Balm of hurt minds

The main character of Haruki Murakami's brilliant and terrifying short story "Sleep" is a perfectly normal middle-class woman living in Tokyo.  Her husband is a dentist, and they've got a lively, cheerful five-year-old son.  Everything about her life is so ordinary that it's hard even to describe.

Then, in one instant, all that changes.

One night, she awakens -- or thinks she has -- to a terrifying vision that even afterward, she's not certain was real or a hallucination during sleep paralysis.  A dark shape is huddled by the foot of her bed, and unfolds itself to reveal the figure of an elderly man, dressed in black, staring at her with an undisguised malevolence.  She attempts to scream, and can't.  After a moment, she forces herself to close her eyes, and when she opens them, the man is gone.  She's drenched with sweat, so she gets up, showers, pours herself a brandy, and waits for morning.

But after that moment, she is completely unable to go to sleep.  Ever.

The remainder of the story could be a teaching text in a fiction writing course lesson about how to create a believable Unreliable Narrator.  She returns to her ordinary life, but everything starts seeming... off.  Some senses are amplified, others dulled into nonexistence.  Everyday objects appear surreal, as if they've changed subtly, but she can't quite tell how.  One evening, she watches her husband as he's sleeping, and realizes that his face suddenly looks ugly to her.  She takes to going out driving at night (once her husband and son are asleep) and meets people who may or may not be real.  Her progressive slide into insanity reaches its apogee in the wee hours of one night, after seventeen days with no sleep, when she drives farther than she has ever driven, and ends up in an empty parking lot overlooking the ocean.  Dark figures raise themselves on either side of her little car, grab it by the handles, and begin to rock it back and forth, harder and harder.  She's thrown around by the motion, slamming against the door and steering wheel, and her last panicked thought is, "It's going to flip over, and there's nothing I can do to stop it."

An apt, if disturbing, summation of what is happening to her mind.

Sleep is an absolutely critical part of human health, but even after decades of research, it is unclear why.  Just about every animal studied sleeps, and many of them seem to dream -- or at least undergo REM sleep -- the same as we do.  (I know my dogs do; both of them bark and twitch in their sleep, and our sweet, gentle little dog Rosie sometimes growls as if she was the biggest meanest Rottweiler on the planet.)

Now, a team at the Binzhou Medical University's Shandong Technology Innovation Center has found one reason why sleep is so critical.  Sleep-deprived mice stop producing a protein called pleiotrophin, which apparently has a protective effect on the cells of the hippocampus.  Reduced pleiotrophin levels lead to cell death -- impairing both memory and spatial awareness.  Pleiotrophin decline has also been implicated in neurodegenerative diseases like Alzheimer's.

[Image licensed under the Creative Commons Sasha Kargaltsev, Sleeping (10765632993), CC BY 2.0]

What's unclear, though, is what direction the causation points.  Does the decline in pleiotrophin from sleeplessness cause the neurodegeneration, or does the neurodegeneration lead to insomnia and a drop in pleiotrophin levels?  The current research suggests the former, as the mice in the study had been genetically engineered to experience sleep disturbances, and the pleiotrophin loss seems to have followed as a consequence of the sleep deprivation.  Then, the question is, if pleiotrophin decline does trigger neurodegeneration, could the damage from Alzheimer's be prevented by increasing the production of the protein?

Uncertain at this point, but it's intriguing to find one piece of a puzzle that has intrigued us for centuries.  It seems fitting to end this musing on the power of sleep with the famous quote from Macbeth:

Methought I heard a voice cry ‘Sleep no more!
Macbeth does murder sleep,’ the innocent sleep,
Sleep that knits up the ravell’d sleave of care,
The death of each day’s life, sore labour’s bath,
Balm of hurt minds, great nature’s second course,
Chief nourisher in life’s feast.

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A consummation devoutly to be wished

When I was in college, I had an eight a.m. calculus class with a woman who used to drag herself in, large coffee in her hand, looking like death warmed over.  The first time this happened, I thought she'd just pulled an all-nighter either studying or partying -- both common occurrences in college -- but then I noticed it was day after day.  The poor woman never looked wide awake, and always seemed just this side of miserable.

Finally, being the subtle and compassionate person you all know me to be, I said to her, "What the hell is wrong with you?", or words to that effect.

She explained to me that she had serious sleep issues.  She'd get back to her dorm from her last class in the afternoon, still feeling exhausted, but then she'd get a second wind in the early evening.  Come a reasonable bedtime -- say, ten-thirty or eleven -- she was wide awake.

