x Abu Dhabi, UAEThursday 27 July 2017

Exploring sleep's twilight zone

A case study of two Italians has called into question the recognised boundaries between sleep and wakefulness. Can your brain take a catnap without you realising and, if so, what are the implications for jobs where alertness can be a matter of life or death?

A man sleeps on a bench at the Abu Dhabi Municipality Main Bus Terminal.
A man sleeps on a bench at the Abu Dhabi Municipality Main Bus Terminal.

Earlier this year, a puzzling report appeared in the journal Sleep Medicine. It described two Italian people who never truly slept. They might lie down and close their eyes, but read-outs of brain activity showed none of the normal patterns associated with sleep. Their behaviour was pretty odd, too. Though largely unaware of their surroundings during these rest periods, they would walk around, yell, tremble violently and their hearts would race. The remainder of the time they were conscious and aware but prone to powerful, dream-like hallucinations.

Both had been diagnosed with a neurodegenerative disorder called multiple system atrophy. According to the report's authors, Roberto Vetrugno and colleagues from the University of Bologna, Italy, the disease had damaged the pair's brains to such an extent that they had entered status dissociatus, a twilight zone in which the boundaries between sleep and wakefulness completely break down. That this can happen contradicts the way we usually think about sleep, but it came as no surprise to Mark Mahowald, the medical director of the Minnesota Regional Sleep Disorders Center, in Minneapolis, who has long contested the dogma that sleep and wakefulness are distinct states. The blurring of sleep and wakefulness is very clear in status dissociatus, but he believes it can happen to us all. If he is right, we will have to rethink our understanding of what sleep is and what it is for.

Dr Vetrugno's description of people with status dissociatus is just one of many disorders that can be explained as a breakdown of the boundaries between sleep and wakefulness, Dr Mahowald believes. One is REM (rapid eye movement) behavioural disorder in which people in REM sleep act out their dreams because the temporary paralysis, or cataplexy, that normally accompanies this state is replaced by the full mobility of wakefulness. In sleep paralysis the opposite is true. Here, cataplexy intrudes into wakefulness, and a person wakes to find him or herself unable to move. It is estimated that up to 40 per cent of people have experienced this disturbing phenomenon.

Also surprisingly common are hypnagogic hallucinations - sensory illusions that occur on the cusp of sleep when the dreaming component of REM intrudes into wakefulness. Dr Mahowald's list also includes sleepwalking, night terrors and narcolepsy. Controversially, the list also includes near-death experiences and alien abductions. The boundaries between sleep and wakefulness are particularly blurred when we are sleep-deprived. Although sleep-deprived volunteers seem to be awake, they have momentary lapses, or "micro-sleeps". These fleeting naps last between half a second and two seconds, and become increasingly frequent the longer we are deprived of sleep, until finally we nod off.

David Dinges, a psychiatrist at the University of Pennsylvania in Philadelphia, has probably deprived more people of sleep in the name of science than anyone else. In one such study in the late 1980s, Dr Dinges and his team revealed how easily the different states of vigilance can become intermingled. When volunteers were subjected to tests of working memory in which they had to subtract numbers, they could do an average of 90 sums in three minutes with few errors. After 52 hours deprived of sleep, their performance fell to around 70 subtractions, with not many more errors. However, after they had slept for two hours the change was dramatic. "When we woke them up abruptly, and they rated themselves as alert and ready to go, they couldn't do even one subtraction," says Dr Dinges. People even seemed to be dreaming as they attempted the task. One subject mused: "What if people ran faster than normal people run home," in the middle of a string of incorrect responses.

Known as sleep inertia, a less extreme version of such disorientation is now generally recognised as the cause of the grogginess some people get after their alarm clock goes off. It is as if they are socially awake but functionally asleep; as if the brain circuits underlying responsiveness are up and running, but those mediating working memory are still offline. This chimes with the ideas of James Krueger, of Washington State University, who has argued that the individual processing units in the brain - known as cortical columns - fall asleep independently when they become tired. In his view, shifts between wakefulness and sleep occur when enough columns are in one state or the other. Dr Krueger believes this mosaic pattern of sleep explains sleep inertia and sleepwalking.

This has implications for all of us, especially those in professions where staying awake can be a matter of life or death. "If you're doing 100kph on a highway and you have a lapse, your fingers go lax on the steering wheel and you drift off the road at a four-degree angle," says Dr Dinges. "Two seconds is all it takes to be completely out of your lane." Up to 20 per cent of traffic accidents are fatigue-related.

Brain imaging has recently revealed a mental back-up system in people who remain alert when sleep-deprived. While other people have reduced brain activity when tired, sleep-resistant individuals manage to maintain their brain activity levels. More interestingly, they also recruit new areas to help compensate for having been awake for so long. These people were selected for the study because they had a gene variant found in around 40 per cent of people that is thought to be associated with resistance to sleep deprivation. It seems likely that such people are also less prone to status dissociatus, although this has not yet been tested.

Another group who appear to be more vigilant than most are sufferers of primary insomnia - insomnia not associated with any other condition. There is evidence to suggest they are in a constant state of hyperarousal, with relatively high metabolic rates and high levels of the stress hormone cortisol. "It's as though somebody just cranked up their alertness over 24 hours, so they are more alert at night, but they are also more alert in the day," says Dr Mahowald.

As the blur between sleep and wakefulness becomes more widely accepted, researchers are devising techniques for capturing the brain's fleeting lapses and vacillations. For example, the neuroscientist Giulio Tononi of the University of Wisconsin, is eavesdropping on sleeping brains using EEGs with 256 electrodes rather than the more usual 32, to improve spatial resolution and help him catch the brain in the act of mosaic napping. Micro-sleeps are just the tip of the iceberg, Dr Tononi says. He is particularly concerned by the possibility that parts of our brain might be going offline without us even realising it. "In many respects, it would be like having a temporary mental disorder without anybody, including yourself, being aware of it," he says. Forgetfulness and daydreaming could be examples of this, but so could more bizarre and even criminal behaviours. Meanwhile, Pierre Maquet, at the University of Liège, in Belgium, has started to use the brain-scan method fMRI to chart the patterns of brain activity associated with different sleep states. His team is already finding that the distinctions between sleep and wakefulness look quite different when you compare patterns of activity across the whole brain, including deep structures, as opposed to using EEG, which measures activity in just the outer few millimetres of the cortex.

Lurking in the background is the hope that these approaches will shed light on the vexed issue of what sleep is for. A leading theory is that it is important for memory consolidation. Yet one of the puzzling aspects of the two Italians with status dissociatus is that, despite complete disruption of both their REM and non-REM sleep, they showed no memory deficit. Does this add grist to the mill of those who believe that sleep has no other purpose than to save energy and keep us safe? Or does it mean, as Dr Mahowald believes, that the two individuals were in fact experiencing some sort of mosaic sleep? Armed with a less black-and-white definition of sleep and wakefulness, and more sensitive tools for measuring them, that question might finally be resolved.

* New Scientist www.newscientist.com