Summary of CMS Seminar Club presentation on Friday, August 25, 2023
Title: The mechanistic role of sleep in fear processes underlying PTSD and anxiety disorders
Speaker: Prof. Sean P.A. Drummond, Ph.D., Professor of Clinical Neurosciences, Turner Institute for Brain and Mental Health, and Director of the Research Programs and Infrastructure, both at the School of Psychological Sciences, Monash University, Clayton, Melbourne, Australia.
On Friday, August 25, Prof. Drummond gave a presentation at Fujita Health University. He told us about sleep in general, and about his experiments that showed how good or poor sleep can affect how we deal with fear.
Recording: For members of Fujita University, a recording of the meeting (without the discussion part) will be available at our Manabi system. Unfortunately, we cannot open the recording for a wider audience.
There were 25 participants. Dr. Carolien de Kovel (whom I consider to be supersmart) wrote to me that she found it a very interesting and well-explained story, and that it was “Mooi onderzoek!” which is Dutch for “Nice study!” It was also nice that a graduate student summarizing the event wrote “From the question-and-answer period we learned lots of practical points to improve the quality of our sleep.”
Personally, I found the part on sleep in general very interesting and easy to follow, whereas the explanation of his own experiments was more difficult. It is always hard, from an oral presentation, to follow a set of positive and negative loops, and expressions as “fear conditioning” and “fear extinction” also need getting used to. However, seeing the recording of the presentation, I realized that also in this part of the talk Prof. Drummond explained everything very well and truly enjoyed it. I strongly recommend those with a general interest in sleep to watch the first part of the recording, and those with an interest in his experiments on sleep and fear to also watch the second part.
There probably were four major takeaways from the presentation and the ensuing discussion:
- Good quality sleep is important for our mental health, including for losing unreasonable fears.
- Especially good quality REM-sleep is important for a healthy way of dealing with fears.
- Good quality sleep cannot be induced by medication/drugs.
- An existing hypothesis that sleep deprivation after a traumatic event may reduce the development of PTSD (post-traumatic stress disorder) because of a reduction in memorization of the event (memorization is one of the functions of sleep) is probably not true.
I feel privileged that we could discuss such an important topic as sleep with such an expert as Prof. Drummond.
(The header image at the top of this post is of the pond Nigori ike, next to Fujita Health University, in the early night)
THE CONTENTS OF THE PRESENTATION
The below only describes a summary and selection of the topics presented by Prof. Drummond.
What is Sleep? (a general introduction)
Sleep is a biological function which is controlled by a set of physiological factors dependent on the amount of sleep we got (such as hunger is dependent on how much we eat) and a roughly 24-h-period-calibrated biological clock (“circadian rhythm”). Sleep is used for enhanced cleaning of the brain (the glymphatic system removes waste products) and for consolidating, removing, and/or modifying of information previously obtained (what and how to remember). Sleep is not a single state but, based on brain activity, can be divided into several states that occur multiple times during a single sleep period. Different sleeping states are REM-sleep–a time of dreaming and Rapid Eye Movements–and Non-REM sleep, which can be divided into levels of superficial to deep sleep from N1 to N3; the N3 state can be further divided into Slow Wave Sleep (SWS) and Deep sleep (Fig. 1). All states have some function in memorizing, but especially REM-sleep is thought to be important for the processing of emotions.
Figure 2 shows examples of the difference in sleep state sequences in a healthy person and a person suffering from insomnia (the inability to sleep properly), the latter person often waking up during the sleep and having little REM-sleep. Sleeping disorders, especially those with reduced REM-sleep, strongly predict a large number of mental disorders (Fig. 3), including the tendency for suicide, and it is cruel that those most in need of an appeasing sleep often don’t get one.
Babies sleep the most, after which the time of sleep decreases to adulthood, from which on it roughly stays the same. Different in the elderly though is that their night sleep tends to become shorter but that they like little naps during the day (because their circadian rhythm changes), keeping the total amount of sleep similar. From the age of 5, the amount of REM-sleep is not very different between the age categories, but children have a larger proportion of SWS sleep – believed to help them with learning new things – and when adults get older they experience a gradual increase in the time that they are awake during a sleeping session after already having fallen asleep.
In the discussion after the presentation, Prof. Drummond agreed that considering the ever-increasing age of the workforce, from biological point of view it may be worthwhile to introduce “nap-times” for the elderly at work.
Sleep and Fear Processes
As explained above, sleep is important for how we memorize things, including the emotions associated with it. This chapter describes the experiments performed by Prof. Drummond and his group to find out if sleep deprivation causes differences in “fear conditioning” (learning that a signal expresses danger) and “fear inhibition” (learning new safety signals and/or “fear extinction” meaning the learning that a signal no longer expresses danger).
