Can REM Sleep Protect You Against Traumatic Experiences?

Cat-nap. Flickr @Jon Brinn

Around one in twenty of us will receive a diagnosis of post-traumatic stress disorder (PTSD) over the course of our lives (Chapter 4). It involves nightmares, flashbacks, memory difficulties, avoidance and hypervigilance, and although not the only cause, sleep has been identified as a contributing factor in the development of these symptoms. This is where Itamar Lerner and colleagues at Rutgers University come in. In a series of studies, they have recently shed light on how REM sleep might play a protective role against PTSD.

REM, or rapid eye movement, is the final stage of our nightly sleep cycles and is associated with brain activity which resembles wakefulness. It has been associated with a range of important functions, including dreaming, but the one which is relevant here is its role in emotional memories. It has been shown that REM sleep is associated with reducing our brain’s response to emotional experiences in an adaptive way. The team at Rutgers University were particularly interested in examining how habitual levels of REM were associated with responses to fear-inducing situations.

To investigate this, they firstly asked participants to record their sleep at home for a week to assess their typical sleep patterns – particularly the amount of REM. The participants then had brain scans using functional magnetic resonance imaging to understand the brain’s response to a fearful situation. This ‘fearful situation’ was created by presenting participants with office scenes with a lamp in the centre – terrifying, I know. Importantly, the colour of the lamp signified whether the participants would receive a mild electric shock or not. Over many trials, the participants learned to associate certain lamp colours with a shock in what is known as a fear conditioning paradigm. This approach is useful for learning how fearful memories are learned, and unlearned, and has implications for anxiety and PTSD.

The team at Rutgers University were interested in whether the brain’s fear network (comprised of the amygdala, hippocampus and ventro-medial prefrontal cortex) was associated with the amount of REM sleep a participant had. They wanted to investigate whether the amount of REM sleep acted as a resilience factor against the fearful situations. Their hypothesis was that REM might be protective against brain activity associated with fearful situations (e.g. receiving a mild electric shock).

In the first study, they found that the average time spent in REM each night (or percentage of time in REM sleep) was correlated with brain activity in the regions associated with fear processing. More specifically, the less REM participants had the stronger this neural network responded to a fearful situation. This, the authors claim, has a clear link to development of PTSD where there is an enhanced and persistent brain response to a traumatic, fearful, situation.

Lerner replicated this finding in a second study which also found that reduced REM sleep was associated with increased amygdala activity and reduced hippocampus and ventro-medial prefrontal cortex activation. Cumulatively, this suggested that REM was associated with how reactive this brain network, linked to fear, was when presented with a fear-inducing situation. Interestingly, these findings were not found when REM data was recorded from only a single night. This suggests that the amount of REM an individual typically gets is more informative for this relationship and it also hints at a potential risk factor for processing memories in a traumatic way.

Together these studies have some interesting implications. If it is possible to identify those who are more likely to show increased fear-network activation following a trauma then might this identify these as candidates for exemption from certain jobs?

This is exactly what Itamer Lerner suggests might be the implication of such research, “For example, when screening individuals enlisting to the army, recruiting to combat units only those with naturally high REM sleep”. Of course, further research is needed before we can be sure that REM is protective against the development of PTSD. This research is somewhat artificial currently. Lerner suggests that “one natural next step would be a longitudinal large study to try and establish a direct link between baseline REM sleep and PTSD.” He goes on to say that “measuring sleep in at-risk populations and then monitoring their anxiety levels, any traumatic events they may have experienced and whether they receive a PTSD diagnosis, for 2-3 years” would be a useful next step. This would allow us to say, with more confidence, that the amount of REM can differentiate between those with or without a diagnosis of PTSD.

Nonetheless, this collection of studies is a great first step towards understanding how REM sleep might be linked to how we process traumatic episodes. Although we are still far off implementing this in areas where traumatic experiences are commonplace, it does lend support to the role of REM in PTSD. For now, it’s worth remembering that quality sleep is beneficial for a number of psychiatric illnesses beyond PTSD and REM sleep will likely be involved in a wide range of disorders where mood is affected. As should be fairly apparent at this point, sleep is something none of us can skimp on.

Inquisitive Tortoise

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Reference

Lerner, I., Lupkin, S. M., Sinha, N., Tsai, A., & Gluck, M. A. (2017). Baseline Levels of Rapid Eye Movement Sleep May Protect Against Excessive Activity in Fear-Related Neural Circuitry. Journal of Neuroscience, 37(46), 11233-11244.

Trauma, Tetris and Memory: A Cheap Way to Reduce the Impact of Intrusive Memories

What if I was to tell you that playing video games can be good for you? That despite derision and their use in political point scoring, games such as Tetris and Candy Crush could one day be used to help people deal with traumatic events in their lives? You might be initially sceptical but there is growing evidence to support this. Although not a new idea, Tetris has been shown to be useful in reducing the uncontrollable intrusions associated with a traumatic experience.

