Omte back in the lab

Daniel Nocera and Angela Belcher - The Role of New Technologies in a Sustainable Energy Economy (1h32min, iTunes). I found this one particularly interesting because Daniel is both an expert in energy and a provocateur regarding the climate change solutions we usually hear about. For example, everyone would have to adopt the lifestyle of the people of Equatorial New Guinea for worldwide energy expenditure to approach a level that's even remotely manageable in terms of green energy. Which makes the silly Earth Hour seem... well, silly. Daniel's solution is new technology, specifically solar power. I agree. And so did the Londoners.

Christine Peterson - Thinking Longer-Term About Technology (58min, iTunes). A very good talk about if and how we can predict future technologies. Mentions something called prediction markets that have made a business out of this. Christine founded Foresight Nanotech Institute and says she has a blog but I can't find it.

Craig Venter - Joining 3.5 billion years of microbial invention (1h49min, FORA.tv). Man Craig is becoming a rock star. Easy to see why though.

Why we should develop electronic modulation of monoamines for human use

(Also available on IEET and Future Blogger)

Deep brain stimulation (DBS) is a surgical procedure involving the insertion of a small electrode into the brain to modulate electrical activity. Over 40.000 patients worldwide have undergone placement of Medtronic Activa, the most popular DBS system (Schwalb & Hamani, 2008).

The connectivity of cortical and subcortical brain tissue is often too intricate to parse information from a single DBS electrode. Generation of meaningful visual perception by stimulation of the visual cortex for example requires a large number of much smaller electrodes (Schmidt et al, 1996). DBS is therefore used merely to suppress or normalise electrical activity in dysfunctional brain regions (hence the nickname 'brain pacemaker').

However, many monoaminergic neurons in the midbrain and brainstem fire in unison and project widely throughout the brain: by stimulating neurons that produce dopamine for instance, researchers can directly modulate dopamine concentrations in diverse cortical and subcortical regions (Hernandez et al, 2006; Garris et al, 1997; Fiorino et al, 1993; Bean & Roth, 1991). Stimulation of dopaminergic neurons, serotonergic neurons or the nerve bundles that carry their axons to cortical and subcortical targets is highly rewarding and is referred to as brain stimulation reward (BSR) in the literature.

BSR motivates animals to perform behaviors with which it is repeatedly associated and has been used to drive behaviors such as heavy physical exercise and learning (Burgess et al, 1991; Garner et al, 1991; Hermer-Vazquez et al, 2005). It seems likely that DBS of monoaminergic regions would support BSR also in humans and that it could be used to motivate behaviors such as physical exercise and learning.

There are two reasons to develop monoamine modulation by DBS (MMDBS) for human use:

• First, MMDBS could have a devastating impact on humanity if developed under autocratic regimes without public oversight and vigorous debate. It could for instance be used to create large factories of workers addicted to manual labour. Even if developed in a democracy there are numerous human rights concerns associated with MMDBS, including access control by the manufacturer, the potential for over-use, and aggravation of societal inequalities. These are very difficult problems whose solution will require the concerted effort of democratic societies.

• Second, MMDBS could be enormously beneficial if developed responsibly. It could help people exercise, thus attenuating the healthcare crisis in general and the obesity epidemic in particular. It could be combined with learning tutorials to aid people with learning difficulties. It could be used to motivate people to complete scientific research protocols, thus accelerating research in critical fields such as renewable energy and biomedicine. Moreover, it might offer a more dynamic alternative to pharmacological modulators of monoamines such as stimulants and antidepressants.

www.iPlant.eu is a discussion group promoting the development of beneficial electronic modulation of monoamines for human use. For more information, please visit our website or join our forum.

Tibet again

Herald Tribune article on China-Tibet, emphasizing an anger among many Chinese, in China and abroad, toward the world press for what they see as a distorted, pro-Tibetan reporting of the riots in Lhasa and elsewhere (look here for reporting that is probably more appreciated.. eeh..). There are (highly recommended) exceptions of course, but I wasn't aware of the balancing act Hu's government has to make in appeasing anti-autocratic human rights sentiments in the West on the one hand, and a national sentiment demanding even harsher treatment of the Tibetan rioters on the other. My question is: why maintain such strong nationalism in the first place?

And did you know the Olympic flame is gonna climb mount everest? :O

Brain stimulation reward papers 3

Medial forebrain bundle (MFB)
Ventral tegmental area (VTA)
Nucleus accumbens (NAcc)
Dopamine (DA)

Feng Zhou-yan et al (2007) A remote control training system for rat navigation in complicated environment. A wireless MFB and whisker sensory cortex stimulator for rat remote control.

