Biology subjects

Cardone, P.

Publications and source records attributed to Cardone, P..

7 recordsLinked to original sources

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.

neuroscience↗

bioRxiv2024

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↗

bioRxiv2024

7 Tesla MRS estimates of GABA concentration relate to physiological measures of tonic inhibition in the human motor cortex

GABAergic neurotransmission within the cortex plays a key role in learning and is altered in several brain diseases. Quantification of bulk GABA in the human brain is typically obtained by Magnetic Resonance Spectroscopy (MRS). However, the interpretation of MRS-GABA is still debated. A recent mathematical simulation contends that MRS detects extrasynaptic GABA, mediating tonic inhibition. Nevertheless, no empirical data have yet confirmed this hypothesis. Here we collected ultra-high field 7 Tesla MRS and Transcranial Magnetic Stimulation coupled with high-density Electroencephalography (TMS-hdEEG) from the motor cortex of twenty healthy participants (age 23.95{+/-}6.4), while they were at rest. We first applied a Neural Mass Model to TMS-evoked potentials to disentangle the contribution of different GABAergic pools. We then assessed to which of these different pools MRS-GABA was related to by means of Parametric Empirical Bayesian (PEB) analysis. We found that MRS-GABA was mostly positively related to the NMM-derived measures of tonic inhibition and overall functionality of the GABAergic synapse. This relationship was reliable enough to predict MRS-GABA from NMM-GABA. These findings clarify the mesoscopic underpinnings of GABA levels measured by MRS and will contribute to the concretization of MRS-GABA promises to improve our understanding of human behaviour, brain physiology and pathophysiology. Key pointsO_LIGABA neurotransmission is essential for synaptic plasticity and learning (especially motor learning) and is altered in several brain disorders, such as epilepsy and stroke. C_LIO_LIQuantification of GABA in the human brain is typically obtained by Magnetic Resonance Spectroscopy (MRS). However, the interpretation of MRS-GABA is still debated. C_LIO_LIBy using a biophysical Neural Mass Model, here we show that MRS-GABA relates to physiological measures of tonic inhibition in the human cortex. C_LI

neuroscience↗

bioRxiv2024

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↗

bioRxiv2024

Exploring Neuroscience Researchers' Trust in Preprints through Citation Analysis

Preprints have emerged as efficient tools for fast and free dissemination of scientific findings. The present study explores the evolving landscape of preprints among the field of neuroscience and examines patterns and evolution of citations to preprints over time in this field. Leveraging bibliometric methods, we identified over 33,000 citations (1993-2022) to preprints within neuroscience publications indexed in Scopus. The findings elucidate a significant temporal increase in the number of documents citing preprints, reaching a peak of around 60 per 1,000 Scopus documents in 2021. Diverse document types, particularly reviews, exhibit a growing reliance on preprints as references. The most frequently cited preprint servers include bioRxiv, ArXiv, medRxiv, and PsyArXiv. Leading journals such as eLife and PLOS Computational Biology have cited preprints more than others. The United States takes the lead in citing preprints, followed by the United Kingdom and Germany. Using Scite.ai, motivations underlying preprint citations and the context in which they were cited were explored and the results are indicative of the "mentioning" nature of 93% of citations to preprints. Furthermore, the introduction and discussion sections have shown to include the highest number of citations to preprints. The findings highlight the dynamic transformation of preprints in neuroscience field.

neuroscience↗

bioRxiv2023

Lateral frontoparietal effective connectivity differentiates and predicts state of consciousness in traumatic disorders of consciousness

Neuroimaging studies have suggested an important role for the default mode network (DMN) in disorders of consciousness (DoC). However, the extent to which DMN connectivity can discriminate DoC states - unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) - is less evident. Particularly, it is unclear whether effective DMN connectivity, as measured indirectly with dynamic causal modelling (DCM) of resting EEG can disentangle UWS from healthy controls and from patients considered conscious (MCS+). Crucially, this extends to UWS patients with potentially "covert" awareness (minimally conscious star, MCS*) indexed by voluntary brain activity in conjunction with partially preserved frontoparietal metabolism as measured with positron emission tomography (PET+ diagnosis; in contrast to PET-diagnosis with complete frontoparietal hypometabolism). Here, we address this gap by using DCM of EEG data acquired from patients with traumatic brain injury in 11 UWS (6 PET- and 5 PET+) and in 12 MCS+ (11 PET+ and 1 PET-), alongside with 11 healthy controls. We provide evidence for a key difference in left frontoparietal connectivity when contrasting UWS PET- with MCS+ patients and healthy controls. Next, in a leave-one-subject-out cross-validation, we tested the classification performance of the DCM models demonstrating that connectivity between medial prefrontal and left parietal sources reliably discriminates UWS PET- from MCS+ patients and controls. Finally, we illustrate that these models generalize to an unseen dataset: models trained to discriminate UWS PET- from MCS+ and controls, classify MCS* patients as conscious subjects with high posterior probability (pp > .92). These results identify specific alterations in the DMN after severe brain injury and highlight the clinical utility of EEG- based effective connectivity for identifying patients with potential covert awareness. Author SummaryOur study investigates the role of the Default Mode Network (DMN) in individuals with disorders of consciousness (DoC), such as unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS). Previous neuroimaging studies have suggested a role for the DMN in DoC, but its ability to differentiate between UWS and MCS remain unclear. Using advance brain imaging and modelling techniques, we analyzed data from DoC patients with traumatic brain injury and healthy controls. Our findings reveal a key difference in left frontoparietal connectivity when comparing UWS to MCS patients and healthy individuals. To validate our results, we employed a robust cross-validation approach, which demonstrated that the connectivity between frontal and left parietal brain regions reliably discriminates UWS patients from MCS patients and controls. Furthermore, we extended our analysis to include patients with potential covert awareness, showcasing the clinical utility of our findings. We successfully classified these patients as conscious with high accuracy. This research significantly contributes to our understanding of the DMN in DoC and highlights the potential use of electroencephalography-based connectivity analysis in clinical settings. By identifying specific alterations in the DMN after severe brain injury, our study may aid in the accurate diagnosis and management of individuals with disorders of consciousness, potentially improving their overall outcomes.

neuroscience↗

bioRxiv2021

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↗