A neurobiologically realistic computational model of whole-brain haemodynamic signals, perturbed to simulate loss of consciousness, reveals two distinct neurobiological paths to unconscious brain activity. Incorporating PET data on GABA receptor distribution shows that spatially-specific local inhibition reproduces fMRI activity observed during propofol anaesthesia. Incorporating diffusion MRI data from patients with disorders of consciousness shows that randomized neuroanatomical connectivity can also produce the dynamics characteristic of loss of consciousness. The results generalize across anaesthesia and injury datasets, suggesting that increased inhibition and connectome perturbation are distinct routes to the same functional brain dynamics.
A network of brain regions called the default mode network breaks down during anesthesia and after brain damage causing disorders of consciousness. The neurochemical reasons for this breakdown were unclear. Using functional MRI, researchers found that the ventral tegmental area, a dopamine-producing brainstem region, disconnects from key default mode network nodes (precuneus and posterior cingulate) during both propofol sedation and disorders of consciousness. Stronger connectivity between the ventral tegmental area and these nodes was associated with a more awake-like configuration of the default mode network. In patients with disorders of consciousness who later improved behaviorally, this connectivity increased toward healthy levels. In a separate group of traumatic brain injury patients, the drug methylphenidate significantly strengthened this connection. The findings suggest that dopamine modulation may be central to maintaining consciousness.