonomic cardiac markers, such as heart rate (HR) and HR variability (HRV), and cardiac cycle phase shifts triggered by the processing of the auditory stimuli. RESULTS: HR and HRV were similar in patients across groups. The cardiac cycle was not sensitive to the processing of local regularities in either the VS/UWS or MCS patients. In contrast, global regularities induced a phase shift of the cardiac cycle exclusively in the MCS group. The interval between the auditory stimulation and the following R peak was significantly shortened in MCS when the auditory rule was violated. When the information for the cardiac cycle modulations and other consciousness-related EEG markers were combined, single patient classification performance was enhanced compared to classification with solely EEG markers. INTERPRETATION: Our work shows a link between residual cognitive processing and the modulation of autonomic somatic markers. These results open a new window to evaluate patients with disorders of consciousness via the embodied paradigm, according to which body-brain functions contribute to a holistic approach to conscious processing. Ann Neurol 2017;82:578-591.

Resting-state Dynamics as a Cortical Signature of Anesthesia in Monkeys.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: The mechanism by which anesthetics induce a loss of consciousness remains a puzzling problem. We hypothesized that a cortical signature of anesthesia could be found in an increase in similarity between the matrix of resting-state functional correlations and the anatomical connectivity matrix of the brain, resulting in an increased function-structure similarity. METHODS: We acquired resting-state functional magnetic resonance images in macaque monkeys during wakefulness (n = 3) or anesthesia with propofol (n = 3), ketamine (n = 3), or sevoflurane (n = 3). We used the k-means algorithm to cluster dynamic resting-state data into independent functional brain states. For each condition, we performed a regression analysis to quantify function-structure similarity and the repertoire of functional brain states. RESULTS: Seven functional brain states were clustered and ranked according to their similarity to structural connectivity, with higher ranks corresponding to higher function-structure similarity and lower ranks corresponding to lower correlation between brain function and brain anatomy. Anesthesia shifted the brain state composition from a low rank (rounded rank [mean ± SD]) in the awake condition (awake rank = 4 [3.58 ± 1.03]) to high ranks in the different anesthetic conditions (ketamine rank = 6 [6.10 ± 0.32]; moderate propofol rank = 6 [6.15 ± 0.76]; deep propofol rank = 6 [6.16 ± 0.46]; moderate sevoflurane rank = 5 [5.10 ± 0.81]; deep sevoflurane rank = 6 [5.81 ± 1.11]; P < 0.0001). CONCLUSIONS: Whatever the molecular mechanism, anesthesia led to a massive reconfiguration of the repertoire of functional brain states that became predominantly shaped by brain anatomy (high function-structure similarity), giving rise to a well-defined cortical signature of anesthesia-induced loss of consciousness.

Pre-stimulus theta power is correlated with variation of motor evoked potential latency: a single-pulse TMS study.

There has been a growing interest in the role of pre-stimulus oscillations on cortical excitability in visual and motor systems. Prior studies focused on the relationship between pre-stimulus neuronal activity and TMS-evoked motor evoked potentials (MEPs) have reported heterogeneous results. We aimed to assess the role of pre-stimulus neural activity on the latency of MEPs, which might enhance our understanding of the variability of MEP signals, and potentially provide information on the role played by cortical activity fluctuations in the excitability of corticospinal pathways. Near-threshold single-pulse TMS (spTMS) was applied at random intervals over the primary motor cortex of 14 healthy participants while they sat passively, to trigger hand muscle contractions. Multichannel EEG was recorded during spTMS blocks. Spearman correlations between both the variation in MEP onset latencies and peak-to-peak MEP amplitudes, and the pre-stimulus power of EEG oscillations were calculated across participants. We found that the variation in MEP latency was positively correlated with pre-stimulus power in the theta range (4-7 Hz) in a broad time window (- 3.1 to - 1.9 s) preceding the spTMS generating the MEP. No correlation between pre-stimulus power in any frequency band and MEP amplitude was found. Our results show that pre-stimulus theta oscillations are correlated with the variation in MEP latency, an outcome measure determined by fiber conduction velocity and synaptic delays along the corticospinal tract. This finding could prove useful for clinicians using MEP latency-based information in pre- or intra-operative diagnostics of corticospinal impairment.

