Tag Archives: Pavel Musienko

Bioinspired, biomimetic stimulation for the next generation of neuroprosthetics

ETH researchers have developed a prosthetic leg that communicates with the brain via natural signals. (Photograph: Keystone) Courtesy: ETH Zurich

A February 21, 2024 ETH Zurich press release by Ori Schipper (also on EurekAlert) announces a ‘nature-inspired’ or bioinspired approach to neuroprosthetics,

Prostheses that connect to the nervous system have been available for several years. Now, researchers at ETH Zurich have found evidence that neuroprosthetics work better when they use signals that are inspired by nature.

In brief

*Neuroprostheses are electro-​mechanical devices that are connected to the nervous system. As yet, these are unable to provide natural communication with the brain. Instead, they often evoke artificial, unpleasant sensations, similar to a feeling of tingles over the skin.
*This paraesthesia might be caused by overstimulation of the nervous system. ETH Zurich researchers together with colleagues in Germany, Serbia and Russia have proposed that neuroprosthetics should transmit biomimetic signals that are easier for the brain to understand.
*These new findings are relevant to arm and leg prostheses as well as various other aids and devices, including spinal implants and electrodes for brain stimulation. 

A few years ago, a team of researchers working under Professor Stanisa Raspopovic at the ETH Zurich Neuroengineering Lab gained worldwide attention when they announced that their prosthetic legs had enabled amputees to feel sensations from this artificial body part for the first time. Unlike commercial leg prostheses, which simply provide amputees with stability and support, the ETH researchers’ prosthetic device was connected to the sciatic nerve in the test subjects’ thigh via implanted electrodes.

This electrical connection enabled the neuroprosthesis to communicate with the patient’s brain, for example relaying information on the constant changes in pressure detected on the sole of the prosthetic foot when walking. This gave the test subjects greater confidence in their prosthesis – and it enabled them to walk considerably faster on challenging terrains. “Our experimental leg prosthesis succeeded in evoking natural sensations. That’s something current neuroprostheses are mainly unable to do; instead, they mostly evoke artificial, unpleasant sensations,” Raspopovic says.

This is probably because today’s neuroprosthetics are using time-​constant electrical pulses to stimulate the nervous system. “That’s not only unnatural, but also inefficient,” Raspopovic says. In a recently published paper, he and his team used the example of their leg prostheses to highlight the benefits of using naturally inspired, biomimetic stimulation to develop the next generation of neuroprosthetics.

Model simulates activation of nerves in the sole

To generate these biomimetic signals, Natalija Katic – a doctoral student in Raspopovic’s research group – developed a computer model called FootSim. It is based on data collected by collaborators in Canada, who recorded the activity of natural receptors, named mechanoreceptors, in the sole of the foot while touching different points on the feet of volunteers with a vibrating rod.

The model simulates the dynamic behaviour of large numbers of mechanoreceptors in the sole of the foot and generates the neural signals that shoot up the nerves in the leg towards the brain – from the moment the heel strikes the ground and the weight of the body starts to shift forward to the outside of the foot until the toes push off the ground ready for the next step. “Thanks to this model, we can see how semsory receptors from the sole, and the connected nerves, behave during walking or running, which is experimentally impossible to measure” Katic says.

Information overload in the spinal cord

To assess how closely the biomimetic signals calculated by the model correspond to the signals emitted by real neurons, Giacomo Valle – a postdoc in Raspopovic’s research group – worked with colleagues in Germany, Serbia and Russia on experiments with cats, whose nervous system processes movement in a similar way to that of humans. The experiments took place in 2019 at the Pavlov Institute of Physiology in St. Petersburg and were carried out in accordance with the relevant European Union guidelines.

The researchers implanted electrodes, connecting some to the nerve in the leg and some to the spinal cord to discover how the signals are transmitted through the nervous system. When the researchers applied pressure to the bottom of the cat’s paw, thereby evoking the natural neural response that occurs when a cat takes a step, the peculiar pattern of activity recorded in the spinal cord did indeed resemble the patterns that were elicited in the spinal cord when the researchers stimulated the leg nerve with biomimetic signals.

By contrast, the conventional approach of time-​constant stimulation of the sciatic nerve in the cat’s thigh elicited a markedly different pattern of activation in the spinal cord. “This clearly shows that the commonly used stimulation methods cause the neural networks in the spine to be flooded with information,” Valle says. “This information overload could be the reason for the unpleasant sensations or paraesthesia reported by some users of neuroprosthetics,” Raspopovic adds.

Learning the language of the nervous system

In their clinical trial with leg amputees, the researchers were able to show that biomimetic stimulation is superior to time-​constant stimulation. Their work clearly demonstrated how the signals that mimicked nature produced better results: not only were the test subjects able to climb steps faster, they also made fewer mistakes in a task that required them to climb the same steps while spelling words backwards. “Biomimetic neurostimulation allows subjects to concentrate on other things while walking,” Raspopovic says, “so we concluded that this type of stimulation is more naturally processed and less taxing on the brain.”

