Category Archives: Neurostimulation and Neuromodulation

First clinical tests!

 

Last friday a milestone was reached in the Biomedical Electronics Group: the first clinical experiments were conducted with the neurostimulator ‘uStim’ designed within the group! This neurostimulator allows the use of arbritrary waveforms for neural stimulation while still assuring safe stimulation by charge cancellation. After extensive electrical characterization of the device in the last couple of months the moment was finally there to test it in real life!

Two subjects were implanted with percutaneous leads. These leads were connected to the stimulator while the EEG activity of the subjects was closely monitored. The subjects were first stimulated using a commercially available stimulator (ANS – St. Jude Medical) and after that using the uStim. 

The first prelimenary results are promising. Both subjects showed clear responses in the EEG as a result of the stimulation pulses generated by our stimulator. The data will need further analysis in order to compare it to the commercially available stimulators, but at least it is possible to conclude that the stimulator is able to generate arbritrary stimulation pulses in a safe manner.

It was a great moment for the researchers to see their work in real action! We are looking forward to working on the next version of uStim!

Marijn

 

Preparing the electronics: 

 

 

Connecting the leads!!

 

 

EEG monitoring showing the response to the stimulator: 

 

All activity is closely monitored. 

 

 

Programmable Implants

This article originally appeared in Delta, April 13, 2011. By Thomas van Dijk

For his PhD research, Dr Christos Strydis rethought the architecture for processors in biomedical implants.

In future implants might be recharged by the brain. (Photo: Ana Laura Santos)

Saying that they are committed to their research into neurostimulation is an understatement. In their quest to develop a treatment for patients with tinnitus, a syndrome where people hear phantom noises, Professor Dirk De Ridder, a neurosurgeon and neuroscientist at  University Hospital Antwerp, and assistant professor Eddy van der Velden, a medical researcher at Antwerp’s Monica hospital, are about to be operated on themselves. During an experiment to be held at the end of this month, the professors will have wires sticking out of the back of their heads, through which electrical pulses will travel to their brains. 

“They are really crazy,” says computer engineer, Dr Christos Strydis, laughing. In his office, Dr Strydis shows an application on his smart phone. With this app he will command the device – which is the size of a packet of cigarettes – that is attached to the guinea pig professors and generates the pulses. Depending on the frequency of the pulses, the test subjects might feel energetic, euphoric or sleepy, to name but a few of the possible states. 

Strydis is part of a large team of researchers from the faculties of Electrical Engineering, Mathematics and Computer Science, and Applied Sciences, who over the years have been working with the Belgian medics on biomedical implants. The team’s goal is to develop tiny, low-energy consuming implants that can be controlled by software, rather than being based solely on hardwired circuits. 

Strydis has been focusing on the type of processor needed for such devices. Last month he defended his PhD thesis, titled ‘Universal processor architecture for biomedical implants.’

Strydis believes that it’s time for a paradigm shift in the field of biomedical implants: “One big problem is that the electrical signals created by implants no longer aid patients with neurological diseases after a certain period of time, because the body simply gets used to the signals and ignores them. So the device should be smarter and more flexible. You should be able to programme it. What’s more, every patient is different, so standard implants with standard signals do not work optimally for everyone.”

It will take at least another five years before the device built by the Delft researchers will be miniaturised enough to be placed directly under the skull of patients, Strydis surmises. Neuroscientist Prof. van der Velden hopes that the battery inside the implant, which ultimately must work at a voltage of no more than half a millivolt, will be recharged by the brain. 

Thoughts over an exam…

Besides many research related posts on this weblog, there is another important aspect in universities: education. Currently the spring examinations take place. It is time to see if our efforts in introducing the students into the exciting world of transistors were good enough. Today I was supervising a retake of a first year BSc-course. In order not to get too bored, I printed out a bunch of papers to read through…

Despite the reading material, I was preparing for a long morning. But nothing could be further from the truth! While the students were sweating and battling their way through the exam, I picked up a paper about the history of electrical stimulation [1]. It was discussing about the very first steps of electricity for medical applications. As it turns out, soon after the development of the first electrical devices in the second half of the 18th century (such as static electricity machines, the Leyden jar or later the volta-cell), these devices were put in use for medical research very soon. Just like myself today, people were fascinated by how our body responds to electricity.

It is incredible to read what achievements were made with the extremely limited equipment that was available. Even more incredible were the experiments that were carried out: the effect of electricity on the human body was demonstrated using the decaptivated heads of executed criminals! Furthermore the functionality of pacemakers was demontrated by over-anesthesthetized animals until cardiac arrest occured, to subsequently reanimate them using electrical stimulation. Remarkably the method was also applied to a human subject, but without success…

Besides experiments, the inguinity of researchers to build machines is very remarkable. Without the availability of vacuum tubes (let alone transistors), it is hard to make pulses with accurate duration in the order to hundred milliseconds (which are required for stimulation). Various mechanical systems are described, of which the most remarkable one is a system in which a gun is fired to cut two wires placed at a certain distance from each other. Only during the time the bullet is travelling from the first wire to the second, the system is injecting electrical energy into the tissue. Imagine how being a researcher was like in those days: shooting rifles the whole day! Quite a difference from running circuit simulations like we do today!

