Quora: Is there proof that slow wave sleep is beneficial?

There have been some studies that attempted to interfere with slow wave sleep while keeping other sleep parameters intact, e.g. sleep duration, REM-sleep, stage 1-2 sleep duration, nocturnal awakenings… Such studies have revealed the importance of slow wave sleep (or at least a complete undisrupted sleep cycle consisting of the different sleep stages including REM and slow wave sleep) for certain memory functions. In addition memory reactivation (or memory replay) as seen during slow wave sleep provides additional evidence for the importance of slow wave sleep in memory consolidation.

An example of a study manipulating one parameter of sleep (i.e. amount of slow wave sleep) while keeping other sleep parameters intact, is an acoustic perturbation experiment conducted in humans [1]. When slow waves were detected an acoustic stimulus was presented, gradually increasing in volume until stage 1-2 sleep was reached and acoustic perturbation was terminated, thus preventing the subject from awakening. Although sleep duration was maintained, as well as the amount of REM-sleep and the number of sleep state transitions, performance on a visual memory encoding task was negatively affected (this task consisted of responding with either ‘yes’ or ‘no’ if a presented image was previously seen in an initial set of 50 images).

Neuroimaging data revealed that during encoding of items that were later recalled successfully, the right anterior hippocampus had lower encoding-related activation following shallow sleep as opposed to normal sleep (see figure). Thus slow-wave sleep interferes with hippocampal functioning and can affect tasks that rely heavily on this brain structure (such as the visual memory encoding task).

As divergent evidence van der Werf et al. (2009) show that performance wasn’t affected on an implicit procedural learning task (a 4-choice serial reaction time task [2]), a task that doesn’t rely on hippocampal function.

Memory reactivation, or so called memory replay, is another phenomenon seen during slow wave sleep, that provides evidence of the importance of this sleep stage in memory consolidation. The figure below (Wilson et al., 1994 [3]) reveals how place cells (as presented by the individual dots in the circle; http://en.wikipedia.org/wiki/Place_cell) that fired together (synchronised activity) during a spatial behavioral task in rats (“run”-phase), also had an increased tendency to fire together during subsequent slow wave sleep (“post”-phase), while this was not the case during slow wave sleep preceding the spatial task (“pre”-phase).

Although I have given some examples of the importance of slow wave sleep, some conceptual frameworks [4] emphasize the complementary or sequential contributions of slow wave sleep and REM-sleep to memory consolidation, and thus the individual sleep cycles and NREM-REM sleep transitions as such to be of importance. So although slow wave sleep has been shown to have a vital function in memory consolidation, this should be seen in the context of the sleep architecture as a whole, as well as individual sleep characteristics/parameters (e.g. hippocampal sharp waves/ripples) that could convey information about how memory consolidation is acquired.

[1] van der Werf, Y.D. et al. Sleep benefits subsequent hippocampal functioning. Nat Neurosci 12, 122–123 (2009).

[2] Robertson, E.M. The serial reaction time task: implicit motor skill learning? The Journal of Neuroscience 27 (38), 10073-10075 (2007) (opens pdf)
-> see section about serial reaction time task for information about this procedure

[3] Wilson, M.A. & McNaughton, B.L. Reactivation of hippocampal ensemble memories during sleep. Science 265, 676–679 (1994). (opens pdf)

[4] Diekelmann, S. & Born, J. The memory function of sleep. Nature Reviews Neuroscience 11, 114–126 (2010).

Other resource:
[5] Born, J. Slow-wave sleep and the consolidation of long-term memory. World J Biol Psychiatry 11, 16–21 (2010).
-> provides conceptual framework and reviews evidence on the specific role of slow wave sleep in memory consolidation

From functional localization to functional networks

Patient H.M. (also see website about project HM: the brain observatory) is a famous case study taught in every introductory psychology textbook about a man who was unable to form new long term memories after surgery, while episodic, short-term and procedural memory remained intact. Or maybe you remember the more “sensational” story about Phineas Gage surviving an explosion which resulted in an iron rod piercing through his brain (more specifically through his left frontal lobe). Although Phineas Gage revealed intact brain functioning on a standard cognitive test battery, he suffered from marked personality changes. Cases as these, as well as other lesion studies (with a very special mention for Broca‘s elaborate examination of the brains of aphasic patients) provided valuable insights into the functional organisation of the cerebral cortex.

