Biology subjects

Naccache, L.

Publications and source records attributed to Naccache, L..

17 recordsLinked to original sources

bioRxiv2026

Spontaneous slow waves index multiple dimensions of recovery in Disorders of Consciousness

Whether and how residual awareness is expressed in patients with Disorders of Consciousness (DoC) depends on the severity of brain damage and the transient functional state of the cortex at assessment. Classically, DoC are associated with electroencephalographic (EEG) slowing, marked by high-amplitude slow waves, even during the day. Yet, slow waves are also a hallmark of healthy sleep, where they are thought to serve restorative functions and to help maintain network homeostasis. Here, we asked whether slow waves in DoC can provide insights into the severity of cortical dysfunction or, conversely, into the preservation of residual awareness and recovery potential, by characterizing their spatial, temporal and morphological properties. We analyzed 256-channel EEG recorded during the Local-Global auditory paradigm in 236 DoC patients, including 123 in Unresponsive Wakefulness Syndrome (UWS), 62 in a Minimally Conscious State minus (MCS-) and 29 in MCS plus (MCS+). High-amplitude slow waves were detected as local events, and their density, amplitude and slopes were quantified scalp-wide and channel-wise, by mean level and temporal variability across the recording. Slow-wave features were related to concurrent (Coma Recovery Scale-Revised - CRS-R, Local-Global paradigm) and follow-up (one-year Glasgow Outcome Scale-Extended - GOS-E) assessments of consciousness and functional recovery. Associations with MRI-derived measures of cortical integrity and structural connectivity, and differences between anoxic and traumatic etiologies, were also examined. Slow waves were more frequent in less severe DoC patients (i.e., MCS) compared to UWS. Slow-wave slopes were also steeper frontally and increased at a faster rate in patients exhibiting higher levels of consciousness and/or markers of conscious access during the Local-Global paradigm. More frequent and steeper slow waves at baseline further predicted recovery of consciousness and of functional independence at one year. At the individual level, slow-wave features classified states of consciousness above chance (AUC = 0.62 and 0.71 for MCS- and MCS+ versus UWS), whereas outcome prediction remained modest (0.56-0.58). These clinical associations had a structural basis: slow-wave occurrence was greater after traumatic than anoxic injury and scaled with the integrity of subcortico-cortical projection fibers and consciousness-related cortical networks. Contrary to the classical view of delta activity as a non-specific marker of impaired consciousness, prominent spontaneous slow waves indexed behavioral and neurophysiological signs of awareness and better recovery. Beyond reflecting a propensity for pathological bistability, they may also signal the integrity of the networks required to generate them, together with their residual capacity for dynamic regulation.

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bioRxiv2026

Classical music in cognitive rehabilitation: Three case studies of spatial neglect

Chronic spatial neglect after right-hemisphere stroke reflects network dysfunction, with recovery influenced by structural connectivity. Music recruits coordinated bi-hemispheric activity and may promote interhemispheric communication after stroke. Following our pilot study in post-stroke aphasia, we asked whether classical music modulates connectivity and behavior in chronic neglect. Three patients completed a crossover protocol comparing two weeks of daily audiovisual classical music with an audiobook control, with neglect, mood, quality-of-life, diffusion MRI, and resting-state high-density EEG measures. All showed right superior longitudinal fasciculus II disconnection with preserved callosal pathways. In N2, line bisection shifted leftward across all five lines after music, together with increased posterior interhemispheric theta-band weighted symbolic mutual information (wSMI), then deteriorated into the pathological range after the audiobook, without mood improvement. N1 showed mixed behavioral effects, with mood and quality of life improving after music. N3 showed no significant spatial improvement and worsened mood after music. These heterogeneous responses motivate larger studies of connectional predictors. The findings support the feasibility of classical music as an adjunct to neglect rehabilitation and suggest that cognitive changes may occur independently of mood, while the audiobook cannot be considered an inert control.

