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Digital Nootropics

Posted: Fri, March 15, 2013 | By: Special Guest



by Andrew J. Vladimirov

You are tired, anxious and stressed, and perhaps suffer from a mild headache. Instead of reaching for a pack from Boots, you put on a fashionable “smarthat” (a neat variation of an “electrocap” with a comfortable 10-20 scheme placement for both small electrodes and solenoids) or, perhaps, its lighter version - a “smart bandanna”. Your phone detects it and a secure wireless connection is instantly established. A Neurostimulator app opens. You select “remove anxiety”, “anti-headache” and “basic relaxation” options, press the button and continue with your business. In 10-15 minutes all these problems are gone. However, there is still much to do, and an important meeting is looming. So, you go to the “enhance” menu of the Neurostimulator and browse through the long list of options which include “thinking flexibility”, “increase calculus skills”, “creative imagination”, “lateral brainstorm”, “strategic genius”, “great write-up”, “silver tongue” and “cram before exam” amongst many others. There is even a separate night menu with functionality such as “increase memory consolidation while asleep”. You select the most appropriate options, press the button and carry on the meeting preparations. There are still 15 minutes to go, which is more than enough for the desired effects to kick in. If necessary, they can be monitored and adjusted via the separate neurofeedback menu, as the smarthat also provides limited EEG measurement capabilities. You may use a tablet or a laptop instead of the phone for that. 

Your neighbour Jane is a trained neuroanalyst, an increasingly popular trade that combines depth psychology and a variety of advanced non-invasive neurostimulation means. Her machinery is more powerful and sophisticated than your average smartphone Neurostim. While you lie on her coach with the mindhelmet on, she can induce a highly detailed memories recall including memories of early childhood to go through as a therapist, or awake dormant mental abilities and skills you’ve never imagined to have with a flick of a switch. For instance, you can become a savant for the session time to solve some particularly hard problem and flip back to your normal state as you leave Jane’s office. Since she is licensed, some ethical modulation options are also at her disposal. For instance, if Jane suspects that you are lying and deceiving her, the mindhelmet can be used to reduce your ability to lie and you won’t even notice it. Sounds like a sci-fi? The bulk of necessary technologies is already there, and with enough effort the vision described can be realised in five years or so.  

While the traditionally heated debate on the use and implications of “smart drugs” continues to rage on, investigation of biophysical neurostimulation methods aimed at human cognition enhancement is steadily gaining pace behind the traditional nootropic scene. While the currently available pharmacological means are still incapable of targeting specific brain areas related to the function to be enhanced, transcranial direct current stimulation (tDCS), its combinations with transcranial alternating current stimulation (tACS) such as the anodal slow oscillation stimulation (tSOS), and transcranial magnetic stimulation (TMS) allow to do just that via elaborate placement of electrodes or solenoids. 

Such methods could complement, amplify, or provide a safer alternative to the use of nootropics (not that, for example, Piracetam and numerous other ampakines except for a few experimental drugs have significant side effects!). For instance, with the exception of strong (~1 Tesla and above) field TMS that can induce muscle twitching with certain stimulation protocols in some test subjects, biophysical neurostimulation approaches are devoid of peripheral side effects. A drug can have metabolites with undesirable biological activity, and large individual or group differences in its kinetics and metabolism. It takes time for it to be fully excreted. If it is lipid soluble (and a compound that has to penetrate the blood-brain barrier will inevitably be!) and not easily biodegradable, elimination of such a drug from the body will take quite a while. With any electromagnetic stimulation method you simply press the “off” button and wait for the effect to wear off. Local skin irritation that can be caused by electrostimulation is easy to prevent by choosing the right electrodes and adjusting the current strength (DC) or voltage (AC). Earlobe electrodes don’t seem to cause any irritation at all at the voltage levels used, and there is no such issue when the stimulating agent is a pulsed magnetic field. While any subtle cognitive trade-offs are surely possible, and there is a recent publication providing an example of such a trade-off , dedicated study and careful design of a stimulation protocol can avoid such shortfalls while retaining the benefits. No doubt, in certain conditions such as epilepsy electromagnetic approaches to cognition enhancement are likely to be a contraindication. However, the very same methods focally applied in reverse (e.g. cathode application in tDCS, or an inhibitory stimulus train in TMS) can provide effective treatment means. In a nutshell, there are no fundamentally impassible rational obstacles for biophysical human cognition enhancement with a possible exception of close minds often operating within the framework of medieval ethics and/or Cartesian dualism. Now, with which neurostimulation protocol can we finally overcome that? 

