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Bonhomme, V.

Publications and source records attributed to Bonhomme, V..

13 recordsLinked to original sources

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.

neuroscience↗

THE FUNCTION AND EVOLUTION OF STEGOSAUR OSTEODERMS AND HYPOTHESIZED SEXUAL DIMORPHISM IN HESPEROSAURUS

Stegosaurus is one of the most iconic organisms in Earths history due to its impressive dermal osteoderms. These consisted of throat ossicles, two pairs of posterior tail spikes, and an estimated 18 large plates arranged in two staggered rows along the neck, back, and tail. The function and evolution of these structures in stegosaurs is a quintessential question in dinosaur paleontology. Although sociosexual display has become a popular explanation of plate function, sexual dimorphism in dinosaurs has been a contentious topic. Spikes are meanwhile often described as defensive structures, but we consider an additional intra-sex combat function worthy of further study. To investigate the questions surrounding stegosaur osteoderms, we reevaluate variation in North American stegosaur osteoderms, with attention to hypothesized sexual dimorphism in Hesperosaurus, a close relative of Stegosaurus with similar osteoderms. We correct errors in previous analyses, address challenges of the dimorphism hypothesis, and use outline analysis and effect size statistics to provide further statistical support that one sex possibly had larger, wide/broad plates (hypothesized male), while the other sex had smaller, tall/narrow plates (hypothesized female). Stegosaur plates are a difficult case study for sexual variation because the multiple plates borne by a single individual can result in datasets that violate assumptions of independence. Despite appreciable variation from head to tail along an individual, the variation in size and shape seen in Hesperosaurus plates is still consistent with the presence of sexual variation as evidenced by both size-independent, two-dimensional outline analysis as well as size-versus-shape regression analysis of principal component data, with high confidence in the latter. We note pathologies on stegosaur caudal vertebrae, particularly in old adults of wide-morph Hesperosaurus, as well as in Stegosaurus tail spikes. These pathologies are consistent with not just predator-prey interactions but also intraspecific combat. There currently is no unambiguous indication of dimorphism in stegosaur thagomizers because alternative hypotheses, such as ontogenetic or interspecific variation, are not yet fully tested. Finally, we present a hypothetical model of stegosaur osteoderm evolution and function based on fossil and extant evidence. Osteoderms adapted for defense in earlier thyreophorans likely became exapted for sexual display (i.e., plates) and intra-sex combat (e.g., tail spikes in stegosaurs, clubs in ankylosaurs). Therefore, sexual selection may have initiated the differentiation of plates from the terminal thagomizer and induced the unique asymmetry of staggered plates in Stegosaurus and Hesperosaurus. Osteoderm development in hypothesized males could have been driven to physiological upper limits by sexual selection, while the intensity of predation pressure dictated osteoderm development in hypothesized females. Increasing predation pressure might correlate with large body size, open habitats, spine-like plate processes, long tail spikes, and gular ossicles. Within this hypothetical evolutionary model, Hesperosaurus would represent a stegosaur taxon with a high magnitude of sexual dimorphism, consistent with its smaller body size, rounder plates, presumed lack of gular ossicles, and niche occupation within a wet, forested, vegetation-rich habitat in the northern Morrison foreland basin. The question of stegosaur plate function requires us to look more broadly at thyreophoran osteoderm variation and evolution and to consider complex, multifactor models that incorporate many previously proposed hypotheses. We must sort between primary versus secondary functions of plates, spikes, and ossicles and how these functions changed over time.

paleontology↗

A virtual clinical trial of psychedelics to treat patients with disorders of consciousness

