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Boly, M.

Publications and source records attributed to Boly, M..

13 recordsLinked to original sources

Neural Signatures of Conscious Experience During Sleep: A Serial Awakening Study Using High-Density EEG

Identifying neural signatures of consciousness remains a central challenge in neuroscience. Sleep offers a tractable model for comparing brain activity in the presence or absence of subjective experience while minimizing behavioral responsiveness confounds. Using overnight 256 electrode high-density EEG in 140 participants and a serial-awakening paradigm, we analyzed 699 non-rapid eye movement (NREM) sleep stage 2 and 3 awakenings (351 dreaming experience, 348 no experience). Features from the 60s preceding awakening included regional spectral power, lagged-coherence connectivity, graph-theoretic metrics and gamma-to-alpha power ratios. Dreaming experiences were associated with shifts in posterior spectral balance, particularly reduced alpha and delta power and increased gamma-related measures, together with altered large scale network organization. In participant-level cross-validated machine-learning analyses, all classifiers performed above chance, with the best ensemble model reaching an ROC-AUC of 0.80 and average precision of 0.80. These findings identify reproducible posterior electrophysiological and network-level signatures of conscious states during NREM sleep.

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Early reactivation of medial temporal lobe neurons during emergence from propofol anesthesia in neurosurgical patients

Although much is known about the molecular and cellular effects of general anesthetics, the neural mechanisms underlying loss and recovery of consciousness during anesthesia remain elusive. We provide the first report of human single neuron activity recorded throughout emergence from general anesthesia. Following cessation of propofol infusion, emergence was assessed as motor response to verbal command (RC). In most cells, firing rates increased during the course of emergence. Analysis of pooled firing rate changes indicated a shift towards criticality during emergence and attractor states during and immediately following anesthesia and immediately after RC. Changes in activity in some regions occurred prior to overt RC, with shortest latencies in the hippocampus, parahippocampal gyrus, and amygdala, followed by cingulate and then insular cortex. This work reveals that brain activity in medial temporal regions may presage restoration of responsiveness in humans following general anesthesia.

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Temporal Interference Stimulation Can Enhance or Disrupt Human Memory Encoding as a Function of Brain Location and Frequency

Visual memory relies on synchronized interactions and rhythms between the medial temporal lobes and neocortical brain regions. Non-invasive manipulation of memory-related brain regions, specifically deeper temporal lobe regions, has been limited by the lack of precision of non-invasive neuromodulation - when targeting deeper structures, the cortex is always stimulated, never deeper structures in isolation. Temporal Interference (TI) stimulation, a novel non-invasive technique, uses high-frequency carrier fields to deliver targeted, physiologically relevant neuromodulation via amplitude-modulated envelopes at specific brain regions. Here, we investigate TIs impact on figure memory encoding in 70 healthy participants using the Rey-Osterrieth and Taylor Complex Figure tasks, with TI applied in several brain regions independently and simultaneously - allowing investigation of combinations of medial temporal lobe and neocortical brain regions. Interestingly, higher frequency TI envelopes (130 Hz offset) targeting bilateral hippocampi and temporal cortices significantly impair recall (p = 6.54e-04), while lower frequency TI envelopes (5 Hz offset) targeting only the bilateral hippocampi significantly enhance recall (p = 0.0447). Stimulation using other combinations of medial temporal lobe and neocortical regions showed no effect, underscoring the critical role of frequency and focality of non-invasive brain stimulation and correct target selection. Finally, functional MRI reveals strong differences between the effects of 130 Hz and 5 Hz envelopes, specifically in hippocampal BOLD signals, brain connectivity, default mode, and attentional networks. These findings demonstrate TIs ability to bidirectionally modulate memory encoding through precise frequency and target tuning, offering a powerful tool for cognitive neuroscience and potential therapeutic applications for memory disorders. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/677714v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@8e9db3org.highwire.dtl.DTLVardef@1135a3corg.highwire.dtl.DTLVardef@189345dorg.highwire.dtl.DTLVardef@ccca8f_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical Abstract:C_FLOATNO Temporal Interference stimulation for bidirectional memory modulation assessed via behavioral testing and MRI scanning. C_FIG

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Neural correlates of pure presence

