Tag Archives: neural activity

Graphene-based neural probes

I have two news bits (dated almost one month apart) about the use of graphene in neural probes, one from the European Union and the other from Korea.

European Union (EU)

This work is being announced by the European Commission’s (a subset of the EU) Graphene Flagship (one of two mega-funding projects announced in 2013; 1B Euros each over ten years for the Graphene Flagship and the Human Brain Project).

According to a March 27, 2017 news item on ScienceDaily, researchers have developed a graphene-based neural probe that has been tested on rats,

Measuring brain activity with precision is essential to developing further understanding of diseases such as epilepsy and disorders that affect brain function and motor control. Neural probes with high spatial resolution are needed for both recording and stimulating specific functional areas of the brain. Now, researchers from the Graphene Flagship have developed a new device for recording brain activity in high resolution while maintaining excellent signal to noise ratio (SNR). Based on graphene field-effect transistors, the flexible devices open up new possibilities for the development of functional implants and interfaces.

The research, published in 2D Materials, was a collaborative effort involving Flagship partners Technical University of Munich (TU Munich; Germany), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS; Spain), Spanish National Research Council (CSIC; Spain), The Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN; Spain) and the Catalan Institute of Nanoscience and Nanotechnology (ICN2; Spain).

Caption: Graphene transistors integrated in a flexible neural probe enables electrical signals from neurons to be measured with high accuracy and density. Inset: The tip of the probe contains 16 flexible graphene transistors. Credit: ICN2

A March 27, 2017 Graphene Flagship press release on EurekAlert, which originated the news item, describes the work,  in more detail,

The devices were used to record the large signals generated by pre-epileptic activity in rats, as well as the smaller levels of brain activity during sleep and in response to visual light stimulation. These types of activities lead to much smaller electrical signals, and are at the level of typical brain activity. Neural activity is detected through the highly localised electric fields generated when neurons fire, so densely packed, ultra-small measuring devices is important for accurate brain readings.

The neural probes are placed directly on the surface of the brain, so safety is of paramount importance for the development of graphene-based neural implant devices. Importantly, the researchers determined that the graphene-based probes are non-toxic, and did not induce any significant inflammation.

Devices implanted in the brain as neural prosthesis for therapeutic brain stimulation technologies and interfaces for sensory and motor devices, such as artificial limbs, are an important goal for improving quality of life for patients. This work represents a first step towards the use of graphene in research as well as clinical neural devices, showing that graphene-based technologies can deliver the high resolution and high SNR needed for these applications.

First author Benno Blaschke (TU Munich) said “Graphene is one of the few materials that allows recording in a transistor configuration and simultaneously complies with all other requirements for neural probes such as flexibility, biocompability and chemical stability. Although graphene is ideally suited for flexible electronics, it was a great challenge to transfer our fabrication process from rigid substrates to flexible ones. The next step is to optimize the wafer-scale fabrication process and improve device flexibility and stability.”

Jose Antonio Garrido (ICN2), led the research. He said “Mechanical compliance is an important requirement for safe neural probes and interfaces. Currently, the focus is on ultra-soft materials that can adapt conformally to the brain surface. Graphene neural interfaces have shown already great potential, but we have to improve on the yield and homogeneity of the device production in order to advance towards a real technology. Once we have demonstrated the proof of concept in animal studies, the next goal will be to work towards the first human clinical trial with graphene devices during intraoperative mapping of the brain. This means addressing all regulatory issues associated to medical devices such as safety, biocompatibility, etc.”

Caption: The graphene-based neural probes were used to detect rats’ responses to visual stimulation, as well as neural signals during sleep. Both types of signals are small, and typically difficult to measure. Credit: ICN2

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

Mapping brain activity with flexible graphene micro-transistors by Benno M Blaschke, Núria Tort-Colet, Anton Guimerà-Brunet, Julia Weinert, Lionel Rousseau, Axel Heimann, Simon Drieschner, Oliver Kempski, Rosa Villa, Maria V Sanchez-Vives. 2D Materials, Volume 4, Number 2 DOI https://doi.org/10.1088/2053-1583/aa5eff Published 24 February 2017

© 2017 IOP Publishing Ltd

This paper is behind a paywall.