Technological advancements, like functional MRI, further expanded possibilities of localising functions to specific brain regions. Although nice colourful brain pictures were posted on multiple blogs and news sites (btw: I like colourful brain pictures, so no offence intended, hence my own use of such pictures) with red spots lighting up to indicate that groups of cells involved in a specific function were doing hard labour… despite this nice technological advancement, a similar increase in our understanding of human brain function was and is still lagging. Now new imaging techniques, like diffusion MRI, come to the forefront with new fancy pictures.

The work that has been done is great, it’s great to see how technology moves so quickly, but as you can see in the scientific community for the past decades, there’s now a shift in how these tools are used as well, or how data derived from these tools are analysed. Like looking at the brain from another point of view, but using the same technique. A shift from functional localization to functional networks. Research interests are now focused on exploring how different brain areas communicate with each other and guide certain functions or behavior and find out how changes in activity on the network level can reveal pathology.

Human brain and gene expression

Today a TED talk of Allan Jones was posted. Since my love for open source (a love that I’ve already mentioned numerous times, but not enough however) I want to share this talk with you, and other great resources that are directly related to Allan Jones’ work.

Allan Jones is the CEO of the Allen Intitute for Brain Science, an institute which provides open source tools and data for gaining understanding into our beloved brain. This non-profit medical organization wants to gain insight into how the brain works. One way they approach this is by mapping gene-brain interactions in the (developing) mouse as well as the human brain.

For anyone interested in the human or mouse brain, I strongly recommend checking out the Brain Atlas website with interactive three dimensional atlasses of the brain. Also check out the different tutorials you can find on their channel (e.g. tutorial on using their Brain Explorer software), to take advantage of the wide range of options the tools provide.

WIRED also provided a nice post of the work that’s being done in this institute.
http://www.wired.com/medtech/health/magazine/17-04/ff_brainatlas?currentPage=all

http://www.brain-map.org/

Quora: Do people who sleep more than average have better memory?

I have recently gotten “active” on Quora. This is a great Q(uestions)&A(nswer) site on a wide range of interesting topics. Although I’ve only answered two questions, I want to share this great site with you and my answer on the following question. Some part of the circadian and homeostatic regulation probably sounds familiar for those who read my blog before, so for a more directed answer on the question, scroll down.

Question: Do people who sleep more than average have better memory?

My answer:

If you sleep “more” than average this doesn’t mean this will result in a better memory. Just like many other physiological aspects of our body, the body strives to an equilibrium or homeostasis. It’s the same with sleep. There’s a build up of sleep pressure during wakefulness, and a decrease of sleep pressure when you go to sleep. In addition recovery sleep after a night of sleep deprivation results in an increase in the so-called slow wave activity or “deep sleep” in the first hours of recovery sleep, thus characterizing this homeostatic regulation.

So there is a homeostatic principle (in addition to a circadian mechanism that has a 24 hour rhythm) that regulates our sleep. How fast this sleep pressure builds up and decreases, as well as the length of your circadian rhythm (it can deviate from 24 hours), and maybe other factors as well that at this point I’m not aware of, will determine the amount of sleep you need.

If you deviate from this equilibrium, this can result in detrimental effects on cognitive function as well as physical and mental health. Even sleeping too long is associated with negative outcomes, although it’s hard to infer if this is a causal aspect.

To address your question specifically. No, people who sleep “more than average” will not show an increase in memory function. There is no additional benefit in sleeping extra than the amount needed homeostatically speaking. One of the major functions that has been proposed for sleep is its role in memory consolidation, in the form of so called memory replay. This memory consolidation is thought to take place during the slow wave activity or deep sleep (although it’s also claimed that the transitions between NREM-REM sleep could play a role, or specific neuronal activity like spindles, although I won’t elaborate on this). However, slow wave activity or deep sleep takes place when sleep pressure is high, so during the first part of sleep. When you sleep longer your sleep pressure won’t be high anymore, thus sleep will be more “superficial”, with no more deep sleep and thus no more additional benefit for memory.