Fiorino et al (1993) Electrical stimulation of reward sites in the VTA increases DA transmission in the NAcc of the rat.

Gallistel & Leon (1991) Measuring the subjective magnitude of BSR by titration with rate of reward.

Mark & Gallistel (1993) Subjective reward magnitude of medial forebrain stimulation as a function of train duration and pulse frequency.

Gallistel et al (1991) Effect of current on the maximum possible reward.

Sax & Gallistel (1991) Characteristics of spatiotemporal integration in the priming and rewarding effects of medial forebrain bundle stimulation.

BSR professor of the day
Randy Gallistel of Rutgers University, New Jersey.
Stemmy (2004) Biography of Charles R Gallistel.
Gallistel (2004) Foraging for brain stimulation: toward a neurobiology of computation.
Gallistel et al (2004) The learning curve: implications of a quantitative analysis. Argues that the 'learning curve' is not smooth but abrupt.

In other articles
Kapogiannis (2008) Reward-related activity in the human motor cortex.

Meeusen et al (2006) Central Fatigue: The Serotonin Hypothesis and Beyond. Very cool, seems buildup of serotonin is generally believed to make you tired during exercise. This paper emphasises a paralel decline in the concentration of catecholamines.

Discham et al (2005) Neurobiology of exercise. General paper on the beneficial effects of exercise on brain function. Go run.

Mind as body

Craig Venter - Advancing the Genomic Revolution (1h26min, iTunes). I'm starting to like Venter more and more, here he's describing the sequencing of the human genome a few years ago. Did NOT know he was on the Celera team.

Chris Phoenix - Molecular Manufacturing (1h2min). Interesting talk, interesting speaker, interesting haircut. Overoptimistic? He says molecular manufacturing is ca 10 years away with singularitarian spinoffs to be expected. One quote in particular stood out: "If we get into an arms race with this technology I'm not at all sure that we'll get out of it. I do not know how to avoid it. This is a serious problem. And.. I don't know how to say it pessimistically enough: there is no known solution to keep us out of an arms race that would lead to devastating war."

Phoenix's presentation includes this 4min demonstration of what molecular manufacturing is aiming for. Science fiction? Sure. Damn cool? Oh yea.


Here's a short example of how to live a green life (solar panels and goats included) and still be a funky person with an internet connection. From BoingBoing TV. The dude also has a blog.


Finally... There is a very good interview on BBC Hard Talk running today, with Chinese writer and human rights defender Liao Yiwu. Liao is censored all over China, spent four years in prison for his books and has been translated to many major languages. The interview is available here but it's in stupid RealPlayer format. For a good analysis of this very salient topic, search for Human Rights and Political Reform in Contemporary China (1h2min, iTunes) with our own Börje Ljunggren (whooo).

iPlant ethics: is electronic neuromodulation too dangerous?

In response to the iPlant video, richardpinder and cromwell1646 write the following (my emphasis):

richardpinder:
I can see where you are coming from with this technology with regards to taking it in a positive direction. However I think that this science is far too dangerous, more so than every other science I have knowledge of to be allowed public. The massive risks of this technology is that it can lead to complete mind control. Anything can be hacked given time thus it wont be possible to make this hack proof. This technology can be used to control free will and should be banned now. I hope you fail.

cromwell1646:
Dear Sir,
I have just watched you video on your iPlant. I think you are coming at a problem from a positive direction. However this technology could be easily and seriously abused.
I am a programmer and I can tell you categorically its possible to hack into anything given enough time. The implications of this technology is it could be used to control someones mind against their will in the wrong hands.
This means that the cult like problems of today and people being bent to do something extremely negative against their will pales into insignificance compared to what this could do.
To spell it out this could be used in countries ruled by a dictator to control its people. It could be used by Religious extreme groups to make the perfect suicide bomber. It could be used by criminal organisations to commit crimes.
In the instance you are not motivated by personal consequences of your actions I will highlight the consequences to you as a business entity. The second someone does something illegal as a result of either your chip being hijacked or malfunctioning you will be sued to pieces.
For these reasons if you really want to contribute something positive I urge you to take this in another direction or look at something else entirely. For the moment in time I am open to discussion on this subject.
However should you be unwilling to debate this I will highlight exactly why this technology should not be allowed in the public eye through the media and this will in all likely hood irreversibly destroy your reputation. I would consider this just and fair and for the greater good. However as I am reasonable I am giving you opportunity to answer this.
James Cromwell

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Both replies exemplify an attitude many people develop toward the iPlant:

(1) it would enable total mind control and
(2) should therefore not be developed

(1) I certainly agree that the iPlant would have considerable potential for abuse. However, let's not overstate the level of control it could give you over another person. Brain stimulation reward generates motivation by repeatedly reinforcing specific, simple behaviors. In animal models this training process takes time and works only for elementary behaviors (e.g. physical exercise). Manchurian candidate scenarios involving total behavioral control over another person may therefore be of lesser concern. A more realistic problem is that of an authoritarian regime using iPlants to create large factories with workers addicted to manual labor. If you think I'm wrong about this technical detail please make it known on the forum as soon as possible. It may be possible to reprogram an iPlant user to endlessly perform some repetitive action against their will, but since the implant would contain no radio receiver this would have to involve kidnapping the person, which seems like an excessively laborious way of causing harm.

