Sunday, July 22, 2018

The Brain during 24 hours: Waking, NREM and REM sleep

(This blog post is written, based on the special presentation lecture at ParkJaSe on the 19th of March, 2017. See the video footage here. I also used relevant pages (Chapter 9) of Dr Park's book and Wikipedia)

  1. Introduction
  2. The cycle of waking, NREM and REM
  3. Change in brain waves in 24 hours
  4. The mechanism of waking, NREM and REM
    1. simplified model of the brain
    2. Change in brain activity
    3. Inhibition and excitation between TC, CT and RE
    4. Encoding and Consolidating Memory
    5. Effect of neurotransmitters
    6. Conclusion
    1. Introduction

    In 24 hours, we are in three states: awake, NREM sleep or REM sleep. This blog post will explain the differences between them - when they appear, the difference in brain waves, their role in memory storage, changes in brain activity, and changes in neurotransmitters.
      2. The cycle of waking, NREM and REM

      The diagram shows the stages of an average night's sleep cycle. The very top line is the waking state, and descends into a deeper sleep, in stages of 1 to 4. The red lines show REM sleep, and stages 1,2,3,4 are non-REM sleep. Stages 3 and 4 are called slow wave sleep.

      Usually, we go through the four stages of NREM sleep, then go through the stages in reverse to REM sleep, until we are awoken. REM sleep increases in duration, while the 4th stage sleep gets shorter until they don't appear at all. REM repeats in a cycle of 90 minutes. 

      We have 80% of our dreams during REM sleep. The remaining 20% are NREM dreams (during slow-wave sleep). We have an average of 5 dreams during a single REM stage, so we dream an average of 25 dreams in total every day. But we don't remember most of our dreams (see the neurotransmitters section to know why).

      REM dreams are characterized by vivid visual imagery (due to ACh and the activity of the visual association area) and full of surprising and unexpected occurrences. By contrast, NREM dreams tend to have repetitive visual imagery have no story.

      3. Change in brain waves in 24 hours

      There are 5 different types of brain waves which appear in different states of the brain. They are, in order of lowest to highest frequency, delta (less than 3Hz), theta (3-7Hz), alpha (8-12Hz), beta (13-30Hz) and gamma (30-90Hz). 

      The diagrams of brain waves below are labelled according to which stage of sleep it corresponds to (The same waves are drawn in miniature at each stage of the very first diagram).

      When waking, the brain usually shows alpha and beta waves, so the waves have low amplitudes and relatively high frequencies. 

      REM sleep also shows low amplitude and high-frequency waves. The waves include theta (θ) waves. 

      On the other hand, NREM sleep generally has higher amplitudes and low frequencies. The first stage of NREM still has theta waves, but in the second stage of NREM, we have two types of waves called sleep spindle (2.5 waves per minute) and the K-complex (1 wave per minute). The third and fourth stages of NREM are called SWS (slow-wave sleep) stages because their brain waves are low-frequency. They both have delta waves - the third stage has delta waves about 20-50% and the fourth stage about 50%.

      4. The mechanism of waking, NREM and REM

      4.1 Simplified model of the brain

      This diagram shows the neocortex as a ring, the hippocampus as a blue-shaded hook at the right end of the neocortex, and the thalamus as a circle on the top of the spinal cord (represented as a rectangle). The hippocampus is hooked because it was an ancient brain area called paleopallium that was pushed out to the side by the evolution of the neocortex. Further, there are four specific areas and nuclei: the CT (corticothalamic), TC (thalamocortical), RE (thalamic reticular nucleus) and RF (reticular formation).

      Below shows the simplified models of the brain for waking, NREM and REM

      The diagrams show four things. 

      4.2 Change in brain activity

      First, they show how brain activity differs for each state.

      What happens when we are awake (far left)? Many areas of the cortex are activated, and they work together to function properly. The red dots show areas where the cortex is activated and the blue arrows signify that each of these areas is sending signals to each other to collaborate effectively. The RF (reticular formation) connects to the neocortex with neurotransmitters like ACh, NE, 5HT. This long-range connection causes cortex arousal - unlike the other two states, the brain is functioning fully.

      Compare this to Non-REM sleep. This is a part of the sleep cycle in which we have basically little dreams (about 20%), and the activity in pyrimidine is low, reduced as much as 30%. So this is the part where the brain rests from working. Notice how the red dots of active neurons are tiny and separate.

      The REM sleep is actually really interesting because it's so similar to the waking state. The red activated parts are the same as a waking state - so this is the part of sleep where the body, not the brain, rests from working. The brain is dreaming. But notice that each area of the activated regions is closed off, and not communicating with other areas. In addition, the connection between the hippocampus and neocortex is broken off. Thus the neocortex is forced to link random memories together. This is why two different dreams often don't fit together. BUT, neurons within each area can interact with one another, which is why each individual dream makes a logical story.