Cortical activity is more stable when sensory stimuli are consciously perceived.

According to recent evidence, stimulus-tuned neurons in the cerebral cortex exhibit reduced variability in firing rate across trials, after the onset of a stimulus. However, in order for a reduction in variability to be directly relevant to perception and behavior, it must be realized within trial--the pattern of activity must be relatively stable. Stability is characteristic of decision states in recurrent attractor networks, and its possible relevance to conscious perception has been suggested by theorists. However, it is difficult to measure on the within-trial time scales and broadly distributed spatial scales relevant to perception. We recorded simultaneous magneto- and electroencephalography (MEG and EEG) data while subjects observed threshold-level visual stimuli. Pattern-similarity analyses applied to the data from MEG gradiometers uncovered a pronounced decrease in variability across trials after stimulus onset, consistent with previous single-unit data. This was followed by a significant divergence in variability depending upon subjective report (seen/unseen), with seen trials exhibiting less variability. Applying the same analysis across time, within trial, we found that the latter effect coincided in time with a difference in the stability of the pattern of activity. Stability alone could be used to classify data from individual trials as "seen" or "unseen." The same metric applied to EEG data from patients with disorders of consciousness exposed to auditory stimuli diverged parametrically according to clinically diagnosed level of consciousness. Differences in signal strength could not account for these results. Conscious perception may involve the transient stabilization of distributed cortical networks, corresponding to a global brain-scale decision.

Signature of consciousness in the dynamics of resting-state brain activity.

At rest, the brain is traversed by spontaneous functional connectivity patterns. Two hypotheses have been proposed for their origins: they may reflect a continuous stream of ongoing cognitive processes as well as random fluctuations shaped by a fixed anatomical connectivity matrix. Here we show that both sources contribute to the shaping of resting-state networks, yet with distinct contributions during consciousness and anesthesia. We measured dynamical functional connectivity with functional MRI during the resting state in awake and anesthetized monkeys. Under anesthesia, the more frequent functional connectivity patterns inherit the structure of anatomical connectivity, exhibit fewer small-world properties, and lack negative correlations. Conversely, wakefulness is characterized by the sequential exploration of a richer repertoire of functional configurations, often dissimilar to anatomical structure, and comprising positive and negative correlations among brain regions. These results reconcile theories of consciousness with observations of long-range correlation in the anesthetized brain and show that a rich functional dynamics might constitute a signature of consciousness, with potential clinical implications for the detection of awareness in anesthesia and brain-lesioned patients.

Disruption of hierarchical predictive coding during sleep.

When presented with an auditory sequence, the brain acts as a predictive-coding device that extracts regularities in the transition probabilities between sounds and detects unexpected deviations from these regularities. Does such prediction require conscious vigilance, or does it continue to unfold automatically in the sleeping brain? The mismatch negativity and P300 components of the auditory event-related potential, reflecting two steps of auditory novelty detection, have been inconsistently observed in the various sleep stages. To clarify whether these steps remain during sleep, we recorded simultaneous electroencephalographic and magnetoencephalographic signals during wakefulness and during sleep in normal subjects listening to a hierarchical auditory paradigm including short-term (local) and long-term (global) regularities. The global response, reflected in the P300, vanished during sleep, in line with the hypothesis that it is a correlate of high-level conscious error detection. The local mismatch response remained across all sleep stages (N1, N2, and REM sleep), but with an incomplete structure; compared with wakefulness, a specific peak reflecting prediction error vanished during sleep. Those results indicate that sleep leaves initial auditory processing and passive sensory response adaptation intact, but specifically disrupts both short-term and long-term auditory predictive coding.