(2) I do not agree that malicious mind control and other risks associated with electronic neuromodulation (see 'concerns' below) can be avoided by banning iPlant research. This is because the iPlant is merely the result of combining an established theory (brain stimulation reward) with an exceedingly popular electrosurgical procedure (deep brain stimulation) (see the Journal of Neuromodulation and the Journal of Brain Stimulation for research in this field). There is no doubt in my mind that other scientists will soon see the enormous potential of this simple idea and quickly develop it. In the iPlant group we feel it is better if iPlants are developed in a democracy, with public oversight and vigorous debate, than under an authoritarian regime. We are trying to understand the impact of iPlants on human life and how they can be used for good, but we are certainly not ignoring the risks: the bulk of the discussion on the forum concerns potential dangers and objections, and these are summarized in the ethics section of the iPlant website.

I truly appreciate your criticism and hope you will add more points to the list of risks below AND join the forum to help us solve these problems. Not merely because iPlants have a much better chance of developing into something good in a democracy, but because they may be of enormous benefit to individuals suffering from poor self-control, and to society as a whole. Please try to sympathize with people whose lives are destroyed because of their inability to exercise self-discipline: people dying in the obesity epidemic; alcoholics and drug addicts; the millions of people living with severe learning difficulties. Moreover, global problems such as climate change and the healthcare crisis could benefit greatly from iPlant-driven research.

I look forward to hearing from you again.
Christopher

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Concerns (from the ethics section on the iPlant website)

This part of the site is under development, with the aim to organize and begin addressing ethical, behavioral and social objections to the development of the iPlant. For a more thorough discussion see the forum. Purely technical or medical problems are discussed in the implant technology section.

Access control
Several factors, such as the potential for over-use, suggest that iPlants will have to be subject to robust access control by their manufacturer. This raises problems of trust on the one hand and of security and hacking on the other.

Addiction
People might bypass the need to perform difficult tasks and self-stimulate ad infinitum (similar to Larry Niven's wireheads). This problem may be avoided by ensuring robust access control by the manufacturer.

De-humanization and over-use (discussed here)
Some people worry that iPlants would blur the line between human being and machine. Concerns have been raised that iPlants would make society rougher and more competitive, and leave less time for relaxation and socializing. It has also been suggested that people could become too dependent on their iPlants and not develop self-dicipline of their own, and, similarly, that their feelings of accomplishment and self-worth might be undermined.

Inequality
iPlants could create a division in society between the haves and the have-nots. This would be a problem for people who can't afford an iPlant, can't have one for medical reasons, or who simply don't want one.

Mind control (discussed above)
The fear that iPlants could be used to control other people against their will.

Unpredictability
The Jurassic Park argument. It seems extremely difficult to predict what the world would be like if people had safe, affordable access to iPlants (see philosophy and fiction).

Easter is over, piglet be gone, back to work

Richard Harrison, 1910 - A conversation with Thomas Harrison (iTunes U, 1h3min). This is without reservation the best, most in-depth conversation about this crucial point in history that I've ever come across. The focus is on expressionist artists and authors, and Richard and his brother Thomas have no illusions about the explosive irrationality and the dark that the people of this time finally probed, and saw in themselves and in the future. I have no difficulty understanding why some of Harrison's listeners write that their sanity depends on his show (listen live on Wednesdays 00:00 GMT). Googled 'scientific expressionism', thinking maybe, maybe, but all that comes up is a 2004 exhibition that I don't have access to.

Let me quote you some Nietzsche while I'm at it. From Ecce Homo, written one year before his mental breakdown, two years before his death, ten years before the publication of the book, and twelve years before 1910:

"I know my fate. One day there will be associated with my name the recollection of something frightful -- of a crisis like no other before on earth, of the profoundest collision of conscience, of a decision evoked against everything that until then had been believed in, demanded, sanctified. I am not a man. I am dynamite."

