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KAIST Presents Game-Changing Technology for Intractable Brain Disease Treatment Using Micro OLEDs
<(From left)Professor Kyung Cheol Choi, Professor Hyunjoo J. Lee, Dr. Somin Lee from the School of Electrical Engineering>
Optogenetics is a technique that controls neural activity by stimulating neurons expressing light-sensitive proteins with specific wavelengths of light. It has opened new possibilities for identifying causes of brain disorders and developing treatments for intractable neurological diseases. Because this technology requires precise stimulation inside the human brain with minimal damage to soft brain tissue, it must be integrated into a neural probe—a medical device implanted in the brain. KAIST researchers have now proposed a new paradigm for neural probes by integrating micro OLEDs into thin, flexible, implantable medical devices.
KAIST (President Kwang Hyung Lee) announced on the 6th of July that professor Kyung Cheol Choi and professor Hyunjoo J. Lee from the School of Electrical Engineering have jointly succeeded in developing an optogenetic neural probe integrated with flexible micro OLEDs.
Optical fibers have been used for decades in optogenetic research to deliver light to deep brain regions from external light sources. Recently, research has focused on flexible optical fibers and ultra-miniaturized neural probes that integrate light sources for single-neuron stimulation.
The research team focused on micro OLEDs due to their high spatial resolution and flexibility, which allow for precise light delivery to small areas of neurons. This enables detailed brain circuit analysis while minimizing side effects and avoiding restrictions on animal movement. Moreover, micro OLEDs offer precise control of light wavelengths and support multi-site stimulation, making them suitable for studying complex brain functions.
However, the device's electrical properties degrade easily in the presence of moisture or water, which limited their use as implantable bioelectronics. Furthermore, optimizing the high-resolution integration process on thin, flexible probes remained a challenge.
To address this, the team enhanced the operational reliability of OLEDs in moist, oxygen-rich environments and minimized tissue damage during implantation. They patterned an ultrathin, flexible encapsulation layer* composed of aluminum oxide and parylene-C (Al₂O₃/parylene-C) at widths of 260–600 micrometers (μm) to maintain biocompatibility.
*Encapsulation layer: A barrier that completely blocks oxygen and water molecules from the external environment, ensuring the longevity and reliability of the device.
When integrating the high-resolution micro OLEDs, the researchers also used parylene-C, the same biocompatible material as the encapsulation layer, to maintain flexibility and safety. To eliminate electrical interference between adjacent OLED pixels and spatially separate them, they introduced a pixel define layer (PDL), enabling the independent operation of eight micro OLEDs.
Furthermore, they precisely controlled the residual stress and thickness in the multilayer film structure of the device, ensuring its flexibility even in biological environments. This optimization allowed for probe insertion without bending or external shuttles or needles, minimizing mechanical stress during implantation.
2025.07.07 View 3151 -
KAIST Research Team Breaks Down Musical Instincts with AI
Music, often referred to as the universal language, is known to be a common component in all cultures. Then, could ‘musical instinct’ be something that is shared to some degree despite the extensive environmental differences amongst cultures?
On January 16, a KAIST research team led by Professor Hawoong Jung from the Department of Physics announced to have identified the principle by which musical instincts emerge from the human brain without special learning using an artificial neural network model.
Previously, many researchers have attempted to identify the similarities and differences between the music that exist in various different cultures, and tried to understand the origin of the universality. A paper published in Science in 2019 had revealed that music is produced in all ethnographically distinct cultures, and that similar forms of beats and tunes are used. Neuroscientist have also previously found out that a specific part of the human brain, namely the auditory cortex, is responsible for processing musical information.
Professor Jung’s team used an artificial neural network model to show that cognitive functions for music forms spontaneously as a result of processing auditory information received from nature, without being taught music. The research team utilized AudioSet, a large-scale collection of sound data provided by Google, and taught the artificial neural network to learn the various sounds. Interestingly, the research team discovered that certain neurons within the network model would respond selectively to music. In other words, they observed the spontaneous generation of neurons that reacted minimally to various other sounds like those of animals, nature, or machines, but showed high levels of response to various forms of music including both instrumental and vocal.
