Biology subjects

Naci, L.

Publications and source records attributed to Naci, L..

18 recordsLinked to original sources

bioRxiv2026

A Shared Entropic Axis Spans States of Consciousness Across Pharmacological and Clinical Conditions

A general account of how diverse states of consciousness arise from brain activity requires a quantitative framework that generalises across them. The Entropic Brain Theory proposes that states of consciousness can be ordered along a single dimension defined by the entropy of spontaneous neural activity, but this prediction has not been tested across pharmacological and clinical perturbations within a common analytical pipeline. Here we quantify the temporal irregularity of time-resolved small-world topology using sample entropy, applying the same pipeline to pharmacological (psychedelics, modafinil, propofol anaesthesia) and clinical (schizophrenia) fMRI datasets. Propofol anaesthesia occupied the low-entropy end of the axis; psychedelic states and schizophrenia occupied the high end. The ordering tracks combined modulations of the level and content of consciousness, ranging from reduced awareness under anaesthesia to the heightened arousal and expanded experience of psychedelic states and the disorganised, dysregulated processing of schizophrenia. Crucially, this result was not reducible to fluctuations in mean functional connectivity, and was supported by convergent reorganisation of higher-order association cortex under psychedelics and anaesthesia, alongside a distributed loss of network specificity in schizophrenia. These findings provide cross-condition empirical support for an entropic continuum of brain states and identify the temporal diversity of large-scale network reconfiguration as a primary axis of conscious dynamics.

neuroscience↗

bioRxiv2026

The blueprint of human functional architecture shifts from cognition to anatomy during perturbations of consciousness

Consciousness and cognition arise from the ongoing interactions between brain regions. Synchronous fluctuations of fMRI signals may indicate that two brain regions perform similar cognitive functions, but neural interactions are also constrained by anatomical connectivity and regions molecular, cytoarchitectonic, and metabolic profiles. Here we disentangle the respective contributions of ongoing cognition and multimodal neurobiological constraints in shaping functional connectivity. We jointly contextualise haemodynamic FC against eight distinct multimodal representations of the human connectome: (i) structural connectivity from diffusion tractography; (ii) spatial embedding; (iii) similarity of transcriptional profiles from gene expression; (iv) similarity of receptor profiles from Positron Emission Tomography; (v) laminar profile similarity from histology; (vi) correlated electrophysiological activity from magnetoencephalography; (vii) correlated metabolic activity from PET glucose uptake; (viii) coordinated activation across 123 cognitive operations from the NeuroSynth meta-analytic engine. We demonstrate that cognitive co-activation is the dominant predictor of inter-regional fMRI synchrony in the awake human brain, even when quantified using intracranial electrical stimulation. Crucially, this predominance of cognitive co-activation for shaping functional connectivity is systematically obliterated across five datasets of pharmacological and pathological perturbations of consciousness (chronic disorders of consciousness; anaesthesia with sevoflurane, propofol, or ketamine) when cognition is disconnected from the environment or altogether abolished. Altogether, we show that multimodal predictors of functional architecture shift away from cognitive co-activation and toward anatomicalmolecular constraints during pharmacological and pathological perturbations of consciousness.

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bioRxiv2024

Diminished functional gradient of the precuneus during altered states of consciousness

The relationship between the default mode network (DMN) and task-positive networks, such as the frontoparietal control network (FPCN), is a prominent feature of functional connectivity (FC) in the human brain. This relationship is primarily anticorrelated at rest in healthy brains and is disrupted in altered states of consciousness. Although the DMN and FPCN seem to perform distinct and even opposing roles, they are anatomically adjacent and exhibit ambiguous boundaries. To test the hypothesis that the DMN-FPCN distinction manifests probabilistically rather than having absolute anatomical boundaries, we examined the differences in FC along the dorsal-ventral (d-v) axis in the posterior precuneus (PCu), which serves a convergence zone between the DMN and FPCN. Our findings indicate that the connectivity differences along this axis are continuous as characterized by linear slopes. Notably, these linear relationships (i.e., functional gradients of the precuneus/FGp) are present only within the territories of the DMN and FPCN, respectively associating with positive and negative slopes. Furthermore, the gradient is functionally relevant, as its spatial configurations change in specific ways in altered states of consciousness (ASC): the magnitude of FGp is similarly impaired across different types of ASC, while the spatial entropy of FGp differs between psychedelic and sedative states. These results suggest that the DMN and FPCN, while appearing distinct, may originate from a single, integrated mechanism. Significance StatementThis research provides new insights into the brains functional organization underlying human conscious states by examining the relationship between two large-scale networks: the default mode network (DMN) and the frontoparietal control network (FPCN). These networks, which are attuned to handle internal and external information respectively, are often viewed as oppositional. However, our findings indicate they form an integrated system with continuous connectivity. We identified the posterior precuneus as a key convergence point, revealing a gradient of connectivity between the two networks. This gradient flattens during altered states of consciousness induced by psychedelics or sedatives, showing a loss of functional differentiation between the DMN and FPCN.

