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Putting Themselves to Sleep
ScienceNOW ^ | 21 November 2012 | Greg Miller

Posted on 11/24/2012 11:24:40 PM PST by neverdem

Enlarge Image
sn-sleep.jpg
Self-medicated. A new study suggests that some people suffer from excessive sleepiness due to a naturally occurring compound that acts like a sedative.
Credit: Digital Vision/Thinkstock

Hitting the wall in the middle of a busy work day is nothing unusual, and a caffeine jolt is all it takes to snap most of us back into action. But people with certain sleep disorders battle a powerful urge to doze throughout the day, even after sleeping 10 hours or more at night. For them, caffeine doesn't touch the problem, and more potent prescription stimulants aren't much better. Now, a study with a small group of patients suggests that their condition may have a surprising source: a naturally occurring compound that works on the brain much like the key ingredients in chill pills such as Valium and Xanax.

The condition is known as primary hypersomnia, and it differs from the better known sleep disorder narcolepsy in that patients tend to have more persistent daytime sleepiness instead of sudden "sleep attacks." The unknown cause and lack of treatment for primary hypersomnia has long frustrated David Rye, a neurologist at Emory University in Atlanta. "A third of our patients are on disability," he says, "and these are 20- and 30-year-old people."

Rye and colleagues began the new study with a hunch about what was going on. Several drugs used to treat insomnia promote sleep by targeting receptors for GABA, a neurotransmitter that dampens neural activity. Rye hypothesized that his hypersomnia patients might have some unknown compound in their brains that does something similar, enhancing the activity of so-called GABAA receptors. To try to find this mystery compound, he and his colleagues performed spinal taps on 32 hypersomnia patients and collected cerebrospinal fluid (CSF), the liquid that bathes and insulates the brain and spinal cord. Then they added the patients' CSF to cells genetically engineered to produce GABAA receptors, and looked for tiny electric currents that would indicate that the receptors had been activated.

In that first pass, nothing happened. However, when the researchers added the CSF and a bit of GABA to the cells, they saw an electrical response that was nearly twice as big as that caused by GABA alone. All of this suggests that the patients' CSF doesn't activate GABAA receptors directly, but it does make the receptors almost twice as sensitive to GABA, the researchers report today in Science Translational Medicine. This effect is similar to that of drugs called benzodiazepines, the active ingredients in antianxiety drugs such as Valium. It did not occur when the researchers treated the cells with CSF from people with normal sleep patterns.

Follow-up experiments suggested that the soporific compound in the patients' CSF is a peptide or small protein, presumably made by the brain, but otherwise its identity remains a mystery.

The idea that endogenous benzodiazepinelike compounds could cause hypersomnia was proposed in the early 1990s by Elio Lugaresi, a pioneering Italian sleep clinician, says Clifford Saper, a neuroscientist at Harvard Medical School in Boston. But several of Lugaresi's patients later turned out to be taking benzodiazepines, which undermined his argument, and the idea fell out of favor. Saper says the new work makes a "pretty strong case."

Based on these results, Rye and his colleagues designed a pilot study with seven patients using a drug called flumazenil, which counteracts benzodiazepines and is often used to treat people who overdose on those drugs. After an injection of flumazenil, the patients improved to near-normal levels on several measures of alertness and vigilance, the researchers report. Rye says these effects lasted up to a couple hours.

In hopes of longer-lasting benefits, the researchers persuaded the pharmaceutical company Hoffmann-La Roche, which makes the drug, to donate a powdered form that can be incorporated into dissolvable tablets taken under the tongue and a cream applied to the skin. One 30-something patient has been taking these formulations for 4 years and has improved dramatically, the researchers report in the paper. She has resumed her career as an attorney, from which her hypersomnia had forced her to take a leave of absence.

The findings are "certainly provocative," Saper says, although they'll have to be replicated in a larger, double-blind trial to be truly convincing.

Even so, says Phyllis Zee, a neurologist at Northwestern University in Evanston, Illinois: "This gives us a new window into thinking about treatments" for primary hypersomnia. "These patients don't respond well to stimulants," Zee says, so a better strategy may be to inhibit the sleep-promoting effects of GABA—or as Rye puts it, releasing the parking brake instead of pressing the accelerator.