In other news, here's the best article I've read on the China-Tibet-Olympics issue: Why China might have Olympic regrets (Dominic Lawson, The Independent). And while I'm on about things I'm ashamed to say I didn't know: the number of civilians killed in the 1989 Tianamen Square protests is a three figure number. That's a big number and an instance of Lawson calls "the Chinese Communist Party's almost pathological inability to cope with any genuine form of political opposition". I've yet to find a good analysis of the reasons for this allergy.

Hu Jintao's new year's speech:


Hu Jintao on the road:


And some utterly unrelated schadenfreude:

Brave New World

Google, financial backer of 23andMe now also funds the Harvard based Personal Genome Project, which aims to sequence the DNA of 100.000 individuals, starting in the UK, US, China and, whooooo, Sweden, later this year. Combined with Google Health, now in pilot stage trials involving thousands of patients, this is personalized medicine. Google Health will be available in a few months if I read it right.

iPlant philosophy: a model of the singularity?

(Also available over on Future Blogger and on the iPlant website)

I sometimes feel that scientists have lost touch with the profound and the sublime, whereas transhumanists and philosophers have lost touch with science - with utility. Hume saw that causality cannot be articulated (Hume, 1739, 1748); he did not say it should therefore be reduced to a topic of rationalization and used only to cultivate one's social loci.

What happens when neruoscience dissolves the distinction between mind and body? What happens when the intimate, subjective and irrational human mind is fully integrated into the logic of science, and a stable, effective and lucid, yet decidedly neuroscientific model (M1) of the mind is realized? Eliminativists speak about the end of our common-sense understanding of the mind, but offer only vague speculations as to what might replace it (Churchland, 1981). Is this a technological singularity - a point in history so complex and fast-moving that we cannot see beyond it?

The iPlant can be used as an intellectual probe, to model and better characterize the social impact of M1. A critical aspect of scientific models is that they allow us to improve on the systems that they describe. The iPlant helps us improve on the strongest current candidate for M1: the cognitive neuroscience of monoamines, particularly the dopamine model of attention-allocation and learning (Lindskog et al, 2006; Djurfeldt et al, 2001). It is a self-help chip.

Monoamine modulation has given us profound social insight and change in the past; I'm thinking of drugs like Ritalin, coffee, Prozac and LSD, all strong modulators of the monoamines. But the iPlant introduces dynamics: the ability to shape monoamine modulation with an unprecedented temporal resolution. Suddenly, our minds become capable of functions such as rewarding brain stimulation, first demonstrated in rodents (Olds & Milner, 1954) and humans (Heath, 1963) half a century ago; and psychological concepts like motivation are reconceptualized as something closer to their true nature: as monoaminergic selection of corticothalamic and corticostriatal loops.

I challenge you to show me that the iPlant is not a good model for a technological singularity, or that the cognitive neuroscience of monoamines is not M1, by describing, with a reasonable level of certainty and detail, a time beyond the event horizon that a few hundred iPlants constitute. To quote the forum:

"Say the iPlant is made available in 2015-2020 but works only with a running machine, a rowing machine and a weight-lifting machine (qua Burgess et al, 1991, Garner et al, 1991). Initially you have to be clinically obese to get the surgery but as the procedure becomes routine all you really need to do is say the right things to your doctor (think Prozac or Ritalin). The implant motivates you to use the machines, but not for more than two hours per day. A few people hack it and screw themselves or others up but it's extremely rare. Within a few years 10% of people have an iPlant but although learning and research programs are being developed they're not yet available. What can we say about this situation?"

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Coming up: interviews with people and experts on their thoughts and feelings about the iPlant, with particular focus on philosophical hot-spots like free will, consciousness and the human condition.

For discussion, see the forum or the blog.

Some night

Arthur C Clark, inventor of the communications satellite, SF demigod, dies in his home in Sri Lanka. He was 90 years old.

Obama, hopefully the next US president, political genius, delivers a monumental speech worthy of King or Malcom (37min). Please do not get assassinated like they did, like Bhutto did. Please.

(Am I posting it again? Yes I'm posting it again, I'm gonna make my whole family watch it tonight)

Demo of the new Android programming language (6min)


State of the art humanoid (3min)


Global warming argument that's got 3.6 million views in a few months (9min). The flaw in his argument, as far as I can see, is that he doesn't take into account the extent to which a slowdown in the economy will reduce our ability to develop new technological solutions to a climate crisis.


Finally, in a scene out of a Stieg Larsson novel, an Indian captive blood donor ring is smashed; the number of freed 'hostages', held for many months, drugged and 'milked' for blood on a daily basis, is at 17 and rising. But how about not ending on that grim note?