This doesn’t implicate however that the first part of sleep is enough. The complete (usually 8h long) sleep episode has a restorative function (and other functions as well of which many still need to be explored), so other aspects like vigilance (or your amount of wakefulness) will affect your functioning during the day and can indirectly affect memory function and cognition. It also depends on the direction you want to look into memory and sleep, e.g. sleep and memory consolidation following learning, or the ability to learn new things after a night of sleep…

Good review article (not free):
Diekelmann, S. & Born, J. The memory function of sleep. Nature Reviews Neuroscience 11, 114–126 (2010).
http://www.nature.com/nrn/journal/v11/n2/abs/nrn2762.html

Donating knowledge

I’m utterly happy about the evolution in open source education, where learning is available to everyone. One important aspect however is that the quality of such open sources remains high, but when reputable institutions and organisations take initiatives to make such high quality educational sources publicly available, I’m really positive of  how this will evolve. Already the resources available range from a wide variety  of topics, from arts to exact sciences. I think there is something to find for everyone (see my previous blog on OpenCourseWare for a couple open courseware providers).

Although I don’t believe open courseware can really replace the classroom (although it can be for the lifelong learner that already had a former education), I do believe they can serve as a great complement. Other important skills, aside from following courses in itself, like the development of social skills, learning to ask questions, communicate ideas and explain yourself verbally…, are still a part of personal development as well, and you have to learn how to learn. There is an important role of the teacher as to guide and tailor programs/knowledge to the individual and intervene where necessary.

This individual guidance in the classrooms is however something I think that is already missing today. I mean no offence to you teachers out there, I think you’re doing as great a job as possible and putting great effort into educating your students, but what I’m missing is a real mentor. Like Socrates was for Plato, and Plato was for Aristoteles. Someone who can intensively guide you, motivate you, inspire you. Someone who allows you to make mistakes and learn from them, someone who’s always available and open for advice. An open source in itself. Although there probably are some teachers who succeed in doing so, I think they are limited. Teacher themselves don’t have the resources to really provide such a guidance, since classes are mostly too large and there is a shortage of teachers at this moment. Maybe a program in which older students (or bright peers) guide younger students could partly cover this problem, but these students should be motivated to put time and effort in providing such guidance and perhaps if they don’t have the answer search for it together with the younger student.

Not only with regard to  educational resources, but also with regard to the public availability of scientific findings, we have come a long way. PloS offers a variety of online journals, open to everyone. In addition, high impact journals like PNAS, Neuron and  Nature now make some of their journal content open access as well.

For those specifically interested in Sleep, there’s the journal Sleep. Articles published more than 6 months ago are available for everyone.

Open access… it’s like donating for charity, but instead of money, you donate knowledge and experiences.

Stumble upon: the neuron

I recently stumbled upon an animated textbook covering some basics about cellular and molecular neuroscience: icarus.med.utoronto.ca/neurons/index.swf. This book explains the different concepts in a very concise and clear way, and provides ample graphics and animations to assist you with understanding the different components.

Optogenetics and its application in sleep research

I must admit, if I hear about something new, flashy and fancy I can’t help but get enthusiastic about it! Optogenetics, chosen method of the year 2010 by Nature Methods, is one of those fancy things that recently caught my attention.

Optogenetics is a technique which allows you to precisely control activity in one cell type by the use of light. In the video below you can see a nice overview of the technique and there are some great primers/introductions as well (see below for references; free content).

Also see this great talk by Ed Boyden on TED:

Rolls et al. (2011) have now applied optogenetics to study the effect of sleep disruption on memory consolidation. By using optogenetics in rats they were able to manipulate one aspect of sleep (i.e. sleep fragmentation) while keeping other sleep parameters such as sleep duration, intact. This way they could isolate the effect of sleep fragmentation on memory consolidation.

Memory consolidation was measured by using an object recognition task. When faced with a familiar object and a new object, rats spend more time exploring the unfamiliar object. This is taken as an indication that the rat “recognizes” the object and thus memory for that object has been consolidated. Sleep fragmentation resulted in impaired performace in such a task as compared to control rats. An additional interesting finding was that the effect of sleep fragmentation could be quantified. When sleep fragmentation was limited to a minimum of about 65%, memory wasn’t affected, while more sleep fragmentation resulted in disrupted memory consolidation.

This research nicely illustrates how optogenetics can be applied to study sleep mechanisms and the role of sleep in cognition. I’m looking forward to see this technique and its applications evolve, and hope it can further guide and direct future research.

References (resources freely available)

• Rolls, A. et al. Optogenetic disruption of sleep continuity impairs memory consolidation. Proceedings of the National Academy of Sciences (2011).
• Yizhar, O., Fenno, L.E., Davidson, T.J., Mogri, M. & Deisseroth, K. Optogenetics in neural systems. Neuron 71, 9–34 (2011). Very elaborate and extensive primer on the use of optogenetics. Opsin genes, opsin targeting, light deliverery and behavioral readout is discussed.  
• Pastrana, E. Optogenetics: controlling cell function with light. Nat Methods 8, 24–25 (2011). Brief primer on optogenetics. Less technical than the paper of Yizhar.