[To give a personal example of how fear extinction is important. I once had a small accident in traffic by a car hitting my bicycle while I was riding it (he was wrong but fled and got caught by the police as cars have number plates). Until a few weeks after, often when I was riding my bicycle and saw cars coming, my whole body felt the exact same feeling again as when hit by that car. I am glad that my “biological me” learned after a few weeks that cars are not dangerous, but I got a glimpse of what people with much more severe traumas may go through.]
The Experiment: The experiments were as described by Prof. Drummond in Marshall et al. 2014 and Straus et al. 2017, which for convenience are summarized together here. Basically, volunteers learned/experienced (Fig. 4):
On Day 1:
- that a blue signal resulted in a small electric shock (fear/danger learning)
- that a yellow signal did not result in a small electric shock (safety learning)
On Day 2:
- that a blue signal was not associated with a small electric shock anymore (fear extinction learning)
- that a yellow signal did not result in a small electric shock (safety recall learning)
On Day 3:
- that a blue signal was again not associated with a small electric shock (fear learning from Day 1 or fear extinction learning from Day 2?)
- that a yellow signal did not result in a small electric shock (safety recall)
The fear responses in the volunteers were measured by eyeblink magnitude. The factors different between the three types of volunteer groups were a normal sleep versus total sleep deprivation (TSD; for 36 h) during either the night from Day 1 to Day 2 or from Day 2 to Day 3, or a good sleep during both nights (Fig. 4). Apart from the fear responses induced by the blue or yellow signals, also the REM-sleep was quantified.
The Results:
The experiments revealed the following:
- Compared to the REM-sleep of the volunteers before the start of the experiment, the REM-sleep during the night from Day 1 to Day 2 (Night 1) became poorer. The volunteers who were best in learning safety signals during day 1 had the best REM-sleep during Night 1.
- The volunteers with the best quality REM-sleep during Night 1 showed the highest ability to distinguish between danger (blue) and safety (yellow) signals on Day 2.
- Sleep deprivation during Night 1 does not interfere with the ability on Day 2 to remember the danger of the blue signal at the beginning of the day (because remembering the shocks on Day 1) and to gradually learn on Day 2 that the blue signal no longer represented danger (fear extinction).
- However, and that was a surprise, these “TSD-Sleep group” volunteers, who had been sleep-deprived in Night 1, were more afraid of the blue signal on Day 3 than the other volunteers, meaning that they were poorer in remembering what they had learned on Day 2 (the fear extinction during Day 2 had not consolidated).
- These TSD-Sleep volunteers had an unusual deep sleep in Night 2, with a lot of deep SWS sleep, which reduced the quality of REM-sleep, and this may explain the observation in (4).
Discussion/Conclusion:
The above listed result (3) is quite important in regard to a controversial hypothesis that says that total sleep deprivation might prevent memory consolidation after a traumatic event and so help to prevent post traumatic stress disorder (PTSD). Namely, the results by Prof. Drummond do not agree at all with that hypothesis, and he stressed that the overall finding is that a good REM-sleep is important for healthy fear processing.
The above results 4 and 5 indicate that that good REM-sleep is necessary to properly consolidate fear extinction memory and the learning of safety signals. This suggests that patients with fear disorders should try to get proper REM-sleep.
By other researchers, in animal models, after fear conditioning (learning danger), REM-sleep was found to be shortened and fragmented. Furthermore, when the REM-sleep was experimentally interrupted, the fear extinction was impaired (thus the animal needed a good REM-sleep for rapid learning that a signal no longer expressed danger). Prof. Drummond said that, according to his experiments, REM-sleep appears also to be of major importance for fear processing in humans, but that his experiments predominantly found an effect on the learning of safety signals. He added though that, possibly, higher levels of danger than small electric shocks might have also found an association with danger signal learning.
Does REM-sleep also play a role in fear processing in PTSD patients?
PTSD, in regard to sleep, is characterized by increased insomnia and nightmares after trauma. PTSD is also associated with defects in fear processing, namely by an increase in fear conditioning and a decrease in fear inhibition (thus, PTSD patients experience unreasonable fear). Professor Drummond’s above-described experimental data could be very important for PTSD patients, but he wanted to be sure that the principles deduced by his experiments also apply to them. Therefore, he investigated a small set of army veterans with PTSD. Overall, he could replicate the observations in this group, finding that a good REM-sleep was associated with a better learning and memorizing (recall) of safety signals.
The important message by Professor Drummond was that good sleep, and particularly good REM-sleep, is important for our mental health and the proper dealing with fear. Unfortunately, as he explained during the discussion, there is still no medication/drug available to achieve this conveniently, so there is still a lot to be researched.