Obama Speech: 'A More Perfect Union'

Deep brain stimulation papers 3

The hypothalamus, apparently a common deep brain stimulation (DBS) target in the treatment of cluster headaches (CH), has also been tried for facial pain, obesity, and aggression. The lateral portion of the hypothalamus contains a segment of the medial forebrain bundle (MFB) and is exceptionally supportive of brain stimulation reward (BSR).

Obesity

Sani et al (2007) DBS for treatment of obesity in rats. Rush University Medical Center. DBS of the lateral hypothalamus decreased food intake in rats. Interestingly, the authors use 0.25mm diameter bipolar electrodes.

Lacan et al (2008) Modulation of food intake following DBS of the ventromedial hypothalamus in the vervet monkey. Laboratory investigation. David Geffen School of Medicine at UCLA. Bilateral DBS of the ventromedial hypothalamus increased food intake in two vervet monkeys.

Hamani et al (2008) Memory enhancement induced by hypothalamuc/fornix DBS. University of Toronto. Hypothalamic DBS inadvertently triggered strong recall.

Aggression

Franzini et al (2007) Chronic high frequency stimulation of the posteromedial hypothalamus in fascial pain syndromes and behaviour disorders. Instituto Nazionale Neurologico Carlo Besta. Posteromedial hypothalamus DBS as a treatment for aggression.

Franzini et al (2005) Stimulation of the posterior hypothalamus for medically intractable impulsive and violent behavior. Instituto Nazionale Neurologico Carlo Besta. Posterior hypothalamus DBS effective treatment for aggression in two patients.

Cluster headache

Vetrugno et al (2007) Effect on sleep of posterior hypothalamus stimulation in CH. University of Bologna. Posterior hypothalamus DBS improved sleep in three CH patients and had no effect on body temperature.

Starr (2007) Chronic stimulation of the posterior hypothalamuc region for CH: technique and 1-year results in four patients. University of California at San Francisco. Posterior hypothalamus DBS produced a 50% reduction in CH intensity/frequency in two of four patients.

Bussone et al (2007) DBS in craniofascial pain: seven years' experience. Fondazione IRCCS Instituto Neurologico Carlo Besta. Posterior inferior hypothalamus DBS resulted in a persistent pain-free or almost pain-free state in 13 of 16 treatment-resistent CH patients. (a similar paper from the same group here.)

May et al (2006) Hypothalamic DBS in positron emission tomography. University of Hamburg. The authors argue against a simple inhibition based model of hypothalamic DBS in CH treatment.

Schoenen et al (2005) Hypothalamic stimulation in chronic cluster headache: a pilot study of efficacy and mode of action. CHR Citadelle. Out of six patients ventroposterior hypothalamus DBS is highly effective in three cases, fatal in one.

Miscellaneous

Cortelli et al (2007) Effect of DBS of the posterior hypothalamic area on the cardiovascular system in chronic CH patients. University of Bologna. Posterior hypothalamic DBS is associated with certain cardiovascular changes.

Cordella et al (2007) Spontaneous neuronal activity of the posterior hypothalamus in trigeminal autonomic cephalalgias. Fondazione IRCCS, Istituto Nazionale Neurologico C. The authors seems to have used the DBS electrodes of three patients to record the activity (24 spikes/s, random, tonic) of a handful of neurons in the posterior hypothalamus. Did not know you could just do that.

Tibet

The first of what I fear will be many articles posted here on the China-Tibet issue.

A longish spiel on the erosion of Tibetan culture. Things like school being taught in Chinese. But then again before the Chinese came flooding in most Tibetans never learned to read and write in the first place. Is it tradition versus progress? Tradition versus progress and state-controlled media :P Anyway, was surprised to learn that the Dalai Lama does not desire a boycott of the Beijing Olympics despite the rising death toll and (accusations of) cultural genocide.

Taket och botten

I hope you speak Swedish, because my mum wrote me an email on my outlook on life a little while ago that I'd like to post. Many similarities to what dad said, and I don't still don't have any clear answers.

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Förresten! Jag pratade med en av våra läkare i gårmorse och berättade lite om dig och din reduktionistiska syn på livet. Det som jag har undrat är, framför allt, om du tycker att livet är mindre värt bara för att vi ser ut som vi gör , med kemiska reaktioner och allt, eller om du tycker att det gör livet alltför förutsägbart och därmed mindre värdelöst. Det har oroat mig faktiskt. Anyway. Jag frågade om han också trodde att vi inte har nån fri vilja. Nej det trodde han inte! Allt är styrt av kemiska reaktioner. Är livet mindre värt för det då? Absolut inte. Han så på livet som en tågresa. Man hoppar på tåget på en station och hoppar av på en annan station. (Man föds och man dör). Så sa han nåt som jag tyckte var bra: din son studerar tågets beskaffenhet, medan du och din man studerar resan.