neuroscience↗

bioRxiv2024

The neural correlates of shared and individual experience

Contemporary neuroscience research typically focuses on shared contents of experience and common neural states. Conversely, we set out to explore the neural correlates of individual- specific experiences that shape the distinct traits of each person. We propose an approach through which we compute individual-specific dynamics of functional connectivity states. These dynamics do not require estimation of common states across individuals and can be directly related to dynamic behavioural ratings of subjective experience. To this end, we leverage a unique functional magnetic resonance imaging dataset where subjects listened to an engaging naturalistic story while awake and under different levels of anaesthesia, altering or abolishing conscious experience. We find that this method can detect correspondences between neural and subjective dynamics. We then show that the dynamics of the default mode network underlie more personal experiences of the story as they are more dissimilar between participants during awareness compared to unconsciousness. On the other hand, the auditory and posterior dorsal attention networks show higher inter-subject similarity in consciousness compared to unconsciousness and suggest that the dynamics of these networks support more "generalisable" experiences of the story. We further characterise individual-specific brain dynamics by showing that they are associated with higher complexity in consciousness, whilst conversely, brain dynamics underlying shared experience become less complex during the conscious experience of the story.

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bioRxiv2024

A thalamic perspective of (un)consciousness in pharmacological and pathological states in humans

Currently, there is substantial ongoing discussion around the functional role of the thalamus in consciousness. What is missing in the literature, however, is a systematic investigation of the relevance of specific thalamic nuclei in pharmacologically and pathologically altered states of consciousness in humans. Using functional neuroimaging in both healthy anaesthetised volunteers and patients with disorders of consciousness (DOC), we sought to identify which specific thalamic subregions in both cohorts may be differentially significant for loss of consciousness. Our findings revealed that the pulvinar (Pu) and ventral-latero-ventral (VLV) nuclei, in anaesthesia, and the VLV, in DOC, had distinct functional connectivity patterns related to the default mode and somatomotor networks. Remarkably, among all nuclei, the Pu was found to have the strongest functional connectivity change with anaesthetic-induced loss of consciousness, while in DOC patients, we found the VLV revealed the strongest connectivity change in comparison with healthy controls. Furthermore, we provide evidence that this neural connectivity biomarker in patients also mirrors the changes observed at the behavioural level, which could have clinical implications for targeted deep brain stimulation in therapy for DOC.

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bioRxiv2023

Dynamical structure-function correlations provide robust and generalizable signatures of consciousness in humans

Resting-state functional magnetic resonance imaging evolves through a repertoire of functional connectivity patterns which might reflect ongoing cognition, as well as the contents of conscious awareness. We investigated whether the dynamic exploration of these states can provide robust and generalizable markers for the state of consciousness in human participants, across loss of consciousness induced by general anaesthesia or slow wave sleep. By clustering transient states of functional connectivity, we demonstrated that brain activity during unconsciousness is dominated by a recurrent pattern primarily mediated by structural connectivity and with a reduced capacity to transition to other patterns. Our results provide evidence supporting the pronounced differences between conscious and unconscious brain states in terms of whole-brain dynamics; in particular, the maintenance of rich brain dynamics measured by entropy is a critical aspect of conscious awareness. Collectively, our results may have significant implications for our understanding of consciousness and the neural basis of human awareness, as well as for the discovery of robust signatures of consciousness that are generalizable among different brain conditions.