For more interesting stories I can highly recommend to read this paper. Or save it for when you have to supervise an exam. For now: time to check the exam!

Marijn

[1] Geddes, L.A., "The first stimulators-reviewing the history of electrical stimulation and the devices crucial to its development", Engineering in Medicine and Biology Magazine, IEEE , vol.13, no.4, pp.532-542, Aug/Sep 1994

Fry in your brain, or fryin’ your brain

Yesterday, I watched a very impressive two-part television documentary made by Stephen Fry, entitled "The Secret Life of the Manic Depressive" and filmed in 2006. The documentary is about his struggle with manic depression, which he prefers to call "bipolar disorder" as this is its official name and definitively does not involve a state of continuous depression. Bipolar disorder is often treated with mood stabilizing medications and, sometimes, other psychiatric drugs. However, these are not always effective and often cause a lot of side-effects.

The second part of the documentary is about Stephen wondering whether he should consider taking drugs or other kinds of psychiatric treatment, as it looks like his symptoms are getting worse over time. So in this part he visits a few people he knows and that have also been diagnosed with bipolar and are using some form of therapy. Among them is Andy Behrman, also known as "Electroboy". According to his website www.electroboy.com, "after two unsuccessful years of experimenting with all different combinations of medication to stabilize his wild mood swings, he opted for intensive bouts of electroshock therapy," [Ed.] also known as "electroconvulsive therapy", or ECT in short, "as a last resort. He was temporarily cured."

Electroshock therapyThis, of course, brings back memories of one of the famous scenes of the movie "One flew over the cuckoo’s nest", in which Jack Nicolson rallies the patients of a mental institution together to take on the oppressive Nurse Ratched, a woman more a dictator than a nurse. He finally receives ECT to calme him down. As you can see from the picture at left, the applied ECT therapy used to be quite agressive, leading to brain convulsions and seizures or even memory loss, and has therefore been classified as "high risk" by the American Food and Drug Administration, or FDA for short.

Coincidentally, the American Psychiatric Association recently stated that the FDA should move the procedure to a medium risk state as they believe the current devices are not as brute force as their older siblings. Opponents, however, state that ECT may lead to memory loss and all sorts of other complications. If you want to decide for yourself, please check out the following YouTube movie: http://www.youtube.com/watch?v=zYl13Relzbs.

My personal opinion is that, though the doctors try to do a professional job, the applied therapy is not very patient specific and the majority of parameters are determined purely on a trial-and-error basis. Adding this to the fact that ECT is not the primary therapy, but merely serves to evoke a seizure (like you have during an epileptic insult), which is the actual therapy, makes me wonder whether there aren’t any prospects of developing a better therapy, which is better tailored to the disorder at hand and, of course, better to the patient.

Anyway, this was my sermon for the late Monday morning. If you are interested in watching "The Secret Life of the Manic Depressive", just let me know and I’ll see what I can do.

Wouter 

Current between the ears…

 "Current between the ears" 

In the weekend edition of a major Dutch newspaper (called the Volkskrant), the science section immediately got my attention. "Current between the ears". Since most people seem to have a brain between their ears, this article might be telling us about neural stimulation.

And so it did! It describes a technique called ‘Transcranial Direct Current Stimulation’ (tDCS). Two external electrodes are placed on the head of the subject. By sending a DC current in the order of 1mA through these electrodes the brain functionality can be influenced.

At the positive electrode, the tissue potential is slightly elevated. This means that the threshold for neurons to become activated is decreased and therefore the part of the brain close to the positive electrode becomes more active. The opposite holds for the negative electrode: this part becomes less active.

In this way it is possible to either stimulate or suppress particular neural functions. It can for example be used to temporarily increase the memory ability of the brain. Or to suppress mechanisms that lead to addiction. Or to help depression patients by suppressing the part that is associated with bad feelings.

The big advantage of this technology is obviously that is is non-invasive. That must however also be a disadvantage. To support 1mA currents, the electrode must be quite big in order not to exceed their charge injection limitations. This means that the spatial resolution of this method must be quite poor: a relatively large area is affected using this method. 

Nevertheless the article shows some interesting results, both obtained by the department of Developmental Psychology of the UvA and by research groups throughout the world. Once again it shows the fascinating world that opens up as soon as we apply (electrical) technology to the most complex organ we have: our brain.

Marijn van Dongen 

Can the upcoming solar storm turn your pacemaker into a killer inside you?