Sleep and caffeine

Getting up in the morning and feeling that desperate need for coffee to get started with the day? We all know about the sleep-suppressing effects of caffeine (a substance of coffee), but how does it work? How come caffeine can keep us awake when we would otherwise fall asleep?

Enough with the questions already! What’s the answer? Well to understand how caffeine interferes with sleep or sleepiness, we need to know how sleep works. In a previous discussion I already talked about Borbély’s two-process model, i.e. the homeostatic and the circadian process that regulates sleep. The circadian process regulates the cyclical secretion of hormones e.g. melatonin, and the homeostatic process is the process referring to the increase of sleep pressure with increased wakefulness and the dissipitation of sleep pressure during sleep.

Adenosine is a neuromodulator (not to be confused with a neurotransmitter) that follows the same course as the homeostatic process, i.e. build up of adenosine during wakefulness and decrease of adenosine during sleep. Adenosine binds to adenosine receptors resulting in an inhibition of neuronal activity. So during prolonged wakefulness inhibition will become more prominent due to increased adenosine concentration and will eventually promote sleep. Caffeine however, is an antagonist that binds to the same receptor as adenosine, and prevents adenosine’s inhibitory action. A picture from palobiofarma illustrates nicely how caffeine interacts with the adenosine A2a receptor and prevents adenosine from binding to the receptor, resulting in a behavioral state of wakefulness/activity.

Animal studies have shown additional effects of caffeine, aside from its antagonistic function of the adenosine receptor, but these effects however occur in larger quantities than what we usually consume. For more information about these additional effects and a comprehensive review on the effects of caffeine on behavior, see the reference below (not freely available).

Nehlig, A., Daval, J. L., & Debry, G. (1992). Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects Brain Research Reviews, 17(2), 139–170.

Blogging

I really respect people being able to maintain a blog. When I searched the web for neuroscience-related blogs and subscribing to some (in my opinion) interesting ones, I always found out that at a relatively early point they failed to keep their blog updated (and I’ve also unfortunately experienced this problem myself ). It’s quite unfortunate because you can read a lot of articles, but you’ll always miss out on some, and well it’s  nice to read someone’s opinions and keep up-to-date with neuroscience-related news, trying to avoid “news”-sites providing a biased view and sites that are more aimed at attracting attention for the “sensation-seeking” public.

Recently however, I came across an interesting blog of Bradley Voytek (he actually has multiple sites). Asides from covering neuroscience papers, he also talks about neuroscience related topics in a very interactive way. The way he writes really adresses the reader and makes his blogs very accessible and fun to read. So if you’re interested in a blog that is more frequently updated I definitely recommend you this one. In addition he also has a list to other neuroscience blogs that might prove useful to you. If you don’t really feel like browsing through all of the blog messages, I recommend reading the blog message “How to be a neuroscientist?” and if you don’t feel like reading at all, I recommend watching his TEDxBerkeley session.

Also… another really useful link I came across thanks to this blog is PubBrain. Just type in a topic of interest, for example “sleep AND aging” and you get a list of brain regions and the respective publications that link the brain regions with the topic of interest you entered. Hope you find something interesting!

Ideas worth spreading

“Ideas worth spreading” that’s the tag-line of TED, a new website I want to share with you!

Technology, entertainment, design, business, science and global issues… those are the topics TED-tv has to offer. For everyone there’s some inspiring person out there sharing his or her ideas. Well, maybe I’m exaggerating, since in my opinion I find the most inspiring people the ones I meet in person. At least those are the ones that influence me the most or that motivate me to try to get the best out of me. But anyway, I didn’t plan to make this a personal blog, so I just want to let you know that it’s a nice site with quite a lot of information. So if you’re getting a bit tired of reading all those articles or books, and just want to hear someone talk about their passions, TED-tv is the place to be.

Just like Stumble Upon, I’ll use this site to occasionally pick a topic that I consider as interesting, or just want to share. I haven’t done this yet so far for Stumble Upon either, but well… we’ll see how it evolves. Anyway you have the site now, so go find out if there’s something for you in there! If not… I hope I can post something else in the future that is useful for you!

Enjoy!