"I don't even bother going to bed," she told me.  "I tried it, more than once, and lay there for hours staring at the ceiling.  Now I just get up and try to be productive."

Until about four-thirty or five in the morning, when she'd finally feel tired.  Then she'd go to sleep, and her alarm would go off at six, and she'd start the whole cycle again -- with about an hour's worth of sleep.

I didn't find out until much later that what she was suffering from has a name; circadian dysrhythmia.  Basically, it's when your biological clock is completely out of sync with the rest of the world.  It's a little like a permanent case of jet lag.  And sadly, even now, forty years later, it's still remarkably resistant to treatment.

It's been the conventional wisdom for some time that circadian rhythms are mediated through a part of the brain called the hypothalamus.  And this is clearly part of the answer; sleepiness is correlated with increased activity in the anterior part of the region, and an increase in the hypothalamic production of the neurotransmitter gamma amino-butyric acid (GABA), which has an inhibitory effect on neural excitation.

[Image is licensed under the Creative Commons Jamain, Sleeping man J1, CC BY-SA 3.0]

But two new papers, published simultaneously last week in the journal Cell, have shown us that things may not be that simple.  (Are they ever?)  Both studies were done at the University of California - Irvine, and have shown that the network of internal clocks that regulates our metabolism, activity, alertness, and other cyclic behaviors are not limited to the brain -- that other parts of the body also have significant contributions to modulating our daily cycles.

In the first, titled, "BMAL1-Driven Tissue Clocks Respond Independently to Light to Maintain Homeostasis," researchers found that a chemically-driven clock exists... in our skin cells.  The authors write:

Circadian rhythms control organismal physiology throughout the day.  At the cellular level, clock regulation is established by a self-sustained Bmal1-dependent transcriptional oscillator network [a cyclic rise and fall of gene activity associated with light levels].  However, it is still unclear how different tissues achieve a synchronized rhythmic physiology.  That is, do they respond independently to environmental signals, or require interactions with each other to do so?  We show that unexpectedly, light synchronizes the Bmal1-dependent circadian machinery in single tissues in the absence of Bmal1 in all other tissues.  Strikingly, light-driven tissue autonomous clocks occur without rhythmic feeding behavior and are lost in constant darkness.

Maybe not so shocking, given that our skin is at least partly exposed to the light.  What is more surprising is the second paper, which found that a light-dependent circadian rhythm takes place in our livers:

Mammals rely on a network of circadian clocks to control daily systemic metabolism and physiology.  The central pacemaker in the suprachiasmatic nucleus (SCN) is considered hierarchically dominant over peripheral clocks, whose degree of independence, or tissue-level autonomy, has never been ascertained in vivo.  Using arrhythmic Bmal1-null mice, we generated animals with reconstituted circadian expression of BMAL1 exclusively in the liver (Liver-RE)...  [R]hythmic clock gene expression is lost in Liver-RE mice under constant darkness.  Hence, full circadian function in the liver depends on signals emanating from other clocks, and light contributes to tissue-autonomous clock function.

"The results were quite surprising," said Paolo Sassone-Corsi, who co-authored both studies.  "No one realized that the liver or skin could be so directly affected by light...  The future implications of our findings are vast.  With these mice, we can now begin deciphering the metabolic pathways that control our circadian rhythms, aging processes and general well-being."

It's undeniable that sleep plays a central role in both mental and physical health, and that the vast majority of us don't get sufficient sleep either in quantity or quality.  The more scientists find out about how our sleep cycles and other circadian rhythms are modulated, the greater the likelihood there'll be a treatment for people like my long-ago college acquaintance -- and even for simple insomniacs like myself.

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As will be obvious to any long-time readers of Skeptophilia, I have a positive fascination with things that are big and scary and can kill you.

It's why I tell my students, in complete seriousness, if I hadn't become a teacher I'd have been a tornado chaser.  There's something awe-inspiring about the sheer magnitude of destruction they're capable of.  Likewise earthquakes, hurricanes, wildfires...

But as sheer destructive power goes, there's nothing like the ones that are produced off-Earth.  These are the subject of Phil Plait's brilliant, funny, and highly entertaining Death From the Skies.  Plait is best known for his wonderful blog Bad Astronomy, which simultaneously skewers pseudoscience and teaches us about all sorts of fascinating stellar phenomena.  Here, he gives us the scoop on all the dangerous ones -- supernovas, asteroid collisions, gamma-ray bursters, Wolf-Rayet stars, black holes, you name it.  So if you have a morbid fascination with all the ways the universe is trying to kill you, presented in such a way that you'll be laughing as much as shivering, check out Plait's book.