The next steps are clear, Rye says: Identify the mystery compound, figure out a faster way to detect it, and conduct a larger clinical trial to test the benefits of flumazenil. However, the researchers first need someone to fund such a study. So far, Rye says, they've gotten no takers.


TOPICS: Culture/Society; News/Current Events; Testing
KEYWORDS: neurology; primaryhypersomnia
Since flumazenil antagonized the effects of benzodiazepines, they thought there were specific benzodiazepine receptors.
1 posted on 11/24/2012 11:24:51 PM PST by neverdem
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To: neverdem

Did that neurologist think to recommend patients to an endocrinologist to have calcium and parathyroid levels checked?


2 posted on 11/24/2012 11:37:10 PM PST by wastedyears (I don't want to live on this planet anymore.)
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To: neverdem
Many years ago I was reading "The Schwartzbein Principle". Schwartzbein discussed sleep issues and said that "GABA" helps "reduce the noise in your head" so you can sleep. I often find myself writing software algorithms instead of normal "dreaming". It's very productive the next day, but often results in being damn tired instead of being rested. On a whim, I picked up a bottle of GABA to evaluate the effects. It turned my normal mental machinations into a full blown circus. A bit like the kind of rave you might see in a heavy metal night club in an over the top Hollywood movie. I certainly didn't sleep well at all. About 6 weeks later, I tested it again. Same effect. GABA does not turn down the "noise" in my head. It might as well be a brass band playing. It turns up the noise for me.

When I'm forced out of bed before I'm adequately rested, I'm tired all day. I just blew off making the 900 mile drive home for Thanksgiving because my employer sent me to a very expensive security training class, then my niece stole the only sleep day I was going to get for a memorial for her dad. 11 days of forced 6:30 AM starts with work finishing at midnight to 1 AM. I was too burned out to safely drive.

3 posted on 11/25/2012 12:11:57 AM PST by Myrddin
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To: neverdem
Many years ago I was reading "The Schwartzbein Principle". Schwartzbein discussed sleep issues and said that "GABA" helps "reduce the noise in your head" so you can sleep. I often find myself writing software algorithms instead of normal "dreaming". It's very productive the next day, but often results in being damn tired instead of being rested. On a whim, I picked up a bottle of GABA to evaluate the effects. It turned my normal mental machinations into a full blown circus. A bit like the kind of rave you might see in a heavy metal night club in an over the top Hollywood movie. I certainly didn't sleep well at all. About 6 weeks later, I tested it again. Same effect. GABA does not turn down the "noise" in my head. It might as well be a brass band playing. It turns up the noise for me.

When I'm forced out of bed before I'm adequately rested, I'm tired all day. I just blew off making the 900 mile drive home for Thanksgiving because my employer sent me to a very expensive security training class, then my niece stole the only sleep day I was going to get for a memorial for her dad. 11 days of forced 6:30 AM starts with work finishing at midnight to 1 AM. I was too burned out to safely drive.

4 posted on 11/25/2012 12:12:10 AM PST by Myrddin
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To: neverdem; John Robinson
FR is double posting tonight.
5 posted on 11/25/2012 12:15:30 AM PST by Myrddin
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To: Myrddin

Been going on for a while. I think it is caused by an unusual delay after people click “Post” which causes one to either forget that you already posted, or think that it didn’t take and click again. Apparently the software does not have a way to tell that you only clicked “Post Reply” once before multiple “Post” clicks.


6 posted on 11/25/2012 1:36:16 AM PST by wideminded
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To: wideminded

By now all old hands presumably know to wait till the browser itself complains of a time out.


7 posted on 11/25/2012 2:40:27 AM PST by HiTech RedNeck (How long before all this "fairness" kills everybody, even the poor it was supposed to help???)
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To: wastedyears
"David Rye, a neurologist at Emory University..."A third of our patients are on disability," he says, "and these are 20- and 30-year-old people."

It looks like he refers them to the Social Security Administration for a check.

Impeach the kenyan or secession.


8 posted on 11/25/2012 4:47:54 AM PST by ex91B10 (We've tried the Soap Box,the Ballot Box and the Jury Box; ONE BOX LEFT!)
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To: ex91B10

That’s what I was thinking. Great way to get more freebies.

Wonder if they ever considered these people are easily bored?


9 posted on 11/25/2012 7:45:52 AM PST by bgill (We've passed the point of no return. Welcome to Al Amerika.)
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To: neverdem; Myrddin

Thanks again neverdem, your posts contain a ton of interesting info!

