Tag Archives: organic brain

Long-term brain mapping with injectable electronics

Charles Lieber and his team at Harvard University announced a success with their work on injectable electronics last year (see my June 11, 2015 posting for more) and now they are reporting on their work with more extensive animal studies according to an Aug. 29, 2016 news item on psypost.org,

Scientists in recent years have made great strides in the quest to understand the brain by using implanted probes to explore how specific neural circuits work.

Though effective, those probes also come with their share of problems as a result of rigidity. The inflammation they produce induces chronic recording instability and means probes must be relocated every few days, leaving some of the central questions of neuroscience – like how the neural circuits are reorganized during development, learning and aging- beyond scientists’ reach.

But now, it seems, things are about to change.

Led by Charles Lieber, The Mark Hyman Jr. Professor of Chemistry and chair of the Department of Chemistry and Chemical Biology, a team of researchers that included graduate student Tian-Ming Fu, postdoctoral fellow Guosong Hong, graduate student Tao Zhou and others, has demonstrated that syringe-injectable mesh electronics can stably record neural activity in mice for eight months or more, with none of the inflammation

An Aug. 29, 2016 Harvard University press release, which originated the news item, provides more detail,

“With the ability to follow the same individual neurons in a circuit chronically…there’s a whole suite of things this opens up,” Lieber said. “The eight months we demonstrate in this paper is not a limit, but what this does show is that mesh electronics could be used…to investigate neuro-degenerative diseases like Alzheimer’s, or processes that occur over long time, like aging or learning.”

Lieber and colleagues also demonstrated that the syringe-injectable mesh electronics could be used to deliver electrical stimulation to the brain over three months or more.

“Ultimately, our aim is to create these with the goal of finding clinical applications,” Lieber said. “What we found is that, because of the lack of immune response (to the mesh electronics), which basically insulates neurons, we can deliver stimulation in a much more subtle way, using lower voltages that don’t damage tissue.”

The possibilities, however, don’t end there.

The seamless integration of the electronics and biology, Lieber said, could open the door to an entirely new class of brain-machine interfaces and vast improvements in prosthetics, among other fields.

“Today, brain-machine interfaces are based on traditional implanted probes, and there has been some impressive work that’s been done in that field,” Lieber said. “But all the interfaces rely on the same technique to decode neural signals.”

Because traditional rigid implanted probes are invariably unstable, he explained, researchers and clinicians rely on decoding what they call the “population average” – essentially taking a host of neural signals and applying complex computational tools to determine what they mean.

Using tissue-like mesh electronics, by comparison, researchers may be able to read signals from specific neurons over time, potentially allowing for the development of improved brain-machine interfaces for prosthetics.

“We think this is going to be very powerful, because we can identify circuits and both record and stimulate in a way that just hasn’t been possible before,” Lieber said. “So what I like to say is: I think therefore it happens.”

Lieber even held out the possibility that the syringe-injectable mesh electronics could one day be used to treat catastrophic injuries to the brain and spinal cord.

“I don’t think that’s science-fiction,” he said. “Other people may say that will be possible through, for example, regenerative medicine, but we are pursuing this from a different angle.

“My feeling is that this is about a seamless integration between the biological and the electronic systems, so they’re not distinct entities,” he continued. “If we can make the electronics look like the neural network, they will work together…and that’s where you want to be if you want to exploit the strengths of both.”

In the 2015 posting, Lieber was discussing cyborgs, here he broaches the concept without using the word, “… seamless integration between the biological and the electronic systems, so they’re not distinct entities.”

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

Stable long-term chronic brain mapping at the single-neuron level by Tian-Ming Fu, Guosong Hong, Tao Zhou, Thomas G Schuhmann, Robert D Viveros, & Charles M Lieber. Nature Methods (2016) doi:10.1038/nmeth.3969 Published online 29 August 2016

This paper is behind a paywall.