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bioRxiv2025

Individualised electrophysiological neural field models for the assessment of thalamocortical function in disorders of consciousness: a multicentre study

Understanding the neural mechanisms underlying disorders of consciousness (DoC) remains a major challenge, particularly in distinguishing limited awareness in minimally conscious state (MCS) and complete unawareness in unresponsive wakefulness syndrome, also coined vegetative state (UWS/VS). In this multicentre study, we fitted a biophysically informed corticothalamic neural field model to high-density EEG data from two large independent datasets, comprising 203 UWS patients, 270 MCS patients and 74 healthy controls. We then used the fitted parameters to simulate EEG time series on a per-subject basis and compared empirical and simulated complexity metrics. The model reliably captured the spectral features across different states of consciousness and revealed reduced corticothalamic integrity in DoC patients that was more pronounced in UWS than in MCS, supporting the mesocircuit hypothesis. Furthermore, the simulated EEG reproduced the complexity patterns of the empirical recordings, with permutation entropy emerging as a sensitive marker capable of distinguishing between MCS and UWS for both real and simulated time series.

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bioRxiv2025

How sleeping minds decide: state-specific reconfigurations of lexical decision-making

Decision-making is a core cognitive function that enables adaptive behavior across diverse contexts. While extensively studied in wakefulness, its persistence and reconfiguration across sleep states remain poorly understood. Here, we use computational modeling to examine lexical decision-making across wakefulness, N1 sleep, and lucid REM sleep in both healthy participants (HP) and participants with narcolepsy (NP). Using facial electromyography (EMG) to capture real-time behavioral responses to spoken words and pseudowords during sleep, we quantify how decision-making strategies adapt under different sleep and consciousness states. Our findings reveal two key insights. First, decision-making mechanisms are dynamically reconfigured across sleep states. In N1 sleep, the advantage for word (vs. pseudoword) judgments is supported by faster sensory encoding and motor preparation, combined with efficient evidence accumulation. In contrast, in lucid REM sleep, the word advantage is driven exclusively by enhanced evidence accumulation, while sensory encoding and motor preparation remain unchanged. Second, cross-state comparisons reveal distinct patterns of preservation and impairment. In N1 sleep, word judgment remains largely intact, whereas pseudoword judgment is significantly impaired, characterized by prolonged stimulus encoding, delayed motor preparation, and reduced evidence accumulation. In contrast, lucid REM sleep is marked by a global reduction in processing efficiency, reflected in slower evidence accumulation and elevated decision thresholds for both words and pseudowords. These results demonstrate that rather than being uniformly degraded, decision-making is dynamically reconfigured across sleep stages, reflecting adaptive neurocognitive strategies that sustain cognition in altered states of consciousness. By identifying state-specific computational mechanisms, this study provides new insights into the brains resilience and flexibility under changing cognitive and physiological conditions.

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bioRxiv2024

Dynamics of EEG Microstates Change Across the Spectrum of Disorders of Consciousness

As a response to the environment and internal signals, brain networks reorganize on a sub-second scale. To capture this reorganization in patients with disorders of consciousness and understand their residual brain activity, we investigated the dynamics of electroencephalography (EEG) microstates. We analyze EEG microstate markers to quantify the periods of semi-stable topographies and the large-scale cortical networks they may reflect. To achieve this, EEG samples are clustered into four groups and then fit back into each time sample. We then obtain a time series of maps with different frequencies of occurrence and duration. One such occurrence of a map with a given duration is called a microstate. The goal of this work is to study the dynamics of these topographical patterns across patients with disorders of consciousness. Using the microstate time series, we calculate static and dynamic markers. In contrast to the static, the dynamic metrics depend on the specific temporal sequences of the maps. The static measure Ratio of Total Time covered (RTT) shows differences between healthy controls and patients, however, no differences were observed between the groups of patients. In contrast, some dynamic markers capture inter-patient group differences. The dynamic markers we investigated are Mean Microstate Durations (MMD), Microstate Duration Variances (MDV), Microstate Transition Matrices (MTM), and Entropy Production (EP). The MMD and MDV decrease with the state of consciousness, whereas the MTM non-diagonal transitions and EP increase. In other words, DoC patients have slower and closer to equilibrium (time-reversible) brain dynamics. In conclusion, static and dynamic EEG microstate metrics differ across consciousness levels, with the latter capturing the subtitler differences between groups of patients with disorders of consciousness. Abbreviated summaryThis study investigates EEG microstate dynamics in patients with disorders of consciousness (DoC) to understand residual brain activity and network reorganization. Entropy production, in addition to static markers, differs between patients and healthy controls, whereas the rest of the dynamic markers show differences across patient groups.