Myrddin...if I’m understanding correctly, what you experience with GABA supplementation is the opposite of what it’s ‘sposed to be. Like Ritalin(!?) for hyperactivity - GABA is causing a paradoxical reaction in you. That’s very interesting.
Could it be the source of supplementation that’s “off”? IDK, but I feel for you. There are lists of various GABA-containing foods, I wonder if your reaction to them would be different?
Also, I’m not as up with the research, but I wonder if it’s a GABA problem, or a hyperactive GABA RECEPTOR problem.

I agree with the poster who mentioned checking endocrine function...
just me, but I’d go for blood testing with an eye toward ‘treatment’ with whole food supplements...YMMV.
FRegards,
spank


10 posted on 11/25/2012 8:17:41 AM PST by spankalib (The downside of liberty is the need to tolerate those who despise it.)
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To: Myrddin

It is a major principal of meditation to “turn off the noise in your head” before meditating. However, I finally got an interesting hypothesis as to why.

Some people who were very expert at meditation discovered that with extended periods of silence in the head, the mind tends to drift to either an unusual degree of focus, which allows it to consider a narrow situation at hand, ignoring distractions; or the mind becomes very unfocused, a very inspirational state of mind for both creativity and “quantum leaps” in problem resolution.

However, the “internal dialogue” disrupts these shifts in either direction, sticking the mind in the middle, where the mind is involved with the overall situation of a person in the here and now.

This middle position is optimal, they concluded, if you are “being chased by a tiger.” That is, it is survival oriented, far more so than with a state of narrow focus *or* inspiration.

So, in the shadowy past, our ancestors came up with the trick of talking to ourselves, and parents unknowingly indoctrinate their children in this technique to this day, “even though tigers are few and far between these days.”

Thus they concluded, if you use any of the techniques to shut up the internal dialogue, that little bit of mind discipline will give you access to both a strong state of focus, and an inspirational unfocused state.

In practical terms, say if you were doing your SAT test. Just the ability to focus on the test and ignore all the distractions around you might be worth 10-20 IQ points. A much more enhanced ability to concentrate.

Likewise, when faced with an irresolute and complicated problem, or just needing a big shot of inspirational creativity, unfocusing your mind could open the gates.

However, there is more to it than that. The internal dialogue, and the vacillations between a slightly more focused and a slightly more unfocused state of mind are very energy consumptive. A person too skilled with talking to themselves both sounds like an “airhead surfer”, and are exhausted by all the energy used to keep them in that state.

When such people use one of the techniques to control their internal dialogue, the change is dramatic. I knew one such surfer airhead type who applied himself to a technique for a good two week, and he was like a different person.

Not just speaking in coherent sentences, but full paragraphs, and his brain filled with energy and good ideas. He was very pleased with the result, but somewhat apprehensive, because were that rate of improvement to continue, he imagined it would be overwhelming.

He did describe his new ability as like having “a knife switch in his head”, so he could turn his dialogue on or off at will.


11 posted on 11/25/2012 8:32:19 AM PST by yefragetuwrabrumuy (DIY Bumper Sticker: "THREE TIMES,/ DEMOCRATS/ REJECTED GOD")
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To: neverdem
Who's to say what's normal, but maybe we're not doing it right, or at least not as we used to.

Look up "First sleep and Second sleep" for another idea about how we might be wired and why some of us struggle with going back to sleep.

12 posted on 11/25/2012 8:56:23 AM PST by GBA (Here in the Matrix, life is but a dream.)
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To: yefragetuwrabrumuy
Controlling one's internal dialog, what it's tuned to and being able to turn it off at will are skills most never master and thus most are rarely free and rarely master much in or of their perceived world.

Unless we develop our will and intent, we are ego ruled creatures, slaved to its whims and desires.

13 posted on 11/25/2012 9:04:55 AM PST by GBA (Here in the Matrix, life is but a dream.)
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To: GBA

In all fairness, most people do not know that they can, and few would be willing to try even if they did know.

There is no motivation unless with are inspired and encouraged by forces beyond ourselves. Otherwise, we live and die, until something comes along and fractures our zeitgeist. Then most people die, and the few that remain either cling to the old ways, or try something new.