Disorders of consciousness (DoC), including the unresponsive wakefulness syndrome (UWS) and the minimally conscious state (MCS), have limited treatment options. Recent research suggests that psychedelic drugs, known for their complexity-enhancing properties, could be promising treatments for DoC. This study uses whole-brain computational models to explore this potential. We created individualised models for DoC patients, optimised with empirical fMRI and diffusion-weighted imaging (DWI) data, and simulated the administration of LSD and psilocybin. We used an in-silico perturbation protocol to distinguish between different states of consciousness, including DoC, anaesthesia, and the psychedelic state, and assess the dynamical stability of the brains of DoC patients pre- and post-psychedelic simulation. Our findings indicate that LSD and psilocybin shift DoC patients brains closer to criticality, with a greater effect in MCS patients. In UWS patients, the treatment response correlates with structural connectivity, while in MCS patients, it aligns with baseline functional connectivity. This virtual clinical trial lays a computational foundation for using psychedelics in DoC treatment and highlights the future role of computational modelling in drug discovery and personalised medicine.

neuroscience↗

Ketamine-Induced Unresponsiveness Shows a Harmonic Shift from Global to Localised Functional Organisation.

Ketamine is classified as a dissociative anaesthetic that, in sub-anaesthetic doses, can produce an altered state of consciousness characterised by dissociative symptoms, visual and auditory hallucinations, and perceptual distortions. Given the anaesthetic-like and psychedelic-like nature of this compound, it is expected to have different effects on brain dynamics in anaesthetic doses than in low, sub-anaesthetic doses. We investigated this question using connectome harmonic decomposition (CHD), a recently developed method to decompose brain activity in terms of the network organisation of the underlying human structural connectome. Previous research using this method has revealed connectome harmonic signatures of consciousness and responsiveness, with increased influence of global network structure in disorders of consciousness and propofol-induced sedation, and increased influence of localised patterns under the influence of classic psychedelics and sub-anaesthetic doses of ketamine, as compared to normal wakefulness. When we applied the CHD analytical framework to resting-state fMRI data of volunteers during ketamine-induced unresponsiveness, we found increased prevalence of localised harmonics, reminiscent of altered states of consciousness. This is different from traditional GABAergic sedation, where instead the prevalence of global rather than localised harmonics seems to increase with higher doses. In addition, we found that ketamines harmonic signature shows higher alignment with those seen in LSD- or psilocybin-induced psychedelic states than those seen in unconscious individuals, whether due to propofol sedation or brain injury. Together, the results indicate that ketamine-induced unresponsiveness, which does not necessarily suppress conscious experience, seems to influence the prevalence of connectome harmonics in the opposite way compared to GABAergic hypnotics. We conclude that the CHD framework offers the possibility to track alterations in conscious awareness (e.g., dreams, sensations) rather than behavioural responsiveness - a discovery made possible by ketamines unique property of decoupling these two facets.

neuroscience↗

Deep learning versus geometric morphometrics for archaeobotanical domestication study and subspecific identification

The identification of archaeological fruits and seeds is crucial for understanding the relationships between humans and plants within the cultural and biological history of both wild and cultivated species. We compared the relative performance of a deep learning approach, namely convolutional neural networks (CNN), and outline analyses via geometric morphometrics using elliptical Fourier transforms (EFT) at identifying pairs of plant taxa. We used their seeds and fruit stones that are the most abundant organs in archaeobotanical assemblages, and whose morphological identification, chiefly between wild and domesticated types, allows to document their domestication and biogeographical history. We used existing modern datasets of four plant taxa (barley, olive, date palm and grapevine) corresponding to photographs of two orthogonal views of their seeds that were analysed separately to offer a larger spectrum of shape diversity. Sample sizes ranged from 473 to 1,769 seeds per class, which constitute a relatively small dataset for training CNNs models yet typical within archaeobotanical research. On these eight datasets, we compared the performance of CNN and EFT coupled with linear discriminant analyses. Our objectives were twofold: i) to test whether CNN can beat geometric morphometrics in taxonomic identification and if so, ii) to test which minimal sample size is required. We ran simulations on the full datasets and also on subsets, starting from 50 images in each binary class. For the CNN network, we deliberately used a candid approach relying on pre-parameterised VGG19 network. For EFT, we used a state-of-the art morphometrical pipeline. The main difference rests in the data used by each model: our CNN used bare photographs where EFT used outline coordinates. This "pre-distilled" geometrical description of seed outlines is often the most time-consuming part of morphometric studies. Results show that our CNN beats EFT in most cases, even for very small datasets. We finally discuss the potential of CNNs for archaeobotany, and how bioarchaeological studies could embrace both approaches, used in a complementary way, to better assess and understand the past history of species.

