Human Brain Project researchers provide a deeper understanding of the dynamics of brain activity during states of unconsciousness, opening doors to potential therapeutic interventions.

When our brains are awake and alert, neuronal circuits in our cerebral cortex are generally in a state of activity dominated by asynchronous neuronal firing. During deep sleep or under anaesthesia, the cerebral cortex still shows activity characteristic of wakefulness, but only during short periods called ’Up states‘. However, these active, awake-like periods, alternate with silent periods in between – the ‘Down states’, also called ‘Off periods‘. Down states, when global, are invariably associated with unconsciousness. This is the case during slow-wave sleep or anaesthesia, and they are also present in patients that remain unconscious after brain injury. In those cases, local brain lesions compromise brain function due to the emergence of lesion-induced, sleep-like wave patterns expressing Down states. When brain activity falls into these silent phases, communication between cortical areas is compromised and information processing is blocked.

Understanding the nature of these silent brain periods is, thus, important because it provides insight into the mechanisms of unconsciousness. At the same time, preventing the occurrence of silent periods can lead into consciousness, which may be of therapeutic interest for treating patients with brain injury.

In an attempt to better understand these silent periods, a group of HBP researchers has now discovered that the silent periods themselves have a pattern with two different phases, and that during one of them, the brain is much more responsive to external stimuli. The HBP research team led by Maria V. Sanchez-Vives analysed the activity and confirmed the findings with virtual models. 

During part of the Down state, the brain is highly synchronised and poorly responsive to environmental or external stimuli. It then gradually enters a different phase in which neuronal firing recovers and becomes increasingly noisy, starting to build up a new cycle. This primes the brain for renewed activity and a transition into the next Up state. 

Importantly, as this transition continues, the brain also becomes increasingly susceptible to external stimulation. The research team showed that the duration of Down states could be shortened by externally stimulating the brain at the right moment. 

The Down state-like activity may cause disconnection in the communication between brain areas. This hypothesis is now being explored by Sanchez-Vives’ group as part of the research project “Neurological mechanisms of injury and sleep-like cellular mechanisms” (NEMESIS), funded by an ERC Synergy grant.

By elucidating the dynamics of Down states and the endogenous and exogenous strategies to control them, the researchers hope to ultimately learn to restore optimal brain function in individuals with brain injury.

Text by Matthijs de Boer

Reference

Alessandra Camassa, Andrea Galluzzi, Maurizio Mattia, Maria V Sanchez-Vives. Deterministic and Stochastic Components of Cortical Down States: Dynamics and Modulation. J Neurosci. 2022 Dec 14;42(50):9387-9400. doi: 10.1523/JNEUROSCI.0914-22.2022