      4.3 Inhibition and excitation between TC, CT and RE

      Second, the diagrams show how specific areas of the brain excite or inhibit each other to create NREM wave oscillations - namely, the sleep spindle and delta wave. This is a simplified diagram of the areas, CT, RE and TC. These areas are linked:

      The diagram on the left shows the three areas of the brain connected to each other: RE (thalamic reticular nucleus), CT (corticothalamic neuron) and TC (thalamocortical neuron). The synapses spray neurotransmitters - either Glutamate for excitation or GABA for inhibition. The V-shaped synapses symbolize excitatory synapses, and the T-shaped synapse symbolizes inhibitory synapses.

      The diagram on the right is a simplified version of the left diagram which shows how they excite and inhibit each other. The TC is an excitatory neuron to the CT. The CT neuron excites the TC neuron in turn. These TC-CT and CT-TC excitatory circuits are controlled by the RE, which inhibits the circuit. A simple diagram of an RE neuron inhibiting a TC neuron is shown below.

      The GABA neurotransmitter is responsible for inhibiting neuron activity. When an electrical impulse reaches the synapse, the chloride ions (Cl-) enter the TC cell. 

      The sleep spindle is the circuit during the 2nd stage of non-REM sleep, and the delta wave shows the circuit during the 3rd and 4th stages of non-REM sleep. So this is another way to see the brain waves described earlier.

      The above diagram uses brain waves to prove that the RE inhibits the TC. When the TC and RE were separated, the TC did not release the sleep spindle but the RE did. This shows that the RE is the initiator of changing brain waves during SWS - the RE still sent signals even if the TC was eliminated, but not vice versa. 

      During slow wave sleep (SWS), the TC decreases in amplitude when RE's increases, and increases in amplitude when the RE's decreases. This is due to the GABA neurotransmitter which inhibits neuron activity in the TC. This inhibition of TC waves by RE is called IPCP. And since TC excites CT, the CT brain waves is similar to that of TC.

      4.4 Encoding and Consolidating Memory

      During the day, we pay attention to novel and important (salient) things - these are stored temporarily in the hippocampus as memories. i.e. we encode memories from the neocortex to the hippocampus. The hippocampus is the part of the brain which controls memory - it stores memories temporarily during the day.

      Memory is transmitted for long-term storage from the hippocampus to the neocortex during NREM, especially during slow-wave sleep. The transmission is done by the interaction between the SPW-R, sleep spindle and delta waves. The sleep spindle (from the inhibition of TC by RE), delta waves (from the circuit between TC and CT), and the SPW-R wave (emitted from the hippocampus) appear. In NREM the three waves move in sync with each other. The thalamus and cortex are in oscillation mode. A single pulse in the hippocampus corresponds to a tenth of a single wave of RE.

      During REM sleep, memory consolidation occurs - this stabilizes the memory to prepare it for long-term storage.

      4.5 Effect of neurotransmitters

      Fourth, they show the difference in neurotransmitters from RF during the three stages.

      During the waking state, neurotransmitters like ACh, NE, and 5HT are firing as normal. But in REM sleep, ACh is doubled while NE and 5HT are turned off. The diagram below shows this in greater detail.

      The table above shows the change in various neurotransmitters during sleep. The left column shows the neurotransmitters, ACh (acetylcholine), NE (norepinephrine), 5HT (serotonin) and DA (dopamine). The last row, cortical connection, shows how far messages between areas of the brain travel, which was discussed when talking about the connection between activated regions before. The dotted arrows mean that the amount of the neurotransmitter is reduced, while the number of arrows indicates the relative amount of neurotransmitter (e.g. two arrows mean twice the amount).

      When awake, we have ordinary levels of all these hormones to function in everyday life. 

      In NREM sleep, the brain is resting and there are lower levels of these neurotransmitters firing overall.

      REM sleep's neurotransmitter firing is interesting because they give us insight into why dreams are so strange. Dreams are vivid, unpredictable, illogical, and is usually forgotten the moment we wake up. Some neurotransmitters - especially NE and Ach - are responsible for these phenomena.

      NE (norepinephrine), the neurotransmitter responsible for bringing about focused attention, is inhibited in REM sleep. To remember something, we have to focus our attention on it, and if we don't pay attention, like in REM sleep, we forget everything that happens. This is why we forget our dreams even though we have many in a night's sleep. It is also closely linked to consciousness, which is why we have no consciousness in sleep.

      Ach (acetylcholine), is responsible for connecting vivid visual imagery. In REM sleep, ACh is fired at twice the amount of the waking state. So that's why dreams are full of vivid imagery.

      REM-ON cells produce acetylcholine at the pedunculopontine tegmental nucleus and lateral dorsal tegmentum nucleus. Acetylcholine enhances memory connection.

      REM-OFF cells produce norepinephrine at the locus ceruleus. Norepinephrine is responsible for concentration and attention. NE disappears in REM, so concentration and attention disappears.

      5. Conclusion

      This blog post described the waking, NREM and REM state with brain waves, TC, CT, RE, RF, Hippocampus, memory consolidation and neurotransmitters. This framework is an important initial gateway for understanding important neuroscience concepts like sensation, perception, memory encoding, consolidation, language, goal-oriented thinking, meditation, ion channel, neurotransmitters, brain waves and so on. I will go into many of these concepts explored here in greater detail in later posts.

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