The neurons in the artificial neural network model showed similar reactive behaviours to those in the auditory cortex of a real brain. For example, artificial neurons responded less to the sound of music that was cropped into short intervals and were rearranged. This indicates that the spontaneously-generated music-selective neurons encode the temporal structure of music. This property was not limited to a specific genre of music, but emerged across 25 different genres including classic, pop, rock, jazz, and electronic.
< Figure 1. Illustration of the musicality of the brain and artificial neural network (created with DALL·E3 AI based on the paper content) >
Furthermore, suppressing the activity of the music-selective neurons was found to greatly impede the cognitive accuracy for other natural sounds. That is to say, the neural function that processes musical information helps process other sounds, and that ‘musical ability’ may be an instinct formed as a result of an evolutionary adaptation acquired to better process sounds from nature.
Professor Hawoong Jung, who advised the research, said, “The results of our study imply that evolutionary pressure has contributed to forming the universal basis for processing musical information in various cultures.” As for the significance of the research, he explained, “We look forward for this artificially built model with human-like musicality to become an original model for various applications including AI music generation, musical therapy, and for research in musical cognition.” He also commented on its limitations, adding, “This research however does not take into consideration the developmental process that follows the learning of music, and it must be noted that this is a study on the foundation of processing musical information in early development.”
< Figure 2. The artificial neural network that learned to recognize non-musical natural sounds in the cyber space distinguishes between music and non-music. >
This research, conducted by first author Dr. Gwangsu Kim of the KAIST Department of Physics (current affiliation: MIT Department of Brain and Cognitive Sciences) and Dr. Dong-Kyum Kim (current affiliation: IBS) was published in Nature Communications under the title, “Spontaneous emergence of rudimentary music detectors in deep neural networks”.
This research was supported by the National Research Foundation of Korea.
2024.01.23 View 11421 -
A KAIST Research Team Observes the Processes of Memory and Cognition in Real Time
The human brain contains approximately 86 billion neurons and 600 trillion synapses that exchange signals between the neurons to help us control the various functions of the brain including cognition, emotion, and memory. Interestingly, the number of synapses decrease with age or as a result of diseases like Alzheimer’s, and research on synapses thus attracts a lot of attention. However, limitations have existed in observing the dynamics of synapse structures in real time.
On January 9, a joint research team led by Professor Won Do Heo from the KAIST Department of Biological Sciences, Professor Hyung-Bae Kwon from Johns Hopkins School of Medicine, and Professor Sangkyu Lee from the Institute for Basic Science (IBS) revealed that they have developed the world’s first technique to allow a real-time observation of synapse formation, extinction, and alterations.
Professor Heo’s team conjugated dimerization-dependent fluorescent proteins (ddFP) to synapses in order to observe the process in which synapses create connections between neurons in real time. The team named this technique SynapShot, by combining the words ‘synapse’ and snapshot’, and successfully tracked and observed the live formation and extinction processes of synapses as well as their dynamic changes.
< Figure 1. To observe dynamically changing synapses, dimerization-dependent fluorescent protein (ddFP) was expressed to observe flourescent signals upon synapse formation as ddFP enables fluorescence detection through reversible binding to pre- and postsynaptic terminals. >
Through a joint research project, the teams led by Professor Heo and Professor Sangkyu Lee at IBS together designed a SynapShot with green and red fluorescence, and were able to easily distinguish the synapse connecting two different neurons. Additionally, by combining an optogenetic technique that can control the function of a molecule using light, the team was able to observe the changes in the synapses while simultaneously inducing certain functions of the neurons using light.
Through more joint research with the team led by Professor Hyung-Bae Kwon at the Johns Hopkins School of Medicine, Professor Heo’s team induced several situations on live mice, including visual discrimination training, exercise, and anaesthesia, and used SynapShot to observe the changes in the synapses during each situation in real time. The observations revealed that each synapse could change fairly quickly and dynamically. This was the first-ever case in which the changes in synapses were observed in a live mammal.
