Post doc Researcher, Michael Taynnan Barros and Director of Research, Sasitharan Balasubramaniam, both of TSSG, are working on an ICT-based approach to Brain Communication, Neurology and Neurodegeneration under the TSSG Brain Initiative.
The TSSG Brain Initiative is multidisciplinary and crosses between multiple Research Units. The decision to start this new initiative and research direction is due to the importance of this new research field globally, where we are witnessing large amount of investments both in Europe (EU FET Flagship “Human Brain Project”) and the US (Obama “BRAIN” initiative). While the field of Brain research has predominantly been driven by Neuroscience, ICT has started to play a role in developing new approaches for understanding the operations of neural systems, as well as diagnosing diseases. TSSG has traditionally been an ICT research centre that focuses on research in communication networks and services, and it is the intention of this initiative to bring theories from traditional “communication and networking” to understand the brain’s communication process. The latter is mainly focused on new solutions to help patients suffering from neurodegenerative diseases. The other motivation for the creation of the initiative is the linkages we are now starting to witness between the brain and machines. This includes development of new brain-inspired algorithms for Artificial Intelligence (e.g. Deep Learning), as well as Brain-Machine Interfaces (BMI).
Neuroscience has exploded in recent years as a major prominent research field with an incredible amount of investment from both public and private sectors globally with the goal of understanding the brain completely as well as transferring this knowledge to engineering and technology in general. However, the slow pacing discoveries are not accompanied by technology advancements and therefore creates a gap. It is being realized, even more recently, that information and communication technology can be, together with nanotechnology and synthetic biology, the novelty needed in neuroscience to help it reach its goals. We explore this possibility by implementing the merge of this areas and studying both neurology and neurodegeneration medicine. We investigate the neuronal communications in the brain, which are separated by many scales and layers, and how their communication affect neurons well functioning and disease starting processes and spreading caused by communication failures. Neurodegeneration has increasingly affected people’s lives in many different forms due to the increase in life expectancy in the ageing society. We also investigate many different strategies for neurodegeneration treatment and diagnosis including optogenetics nanonetworks, synthetic biology, nanoparticles and silicon-in-a-cell chips. The TSSG Brain Initiative (TBI) is currently pursuing research in this area based on the Internet of Bio-Nano-Things vision , where both synthetic and natural nanomachines will be connected to the Internet to perform both sensing and actuation tasks, and in this case, inside the Brain. In the following you will find a review of two main strands in the TBI, which has been successful in terms of grants, publications and public engagement.
Wireless Optogenetics Nanonetworks
Innovative treatments for many neurodegenerative diseases frequently involve the use of long-term implants able to monitor and stimulate different regions of the human brain. Such Brain Machine Interfaces (BMI) can generally be classified in two categories, namely, electrical BMIs and optical BMIs. The former rely on implanting electrodes into the skull to stimulate specific areas of the brain, such as the technique used to eliminate the shaking effects for patients suffering from Parkinson’s disease. The latter involves the use of light to stimulate individual or small sets of genetically engineered neurons—a concept known as optogenetics. Although the original design of optogenetic BMIs required optical fibers to be inserted into the skull, tremendous advancements have been made since towards wireless units that can be implanted into the cortex. Unfortunately, the majority of solutions have yet to address the challenges related to long-term applications. These include, among others, (i) the miniaturization of the optogenomic mote (i.e., light-source, controller and battery) to enable single neuron level stimulation, and (ii) the development of energy-harvesting systems to ensure everlasting operation. While the neural dust referenced in  satisfies the miniaturization at the micrometer scale, the devices are currently focused on monitoring rather than stimulation. The wireless optogenetic device proposed in  utilizes radio-frequency power source for charging the device. However, the size of unit is still currently at the millimeter scale. The concept of optogenetic neural dust has been recently proposed  to realize the challenges addressed above. The proposed architecture extends the neural dust model and architecture proposed in , but includes the required optical source to stimulate the neurons. These devices can be scattered into the brain, more specifically into the micro neuronal network that compose the circuitry of the cortex. This can create an opportunity to achieve neuronal stimulation of specific neurons in the cortex . We recently have demonstrated in , that the successful stimulation of these devices inserted inside a cortical microcircuit can achieve regeneration of neuronal spike activity that was previously know. This open the doors for the design of future and incredibly precise brain-machine interfaces accompanied with more efficient methods for deep brain stimulation.
Figure 1- Wireless Optogenetics Nanonetworks is an attempt to achieve deep brain stimulation of neurons though nano-scale machines that perform light stimulation of neurons. This network is shown efficient to replicate known firing activity into a cortical microcircuit .