While strong field TMS which involves high power, high voltage equipment and thus has to be done with care will probably remain within the realm of research institutions and hospitals for a foreseeable time, this is not so with the other methods discussed. In fact, they provide a highly dynamic, enthralling sphere for what I would define as “electromagnetic biohacking” by knowledgeable enthusiasts. Just as numerous people experiment with nootropics on themselves, similar biophysical cognition enhancement experiments can be done (and are already under way) by garage scientists. Unless you own a pharmaceutical company, designing and testing an electromagnetic neurostimulation method and acquiring or building its implementation device is far more accessible than producing a novel nootropic drug. This opens some rather interesting opportunities for neurotech SME’s. Reproducing a method already known to work with a commercial, or even a custom built appliance could be more reliable than buying nootropics online from questionable sources, and fewer regulations to control distribution of such appliances are going to be in place. There is little doubt that apart from those already involved in biotech, electromagnetic biohacking will become exceedingly popular with electronics engineers/hackers around the world, just as there are numerous biofeedback acolytes in this milieu. Of course, a due care has to be exercised and potential risks properly gauged, but there is little out there to stop the “heroic enthusiast” (in the words of Giordano Bruno) from moving forward. Neither should the data obtained in such a way be ignored by the academic community without a thorough investigation. 

There is already a start-up aiming at offering an affordable, easy-to-use tDCS kit  which unfortunately seems to be quiet for a few months now. However, tDCS is technologically very simple and can be literally done with a 9V battery, a resistor and a pair of electrodes. The trick is to know functional neuroanatomy well enough to select the required electrodes placement locations while taking into account that an opposite, “inhibitory” effect will take place at the cathode. Stimulation time and current intensity will have to be adjusted so that the maximal beneficial effect is reached. Regular sessions can ensure that it is also long lasting. Typically, tDCS is applied during the learning task it is supposed to enhance. I expect it to be the first method of biophysical cognition enhancement to gain a widespread use in the not-so-distant future. A combination of tDCS and tDAC, or rather tRNS (transcranial random noise stimulation) is to follow. While pocket tDAC devices are already used (and prescribed) for anxiety, mild depression, sleep disturbances, chronic pain and cessation treatments, this method is significantly less researched in regard to its cognition enhancement potential as compared to tDCS and high power TMS. However, the potential is clearly there, and there are published studies indicating it. Note that all these methods do require a specialised device however portable it might be, the main reason being to provide sufficient current or voltage for long enough time to induce the desired effect(s). Such a device could be available as a programmable gadget which is software controlled from a smartphone, tablet, or any other computer. Unless you feed it from an external adaptor, the largest part of this gadget will be the battery. Of course, it will also require two, or in some cases more electrodes coated with conductive gel and placed on the skin above the stimulated locus. This might present a minor usability problem for an “application on the fly” as mentioned in the intro story here (if that locus is covered with long hair).   

In contrast, weak field TMS input can be directly fed from any sound jack using a software function generator (in some cases a micro-amplifier may come handy). All you need is to plug suitable small solenoids in and place them above the stimulated area (direct skin contact is not necessary). I can easily kick up to 2 microTesla next to the solenoids powered with my Android phone - this is more than sufficient to induce (subjectively felt and EEG-measurable) neurostimulating effects with a protocol I’m currently testing. So, an easy-to-use hands-on technology is already there, but its potential for human cognition enhancement is unfortunately little explored. The major reason for it is the controversy surrounding the very approach itself, even though numerous studies clearly demonstrating biological effects of weak pulsed magnetic fields have been performed since 1960-es. This controversy primarily goes down to the so-called “kT problem” which is, in layman terms, the strength of such pulsed magnetic fields at the low frequencies applied being six or more orders of magnitude below the level necessary to induce biochemical response. Due to this problem some researchers are still firmly convinced that weak field TMS simply can not work, even though a bulk of publications proving the opposite is out there. Discussing this issue goes well beyond this brief overview. However, it should be mentioned that modern biophysics possess a variety of satisfactory kT problem solutions, many of which belong to the field of quantum rather than classical electrodynamics. At the same time, the kT problem underlines extreme safety of weak field TMS, as no thermal or magneto/ electrochemical effects that can present risks with the “traditional” high power TMS will ever take place. So far, I find weak field TMS the most promising, yet expect its widespread use to come the last after the rest of the biophysical cognition enhancement avenues discussed (as the exact physical mechanisms of its action are yet to be decisively determined and defined prior to effective neurostimulation protocols being designed). At the same time, both investigation and use of weak field TMS can have tremendous general impact due to its high relevance to the fundamental questions of cognition science such as the nature of the “binding factor” and even various electromagnetic theories of consciousness. In a meanwhile, its the time to take these solenoids off my left frontal and temporal lobes and turn the function generator off. 



Comments:

I don’t understand why you say, “So far, I find weak field TMS the most promising” given that there is no evidence showing any effect at all. At least I haven’t read anything that was repeatable and most of it was abstract mathematical descriptions of stochastic resonance. What’s new in that regard that validates your personal perceptions in a non-blinded self study?