< Figure 2. Microscopic photos observed through changes of the flourescence of the synapse sensor (SynapShot) by cultivating the neurons of an experimental rat and expressing the SynapShot. The changes in the synapse that is created when the pre- and post-synaptic terminals come into contact and the synapse that disappears after a certain period of time are measured by the fluorescence of the SynapShot. >
Professor Heo said, “Our group developed SynapShot through a collaboration with domestic and international research teams, and have opened up the possibility for first-hand live observations of the quick and dynamic changes of synapses, which was previously difficult to do. We expect this technique to revolutionize research methodology in the neurological field, and play an important role in brightening the future of brain science.”
This research, conducted by co-first authors Seungkyu Son (Ph.D. candidate), Jinsu Lee (Ph.D. candidate) and Dr. Kanghoon Jung from Johns Hopkins, was published in the online edition of Nature Methods on January 8 under the title “Real-time visualization of structural dynamics of synapses in live cells in vivo”, and will be printed in the February volume.
< Figure 3. Simultaneous use of green-SynapShot and red-SynapShot to distinguish and observe synapses with one post-terminal and different pre-terminals. >
< Figure 4. Dimer-dependent fluorescent protein (ddFP) exists as a green fluorescent protein as well as a red fluorescent protein, and can be applied together with blue light-activated optogenetic technology. After activating Tropomyosin receptor kinase B (TrkB) by blue light using optogenetic technology, the strengthening of synaptic connections through signals of brain-derived neurotrophic factor is observed using red-SynapShot. >
< Figure 5. Micrographs showing real-time changing synapses in the visual cortex of mice trained through visual training using in vivo imaging techniques such as two-photon microscopy as well as at the cellular level. >
This research was supported by Mid-Sized Research Funds and the Singularity Project from KAIST, and by IBS.
2024.01.18 View 10629 -
Neuromorphic Memory Device Simulates Neurons and Synapses
Simultaneous emulation of neuronal and synaptic properties promotes the development of brain-like artificial intelligence
Researchers have reported a nano-sized neuromorphic memory device that emulates neurons and synapses simultaneously in a unit cell, another step toward completing the goal of neuromorphic computing designed to rigorously mimic the human brain with semiconductor devices.
Neuromorphic computing aims to realize artificial intelligence (AI) by mimicking the mechanisms of neurons and synapses that make up the human brain. Inspired by the cognitive functions of the human brain that current computers cannot provide, neuromorphic devices have been widely investigated. However, current Complementary Metal-Oxide Semiconductor (CMOS)-based neuromorphic circuits simply connect artificial neurons and synapses without synergistic interactions, and the concomitant implementation of neurons and synapses still remains a challenge. To address these issues, a research team led by Professor Keon Jae Lee from the Department of Materials Science and Engineering implemented the biological working mechanisms of humans by introducing the neuron-synapse interactions in a single memory cell, rather than the conventional approach of electrically connecting artificial neuronal and synaptic devices.
Similar to commercial graphics cards, the artificial synaptic devices previously studied often used to accelerate parallel computations, which shows clear differences from the operational mechanisms of the human brain. The research team implemented the synergistic interactions between neurons and synapses in the neuromorphic memory device, emulating the mechanisms of the biological neural network. In addition, the developed neuromorphic device can replace complex CMOS neuron circuits with a single device, providing high scalability and cost efficiency.
The human brain consists of a complex network of 100 billion neurons and 100 trillion synapses. The functions and structures of neurons and synapses can flexibly change according to the external stimuli, adapting to the surrounding environment. The research team developed a neuromorphic device in which short-term and long-term memories coexist using volatile and non-volatile memory devices that mimic the characteristics of neurons and synapses, respectively. A threshold switch device is used as volatile memory and phase-change memory is used as a non-volatile device. Two thin-film devices are integrated without intermediate electrodes, implementing the functional adaptability of neurons and synapses in the neuromorphic memory.