Control of Neuronal and Non-Neuronal Cells Towards Neurodegeneration Treatement
Approximately 24 million people worldwide suffer from dementia, of which 60% is due to Alzheimer’s disease . Alzheimer’s is the sixth leading cause of death for all ages and the fifth leading cause of death for those 65 years of age and older, with an annual cost of approximately $226 billion in the U.S. alone. But its treatment remains with symptom-preventing drugs that neglect the diseases progression or do not cure the disease. The blood-brain barrier also prevents the effectiveness of current Alzheimer’s drugs, blocking the flow of drug molecules to the brain by the central nervous system. Researchers have found that nanoparticles can potentially bypass the blood-brain barrier. Therefore, nanotechnology alongside with biotechnology is an exciting approach that not only provides new drugs and treatments to Alzheimer’s, but can also enable a cure for the disease. Alzheimer’s main cause is the lack of glutamate in the tripartite synapses (three way molecular communication between neurons and astrocytes), which leads to poor synaptic transmission and therefore lack of memory, bad sleep, depression, and so on. The control of the concentration of glutamate can therefore increase the synaptic quality, providing a new and potentially more efficient way to treat Alzheimer’s.
Since, glutamate release is controlled by the intracellular Ca2+ signalling in the astrocytes of the tripartite synapses, providing desired levels of Ca2+ can result in the desired regulation of glutamate. The goal of this research is to investigate a potential way of obtaining such an outcome. We use the feed-forward feedback control theory, combined with communication theory and synthetic biology, to regulate the internal Ca2+ signalling of astrocytes in the tripartite synapses, providing sufficient levels of glutamate to control the quality of the synaptic transmission . This is not only applicable to Alzheimer’s but also to other neurodegenerative diseases, because it enables a new way of maintaining the stability and health of the brain tissues using nanotechnology and engineering principles. We believe that such a control system can be implemented using the previous technology, the wireless optogenetics nanonetworks. This interdisciplinary approach will cause a significant impact on biotechnology, nanotechnology, Alzheimer’s disease and drug delivery system research fields with also an important economic potential effect .
Figure 2 The feed-forward feedback control of neuronal and non-neuronal cells activity for possible neurodegeneration treatment. By controlling the ca2+ regulation in astrocyte we intend to achieve the control of the amount of glutamate in the synaptic channel.
This work is funded by the Irish Research Council under the grant GOIPD/2016/650.
I. F. Akyildiz, M. Pierobon, S. Balasubramaniam, Y.Koucheryavy, “Internet of Bio-Nano Things”, IEEE Communications Magazine, vol. 53, no. 3, March 2015.
D. Seo, J. M. Carmena, J. M. Rabaey, E. Alon, and M. M. Maharbiz. “Neural dust: An ultrasonic, low power solution for chronic brain machine interfaces”. arXiv preprint:1307.2196, 2013.
K. L. Montgomery et al., “Wirelessly powered, fully internal optogenetics for brain, spinal and peripheral circuits in mice”, Nature Methods, vol. 12, no.19, October 2015.
S. Wirdatmaja, S. Balasubramaniam, J. M. Jornet, Y. Koucheryavy, “Wireless Optogenetic Neural Dust for Deep Brain Stimulation”, in Proc.of IEEE Healthcom, Munich, Germany, September 2016.
S. Balasubramaniam, S. Wirdatmadja, M. T. Barros, Y. Koucheryavy, M. Stachowiak and J. Jornet. Wireless Communications for Optogenetics: Present Technology and Future Challenges. Accepted in IEEE Communications Magazine. 2018.
S. A. Wirdatmadja, M. T. Barros, Y. Koucheryavy, J. M. Jornet, S. Balasubramaniam. Wireless Optogenetic Nanonetworks for Brain Stimulation: Device Model and Charging Protocols. IEEE Transactions on Nanobioscience. v. 16, no. 8, pp. 859-872. 2017.
M. T. Barros. “Ca2+-signaling-based molecular communication systems: design and future research directions.” Elsevier Nano Communication Networks. vol 11, pp 103–113. 2017.
M. T. Barros and S. Dey. Feed-forward and Feedback Control in Astrocytes for Ca2+-based Molecular Communications Nanonetworks. BioXiV. 2017.
M. T. Barros and S. Dey. “Set Point Regulation of Astrocyte Intracellular Ca2+ Signalling”. The 17th IEEE International Conference on Nanotechnology (IEEE NANO 2017). Pittsburg, USA. 2017.