Local fields potentials can help DBS programming in Parkinson's disease in clinical practice

[00:00:30] Prof. Andrew Kuhn: Hello, thanks for inviting me.

[00:00:32] Michele Matarazzo: Let's dive right in. Could you start by giving us an overview of the current use and indication of deep brain stimulation in Parkinson's disease.

[00:00:40] Prof. Andrew Kuhn: Parkinson's disease is one of the main indications for deep brain stimulation at the stage when patients start fluctuating. So they have severe off periods and dyskinesias. Sometimes also a severe tremor could be an indication for DBS.

[00:00:56] Michele Matarazzo: Well, in this case, your research focused on the use of local [00:01:00] field potentials in deep brain simulations for PD. As you explained in the article, this is one of the hot areas within the DBS research. What prompted you to investigate this?

[00:01:09] Prof. Andrew Kuhn: Yeah. So I investigated this for a long time already because as I mentioned, people fluctuate with Parkinson's disease, but deep brain stimulation still is a therapy that is 24 hours a day, the same, and it's not adjusted to the individual needs of the patient and the fluctuations over the day.

And the ultimate goal is to understand the neuronal activity in such a way that we can use it as a biomarker for the motor state of the patient and feed the signal back to the stimulator and adjust the simulation. So what we want to understand is really how the brain speaks to us and how we can translate this to better treat the patients.

[00:01:53] Michele Matarazzo: So you want to have a live conversation with the brain while you simulate, right?

[00:01:57] Prof. Andrew Kuhn: Yes. And the hot topic now is [00:02:00] that we are one step further to it. It's not adaptive simulation yet, but we have a new type of stimulator which allows a chronic sensing so we can really read out the neuronal signal, once the stimulators implanted in the patients, and that's a new development which allows us also for the first time to really read out the signal during everyday life activities in the patients.

And that sets a whole new story. So we can also use this information in patients to better program and find the stimulation parameters. And that's what the article is about.

[00:02:38] Michele Matarazzo: Great. Now could you describe how you did the specific research? I mean, how you measure the LFPs? How did you address the motor performance in your patients while you were also measuring the LFPs? And how does all this work?

[00:02:54] Prof. Andrew Kuhn: Yeah. So we used the capability of this new device where we can chronically record [00:03:00] activities and for this article, we asked the patients at their three months follow up to have an overnight withdrawal of medication. So they were in the off medication state when they are pretty kinetic, when the motor symptoms are more severe.

And at that stage, we find this typical pathological activity, which is in the beta frequency range, so about 20 hertz in Parkinsonian patients. And we measured from all possible contacts from the deep brain electrodes. the neuronal activity. And we also did a so called monopolar review. So we tested each contact separately, the stimulation and recorded at the same time.

So there are some restrictions you can only record from contact that are adjacent to the contact that is stimulated. So it's not every contact the lowermost and the uppermost contact we could not use for the stimulation. But the middle two contact they are now separated for so called directional stimulation.

So [00:04:00] they have three segments each and that makes it very difficult in everyday clinical routine to really select the best contact for the patient. And we are now trying to find biomarkers, whether this is imaging or electrophysiology to tell us which contact to use to get the best effect out of the stimulation for our patients.

And here we use the electrophysiology. So we tested the effect of stimulation also but also just rest recording. So these two types of recordings we did the stimulation induced changes and the rest recordings. And as a third measure, we also used a rotating device. So we called it rotometer.

I once came up with this idea just to build it. So the patient's doing a rotating movement for 30 seconds and we can measure the bradykinesia.

[00:04:50] Michele Matarazzo: And what were the main results and also even before you go to the results, how long does it take to go through the whole process of assessing a patient [00:05:00] with all possibilities that you have with the simulation.

[00:05:02] Prof. Andrew Kuhn: Yeah. That took about one and a half hour for each patient. So it was also a bit of a tiring study, but once we have these results and we can understand it better, then a rest recording would just take two minutes if you can extract the biomarker from such a short intervention, then it would be great.

So our results show that these contact that showed the highest beta activity are also being more likely selected post operative in the standard of care settings to be used for chronic stimulation. And what we could show also is that when we use the directional contacts for stimulation that they lead to a suppression of beta activity that has been described before.

But we could show that the maximum suppression of beta activity is related to this better motor performance. And this parameter seems even better as compared to just rest recordings. So [00:06:00] also where we have during the rest recordings, the highest beta that's related. If this contact is less stimulated, that's related to a better motor performance.

So that could help us for selecting the contacts. But even more a stronger correlation we found for those contacts that show the best suppression of this pathological high beta activity.

[00:06:20] Michele Matarazzo: And is there any advantage of doing this three months later than the recording that you can do during the implant of DBS?

[00:06:27] Prof. Andrew Kuhn: Yes, but during implantation, usually we use microelectrode recordings. And then, of course, from the permanent electrode, you can have a short recording. But this is sometimes under anesthesia, it's in a surgery setting, which has limitations, that not all patients are operated awake. Of course, we also have edema, so once the permanent electrode is inserted, it also has been shown in studies before, that this already leads to a suppression of the beta activity.

