Hi everyone.

I've been familiar with a potent method of stimulating the brain non-invasively for some time (the source for my information has mainly been this yahoo group http://groups.yahoo.com/group/magnetikon).

This technology, LED infrared radiation, has been used by NASA to heal wounds in space, where wound healing does not otherwise happen. It is also being investigated to be used by the military.

The reason I'm here to tell you about it, is that there's a problem to solve. Laser stimulation (there are no studies of radicals using leds AFAIK), according to the research I've seen so far, produces free radicals. A lot. Like increasing the amount of peroxynitrites by a factor of 2-5 with the usual times and dosages. That's bad news; not only for accelerated aging but also straightforward brain cell apoptosis/necrosis. T. Karu has this to say about the specific location of this system:

Since laser radiation increased production of radicals is
approximately one order smaller than the one that is
induced by phagocytosis defending microorganism, one
assumes, that radicals develop in the latter part of the
respiratory chain (cytochrome a/a3).

Now, assuming the effect of LEDs is approximately the same on the cytochrome a/a3 system, what could be done to tune down the production of radicals (AFAIK, the most important in this cascade being superoxide anion or O2- which reduces NO) in that system to make this technology reasonably safe for the brain (it is probably impossible to make it 100% beneficial? Anyone know enough of biochemistry to point out something? From what I've read, SOD (superoxide dismutase) and catalases can reduce O2-. Any comments on that?

this magnetikon group proposes that stimulation of the cerebellar vermis will help humankind? Unlikely. Interesting Yahoo! group otherwise. Seems to be quite a bit of info on neurostimulation. About toning down free radicals, I recall reading of various pharmacological agents that work well, though I don't recall unfortunately the details. Try vitamin C + vitamin E + alpha lipoic acid.

Hey, you're ruining my party! No, seriously, why would cerebellar vermis not help, at least be a part of the solution? Everything that turns down the fight-or-flight response, is good in moderation, right?

And dont' think this particular method is limited to the vermis. Not so. It can hit the amygdala too (if you want) so it goes way deep.


Certainly. I'm also interested in a DIY TMS, but that project didn't really take off when it was suggested there. I think that would be definitely an interesting area.


Those might do some good. Yet from what I've read, really controlling free radicals is a whole lot more complicated than just taking the traditional supplements.

hi mayonaise. I took back my words soon after someone posted this here. The cerebellar vermis just seems such an unlikely region you'd want stimulated. I mean, besides a little bit of motor coordination problems, people can otherwise live just fine without their cellebellum, so why would you expect that stimulating it would be of any benefit.

Lucid dream, actually an MD friend of mine said that cerebellum is one of the most commonly underveloped regions in people. And a lot of that is due to lack of enough affection in childhood.

Cerebellum affects giving of emotional and physical affection. More data is coming in about it's involvement in learning. It's important.

But I don't think the cerebellum is the most important point here. The method is.

What sites do you think are important?

cingulate cortex, medial forebrain bundle, ascending reticular activating system (ARAS), maybe thalamus

Agreed, very important ones, only I don't know why you'd especially consider thalamus. The developer of the IR gadget claims that RAS can be stimulated with it. Cingulate cortex is quite deep but if I was able to influence amygdala (I could tell by the increase of fear and anger), then I guess it's not off limits.

I just looked up a substance called EUK-134 that in studies has been very successful in wiping out ROS damage. But 1) it costs a lot so I would need a chemist to do it for me or something and 2) there's no telling how much it would diminish the effects of the IR. But if the neurotoxicity could be abolished and enough noticiable effects would remain, it would make a good tool I suppose.

are there any good studies assessing the extent of free radical damage to neurons undergoing various stimulation protocols? What I would like to see are actual light and electron microscopic changes in neurons due to free radicals produced by laser stimulation or other types of stimulation.

No, we're still in Kansas or something

I didn't even know that it was possible to study neurons non-invasively on a micro-scale. Do you have a link to that? I tried to google a bit but it seemed that the studies were still in their early phases and they seemed pretty invasive to me (wait a minute, maybe quantum dots or a similar technology might help here...)

Come to think of it, I'm not sure any brain stimulation technique has been proven safe by that measure. I think the "applied neuroscience" of today tends to take a little more risks than that.

Personally I wouldn't need that much proof (can't say how much I'd settle for exactly) because it might pose more of a "risk" as in lost possibilities/abilities to not use a technology than use it.

I wasn't thinking of studying neurons non-invasively (that would be hard and I'm not sure of the best way to do it), but invasively. For example, laser stimulate a bunch of rats while alive, sacrifice, cut up their brains, and then examine under light and electron microscopy to see if laser stimulation produces structural changes in neurons.