Var inte det fint va! Jag blev jätteglad! Hoppas du kan instämma i denna enkla förklaringsmodell för våra olika ståndpunkter.

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Coolest thing I've seen in years!

π day :)

Brain stimulation reward papers 2

Brain stimulation reward (BSR) research seems focused mainly on understanding the anatomy, chemical contingiencies and optimal stimulation parameters of the circuit, and less on developing operant conditioning protocols. Authors like Burgess et al (1991), Garner et al (1991), Talwar et al (2002), Hermer-Vasquez et al (2005), who use BSR to generate specific, useful behaviors, are, at the moment, in minority. The limits and potential usefulness of complex operational conditioning by BSR remain largely unexplored.

Brain stimulation reward (BSR)
Medial forebrain bundle (MFB)

Waraczynski (2006) The central extended amygdala network as a proposed circuit underlying reward valuation. University of Wisconsin-Whitewater. Review suggesting that the anatomical substrate of BSR is largely contained in the extended amygdala.

Waraczynski (2008) GABA receptor agonism in the sublenticular central extended amygdala impairs MFB self-stimulation but GABA blockade does not enhance it. University of Wisconsin - Whitewater.

Ludvig et al (2007) The effects of reinforcer magnitude on timing in rats. University of Alberta.

Spiller et al (2008) The selective dopamine D(3) receptor antagonists SB-277011A and NGB 2904 and the putative partial D(3) receptor agonist BP-897 attenuate methamphetamine-enhanced BSR in rats. National Institute on Drug Abuse.

Kentner (2007) Investigating the hedonic effects of interferon-alpha on female rats using BSR. University of Ottawa. Using BSR to investigate the hedonic impact of a cytokine cancer treatment (no effect).

Schulteis & Liu (2006) Brain reward deficits accompany withdrawal (hangover) from acute ethanol in rats. UC San Diego School of Medicine, VA San Diego Healthcare System. Alcohol intoxication attenuates BSR efficiency.

Bespalov (2006) Lowered BSR thresholds in rats treated with a combination of caffeine and N-methyl-D-aspartate but not alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate or metabotropic glutamate receptor-5 receptor antagonists. IP Pavlov Medical University.

Waraczynski & Bemco (2006) Lidocaine inactivation of the ventral pallidum affects responding for BSR more than it affects the stimulation's reward value. University of Wisconsin at Whitewater. Inactivation of the ventral pallidum reduces maxium behavioural BSR response. Sometimes.

Kornetsky & Bain (1992) BSR: a model for the study of the rewarding effects of abused drugs. Boston University School of Medicine.

Milner (1991) BSR: a review. McGill University.

Brain stimulation reward papers 1

Brain stimulation reward (BSR)
Medial forebrain bundle (MFB)
Ventral tegmental area (VTA)
Nucleus accumbens (NAcc)
Dopamine (DA)

Mauge et al (2005) Early developmental exposure to methylphenidate reduces cocaine-induced potentiation of BSR in rats. Harvard Medical School.

Fulton et al (2006) Potentiation of BSR by weight loss: Evidence for functional heterogeneity in brain reward circuitry. Concordia University. BSR is potentiated by chronic food restriction, but this effect depends on the exact site of stimulation along the MFB.

Eiler et al (2007) Responding for brain stimulation reward in the bed nucleus of the stria terminalis in alcohol-preferring rats following alcohol and amphetamine pretreatments. Indiana University-Purdue University at Indianapolis. Rats bred to prefer alcohol are sensitive to RBS in a new region of the basal ganglia.

Morissette & Boye (2008) Electrolytic lesions of the habenula attenuate brain stimulation reward. University of Montreal. Electrolytic lesions (?!) of the habenula (thalamic region that projects to midbrain monoamine nuclei) attenuates RBS in posterior lateral hypothalamus, VTA, dorsal and median raphe nuclei.

Miguelez & Bielajew (2004) Mapping the neural substrate underlying BSR with the behavioral adaptation of double-pulse methods. University of Ottawa.

Valchou et al (2006) Effects of endocannabinoid neurotransmission modulators on brain stimulation reward. University of Crete, Eli Lilly. Cannabinoids attenuate BSR.

Lassen et al (2007) BSR is integrated by a network of electrically coupled GABA neurons. Brigham Young University, University of New Mexico, Western University of Health Sciences. Electrical coupling in a large network of GABA neurons is required for BSR.

Eiler et al (2006) Amphetamine lowers brain stimulation reward (BSR) threshold in alcohol-preferring (P) and -nonpreferring (NP) rats: regulation by D-sub-1 and D-sub-2 receptors in the nucleus accumbens. Indiana University-Purdue University at Indianapolis. Rats bred to prefer alcohol are no more sensitive to BSR curve-shift by DA agonists and antagonists.

