March 30 2009 / by iPlant / In association with Future Blogger.net
Category: Biotechnology Year: General Rating: 7 Hot
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.