Pure presence (PP) is described in several meditative traditions as an experience of a vast, vivid space devoid of perceptual objects, thoughts, and self. Integrated information theory (IIT) predicts that such vivid experiences may occur when the cortical substrate of consciousness is virtually silent. To test this, we analyzed high-quality 256-electrode high-density electroencephalography (hdEEG) from twenty-two long-term Vajrayana and Zen meditators who reported reaching PP during a week-long retreat. Because neural activity typically increases gamma power, we predicted PP would show widespread gamma reductions. Across both traditions, PP was associated with broadband power decrease compared to within-meditation mind-wandering, most consistent in the gamma range (30- 45 Hz). Source reconstruction revealed widespread gamma decreases, strongest in posteromedial cortex. PP gamma power was lower than in all other control states, including watching or imagining a movie, active thinking, and open-monitoring. PP delta power (1-4Hz) was also markedly reduced compared to dreamless sleep. Meditative states resembling PP--with minimal perceptual contents or accompanied by bliss-- showed similar signatures. Overall, PP appears to be a state of vivid consciousness during which the cortex is highly awake (low delta) yet widely quiescent (low gamma), in line with IITs predictions.

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Traveling waves shape neural population dynamics enabling predictions and internal model updating

The brain generates predictions based on statistical regularities in our environment. However, it is unclear how predictions are optimized through iterative interactions with the environment. Because traveling waves (TWs) propagate across the cortex shaping neural excitability, they can carry information to serve predictive processing. Using human intracranial recordings, we show that anterior-to-posterior alpha TWs correlated with prediction strength. Learning about priors altered neural state space trajectories, and how much it altered correlated with trial-by-trial prediction strength. Learning involved mismatches between predictions and sensory evidence triggering alpha-phase resets in lateral temporal cortex, accompanied by stronger alpha phase-high gamma amplitude coupling and high-gamma power. The mismatch initiated posterior-to-anterior alpha TWs and change in the subsequent trials state space trajectory, facilitating model updating. Our findings suggest a vital role of alpha TWs carrying both predictions to sensory cortex and mismatch signals to frontal cortex for trial-by-trial fine-tuning of predictive models.

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Criticality of resting-state EEG predicts perturbational complexity and level of consciousness during anesthesia

1Consciousness has been proposed to be supported by electrophysiological patterns poised at criticality, a dynamical regime which exhibits adaptive computational properties, maximally complex patterns and divergent sensitivity to perturbation. Here, we investigated dynamical properties of the resting-state electroencephalogram of healthy subjects undergoing general anesthesia with propofol, xenon or ketamine. We then studied the relation of these dynamic properties with the perturbational complexity index (PCI), which has shown remarkably high sensitivity in detecting consciousness independent of behavior. All participants were unresponsive under anesthesia, while consciousness was retained only during ketamine anesthesia (in the form of vivid dreams)., enabling an experimental dissociation between unresponsiveness and unconsciousness. We estimated (i) avalanche criticality, (ii) chaoticity, and (iii) criticality-related measures, and found that states of unconsciousness were characterized by a distancing from both the edge of activity propagation and the edge of chaos. We were then able to predict individual subjects PCI (i.e., PCImax) with a mean absolute error below 7%. Our results establish a firm link between the PCI and criticality and provide further evidence for the role of criticality in the emergence of consciousness. 2 Significance StatementComplexity has long been of interest in consciousness science and had a fundamental impact on many of todays theories of consciousness. The perturbational complexity index (PCI) uses the complexity of the brains response to cortical perturbations to quantify the presence of consciousness. We propose criticality as a unifying framework underlying maximal complexity and sensitivity to perturbation in the conscious brain. We demonstrate that criticality measures derived from resting-state electroencephalography can distinguish conscious from unconscious states, using propofol, xenon and ketamine anesthesia, and from these measures we were able to predict the PCI with a mean error below 7%. Our results support the hypothesis that critical brain dynamics are implicated in the emergence of consciousness and may provide new directions for the assessment of consciousness.

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An adversarial collaboration to critically evaluate theories of consciousness

Different theories explain how subjective experience arises from brain activity1,2. These theories have independently accrued evidence, yet, confirmation bias and dependence on design choices hamper progress in the field3. Here, we present an open science adversarial collaboration which directly juxtaposes Integrated Information Theory (IIT)4,5 and Global Neuronal Workspace Theory (GNWT)6-10, employing a theory-neutral consortium approach11,12. We investigate neural correlates of the content and duration of visual experience. The theory proponents and the consortium developed and preregistered the experimental design, divergent predictions, expected outcomes, and their interpretation12. 256 human subjects viewed suprathreshold stimuli for variable durations while neural activity was measured with functional magnetic resonance imaging, magnetoencephalography, and electrocorticography. We find information about conscious content in visual, ventro-temporal and inferior frontal cortex, with sustained responses in occipital and lateral temporal cortex reflecting stimulus duration, and content-specific synchronization between frontal and early visual areas. These results confirm some predictions of IIT and GNWT, while substantially challenging both theories: for IIT, a lack of sustained synchronization within posterior cortex contradicts the claim that network connectivity specifies consciousness. GNWT is challenged by the general lack of ignition at stimulus offset and limited representation of certain conscious dimensions in prefrontal cortex. Beyond challenging the theories themselves, we present an alternative approach to advance cognitive neuroscience through a principled, theory-driven, collaborative effort. We highlight the challenges to change peoples mind 13 and the need for a quantitative framework integrating evidence for systematic theory testing and building.