bioinformatics↗

Low-dimensional organization of global brain states of reduced consciousness

Brain states are frequently represented using a unidimensional scale measuring the richness of subjective experience (level of consciousness). This description assumes a mapping between the high-dimensional space of whole-brain configurations and the trajectories of brain states associated with changes in consciousness, yet this mapping and its properties remain unknown. We combined whole-brain modelling, data augmentation and deep learning for dimensionality reduction to determine a mapping representing states of consciousness in a low-dimensional space, where distances parallel similarities between states. An orderly trajectory from wakefulness to brain injured patients is revealed in a latent space whose coordinates represent metrics related to functional modularity and structure-function coupling, both increasing alongside loss of consciousness. Finally, we investigated the effects of model perturbations, providing geometrical interpretation for the stability and reversibility of states. We conclude that conscious awareness depends on functional patterns encoded as a low-dimensional trajectory within the vast space of brain configurations.

neuroscience↗

Depth of sedation with dexmedetomidine modulates cortical excitability non-linearly

BackgroundCortical excitability changes across conscious states, being higher in unconsciousness compared to normal wakefulness. Anaesthesia offers controlled manipulation to investigate conscious processes and underlying brain dynamics. Among commonly used anaesthetic agents, dexmedetomidine (DEX) effects are not completely known. In this study, we investigated cortical excitability as a function of DEX sedation depth. MethodsTranscranial magnetic stimulation coupled with electroencephalography was recorded in 20 healthy subjects undergoing DEX sedation in four conditions (baseline, light sedation, deep sedation, recovery). Frontal and parietal cortices were stimulated using a neuronavigation system. Cortical excitability was inferred by slope, amplitude, positive and negative peak latencies of the first component (0-30 ms) of the TMS-evoked potential. Four Generalized Linear Mixed Models (GLMM) were used to test the effect of condition and brain region over cortical excitability. ResultsDexmedetomidine modulated amplitude (P<0.001), slope (P=0.0001) and positive peak (P=0.042), while the targeted brain region affected amplitude (P<0.001), slope (P<0.001), and negative peak (P=0.001). The interaction between dexmedetomidine and region had an effect over amplitude (P=0.004), and slope (P=0.009) such that cortical excitability was higher during all conditions where DEX was present as compared to the baseline. ConclusionsCortical excitability changes non-linearly as a function of the depth of DEX sedation, with a paradoxical non dose-dependent increase. The effect is region-specific, being present in the frontal but not in the parietal region. Future research should extend the current results with other anaesthetics to better understand the link between cortical excitability and depth of sedation.

neuroscience↗

How hot is the hot zone? Computational modelling clarifies the role of parietal and frontoparietal connectivity during anaesthetic-induced loss of consciousness