[Note:  If you purchase this book using the image/link below, part of the proceeds goes to support Skeptophilia!]

A consummation devoutly to be wished

Like a lot of people, I'm struggling right now against sleep loss because of the silly switch from Standard to Daylight Savings Time, a switch I've heard compared to "cutting the top off a blanket and sewing the piece on the bottom to make it longer."

Don't get me wrong, I like the fact that it's still light when I get home from work, but given how far north I live, that'd have happened eventually anyhow.  And seems to me that since a lot of people like having more daylight hours after work, it'd make sense just to keep it that way, and not to return to Standard Time in November, further fucking up everyone's biological clock.

I mean, I have enough trouble sleeping as it is.  I've been an insomniac since my teenager years.  I never have trouble falling asleep -- my problem is staying asleep.  I'll wake up at 1:30 in the morning with my thoughts galloping full tilt, or (more often) with a piece of some song running on a tape-loop through my head, like a couple of nights ago when my brain thought it'd be fun to sing the Wings song "Silly Love Songs" to me over and over.

I hated that song even before this, but now I really loathe it.

[Image licensed under the Creative Commons Evgeniy Isaev from Moscow, Russia, Sleeping man. (7174597014), CC BY 2.0]

In any case, it was with great interest that I read some recent research from Bar-Ilan University (Israel) that has elucidated the purpose of sleep -- something that up till now has been something of a mystery.

In "Sleep Increases Chromosome Dynamics to Enable Reduction of Accumulating DNA Damage in Single Neurons," by David Zada, Tali Lerer-Goldshtein,  Irina Bronshtein, Yuval Garini, and Lior Appelbaum, which appeared last week in Nature, the authors write:

Sleep is essential to all animals with a nervous system.  Nevertheless, the core cellular function of sleep is unknown, and there is no conserved molecular marker to define sleep across phylogeny.  Time-lapse imaging of chromosomal markers in single cells of live zebrafish revealed that sleep increases chromosome dynamics in individual neurons but not in two other cell types.  Manipulation of sleep, chromosome dynamics, neuronal activity, and DNA double-strand breaks (DSBs) showed that chromosome dynamics are low and the number of DSBs accumulates during wakefulness.  In turn, sleep increases chromosome dynamics, which are necessary to reduce the amount of DSBs.  These results establish chromosome dynamics as a potential marker to define single sleeping cells, and propose that the restorative function of sleep is nuclear maintenance.

"It's like potholes in the road," said study co-author Lior Appelbaum in an interview with Science Daily.  "Roads accumulate wear and tear, especially during daytime rush hours, and it is most convenient and efficient to fix them at night, when there is light traffic."

This repair function is critical for cellular and organismal health.  If mutations and chromosomal breaks aren't fixed, it can trigger the death of the cell -- which, in the case of neurons, can create havoc.  You have to wonder if some of the age-related degradation of memory, not to mention more acute cases of dementia, are correlated with a reduction in sleep-induced genetic repair.

"We've found a causal link between sleep, chromosome dynamics, neuronal activity, and DNA damage and repair with direct physiological relevance to the entire organism," Appelbaum said.  "Sleep gives an opportunity to reduce DNA damage accumulated in the brain during wakefulness...  Despite the risk of reduced awareness to the environment, animals -- ranging from jellyfish to zebrafish to humans -- have to sleep to allow their neurons to perform efficient DNA maintenance, and this is possibly the reason why sleep has evolved and is so conserved in the animal kingdom."

What it doesn't explain is why some of us have so damn much trouble actually doing what we're evolved to do.  Shutting my brain off so it can do some road maintenance is really appealing, but for some reason it just doesn't cooperate most nights.

Which explains why I'm so tired this morning.  But what's wrong with that, I'd like to know?  So here I go AGAAAIIIIINNNNN....

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This week's Skeptophilia book recommendation is an entertaining one -- Bad Astronomy by astronomer and blogger Phil Plait.  Covering everything from Moon landing "hoax" claims to astrology, Plait takes a look at how credulity and wishful thinking have given rise to loony ideas about the universe we live in, and how those ideas simply refuse to die.

