NIHRDataInsights/HRCSData huggingface dataset:
Title: Telehealth in Motor Neurone Disease: the TiM trial. A randomised controlled pilot study of the use of the TiM system to deliver highly specialised care to patients and carers of those living with motor neurone disease.
Funder: Department of Health (England)

Abstract: Motor neurone disease (MND) is a rare but debilitating condition. Patients struggle to travel to specialist MND centres and expert care is often unavailable at home. We have developed a handheld telehealth device which enables patients to be monitored from their homes in order to provide specialist care when it is required. We predict this will improve patients’ quality of life and lead to more effective use of resources. We wish to undertake a pilot study to learn how a larger trial could evaluate the clinical and cost-effectiveness of this telehealth system.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;6.3 MEDICAL DEVICES
Health categories: NEUROLOGICAL
Title: PDP-squared: Meaningful PDP language models using parallel distributed processors.
Funder: Engineering and Physical Sciences Research Council

Abstract: Parallel Distributed Processing (PDP) is a form of computation where a large number of processing units performing simple calculations can be employed all together to solve much more complex problems Perhaps the best example of this is the human brain, which contains approximately one hundred billion neurones. Individually these neurones simply have to decide whether to fire or not, and they do this based upon how many other neurones that are connected to them have fired recently. When this simple local computation is distributed over billions of neurones it is capable of supporting all the extremely complex behaviours that humans exhibit / talking, reading, walking, running etc / behaviours that are well beyond the abilities of more traditional computers. For this and other reasons, many psychologists believe that PDP models are the best way of describing human cognition. Unfortunately, at the moment these models are invariably simulated using standard PCs, which means that each unit in the model has to be dealt with one after the other in a serial process. This serial processing imposes severe limitations upon the complexity of problems that can be tackled. Our goal is to us to understand how the brain supports language function, how this breaks down after brain damage and the mechanisms that support recovery/rehabilitation. This will require a model of language that is capable of simulating speech, repetition, comprehension, naming and reading. To train such a model using existing pc-based simulators would take far too long /possibly more than a lifetime. So the first objective of this project is to produce a parallel distributed processing machine that is truly parallel (PDP-squared). We intend to use an array of 10,000 ARM processors incorporated into a machine that will be able to run our simulations of human behaviour 500-1000 times faster than is currently possible on a single pc. Once we have successfully produced this machine (Phase1 of the project), we will use it to build a model of normal human language function that can support reading (both aloud and for meaning), comprehension, speech, naming and repetition for all of the single monosyllabic words in English. We will validate this model by showing that damaging it can lead to the same patterns of behaviour as found in brain damaged individuals (Phase 2). Finally we will use the model to predict the results of different speech therapy strategies and will test these predictions in a population of stroke patients who have linguistic problems


Research activity codes: 1.4 METHODOLOGIES AND MEASUREMENTS
Health categories: NEUROLOGICAL
Title: Imaging Membrane Potential via Second Harmonic Generation
Funder: Engineering and Physical Sciences Research Council

Abstract: Understanding how the brain works is one of the great unsolved scientific challenges. In order to learn how neuronal networks process information, we need a way of mapping the voltage changes in neurons, with high sensitivity, high spatial resolution and high temporal resolution. Microelectrodes are currently the primary method for measuring membrane potentials; they give excellent sensitivity and temporal resolution, but very limited spatial resolution. Optical microscopy has the potential to revolutionise this field by allowing the non-invasive, real-time, high resolution imaging of voltages along individual neurons, or groups of neurons, within their native networks. The huge advantage of optical probes, compared to electrodes, is the ability to map potential across many neurones at once.At present, the most effective optical probes for membrane potential are fluorescent calcium indicators, which measure membrane potential indirectly, via the concentration of Ca2+. However changes in calcium concentration do not accurately reflect voltage transients, and provide no information on the voltage waveform. Fluorescent voltage-sensitive dyes were developed 30 years ago for this application, but in most cases their response is weak and obscured by background fluorescence. They also have severe problems of photo-instability and photo-toxicity.Recently, second harmonic generation (SHG) imaging has emerged as a powerful alternative. SHG arises from polarisable molecules in asymmetric environments. Push-pull chromophores orientated in the neuronal plasma membrane generate a high contrast signal that is sensitive to the local electric field. The high polarisability and intense optical transitions of porphyrins make them excellent candidates for engineering efficient SHG voltage-sensitive probes. Furthermore, SHG is a scattering effect and it does not require the population of excited-states, so it should be possible to design SHG dyes which are free from photobleaching and photo-induced degradation.Our first studies on porphyrin-based voltage probes led to dyes which exhibit strong SHG and have high affinities for biological membranes, allowing observation of strong SHG signals from ex vivo neuronal slices. The purpose of this proposal is to build on these initial results, to create a new series of voltage-sensitive porphyrin-based dyes for studying neuronal networks, and to explore the scope of this technology for imaging membrane potential in the brain.This collaborative interdisciplinary project combines synthesis of new probe molecules, development of new membrane technology for screening voltage sensitive dyes, multiphoton microscopy and testing of new probe compounds, within vitro cell cultures and ex vivo neuronal networks.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: NEUROLOGICAL
Title: Novel vibrational spectroscopic techniques: long-range order in amyloid fibrils
Funder: Engineering and Physical Sciences Research Council