Korea

While this research from Korea was published more recently, the probe itself has not been subjected to in vivo (animal testing). From an April 19, 2017 news item on ScienceDaily,

Electrodes placed in the brain record neural activity, and can help treat neural diseases like Parkinson’s and epilepsy. Interest is also growing in developing better brain-machine interfaces, in which electrodes can help control prosthetic limbs. Progress in these fields is hindered by limitations in electrodes, which are relatively stiff and can damage soft brain tissue.

Designing smaller, gentler electrodes that still pick up brain signals is a challenge because brain signals are so weak. Typically, the smaller the electrode, the harder it is to detect a signal. However, a team from the Daegu Gyeongbuk Institute of Science & Technology [DGIST} in Korea developed new probes that are small, flexible and read brain signals clearly.

This is a pretty interesting way to illustrate the research,

Caption: Graphene and gold make a better brain probe. Credit: DGIST

An April 19, 2017 DGIST press release (also on EurekAlert), which originated the news item, expands on the theme (Note: A link has been removed),

The probe consists of an electrode, which records the brain signal. The signal travels down an interconnection line to a connector, which transfers the signal to machines measuring and analysing the signals.

The electrode starts with a thin gold base. Attached to the base are tiny zinc oxide nanowires, which are coated in a thin layer of gold, and then a layer of conducting polymer called PEDOT. These combined materials increase the probe’s effective surface area, conducting properties, and strength of the electrode, while still maintaining flexibility and compatibility with soft tissue.

Packing several long, thin nanowires together onto one probe enables the scientists to make a smaller electrode that retains the same effective surface area of a larger, flat electrode. This means the electrode can shrink, but not reduce signal detection. The interconnection line is made of a mix of graphene and gold. Graphene is flexible and gold is an excellent conductor. The researchers tested the probe and found it read rat brain signals very clearly, much better than a standard flat, gold electrode.

“Our graphene and nanowires-based flexible electrode array can be useful for monitoring and recording the functions of the nervous system, or to deliver electrical signals to the brain,” the researchers conclude in their paper recently published in the journal ACS Applied Materials and Interfaces.

The probe requires further clinical tests before widespread commercialization. The researchers are also interested in developing a wireless version to make it more convenient for a variety of applications.

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

Enhancement of Interface Characteristics of Neural Probe Based on Graphene, ZnO Nanowires, and Conducting Polymer PEDOT by Mingyu Ryu, Jae Hoon Yang, Yumi Ahn, Minkyung Sim, Kyung Hwa Lee, Kyungsoo Kim, Taeju Lee, Seung-Jun Yoo, So Yeun Kim, Cheil Moon, Minkyu Je, Ji-Woong Choi, Youngu Lee, and Jae Eun Jang. ACS Appl. Mater. Interfaces, 2017, 9 (12), pp 10577–10586 DOI: 10.1021/acsami.7b02975 Publication Date (Web): March 7, 2017

Copyright © 2017 American Chemical Society

This paper is behind a paywall.

Bidirectional prosthetic-brain communication with light?

The possibility of not only being able to make a prosthetic that allows a tetraplegic to grab a coffee but to feel that coffee  cup with their ‘hand’ is one step closer to reality according to a Feb. 22, 2017 news item on ScienceDaily,

Since the early seventies, scientists have been developing brain-machine interfaces; the main application being the use of neural prosthesis in paralyzed patients or amputees. A prosthetic limb directly controlled by brain activity can partially recover the lost motor function. This is achieved by decoding neuronal activity recorded with electrodes and translating it into robotic movements. Such systems however have limited precision due to the absence of sensory feedback from the artificial limb. Neuroscientists at the University of Geneva (UNIGE), Switzerland, asked whether it was possible to transmit this missing sensation back to the brain by stimulating neural activity in the cortex. They discovered that not only was it possible to create an artificial sensation of neuroprosthetic movements, but that the underlying learning process occurs very rapidly. These findings, published in the scientific journal Neuron, were obtained by resorting to modern imaging and optical stimulation tools, offering an innovative alternative to the classical electrode approach.

