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The Brain Initiative

The Brain Initiative in Walton Institute is multidisciplinary and crosses between multiple research divisions. 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 amounts of investments both in Europe (EU FET Flagship “Human Brain Project”) and the US (Obama “BRAIN” initiative).

Our Focus

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. It is the intention of Walton Institute to bring traditional communication and networking theories to understand the brain’s communication process, and to engineer new generation of implantable devices. This is divided into two areas:

  1. Use communication theory and networking to understand neural signaling within the brain, as well as communication properties for neurodegenerative diseases.
  2. Develop new generation implantable devices that includes bioelectronics as well as engineered synthetic cells that can control neural molecular communications.

There are five strands in the Brain Initiative:

Artificial neural stimulation uses electrical current to stimulate specific parts of the human nervous system. At present it is used to treat neurological conditions (e.g. Parkinson’s Disease), neural impairments or to enhance neural connectivity for prosthetics. Stimulation may be delivered by externally powered electrodes placed on the skin surface (transcutaneous) or under the skin (subcutaneous) in close proximity to muscles or nerves.

This research models the use of ultrasound as a method of wirelessly activating an implanted neural-stimulation device at a shallow depth of the tissue. The medical use of ultrasound for imaging is widespread, well understood and has recommended safety levels. Arrays of devices containing piezoelectric nanowires can convert incident ultrasound energy into electrical pulses. These pulses can stimulate nerve bundles (fascicles) to generate a stream of modulated signals along the nerve and deliver data packets to a more deeply embedded receiver. The maximum bit rate is 200 bit/s, limited by the rate at which nerves can generate electrical signals. The modulation is simple on-off keying (OOK) to create a stream of logic “ones” and “zeroes”.

The research also targets stimulus system on the vagus nerve in the neck sending modulated data pulses to an embedded multi-reservoir drug-delivery system in the brain. The drug-delivery system could use cerebrospinal glucose as a source for energy harvesting.

This strand also covers wireless optogenetic devices, where devices constructed from nanocomponents are assembled into devices that can be implanted into the brain to simulate engineered cells using light. The research has investigated techniques for charging the devices wirelessly using ultrasound, as well as modeling propagation of light through a group of neurons to understand how they are affected by the shapes of the neurons.

Research Objectives

  • Modeling the input ultrasound energy (maximum 720 mW/cm2) and harvested power for single fixed-size nanowire-based nanodevices (1000µm2 with 20 nanowires per µm2) at different tissue depths and comparing these with the current and voltage levels required for peripheral neural stimulation.
  • Modelling the dimensions of nanodevice arrays, embedded in biocompatible tissue patches, to meet neural stimulation requirements. The effect of degrees of tilt of the nanowire unit is also calculated.
  • Using transmission theory to calculate the data capacity and transmission range of a stimulated nerve for different modulation techniques, subject to an overall limit of 200 bits/s.
  • Modeling the propagation of light through neurons for stimulation, as well as group of neurons where multiple devices can use light to communicate and coordinate distributed stimulation.

Bio-compatible patch containing nanodevice array powered by externally generated ultrasound waves. The array sends current pulses to stimulate specific fascicles (nerve fibre bundles). 

Collaborators

  • Prof. Josep Miquel Jornet, Northeastern University, Boston, USA
  • Prof. Yevgeni Koucheryavy, Tampere University, Finland

In recent years, new forms of molecular drug delivery within the brain have been investigated. An example of this is the use of exosomes for detecting tumour as well as for treatment. The study of molecular diffusion in the brain is very complex due to various factors, where an example is obstacles that can block the diffusion of molecules as they are propagating witin the extracellular space (ECS). Other factors can include the geometric configurations or the volume size of the ECS. A digital reconstruction of the brain ECS can allow for the understanding of molecular diffusion and consequently targeted drug-delivery systems. The aim of this research is to create a simulated model of the a 3D ECS, where we can study molecular diffusion of exosomes that can be delivered to the tumour cells. The construction is based on utilizing data from electron microscopy images and development characteristics such as tortuosity and volume fraction of the ECS, which can allow accurate prediction of exosome concentration that is required for delivering during the treatment process.

