norman swan: Deep Brain Stimulation is exactly what it sounds like. The electrodes are placed deep in the brain to treat movement problems like Parkinson's disease and more recently to try to help people with what is known as treatment-resistant depression. But deep brain stimulation for depression initially showed promise but disappointment. Susannah Tye tries to figure out why and then comes up with better ways to use the technique. Susannah is a Senior Research Fellow at the Queensland Brain Institute.
Suzanne tie: Deep brain stimulation is a form of neuromodulation in which electrodes are implanted in specific nodes in the brain and the electrode is continuously activated, which is thought to act as a pacemaker for the brain.
norman swan: And it's been working for a while now, but they've put it into parts of the brain that might support your movement if you have Parkinson's disease, for example.
Suzanne tie: Is correct. Therefore, it is currently best used in movement disorders, it is very well established to be effective as a therapeutic treatment for patients who no longer respond to drug therapies. And we know that in movement disorders, it modulates abnormal cell activity in the brain.
norman swan: So when you say modular, you mean change.
Suzanne tie: change, essentially replace. They fire directly and continuously according to the tremor itself.
norman swan: You have that tremor that gets worse when you're really trying to do something and it adds to the stiffness you feel with Parkinson's disease and stiffness.
Suzanne tie: Correct, deep brain stimulation can target different aspects of the disease itself, and tremor is particularly responsive to stimulation. We think that's because it essentially silences the activity in the brain that's causing that particular movement.
norman swan: How do you know which part of the brain to target and how that affects the entire brain, if any?
Suzanne tie: So we know that in certain parts of the brain there is this abnormal activity, so the hypothesis was to go in and target this abnormal activity and mainly have the improvement in motor dysfunction as a result.
norman swan: Motor is movement.
Suzanne tie: Is correct. There are several aspects of the disease that are unresponsive to DBS, so there is a lot of research going on into what causes DBS and whether it can be tweaked to affect things like mood, which can also be dysfunctional in Parkinson's. as well as cognitive impairments.
norman swan: And you look for depression.
Suzanne tie: That is correct to try to understand how deep brain stimulation can be used in psychiatric disorders that do not respond effectively to interventions.
norman swan: So this is like an electrical version of deep brain surgery, the lobotomy?
Suzanne tie: Not quite a version of the lobotomy, but that's the obvious first question. Deep brain stimulation is a form of targeted therapy. It's considered relatively less invasive than going in and hurting where the field was before deep brain stimulation was used.
norman swan: But it didn't work so well for depression.
Suzanne tie: Is correct. In depression, recent clinical trials have largely failed.
norman swan: And is it because it's a widespread problem of many more than one point in the brain?
Suzanne tie: That is exactly right.
norman swan: What about people who don't respond well to medication?
Suzanne tie: Is correct. Therefore, deep brain stimulation for depression was performed experimentally and several groups were able to show that it was an effective procedure and that patients who did not respond to any other available treatment could obtain lasting benefit and recovery from their depression, which they had been incredibly handicapped. Now that DBS has been deployed at multiple sites, there are many questions as to why it failed at this particular level.
norman swan: So you're saying it helped some people, but not all.
Suzanne tie: Is correct.
norman swan: But you couldn't predict who would help.
Suzanne tie: Is correct. And now that the research has advanced, we know who is most likely to respond, what types of depressive symptoms make someone a good candidate for DBS for depression, and the specific neural networks to target.
norman swan: What is the process? You're put into an fMRI scanner one at a time and you see what's wrong with a particular person's brain, and that's what you're looking for?
Suzanne tie: Is correct.
norman swan: Presumably the way you activate the electrode and the frequency you stimulate, whether you do it all day or all night, all these things can affect you, it's not just about putting an electrode and putting it on connect the main power supply.
Suzanne tie: Is correct. I think now we're as a field to better understand how to optimize this and how to optimize it for different diseases. So it really evolved out of the movement disorder realm where this continuous high frequency stimulation was effective in helping patients move more efficiently.
norman swan: But there's an element of exhaustion, isn't there? You have to adapt and get used to the stimulus and it doesn't necessarily last long.
Suzanne tie: That's right, and what we know now is that the brain adapts, so with psychiatric disorders we need to look at how we can optimize that particular adaptation, because that's what drives recovery. It does not occur acutely like movement disorders, patients need months or years to fully recover.
norman swan: So what does your research here remove that might improve treatment?
Suzanne tie: So we're looking at different types of stimulation parameters that more closely mimic the natural firing in the brain, and we're also looking at the activated networks and how we can amplify those changes, those long-term adaptive changes. 🇧🇷 Changes.
norman swan: And you're trying to see how this might work with drugs instead of...?
Suzanne tie: Is correct. As we better understand the molecular mechanisms that alter or remodel the brain, there is good potential to scale them up. I think there is a lot of potential for new treatments that promote neurotrophic responses or nerve growth...
norman swan: Well, that's exercise, isn't it?
Suzanne tie: Is that so. And antidepressants, regardless of the specific target or pharmacological target of the drug, the main mechanism for producing the therapeutic effect of all antidepressants is believed to be the promotion of brain plasticity and repair.
norman swan: You'd have to be pretty badass to let a neurosurgeon into your brain, even if it's an electrode that could be removed.
Suzanne tie: Absolutely, and that's why these patients and their families are desperate for help, they're really looking for a way to get their lives back on track. I also have to say that I think it's not just about doing deep brain stimulation, it's about having a whole team of doctors working together to help patients. It requires psychiatrists to actually conduct rehabilitative psychotherapy and...
norman swan: So it's more than just a push of a button.
Suzanne tie: Absolut.
norman swan: DR. Susannah Tye ist Senior Research Fellow am Queensland Brain Institute.