Showing posts with label brain enhancement. Show all posts
Showing posts with label brain enhancement. Show all posts

14 March 2009

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.

09 December 2008

How compliant do we want our children to be?

Deep tip of the hat to Laura for sharing this seminal paper, due to appear in Nature on Dec 11.

Greely, Shakain, Harris, Kessler, Gazzaniga, Campbel & Farah (2008) Towards responsible use of cognitive-enhancing drugs by the healthy. Nature.

I'm obviously thrilled to see a paper like this in such a high-impact journal and with such distinguished authors. Few things seem as capable of speeding up scientific development and the spread of a modern, progressive mind-set as does the prospect of widespread brain enhancement. But I want us to acknowledge how enormous this transition will be. Many social norms will not survive the change and many others will need to be updated.

One issue I'm baffled by is how we will think about the use of drugs to make school-children more attentive and compliant. The authors in the current paper call for policy to prevent coercive use of cognitive enhancers in children. But at the end of the day the fact is that teachers are already doing everything they can (often unsuccessfully) to focus the attention of their pupils. A drug that enhances attention seems like a natural next step. Would it damage creative thinking in children if they went through school on Adderall? I guess that's one of the topics the authors call for more research on, but it's also a social or existential issue: how compliant do we want our children to be? I was a hell-raiser in school; I would have been VERY different on Adderall and would be a different person now. But maybe this is just our first shaky step into a new era of responsibe, neuroscientific design of children; maybe the next generations of Ritalin, Adderall and Modafinil will be designed specifically to enhance creative thinking and brain growth (BDNF anyone?).

Anyway, it's a great paper, I strongly recomended it.
"The new methods of cognitive enhancement are 'disruptive technologies' that could have a profound effect on human life in the twenty-first century. A laissez-faire approach to these methods will leave us at the mercy of powerful market forces that are bound to be unleashed by the promise of increased productivity and competitive advantage. The concerns about safety, freedom and fairness, just reviewed, may well seem less important than the attractions of enhancement, for sellers and users alike...

We call for a programme of research into the use and impacts of cognitive-enhancing drugs by healthy individuals...

We call for physicians, educators, regulators and others to collaborate in developing policies that address the use of cognitive-enhancing drugs by healthy individuals...

We call for information to be broadly disseminated concerning the risks, benefits and alternatives to pharmaceutical cognitive enhancement...

We call for careful and limited legislative action to channel cognitive-enhancement technologies into useful paths..."


The basic amphetamine (Adderall) molecule. Click to interact (requires Java).