In recent years, specific cortical networks have been proposed to be crucial for sustaining consciousness, including the posterior hot zone and frontoparietal resting state networks (RSN). Here, we computationally evaluate the relative contributions of three RSNs - the default mode network (DMN), the salience network (SAL), and the central executive network (CEN) - to consciousness and its loss during propofol anaesthesia. Specifically, we use dynamic causal modelling (DCM) of 10 minutes of high-density EEG recordings (N = 10, 4 males) obtained during behavioural responsiveness, unconsciousness and post-anaesthetic recovery to characterise differences in effective connectivity within frontal areas, the posterior "hot zone", frontoparietal connections, and between-RSN connections. We estimate - for the first time - a large DCM model (LAR) of resting EEG, combining the three RSNs into a rich club of interconnectivity. Consistent with the hot zone theory, our findings demonstrate reductions in inter-RSN connectivity in the parietal cortex. Within the DMN itself, the strongest reductions are in feed-forward frontoparietal and parietal connections at the precuneus node. Within the SAL and CEN, loss of consciousness generates small increases in bidirectional connectivity. Using novel DCM leave-one-out cross-validation, we show that the most consistent out-of-sample predictions of the state of consciousness come from a key set of frontoparietal connections. This finding also generalises to unseen data collected during post-anaesthetic recovery. Our findings provide new, computational evidence for the importance of the posterior hot zone in explaining the loss of consciousness, highlighting also the distinct role of frontoparietal connectivity in underpinning conscious responsiveness, and consequently, suggest a dissociation between the mechanisms most prominently associated with explaining the contrast between conscious awareness and unconsciousness, and those maintaining consciousness. HighlightsO_LIModelling shows that connectivity within hot zone tracks change of conscious state C_LIO_LISeparately, frontoparietal connections support maintenance of conscious state C_LIO_LIStrength of frontoparietal connections predicts conscious state in unseen data C_LIO_LIBoth parietal hot zone and frontoparietal connectivity important for consciousness C_LI FundingThis work was supported by the UK Engineering and Physical Sciences Research Council (EP/P033199/1), Belgian National Funds for Scientific Research (FRS-FNRS), the University and University Hospital of Liege, the Fund Generet, the King Baudouin Foundation, the AstraZeneca Foundation, the European Unions Horizon 2020 Framework Programme for Research and Innovation under the Specific Grant Agreement No. 945539 (Human Brain Project SGA3), DOCMA project (EU-H2020-MSCA-RISE-778234), the BIAL Foundation, the European Space Agency (ESA) and the Belgian Federal Science Policy Office (BELSPO) in the framework of the PRODEX Programme, the Center-TBI project (FP7-HEALTH-602150), the Public Utility Foundation Universite Europeenne du Travail, "Fondazione Europea di Ricerca Biomedica", the Mind Science Foundation, the European Commission, and the Special Research Fund of Ghent University. O.G. is research associate and S.L. is research director at the F.R.S-FNRS. Declaration of interestNone. Significance StatementVarious connectivity studies have suggested multiple network-level mechanisms driving changes in the state of consciousness, such as the posterior hot zone, frontal-, and large-scale frontoparietal networks. Here, we computationally evaluate evidence for these mechanisms using dynamic causal modeling for resting EEG recorded before and during propofol-anaesthesia, and demonstrate that, particularly, connectivity in the posterior hot zone is impaired during propofol-induced unconsciousness. With a robust cross-validation paradigm, we show that connectivity in the large-scale frontoparietal networks can consistently predict the state of consciousness and further generalise these findings to an unseen state of recovery. These results suggest a dissociation between the mechanisms most prominently associated with explaining the contrast between conscious awareness and unconsciousness, and those maintaining consciousness.

neuroscience↗

Perturbations in dynamical models of whole-brain activity dissociate between the level and stability of consciousness

Consciousness transiently fades away during deep sleep, more stably under anesthesia, and sometimes permanently due to brain injury. The development of an index to quantify the level of consciousness across these different states is regarded as a key problem both in basic and clinical neuroscience. We argue that this problem is ill-defined since such an index would not exhaust all the relevant information about a given state of consciousness. While the level of consciousness can be taken to describe the actual brain state, a complete characterization should also include its potential behavior against external perturbations. We developed and analyzed whole-brain computational models to show that the stability of conscious states provides information complementary to their similarity to conscious wakefulness. Our work leads to a novel methodological framework to sort out different brain states by their stability and reversibility, and illustrates its usefulness to dissociate between physiological (sleep), pathological (brain-injured patients), and pharmacologically-induced (anesthesia) loss of consciousness.

neuroscience↗

Berry and pip form covariation in wild and domesticated grapevines: eco-evo-devo implications and archaeobotanical perspectives