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bioRxiv2024

Mind the blank: behavioral, experiential, and physiological signatures of absent-mindedness

Does being awake necessarily mean being conscious of something? This study investigates the phenomenon of Mind Blanking (MB), characterized by an "emptiness of mind", comparing it with Mind Wandering (MW) and On-task (ON) states. Using a sustained attention task and electroencephalogram monitoring, behavioral and neurophysiological signatures of MB were examined in 62 participants. MB exhibited a specific pattern of behavioral lapses, as well as decreased fast oscillatory activity and complexity over posterior electrodes compared to MW. Functional connectivity analyses revealed decreased long-range inter-areal connectivity during MB, compared to both ON and MW states. Event-related potentials with source reconstruction and temporal decoding techniques indicated a significant disruption in visual processing during MB, starting from 200 ms post stimulus and echoing into the late-stage of visual processing, suggesting a disruption of conscious access to sensory information during MB. EEG-derived markers allowed the prediction of mental states at the trial level, offering a finer view of conscious dynamics than subjective reports alone. Overall, these findings challenge the notion of the wakeful conscious mind as inherently content-oriented, suggesting that MB reflects genuine gaps in the stream of conscious thoughts, arising from disruptions in the generation or accessibility of thought content. SIGNIFICANCE STATEMENTEmploying cutting-edge neurophysiological techniques on high-density electroencephalographic recordings, our study unveils unique neurophysiological markers of mind blanking, a phenomenon characterized by lapses in conscious content amidst the flow of wakeful consciousness. Distinguished from content-oriented states such as on-task and mind-wandering, mind blanking appears to be a distinct mental state. Furthermore, we demonstrate the feasibility of decoding consciousness dynamics solely from EEG features, transcending the limitations of intermittent subjective reports. Our findings thus not only provide a novel framework for investigating the stream of consciousness but also challenge the conventional notion that wakefulness invariably signifies being conscious of something.

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bioRxiv2024

Dynamic connectivity profiles characteristic of conscious states are associated with enhanced conscious processing of external stimuli

One of the goals of the neuroscience of consciousness is to identify neural markers capable of distinguishing brain dynamics in awake, healthy individuals from unconscious conditions. This problem also has a clinical diagnostic interest in disorders of consciousness. Recent research has shown that brain connectivity patterns characterized by long-range interactions and anticorrelations are associated with conscious states and diminish with loss of consciousness in human and non-human primates. However, the precise contribution of these patterns to conscious processing and subjective experience formation remains unclear. In this study, we investigated the functional role of these brain patterns in shaping conscious content by examining their influence on participants ability to process external information during wakefulness. Participants underwent fMRI recordings during an auditory detection task. Phase coherence-based functional connectivity and k-means clustering confirmed that the ongoing dynamics were underpinned by brain patterns consistent with those identified in previous research, including the "high pattern" characteristic of conscious states. We found that the detection of auditory stimuli at threshold was specifically improved when the connectivity pattern at the time of presentation corresponded to this high-pattern. In return, the occurrence of the high-pattern increased after detection, indicating that participants were more likely to transition to a high-pattern following stimulus detection. Our findings suggest that ongoing brain dynamics and conscious perception mutually influence each other and that certain brain configurations are more favorable for conscious processing of external stimuli. In the future, targeting these moments of favorable patterns in patients with disorders of consciousness may help us identify windows of greater receptivity to the external world, paving the way for developing individualized patient care protocols.

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bioRxiv2023

Whole-brain modelling supports the use of serotonergic psychedelics for the treatment of disorders of consciousness

Disorders of consciousness (DoC) are a challenging and complex group of neurological conditions characterised by absent or impaired awareness. The current range of therapeutic options for DoC patients is limited, offering few non-invasive pharmacological alternatives. This situation has sprung a growing interest in the development of novel treatments, such as the proposal to study the efficacy of 5HT2A receptor agonists (also known as psychedelics) to restore impaired consciousness. Given the ethical implications of exploring novel compounds in non-communicative individuals, we assessed in silico their effects in the whole-brain dynamics of DoC patients. We embedded the whole-brain activity of patients in a low-dimensional space, and then used this representation to visualise the effects of simulated neuromodulation across a range of receptors representing potential drug targets. Our findings show that activation of serotonergic and opioid receptors shifted brain dynamics of DoC patients towards patterns typically seen in conscious and awake individuals, and that this effect was mediated by the brain-wide density of activated receptors. These results showcase the role of whole-brain models in the discovery of novel pharmacological treatments for neuropsychiatric conditions, while also supporting the feasibility of accelerating the recovery of consciousness with serotonergic psychedelics.