Raspopovic, whose lab forms part of the ETH Institute of Robotics and Intelligent Systems, believes that these new findings are not only relevant to the limb prostheses he and his team have been working on for over half a decade. He argues that the need to move away from unnatural, time-​constant stimulation towards biomimetic signals also applies to a whole series of other aids and devices, including spinal implants and electrodes for brain stimulation. “We need to learn the language of the nervous system,” Raspopovic says. “Then we’ll be able to communicate with the brain in ways it really understands.”

Here’s a link to and a citation for the paper,

Biomimetic computer-to-brain communication enhancing naturalistic touch sensations via peripheral nerve stimulation by Giacomo Valle, Natalija Katic Secerovic, Dominic Eggemann, Oleg Gorskii, Natalia Pavlova, Francesco M. Petrini, Paul Cvancara, Thomas Stieglitz, Pavel Musienko, Marko Bumbasirevic & Stanisa Raspopovic. Nature Communications volume 15, Article number: 1151 (2024) DOI: https://doi.org/10.1038/s41467-024-45190-6 Published: 20 February 2024

This paper is open access.

It was a bit of a surprise to see mention of some Canadian collaborators with regard to the earlier work featuring FootSim, a computer model Here’s a link to and a citation to that paper, this version is housed at ETH Zurich,

Modeling foot sole cutaneous afferents: FootSim by Natalija Katic, Rodrigo Kazu Siqueira, Luke Cleland, Nicholas Strzalkowski, Leah Bent, Stanisa Raspopovic, and Hannes Saal. Originally published in: iScience 26(1), DOI https://doi.org/10.1016/j.isci.2022.105874 Publication date: 2023-01-20 Permanent link: https://doi.org/10.3929/ethz-b-000591102

This paper too is open access.

Spinal cords, brains, implants, and remote control

I have two items about implants and brains and an item about being able to exert remote control of the brain, all of which hint at a cyborg future for at least a few of us.

e-Dura, the spinal column, and the brain

The first item concerns some research, at the École Polytechnique de Lausanne (EPFL) which features flexible electronics. From a March 24, 2015 article by Ben Schiller for Fast Company (Note: Links have been removed),

Researchers at the Swiss Federal Institute of Technology, in Lausanne, have developed the e-Dura—a tiny skinlike device that attaches directly to damaged spinal cords. By sending out small electrical pulses, it stimulates the cord as if it were receiving signals from the brain, thus allowing movement.

“The purpose of the neuro-prosthesis is to excite the neurons that are on the spinal cord below the site of the injury and activate them, just like if they were receiving information from the brain,” says Stéphanie Lacour, a professor at the institute.

A January 8, 2015 (?) EPFL press release provides more information about the research,

EPFL scientists have managed to get rats walking on their own again using a combination of electrical and chemical stimulation. But applying this method to humans would require multifunctional implants that could be installed for long periods of time on the spinal cord without causing any tissue damage. This is precisely what the teams of professors Stéphanie Lacour and Grégoire Courtine have developed. Their e-Dura implant is designed specifically for implantation on the surface of the brain or spinal cord. The small device closely imitates the mechanical properties of living tissue, and can simultaneously deliver electric impulses and pharmacological substances. The risks of rejection and/or damage to the spinal cord have been drastically reduced. An article about the implant will appear in early January [2015] in Science Magazine.

So-called “surface implants” have reached a roadblock; they cannot be applied long term to the spinal cord or brain, beneath the nervous system’s protective envelope, otherwise known as the “dura mater,” because when nerve tissues move or stretch, they rub against these rigid devices. After a while, this repeated friction causes inflammation, scar tissue buildup, and rejection.

Here’s what the implant looks like,

Courtesy: EPFL

Courtesy: EPFL

The press release describes how the implant is placed (Note: A link has been removed),

Flexible and stretchy, the implant developed at EPFL is placed beneath the dura mater, directly onto the spinal cord. Its elasticity and its potential for deformation are almost identical to the living tissue surrounding it. This reduces friction and inflammation to a minimum. When implanted into rats, the e-Dura prototype caused neither damage nor rejection, even after two months. More rigid traditional implants would have caused significant nerve tissue damage during this period of time.

The researchers tested the device prototype by applying their rehabilitation protocol — which combines electrical and chemical stimulation – to paralyzed rats. Not only did the implant prove its biocompatibility, but it also did its job perfectly, allowing the rats to regain the ability to walk on their own again after a few weeks of training.