Bedside quantitative electroencephalography improves assessment of consciousness in comatose subarachnoid hemorrhage patients.

OBJECTIVE: Accurate behavioral assessments of consciousness carry tremendous significance in guiding management, but are extremely challenging in acutely brain-injured patients. We evaluated whether electroencephalography (EEG) and multimodality monitoring parameters may facilitate assessment of consciousness in patients with subarachnoid hemorrhage. METHODS: A retrospective analysis was performed of 83 consecutively treated adults with subarachnoid hemorrhage. All patients were initially comatose and had invasive brain monitoring placed. Behavioral assessments were performed during daily interruption of sedation and categorized into 3 groups based on their best examination as (1) comatose, (2) arousable (eye opening or attending toward a stimulus), and (3) aware (command following). EEG features included spectral power and complexity measures. Comparisons were made using bootstrapping methods and partial least squares regression. RESULTS: We identified 389 artifact-free EEG clips following behavioral assessments. Increasing central gamma, posterior alpha, and diffuse theta-delta oscillations differentiated patients who were arousable from those in coma. Command following was characterized by a further increase in central gamma and posterior alpha, as well as an increase in alpha permutation entropy. These EEG features together with basic neurological examinations (eg, pupillary light reflex) contributed heavily to a linear model predicting behavioral state, whereas brain physiology measures (eg, brain oxygenation), structural injury, and clinical course added less. INTERPRETATION: EEG measures of behavioral states provide distinctive signatures that complement behavioral assessments of patients with subarachnoid hemorrhage shortly after the injury. Our data support the hypothesis that impaired connectivity of cortex with both central thalamus and basal forebrain underlies decreasing levels of consciousness. Ann Neurol 2016;80:541-553.

An accumulator model for spontaneous neural activity prior to self-initiated movement.

A gradual buildup of neuronal activity known as the "readiness potential" reliably precedes voluntary self-initiated movements, in the average time locked to movement onset. This buildup is presumed to reflect the final stages of planning and preparation for movement. Here we present a different interpretation of the premovement buildup. We used a leaky stochastic accumulator to model the neural decision of "when" to move in a task where there is no specific temporal cue, but only a general imperative to produce a movement after an unspecified delay on the order of several seconds. According to our model, when the imperative to produce a movement is weak, the precise moment at which the decision threshold is crossed leading to movement is largely determined by spontaneous subthreshold fluctuations in neuronal activity. Time locking to movement onset ensures that these fluctuations appear in the average as a gradual exponential-looking increase in neuronal activity. Our model accounts for the behavioral and electroencephalography data recorded from human subjects performing the task and also makes a specific prediction that we confirmed in a second electroencephalography experiment: Fast responses to temporally unpredictable interruptions should be preceded by a slow negative-going voltage deflection beginning well before the interruption itself, even when the subject was not preparing to move at that particular moment.

Distinct dynamic connectivity profiles promote enhanced conscious perception of auditory stimuli.

The neuroscience of consciousness aims to identify neural markers that distinguish brain dynamics in healthy individuals from those in unconscious conditions. Recent research has revealed that specific brain connectivity patterns correlate with conscious states and diminish with loss of consciousness. However, the contribution of these patterns to shaping conscious processing remains unclear. Our study investigates the functional significance of these neural dynamics by examining their impact on participants' ability to process external information during wakefulness. Using fMRI recordings during an auditory detection task and rest, we show that ongoing dynamics are underpinned by brain patterns consistent with those identified in previous research. Detection of auditory stimuli at threshold is specifically improved when the connectivity pattern at stimulus presentation corresponds to patterns characteristic of conscious states. Conversely, the occurrence of these conscious state-associated patterns increases after detection, indicating a mutual influence between ongoing brain dynamics and conscious perception. Our findings suggest that certain brain configurations are more favorable to the conscious processing of external stimuli. Targeting these favorable patterns in patients with consciousness disorders may help identify windows of greater receptivity to the external world, guiding personalized treatments.