So, how can we use a video game such as Tetris to interfere with traumatic memories? Well, in much the same way that you would interfere with any memory. As you create a new memory and have converted all the constituent parts into a form which the brain can understand, it goes through a period of consolidation. That is where the memory is stored within your brain so you are able to recall it at a later point. Now if we interfere with the memory during this period of consolidation it is less likely that we will recall said memory. For example, if we can provide some competition for the neural real estate the original memory is vying for then we can weaken the strength of that original memory. It seems to be important that the type of memory is relatively specific and needs to match the original memory’s modality (e.g. a visual-spatial task needs another visual-spatial task to compete with it effectively). This is essentially where Tetris comes in. The authors argued that if both the trauma memory and Tetris rely on the same visual-spatial resources then you can reduce the intrusiveness of the initial trauma memory.

This is exactly what Emily Holmes at the University of Oxford and her collaborators found in studies conducted over the past eight years. If you ask a participant to play Tetris 30 minutes after a lab-controlled trauma induction you can reduce the impact of the traumatic memory compared to a control condition. These early studies showed that, at least in the lab, you could interfere with traumatic memories in a therapeutic way by reducing their intrusive nature. Although they were not carried out in a naturalistic setting they provided evidence that the proposed mechanism existed and could be manipulated. It is also key to keep in mind that this study showed that playing Tetris reduced specifically the intrusiveness of the traumatic memories and not the deliberate recall memory for the event. As the uncontrollable nature of the traumatic memory is a source of considerable distress in PTSD it is important that any intervention can have a targeted effect. What about evidence for the use of Tetris to deal with naturally occurring trauma outside of the lab? This is where their latest study, published in Molecular Psychiatry, last week comes into play (it’s open access so you can read the full article yourself here).

In a small-scale naturalistic study in Oxford, Emily Holmes, and colleagues at the Karolinska Institute in Sweden, examined individuals in A&E who had recently (within 6 hours) experienced a motor accident as a driver, passenger or pedestrian.  They randomised 71 eligible participants to either an intervention or control condition to test the real-life application of their previous findings. In the intervention condition, participants were asked to recall the traumatic event initially and to then spend at least 10 minutes (maximum 20 minutes) playing Tetris. By contrast, the control condition asked participants to write down all the activities they carried out during their time in A&E (e.g. completing a crossword, speaking to a friend, etc.). Participants were assessed at one week and one month following either the control or intervention task. During the initial week participants were required to complete a daily diary of the number of intrusive memories they experienced which were related to the trauma (e.g. motor accident). The participants were instructed not to report “memories recalled deliberately or general verbal thoughts”. The number of intrusions provided a primary way to assess the success of the use of the intervention (memory cue and Tetris).

So, what did the researchers find? Primarily, they showed that the use of Tetris and memory recall was an effective intervention. The number of intrusions was significantly reduced in the intervention group after one week (9 intrusions on average) compared to the control condition (23 intrusions on average). Furthermore, they also found that the intervention group also reported significantly less distress after one week. However, this reduction in distress did not remain when participants were followed up after one month. To supplement this data, the authors also asked the participants about their subjective experience of using the intervention. Their reports were positive and it was apparent that they appreciated the distraction from the accident which playing Tetris offered. One participant highlighted this clearly with, “it certainly took my mind off of it at a time when I probably would have sat brooding and feeling very sorry for myself…”. Another participant, who had not played Tetris before, was keen to keep playing it following the allotted 20 minutes. The intervention thus proved to be both feasible and acceptable.

Together, these findings support the usefulness and viability of using Tetris to combat intrusive traumatic memories in a real-life setting. The reduction in the number of intrusions following a natural traumatic event (e.g. motor accident) supports the intervention and suggests it could be a low-cost, easy to administer, therapy. As the authors highlight in the paper, waiting times in A&E can be as long as 4 hours and this would be an ideal time to target individuals who have experienced a traumatic accident. As a well-tolerated, and simple, intervention it seems ideal. However, this study is simply the beginning of translating Tetris, or similar aproaches, into the realms of clinical practice. Although this trial did not show an effect on distress at a one month follow-up, a larger trial may be better suited to pick out subtle effects for longer periods of time. Furthermore, additional doses of the intervention may also prove effective as a ‘booster’ to the initial dose. As any good piece of research, this trial raises more questions and exciting avenues for further study.