Researchers at Karolinska Institute (Sweden) build an artificial neuron

Unlike my post earlier today (June 26, 2015) about BrainChip, this is not about neuromorphic engineering (artificial brain), although I imagine this new research from the Karolinska Institute (Institutet) will be of some interest to that community. This research was done in the interest of developing* therapeutic interventions for brain diseases. One aspect of this news item/press release I find particularly interesting is the insistence that “no living parts” were used to create the artificial neuron,

A June 24, 2015 news item on ScienceDaily describes what the artificial neuron can do,

Scientists have managed to build a fully functional neuron by using organic bioelectronics. This artificial neuron contain [sic] no ‘living’ parts, but is capable of mimicking the function of a human nerve cell and communicate in the same way as our own neurons do. [emphasis mine]

A June 24, 2015 Karolinska Institute press release (also on EurekAlert), which originated the news item, describes how neurons communicate in the brain, standard techniques for stimulating neuronal cells, and the scientists’ work on a technique to improve stimulation,

Neurons are isolated from each other and communicate with the help of chemical signals, commonly called neurotransmitters or signal substances. Inside a neuron, these chemical signals are converted to an electrical action potential, which travels along the axon of the neuron until it reaches the end. Here at the synapse, the electrical signal is converted to the release of chemical signals, which via diffusion can relay the signal to the next nerve cell.

To date, the primary technique for neuronal stimulation in human cells is based on electrical stimulation. However, scientists at the Swedish Medical Nanoscience Centre (SMNC) at Karolinska Institutet in collaboration with collegues at Linköping University, have now created an organic bioelectronic device that is capable of receiving chemical signals, which it can then relay to human cells.

“Our artificial neuron is made of conductive polymers and it functions like a human neuron,” says lead investigator Agneta Richter-Dahlfors, professor of cellular microbiology. “The sensing component of the artificial neuron senses a change in chemical signals in one dish, and translates this into an electrical signal. This electrical signal is next translated into the release of the neurotransmitter acetylcholine in a second dish, whose effect on living human cells can be monitored.”

The research team hope that their innovation, presented in the journal Biosensors & Bioelectronics, will improve treatments for neurologial disorders which currently rely on traditional electrical stimulation. The new technique makes it possible to stimulate neurons based on specific chemical signals received from different parts of the body. In the future, this may help physicians to bypass damaged nerve cells and restore neural function.

“Next, we would like to miniaturize this device to enable implantation into the human body,” says Agneta Richer-Dahlfors. “We foresee that in the future, by adding the concept of wireless communication, the biosensor could be placed in one part of the body, and trigger release of neurotransmitters at distant locations. Using such auto-regulated sensing and delivery, or possibly a remote control, new and exciting opportunities for future research and treatment of neurological disorders can be envisaged.”

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

An organic electronic biomimetic neuron enables auto-regulated neuromodulation by Daniel T. Simon, Karin C. Larsson, David Nilsson, Gustav Burström, b, Dagmar Galter, Magnus Berggren, and Agneta Richter-Dahlfors. Biosensors and Bioelectronics Volume 71, 15 September 2015, Pages 359–364         doi:10.1016/j.bios.2015.04.058

This paper is behind a paywall.

As to anyone (other than myself) who may be curious about exactly what they used (other than “living parts”) to create an artificial neuron, there’s the paper’s abstract,

Current therapies for neurological disorders are based on traditional medication and electric stimulation. Here, we present an organic electronic biomimetic neuron, with the capacity to precisely intervene with the underlying malfunctioning signalling pathway using endogenous substances. The fundamental function of neurons, defined as chemical-to-electrical-to-chemical signal transduction, is achieved by connecting enzyme-based amperometric biosensors and organic electronic ion pumps. Selective biosensors transduce chemical signals into an electric current, which regulates electrophoretic delivery of chemical substances without necessitating liquid flow. Biosensors detected neurotransmitters in physiologically relevant ranges of 5–80 µM, showing linear response above 20 µm with approx. 0.1 nA/µM slope. When exceeding defined threshold concentrations, biosensor output signals, connected via custom hardware/software, activated local or distant neurotransmitter delivery from the organic electronic ion pump. Changes of 20 µM glutamate or acetylcholine triggered diffusive delivery of acetylcholine, which activated cells via receptor-mediated signalling. This was observed in real-time by single-cell ratiometric Ca2+ imaging. The results demonstrate the potential of the organic electronic biomimetic neuron in therapies involving long-range neuronal signalling by mimicking the function of projection neurons. Alternatively, conversion of glutamate-induced descending neuromuscular signals into acetylcholine-mediated muscular activation signals may be obtained, applicable for bridging injured sites and active prosthetics.

While it’s true neither are “living parts,” I believe both enzymes and organic electronic ion pumps can be found in biological organisms. The insistence on ‘nonliving’ in the press release suggests that scientists in Europe, if nowhere else, are still quite concerned about any hint that they are working on genetically modified organisms (GMO). It’s ironic when you consider that people blithely use enzyme-based cleaning and beauty products but one can appreciate the* scientists’ caution.

* ‘develop’ changed to ‘developing’ and ‘the’ added on July 3, 2015.