It has been predicted that today (Febr. 17, 2011) one of the largest solar storms in years will reach the earth and may interfere with sensitive electronic equipment, such as GPS receivers in cars and PDAs. Also air traffic and power grids may suffer from this kind of interference.

 Solar Storm 

Solar storms, also called geomagnetic storms, are caused by solar coronal mass ejections and modify the electromagnetic fields in the ionosphere, magnetosphere and heliosphere. They usually last only one or two days and can cause auroras further away from the poles than usually. According to Wikipedia, "On March 13, 1989 a severe geomagnetic storm caused the collapse of the Hydro-Québec power grid in a matter of seconds as equipment protection relays tripped in a cascading sequence of events. Six million people were left without power for nine hours, with significant economic loss."

So how dangerous are these solar storms for life-supporting devices like pacemakers and neurostimulators? In order to answer this question, we need to understand the physical and electrical effects of solar storms. Solar storms induce fluctuations in the Earth’s magnetic field. These fluctuations, in turn, can induce currents in large electrically conducting structures, such as power grids and metal pipelines, leading to damaged transformers and corrosion. Solar storms also influence the electrical currents in the magnetosphere and the ionosphere and thereby affect wireless communication that propagates through them.

So my conclusion: as long as you do not use your shortwave radio or CB set to control your implantable device remotely and you do not power it from the mains, you’re safe. Ain’t that a relief?

Wouter

Ice skating and guitar solos

I’m writing this little contribution on Saturday night. Most people must be either watching the World Championships Ice Skating or enjoying themselves in the nightlife. Maybe you are lucky and you are in the Oosterpoort (Groningen) tonight listening to a concert by ‘Gare du Nord‘. Or you prefer to immerse yourself in the sounds of fabulous guitar solos and keep dancing like there’s no tomorrow. 

But there will be a tomorrow. And the more successful last night was, the harder the Sunday morning is. With a liver getting in overdrive and a brain complaining about a lack of water, you wonder why you cannot sleep any further. Soon you realize it must be that annoying beep in your head. Maybe standing next to the big loudspeakers was not a good idea after all. Well, let’s first take a shower, the beep will be gone during the course of this lazy Sunday.

 woman suffering from tinnitus 

Or not… Imagine this beep will stay with you. Always. More than a million people in Holland suffer from a disease called Tinittus. In about 10% of the cases the beep (or noise) is so loud that it limits them in their daily life. No effective treatment exists until today. But we are working on it. Brain stimulation can be an effective treatment method. And in our group we are developing the ‘uStim’-stimulator: it can stimulate the brain in a unique manner so that we can stop the beep. We use technology to manipulate faulty activity in the brain.

Sounds interesting? Keep reading this blog for updates about this little device. Oh, and keep enjoying yourselves on (Saturday) nights. But just as with all things in life: keep it safe. Unless you are watching the World Championships Ice Skating. I cannot think of any way how you can harm yourself while doing that…

Marijn van Dongen 

Electric stimulation turns geek into sex god

"Electrical stimulation of certain hypothalamic regions in cats and rodents can elicit attack behaviour," is what we can read in Nature today. But also "Neurons activated during attack are inhibited during mating, suggesting a potential neural substrate for competition between these opponent social behaviours." If the same holds for human beings, which is highly probable, then we are not far away from the situation in which we can replace Cialis by a healthy dosis of instant neurostimulation or switch the neurostimulator to Arousal Mode No. 2 to beat the guy that left the bar with another one’s girlfriend. As long as they do not take my Erdinger, I’m fine.

Jokes aside, it is known that both regions in the brain are closely located to one another, together with the part that controls voluntary urination. So my advice: don’t try this at home.

How I lost my blogging virginity?

It has been more than eight months since I have graduated from TU Delft. Since then I have been working on pursuing my intentions to do a PhD. As many others, I have a great idea for my PhD project with huge scientific and societal relevance, but no funding (yet). For more information about my intended project, please visit my website

Currently, I am waiting for the first results of personal grant proposal submitted to the Netherlands Organisation for Scientific Research (NWO), Mosaic programme. Mosaic aims to attract more excellent ethnic minority graduates into academic research. And of course, I am one of them 🙂 
Obviously, I will share the results from NWO with you, as soon as I get them. 
More information about NWO Mosaic can be found here.

As a first time blogger I realize that this post has a twofold meaning. Firstly, it is a great opportunity to say a few words about me and, secondly, like I just realized, by placing this post I will lose my blogging virginity. The things we do for science… 

Senad 

Li-Ion batteries on silicon come to the rescue

Yesterday, Erik Kelder (NSM group, TU Delft) explained us how thin-film microbatteries can be made in silicon. These batteries seem to be naturally suited for the next generation of implantable neurostimulators. Read more about the newly initiated FP7 project at: http://www.tudelft.nl/live/pagina.jsp?id=39d5ebc3-7ec3-4b26-a298-058bb5f8a24c&lang=en