Alongside the compelling results, why should we be so excited about this research? It provides clear evidence that marrying cognitive neuroscience and clinical practice are vital for progress in both fields. It is still early days for this collaborative approach but hopefully this soon blossoms into a powerful and fruitful relationship. Basic science studies can be blamed for being too distant from the disorders and clinical fields they are trying to unpick and affect. However, with a greater understanding of the mechanisms at work behind mental distress we can develop novel therapies, like the use of Tetris, to target them and help real people. Personally, that is one of the amazing things about research and one of the reasons why I fell in love with science in the first place. More work is needed to validate these findings but, at least for the time being, they provide you with a great retort to anyone who claims video games are good for nothing. To quote Emily Holmes’ original Tetris paper in 2009, “…clearly not all computer games are bad for you.”

Iyadurai, L., Blackwell, S., Meiser-Stedman, R., Watson, P., Bonsall, M., Geddes, J., Nobre, A., & Holmes, E. (2017). Preventing intrusive memories after trauma via a brief intervention involving Tetris computer game play in the emergency department: a proof-of-concept randomized controlled trial Molecular Psychiatry DOI: 10.1038/mp.2017.23

Additional References:

Holmes, E. A., James, E. L., Coode-Bate, T., & Deeprose, C. (2009). Can playing the computer game “Tetris” reduce the build-up of flashbacks for trauma? A proposal from cognitive science. PloS one, 4(1), e4153.
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Tetris (Header)

Tetris Building (Body)

Sleep’s Positive Impact on Traumatic Memories

Sleep is inescapable. Some will see it as a necessary evil and others will claw at it with limited success. It may leave us (largely) immobile but it is anything but a passive state. Sleep paves the way for new neural connections to be made, clears the brain of harmful waste products, is protective against mental and physical illness, and is preferable to leaving the bed on a cold Monday morning. There is still plenty of debate as to the true function of sleep, but one key area which it appears to be important for is memory.

Broadly speaking, it is argued that sleep enhances the consolidation of recently learned information compared to wakefulness. For example, a nap as short as 5-10 minutes has been shown to enhance memory and improve problem solving compared to wakefulness following learning. Moreover, rapid eye movement sleep has been linked to enhanced memory for emotional information, and to reducing the emotional strength of such memories. This suggests that different aspects of sleep are important for different types of memories and highlights some potential ways we can modify the impact of negative ones. What if we could interfere with the brain’s ability to form negative memories? More specifically, what if we could interfere with traumatic and intrusive memories which form the basis of illnesses such as post-traumatic stress disorder (PTSD)? Recent research seems to suggest this may be possible.

PTSD is a psychiatric disorder characterised by flashbacks and nightmares, avoidance of the situation in which the trauma occurred, and emotional numbing. It is the result of a traumatic event which can be wide in scope (e.g. warfare, sexual abuse, hospital admission) and individuals with PTSD will often find themselves transported back to the event. These ‘memories’ are intrusive in nature and, understandably, highly distressing. It has been suggested that interfering with the consolidation of intrusive memories at the time they are formed (or shortly afterwards) may help those who are likely to go on to experience PTSD. Evidence to support this would unlock a powerful early intervention tool for those likely to experience trauma (e.g. refugees or soldiers). One way this can be achieved, as you have likely guessed, is through manipulating sleep.

In 2015, a study conducted at the University of Oxford explored whether sleep deprivation might be protective against intrusive traumatic memories. Participants were brought into the laboratory and randomised to either a sleep deprivation or sleep group. They were then shown a film containing traumatic scenes which lasted just over 15 minutes. Following the film, participants were either kept awake or allowed to sleep. On the following day, participants completed a questionnaire measure of PTSD symptomology and were then asked to complete a diary to track the intrusiveness, content, distress, and presence of mental imagery associated with the traumatic film for 6 days.

The Oxford group, led by Dr. Kate Porcheret, found that a night of sleep deprivation, compared to sleep as normal, reduced the intrusiveness of experimental-trauma memories. The sleep deprivation group reported fewer intrusive memories, lower PTSD symptoms scores, and (non-significantly) reduced distress of the intrusive memories. However, this effect was only found for the first two days and sleep deprivation was found to confer no protection against intrusive memories after 6 days. This suggests that sleep deprivation immediately after the traumatic experience can reduce its intrusiveness but only in the short term. Sorted. Sleep deprivation, paradoxically, confers some protective against traumatic memories. Right? Well, to quote Ben Goldacre, “I think you’ll find it’s a bit more complicated than that”.

A study published last December in the aptly named journal SLEEP has injected additional complexity to this issue. Dr. Birgit Kleim and colleagues assessed the impact of a single night of sleep deprivation on distress and intrusiveness of traumatic memories for seven, rather than six, days. They asked 65 female participants to watch two 12 minute films of a neutral (nature documentary) or traumatic (horror film) nature in a randomised order. Participants were either allowed to sleep at home or kept awake. They were then asked to keep an intrusion diary which required participants to note when they experienced intrusive memories related to the film and rate their vividness, intrusiveness, content, and distress each day. The participants were then followed-up a week later.

