Distributed harmonic patterns of structure-function dependence orchestrate human consciousness

Abstract

A central question in neuroscience is how cognition and consciousness arise from human brain activity. Here, we decompose cortical dynamics of resting-state functional MRI into their constituent elements: the harmonics of the human connectome. Mapping a wide spectrum of consciousness onto these elementary brain states reveals a generalisable connectome harmonic signature of loss of consciousness, whether due to anaesthesia or severe brain injury. Remarkably, its mirror-reversed image corresponds to the harmonic signature of the psychedelic state induced by ketamine or LSD, identifying meaningful relationships between neurobiology, brain function, and conscious experience. The repertoire of connectome harmonics further provides a fine-tuned indicator of level of consciousness, sensitive to differences in anaesthetic dose and clinically relevant sub-categories of patients with disorders of consciousness. Overall, we reveal that the emergence of consciousness from human brain dynamics follows the same universal principles shared by a multitude of physical and biological phenomena: the mathematics of harmonic modes.

Paths to Oblivion: Common Neural Mechanisms of Anaesthesia and Disorders of Consciousness

“…Our results demonstrate that GABA-mediated inhibition plays a mechanistic role in the emergence of the characteristic macroscale dynamics observed during propofol-induced unconsciousness. These results align with neurophysiological evidence indicating that propofol is primarily a GABA-A receptor agonist 46,47 Crucially, the present results are consistent with the recent findings of 41 world" organisation that characterises many real-world networks, including the human brain 104,105 (but see 106 ) is defined as being the topological middle ground between these two extremes of possible network configurations 95,107 .…”

“…Taken together, our results from a neurobiologically plausible whole-brain computational model demonstrate fundamental similarities, not just between the macroscale brain dynamics that characterise anaesthesia and disorders of consciousness 13,[38][39][40][41][42] but also between the neurobiological mechanisms from which they can arise -despite the fact that anaesthesia is a…”

“…Recently, converging evidence from multimodal neuroimaging has further shown that brain dynamics are substantially and consistently altered when consciousness is lost, which suggests that specific aspects of neural dynamics may play a central role in supporting human consciousness. In particular, striking similarities have been observed across brain dynamics induced by different ways of losing consciousness, such as acute pharmacological intervention with different anaesthetic drugs, but also chronic disorders of consciousness 13,[38][39][40][41][42][43][44] . These findings suggest that spatio-temporal dynamics may provide a "common currency" between brain and mind 45 capable of encoding the difference between consciousness and unconsciousness.…”

“…In contrast, disorders of consciousness (DOC) arise from severe brain injury, typically due to anoxia or head trauma, which cause brain lesions of variable severity and location often including alterations of the physical connectivity between patients' brain regions 10,[48][49][50][51][52][53][54][55][56] . This similarity of outcomes and neural signatures 13,[38][39][40][41][42] despite arising from radically different causes, begs the question: How can (transient) pharmacological and (chronic) structural perturbations converge to similar effects on brain dynamics, and the corresponding state of unconsciousness?…”

“…We also studied the fMRI dynamics of a cohort (N=21) of patients suffering from chronic disorders of consciousness (DOC) as a result of severe brain injury (traumatic or anoxic), comparing them with a group of N=20 healthy controls. By subjecting the models to "virtual anaesthesia" (local modulation of inhibitory gain based on empirical GABA-A receptor distribution) and "virtual DOC" (alteration of the model's structural connectome), we sought to identify the neurobiological mechanisms underlying a fundamental question of modern neuroscience: how can transient perturbations of neurotransmission and chronic lesions to the structural connectome, both give rise to unconsciousness and its characteristic similar brain dynamics 13,38,39,41,93 ? Based on a cortical parcellation with 68 regions of interest, each node (cortical region) is modelled through a neurophysiologically realistic biophysical model incorporating excitatory (NMDA) as well as inhibitory (GABA) synaptic dynamics.…”