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bioRxiv2023

General anaesthesia reduces the uniqueness of brain connectivity across individuals and across species

The human brain is characterised by idiosyncratic patterns of spontaneous thought, rendering each brain uniquely identifiable from its neural activity. However, deep general anaesthesia suppresses subjective experience. Does it also suppress what makes each brain unique? Here we used functional MRI under the effects of the general anaesthetics sevoflurane and propofol to determine whether anaesthetic-induced unconsciousness diminishes the uniqueness of the human brain: both with respect to the brains of other individuals, and the brains of another species. We report that under anaesthesia individual brains become less self-similar and less distinguishable from each other. Loss of distinctiveness is highly organised: it co-localises with the archetypal sensory-association axis, correlating with genetic and morphometric markers of phylogenetic differences between humans and other primates. This effect is more evident at greater anaesthetic depths, reproducible across sevoflurane and propofol, and reversed upon recovery. Providing convergent evidence, we show that under anaesthesia the functional connectivity of the human brain becomes more similar to the macaque brain. Finally, anaesthesia diminishes the match between spontaneous brain activity and meta-analytic brain patterns aggregated from the NeuroSynth engine. Collectively, the present results reveal that anaesthetised human brains are not only less distinguishable from each other, but also less distinguishable from the brains of other primates, with specifically human-expanded regions being the most affected by anaesthesia.

neuroscience↗

bioRxiv2023

Converging on consistent functional connectomics

Functional interactions between brain regions can be viewed as a network, empowering neuroscientists to leverage network science to investigate distributed brain function. However, obtaining a brain network from functional neuroimaging data involves multiple steps of data manipulation, which can drastically affect the organisation and validity of the estimated brain network and its properties. Here, we provide a systematic evaluation of 576 unique data-processing pipelines for functional connectomics from resting-state functional MRI, obtained from all possible recombinations of popular choices for brain atlas type and size, connectivity definition and selection, and global signal regression. We use the portrait divergence, an information-theoretic measure of differences in network topology across scales, to quantify the influence of analytic choices on the overall organisation of the derived functional connectome. We evaluate each pipeline across an entire battery of criteria, seeking pipelines that (i) minimise spurious test-retest discrepancies of network topology, while simultaneously (ii) mitigating motion confounds, and being sensitive to both (iii) inter-subject differences and (iv) experimental effects of interest, as demonstrated by propofol-induced general anaesthesia. Our findings reveal vast and systematic variability across pipelines suitability for functional connectomics. Choice of the wrong data-processing pipeline can lead to results that are not only misleading, but systematically so, distorting the functional connectome more drastically than the passage of several months. We also found that the majority of pipelines failed to meet at least one of our criteria. However, we identified 8 candidates satisfying all criteria across each of four independent datasets spanning minutes, weeks, and months, ensuring the generalisability of our recommendations. Our results also generalise to alternative acquisition parameters and preprocessing and denoising choices. By providing the community with a full breakdown of each pipelines performance across this multi-dataset, multi-criteria, multi-scale and multi-step approach, we establish a comprehensive set of benchmarks to inform future best practices in functional connectomics.

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bioRxiv2023

Typical and disrupted small-world architecture and regional communication in full-term and preterm infants

One fundamental property of conscious experiences is that they are both differentiated and integrated. Adult functional brain networks exhibit an elegant "small-world" architecture. This optimal architecture enables efficient and cost-effective localized information processing and information integration between long-distance regions across the brain. It remains unclear whether the functional small-world architecture is developed in neonates at birth and how this development may be altered by premature birth. To address this gap, we investigated the development of small-world architecture in neonates. To understand the effect of early neonate age on small-world architecture, we also assessed neonates born prematurely or before term-equivalent age (TEA). We used the Developing Human Connectome Project (dHCP), a large neonatal functional magnetic resonance imaging (MRI) dataset with high temporal and spatial resolution. Resting-state functional MRI data for full- term neonates (N = 278, age 41.2 weeks {+/-} 12.2 days) and preterm neonates scanned at TEA (N = 72, 40.9 weeks {+/-} 14.6 days), or before TEA (N = 70, 34.7 weeks {+/-} 12.7 days), were obtained from the dHCP, and for a reference adult group (N = 176, 22-36 years), from the Human Connectome Project. Whole-brain functional network properties were evaluated with comprehensive spatial resolution using graph theoretical analyses. Although different from the adults, small-world architecture was developed in full-term born neonates at birth. Premature neonates before TEA showed dramatic underdevelopment of small-world architecture and regional communication in 9/11 brain networks, with disruption in 32% of nodes primarily distributed within the somatomotor, dorsal attention, cingulo-opercular, and frontoparietal control network. By TEA, premature neonates showed large-scale recuperation of regional communication, with 1.4% of nodes, distributed in the frontoparietal, salience, and visual networks remaining significantly underdeveloped. Our results suggest that, at full- term birth or by term-equivalent age, infants possess well-developed small-world architecture, which facilitates differentiated and integrated neural processes that give rise to conscious experiences. Conversely, they suggest that this brain infrastructure is significantly underdeveloped before infants reach term-equivalent age. These findings improve understanding of the ontogeny of functional small-world architecture and efficiency of neural communication across distinct brain networks in infants at birth.