Content-state dimensions characterize different types of neuronal markers of consciousness.

Identifying the neuronal markers of consciousness is key to supporting the different scientific theories of consciousness. Neuronal markers of consciousness can be defined to reflect either the brain signatures underlying specific conscious content or those supporting different states of consciousness, two aspects traditionally studied separately. In this paper, we introduce a framework to characterize markers according to their dynamics in both the "state" and "content" dimensions. The 2D space is defined by the marker's capacity to distinguish the conscious states from non-conscious states (on the x-axis) and the content (e.g. perceived versus unperceived or different levels of cognitive processing on the y-axis). According to the sign of the x- and y-axis, markers are separated into four quadrants in terms of how they distinguish the state and content dimensions. We implement the framework using three types of electroencephalography markers: markers of connectivity, markers of complexity, and spectral summaries. The neuronal markers of state are represented by the level of consciousness in (i) healthy participants during a nap and (ii) patients with disorders of consciousness. On the other hand, the neuronal markers of content are represented by (i) the conscious content in healthy participants' perception task using a visual awareness paradigm and (ii) conscious processing of hierarchical regularities using an auditory local-global paradigm. In both cases, we see separate clusters of markers with correlated and anticorrelated dynamics, shedding light on the complex relationship between the state and content of consciousness and emphasizing the importance of considering them simultaneously. This work presents an innovative framework for studying consciousness by examining neuronal markers in a 2D space, providing a valuable resource for future research, with potential applications using diverse experimental paradigms, neural recording techniques, and modeling investigations.

Intracortical recordings reveal vision-to-action cortical gradients driving human exogenous attention.

Exogenous attention, the process that makes external salient stimuli pop-out of a visual scene, is essential for survival. How attention-capturing events modulate human brain processing remains unclear. Here we show how the psychological construct of exogenous attention gradually emerges over large-scale gradients in the human cortex, by analyzing activity from 1,403 intracortical contacts implanted in 28 individuals, while they performed an exogenous attention task. The timing, location and task-relevance of attentional events defined a spatiotemporal gradient of three neural clusters, which mapped onto cortical gradients and presented a hierarchy of timescales. Visual attributes modulated neural activity at one end of the gradient, while at the other end it reflected the upcoming response timing, with attentional effects occurring at the intersection of visual and response signals. These findings challenge multi-step models of attention, and suggest that frontoparietal networks, which process sequential stimuli as separate events sharing the same location, drive exogenous attention phenomena such as inhibition of return.

Processing of the same narrative stimuli elicits common functional connectivity dynamics between individuals.

It has been suggested that conscious experience is linked to the richness of brain state repertories, which change in response to environmental and internal stimuli. High-level sensory stimulation has been shown to alter local brain activity and induce neural synchrony across participants. However, the dynamic interplay of cognitive processes underlying moment-to-moment information processing remains poorly understood. Using naturalistic movies as an ecological laboratory model of the real world, here we investigate how the processing of complex naturalistic stimuli alters the dynamics of brain network interactions and how these in turn support information processing. Participants underwent fMRI recordings during movie watching, scrambled movie watching, and resting. By measuring the phase-synchrony between different brain networks, we analyzed whole-brain connectivity patterns. Our finding revealed distinct connectivity patterns associated with each experimental condition. We found higher synchronization of brain patterns across participants during movie watching compared to rest and scrambled movie conditions. Furthermore, synchronization levels increased during the most engaging parts of the movie. The synchronization dynamics among participants were associated with suspense; scenes with higher levels of suspense induced greater synchronization. These results suggest that processing the same high-level information elicits common neural dynamics across individuals, and that whole-brain functional connectivity tracks variations in processed information and subjective experience.