“Our e-Dura implant can remain for a long period of time on the spinal cord or the cortex, precisely because it has the same mechanical properties as the dura mater itself. This opens up new therapeutic possibilities for patients suffering from neurological trauma or disorders, particularly individuals who have become paralyzed following spinal cord injury,” explains Lacour, co-author of the paper, and holder of EPFL’s Bertarelli Chair in Neuroprosthetic Technology.

The press release goes on to describe the engineering achievements,

Developing the e-Dura implant was quite a feat of engineering. As flexible and stretchable as living tissue, it nonetheless includes electronic elements that stimulate the spinal cord at the point of injury. The silicon substrate is covered with cracked gold electric conducting tracks that can be pulled and stretched. The electrodes are made of an innovative composite of silicon and platinum microbeads. They can be deformed in any direction, while still ensuring optimal electrical conductivity. Finally, a fluidic microchannel enables the delivery of pharmacological substances – neurotransmitters in this case – that will reanimate the nerve cells beneath the injured tissue.

The implant can also be used to monitor electrical impulses from the brain in real time. When they did this, the scientists were able to extract with precision the animal’s motor intention before it was translated into movement.

“It’s the first neuronal surface implant designed from the start for long-term application. In order to build it, we had to combine expertise from a considerable number of areas,” explains Courtine, co-author and holder of EPFL’s IRP Chair in Spinal Cord Repair. “These include materials science, electronics, neuroscience, medicine, and algorithm programming. I don’t think there are many places in the world where one finds the level of interdisciplinary cooperation that exists in our Center for Neuroprosthetics.”

For the time being, the e-Dura implant has been primarily tested in cases of spinal cord injury in paralyzed rats. But the potential for applying these surface implants is huge – for example in epilepsy, Parkinson’s disease and pain management. The scientists are planning to move towards clinical trials in humans, and to develop their prototype in preparation for commercialization.

EPFL has provided a video of researcher Stéphanie Lacour describing e-Dura and expressing hopes for its commercialization,

Here’s a link to and a citation for the paper,

Electronic dura mater for long-term multimodal neural interfaces by Ivan R. Minev, Pavel Musienko, Arthur Hirsch, Quentin Barraud, Nikolaus Wenger, Eduardo Martin Moraud, Jérôme Gandar, Marco Capogrosso, Tomislav Milekovic, Léonie Asboth, Rafael Fajardo Torres, Nicolas Vachicouras, Qihan Liu, Natalia Pavlova, Simone Duis, Alexandre Larmagnac, Janos Vörös, Silvestro Micera, Zhigang Suo, Grégoire Courtine, Stéphanie P. Lacour. Science 9 January 2015: Vol. 347 no. 6218 pp. 159-163 DOI: 10.1126/science.1260318

This paper is behind a paywall.

Carbon nanotube fibres could connect to the brain

Researchers at Rice University (Texas, US) are excited about the possibilities that carbon nanotube fibres offer in the field of implantable electronics for the brain. From a March 25, 2015 news item on Nanowerk,

Carbon nanotube fibers invented at Rice University may provide the best way to communicate directly with the brain.

The fibers have proven superior to metal electrodes for deep brain stimulation and to read signals from a neuronal network. Because they provide a two-way connection, they show promise for treating patients with neurological disorders while monitoring the real-time response of neural circuits in areas that control movement, mood and bodily functions.

New experiments at Rice demonstrated the biocompatible fibers are ideal candidates for small, safe electrodes that interact with the brain’s neuronal system, according to the researchers. They could replace much larger electrodes currently used in devices for deep brain stimulation therapies in Parkinson’s disease patients.

They may also advance technologies to restore sensory or motor functions and brain-machine interfaces as well as deep brain stimulation therapies for other neurological disorders, including dystonia and depression, the researchers wrote.

A March 25, 2015 Rice University news release (also on EurekAlert*), which originated the news item, provides more details,

The fibers created by the Rice lab of chemist and chemical engineer Matteo Pasquali consist of bundles of long nanotubes originally intended for aerospace applications where strength, weight and conductivity are paramount.

The individual nanotubes measure only a few nanometers across, but when millions are bundled in a process called wet spinning, they become thread-like fibers about a quarter the width of a human hair.

“We developed these fibers as high-strength, high-conductivity materials,” Pasquali said. “Yet, once we had them in our hand, we realized that they had an unexpected property: They are really soft, much like a thread of silk. Their unique combination of strength, conductivity and softness makes them ideal for interfacing with the electrical function of the human body.”

The simultaneous arrival in 2012 of Caleb Kemere, a Rice assistant professor who brought expertise in animal models of Parkinson’s disease, and lead author Flavia Vitale, a research scientist in Pasquali’s lab with degrees in chemical and biomedical engineering, prompted the investigation.

“The brain is basically the consistency of pudding and doesn’t interact well with stiff metal electrodes,” Kemere said. “The dream is to have electrodes with the same consistency, and that’s why we’re really excited about these flexible carbon nanotube fibers and their long-term biocompatibility.”