It seemst to me the problem still remains the same as with tests with free radicals... will your brain react the same like the mouse brain?

Some tests have been made to neurons with leds:

http://www.jbc.org/cgi/content/full/280/6/4761
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Remarkably, only 10 min of LED pretreatment at a total energy density of 30 joules/cm2 effectively reduced by 48% the number of neurons exhibiting cell death in 300 µM KCN. Likewise, LED pretreatment significantly reduced the percentage of dying cells with condensed chromatin induced by another inhibitor of cytochrome c oxidase, sodium azide. The cause of the KCN-induced apoptosis is thought to be the generation of reactive oxygen species (20).
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This is interesting, if I remember right the NASA study said the led works partlly through increasing ROS... but maybe I'm wrong. And it could be that although the LED might decrease the poison induced ROS increase, itself would still raise the radical levels above control levels.

--------------------
The fact that LED treatment caused a reduction in the "a" value of the constants for both cyanide and azide strongly indicates that LED induced an increase in the synthesis of cytochrome c oxidase consistent with our deductions discussed above. Such synthesis undoubtedly involves a signaling molecule (or molecules) that directly or indirectly caused transcription and translation of cytochrome c oxidase subunit genes from both the mitochondrial and nuclear genomes. The prolonged cellular effect of brief LED treatments further suggests that there is an induction of a cascade of events leading to the activation and repression of a variety of genes (28, 29). Karu et al. (30) have proposed that intracellular signaling secondary to photon interaction with cytochrome c oxidase could be mediated by redox changes in the electron transport chain, by the generation of reactive oxygen species or nitric oxide signaling molecules, as well as by pathways involving the Na+,K+-ATPase and the Na+/H+ exchanger. Additional signaling molecules that may link light absorption with DNA induction such as phytochromes (in plants) (31) and cryptochromes (in plants and animals) (32) also warrant further investigation.
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Cascade effects... somewhere it was suggested that whereas 660 increases cytochrome c activity, 880 vibrates the cell walls, making them communicate more chemically or something. But this is just one theory.

In a study with retinal cells the gene transcription that happened was, I believe, entirely positive. I tend to trust that study; more worried about the free radical effect. If there are other things you could be worried about, please share. Here's the retinal study (I remember it was figure 6 that featured the up/down regulated genes):

http://www.ndu.edu/ctnsp/NATO%20RTO%20MP-HFM-109-P19.pdf

interesting

If you got any questions, you want to understand something better, just ask and I'll try to give you an answer.

Mean while, this news just came in... and I think it may give offer support for the idea that NO really isn't toxic - the byproducts are):

Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS.

Nisoli E, Tonello C, Cardile A, Cozzi V, Bracale R, Tedesco L, Falcone S, Valerio A, Cantoni O, Clementi E, Moncada S, Carruba MO.

Integrated Laboratories Network, Department of Preclinical Sciences, Luigi Sacco Hospital, Milan University, 20157 Milan, Italy. enzo.nisoli@unimi.it

Calorie restriction extends life span in organisms ranging from yeast to mammals. Here, we report that calorie restriction for either 3 or 12 months induced endothelial nitric oxide synthase (eNOS) expression and 3',5'-cyclic guanosine monophosphate formation in various tissues of male mice. This was accompanied by mitochondrial biogenesis, with increased oxygen consumption and adenosine triphosphate production, and an enhanced expression of sirtuin 1. These effects were strongly attenuated in eNOS null-mutant mice. Thus, nitric oxide plays a fundamental role in the processes induced by calorie restriction and may be involved in the extension of life span in mammals.

thanks mayonaise. The longevity and health effects of CR have been known for decades; unfortunately, I have never been able to benefit from it, healthwise. Whenever I attempt CR, I feel like crap and give up. Maybe I'm not sticking through with it long enough.

I've heard that CR can be induced by following the Sears Zone-diet. I'm doing that now. This is maybe my 3rd week. In the beginning it was hard but not anymore. I used to eat a lot of bread and now that I don't, I feel better.

I also heard the indicator that it's working should be lowering of the body temperature but I haven't tested 'cause I haven't got the meter so there's nothing to compare to but there's no reason to stop.

I believe CR lowers quality of life in humans. Just look at those starving ethiopians. I don't know about mice though.

Cerebral, you made me speechless. I cannot refute an argument like that.

"starving ethiopians" would suffer from malnutrition, including vitamin, mineral and protein deficiencies. CR is only useful if you're otherwise well-nourished. I've read somewhere that choline supplementation is beneficial for CR.