So, what did they find? For the first two days following the films, there was no significant difference between the sleep or wake groups on distress or intrusiveness of the traumatic film. However, by days 6 and 7 there was a significant reduction in distress and intrusiveness for the sleep compared to wake group. By contrast, there were no difference in intrusiveness or distress of the neutral film for the sleep and wake groups. The effects found were specific for the traumatic, emotional, memory.

This second study showed that sleep deprivation does not provide a protective effect against intrusive emotional memories. Instead, they argued that sleep immediately following the trauma experience has long-term benefits on reducing the distress and intrusions associated with the traumatic memory. Nonetheless, this study does not directly contradict the one conducted by Porcheret and colleagues at Oxford. Although non-significant, distress was higher for the sleep compared to sleep deprivation group which suggests that sleep deprivation may serve an immediate protective role against traumatic memories. However, this effect seems to reverse in the relative long-term.

Why should this be so? Well, we know that memories – particularly emotional ones – are strengthened by a period of sleep. This would suggest that sleep following a traumatic experience would strengthen the memory for that experience and thus enhance the intrusiveness of a traumatic memory. This could explain why sleep deprivation produced a reduction in intrusiveness and distress for the Oxford study as the lack of sleep interfered with the ability to lay down the negative memory. However, the explanation for these studies is less clear. The authors argue that sleep deprivation is protective against intrusive memories in the short term but not the long-term. Kleim and colleagues claim that sleep following the traumatic experience may initially make it more distressing but also encourage appropriate integration of the memory alongside existing memories. This, they argue, reduces the chance that the traumatic memory will be intrusive and uncontrollable – a cardinal symptom of PTSD.

We already know that rapid eye movement sleep (REM) is associated with a reduction in the intensity of emotional images (van der Helm et al., 2011). Kleim’s study found that increased REM was associated with more, not less, intrusions. Instead, they argue that other stages of sleep are responsible for the reduction in distress and intrusions seen perhaps through a different mechanism. However, this does not state that the memory should be remembered more poorly (i.e. deliberate recall of the film would be unaffected). Rather it seems that deliberate memory recall and intrusive memories may be guided by different mechanisms and differentially affected by sleep. Neither the Porcheret or Kleim study asked participants to take a memory test of their explicit recall of the films. However, the diary studies suggest that all participants were accurate in recalling the films throughout the study period and deliberate recall does not appear to be associated with intrusive memory frequency.

A similar distinction between intrusive and deliberate recall of memories was found by another study attempting to reduce the negative impact of traumatic memories. Indeed, these are the not the first studies which have attempted to interfere with the consolidation of traumatic memories. A more colourful way of achieving this has been shown through getting people to play Tetris. For the uninitiated, Tetris is a simple game whereby you match coloured bricks of different shapes into lines of 4. They fall from the top of the screen and you have to rotate the shapes to make them line-up and disappear. In 2009, Dr Emily Holmes and colleagues at the University of Oxford showed that if they got participants to play Tetris for 10 minutes, half an hour after a traumatic film, they saw a reduction in subsequent intrusions or “flashbacks”. This effect was found for over a week follow-up during which an intrusion diary was kept. Interestingly, deliberate recall of the film was not impaired when tested at one-week follow-up. This also suggests it is possible to reduce the intrusive nature of a traumatic memory without reducing the memory for the event.

Of course, it is difficult to get someone in a warzone to take out their Tetris ration or take a nap following a fire-fight, but it highlights that it is possible to reduce the negative impact of traumatic memories. These pieces of research suggest that manipulating sleep is a viable way to reduce the ‘flashback’ quality of traumatic memories. Although promoting sleep for those having recently experienced a traumatic episode might raise its own difficulties, it heralds a step towards early intervention for PTSD. If nothing else, they remind us that sleep is important for the consolidation of memory alongside existing memory networks and how little we know about the effect of sleep on memory.

One thing we do know for sure: sleep is anything but a passive and simple state.

Inquisitive Tortoise

References:

Holmes, E. A., James, E. L., Coode-Bate, T., & Deeprose, C. (2009). Can playing the computer game “Tetris” reduce the build-up of flashbacks for trauma? A proposal from cognitive science. PloS one, 4(1), e4153.

Kleim, B., Wysokowsky, J., Schmid, N., Seifritz, E., & Rasch, B. (2016). Effects of Sleep After Experimental Trauma on Intrusive Emotional Memories. Sleep.

Porcheret, K., Holmes, E. A., Goodwin, G. M., Foster, R. G., & Wulff, K. (2015). Psychological effect of an analogue traumatic event reduced by sleep deprivation. SLEEP, 38(7).

van der Helm, E., Yao, J., Dutt, S., Rao, V., Saletin, J. M., & Walker, M. P. (2011). REM sleep depotentiates amygdala activity to previous emotional experiences. Current Biology, 21(23), 2029-2032.

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Bad Memory (Header)