Sleep 'resets' brain connections crucial for memory and learning, s...

https://www.theguardian.com/science/2016/aug/23/sleep-resets-br...

Sleep 'resets' brain connections crucial for

memory and learning, study reveals
Discovery that sleeplessness causes neurons to become muddled with electrical
activity could help develop new treatments for mental health disorders
Ian Sample Science editor
Tuesday 23 August 2016 16.22BST

For Jules Verne it was the friend who keeps us waiting. For Edgar Allan Poe so many little
slices of death. But though the reason we spend a third of our lives asleep has so far
resisted scientic explanation, research into the impact of sleepless nights on brain
function has shed fresh light on the mystery - and also oered intriguing clues to
potential treatments for depression.
In a study published on Tuesday, researchers show for the rst time that sleep resets the
steady build-up of connectivity in the human brain which takes place in our waking
hours. The process appears to be crucial for our brains to remember and learn so we can
adapt to the world around us.
The loss of a single nights sleep was enough to block the brains natural reset
mechanism, the scientists found. Deprived of rest, the brains neurons seemingly
became over-connected and so muddled with electrical activity that new memories
could not be properly laid down.
But Christoph Nissen, a psychiatrist who led the study at the University of Freiburg, is
also excited about the potential for helping people with mental health disorders. One
radical treatment for major depression is therapeutic sleep deprivation, which Nissen
believes works through changing the patients brain connectivity. The new research
oers a deeper understanding of the phenomenon which could be adapted to produce
more practical treatments.
Why we sleep is a fundamental question. Why do we spend so much of our lives in this
brain state? This work shows us that sleep is a highly active brain process and not a
waste of time. Its required for healthy brain function, said Nissen.
The results are a boost for what is called the synaptic homeostasis hypothesis of sleep,
which was developed by scientists at the University of Wisconsin-Madison in 2003. It
explains why our brains need to rest after a day spent absorbing all manner of
information, from the morning news and the state of the weather, to a chat over lunch
and what we must buy for tea.
Known more simply as SHY, the hypothesis states that when we are awake, the synapses
that form connections between our brain cells strengthen more and more as we learn
and eventually saturate our brains with information. The process requires a lot of
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Sleep 'resets' brain connections crucial for memory and learning, s...

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energy, but sleep allows the brain to wind down its activity, consolidate our memories,
and be ready to start again the next morning.
Writing in the journal Nature Communications, Nissen describes a series of tests that 11
men and nine women aged 19 to 25 took part in, either after a good nights sleep, or after
a night without sleep. On the sleepless night, participants played games, went for walks
and cooked food, but were not allowed caeine. Sta watched them throughout to make
sure they stayed awake.
In the rst round of experiments, Nissen used magnetic pulses to make neurons re in
the volunteers brains and cause a muscle in the left hand to twitch. When sleep
deprived, far weaker pulses were sucient to make the muscles move. This implied that
sleepless brains are in a more excitable state, with their neurons more strongly
connected than they are after a good nights sleep.
Nissen next turned to another form of brain stimulation to mimic the way neurons re
when memories are laid down. He found it harder to get the neurons to respond in sleepdeprived people, a sign that the process of writing memories was impaired by sleep loss.
Taken together, the results suggest that sleep allows the brain to calm its activity so
memories can be written down. In contrast, the sleep-deprived brain becomes noisy
with electrical activity and so feeble at laying down memories that the process is all but
blocked. The consequences of sleep loss were clear in a simple memory test, with tired
volunteers faring worse than those who were well-rested.
Teasing out how sleep aects brain connections could do more than answer why we
snooze so much. Shift workers and military personnel that have to cope with sleep
deprivation could benet from new drugs or countermeasures that restore normal brain
connectivity. Blood samples taken from volunteers in the study showed that sleep
deprivation lowered levels of a molecule called BDNF, or brain-derived neurotrophic
factor, which regulates synaptic connections in the brain.
But Nissen is more excited about the studys implications for understanding therapeutic
sleep deprivation and its impact on depression. If you deprive people with major
depression of sleep for one night, about 60% show a substantial improvement in mood,
motivation and cognitive function. We think it works by shifting these patients into a
more favourable state, he said.
Though striking when it works, therapeutic sleep deprivation is not much use because
many patients relapse after the subsequent nights sleep. But that is not the point,
Nissen says. It proves that its possible to shift a persons mood from one state to
another within hours. The idea is that we use sleep and sleep deprivation to understand
the brain and develop new treatments. If you think about antidepressants or
psychotherapy, it can take weeks or months to see any eects.
Giulio Tononi, a professor of sleep medicine who rst proposed SHY at the University of
Wisconsin-Madison, said the new study was truly elegant and powerful and conrmed
experiments that until now had only been performed in animals.
Sleep is essential, and one main reason is that it allows the brain to learn new things
every day while preserving and consolidating the old memories, Tononi said. Learning

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Sleep 'resets' brain connections crucial for memory and learning, s...

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and memory require synaptic activity, which is very energetically expensive and prone
to saturation. Sleep allows the brain to renormalize this synaptic activity after it
increases in the waking day.
Lars Westlye, a psychologist at University of Oslo, called the study wonderful and said
the results could throw light on links between the biology of sleep, more complex brain
functions, and severe mental disorders such as schizophrenia and depression. Like
Nissen he believes that a clearer understanding of brain connectivity might explain why
sleep deprivation can be so eective in people with depression, and plans to study the
eect in patients.
These new results should strongly motivate further studies in patient groups, both to
learn more about the roots of the disorders and how to treat them, Westlye said.
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