neuroscience↗

bioRxiv2022

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

It has been suggested that the richness of conscious experience can be directly linked to the richness of brain state repertories. Brain states change depending on our environment and activities we engage in by taking both external and internally derived information into account. It has been shown that high-level sensory stimulation changes local brain activity and induces neural synchrony across participants. However, the dynamic interplay of cognitive processes that underlie moment-to-moment information processing remains poorly understood. Using naturalistic movies as an ecological laboratory model of the real world, here we assess how the processing of complex naturalistic stimuli alters the dynamics of brain networks interactions, and how these in turn support information processing. Participants underwent fMRI recordings during movie watching, scrambled movie watching, and rest. Measuring phase-synchrony between different brain networks, we computed whole-brain connectivity patterns. We showed that specific connectivity patterns were associated with each experimental condition. We found a higher synchronization of brain patterns across participants during movie watching compared to resting state and scrambled movie conditions. Moreover, synchronization increased during the most engaging parts of the movie. The synchronization dynamics across participants were associated with suspense; more suspenseful scenes induced higher synchronization. These results suggest that processing of the same high-level information elicits common neural dynamics among individuals and that whole-brain functional connectivity tracks variations in the processed information and the subjective experience.

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bioRxiv2022

Mapping Pharmacologically-induced Functional Reorganisation onto the Brain's Neurotransmitter Landscape

To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brains rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically-induced macroscale functional reorganisation, by relating the regional distribution of 19 neurotransmitter receptors and transporters obtained from Positron Emission Tomography, and the regional changes in functional MRI connectivity induced by 10 different mind-altering drugs: propofol, sevoflurane, ketamine, LSD, psilocybin, DMT, ayahuasca, MDMA, modafinil, and methylphenidate. Our results reveal that psychoactive drugs exert their effects on brain function by engaging multiple neurotransmitter systems. The effects of both anaesthetics and psychedelics on brain function are organised along hierarchical gradients of brain structure and function. Finally, we show that regional co-susceptibility to pharmacological interventions recapitulates co-susceptibility to disorder-induced structural alterations. Collectively, these results highlight rich statistical patterns relating molecular chemoarchitecture and drug-induced reorganisation of the brains functional architecture.

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bioRxiv2021

Typical and disrupted brain circuitry for conscious awareness in full-term and preterm infants

One of the great frontiers of consciousness science is understanding how early consciousness arises in the development of the human infant. The reciprocal relationship between the default mode network (DMN) and frontoparietal networks -- the dorsal attention network (DAN) and executive control network (ECN) -- is thought to facilitate integration of information across the brain and its availability for conscious access to a wide set of mental operations. It remains unknown whether the brain mechanism of conscious awareness is instated in infants from birth. To address this gap, we asked what the impact of prematurity and neonate age is on the development the default mode and fronto-parietal networks, and of their reciprocal relationship. To address these questions, we used the Developing Human Connectome Project (dHCP), a unique Open Science project which provides a large sample of neonatal functional Magnetic Resonance Imaging (fMRI) data with high temporal and spatial resolution. Resting state fMRI data for full-term neonates (N = 282, age 41.2 w {+/-} 12 d), and preterm neonates scanned at term-equivalent age (TEA) (N = 73, 40.9 w {+/-} 14.5 d), or before TEA (N = 73, 34.6 w {+/-} 13.4 d) were obtained from the dHCP, and for a reference adult group (N = 176, 22 - 36 years), from the Human Connectome Project. For the first time, we show that the reciprocal relationship between the DMN and DAN was present at full-term birth or TEA. Although different from the adult networks, the DMN, DAN and ECN were present as distinct networks at full-term birth or TEA, but premature birth disrupted network development. By contrast, neonates before TEA showed dramatic underdevelopment of high-order networks. Only the DAN was present as a distinct network and the reciprocal network relationship was not yet formed. Our results suggest that, at full-term birth or by term-equivalent age, infants possess key features of the neural circuitry that enables integration of information across diverse sensory and high-order functional modules, giving rise to conscious access. Conversely, they suggest that this brain infrastructure is not present before infants reach term-equivalent age. These findings improve understanding of the ontogeny of high-order network dynamics that support conscious awareness, and of their disruption by premature birth.