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bioRxiv2023

Listening to classical music influences brain connectivity in post-stroke aphasia: a pilot study

Stroke-induced aphasia is a leading cause of cognitive disability. The healthy right hemisphere may play a role in aphasia compensation. Music-based therapy, known to enhance cognitive functions after stroke, offers a potential intervention due to its impact on brain connectivity, engaging both hemispheres. In this proof-of-concept study, we aimed to assess the feasibility and effectiveness of music-assisted therapy for language disorders following left hemisphere strokes. We also sought preliminary insights into the impact of music on post-stroke brain connectivity. We enrolled four right-handed patients (one female and three males, mean age 57.75 years, SD 7.63) who experienced their first left-hemisphere stroke inducing chronic aphasia symptoms three months post-stroke. Patients were randomly assigned to receive either two weeks of music therapy, involving daily 2-hour sessions of listening to instrumental music by Haydn, Mozart, and Beethoven, in addition to standard rehabilitation, or two weeks of standard care, using a crossover design. Patients underwent cognitive and neuroimaging assessments at baseline, crossover, and study end, with preliminary evaluation one week before the study to confirm stable deficits. All patients listened to the same curated playlist, accompanied by narrations situating the music in its with historical context. Cognitive assessments included the Core Assessment of Language Processing (CALAP) and a French aphasia battery (Bilan Informatise dAphasie, BIA). EEG and MRI data were analyzed, focusing on functional connectivity metrics (weighted symbolic mutual information, permutation entropy) and white matter tractography. Preliminary findings indicate that music therapy may be a feasible and promising approach to aphasia rehabilitation, with improvements observed in language tests and brain connectivity metrics. Despite limitations such as a small sample size and patient heterogeneity, these preliminary results suggest that intensive classical music listening may enhance language abilities in post-stroke aphasia patients. Additionally, using EEG connectivity metrics originally designed for non-communicative patients provides a novel avenue for monitoring brain plasticity during rehabilitation.

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bioRxiv2022

Behavioral and brain responses to verbal stimuli reveal transient periods of cognitive integration of external world in all sleep stages

Sleep has long been considered as a state of disconnection from the environment, with absent reactivity to external stimuli. Here, we questioned this sleep disconnection dogma by directly investigating behavioral responsiveness in 49 napping subjects (27 with narcolepsy and 22 healthy volunteers) engaged in a lexical decision task. Participants were instructed to frown or smile depending on the stimulus type (words vs pseudo-words). We found accurate behavioral responses, visible via contractions of the corrugator or zygomatic muscles, in all sleep stages in both groups (except slow-wave sleep for healthy volunteers). Stimuli presented during states with high (vs. low) values of neural markers indexing rich cognitive states more often yielded responses. Our findings suggest that transient windows of reactivity to external stimuli exist in all sleep stages, even in healthy individuals. Such windows of reactivity could be used to probe sleep-related mental and cognitive processes in real-time across all sleep stages.

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bioRxiv2021

Unifying turbulent dynamics framework distinguishes different brain states

Recently, significant advances have been made by identifying the levels of synchronicity of the underlying dynamics of a given brain state. This research has demonstrated that unconscious dynamics tend to be more synchronous than those found in conscious states, which are more asynchronous. Here we go beyond this dichotomy to demonstrate that the different brain states are always underpinned by spatiotemporal chaos but with dissociable turbulent dynamics. We investigated human neuroimaging data from different brain states (resting state, meditation, deep sleep, and disorders of consciousness after coma) and were able to distinguish between them using complementary model-free and model-based measures of turbulent information transmission. Our model-free approach used recent advances describing a measure of information cascade across spatial scales using tools from turbulence theory. Complementarily, our model-based approach used exhaustive in silico perturbations of whole-brain models fitted to the empirical neuroimaging data, which allowed us to study the information encoding capabilities of the brain states. Overall, the current framework demonstrates that different levels of turbulent dynamics are fundamental for describing and differentiating between brain states.