14 posted on 11/25/2012 10:03:44 AM PST by yefragetuwrabrumuy (DIY Bumper Sticker: "THREE TIMES,/ DEMOCRATS/ REJECTED GOD")
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To: yefragetuwrabrumuy
Yes, I agree and see how the universal truth of the Bell curve predicts that.

Many of us are essentially lazy, often fearful creatures who do little more than necessary.

However, we bore easily and thus there are a few seekers, inventors, explorers and adventurers who will boldly go where others fear to tread, either on their own or by following another's example.

Outside factors can change the nature of things and whether we look outside or inside. For example, I wonder how much has been displaced/lost by the ubiquitous television/idiot box.

15 posted on 11/25/2012 11:31:24 AM PST by GBA
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To: yefragetuwrabrumuy

” ...who applied himself to a technique...”

What does that mean?


16 posted on 11/25/2012 1:05:03 PM PST by fanfan ("But if Muslims were asked to go to church on Sunday and take Holy Communion there would be war.")
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To: fanfan

He took the technique seriously and performed it a lot.


17 posted on 11/25/2012 1:18:20 PM PST by yefragetuwrabrumuy (DIY Bumper Sticker: "THREE TIMES,/ DEMOCRATS/ REJECTED GOD")
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To: yefragetuwrabrumuy

Which technique?

What helped him so much?


18 posted on 11/25/2012 1:27:12 PM PST by fanfan ("But if Muslims were asked to go to church on Sunday and take Holy Communion there would be war.")
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To: wastedyears
Did that neurologist think to recommend patients to an endocrinologist to have calcium and parathyroid levels checked?

Any doc worth his/her salt would order standard chemistry tests that include calcium just to have a baseline after getting a chief complaint as well as complete prior medical and surgical history. Parathyroid levels would be checked only if the calcium result is abnormal, possibly only if that calcium result is confirmed by a repeat test.

19 posted on 11/25/2012 4:53:27 PM PST by neverdem ( Xin loi min oi)
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To: Myrddin; wideminded; HiTech RedNeck; spankalib; yefragetuwrabrumuy; GBA; fanfan
Many years ago I was reading "The Schwartzbein Principle". Schwartzbein discussed sleep issues and said that "GABA" helps "reduce the noise in your head" so you can sleep. I often find myself writing software algorithms instead of normal "dreaming". It's very productive the next day, but often results in being damn tired instead of being rested. On a whim, I picked up a bottle of GABA to evaluate the effects. It turned my normal mental machinations into a full blown circus. A bit like the kind of rave you might see in a heavy metal night club in an over the top Hollywood movie. I certainly didn't sleep well at all. About 6 weeks later, I tested it again. Same effect. GABA does not turn down the "noise" in my head. It might as well be a brass band playing. It turns up the noise for me.

I wonder how much genetic/epigenetic testing might explain it, what the bill would be and if you could get a definitive answer. It's possible that they could just rule out what they know to test for on a routine basis.

I always thought of GABA as an inhibitory neurotransmitter, but medicine always has something new to teach me.

Coexistence of excitatory and inhibitory GABA synapses in the cerebellar interneuron network.

20 posted on 11/25/2012 5:26:51 PM PST by neverdem ( Xin loi min oi)
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To: neverdem

Myrddin just has a weird brain.

Computer programming in his dreams. I can’t even get something in a dream to stay constant from one “look” to the next. Occasionally when very intensely involved with a project I get prolonged dreams about generalities and that’s about it.


21 posted on 11/25/2012 5:32:46 PM PST by HiTech RedNeck (How long before all this "fairness" kills everybody, even the poor it was supposed to help???)
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To: HiTech RedNeck
I composed most of my college papers in my head and whipped out 5 to 10 pages as quickly as the old Selectric would tolerate. The same behavior continues over 30 years as a software developer. The whole solution is cooked and dependent on my typing speed to come out in the real world. When working with customers on a problem, I have to be careful not to solve the problem before the customer has fully explained it.

The dream connection is more interesting. I have some dreams that go "on hold" in the morning and resume during the night. Most of it is in 3D and color. Who needs a TV with that going on :-) GABA interferes with that experience by tossing in noise and distractions. It was a harmless investigation to be avoided in the future. The anomaly isn't something I need to have fixed.