Professor Keon Jae Lee explained, "Neurons and synapses interact with each other to establish cognitive functions such as memory and learning, so simulating both is an essential element for brain-inspired artificial intelligence. The developed neuromorphic memory device also mimics the retraining effect that allows quick learning of the forgotten information by implementing a positive feedback effect between neurons and synapses.”
This result entitled “Simultaneous emulation of synaptic and intrinsic plasticity using a memristive synapse” was published in the May 19, 2022 issue of Nature Communications.
-Publication:Sang Hyun Sung, Tae Jin Kim, Hyera Shin, Tae Hong Im, and Keon Jae Lee (2022) “Simultaneous emulation of synaptic and intrinsic plasticity using a memristive synapse,” Nature Communications May 19, 2022 (DOI: 10.1038/s41467-022-30432-2)
-Profile:Professor Keon Jae Leehttp://fand.kaist.ac.kr
Department of Materials Science and EngineeringKAIST
2022.05.20 View 19594 -
A Mechanism Underlying Most Common Cause of Epileptic Seizures Revealed
An interdisciplinary study shows that neurons carrying somatic mutations in MTOR can lead to focal epileptogenesis via non-cell-autonomous hyperexcitability of nearby nonmutated neurons
During fetal development, cells should migrate to the outer edge of the brain to form critical connections for information transfer and regulation in the body. When even a few cells fail to move to the correct location, the neurons become disorganized and this results in focal cortical dysplasia. This condition is the most common cause of seizures that cannot be controlled with medication in children and the second most common cause in adults.
Now, an interdisciplinary team studying neurogenetics, neural networks, and neurophysiology at KAIST has revealed how dysfunctions in even a small percentage of cells can cause disorder across the entire brain. They published their results on June 28 in Annals of Neurology.
The work builds on a previous finding, also by a KAIST scientists, who found that focal cortical dysplasia was caused by mutations in the cells involved in mTOR, a pathway that regulates signaling between neurons in the brain.
“Only 1 to 2% of neurons carrying mutations in the mTOR signaling pathway that regulates cell signaling in the brain have been found to include seizures in animal models of focal cortical dysplasia,” said Professor Jong-Woo Sohn from the Department of Biological Sciences. “The main challenge of this study was to explain how nearby non-mutated neurons are hyperexcitable.”
Initially, the researchers hypothesized that the mutated cells affected the number of excitatory and inhibitory synapses in all neurons, mutated or not. These neural gates can trigger or halt activity, respectively, in other neurons. Seizures are a result of extreme activity, called hyperexcitability. If the mutated cells upend the balance and result in more excitatory cells, the researchers thought, it made sense that the cells would be more susceptible to hyperexcitability and, as a result, seizures.
“Contrary to our expectations, the synaptic input balance was not changed in either the mutated or non-mutated neurons,” said Professor Jeong Ho Lee from the Graduate School of Medical Science and Engineering. “We turned our attention to a protein overproduced by mutated neurons.”
The protein is adenosine kinase, which lowers the concentration of adenosine. This naturally occurring compound is an anticonvulsant and works to relax vessels. In mice engineered to have focal cortical dysplasia, the researchers injected adenosine to replace the levels lowered by the protein. It worked and the neurons became less excitable.
“We demonstrated that augmentation of adenosine signaling could attenuate the excitability of non-mutated neurons,” said Professor Se-Bum Paik from the Department of Bio and Brain Engineering.
The effect on the non-mutated neurons was the surprising part, according to Paik. “The seizure-triggering hyperexcitability originated not in the mutation-carrying neurons, but instead in the nearby non-mutated neurons,” he said.
The mutated neurons excreted more adenosine kinase, reducing the adenosine levels in the local environment of all the cells. With less adenosine, the non-mutated neurons became hyperexcitable, leading to seizures.
“While we need further investigate into the relationship between the concentration of adenosine and the increased excitation of nearby neurons, our results support the medical use of drugs to activate adenosine signaling as a possible treatment pathway for focal cortical dysplasia,” Professor Lee said.