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bioRxiv2020

Conscious processing of narrative stimuli synchronizes heart rate between individuals

Heart rate has natural fluctuations that are typically ascribed to autonomic function. Recent evidence suggests that conscious processing can affect the timing of the heartbeat. We hypothesized that heart rate is modulated by conscious processing and therefore dependent on attentional focus. To test this, we leverage the observation that neural processes can be synchronized between subjects by presenting an identical narrative stimulus. As predicted, we find significant inter-subject correlation of the heartbeat (ISC-HR) when subjects are presented with an auditory or audiovisual narrative. Consistent with the conscious processing hypothesis, we find that ISC-HR is reduced when subjects are distracted from the narrative, and that higher heart rate synchronization predicts better recall of the narrative. Finally, patients with disorders of consciousness who are listening to a story have lower ISC-HR, as compared to healthy individuals, and that individual ISC-HR might predict a patients prognosis.. We conclude that heart rate fluctuations are partially driven by conscious processing, depend on attentional state, and may represent a simple metric to assess conscious state in unresponsive patients.

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bioRxiv2020

Learning to see the Ebbinghaus illusion in the periphery reveals a top-down stabilization of size perception across the visual field

Our conscious visual perception relies on predictive signals, notably in the periphery where sensory uncertainty is high. We investigated how such signals could support perceptual stability of objects size across the visual field. When attended carefully, the same object appears slightly smaller in the periphery compared to the fovea. Could this perceptual difference be encoded as a strong prior to predict the peripheral perceived size relative to the fovea? Recent studies emphasized the role of foveal information in defining peripheral size percepts. However, they could not disentangle bottom-up from top-down mechanisms. Here, we revealed a pure top-down contribution to the perceptual size difference between periphery and fovea. First, we discovered a novel Ebbinghaus illusion effect, inducing a typical reduction of foveal perceived size, but a reversed increase effect in the periphery. The size percept was similar at both retinal locations and deviated from the classic perceptual difference. Then through an updating process of successive peripheral-foveal viewing, the unusual peripheral perceived size decreased. The classic perceptual eccentricity difference was restored and the peripheral illusion effect changed into a fovea-like reduction. Therefore, we report the existence of a prior that actively shapes peripheral size perception and stabilizes it relative to the fovea.

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bioRxiv2019

Functional cortico-subcortical reorganization after complete hemispheric disconnection for intractable epilepsy

Hemispherotomy is a treatment for drug-resistant epilepsy with the whole hemisphere involved in seizure onset. As recovery mechanisms are still debated, we characterize functional reorganization with multimodal MRI in two children operated on the right hemisphere (RH). We found that interhemispheric functional connectivity was abolished in both patients. The healthy left hemispheres (LH) displayed focal hyperperfusion in motor and limbic areas, and preserved network-level organization. The disconnected RHs were hypoperfused despite sustained network-level organization. Functional connectivity was increased in the left thalamo-cortical loop and between the cerebelli. The classification probability of the RH corresponding to a minimally conscious state was smaller than for the LH. We conclude that after hemispherotomy, neurological rehabilitation is sustained by cortical disinhibition and reinforcement of connectivity driven by subcortical structures in the remaining hemisphere. Our results highlight the effect of vascularization on functional connectivity and raise inquiries about the conscious state of the isolated hemisphere.

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bioRxiv2019

Slow cortico-cortical connectivity (2-5Hz) is a new robust signature of conscious states

While long-range cortico-cortical functional connectivity has been reported by several studies as a necessary condition of conscious state, precise empirical evidence is still scarce. In the present work we provide such a direct and conclusive evidence in a set of three experiments. In the two first experiments intracranial-EEG was recorded during four distinct states in the same individuals: conscious wakefulness (CW), rapid-eye-movement sleep (REM), stable periods of slow-wave sleep (SWS) and deep propofol anaesthesia (PA). We discovered that long-range FC, computed by the weighted Symbolic-Mutual-Information (wSMI) in the 2-5Hz frequency band was a specific marker of conscious states that could discriminate CW and REM from SWS and PA. In the third experiment, we generalized this original finding on a large cohort of brain-injured patients by revealing that wSMI in the 2-5 Hz range was also able to accurately discriminate patients in the vegetative state (or unresponsive wakefulness syndrome) from patients in the minimally conscious state. Taken together the present results suggest that 2-5Hz FC is a new and robust signature of conscious states.