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Distinct signatures of loss of consciousness during Focal Impaired Awareness (FIA) versus Focal to Bilateral Tonic-Clonic (FBTC) seizures

Loss of consciousness (LOC) is a hallmark of many epileptic seizures and carries risks of serious injury and sudden death. While cortical sleep-like activities accompany LOC during focal impaired awareness (FIA) seizures, the mechanisms of LOC during focal to bilateral tonic-clonic (FBTC) seizures remain unclear. Quantifying differences in markers of cortical activation and ictal recruitment between FIA and FBTC seizures may also help to understand their different consequences for clinical outcomes and to optimize neuromodulation therapies. We quantified clinical signs of LOC and intracranial EEG (iEEG) activity during 129 FIA and 50 FBTC from 41 patients. We characterized iEEG changes both in the seizure onset zone (SOZ) and in areas remote from SOZ with a total of 3386 electrodes distributed across brain areas. First, we compared the dynamics of iEEG sleep-like activities: slow-wave activity (SWA; 1-4 Hz) and beta/delta ratio (B/D; a validated marker of cortical activation) during FIA vs. FBTC. Second, we quantified differences between FBTC and FIA for a marker validated to detect ictal cross-frequency coupling: phase-locked high-gamma (PLHG; high gamma phased locked to low frequencies) and a marker of ictal recruitment: the epileptogenicity index (i.e. the number of channels crossing an energy ratio threshold for high vs. low frequency power). Third, we assessed changes in iEEG activity preceding and accompanying behavioral generalization onset and their correlation with electromyogram (EMG) channels. In addition, we analyzed human cortical multi-unit activity recorded with Utah arrays during three FBTC. Compared to FIA, FBTC seizures were characterized by deeper LOC and by stronger increases in SWA in parieto-occipital cortex. FBTC also displayed more widespread increases in cortical activation (B/D), ictal cross-frequency coupling (PLHG) and ictal recruitment (epileptogenicity index). Even before generalization, FBTC displayed deeper LOC; this early LOC was accompanied by a paradoxical increase in B/D in fronto-parietal cortex. Behavioral generalization coincided with complete loss of responsiveness and a subsequent increase in high-gamma in the whole brain, which was especially synchronous in deep sources and could not be explained by EMG. Similarly, multi-unit activity analysis of FBTC revealed sustained increases in cortical firing rates during and after generalization onset in areas remote from the SOZ. Unlike during FIA, LOC during FBTC is characterized by a paradoxical increase in cortical activation and neuronal firing. These findings suggest differences in the mechanisms of ictal LOC between FIA and FBTC and may account for the more negative prognostic consequences of FBTC.

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BOLD signatures of sleep

Sleep can be distinguished from wake by changes in brain electrical activity, typically assessed using electroencephalography (EEG). The hallmark of non-rapid-eye-movement sleep are two major EEG events: slow waves and spindles. Here we sought to identify possible signatures of sleep in brain hemodynamic activity, using simultaneous fMRI-EEG. We found that, during the transition from wake to sleep, blood-oxygen-level-dependent (BOLD) activity evolved from a mixed-frequency pattern to one dominated by two distinct oscillations: a low-frequency (~0.05Hz) oscillation prominent in light sleep and a high-frequency (~0.17Hz) oscillation in deep sleep. The two BOLD oscillations correlated with the occurrences of spindles and slow waves, respectively. They were detectable across the whole brain, cortically and subcortically, but had different regional distributions and opposite onset patterns. These spontaneous BOLD oscillations provide fMRI signatures of basic sleep processes, which may be employed to study human sleep at spatial resolution and brain coverage not achievable using EEG. HIGHLIGHTSspontaneous BOLD oscillations differentiate sleep from wake low-frequency BOLD oscillation tracks sleep spindles high-frequency BOLD oscillation tracks sleep slow waves BOLD oscillations provide fMRI signatures of key sleep processes

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A fast and general method to empirically estimate the complexity of distributed causal interactions in the brain

