Conserved thalamic mechanisms for attention and sleep

One of the defining characteristics of sleep is a change in the way the brain deals with external stimuli, like sights and sounds. While still being able to process information from the outside world (for example, if someone calls your name you may wake up), the complexity and nuance of the brain's response is considerably decreased. A similar process happens on a much shorter timescale when you are awake.

Then, it is called attention, which refers to the ability to switch dynamically between reacting to or ignoring multiple co-occurring stimuli. To date, study of the brain networks underpinning these fundamental mechanisms of sleep and attention has been limited in humans. While insights from animal models provide us with crucial guidance, the ability to understand these processes in the human brain will provide rich new avenues of research in healthy brains and disorders like schizophrenia where these circuits are disrupted.

Recent work in animals has suggested that the brain networks controlling responsiveness during sleep are the same as those responsible for attention during wakefulness. This project aims to study those networks in the human brain. This has not previously been possible, largely because the brain structures involved are difficult to visualise using MRI, the main technique to study structures that are deep within the human brain.

However, in pilot data we have developed advanced brain imaging techniques which allow us to address these questions non-invasively and with unprecedented detail.

Central to the control of sleep and attention, and the focus of this project, is a brain circuit involving the thalamus, the thalamic reticular nucleus (TRN) and the cortex. The thalamus is a deep brain structure that controls whether incoming information reaches the cerebral cortex. The TRN is a thin structure surrounding the thalamus which can block the transmission of signals from the senses to the cerebral cortex.

Without access to this information, the computational power of the cerebral cortex is cut off from the environment, leading to the disengagement from the world that we experience during sleep. While small, around 3mm thick and 50-60mm long, the TRN therefore plays a role that is disproportionately important compared to its size.

Functional MRI (fMRI) allows brain activity from throughout the brain to be recorded, and with current methods we can record from the thalamus and cortex. As it is smaller, the TRN is more difficult to see on MRI scans, but we have developed new MRI approaches which reliably identify it. These are based on MRI using a magnetic field strength more than twice that of a standard hospital scanner.

With these cutting-edge techniques we can measure how the brain circuits identified from animal work are altered as people fall asleep or perform tasks which manipulate attention.

Each participant will undergo an ultra-high field MRI scan to define their individual TRN. They will then take part in two sessions in a standard MRI scanner: one at night in which they will sleep, and another in the day in which they will perform an attention task that engages the thalamus-TRN-cortex circuit. They will wear a cap with electrodes to measure their electrical brain activity.

This allows us to define when and how deeply they are sleeping and how their brain rhythms change with the task. Brain activity in the thalamus, TRN and cortex will be measured at the same time using fMRI. Despite the MRI scanner being an unusual place to sleep, we are experienced in this type of study and find that most people, if properly selected, are able to fall asleep.

We will test the hypothesis that there is a common brain circuit underlying the change in responses to sensory stimulation during sleep and attention. It will provide fundamental new insights into the mechanisms by which information flow is controlled in the human brain, and open new ways to study brain disorders.