A Feb. 22, 2017 Université de Genève press release on EurekAlert, which originated the news item, provides more detail,

Motor function is at the heart of all behavior and allows us to interact with the world. Therefore, replacing a lost limb with a robotic prosthesis is the subject of much research, yet successful outcomes are rare. Why is that? Until this moment, brain-machine interfaces are operated by relying largely on visual perception: the robotic arm is controlled by looking at it. The direct flow of information between the brain and the machine remains thus unidirectional. However, movement perception is not only based on vision but mostly on proprioception, the sensation of where the limb is located in space. “We have therefore asked whether it was possible to establish a bidirectional communication in a brain-machine interface: to simultaneously read out neural activity, translate it into prosthetic movement and reinject sensory feedback of this movement back in the brain”, explains Daniel Huber, professor in the Department of Basic Neurosciences of the Faculty of Medicine at UNIGE.

Providing artificial sensations of prosthetic movements

In contrast to invasive approaches using electrodes, Daniel Huber’s team specializes in optical techniques for imaging and stimulating brain activity. Using a method called two-photon microscopy, they routinely measure the activity of hundreds of neurons with single cell resolution. “We wanted to test whether mice could learn to control a neural prosthesis by relying uniquely on an artificial sensory feedback signal”, explains Mario Prsa, researcher at UNIGE and the first author of the study. “We imaged neural activity in the motor cortex. When the mouse activated a specific neuron, the one chosen for neuroprosthetic control, we simultaneously applied stimulation proportional to this activity to the sensory cortex using blue light”. Indeed, neurons of the sensory cortex were rendered photosensitive to this light, allowing them to be activated by a series of optical flashes and thus integrate the artificial sensory feedback signal. The mouse was rewarded upon every above-threshold activation, and 20 minutes later, once the association learned, the rodent was able to more frequently generate the correct neuronal activity.

This means that the artificial sensation was not only perceived, but that it was successfully integrated as a feedback of the prosthetic movement. In this manner, the brain-machine interface functions bidirectionally. The Geneva researchers think that the reason why this fabricated sensation is so rapidly assimilated is because it most likely taps into very basic brain functions. Feeling the position of our limbs occurs automatically, without much thought and probably reflects fundamental neural circuit mechanisms. This type of bidirectional interface might allow in the future more precisely displacing robotic arms, feeling touched objects or perceiving the necessary force to grasp them.

At present, the neuroscientists at UNIGE are examining how to produce a more efficient sensory feedback. They are currently capable of doing it for a single movement, but is it also possible to provide multiple feedback channels in parallel? This research sets the groundwork for developing a new generation of more precise, bidirectional neural prostheses.

Towards better understanding the neural mechanisms of neuroprosthetic control

By resorting to modern imaging tools, hundreds of neurons in the surrounding area could also be observed as the mouse learned the neuroprosthetic task. “We know that millions of neural connections exist. However, we discovered that the animal activated only the one neuron chosen for controlling the prosthetic action, and did not recruit any of the neighbouring neurons”, adds Daniel Huber. “This is a very interesting finding since it reveals that the brain can home in on and specifically control the activity of just one single neuron”. Researchers can potentially exploit this knowledge to not only develop more stable and precise decoding techniques, but also gain a better understanding of most basic neural circuit functions. It remains to be discovered what mechanisms are involved in routing signals to the uniquely activated neuron.

Caption: A novel optical brain-machine interface allows bidirectional communication with the brain. While a robotic arm is controlled by neuronal activity recorded with optical imaging (red laser), the position of the arm is fed back to the brain via optical microstimulation (blue laser). Credit: © Daniel Huber, UNIGE

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

Rapid Integration of Artificial Sensory Feedback during Operant Conditioning of Motor Cortex Neurons by Mario Prsa, Gregorio L. Galiñanes, Daniel Huber. Neuron Volume 93, Issue 4, p929–939.e6, 22 February 2017 DOI: http://dx.doi.org/10.1016/j.neuron.2017.01.023 Open access funded by European Research Council

This paper is open access.