Biology subjects

Signorelli, C. M.

Publications and source records attributed to Signorelli, C. M..

5 recordsLinked to original sources

bioRxiv2025

Comprehensive profiling of anaesthetised brain dynamics across phylogeny

Intrinsic dynamics of neuronal circuits shape information processing. Combining neuroimaging with causal perturbation offers the opportunity to understand how local dynamics mediate the link between neurobiology and functional repertoire. We compile a unique dataset of multi-scale neural activity during wakefulness and anaesthetic-induced suppression of information processing encompassing human, macaque, marmoset, mouse, zebrafish and nematode. Applying massive feature extraction, we comprehensively characterise local neural dynamics across >6,000 time-series features. Using dynamics as a common space for cross-species comparison reveals a conserved dynamical profile of anaesthesia across species, characterised by shorter intrinsic timescales of neural activity and dampened interregional synchrony. This dynamical regime is experimentally reversed in vivo by deep-brain stimulation of the macaque centromedian thalamus, restoring behavioural responsiveness. Spatially, this conserved dynamical phenotype covaries with conserved transcriptional profiles of excitatory and inhibitory neurotransmission across human, macaque, marmoset and mouse cortex. Biophysical modelling provides a mechanistic link between the macroscale dynamical phenotype of anaesthesia, and microscale effects of key molecular targets on the timescales of synaptic excitation and inhibition. Altogether, comprehensive dynamical phenotyping reveals a shared neural endpoint of anaesthesia: across species and scales, anaesthetics induce spatio-temporal isolation of local neural activity.

neuroscience↗

bioRxiv2024

Transcranial direct current stimulation modulates primate brain dynamics across states of consciousness.

The resting primate brain is traversed by spontaneous functional connectivity patterns that show striking differences between conscious and unconscious states. Transcranial direct current stimulation, a non-invasive neuromodulatory technique, can improve signs of consciousness in disorders of consciousness; however, can it influence both conscious and unconscious dynamic functional connectivity? We investigated the modulatory effect of prefrontal cortex (PFC) transcranial direct current stimulation (tDCS) on brain dynamics in awake and anesthetized non-human primates using functional MRI. In awake macaques receiving either anodal or cathodal tDCS, we found that cathodal stimulation robustly disrupted the repertoire of functional connectivity patterns, increased structure-function correlation, decreased Shannon entropy, and favored transitions towards anatomically-based patterns. Under deep sedation, anodal tDCS significantly altered brain pattern distribution and reduced structure-function correlation. The prefrontal stimulation also modified dynamic connectivity arrangements typically associated with consciousness and unconsciousness. Our findings offer compelling evidence that PFC tDCS induces striking modifications in the fMRI-based dynamic organization of the brain across different states of consciousness. This study contributes to an enhanced understanding of tDCS neuromodulation mechanisms and has important clinical implications for disorders of consciousness.

neuroscience↗

bioRxiv2023

Local Orchestration of Global Functional Patterns Supporting Loss and Restoration of Consciousness in the Primate Brain

AbstractA central challenge of neuroscience is to elucidate how the orchestration of brain function is modulated by different states of consciousness. Here, we investigate the link between distributed structural and functional brain organisation in functional MRI signals of non-human primates, through bi-directional causal manipulations of consciousness. During varying levels of propofol, sevoflurane, or ketamine anaesthesia, and subsequent restoration of responsiveness by deep brain stimulation of the central thalamus, we investigate how loss of consciousness impacts distributed patterns of structure-function organisation across scales. Combining the specificity of electrical stimulation with global fMRI coverage of the entire cortex, we report that distributed brain activity under anaesthesia is increasingly constrained by brain structure across scales, coinciding with anaesthetic-induced collapse of multiple dimensions of hierarchical cortical organisation. Crucially, we show that these distributed signatures of anaesthetic-induced loss of consciousness are observed across different anaesthetics, and they are reversed by electrical stimulation of the central thalamus, coinciding with recovery of behavioural markers of consciousness during propofol anaesthesia. No such effects were observed upon stimulation of a control anatomical site, ventral lateral thalamus, demonstrating specificity. Through causal manipulations of consciousness that integrate pharmacology and electrical intracranial stimulation of the thalamus, our results identify global signatures of consciousness that are under local causal control by specific nuclei of the thalamus. Overall, the present work broadens our understanding of the link between brain network organisation and distributed function in supporting consciousness, and the interplay between local and global functional architecture.

neuroscience↗

bioRxiv2021

Macroscopic quantities of collective brain activity during wakefulness and anesthesia

The study of states of arousal is key to understand the principles of consciousness. Yet, how different brain states emerge from the collective activity of brain regions remains unknown. Here, we studied the fMRI brain activity of monkeys during wakefulness and anesthesia-induced loss of consciousness. Using maximum entropy models, we derived collective, macroscopic properties that quantify the systems capabilities to produce work, to contain information and to transmit it, and that indicate a phase transition from critical awake dynamics to supercritical anesthetized states. Moreover, information-theoretic measures identified those parameters that impacted the most the network dynamics. We found that changes in brain state and in state of consciousness primarily depended on changes in network couplings of insular, cingulate, and parietal cortices. Our findings suggest that the brain state transition underlying the loss of consciousness is predominantly driven by the uncoupling of specific brain regions from the rest of the network.

neuroscience↗

bioRxiv2020

Hierarchical disruption in the cortex of anesthetized monkeys as a new signature of consciousness loss

Anesthesia induces a reconfiguration of the repertoire of functional brain states leading to a high function-structure similarity. However, it is unclear how these functional changes lead to loss of consciousness. Here we suggest that the mechanism of conscious access is related to a general dynamical rearrangement of the intrinsic hierarchical organization of the cortex. To measure cortical hierarchy, we applied the Intrinsic Ignition analysis to resting-state fMRI data acquired in awake and anesthetized macaques. Our results reveal the existence of spatial and temporal hierarchical differences of neural activity within the macaque cortex, with a strong modulation by the depth of anesthesia and the employed anesthetic agent. Higher values of Intrinsic Ignition correspond to rich and flexible brain dynamics whereas lower values correspond to poor and rigid, structurally driven brain dynamics. Moreover, spatial and temporal hierarchical dimensions are disrupted in a different manner, involving different hierarchical brain networks. All together suggest that disruption of brain hierarchy is a new signature of consciousness loss.

neuroscience↗