The Suh Kyungbae Foundation, the Korea Health Technology Research and Development Project, the Ministry of Health & Welfare, and the National Research Foundation in Korea funded this work.
-Publication:Koh, H.Y., Jang, J., Ju, S.H., Kim, R., Cho, G.-B., Kim, D.S., Sohn, J.-W., Paik, S.-B. and Lee, J.H. (2021), ‘Non–Cell Autonomous Epileptogenesis in Focal Cortical Dysplasia’ Annals of Neurology, 90: 285 299. (https://doi.org/10.1002/ana.26149)
-ProfileProfessor Jeong Ho Lee Translational Neurogenetics Labhttps://tnl.kaist.ac.kr/ Graduate School of Medical Science and Engineering KAIST
Professor Se-Bum Paik Visual System and Neural Network Laboratory http://vs.kaist.ac.kr/ Department of Bio and Brain EngineeringKAIST
Professor Jong-Woo Sohn Laboratory for Neurophysiology, https://sites.google.com/site/sohnlab2014/home Department of Biological SciencesKAIST
Dr. Hyun Yong Koh Translational Neurogenetics LabGraduate School of Medical Science and EngineeringKAIST
Dr. Jaeson Jang Ph.D.Visual System and Neural Network LaboratoryDepartment of Bio and Brain Engineering KAIST
Sang Hyeon Ju M.D.Laboratory for NeurophysiologyDepartment of Biological SciencesKAIST
2021.08.26 View 19246 -
Brain-Inspired Highly Scalable Neuromorphic Hardware Presented
Neurons and synapses based on single transistor can dramatically reduce the hardware cost and accelerate the commercialization of neuromorphic hardware
KAIST researchers fabricated a brain-inspired highly scalable neuromorphic hardware by co-integrating single transistor neurons and synapses. Using standard silicon complementary metal-oxide-semiconductor (CMOS) technology, the neuromorphic hardware is expected to reduce chip cost and simplify fabrication procedures.
The research team led by Yang-Kyu Choi and Sung-Yool Choi produced a neurons and synapses based on single transistor for highly scalable neuromorphic hardware and showed the ability to recognize text and face images. This research was featured in Science Advances on August 4.
Neuromorphic hardware has attracted a great deal of attention because of its artificial intelligence functions, but consuming ultra-low power of less than 20 watts by mimicking the human brain. To make neuromorphic hardware work, a neuron that generates a spike when integrating a certain signal, and a synapse remembering the connection between two neurons are necessary, just like the biological brain. However, since neurons and synapses constructed on digital or analog circuits occupy a large space, there is a limit in terms of hardware efficiency and costs. Since the human brain consists of about 1011 neurons and 1014 synapses, it is necessary to improve the hardware cost in order to apply it to mobile and IoT devices.
To solve the problem, the research team mimicked the behavior of biological neurons and synapses with a single transistor, and co-integrated them onto an 8-inch wafer. The manufactured neuromorphic transistors have the same structure as the transistors for memory and logic that are currently mass-produced. In addition, the neuromorphic transistors proved for the first time that they can be implemented with a ‘Janus structure’ that functions as both neuron and synapse, just like coins have heads and tails.
Professor Yang-Kyu Choi said that this work can dramatically reduce the hardware cost by replacing the neurons and synapses that were based on complex digital and analog circuits with a single transistor. "We have demonstrated that neurons and synapses can be implemented using a single transistor," said Joon-Kyu Han, the first author. "By co-integrating single transistor neurons and synapses on the same wafer using a standard CMOS process, the hardware cost of the neuromorphic hardware has been improved, which will accelerate the commercialization of neuromorphic hardware,” Han added.This research was supported by the National Research Foundation (NRF) and IC Design Education Center (IDEC).