BackgroundThe Perturbational Complexity Index (PCI) was recently introduced to assess the capacity of thalamocortical circuits to engage in complex patterns of causal interactions. While showing high accuracy in detecting consciousness in brain injured patients, PCI depends on elaborate experimental setups and offline processing and has restricted applicability to other types of brain signals beyond transcranial magnetic stimulation and high-density EEG (TMS/hd-EEG) recordings. ObjectiveWe aim to address these limitations by introducing PCIST, a fast method for estimating perturbational complexity of any given brain response signal. MethodsPCIST is based on dimensionality reduction and state transitions (ST) quantification of evoked potentials. The index was validated on a large dataset of TMS/hd-EEG recordings obtained from 108 healthy subjects and 108 brain injured patients, and tested on sparse intracranial recordings (SEEG) of 9 patients undergoing intra-cerebral single-pulse electrical stimulation (SPES). ResultsWhen calculated on TMS/hd-EEG potentials, PCIST performed with the same accuracy as the original PCI, while improving on the previous method by being computed in less than a second and requiring a simpler set-up. In SPES/SEEG signals, the index was able to quantify a systematic reduction of intracerebral complexity during sleep, confirming the occurrence of state-dependent changes in the effective connectivity of thalamocortical circuits, as originally assessed through TMS/hd-EEG. ConclusionsPCIST represents a fundamental advancement towards the implementation of a reliable and fast clinical tool for the bedside assessment of consciousness as well as a general measure to explore the neuronal mechanisms of loss/recovery of brain complexity across scales and models.

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Sleep-like bistability, loss of causality and complexity in the brain of Unresponsive Wakefulness Syndrome patients

Unresponsiveness Wakefulness Syndrome (UWS) patients may retain intact portions of the thalamocortical system that are spontaneously active and responsive to sensory stimuli. In these patients, Transcranial Magnetic Stimulation combined with electroencephalography (TMS/EEG) also reveals preserved cortical reactivity, but in most cases, the residual thalamocortical circuits fail to engage complex causal interactions, as assessed by the perturbational complexity index (PCI). Another condition during which thalamocortical circuits are intact, active and reactive, yet unable to generate complex responses, is physiological non-rapid eye movement (NREM) sleep. The underlying mechanism is bistability: the tendency of cortical neurons to fall into a silent period (OFF-period) upon receiving an input. Here we tested whether a pathological form of bistability may be responsible for loss of brain complexity in UWS patients. Time-frequency decomposition analysis of TMS/EEG responses in UWS patients revealed the occurrence of OFF-periods (detected as a transient suppression of high-frequency oscillations in the EEG) similar to the ones evoked by TMS in the cortex of healthy sleeping subjects. Pathological OFF-periods were detected in any cortical area, significantly impaired local causal interactions (as measured by PLF) and prevented the build-up of global complexity (as measured by PCI) in the brain of UWS patients. Our results draw a first link between neuronal events (OFF-periods) and global brain dynamics (complexity) in UWS patients. To the extent that sleep-like bistability represents the common functional endpoint of loss of complexity, detecting its presence and tracking its evolution over time, may offer a valuable read-out to devise, guide and titrate therapeutic strategies aimed at restoring consciousness.

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Propofol-Induced Unresponsiveness is Associated with Impaired Feedforward Connectivity in the Cortical Hierarchy

BackgroundImpaired consciousness has been associated with impaired cortical signal propagation following transcranial magnetic stimulation (TMS). Herein we hypothesized that the reduced current propagation under propofol-induced unresponsiveness is associated with changes in both feedforward and feedback connectivity across the cortical hierarchy.\n\nMethodsEight subjects underwent left occipital TMS coupled with high-density electroencephalograph (EEG) recordings during wakefulness and propofol-induced unconsciousness. Spectral analysis was applied to responses recorded from sensors overlying six hierarchical cortical sources involved in visual processing. Dynamic causal modelling (DCM) of evoked and induced source-space responses was used to investigate propofols effects on connectivity between regions.\n\nResultsPropofol produced a wideband reduction in evoked power following TMS in five out of six electrodes. Bayesian Model Selection supported a DCM with hierarchical feedforward and feedback connections to best fit the data. DCM of induced responses revealed that the primary effect of propofol was impaired feedforward responses in cross frequency theta/alpha-gamma coupling and within frequency theta coupling (F contrast, Family Wise Error corrected p<0.05). An exploratory analysis (thresholded at uncorrected p<0.001) also suggested that propofol impaired feedforward and feedback beta band coupling. Posthoc analyses showed impairments in all feedforward connections and one feedback connection from parietal to occipital cortex. DCM of the evoked response potential showed impaired feedforward connectivity between left sided occipital and parietal cortex (T contrast p=0.004, Bonferroni corrected).\n\nConclusionsOur data suggest that propofol-induced loss of consciousness is associated with reduced evoked power and impaired hierarchical feedforward connectivity following occipital TMS.

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