Ben Greenburg, Brown Medical School
Chris - OCD or obsessive compulsive disorder is an extremely disabling condition that causes sufferers to adopt futile behaviours like locking and unlocking doors multiple times, repeated hand washing or getting dressed and undressed several times before they can leave the house.
For people for whom behaviour therapies or drugs just don’t work, previously there was little that could be done. But now doctors are reporting significant success using DBS – deep brain stimulation – which is carried out by implanting electrodes into patients’ brains. Ben Greenberg...
Ben - The lesions and DBS for OCD that we’ve been working on affect connections between the thalamus, which is a sub-cortical nucleus that does lots of things in the brain and projects throughout the pre-frontal cortex. We’re particularly interested in connections between the thalamus and the bottom part, the ventral part of the pre-frontal cortex, which lots of evidence suggests is important in OCD.
Chris - And you can either cut that region, or you implant these electrodes that will enable you to do deep brain stimulation. Does the deep brain stimulation effectively render that area of brain inactive then?
Ben - The truth is that we don’t know. The original idea, both in movement disorders – where about 70,000 patients worldwide have had DBS – and our work in OCD, was that DBS represented some kind of functional lesion. It blocked transmission. That doesn’t seem to be right. It’s probably better to say that DBS may bias activity in pathways. Bias what kinds of information they’re likely to carry. The other thing that DBS may do is affect different nodes of the circuit so that they’re actually released from abnormal inputs. Lesions may do this too. One particular region that we’re interested in may have to do with the mechanism of action of behaviour therapy.
Chris - Do you have to put the electrodes on both sides of the brain, or do you just stimulate one region?
Ben - We typically put them bilaterally, both sides of the brain, although it is not uncommon for patients to have the best response when we only use one of them. We’re trying, with colleagues in an NIH-funded Conte Centre, which includes an anatomist as the head of this project, to really understand exactly where the most effective stimulation is, and then to understand what the network of that stimulation is. So where do you need to go to get where you need to?
Chris - How do you tune it up so that you know whether the patient is responding or not? How do you know how hard to stimulate?
Ben - The first thing you do is try to avoid side effects. And then the second thing you do is look clinically – it’s not as nice as stimulating for tremor where you can see the tremor stop right in front of you. What we can see is patients changing in subtle ways, we want them to be subtle, in terms of their affect. So they will look like they’re more present, affectively, they’ll look calmer, they’ll interact with you more, they’ll make better eye contact, they’ll be more spontaneous in their speech. And those kinds of very non-specific effects seem to be predictive of a good response to DBS for OCD. That relates to another thing that’s really quite interesting – we do DBS at exactly the same target for major depression without OCD. So it looks as if a lot of the treatment effects may be non-specific at the behavioural level, which is also true, I think, in terms of the effect of anti-depressants which we give to all of these kinds of patients.
Chris - And when you’re running the DBS, does that have to continue indefinitely for the person to continue to derive some kind of benefit, or is there some kind of brain re-wiring that happens around the stimulus, so if it is subsequently withdrawn, then the symptoms stay in abeyance?
Ben - It looks as if you need it indefinitely. We had hopes that if someone then successfully did behaviour therapy after DBS, that we would be able to withdraw the stimulation. In fact, we did that and we reported on that in a couple of patients. One actually maintained his gains for about six months with DBS off, another probably for that much time or maybe even longer. But ultimately in the case we followed, DBS needed to be turned back on, or the illness re-established itself.
Chris - Practically, do you have to have wires coming out of people’s heads and that kind of thing in order to make this happen, or is it very self contained?
Ben - It’s like a cardiac pacemaker really, everything is under the skin. You put the pacemaker typically in the chest, but instead of the wires going to the heart they go to the brain. Under the skin; through holes in the skull; into the brain.
Chris - Ben Greenburg, from Brown medical school.