Along the way, Plait makes sure to teach some good astronomy, explaining why you can't hear sounds in space, why stars twinkle but planets don't, and how we've used indirect evidence to create a persuasive explanation for how the universe began.  His lucid style is both informative and entertaining, and although you'll sometimes laugh at how goofy the human race can be, you'll come away impressed by how much we've figured out.

[If you purchase the book from Amazon using the image/link below, part of the proceeds goes to supporting Skeptophilia!]

Perchance to dream

Insomnia sucks, something I am frequently heard to mutter under my breath at 3:30 AM.  I've been a bad sleeper for decades, and have not been able to figure out any particular pattern to it -- I have sleepless nights on days I've gotten lots of exercise and days I haven't, after spending several hours of staring into the computer screen and not, after drinking alcohol and not.  Nothing has really worked to alleviate it, although when I am desperate I take a Benadryl tablet, which works well even though it's something I don't like to do often.  (In fact, taking Benadryl works so well that after taking one, it's a miracle I make it back to bed before I pass out, to be found the next morning on the floor in the hallway in a puddle of drool.)

Sleep is critical to health, both mental and physical, but scientists have been working for ages to try and elucidate why.  It's known that when deprived of sleep short-term, people are groggy, irritable, and perform more poorly on every cognitive assessment there is; long-term sleep deprivation causes hallucinations, paranoia, and (ultimately) death.  Further, sleep is not the same as simple bodily relaxation; in some phases of sleep, the brain is as active as it is during wakefulness.

[image courtesy of photograph Evgeniy Isaev and the Wikimedia Commons]

It's been suggested -- and there is some experimental evidence to support it -- that sleep has something to do with memory consolidation.  It's been shown pretty conclusively that if you want to improve cognitive performance on a test, studying the night before and getting a good night's sleep works far better than spending an equal amount of time studying the day of the test.  I wish I'd known this back in college, where I was known to do things like doing my first and only studying for my 8 AM sociology midterm on the bus en route to school.

This doesn't, however, explain sleep's function in other animals, as few fluffy bunnies are known to take sociology classes.  But a study published last week in Nature: Communications has shown that sleep definitely influences memory -- even to the extent of fostering the formation of new memories while we're asleep.

The paper, "Formation and Suppression of Acoustic Memories During Human Sleep," by Thomas Andrillon, Daniel Pressnitzer, Damien Léger, and Sid Kouider of the École Normale Supérieure/PSL Research University of Paris, France, found that people form memories during REM (rapid eye movement) sleep -- but stimuli given during deep non-REM sleep actually suppress memory.  The authors write:

Sleep and memory are deeply related, but the nature of the neuroplastic processes induced by sleep remains unclear.  Here, we report that memory traces can be both formed or suppressed during sleep, depending on sleep phase.  We played samples of acoustic noise to sleeping human listeners.  Repeated exposure to a novel noise during Rapid Eye Movements (REM) or light non-REM (NREM) sleep leads to improvements in behavioral performance upon awakening.  Strikingly, the same exposure during deep NREM sleep leads to impaired performance upon awakening.  Electroencephalographic markers of learning extracted during sleep confirm a dissociation between sleep facilitating memory formation (light NREM and REM sleep) and sleep suppressing learning (deep NREM sleep).  We can trace these neural changes back to transient sleep events, such as spindles for memory facilitation and slow waves for suppression.  Thus, highly selective memory processes are active during human sleep, with intertwined episodes of facilitative and suppressive plasticity.

It's important to add, however, that experiments involving attempts to learn something complex -- such as a foreign language -- while you're asleep have all been abject failures.  The (alleged) phenomenon, called hypnopaedia, was all the rage back in the 1920s and 1930s, when people not only used it to try to learn, they used it to modify how they were perceived by others.  One such program, developed by hypnopaedia's main proponent, New York psychologist A. B. Saliger, was designed to help people get laid.  It involved listening while asleep to the following message played over and over:  "I desire a mate.  I radiate love...  My conversation is interesting.  My company is delightful. I have a strong sex appeal."

Unfortunately, all that this accomplished was making the test subjects wake up even hornier than they were before.

Study author Thomas Andrillon is cautious about applications of his work to the practical world.  "The sleeping brain is including a lot of information that is happening outside, and processing it to quite an impressive degree of complexity," Andrillon said.  But as far as using this research to facilitate the development of methods to influence memory in a bigger way, he added, "We are in the big unknown...  Keep in mind that sleep is not just about memory.  Trying to hijack the recommended seven-plus hours of sleep could disrupt normal brain function."

