Reduced emergent character of neural dynamics in patients with a disrupted connectome.

High-level brain functions are widely believed to emerge from the orchestrated activity of multiple neural systems. However, lacking a formal definition and practical quantification of emergence for experimental data, neuroscientists have been unable to empirically test this long-standing conjecture. Here we investigate this fundamental question by leveraging a recently proposed framework known as "Integrated Information Decomposition," which establishes a principled information-theoretic approach to operationalise and quantify emergence in dynamical systems - including the human brain. By analysing functional MRI data, our results show that the emergent and hierarchical character of neural dynamics is significantly diminished in chronically unresponsive patients suffering from severe brain injury. At a functional level, we demonstrate that emergence capacity is positively correlated with the extent of hierarchical organisation in brain activity. Furthermore, by combining computational approaches from network control theory and whole-brain biophysical modelling, we show that the reduced capacity for emergent and hierarchical dynamics in severely brain-injured patients can be mechanistically explained by disruptions in the patients' structural connectome. Overall, our results suggest that chronic unresponsiveness resulting from severe brain injury may be related to structural impairment of the fundamental neural infrastructures required for brain dynamics to support emergence.

The complexity of the stream of consciousness.

Typical consciousness can be defined as an individual-specific stream of experiences. Modern consciousness research on dynamic functional connectivity uses clustering techniques to create common bases on which to compare different individuals. We propose an alternative approach by combining modern theories of consciousness and insights arising from phenomenology and dynamical systems theory. This approach enables a representation of an individual's connectivity dynamics in an intrinsically-defined, individual-specific landscape. Given the wealth of evidence relating functional connectivity to experiential states, we assume this landscape is a proxy measure of an individual's stream of consciousness. By investigating the properties of this landscape in individuals in different states of consciousness, we show that consciousness is associated with short term transitions that are less predictable, quicker, but, on average, more constant. We also show that temporally-specific connectivity states are less easily describable by network patterns that are distant in time, suggesting a richer space of possible states. We show that the cortex, cerebellum and subcortex all display consciousness-relevant dynamics and discuss the implication of our results in forming a point of contact between dynamical systems interpretations and phenomenology.

Whole-brain modelling identifies distinct but convergent paths to unconsciousness in anaesthesia and disorders of consciousness.

The human brain entertains rich spatiotemporal dynamics, which are drastically reconfigured when consciousness is lost due to anaesthesia or disorders of consciousness (DOC). Here, we sought to identify the neurobiological mechanisms that explain how transient pharmacological intervention and chronic neuroanatomical injury can lead to common reconfigurations of neural activity. We developed and systematically perturbed a neurobiologically realistic model of whole-brain haemodynamic signals. By incorporating PET data about the cortical distribution of GABA receptors, our computational model reveals a key role of spatially-specific local inhibition for reproducing the functional MRI activity observed during anaesthesia with the GABA-ergic agent propofol. Additionally, incorporating diffusion MRI data obtained from DOC patients reveals that the dynamics that characterise loss of consciousness can also emerge from randomised neuroanatomical connectivity. Our results generalise between anaesthesia and DOC datasets, demonstrating how increased inhibition and connectome perturbation represent distinct neurobiological paths towards the characteristic activity of the unconscious brain.

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 small world dynamics (quantified by sample entropy; dSW-E1) 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. We find that the network dynamics of intermodular communication in the cerebellum also have unique predictive power for levels of awareness. 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.

Preserved fractal character of structural brain networks is associated with covert consciousness after severe brain injury.

Self-similarity is ubiquitous throughout natural phenomena, including the human brain. Recent evidence indicates that fractal dimension of functional brain networks, a measure of self-similarity, is diminished in patients diagnosed with disorders of consciousness arising from severe brain injury. Here, we set out to investigate whether loss of self-similarity is observed in the structural connectome of patients with disorders of consciousness. Using diffusion MRI tractography from N = 11 patients in a minimally conscious state (MCS), N = 10 patients diagnosed with unresponsive wakefulness syndrome (UWS), and N = 20 healthy controls, we show that fractal dimension of structural brain networks is diminished in DOC patients. Remarkably, we also show that fractal dimension of structural brain networks is preserved in patients who exhibit evidence of covert consciousness by performing mental imagery tasks during functional MRI scanning. These results demonstrate that differences in fractal dimension of structural brain networks are quantitatively associated with chronic loss of consciousness induced by severe brain injury, highlighting the close connection between structural organisation of the human brain and its ability to support cognitive function.

Dopaminergic brainstem disconnection is common to pharmacological and pathological consciousness perturbation.

Clinical research into consciousness has long focused on cortical macroscopic networks and their disruption in pathological or pharmacological consciousness perturbation. Despite demonstrating diagnostic utility in disorders of consciousness (DoC) and monitoring anesthetic depth, these cortico-centric approaches have been unable to characterize which neurochemical systems may underpin consciousness alterations. Instead, preclinical experiments have long implicated the dopaminergic ventral tegmental area (VTA) in the brainstem. Despite dopaminergic agonist efficacy in DoC patients equally pointing to dopamine, the VTA has not been studied in human perturbed consciousness. To bridge this translational gap between preclinical subcortical and clinical cortico-centric perspectives, we assessed functional connectivity changes of a histologically characterized VTA using functional MRI recordings of pharmacologically (propofol sedation) and pathologically perturbed consciousness (DoC patients). Both cohorts demonstrated VTA disconnection from the precuneus and posterior cingulate (PCu/PCC), a main default mode network node widely implicated in consciousness. Strikingly, the stronger VTA-PCu/PCC connectivity was, the more the PCu/PCC functional connectome resembled its awake configuration, suggesting a possible neuromodulatory relationship. VTA-PCu/PCC connectivity increased toward healthy control levels only in DoC patients who behaviorally improved at follow-up assessment. To test whether VTA-PCu/PCC connectivity can be affected by a dopaminergic agonist, we demonstrated in a separate set of traumatic brain injury patients without DoC that methylphenidate significantly increased this connectivity. Together, our results characterize an in vivo dopaminergic connectivity deficit common to reversible and chronic consciousness perturbation. This noninvasive assessment of the dopaminergic system bridges preclinical and clinical work, associating dopaminergic VTA function with macroscopic network alterations, thereby elucidating a critical aspect of brainstem-cortical interplay for consciousness.