-PublicationJoon-Kyu Han, Sung-Yool Choi, Yang-Kyu Choi, et al.“Cointegration of single-transistor neurons and synapses by nanoscale CMOS fabrication for highly scalable neuromorphic hardware,” Science Advances (DOI: 10.1126/sciadv.abg8836)
-ProfileProfessor Yang-Kyu ChoiNano-Oriented Bio-Electronics Labhttps://sites.google.com/view/nobelab/
School of Electrical EngineeringKAIST
Professor Sung-Yool ChoiMolecular and Nano Device Laboratoryhttps://www.mndl.kaist.ac.kr/
School of Electrical EngineeringKAIST
2021.08.05 View 15930 -
Two Dimensions of Value: Dopamine Neurons Represent Reward but not Aversiveness
Professor Christopher D. Fiorillo of the Bio & Brain Engineering (http://ineuron.kaist.ac.kr/web/home.html) at KAIST published a research paper in the August 2 issue of Science. The title of the paper is “Two Dimensions of Value: Dopamine Neurons Represent Reward but not Aversiveness.” The following is an introduction of his research work:
To make decisions, we need to estimate the value of sensory stimuli and motor actions, their “goodness” and “badness.” We can imagine that good and bad are two ends of a single continuum, or dimension, of value. This would be analogous to the single dimension of light intensity, which ranges from dark on one end to bright light on the other, with many shades of gray in between. Past models of behavior and learning have been based on a single continuum of value, and it has been proposed that a particular group of neurons (brain cells) that use dopamine as a neurotransmitter (chemical messenger) represent the single dimension of value, signaling both good and bad.
The experiments reported here show that dopamine neurons are sensitive to the value of reward but not punishment (like the aversiveness of a bitter taste). This demonstrates that reward and aversiveness are represented as two discrete dimensions (or categories) in the brain. “Reward” refers to the category of good things (food, water, sex, money, etc.), and “punishment” to the category of bad things (stimuli associated with harm to the body and that cause pain or other unpleasant sensations or emotions).
Rather than having one neurotransmitter (dopamine) to represent a single dimension of value, the present results imply the existence of four neurotransmitters to represent two dimensions of value. Dopamine signals evidence for reward (“gains”) and some other neurotransmitter presumably signals evidence against reward (“losses”). Likewise, there should be a neurotransmitter for evidence of danger and another for evidence of safety. It is interesting that there are three other neurotransmitters that are analogous to dopamine in many respects (serotonin, norepinephrine, and acetylcholine), and it is possible that they could represent the other three value signals.
For the research article, please visit: http://www.sciencemag.org/content/341/6145/546.abstract
For the Science 2nd issue, please visit: http://www.sciencemag.org/content/current#ResearchArticles
Illustration of Value Dimension
2013.08.08 View 10671 -
Nerve-protecting gene discovered
Korean scientists for the first time have identified a gene that blocks nerve damage from fevers and the use of narcotics, a state-run research institute said yesterday.
The finding may open the way for new medicine that can prevent the loss of brain function which is frequently caused by excessive stimulation of nerves and abnormally high body temperature.
"The research is in an early stage. But this approach has the potential to develop genetics-based preventatives against brain-attacking diseases," said Kim Jae-seob, a bioscience professor of the Korea Advanced Institute of Science and Technology, who led the study.
The researchers named the gene Pyrexia, which means fever. Kim"s team extracted it from genetically engineered fruit flies using a genome-screening system. In laboratory tests, they found that the gene is activated to 39 degrees Celsius or higher.
The researchers enhanced Pyrexia"s functionality in some fruit flies while removing the gene from others to observe their different reactions when exposed to high temperature.
"The fruit flies without the gene showed severe nerve disorder and suffered paralysis of brain function, while Pyrexia-enhanced flies maintained their normal brain conditions," the professor said.
The researchers got the same result from experiments with human cells, he said.
There are a lot of channel proteins, which enable ions to enter and exit the cell, that react to the level of temperature, but Pyrexia is the first of its kind that actually protects the neurons from external stimulus, he said.
The finding will appear on the March edition of the London-based science magazine Nature Genetics.
THE KOREA HERALD 2005.1.31 (thkim@heraldm.com) By Kim Tong-hyung
2005.02.02 View 21225