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bioRxiv2019

Combined behavioral and electrophysiological evidence for a direct cortical effect of prefrontal tDCS on disorders of consciousness

Severe brain injuries can lead to long-lasting disorders of consciousness (DoC) such as vegetative state/unresponsive wakefulness syndrome (VS/UWS) or minimally conscious state (MCS). While behavioral assessment remains the gold standard to determine conscious state, EEG has proven to be a promising complementary tool to monitor the effect of new therapeutics. Encouraging results have been obtained with invasive electrical stimulation of the brain, and recent studies identified transcranial direct current stimulation (tDCS) as an effective approach in randomized controlled trials. This non-invasive and inexpensive tool may turn out to be the preferred treatment option. However, its mechanisms of action and physiological effects on brain activity remain unclear and debated. Here, we stimulated 60 DoC patients with the anode placed over left-dorsolateral prefrontal cortex in a prospective open-label study. Clinical behavioral assessment improved in twelve patients (20%) and none deteriorated. This behavioral response after tDCS coincided with an enhancement of putative EEG markers of consciousness: in comparison with non-responders, responders showed increases of power and long-range cortico-cortical functional connectivity in the theta-alpha band, and a larger and more sustained P300 suggesting improved conscious access to auditory novelty. The EEG changes correlated with electric fields strengths in prefrontal cortices, and no correlation was found on the scalp. Taken together, this prospective intervention in a large cohort of DoC patients strengthens the validity of the proposed EEG signatures of consciousness, and is suggestive of a direct causal effect of tDCS on consciousness.

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bioRxiv2018

\"DoC-feeling\": a new behavioural tool to help diagnose the Minimally Conscious State.

ObjectivesThe clinical distinction between vegetative state/unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) is a key step to elaborate a prognosis and formulate an appropriate medical plan for any patient suffering from disorders of consciousness (DoC). However, this assessment is often challenging and may require specialized expertise. In this study, we hypothesized that pooling subjective reports of the level of consciousness of a given patient across several nursing staff members can be used to clinically detect MCS.\n\nSetting and ParticipantsPatients referred for consciousness assessment were prospectively screened. MCS (target condition) was defined according to the best Coma Recovery Scale-Revised score (CRS-R) obtained from expert physicians (reference standard). \"DoC-feeling\" score consisted in the median value of multiple ratings of patients behavior observation pooled from multiple staff members during a week of hospitalisation (index test). Individual ratings were collected at the end of each shift using a 100mm visual analog scale, blinded from the reference standard. Diagnostic accuracy was evaluated using area under the receiver operating characteristic curve (AUC), sensitivity and specificity metrics.\n\nResults692 ratings performed by 83 nursing staff members were collected from 47 patients. Twenty patients were in a UWS and 27 in a MCS. DoC-feeling scores obtained by pooling all individual ratings obtained for a given patient were significantly greater in MCS than in UWS patients (59.2 mm [IQR: 27.3-77.3] vs. 7.2 mm [IQR: 2.4-11.4]; p<0.001) yielding an AUC of 0.92 (95%CI: 0.84-0.99).\n\nConclusionsDoC-feeling capitalizes on the expertise of nursing staff to evaluate patients consciousness. Together with the CRS-R as well as with brain imaging, DoC-feeling might improve diagnostic and prognostic accuracy of DoC patients.\n\nStrengths and limitations of this studyO_LIWe designed a new behavioural tool called \"DoC-feeling\" to help face the clinical challenge of the detection of Minimally Conscious State in patients suffering from disorders of consciousness (DoC)\nC_LIO_LI\"DoC-feeling score\" quantifies nursing staffs subjective perception of patients consciousness by pooling multiple assessments obtained from multiple caregivers (\"wisdom of the crowds\")\nC_LIO_LIThis score which requires no particular training showed a very good accuracy when compared to the gold standard (repeated expert clinical assessment using the Coma Recovery Scale - Revised (CRS-R))\nC_LIO_LIA validation in a separate cohort would help to determine its place in consciousness assessment\nC_LIO_LIThis score should be tested not only against the CRS-R but also against brain-imaging techniques to test for its capacity to detect covert signs of consciousness\nC_LI

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