Choi et al (2004) Simultaneous AMPA/kainate receptor blockade and dopamine D2/3 receptor stimulation in the nucleus accumbens decreases brain stimulation reward in rats. University of Texas, University of Alberta. AMPA and D2/3 receptor blockade in the NAcc must be simultaneous to attenuate BSR.

Meh

Scientific American is running a self-experimentation special starting with Kevin Warwick's 2003 feat, and Developing Intelligence has a caffeine how-to post (thanks Laura).

Brainmaps.org has some pretty neat high res images of... well... everything.

Finally, an ambitious Craig Venter at TED. Good speaker (34min, TEDtalks).

Shameless rip

Rejuvenation breakthrough: hat tip to Kristella for putting me onto this video of Phun, the (Swedish! whooo!) 2D physics program that temporarily made me 10 years old again. For a more permanent effect, download the program here.

Mixed links

Official website of the Beijing 2008 Olympics
Kevin Warwick's 2003 self-implant paper (5 pages pdf)

Synofzik (2007) Intervening in the neural basis of one's personality: a practice-oriented ethical analysis of neuropharmacology and deep-brain stimulation. Deutsche medizinische Wochenschrift 132(50), p2711-2713.

McGee & Maguire (2007) Becoming Borg to Become Imortal: Regulating Brain Implant Technologies. Cambridge Quarterly of Healthcare Ethics 16, p291-302.

Ford & Kubu (2006) Stimulating debate: ethics in a multidiciplinary functional neurosurgery committee. Journal of Medical Ethics 32, p106-109.

Deep brain stimulation papers 2

(13 page pdf) Anderson et al (2004) Mechanisms of deep brain stimulation: an intracellular study in rat thalamus. J Physiol 559(pt1), p301-313. Intracellular recordings from thalamic rat slices during 125hz electrical stimulation. The authors find two distinct membrane responses that may underlie 'functional inactivation'.

(11 page pdf) McIntyre et al (2004) How does deep brain stimulation work? Present understanding and future questions. J Clin Neurophysiol 21(1), p40-50. Review paper that looks at four hypotheses for the mechanism of DBS in movement disorders: depolarization blockade, synaptic inhibition, synaptic depression and stimulation-induced modulation of pathologic network activity.

(20 page pdf) Feng et al (2007) Toward closed-loop optimization of deep brain stimulation for Parkinson's disease: Concepts and lessons from a computational model. J Neural Engineering 4(2), l14-21. The authors describe an algorithm for closed-loop selection of novel, more efficient DBS waveforms.

(3 page pdf) Kiss et al (in press) Frequency dependent effects of deep brain stimulation: Clinical manifestations and neural network modelling. When low DBS frequencies (2,5hz-20hz) are applied to traditional targets there is a worsening of motor symptoms, suggesting an activating as opposed to inhibiting effect and possibly indicating appropriate frequencies for DA(t) and 5HT(t).

Bekar et al (2007) Adenosine is crucial for deep brain stimulation-mediated attenuation of tremor. Nature Medicine 14, p75-80. The authors suggest that DBS induced inhibition of thalamic tissue is mediated by stimulation of local adenosine receptors.

In other news, Entitled Opinions is a Stanford University radio show hosted by Italian lit prof Robert Harrison. The 1hr long discussions are on iTunes (why does everything academic on iTunes seem to come out of Stanford or Berkeley? Mostly litterature, including some gems like Heidegger, Freud, Nabokov and the Historical Jesus. I've only heard one full interview (a stimulating interview with a gloomy Richard Rorty) but they all seem very authentic, if you're in that kind of mood.

Posthuman, all too posthuman?

"Deep brain stimulation should be confined to therapeutic contexts and to severe, otherwise treatment-refractory disorders in which the aim is to normalize brain functioning. Apart from this, it should not be used to modify a person's individual character traits and behaviour or to enhance human traits." - Hildt (2006) Electrodes in the brain: some anthropological and ethical aspects of deep brain stimulation (7 pages, pdf)

Hildt draws on two lines of argument to reach this conclusion. One involves medical risks and side-effects associated with brain surgery. The other is the Dehumanization Argument, characterized by concerns such as "technicalization of the human body, the encouragement of a reductionist, technological view on human beings, the fear of losing human identity, and speculations relating to cyborgs".

The fear of losing human identity is something I encounter often in discussion about the iPlant. We all accept that it is better if human nature is civilized - no one likes a brute - but we also feel that too much civilization, by a totalitarian state or exceptionally strict parents for example, takes away too much of our initial, organic human nature. Many people place psychopharmaca and brain implants in this category of things that may supress, damage or pervert the human spirit.

