sleeping-brainCan you imagine crashing waves freezing instantly into arctic icecaps-within your sleeping brain? Well, maybe not, but from the question you might be able to infer that the sleeping brain is far from tranquil. It’s neural activity switches back and forth between states of crashing waves and frozen icecaps. This analogy may be confusing, so allow me walk you through the brain’s ocean waves first.

When researchers first discovered how to measure electrical signals on the skull, using electro encephalogram recording (EEG), people immediately noticed that the sleeping brain is not resting at all (in the sense of brain activity). When a human or other mammal falls into sleep, electrodes recording from the skulls surface will start to show what is termed ‘slow-wave’ activity. Large in amplitude, low in frequency (hence the name “slow-wave”), this type of activity can be seen over a large part of brain skull. As one falls deeper into sleep, this slow-wave activity appears more frequently, up to one cycle per second (1 Hz). We call this part of sleep “slow-wave sleep.” Because slow wave can be characterized by highly correlated neural activity, it is also referred to as the “synchronized state.”

However, around 90 minutes into the sleep cycle, dramatic events occur-the brain freezes, at least in terms of large-scale oscillations-and the big, slow waves over the entire brain are nowhere to be found. Instead, high-frequency, small-amplitude activity prevails, with greatly reduced correlation. This phase is appropriately referred to as the “desynchronized state.” In this phase, our eyes move rapidly back and forth in what scientists call “rapid eye movement” (REM) sleep. Most of our dreams happen during REM sleep and, in adults, this activity occupies about 20-25% of the total duration of sleep (or about 90-120 minutes per night). However, REM sleep occurs over approximately four or five cycles throughout the night, with each cycle being slightly longer than the previous one. Slow wave oscillation and memory consolidation

Why do we care whether the brain is in a slow wave or REM state? One reason is that controlling sleep stages is critical for narcolepsy, a strange sleep disorder that affects about one out of every 1,000 people in the United States. Why is it important for the other 999 people as well? The answer to this question is actually one of the most active research areas in neuroscience: Slow wave oscillation appears to contribute to memory consolidation. That is, without slow wave sleep, memories don’t get “burned” into your brain.

We typically feel best after a good night’s sleep, so you may not be surprised to know that sleep can improve results in memory tests. Indeed, there is a long list of studies demonstrating the importance of sleep, especially slow wave sleep, to memory consolidation. You may be surprised to learn, however, that applying current your forehead at the frequency of slow-wave oscillation can selectively improve performance on so-called declarative memory tasks, where you are required to answer “fact” type questions.

An amazing study demonstrating this phenomenon was done by Marshall, Helgadottir, Molle and Born, at Germany’s University of Lubeck in 2006. The researchers asked human subjects (13 lucky medical students) to remember the English translation of some German words right before going into sleep. During the first phase of slow-wave sleep, the experimenters induced slow-wave activity by applying oscillating currents (to the forehead) with the right frequency (0.75 Hz). The next morning, after the subjects woke up, they were asked to try to remember the words they had learned the previous day. The students who had the currents applied to their foreheads were able to remember more.

The authors went on to show that applying current during REM sleep phase did not improve memory performance. Also, applying the wrong frequency-for example, 5 Hz, which normally can be seen during REM sleep-didn’t have the same effect.

Clearly this finding raises many questions about both theory as well as practice. Theoretically, this is one of the best examples showing that distinct brain oscillations do have sufficient effect on specific brain functions. Equally important, it provides new approaches to answer the question of how our brains consolidate memories. Practically, I can almost imagine that some people will start to apply currents to their heads right before a final exam or other important memory test! Maybe we will soon see some “MemoImprov” devices selling on eBay. I guess you need to make sure that you don’t crank up the potential too much and fry your brain!

Ok, but why am I interested in this topic? One of my own research projects is looking at the synaptic learning rule, which is important for memory, in different oscillation states.

How are slow waves and REM brain oscillatory states generated?
Hopefully I have persuaded you that slow wave vs. REM brain states do make a difference. If so, the logical next step will be to learn how different brain oscillation states are generated, maintained, and switch between one another. Only after we understand these can we start to answer the theoretical and practical questions mentioned above.