22 posted on 11/25/2012 7:43:59 PM PST by Myrddin
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To: Myrddin

hey, why fix a winning formula. when the going gets weird, the weird turn pro!


23 posted on 11/25/2012 8:00:35 PM PST by HiTech RedNeck (How long before all this "fairness" kills everybody, even the poor it was supposed to help???)
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To: HiTech RedNeck

Yup. Might as well turn it into an advantage.


24 posted on 11/25/2012 10:44:12 PM PST by Myrddin
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To: El Gato; Ernest_at_the_Beach; Robert A. Cook, PE; lepton; LadyDoc; jb6; tiamat; PGalt; Dianna; ...
The Hazards of Growing Up Painlessly

Detecting cancer cells and parasites

A Wet Way to Better Burning?

Doctor disputes common acceptance of ‘brain death’ The link in comment# 19 is quite a read.

FReepmail me if you want on or off my health and science ping list.

25 posted on 11/25/2012 11:03:07 PM PST by neverdem ( Xin loi min oi)
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To: neverdem

This brain death thing looks like it sure has gotten sloppy. In the name of getting transplant organs, they’ve killed or “killed” many humans or “bodies” in conditions outwardly identical to those in which some degree of recovery to a recognized living state has occurred, if not also recovery to lucidity. We trusted doctors to be sane, humane, and moral. Instead too often it’s nod and wink, and Obamacare can only make it worse.


26 posted on 11/25/2012 11:14:25 PM PST by HiTech RedNeck (How long before all this "fairness" kills everybody, even the poor it was supposed to help???)
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To: Myrddin

And, trying not to run ahead of the customer is only logical. You haven’t really solved the problem until you maximally understood what the problem IS. Knowing the right questions to ask helps a lot, of course.


27 posted on 11/25/2012 11:17:29 PM PST by HiTech RedNeck (How long before all this "fairness" kills everybody, even the poor it was supposed to help???)
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To: neverdem

Calcium could vary from normal to high normal, to above normal. I’ve been borderline above normal for years and I’m only 27.


28 posted on 11/25/2012 11:41:16 PM PST by wastedyears (I don't want to live on this planet anymore.)
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To: neverdem

I didn’t say what I wanted to. Calcium doesn’t have to be above normal to have parathyroid disease.


29 posted on 11/26/2012 12:16:37 AM PST by wastedyears (I don't want to live on this planet anymore.)
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To: Myrddin
I often find myself writing software algorithms instead of normal "dreaming".

"Those idiots! I could have written that program in my sleep!"

My condolences. I don't dream of software coding but I do have occasional insomnia -- my blood sugar crashes at 4:00 AM and I am unable to go back to sleep.

Cheers!

30 posted on 11/26/2012 3:19:09 AM PST by grey_whiskers (The opinions are solely those of the author and are subject to change without notice.)
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To: yefragetuwrabrumuy
Can you post information (or links thereunto) for how to control the brain's inner dialogue?

(The middle setting would be *very* advantageous for a programmer, when one has has the intuition, and needs to turn it into working code.)

Cheers!

31 posted on 11/26/2012 3:23:43 AM PST by grey_whiskers (The opinions are solely those of the author and are subject to change without notice.)
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To: bgill
Wonder if they ever considered these people are easily bored?

I wonder if they've ever been treated with Ritalin or other ADHD drugs as a child?

32 posted on 11/26/2012 5:22:21 AM PST by raybbr (People who still support Obama are either a Marxist or a moron.)
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To: yefragetuwrabrumuy; GBA

It’s very easy to clear one’s mind. Meditation, self-hypnosis, and the ability to concentrate can all be learned and practiced to great effect.

It takes effort, but it can be accomplished with perseverance.


33 posted on 11/26/2012 6:12:01 AM PST by TheOldLady
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To: grey_whiskers

My favorite technique comes with an explanation of why it works.

It is based on the idea that the small part of the brain responsible for the internal dialogue is the same part of the brain responsible for attention in general, and that as more attention is needed, it takes priority over maintaining the internal dialogue.

It is difficult for the brain to provide the energy needed to even support attention, much less the internal dialogue, so we use lots of brain tricks to shut out data that might be considered extraneous, and thus conserve energy.