neuroscience↗

bioRxiv2021

Network dynamics scale with levels of awareness

Small world topologies are thought to provide a valuable insight into human brain organisation and consciousness. However, functional magnetic resonance imaging studies in consciousness have not yielded consistent results. Given the importance of dynamics for both consciousness and cognition, here we investigate how the diversity of brain dynamics pertaining to small world topology (quantified by sample entropy; dSW-E) scales with decreasing levels of awareness (i.e., sedation and disorders of consciousness). Paying particular attention to result reproducibility, we show that dSW-E is a consistent predictor of levels of awareness even when controlling for the underlying functional connectivity dynamics. We find that dSW-E of subcortical and cortical areas are predictive, with the former showing higher and more robust effect sizes across analyses. Consequently, we propose that the dynamic reorganisation of the functional information architecture, in particular of the subcortex, is a characteristic that emerges with awareness and has explanatory power beyond that of the complexity of dynamic functional connectivity.

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bioRxiv2021

Paths to Oblivion: Common Neural Mechanisms of Anaesthesia and Disorders of Consciousness

The human brain generates a rich repertoire of spatiotemporal dynamics during normal wakefulness, supporting a wide variety of conscious experiences and cognitive functions. However, neural dynamics are reconfigured, in comparable ways, when consciousness is lost either due to anaesthesia or disorders of consciousness (DOC). Here, leveraging a neurobiologically realistic whole-brain computational model informed by functional MRI, diffusion MRI, and PET, we sought to identify the neurobiological mechanisms that explain the common reconfiguration of neural dynamics observed both for transient pharmacological intervention and chronic neuroanatomical injury. Our results show that, by incorporating local inhibitory action through a PET-based GABA receptor density map, our model can reproduce the brain dynamics of subjects undergoing propofol anaesthesia, and that this effect depends specifically on the spatial distribution of GABA receptors across cortical regions. Additionally, using a structural connectome obtained from DOC patients, we demonstrate how the dynamics that characterise loss of consciousness can emerge from changes in neuroanatomical connectivity. Crucially, we find that each of these two interventions generalises across datasets: a model with increased GABA-mediated inhibition can reproduce the dynamics of DOC patients brains, and a model with a DOC connectome is also compatible with brain dynamics observed during propofol anaesthesia. These results demonstrate how increased inhibition and connectome randomisation represent different neurobiological paths towards the characteristic dynamics of the unconscious brain. Overall, the present findings begin to disentangle the neurobiological mechanisms by which highly dissimilar perturbations of the brains neurodynamics can lead to unconsciousness.

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bioRxiv2020

A Synergistic Workspace for Human Consciousness Revealed by Integrated Information Decomposition

A central goal of neuroscience is to understand how the brain orchestrates information from multiple input streams into a unified conscious experience. Here, we address two fundamental questions: how is the human information-processing architecture functionally organised, and how does its organisation support consciousness? We combine network science and a rigorous information-theoretic notion of synergy to delineate a "synergistic global workspace", comprising gateway regions that gather synergistic information from specialised modules across the brain. This information is then integrated within the workspace and widely distributed via broadcaster regions. Through functional MRI analysis, we show that gateway regions of the synergistic workspace correspond to the brains default mode network, whereas broadcasters coincide with the executive control network. Demonstrating the empirical relevance of our proposed architecture for neural information processing, we show that loss of consciousness due to general anaesthesia or disorders of consciousness corresponds to a diminished ability of the synergistic workspace to integrate information, which is restored upon recovery. Thus, loss of consciousness coincides with a breakdown of information integration within the synergistic workspace of the human brain. This work contributes to conceptual and empirical reconciliation between two prominent scientific theories of consciousness, the Global Neuronal Workspace and Integrated Information Theory. Taken together, this work provides a new perspective on the role of prominent resting-state networks within the human information-processing architecture, while also advancing our understanding of how the human brain supports consciousness through the synergistic integration of information.