Which I can certainly attest to, as I rarely if ever get seven hours of uninterrupted sleep, and I don't think I've ever had the word "normal" applied to my behavior.  I have to admit that the Andrillon et al. research is fascinating, however, not least because it gives us another piece of the puzzle of why all higher animals sleep.

Now you'll have to excuse me, because I got about three hours of sleep last night, and I think I'm gonna go take a nap.

Sleepless in upstate New York

Any regular reader of Skeptophilia who pays attention to the timestamp on my posts knows that I'm a bit of an insomniac.

I have suffered from chronic insomnia since I was a teenager.  It started with bizarre, vivid dreams, which often would wake me up (sometimes because I'd thrashed around so much I'd fallen out of bed).  Once awakened in the wee hours, it takes me long enough to fall back to sleep that I frequently just give up and get up.  Most of the conventional sleep aids haven't helped; the mild ones (like valerian and melatonin) are ineffective, and the stronger ones worry me because of their capacity to become addictive.  So mostly, I've just put up with it, living and working on a chronic sleep deficit, and trying to catch time to take catnaps whenever I can.

So, naturally, I was pretty intrigued when I ran across an article called "Life Without Sleep," by Jessa Gamble.  Her piece begins with a bit of a history of sleep deprivation, and includes the efforts by the military to come up with a way to combat fatigue in soldiers (most of which, by the way, were either ineffective in the long term or had dreadful side effects).  But my attention really perked up when she started talking about two potential therapies for chronic insomnia -- transcranial direct-current stimulation (TCDS) and transcranial magnetic stimulation (TMS) -- which work not by getting you to sleep, but by reducing the amount of sleep you need.

TCDS and TMS both work on the same principle; using an external energy source to trigger neuronal firing in the brain.  Both of these treatment modalities are, pretty much, what they sound like.  TCDS involves placing electrodes on the scalp, and introducing a electric current into the brain; TMS places the head in a powerful magnetic field.  Both of them have been used, with results that I'd file in the "interesting" column, to treat depression, anxiety disorders, and schizophrenia.  Both have no known long-term side effects, although TMS apparently has a low risk of causing seizure or fainting.  (For me, the main risk of TCDS is that I would spend the entire time worrying that I was participating in a reenactment of the climax of One Flew Over the Cuckoo's Nest.)

According to Gamble, both of these treatments show great promise in helping with insomnia.  About TCDS, she says:

After a half-hour session of the real treatment, subjects are energised, focused and keenly awake. They learn visual search skills at double the speed, and their subsequent sleep — as long as it does not fall directly after the stimulation session — is more consolidated, with briefer waking periods and longer deep-sleep sessions.

TMS apparently has shown similar results:

Using a slightly different technique — transcranial magnetic stimulation (TMS), which directly causes neurons to fire — neuroscientists at Duke University have been able to induce slow-wave oscillations, the once-per-second ripples of brain activity that we see in deep sleep. Targeting a central region at the top of the scalp, slow-frequency pulses reach the neural area where slow-wave sleep is generated, after which it propagates to the rest of the brain...  TMS devices might be able to launch us straight into deep sleep at the flip of a switch. Full control of our sleep cycles could maximise time spent in slow-wave sleep and REM, ensuring full physical and mental benefits while cutting sleep time in half. Your four hours of sleep could feel like someone else’s eight. Imagine being able to read an extra book every week — the time adds up quickly.

What I'm imagining, at the moment, is not feeling chronically exhausted, and not having to worry about falling asleep at the wheel during my ten-minute drive home from work (a fear I deal with on more days than I'd like to admit).  I imagine not constantly wondering when I'm going to have time to take a nap so I can actually be wide awake after eight o'clock at night.

It's a happy picture.

Of course, the worrywart side of me wonders what the long-term effects of this might be.  We still understand very little about why animals need sleep, and less still about why they dream.  Messing about with a physiological system we don't fully comprehend seems rather foolhardy.  On the other hand, the tests that have been done so far support the contention that TCDS and TMS are relatively safe, are non-invasive, and show great promise in dealing with chronic insomnia, a condition which according to the National Sleep Foundation plagues 10-15% of adults.

I'd volunteer to give it a try, even given the iffy status of the risks.

But right now, I think I'd better wrap this up, because the coffee's done brewing, and given how little sleep I got last night,  I could sure use a cup or two.  Or five.