It’d be fine to say, “promising”. The potential reward of it’s intrinsic safety and low entry cost would be wonderful but it is unproven and unsupported at this time.

Anyway my personal pick for “most promising” would have to be transcranial low-power ultrasound. Using arrays of emitters multiple very lower power “beams” can be combined to do precise stimulation of small volumes in the deep brain. Check out http://www.tylerlab.com/projects/ultrasound for an introduction.

By superkuh on Mar 15, 2013 at 8:29pm

This is a fascinating area.  Enough so I would consider shaving my head an wearing a wired up with electrodes skin-head cap all the time.  Which electrodes are firing at any time controlled by on person software.  Continuous readings being collected.  If the skull cap is wireless and you wear wigs over it then most people never even know.  Hmm.  This is beginning to sound to cool to not do.  smile

By Samantha Atkins on Mar 16, 2013 at 2:08pm

I worry about using ultrasound, partly because of heating or cavitation efects. Anyway, currently Andrew is experimenting with low field TMS. I’ll be seeing him this weekend, where he’s giving a talk at London Futurists. Not sure whether he’s a member of ZS. I have a 1 metre diameter coil to lend him for some wide area experiments. If you want info on low field effects google “Persinger”

By Dirk Bruere on Mar 16, 2013 at 2:29pm

One other possibility - I am not sure if anyone has tried it yet.
Once had a discussion on extrobritannia list about IR light and whether it could penetrate the skull, so I did a bit of research. It seems the skull is reasonably transparent at 880nm. So, would a high power modulated IR diode have a noticeable effect on the brain? I am thinking of average power approximating sunlight ie around 100mW per sq cm, but with peaks much higher.

By Dirk Bruere on Mar 16, 2013 at 2:35pm

Hi superkuh, I’ll try to answer your questions below:

> I don’t understand why you say, “So far, I find weak field TMS the most promising” given that there is no evidence showing any effect at all.

1. Dirk has mentioned Persinger below, there is also Koren, Tsang, Cook, Sandyk and many others, Journal of Bioelectromagnetics will be the best to search for relevant publications:
http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1521-186X/issues

2. I have access to volumes of Russian data very little of which was ever translated into other languages spanning across more than 50 years of research on the topic starting from Presman and Kholodov to groups that continue to work now (Binhi, Zhadin, Vladimirskiy, IZMIRAN group etc.). There are two annual conferences that take place there which I monitor (three, if Moscow cosmobiology conference where such topics are frequently covered in relation to hypomagnetic conditions exposure on orbit etc. is counted)  As an illustration, the official Soviet (and then post-Soviet) TLVs for EMF are often orders of magnitude lower than their Western counterparts, and for a good reason (being based on non-thermal effects since Presman times).

3. I do have my own observations grin

> At least I haven’t read anything that was repeatable and most of it was abstract mathematical descriptions of stochastic resonance.

Binhi lists at least 15 such action mechanisms which include parametric (Lednev studies) and ion-cyclotron (Zhadin studies) apart from the stochastic resonance. One such mechanism is influence on magnetosensitive free radical reactions (and other spin-related mechanisms) and note that nitric oxide is a free radical. Google for Magnetic field sensitivity in the hippocampus Stefan Engstro¨m, Suzanne Bawin andW. Ross Adey (page 216 in a book you’ll find) - this is a rather interesting study where NO-based mechanism of microtesla range magnetic field action is implicated.

> What’s new in that regard that validates your personal perceptions in a non-blinded self study?

I’m using blind studies on healthy volunteers and plan to build a strong case for the stimulation algorithm employed when I gather enough EEG data. As for the topical publications please check PubMed - they keep coming grin

By Andrew on Mar 17, 2013 at 8:41am

> It’d be fine to say, “promising”. The potential reward of it’s intrinsic safety and low entry cost would be wonderful but it is unproven and unsupported at this time.

There are many other rewards, the main being the ability to aim at specific molecular targets, e.g. ligand-receptor interactions, ion-protein complexes etc. Also, rather complex signals can be injected, spatial resolution when using small coils is not bad at all (although not as great as in the ultrasound studies you’ve mentioned), and since the acting agent is not the induced current but the magnetic field itself, real time EEG monitoring is possible without any specific filtering and other measures needed to do it when the “traditional” strong field TMS is used.

By the way, many thanks for the tylerlab link, I shall add some basic info on their research to the slides of the upcoming talk.

By Andrew on Mar 17, 2013 at 8:48am

> Anyway my personal pick for “most promising” would have to be transcranial low-power ultrasound.

Sounds great! (pun intended) But will the differences in mechanosensitivity between different ion channels etc. be sufficient to target a specific channel type?

Also, for obvious technical reason such protocols, within the analogies of this article, are far more likely to belong to the arsenal of “Jane the neuroanalyst” rather than “Joe the mobile Neurostim user”.

