Dopamine and the frontal lobes

Idiot (update 3)

I just deleted my most frequently viewed youtube video by accident.

Very unhappy now.

It was called 'What is dopamine?' and is still available here on facebook but I seem to be too stupid to capture the sound without muffling it.

I put up $1 on Mahalo for anyone who can help me get it back but I had a look around myself and I'm not hopeful. Started a YouTube forum discussion too.

Maybe this is an opportunity to do a new one, speak slower and so on. Great.


Update: Mahalo linked me to a YouTube forum that already covered this. No undelete. Fuck.

Update 2: Laura linked me to a greasemonkey script that let me download the facebook video. It's now back on YouTube :)

Update 3: The video got picked up by Bora Zivkovic over at Scienceblogs.com :)

Philoctetes Center, I love you

Techno-Buddhism

Strongly recommend a recent NPR interview with J Hughes on technological change. The interview starts 45 min into the mp3 and is 8 min long. Interviewer Steve Paulson's knee-jerk reactions are textbook. Quote:

"This is really a profound challenge to the way most of us think about ourselves. I mean we we we think there is some core to who I am, to who you are, there is something essential that is continuous that kinda defines who we are. You're saying, from this scientific perspective you're mapping out, that that's an illusion."

Personally, I don't think like that, but I'm happy to listen to people who do.

Slippery slopes

Heard on the latest episode of Philosophy Bites:

"The slippery slope I think is a very unhelpful metaphor. When you're thinking about slippery slopes you need to know how slippery they are, what the coefficient of friction is and indeed what way they're pointing."

Enormously true. Made me lol heartily.

Me reading iPlant fiction

Having finally aquired a decent microphone I decided to do a reading of the first two chapters of my novel-in-writing, creatively named iPlant. Wish I didn't sound so morose but if you go back and change things every time it doesn't sound right you never get anything uploaded. My hope is that I'll be able to record chapter three without actually doing any writing; have it be a bit more like storytelling and then simply cut away everything I don't want before finally converting it back to text. We'll see. Anyway, here's chapter one and two.

Using Medtronic's Reclaim implant to generate artificial motivation

(This post was re-printed on the Institute for Ethics and Emerging Technologies website and on Future Blogger)

I recently blogged and vlogged about Medtronic starting a clinical trial where deep brain stimulation (DBS) would be applied to the ventral striatum (part of the human reward circuit) to treat depression in up to 200 patients. Then the article on CNNmoney that I was basing this on disappeared and I worried that the whole thing might have been a mistake or a hoax. But the article has resurfaced on the Wall Street Journal and elsewhere, and I finally got around to digging up Medtronic's original press release from 19 Feb 2009, which confirms that they are conducting a clinical trial of DBS as a treatment for depression.

But more than that. It turns out that the entire implant procedure that they're using isn't new at all - it's the same procedure they use to treat OCD (recently FDA approved for up to 4000 patients). The implant is called Reclaim and (quoting the press release) "the anatomical target in the brain is the.. ventral striatum.. which is a central node in the neural circuits believed to regulate mood and anxiety". So it seems DBS implants have been placed in the human reward circuit since the OCD trials started, many years ago. This is good news because it means we're even better at putting DBS implants in the human reward circuit than I thought we were. Basically, DBS applied to the ventral striatum (VS) didn't just alleviate the behavioural tics of OCD patients but also improved their mood. Studies like Schlaepfer et al 2008 (3 patients) and Malone et al 2009 (15 patients), which I thought were ground-breaking, merely confirmed that DBS applied to the VS improves the mood of severely depressed patients as well.



My interest in all this, as always, is that electrical stimulation of the reward circuit is how rewarding brain stimulation (RBS) is generated in experimental animals (see Wise 1996 for a review). By changing the stimulation parameters of the Reclaim implant to match those used in RBS-experiments we should thus be able to use the Reclaim implant to generate RBS in humans. Such RBS could subsequently be used as an operant reinforcer (a pleasurable reward) to motivate difficult behaviors in people lacking self-discipline, as described in the programming section on the iPlant website, and as demonstrated in animal experiments such as Burgess et al 1991, Garner et al 1991 and Hermez-Vasquez et al 2005. It would be an important step toward artificial motivation.