Research Objectives

  • Collect data related to cell types and densities of cells and Electron Microscopy (EM) images, and use as reference and inputs to reconstruct a realistic configuration of the brain ECS;
  • Model the brain ECS according to data regarding the tortuosity and volume fraction;
  • Run simulations in the 3D reconstructed brain ECS configurations and use molecular communications theory to study the molecular diffusion and targeted drug-delivery systems in the ECS

3D reconstruction of neurons that can be used to model the ECS in order to understand the propagation properties of exosomes.

Collaborators

  • Andriani Odysseos, EPOS, Cyprus

Projects

Using EEG/HEG and facial coding to monitor a users emotional state to develop immersive content. Using brain stimulation methods encoded in the AR/VR content to identify ERPs such as P300 responses. Using these auditory and visual stimulations we can identify key brain reactions to this content. These stimulations in turn affect the current brain activity and allow us to determine normal and abnormal reactions to the stimulations.

By focusing initially on the visual ERP reaction to visual stimuli we can determine how the brain itself perceives the virtual world as opposed to real world stimuli. Utilising this we can develop dynamically changing content for neurorehabilitation.

We investigate both the event and the resulting signals to determine its effects on overall brain activity. The activity of the brain is used to train a basic prediction model. This prediction model can be further trained based on the neurofeedback system supplying new stimulations to achieve the desired brain activity reaction and thus the approximated network topology. These stimulations devised by deep learning model are encoded as parts of dynamic content in the neurotherapy feedback to allow the users activity to directly affect the experience. As more subjective data is gathered these predictions gain accuracy. Based on the functionally healthy brain topologies, weightings can be determined based on the subjective reactions to the stimulations that allow a dynamic rehabilitation system to be developed.

Validation of the emotional pattern recognition algorithm through use of facial coding methods and HEG. This research focuses on creating a validation mechanism for the algorithm by testing FER (Facial emotional recognition) and HEG (hemoencelopgraphy) to determine current state while partially occluded by the headset.

Research Objectives

  • Understanding how the brain interrupts and processes virtualised content is fundamental to creating more immersive and engaging content. From results so far we see a heightened attentive allocation in VR while performing a key attentive visual task. By demonstrating this heightened sense of attentiveness, it can be utilised to create more immersive VR content, and adapt this content based on the evoked responses to help reduce the overall time needed for neurorehabilitation
  • Those undergoing neurorehabilitation are often frustrated and fatigued by long months of visual and motor control tasks to improve their conditions. By introducing new methods of interaction that show a heightened sense of attentiveness in the participant, we hope to allow the rehabilitation program to impact these users more effectively than traditional methods.

Projects

  • VisionaryCF: Utilising virtual reality to gauge visual perception. Expanding on this is how the visual cortex perceives the VR world as well as differences between them. This allows for the mapping of locked state visual stimulus allowing mapping of visual inputs to neurological outputs in the occipital lobe.

With the advancement of synthetic biology and cellular reprogramming techniques we should be able to push the limits of the new generation brain implants that can be used to stimulate natural neurons in order to augment their function. Although biological computing is pervasive in living systems, having the capability to engineer new molecular computing capabilities, can provide new capabilities of controlling and changing neural signaling patterns. As part of this research, we investigate how we can develop boolean logic gates from engineered neural cells. Our research includes both computer simulations as well as wet lab experiments that demonstrate how astrocyte cells can be engineered into AND and OR gates, based on controlling the calcium signaling through the population of neurons. An example application of the digital logic circuits constructed from neural cells is a spike filter that attenuates high-frequency activity in a neuronal network that can be used to minimize the effects of neurodegenerative disorders such as epilepsy.

Research Objectives

  • Create a framework that can be used to engineer the calcium signaling within astrocyte cells, in order to create Boolean logic gates.
  • Utilise theoretical concepts from information and communication engineering as well as control systems engineering to analytically approach the molecular communication performed by the pre- and post-synaptic neurons and analyse its role in the cortical networks.
  • Investigate potential applications such as the precise treatment of neurodegenerative disorders and possible enhancement of cognitive functions.

