Camilo Miguel Signorelli’s research while affiliated with University of Oxford and other places

The intrinsic dynamics of neuronal circuits shape information processing and cognitive function. Combining non-invasive neuroimaging with anaesthetic-induced suppression of information processing provides a unique opportunity to understand how local dynamics mediate the link between neurobiology and the organism's functional repertoire. To address this question, we compile a unique dataset of multi-scale neural activity during wakefulness and anesthesia encompassing human, macaque, marmoset, mouse and nematode. We then apply massive feature extraction to comprehensively characterize local neural dynamics across >6,000 time-series features. Using dynamics as a common space for comparison across species, we identify a phylogenetically conserved dynamical profile of anaesthesia that encompasses multiple features, including reductions in intrinsic timescales. This dynamical signature has an evolutionarily conserved spatial layout, covarying with transcriptional profiles of excitatory and inhibitory neurotransmission across human, macaque and mouse cortex. At the network level, anesthetic-induced changes in local dynamics manifest as reductions in inter-regional synchrony. This relationship between local dynamics and global connectivity can be recapitulated in silico using a connectome-based computational model. Finally, this dynamical regime of anaesthesia is experimentally reversed in vivo by deep-brain stimulation of the centromedian thalamus in the macaque, resulting in restored arousal and behavioural responsiveness. Altogether, omprehensive dynamical phenotyping reveals that spatiotemporal isolation of local neural activity during anesthesia is conserved across species and anesthetics.

The science of consciousness requires multiple disciplines. There are complex philosophical questions that need to be understood, physical restrictions to consider, biological organisation that seems relevant to conscious beings, and phenomenological and psychological aspects that can not be studied under quantitative methods only. Today, however, scientific models of consciousness target a few aspects and little dialogue is found among them, even less among fields. In this article, we react to this current state of consciousness research and motivate a transdisciplinary, diverse and rigorous approach. We first introduce how the primacy of experience generates an explanatory paradox for mechanistic accounts and how to avoid it with a broader perspective. We follow by presenting tools such as mereological distinctions (constitution and causation), constraint-types of explanations and a sound axiomatic strategy for empirical and theoretical research. This critical and constructive reading motivates open dialogue and intellectual humility. We end our contribution by offering collaborative paths beyond neuroscience and calling for a fruitful exchange between different models of consciousness. This, we argue, might be the only way to solve and/or dissolve the "problem" of consciousness.

Integrated Information Theory 4.0 (IIT) aims to explain consciousness by mathematically formalizing it in terms of existence as causal power and employing computational tools for experimental assessment. IIT conceives consciousness as an intrinsic structure of cause-effect powers, postulating that any conscious system exists for itself as a maximally unitary whole, irreducible to its parts, mathematically assessed in terms of maximal system integrated information (φ_s^*). In this theoretical article, we critique IIT’s conceptual interpretation of φ_s^*, which is grounded in problematic ontological assumptions that exclude non-φ_s^*, non-conscious systems—such as the body—from true existence. This exclusion leads to theoretical tensions within IIT and with standard neuroscience. We propose minimal conceptual adjustments to resolve these issues, enabling IIT to adopt causal-physical realism by: i) rejecting the so-called principle of true existence (and the associated Great Divide of Being), ii) modifying the principle of maximal existence, and iii) adopting a fully realistic principle of being. These changes preserve IIT’s mathematical rigor while enhancing its theoretical robustness and compatibility with standard neuroscience, allowing IIT theorists to investigate the physical substrates of consciousness and their cause-effect structures computationally, without denying the genuine existence of the non-conscious parts of their own brains and bodies.

In this article we present two ontological problems for the Integrated Information Theory of Consciousness 4.0: what we call the (i) the intrinsicality 2.0 problem, and (ii) the engineering problem. These problems entail that truly existing, conscious entities can depend on, and be engineered from, entities that do not objectively exist, which is problematic: if something does not exist in objective reality (i.e., in itself, independently of another entity’s consciousness), then it seems that it cannot be part of the material basis and determinants of other entities that do exist on their own. We argue that the core origin of these problems lies in IIT’s equation between true existence and phenomenal existence (consciousness), and the corresponding ontological exclusion of non-conscious physical entities (i.e., extrinsic entities) from objective reality. In short, these two problems seem to show that IIT should reconsider the ontological status of these extrinsic entities, because they need to exist objectively to account for the ontological implications of the scenarios we present here, which are permitted by the operational framework of the theory.