Weeks-long tests on cells and then in rats with Parkinson’s symptoms proved the fibers are stable and as efficient as commercial platinum electrodes at only a fraction of the size. The soft fibers caused little inflammation, which helped maintain strong electrical connections to neurons by preventing the body’s defenses from scarring and encapsulating the site of the injury.

The highly conductive carbon nanotube fibers also show much more favorable impedance – the quality of the electrical connection — than state-of-the-art metal electrodes, making for better contact at lower voltages over long periods, Kemere said.

The working end of the fiber is the exposed tip, which is about the width of a neuron. The rest is encased with a three-micron layer of a flexible, biocompatible polymer with excellent insulating properties.

The challenge is in placing the tips. “That’s really just a matter of having a brain atlas, and during the experiment adjusting the electrodes very delicately and putting them into the right place,” said Kemere, whose lab studies ways to connect signal-processing systems and the brain’s memory and cognitive centers.

Doctors who implant deep brain stimulation devices start with a recording probe able to “listen” to neurons that emit characteristic signals depending on their functions, Kemere said. Once a surgeon finds the right spot, the probe is removed and the stimulating electrode gently inserted. Rice carbon nanotube fibers that send and receive signals would simplify implantation, Vitale said.

The fibers could lead to self-regulating therapeutic devices for Parkinson’s and other patients. Current devices include an implant that sends electrical signals to the brain to calm the tremors that afflict Parkinson’s patients.

“But our technology enables the ability to record while stimulating,” Vitale said. “Current electrodes can only stimulate tissue. They’re too big to detect any spiking activity, so basically the clinical devices send continuous pulses regardless of the response of the brain.”

Kemere foresees a closed-loop system that can read neuronal signals and adapt stimulation therapy in real time. He anticipates building a device with many electrodes that can be addressed individually to gain fine control over stimulation and monitoring from a small, implantable device.

“Interestingly, conductivity is not the most important electrical property of the nanotube fibers,” Pasquali said. “These fibers are intrinsically porous and extremely stable, which are both great advantages over metal electrodes for sensing electrochemical signals and maintaining performance over long periods of time.”

Here’s a link to and a citation for the paper,

Neural Stimulation and Recording with Bidirectional, Soft Carbon Nanotube Fiber Microelectrodes by Flavia Vitale, Samantha R. Summerson, Behnaam Aazhang, Caleb Kemere, and Matteo Pasquali. ACS Nano, Just Accepted Manuscript DOI: 10.1021/acsnano.5b01060 Publication Date (Web): March 24, 2015

Copyright © 2015 American Chemical Society

The paper is open access provided you register on the website.

Remote control for stimulation of the brain

Mo Costandi, neuroscientist and freelance science writer, has written a March 24, 2015 post for the Guardian science blog network focusing on neuronal remote control,

Two teams of scientists have developed new ways of stimulating neurons with nanoparticles, allowing them to activate brain cells remotely using light or magnetic fields. The new methods are quicker and far less invasive than other hi-tech methods available, so could be more suitable for potential new treatments for human diseases.

Researchers have various methods for manipulating brain cell activity, arguably the most powerful being optogenetics, which enables them to switch specific brain cells on or off with unprecedented precision, and simultaneously record their behaviour, using pulses of light.

This is very useful for probing neural circuits and behaviour, but involves first creating genetically engineered mice with light-sensitive neurons, and then inserting the optical fibres that deliver light into the brain, so there are major technical and ethical barriers to its use in humans.

Nanomedicine could get around this. Francisco Bezanilla of the University of Chicago and his colleagues knew that gold nanoparticles can absorb light and convert it into heat, and several years ago they discovered that infrared light can make neurons fire nervous impulses by heating up their cell membranes.

Polina Anikeeva’s team at the Massachusetts Institute of Technology adopted a slightly different approach, using spherical iron oxide particles that give off heat when exposed to an alternating magnetic field.

Although still in the experimental stages, research like this may eventually allow for wireless and minimally invasive deep brain stimulation of the human brain. Bezanilla’s group aim to apply their method to develop treatments for macular degeneration and other conditions that kill off light-sensitive cells in the retina. This would involve injecting nanoparticles into the eye so that they bind to other retinal cells, allowing natural light to excite them into firing impulses to the optic nerve.

Costandi’s article is intended for an audience that either understands the science or can deal with the uncertainty of not understanding absolutely everything. Provided you fall into either of those categories, the article is well written and it provides links and citations to the papers for both research teams being featured.

Taken together, the research at EPFL, Rice University, University of Chicago, and Massachusetts Institute of Technology provides a clue as to how much money and intellectual power is being directed at the brain.

* EurekAlert link added on March 26, 2015.