The phenotypic changes that occurred during the domestication and diversification of grapevine are well known, particularly changes in seed morphology, but the functional causes and consequences behind these variations are poorly understood. Wild and domesticate grapes differ, among others, in the form of their pips: wild grapes produce roundish pips with short stalks and cultivated varieties have more elongated pips with longer stalks. Such variations of form are of first importance for archaeobotany since the pip form is, most often, the only remaining information in archaeological settings. This study aims to enlight archaeobotanical record and grapevine pip development by better understanding how size and shape (co)variates between pip and berry in both wild and domesticated Vitis vinifera. The covariation of berry size, number of seeds per berry ("piposity"), pip size and pip shape were explored on 49 grapevine accessions sampled among Euro-Mediterranean traditional cultivars and wild grapevines. We show that for wild grapevine, the higher the piposity, the bigger the berry and the more elongated the pip. For both wild and domesticated grapevine, the longer is the pip, the more it has a "domesticated" shape. Consequences for archaeobotanical studies are tested and discussed, and these covariations allowed the inference of berry dimensions from archaeological pips from a Southern France Roman site. This systematic exploration sheds light on new aspects of pip-berry relationship, in both size and shape, on grapevine eco-evo-devo changes during domestication, and invites to explore further the functional ecology of grapevine pip and berry and notably the impact of cultivation practices and human selection on grapevine morphology.

plant biology↗

Evolutionary inference from QST-FST comparisons: disentangling local adaptation from altitudinal gradient selection in snapdragon plants

Phenotypic differentiation among natural populations can be explained by natural selection or by neutral processes such as drift. There are many examples in the literature where comparing the effects of these processes on multiple populations has allowed the detection of local adaptation. However, these studies rarely identify the agents of selection. Whether population adaptive divergence is caused by local features of the environment, or by the environmental demand emerging at a more global scale, for example along altitudinal gradients, is a question that remains poorly investigated. Here, we measured neutral genetic (FST) and quantitative genetic (QST) differentiation among 13 populations of snapdragon plants (Antirrhinum majus) in a common garden experiment. We found low but significant genetic differentiation at putatively neutral markers, which supports the hypothesis of either ongoing pervasive homogenisation via gene flow between diverged populations or reproductive isolation between disconnected populations. Our results also support the hypothesis of local adaptation involving phenological, morphological, reproductive and functional traits. They also showed that phenotypic differentiation increased with altitude for traits reflecting the reproduction and the phenology of plants, thereby confirming the role of such traits in their adaptation to environmental differences associated with altitude. Our approach allowed us to identify candidate traits for the adaptation to climate change in snapdragon plants. Our findings imply that environmental conditions changing with altitude, such as the climatic envelope, influenced the adaptation of multiple populations of snapdragon plants on the top of their adaptation to local environmental features. They also have implications for the study of adaptive evolution in structured populations because they highlight the need to disentangle the adaptation of plant populations to climate envelopes and altitude from the confounding effects of selective pressures acting specifically at the local scale of a population.

evolutionary biology↗

Genotype by environment interactions for the shade avoidance syndrome in the plant Antirrhinum majus, the snapdragon

A classical example of phenotypic plasticity in plants is the set of trait changes in response to shade, i.e. the shade avoidance syndrome. There is widespread evidence that plants in low light conditions often avoid shade by growing taller or by increasing their photosynthetic efficiency. This plastic response is expected to have evolved in response to selection in several species, yet there is limited evidence for its genetic variation within populations, which is required for any evolutionary response to selection. In this study, we investigated the shade avoidance syndrome in snapdragon plants (Antirrhinum majus) by using a common garden approach on four natural populations from the Mediterranean region. Our results showed that, in the four populations, individual plants reacted strongly to the presence of shade by growing longer shoots, longer internodes, and increasing their specific leaf area. Our results also revealed genetic variation for the plastic response within these populations, as well as few genetic constraints to its evolution. Our findings imply that the plastic response to shade has the potential to evolve in response to selection in natural populations of A. majus.

evolutionary biology↗

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.

neuroscience↗