By Andrew on Mar 17, 2013 at 8:52am

Hi Dirk, there is indeed quite a lot of information on such IR application - google for transcranial near infrared laser therapy. Unfortunately I don’t know a lot about it.

By Andrew on Mar 17, 2013 at 8:58am

Hi Samantha, with the current development of dry electrodes by the time such technologies arrive most likely this issue will be sorted out anyway. And if you look at Emotiv, only wetting the electrodes with saline is required. So, most likely your hair won’t be in danger, although I have nothing against wigs grin

By Andrew on Mar 17, 2013 at 9:05am

As for the electrodes and hair issue, I imagine an electrode patch which included a bed of needles contact might work well

By Dirk Bruere on Mar 17, 2013 at 9:19am

Thanks Andrew. The free radical mechanism is interesting and definitely a weak point in my current beliefs. I see it popping up all the time these days with regard to bird navigation by geomagnetic field in 1st tier journals.

I am more confused about ion cyclotron resonance. It is my understanding that the mean free path for even the lightest ion (proton) in the brain would be far under a nanometer. Since I cannot read Russian I do not know what argument these papers make for ion cyclotron resonance in such a high density and pressure environment as the brain. It seems like they wouldn’t by able to gyrate along the field at all before hitting something else. How do they get around it? Or, what premise am I assuming that is incorrect?

Mechanism of action aside, is the claim for weak field effects on the brain uncontroversial in Russia? I have been aware that there are many more studies of it over there than in the “west” but I thought these were mostly marginalized groups and not accepted by the main stream. These are really bold claims that require a high standard of proof.

Will you be putting the talk slides online anywhere afterwords?

By superkuh on Mar 17, 2013 at 6:22pm

> I see it popping up all the time these days with regard to bird navigation by geomagnetic field in 1st tier journals.

This is an old survey of such mechanisms by Binhi: biomag.narod.ru/pdf/1999.Binhi.WHO.pdf
It has been much updated since (into a 590 pp book published the last year grin. As for the ion-cyclotron resonance, this was a very hot discussion topic in the J. of Bioelectromagnetics a while ago, triggered by Liboff. The basic claims for it, for instance, include a claim that it can affect kinetics of ions movement inside an ion channel. You are correct, there are more arguments against it than for it, however we can’t fully discard it yet, and there is still the need to explain why ion-cyclotron/Larmour frequencies of common ions, in particular Ca2+, are biologically active. Binhi’s model of ion-protein complexes dissociation at such frequencies is probably the best explanation so far.

If you can somehow provide me your contact address (without giving it away to spammers grin I can send you quite a few papers on the topic that were actually translated.

> Mechanism of action aside, is the claim for weak field effects on the brain uncontroversial in Russia?

The claims are completely uncontroversial, the studies are mainstream, here are the organisers of the St. Petersburg conference I’ve mentioned - http://lfbm-congress.spb.ru/index.php/en/organizers (the second conference happens in Crimea).

Yes, the slides will be available after the talk at the meetup site. The first part (general mechanisms of nootropics action and pharmacology) is already there.

By Andrew on Mar 17, 2013 at 8:43pm

I’ve read the review paper you linked a couple times. Like the forefront of any research field it mostly covered the problems with the proposed mechanisms. They all had many but that’s okay and normal. It was very useful background and I have to admit it was my first introduction to the ion-protein complex theory.

As an aside, it might be interesting to note that calcium (and other divalent ions) tend to associate 3:1 (ion:lipid) with the negatively charged carboxyl groups at the head of the membrane phospholipids. And the replacement of monovalent by divalent cations causes a change in heat capacity as well as membrane fluidity.

But… I just cannot accept your claim that this field is uncontroversial or mainstream. The conference you linked to included topics such as homeopathy, structured water, “Noosphere equilibrium” and “Cosmic rhythms” as well as the relevant topic of weak magnetic field interactions with biology. This is not mainstream science and it is very controversial.

Thanks for the offer of the translated papers. I have a pretty good system for dealing with spam. Send them to weakfield@superkuh.com

By superkuh on Mar 18, 2013 at 3:15am

> But… I just cannot accept your claim that this field is uncontroversial or mainstream.

I stand corrected: uncontroversial and mainstream in Russia and ex-USSR in general.

> The conference you linked to included topics such as homeopathy, structured water, “Noosphere equilibrium” and “Cosmic rhythms” as well as the relevant topic of weak magnetic field interactions with biology.

Unfortunately the topic of weak stimuli effects traditionally attracts numerous “science freaks” and it is evident that for some reason the organisers of the conference did not do a good jobs filtering these out. However, I am referring to the relevant publications from well-established authors and groups such as previously mentioned.

I will mail you the papers when back from the office tonight.

By Andrew on Mar 18, 2013 at 6:09am


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