This is what happens in your brain when you don't sleep for two days

Ever wondered what happens inside your brain when you stay awake for a day, a night and another day, before you finally go to sleep? Well, we just found out.

It has been known for many years that how sleepy we are, how well we can add up numbers, pay attention or conduct a working memory task depends on how long we have been awake and the time of day. Typically if we stay awake over a period of two days (a day, a night and then the next day) the first 16 hours or so is of wakefulness – performance is good and doesn’t change much.

But then, as we enter the “biological night time”, as indicated by a rise of the hormone melatonin, performance deteriorates rapidly and reaches a minimum at around 6-8am the following morning. On the second day, performance can get a little better (but still well below that of day one) and only returns to normal, baseline levels after a good night’s sleep.

The key characteristic of this performance timeline is that it doesn’t deteriorate linearly based on how long you’ve been awake but is instead modulated by the time of day. In fact, we know now that it isn’t actually “time of day” but “internal biological time of day” that causes the effects of sleep loss. At the behavioural level, then, brain function is determined by the combined effects of circadian rhythmicity and sleep homeostasis – the sleep pressure that builds up during wakefulness and dissipates during sleep.

Circadian rhythm

Circadian rhythmicity can be observed in many aspects of behaviour and physiology and is generated by circadian clocks in nearly every cell in the brain and body. Locally, these rhythms are generated by a feedback loop of clock proteins onto clock genes that express genetic information that is then translated into proteins.

All these clocks – including brain clocks – are synchronised by a central director/conductor located in a brain area called the suprachiasmatic nucleus in the hypothalamus. This area of the brain also drives the rhythm of melatonin in blood and saliva.

So how does this combined action of circadian rhythmicity and sleep homeostasis work? Well, during the biological day the circadian clock generates an alerting or wakefulness promoting signal that becomes stronger as the day progresses and reaches maximum strength in the evening. This may seem a bit paradoxical, but this signal needs to become stronger as the day progresses because sleep pressure also increases the longer we’re awake – so something needs to keep us alert.

But as we enter the biological night, the wakefulness promoting circadian signal dissipates and turns into a sleep promoting signal with a maximum strength at around 6-8am. Again, this may seem a bit paradoxical but under normal conditions when we sleep at night, this comes in handy because the sleep promoting signal allows us to continue to sleep well even after six or seven hours when the sleep pressure has dissipated.

Problems arise when we stay awake at night and the next day, however. During the night, sleep pressure remains high and even increases because we are awake. The circadian signal no longer opposes this pressure and we struggle to stay awake and to perform. The next day, the circadian clock, which still ticks whether we are asleep or not, starts promoting awake signals again so it becomes a little bit easier to perform and stay awake.

What does this look like in the brain?

This is all fine and good and makes sense. Indeed, this working model is widely accepted from what we’ve seen happen when it comes to behaviour. But what does this combined action of circadian rhythm and sleep homeostasis look like within the human brain?

Our team of researchers, from the University of Liege and the University of Surrey, scanned the brains of 33 people using functional magnetic resonance imaging (fMRI) – which gives a detailed picture of levels of neuronal activity throughout the brain – who were sleep deprived over two days and following a period of recovery sleep. We also measured melatonin levels to have a good indicator of internal biological time, which varies between individuals. Our results are published in Science.

For each participant, 13 brain images were obtained while they were conducting a simple reaction time task. Twelve brain images were collected during the sleep deprivation at times characterised by those rapid changes previously observed for performance in the evening and in the morning. The thirteenth image was taken after recovery sleep.

Activity in several brain regions, and in particular subcortical areas (such as the thalamus, a major centre for relaying information to the cortex), followed a 24-hour rhythmic (circadian) pattern the timing of which, surprisingly, varied across brain regions. Other brain regions – in particular frontal brain areas including higher-order association areas – showed a reduction in activity with time awake followed by a return to pre-sleep deprivation levels after recovery sleep. Some brain regions displayed a pattern which was a combination of a rhythmic pattern and a decline associated with time awake.

Even more surprising, these effects of sleep loss on brain activity were much more widespread when the participants performed a simple reaction time task compared to a more complex memory-reliant task.

What all this means is that various brain regions appear to be differently affected by sleep loss and the circadian rhythm, and overall the results demonstrate both the pervasiveness of these effects, but also the similarity and local nature of these influences.

The variety in brain responses shows just how complex the mechanisms are by which the brain responds to sleep loss. It helps us to understand how the brain might maintain performance during the day and night. These results may reassure shift workers and people working very long hours struggling to pay attention and concentrate on their job, particularly in the early morning hours. Yes, your brain is going to be different at night than during the day. They also suggest that if you’re working late, it might be better to wrap it up, get some sleep and start again in the morning.

It may even help us to better understand why many symptoms in psychiatric and neurodegenerative conditions wax and wane, and why in the early morning after a night without sleep we struggle to maintain attention, whereas in the evening it is not an issue.