Boolean logic gates created from engineered neural cells that controls the calcium signaling propagation within the population

Engineered astrocytes with manipulated calcium signaling that results in AND and OR gates (wet lab experiments developed at Tampere University)

Collaborators

  • Nicola Marchetti (Trinity College Dublin)
  • Harun Siljak (Trinity College Dublin)
  • Meenakshisundaram Kandhavelu (Tampere University, Finland)

Glioblastoma Multiforme is the most prevalent and devastating brain disease whose treatment have the lowest success rates compared to other therapeutic cancer technologies. The development of brain drug delivery systems for this type of cancer is very challenging because of side effects, the complexity of the structures of the brain, and the stringent Blood-Brain Barrier (BBB) that protects the brain from damage and potentially toxic blood-borne molecules. In addition, the lack of efficient technologies to deliver drugs in the deep located and functional brain regions, such as the brain parenchyma, and across the BBB hinders treatment of brain pathologies. Hence, novel technologies for Glioblastoma cancer therapy must emerge to overcome the BBB blockage while efficiently reaching the brain parenchyma within safety guidelines. An externally controllable molecular communication platform that consists of stem cells acting as therapeutic, reporting and diagnostic bio-nanomachines has been proposed, and is part of the EU H2020 FET project GLADIATOR: Next-generation Theranostics of Brain Pathologies with Autonomous Externally Controllable Nanonet- works: a Trans-disciplinary Approach with Bio-nanodevice Interfaces.

A key characteristic of molecular communication is the use of molecules as the information carrier. Towards this objective we use the concepts of molecular communication networks to model the evolution of GBM cancer as a result of (a) self-renewal (Grow) of Glioblastoma stem cells and (b) invasion (Go) potential of glioma cells as shown in Figure 1. For this purpose we develop a voxel model where each cell is represented by a cubic voxel accounting for both the diffusion and reaction events within the molecular communication system. We develop a novel mathematical model based on ordinary differential equations which quantifies output of the end-to-end inter-cellular communication between cells. We use this mathematical model and apply concepts from communication theory to study one key property associated with this end to end communication system i.e. mutual information and its relation with tumour growth rate.

Research Objectives

GLADIATOR establishes a baseline of feasibility and innovation potential and envisions taking a radical step towards a drastic transformation in the way we investigate and manage complex malignancies and potentially other major pathologies with long term radical advances:  For pre-clinical oncology research: an emerging supra-discipline of “bio-nanomachine diagnostics” which lays the grounds for future autonomous treatments of diseases that require micro-scale devices, monitored and controlled externally, advancing ICT, engineering and synthetic biology research.  For clinical oncology: a radical shift towards “nanonetwork therapeutics” which includes fully functional autonomous closed loop disease management systems; (ii) drastic renewal of ideas in tumour theranostic, by MC sub-disciplines, affecting pharmacology, biotechnology, therapy selection and disease monitoring.

Impact on society and economy: Patients’ prognosis: minimal recurrences, reduced drug toxicity, prolonged survival. Caregivers’ workload: drastically improved patient response, reduced return visits. Health Care Systems: improved health, life expectancy and productivity, reduced sick-leaves, shorter hospitalizations, less personnel involved. Policy Makers: technology-driven novel strategies for autonomous therapeutics, transformation of healthcare concepts. Patient support groups: paradigm shift in the advocacy for adoption and endorsement of the new technology by regulatory bodies and insurances.

Impact on market creation: The project aims to deliver innovative biological and nanotechnology-based materials and theoretical underpinnings, development methods, computational and analytical tools to create a new transformational market in the fields of “bio-nanomachine diagnostics and nanonetwork therapeutics”.

Initiation and progression of Glioblastoma Multiforme showing an interplay between Go and Grow phenotypes, and showing the invasiveness process.

Collaborators

Projects