Now, the researchers who apply DBS to the human reward circuit are fully aware that the procedure could generate RBS but try to avoid it. Quoting Schlaepfer et al 2008: "Subjective effects were assessed using the morphine-benzedrine group subscale of the Addiction research center inventory.. scores were 0 for all patients.. there was no 'liking'.. in contrast to findings reported by Heath, who observed that.. electrodes in subcortical structures induced extreme rewarding effects (Heath 1972)." Basically, clinicians today use DBS electrodes to disrupt or normalize electrical activity in dysfunctional brain regions, not to stimulate. They use stimulation parameters different from those applied in RBS-experiments. But by not engaging in discussion and research into beneficial applications of RBS in human beings we are missing an important opportunity.

For example, human RBS could be used to motivate heavy physical exercise, as previously demonstrated in rats (Burgess et al 1991, Garner et al 1991). At the time of writing DBS has been applied twice to treat obesity by suppressing hunger, with varying degrees of success (eg Hamani et al 2008). Human RBS made conditional on the patient engaging in physical exercise might have a more reliable effect, especially considering the health benefits of rigorous exercise. Conditional RBS could also be used to motivate learning and other behaviors that some individuals find exceedingly difficult, as previously demonstrated in rats (Hermez-Vasquez et al 2005).

Conditional RBS in humans would require a patient-doctor agreement and supporting technology to ensure that RBS is delivered if and only if the patient engages in desirable, pre-specified behaviours, such as the use of a rowing machine or an exercise cycle. Such an arrangement, where the patient voluntarily accepts restrictions on his/her ability to activate the Reclaim implant, raises a number of ethical issues that need to be articulated and discussed.

There is also a more practical question as to what stimulation parameters would best support RBS in the human VS. I think the reason DBS to the human VS does not have rewarding effects in current studies is that researchers are using too high a frequency, too narrow a pulse-width and/or a biphasic as opposed to a monophasic pulse. This question could be addresed immediately if some of the patients who have already recieved a Reclaim implant would be willing to participate in a study to assess the effects of temporarily changing the stimulation parameters of their implants to match those used in animal experiments involving RBS.

Wired-article-induced neuroscience rant

Part of the reason I enjoy researching, writing and talking about neuroscience is sheer awe. Gradually realiazing how one's conscious will can be understood as a physical process is threatening to some but I find it enormously fascinating and liberating. Neuroscientific understanding is often counterintuitive, because our cultural understanding of ourselves has been - and still is - uninformed by neuroscientific fact. But that growing body of fact is true, and potentially enormously empowering.

That brings me to another reason I do what I do: I want to help people redesign their brains, should they want to. Quoting a recent article in Wired about transcranial magnetic stimulation (TMS) and neuroengineering:

"However odd or uncomfortable the idea of engineering the human brain might seem, if yours is broken enough, the philosophical arguments cease to hold any water: You just want it fixed."

and

"What bit of themselves would each of us wish to control? Where would we direct our own TMS, if we could? It's a terrible responsibility to consciously shoulder. What is the mind that's choosing the shape of its own brain?"

So, what are the options?

Pharmaceutical drugs and other psychoactive substances is the obvious one. Keep an eye out for over-the-counter stimulants in the next few years (see this recent article in Nature on cognitive-enhancing drugs).

Transcranial magnetic stimulation (TMS) is another important technology. Look for TMS equipment that can be used in the privacy of your own home (open-source initiative here, dedicated blogs here and here).

And finally there is deep brain stimulation: currently rare and somewhat dangerous but poised to go mainstream given its extraordinary potential as well as the willingness of people and surgeons alike to operate on healthy individuals (plastic surgery). Look for success in Medtronic's rumoured depression trial and pilot studies applying conditional rewarding brain stimulation to treat obesity and related problems.

Anyway, enough of this, spring is here - time to go buy the year's first football.