Oscillation is everywhere-clock clicks, the light we see, the sound we hear, and even our daily life experiences are all oscillations. To me, the analogy of the ocean can still help to illustrate brain oscillation. Water and ice are both made of H2O but exist in two totally different states. The difference between liquid water and solid ice is determined by certain parameters, like temperature or pressure. When H2O is in the liquid state, like on the beach of Hawaii, crashing waves can be formed. However, on an ice cap in the Arctic, the ocean is covered by solid state H2O which only allows for small vibrations of the ice.

Now, the same brain consisting of the same cells can exist in different states, which are distinct like water and ice (both made of H2O). The basic building block of the brain is the neuron, which uses electrical and chemical signals to carry information. In each wave of slow-wave oscillation, neurons elevate their activities in a plateau form, termed the “UP” state. Just as water molecules influence nearby water with chemical forces, neurons can also change the activation level of other nearby neurons by specific connections called synapses. The waves can propagate across large regions of the brain by the collective action of many neurons through synapses. Following closely after the UP state, however, a silent phase follows, called the “DOWN” state. Each neuron only has about 20 millivolts (one thousandth of a volt) difference between UP and DOWN states. It may sound small, but because nearly all of the millions of neurons in brain take part in the oscillation between UP and DOWN states, the summation of the UP/DOWN states can be measured through the skull as EEG signals (with each state being very distinct from the other).

However, in REM sleep, all the neurons essentially stay in the same activation state, namely the UP state; one cannot find any large-scale propagation of activity or cycling between UP/DOWN states. There is still high frequency activity, usually in a local area, but this is drastically different from the global, synchronized slow-wave.

What state your brain is in largely depends on chemicals called “neurotransmitters” that are secreted by neurons. These neurotransmitters change the activity of neurons directly, and subsequently cause neurons to influence one another differently. A large amount of research has been published on this topic, so it would be difficult to provide a detailed background here. Instead I will provide an example of one informative study about the controlling of brain state, as I did for slow-wave oscillation and memory consolidation above.

The study was carried out by Lu, Sherman, Devor, and Saper at Harvard Medical School and Hebrew University in Israel. In 2006 they found a flip-flop switch in a brain region known as the brainstem, which lies near the back of the brain and just above the neck. The researchers found that there are two tightly coupled groups of neurons controlling the oscillations between slow-wave and REM sleep. They call them “REM-on” and “REM-off” areas. These two regions exert mostly inhibitory influence on one another. The REM-on area also contains excitatory neurons that influence other brain regions that regulate EEG of REM sleep, as well as brain regions controlling muscle activity during REM sleep. The mutually inhibitory interactions of the REM-on and REM-off areas may act like a flip-flop switch that sharpens state transitions.

Such a tight mutual control of REM-on/off areas is why the finding is so important. It means that even a tiny bit of imbalance between those two areas could switch the entire brain state from one to the other. Why slow-wave and REM? Why sleep at all?

Although we now know a lot about brain oscillation in sleep, pressing questions remain unanswered. In slow-wave sleep, most of the neurons will participate in the slow-wave oscillations. In REM sleep, most of the neurons stay in the UP state. But why? We don’t need to respond to the outside world during sleep, so why waste precious energy on an UP state? Furthermore, we all spend about one third of life asleep. Is it as big of a waste of time as it seems? Even worse, sleep seems to be dangerous since we are basically helpless to respond to threats, and when we lived in the wild, this could be fatal.

However, given all these hard questions, evolutionarily sleep is still conserved throughout the animal kingdom. So much so, that even a kind of earthworm (C. elegans) has been found to sleep from time to time. To me, sleep and the oscillation states must play important functions in the success of animals-we just need to find them! Memory consolidation is a good one, but we will need to know more in order to sleep without the guilt of wasting another night. Until that time, though, let’s continue to enjoy the comfort of a good night’s sleep.

Chengyu Li has a Ph.D. in neuroscience from the Institute of Neuroscience, Chinese Academy of Sciences, Shanghai. Li has done post doctorate work at the University of California, Berkeley, Howard Hughes Medical Institute. Li’s research is partly funded by Temporal Dynamic Learning Center (TDLC). Li’s main research interests are in synaptic plasticity, learning, memory, and brain states.