And we have now been using this chronic sensing device, and he could [00:07:00] show that over the first months, at least, we have a slow recovery of this beta activity. So the beta activity is really suppressed due to the edema. And we know it as a stun effect from the clinical perspective. 

So patients also have less bradykinesia in these first few days or weeks after implantation.

So we don't have a stable setting yet. This is why we used the three months period when our patients routinely come back to the clinic to get a fine adjustment of stimulation settings. And that's a more stable period. And that's why we can use the recording. And that's the big advantage of these new devices where we can still record even three months after surgery and the patients are fully awake and can attend such a session of recording and there's no edema anymore and the medication has been adjusted.

So it's a more stable situation. And our perspective is to develop an algorithm that will help us [00:08:00] using this recording. To then predict which contact would be the best to choose.

[00:08:06] Michele Matarazzo: Oh, that sounds great. And in your experience, do you think that the activity that you record will change over time? What I mean is well, you're saying that three months, you don't have the edema, so you can assess the patient in their stable, clinical, regular situation with their home.

But what will happen when you compare three months with four years, for example, probably you don't have the data. 

[00:08:27] Prof. Andrew Kuhn: We don't have four years yet.

[00:08:29] Michele Matarazzo: Yeah, but what do you envision? 

[00:08:31] Prof. Andrew Kuhn: So far we have a follow up in a few patients for 24 months, so two years. And what we can see is a pretty stable situation after three months follow up. So comparing direct post operative recording with three months follow up. The peak can change the peak frequency, but also the contact which shows the highest peak is still more variable when comparing these two time points.

We also compared 3 months to 12 months, [00:09:00] 18 months, 24 months follow up, and this situation gets more stable. That's not published yet, but we can send it to Movement Disorders soon.

[00:09:08] Michele Matarazzo: Well, the good thing about discussing about things is that I can extract more information from you. Now how do you see your findings impacting the clinical practice? And when do you think this will happen and be available routinely for all the rest of us? And what do you think are the potential benefits for patients that undergo DBS when this will be available for everybody?

[00:09:30] Prof. Andrew Kuhn: So the simple rest recordings are available for everybody who's using the chronic sensing device. So the percept and it's quick and easy to do a power spectrum so that, everybody will be capable to do it. The limitation we have so far is that it's always a bipolar recording. And of course that gives us two contexts that show the highest peak than if it's a bipolar recording. So potentially there will be an option for monopolar recordings. Otherwise [00:10:00] you have to reanalyze the data and recalculate using an algorithm to recalculate for a monopolar setting. There have been other groups also studying this phenomenon and have found similar results with beta activity being a good predictor for contact selection.

And I think pretty soon we will have algorithms that help us to then select the best contacts. But everybody could use it right now and have a look where he sees the highest beta power and that can already give us a hint which contacts you can test, but still the clinical effect is the main information that we have and we should not just rely on the neuronal recordings, but it can be an additive value.

And I hope in the near future we will have prospective clinical trial that really showed how to use it in everyday practice.

[00:10:52] Michele Matarazzo: Great. Thank you. Finally, what are the next steps in your research? Are there any other application of LFPs or what you were [00:11:00] discussing about algorithms. So what are you exploring for the future of DBS in PD and specifically of the LFB recording?

[00:11:08] Prof. Andrew Kuhn: We will work further on using the beta power for contact selection. I think this is a very important point, especially because we get more and more technical advancement in electrode designs with more contacts, which makes it more difficult in clinical practice to choose the right contact.

But the ultimate goal is the adaptive stimulation. So the next step would be really to get a good feedback signal to adjust stimulation amplitude. And there is a study underway already, but we also still try to find biomarkers that are not only related to bradykinesia, but give us maybe information on dyskinesias and other aspects. We still have to understand the signatures of the brain better to use this information for optimal treatment.

[00:11:55] Michele Matarazzo: Perfect. Is there anything else that you want to share with our listeners?

[00:11:58] Prof. Andrew Kuhn: I think it's a [00:12:00] great opportunity and everybody should try and use the devices if available for the chronic sensing to get familiar to this. And we have the first time, the opportunity to really go out of the lab and have. A broad community that can work with it, but also together we could gather a lot of data and get more information and understand the brain and also the diseases better.

[00:12:24] Michele Matarazzo: Andrea, it's been a pleasure discussing your work with you. Your insights are very valuable to our understanding of DBS treatment and more specifically advancing the DBS treatment for Parkinson's disease. Thank you for joining us today.

[00:12:38] Prof. Andrew Kuhn: Thanks a lot. Bye bye.

[00:12:40] Michele Matarazzo: We have had Dr. Andrea Kuhn and we have discussed the article Local Field Potential Predicts Motor Performance in Deep Brain Stimulation for Parkinson's Disease from the Movement Disorder Journal. Download and read the article that is available on the website of the journal. Thank you all for listening. [00:13:00]