In his fantastic talk entitled 'Ambivalence of the Posthuman Condition' (20min, Changesurfer Radio) Erik Davis (personal website) offers a much more nuanced view. He attempts to find a middle-ground between this kind of anthropocentric bioconservatism and over-optimistic transhumanism. The posthuman condition like the postmodern condition, he speculates, is characterized by a loss of 'grand narratives', such as a static human nature and the inevitability of aging and death. Unlike Hilde, Davis doesn't 'take issue' with this, it's just the way it is, progress won't stop. He simply (for want of a better word) urges us to remain critical and creative, and not to loose sight of the quality and richness of the means in our messy technological pursuit of "crude or psychologically obvious" ends. It's an excellent talk. Good night.

Deep brain stimulation papers 1

Today's catch for the implant technology section.

Rossi et al (2007) An electronic device for artefact suppression in human local field potential recordings during deep brain stimulation. Journal of Neural Engineering 4, p96-106. This paper describes 'FilterDBS' - an algorithm for filtering out the DBS stimulus artefact so that LFP recordings can be made during DBS.

Motta & Judy (2005) Multielectrode microprobes for deep-brain stimulation fabricated with a customizable 3-D electroplating process. IEEE Transactions on Biomedical Engineering 52(5), p923-933. To facilitate long-term DBS of the small and inaccessible rat STN the authors describe a novel DBS implant. This is particularly relevant to iPlant research since monoamine nuclei are also very small and inaccessible, even in humans.

Gross et al (2006) Electrophysiological mapping for the implantation of deep brain stimulators for Parkinson's disease and tremor. Movement Disorders Suppl 14, p259-283. A review of the various electrophysiological techniques used to finalize target selection during DBS surgery.

Li & Andrews (2007) Trimodal nanoelectrode array for precise deep brain stimulation: prospects of a new technology based on carbon nanofiber arrays. Acta Neurochirurgica Suppl 97 (pt2), p537-545. A new generation of DBS electrodes constructed from carbon nanofibres?

McCreery et al (2006) Microelectrode array for chronic deep-brain microstimulation and recording. IEEE Transactions on Biomedical Engineering 53(4) 726-737. The effect of electrode and stimulus properties on tissue modulation.

[full article] Moss et al (2004) Electron microscopy of tissue adherent to explanted electrodes in dystonia and Parkinson's disease. Brain 127 (pt 12), p2755-2763. Electron microscopy of tissue remains on explanted DBS electrodes.

Wei & Grill (2005) Current density distributions, field distributions and impedance analysis of segmented deep brain stimulation electrodes. Journal of Neural Engineering 2(4), p139-147. How variations in electrode design affects stimulation properties.

Chou et al (2007) Surgical and hardware complications in subthalamic nucleus deep brain stimulation. Journal of Clinical Neuroscience 14/7), p643-649.Rodriguez-Oroz et al (2005) Bilateral deep brain stimulation in Parkinson's disease: a multicentre study with 4 years follow-up. Brain 128(pt10), p2240-2249. Follow-up study of 69 DBS patients at four years.

Nielsen et al (2007) Chronic subthalamic high-frequency deep brain stimulation in Parkinson's disease--a histopathological study. European Journal of Neuroscience 14(2), p132-138. Limited histopathological changes in the vincinity of DBS electrodes appear to be related to the electrode itself rather than electrical stimulation.

Butson & McIntyre (2006) Role of electrode design on the volume of tissue activated during deep brain stimulation. Journal of Neural Engineering 3(1), p1-8. Effect of variations in electrode design on stimulation properties.

Benabid (2007) What the future holds for deep brain stimulation. Expert Review of Medical Devices 4(6), p895-903. Discussion of the future of DBS.

Holy shit

Google CEO Eric Schmidt presents Google Health at the HMISS conference in Orlando. This is HUGE! Trust and effectiveness will be crucial. Anyway, here it is, 49 min:

In the news

Federal judge withdraws an earlier court order, letting WikiLeaks.org have it's domain name back. Damn right. Jonathan Glater discusses the issue further.

Israel kills 61 people in one day. I can't find words.

Women voters are moving away from Clinton towards Obama; enraging some feminists, whilst others say they won't vote for an early supporter of the Iraq war just because she is a woman. Robin Tuner discusses the gender issue further.

Check this out, even I get a bit worried: Savulescu & Sandbert (2008) Neuroenhancement of Love and Marriage: The Chemicals Between Us. Neuroethics 1(1), p31-44.

What is an iPlant?