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bioRxiv2020

The brain-bases of responsiveness variability under moderate anaesthesia

Anaesthesia combined with functional neuroimaging provides a powerful approach for understanding the brain mechanisms of consciousness. Although propofol is used ubiquitously in clinical interventions that reversibly suppress consciousness, it shows large inter-individual variability, and the brain bases of this variability remain poorly understood. We asked whether three networks key to conscious cognition -- the dorsal attention (DAN), executive control (ECN), and default mode (DMN) -- underlie responsiveness variability under anaesthesia. Healthy participants (N=17) were moderately anaesthetized during narrative understanding and resting state conditions inside the Magnetic Resonance Imaging scanner. A target detection task measured behavioural responsiveness. An independent behavioural study (N=25) qualified the attention demands of narrative understanding. 30% of participants were unaffected in their response times, thus thwarting a key aim of anaesthesia -- the suppression of behavioural responsiveness. Individuals with stronger functional connectivity within the DAN and ECN, between them, and to the DMN, and with larger grey matter volume in frontal regions were more resilient to anaesthesia. For the first time, we show that responsiveness variability during propofol anaesthesia relates to inherent differences in brain structure and function of the fronto-parietal networks, which can be predicted prior to sedation. Results highlight novel markers for improving awareness monitoring during clinical anaesthesia. Key pointsO_LIModerate propofol anaesthesia showed highly variable effects across individuals C_LIO_LI30% of healthy participants response times were unaffected by anaesthesia and 70% had significantly delayed, fragmented, or fully omitted responses C_LIO_LIGrey matter volume in frontal cortex and functional connectivity of the fronto-parietal networks predicted resilience to anaesthesia C_LI

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bioRxiv2019

Consciousness & Brain Functional Complexity in Propofol Anaesthesia

The brain is possibly the most complex system known to mankind, and its complexity has been called upon to explain the emergence of consciousness. However, complexity can take many forms: here, we investigate measures of algorithmic and process complexity in both the temporal and topological dimension, testing them on functional MRI data obtained from individuals undergoing various levels of sedation with the anaesthetic agent propofol, in two separate datasets. We demonstrate that the various measures are differently able to discriminate between levels of sedation, with temporal measures showing higher sensitivity. Further, we show that all measures are strongly related to a single underlying construct explaining most of the variance, as assessed by Principal Component Analysis, which we interpret as a measure of overall complexity of our data. This overall complexity was also able to discriminate between levels of sedation, supporting the hypothesis that consciousness is related to complexity - independent of how the latter is measured.

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bioRxiv2018

Functional diversity of brain networks supports consciousness and verbal intelligence

How are the myriad stimuli arriving at our senses transformed into conscious thought? To address this question, in a series of studies, we asked whether a common mechanism underlies loss of information processing in unconscious states across different conditions, which could shed light on the brain mechanisms of conscious cognition. With a novel approach, we brought together for the first time, data from the same paradigm--a highly engaging auditory-only narrative--in three independent domains: anesthesia-induced unconsciousness, unconsciousness after brain injury, and individual differences in intellectual abilities during conscious cognition. During external stimulation in the unconscious state, the functional differentiation between the auditory and fronto-parietal systems decreased significantly relatively to the conscious state. Conversely, we found that stronger functional differentiation between these systems in response to external stimulation predicted higher intellectual abilities during conscious cognition, in particular higher verbal acuity scores in independent cognitive testing battery. These convergent findings suggest that the responsivity of sensory and higher-order brain systems to external stimulation, especially through the diversification of their functional responses is an essential feature of conscious cognition and verbal intelligence.

neuroscience↗