For example, when we look at a picture of a person, we do not try to focus our attention on the entire image, but only on a “darting point”, looking at a small part, then another small part, then another, using our short term memory to imagine the whole picture at once. Importantly, when we look at a picture of a human face, the most frequently looked at points are the eyes. Here is a scan of eye movements of the darting point.

http://i.imgur.com/uM0PQ.jpg

So the trick of the technique is to create more and more demand on our attention, which deprives the internal dialogue of the energy it needs to function, so it is quieted. And the longer it can voluntarily be turned off, the greater our control over it becomes.

The technique involves walking. Just ordinary walking is not easy, and demands considerable attention directed towards the legs. The next part is as you are walking, to hold the fingers in some unusual way, it doesn’t matter how, as long as it is unusual enough to attract your attention to your arms as well. Your arms just hang normally as they do when you typically walk, so it’s just the fingers that are odd.

So now your attention is in two directions. But the third part is the real attention grabber. By unfocusing your eyes, you defeat the “darting point” of your visual focus, and instead, everything in a 180 degree view in front of you becomes of equal importance to your attention. Which consumes an enormous amount of attention.

It takes just a little practice to learn how to walk with unfocused eyes, either looking at the ground 10-15 feet in front of you, or over the horizon, but it is not terribly difficult to learn.

So there is the technique. Walking, holding your fingers in an unusual way or ways, and unfocusing your eyes. Not very hard at all.

A few personal observations about the technique:

Don’t carry physical objects in your hands, as it can get annoying. I dislike even wearing a wristwatch when doing this. Rings are right out.

Never listen to music while you are doing this, or you may get a ferocious “ear worm”, the song endlessly repeating in your head. But if you have an annoying “ear worm” on its own while doing this technique, it will totally burn itself out and won’t trouble you any longer. Yippee!, if such things annoy you.

You can do the technique day or night, as long or short a walk as you like, because the effects are generally cumulative. Some people stop after a couple of weeks because even though they are getting a better state of mental focus and unfocus, they dislike the feeling of silence, like some people dislike quiet, so bring a boom box with them when they go camping.

One thing that some people notice after doing this technique for a while is that they start to get unusual sensations. Typically we ignore or block the vast majority of sensory input available to us, and sustained silence is bound to let some sensations we previously ignored through. I’ve never quite understood why a few people find this so disturbing, but a few do. Most just think it is cool.


34 posted on 11/26/2012 6:39:51 AM PST by yefragetuwrabrumuy (DIY Bumper Sticker: "THREE TIMES,/ DEMOCRATS/ REJECTED GOD")
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To: grey_whiskers
I eat a Zone Bar with my evening mix of pills to avoid both the empty stomach and the wake up from the blood sugar crash. That carries me a good 6 hours before a blood sugar crash wakes me. Ibuprofen or aspirin is necessary at bed time or the pain in my back makes sleeping impossible.
35 posted on 11/26/2012 10:47:44 AM PST by Myrddin
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To: wastedyears
Calcium could vary from normal to high normal, to above normal. I’ve been borderline above normal for years and I’m only 27.

I wouldn't go chasing borderline numbers without a complaint. Is your albumin also borderline high? Most of the ionized calcium is bound to it.

Ionized calcium.

36 posted on 11/26/2012 4:30:55 PM PST by neverdem ( Xin loi min oi)
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To: neverdem
Is your albumin also borderline high?

Never heard of that, what is it? I'd look it up myself but I need to get ready for an overnight job, so that the information might be there when I get home.

37 posted on 11/26/2012 5:25:46 PM PST by wastedyears (I don't want to live on this planet anymore.)
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To: wastedyears
This is a good reference about albumin. Odds are that the first time your blood was checked for calcium, they also checked for albumin along with 12 - 16 other elements and biochemicals.

After you're finished reading it, click on Home at the top of the page on the left. It's a good source for the general public's medical questions. Save it for future reference.

38 posted on 11/26/2012 7:57:33 PM PST by neverdem ( Xin loi min oi)
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To: neverdem; wastedyears

A reminder for after I’ve slept. I’ll make sure to check out that link. Thank you


39 posted on 11/27/2012 5:18:50 AM PST by wastedyears (I don't want to live on this planet anymore.)
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To: neverdem

I checked it out; I don’t think I have a problem metabolizing protein, but I won’t dismiss it completely because I haven’t had it tested.


40 posted on 11/27/2012 10:55:12 AM PST by wastedyears (I don't want to live on this planet anymore.)
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