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, but can it influence 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 high-density tDCS (HD-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 HD-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.

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, but can it influence 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 high-density tDCS (HD-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 HD-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.

This paper addresses a problem that arises from the ontological commitments of Integrated Information Theory (IIT) 4.0, particularly its stance that only conscious entities truly exist. This position leads to the "origin of consciousness problem": if non-conscious entities do not truly exist, how could consciousness have evolved from non-conscious ancestors? We explore several responses IIT might offer, such as the co-origin of life and consciousness, or the idea that non-conscious ancestors might have been constituted by "ontological dust"—minimally conscious, intrinsic micro-entities collectively aggregated to form bigger objects lacking unified consciousness. Our analysis shows that IIT’s ontological framework, along with scientific knowledge regarding biological evolution, prebiotic chemical structures, and physical cosmology, ultimately forces the theory into positing a form of "Big Bang consciousness", that is, a primordial ontological dust constituted by minimally conscious elementary particles created soon after the Big Bang. Although IIT may accept this striking implication, we think that it introduces tensions with both the received scientific view of the evolutionary origin of consciousness and the cosmological understanding of early universe components. We also present but ultimately reject an alternative option based on what we call the “formless stuff hypothesis”, which might avoid the implication that consciousness originates from nothing as well as the necessity of a "Big Bang consciousness”. We conclude by suggesting that IIT's metaphysical commitments, especially the equation true existence=phenomenal existence, require re-examination to reconcile its framework with standard scientific knowledge, and in particular, with the received view about the phylogenetic origin of consciousness.

Background: Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation approach that has been reported to perturb task activity and to benefit patients with a variety of diseases. Nevertheless, the effects of tDCS on brain dynamics and transitions in brain patterns across states of consciousness remain poorly understood. Objective: Here, we investigated the modulatory effect of prefrontal cortex (PFC) tDCS on brain dynamics, both in the awake state and during anesthesia-induced loss of consciousness in non-human primates. Methods: We acquired functional magnetic resonance imaging (fMRI) data before, during, and after the application of high-density tDCS (HD-tDCS) utilizing a prefrontal-occipital montage with two electrodes. In the awake state, macaques received either anodal or cathodal PFC stimulation. Under anesthesia, macaques underwent two consecutive anodal PFC stimulations of increasing intensity. Dynamical functional connectivity was measured using fMRI, and the resulting connectivity matrices were clustered into distinct brain patterns. Results: We found that cathodal PFC HD-tDCS robustly disrupted the rich dynamic repertoire of brain patterns of the awake state. It increased the brain structure-function correlation, decreased Shannon entropy, and strongly favored Markov chain transition probabilities towards patterns closest to anatomy. Under anesthesia, 2 mA anodal PFC HD-tDCS significantly changed the distribution of brain patterns and reduced the structure-function correlation. Conclusion: Our findings offer compelling evidence that prefrontal tDCS induces a striking modification in the fMRI-based dynamic organization of the brain across varying states of consciousness. This contributes to an enhanced understanding of the neural mechanisms underlying tDCS neuromodulation.

An algebraic interpretation of multigraph networks is introduced in relation to conscious experience, brain and body. These multigraphs have the ability to merge by an associative binary operator $\odot$, accounting for biological composition. We also study a mathematical formulation of splitting layers, resulting in a formal analysis of the transition from conscious to non-conscious activity. From this construction, we recover core structures for conscious experience, dynamical content and causal constraints that conscious interactions may impose. An important result is the prediction of structural topological changes after conscious interactions. These results may inspire further use of formal mathematics to describe and predict new features of conscious experience while aligning well with formal tries to mathematize phenomenology, phenomenological tradition and applications to artificial consciousness.

A central challenge of neuroscience is to elucidate how brain function supports consciousness. Here, we combine the specificity of focal deep brain stimulation with fMRI coverage of the entire cortex, in awake and anaesthetised non-human primates. During propofol, sevoflurane, or ketamine anaesthesia, and subsequent restoration of responsiveness by electrical stimulation of the central thalamus, we investigate how loss of consciousness impacts distributed patterns of structure-function organisation across scales. 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. These distributed signatures are observed across different anaesthetics, and they are reversed by electrical stimulation of the central thalamus, coinciding with recovery of behavioural markers of arousal. No such effects were observed upon stimulating the ventral lateral thalamus, demonstrating specificity. Overall, we identify consistent distributed signatures of consciousness that are orchestrated by specific thalamic nuclei.