Abstract: Amyloid diseases are a major health problem and include neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's disease, as well as type II diabetes and infectious prion diseases, such as Creutzfeldt-Jakob disease (CJD). They are characterised by the deposition of large fibrillar aggregates of protein, both within cells and in the extra cellular matrix, that were thought to cause cell death and result in the observed pathology. The constituent fibres of these fibrils have a common beta-sheet architecture with long-range order despite being able to form from many different proteins. More recently, attention has shifted to precursor soluble oligomer species as the toxic agents in these diseases. However, the precise structure and degree of long-range order in these oligomers has not yet been determined and is difficult to probe using existing biophysical techniques, hampering the development of drugs targeted at this stage of the disease. My Fellowship will make use of terahertz frequency time-domain spectroscopy (THz-TDS) to study long-range order of amyloid fibrils and their precursors. This will be complemented by Raman spectroscopy and molecular modelling calculations to gain an understanding of the inter- and intra-molecular interactions within this important class of biological molecules. THz-TDS is an emerging technique that is proving to be of particular importance for the investigation of organic crystalline compounds. This is because THz spectroscopy has been shown to excite inter-molecular vibrations, thus not only probing chemical composition, but also proving to be extremely sensitive to small changes in crystalline structure. During the Fellowship, I will develop new THz frequency spectroscopic techniques. For example, the inclusion of polarisation sensitive detection will, for the first time at THz frequencies, allow spectroscopic information to be obtained related to the chirality of the molecules, including the secondary structure of proteins and small peptides.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL
Title: Quantifying the Sources of Phase Contrast in High Resolution Magnetic Resonance Imaging of the Human Brain.
Funder: Engineering and Physical Sciences Research Council

Abstract: Magnetic Resonance Imaging (MRI) is a widely used technique that allows non-invasive imaging of soft tissues in the human body and brain. One of the strengths of MRI is its flexibility in producing images that contain different contrast properties based on differences in the composition of tissues. The research proposed here will attempt to characterise fully the contrast seen in the human brain using one such technique called gradient-echo phase imaging.Phase imaging of the human brain is a relatively new technique for providing information on the properties of tissue. The popularity of this technique has risen with the increased availability of ultra high field MRI scanners which use magnetic field strengths in excess of 3tesla (T). At high field strengths the contrast seen in phase images is amplified to the point where tissue structures that could previously only be seen in histology can now be visualised in vivo. The achievable spatial resolution of phase images measured at 7T is now approaching the 100 micron length-scale yielding important information on tissue structure and composition for researchers in the field neuroscience. Until recently, the contrast seen in phase images was thought to be solely due to differences in the isotropic, volume magnetic susceptibility of tissues, arising from variations in the concentrations of materials like iron and myelin. Over the last two years, the explanation of phase contrast in the human brain has grown in complexity as result of work showing that three new mechanisms could all potentially contribute to phase contrast. These mechanisms are: anisotropic susceptibility, frequency offsets due to long range order in the microstructure of tissue, and offsets due to the exchange of magnetisation between water protons and larger molecules. The goal of the work described in this proposal is to unravel the contribution of each of the different mechanisms to phase images of the human brain and to provide a clear understanding of the origin of each contrast mechanism. The research will primarily focus on post mortem tissue samples that allow more direct measurement of phase information and histology. The information gained from the analysis of these samples will then be applied to human phase images acquired in vivo. Quantification of the different sources of contrast in vivo will provide information about iron and myelin content, and nerve fibre orientation and composition, which could in future be used to improve our understanding and ability to diagnose diseases such as Alzheimer's disease, Parkinson's disease and multiple sclerosis.


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: NEUROLOGICAL
Title: X-ray Spectromicroscopy Studies of Magnetic Iron Biominerals related to Alzheimer’s Disease
Funder: Engineering and Physical Sciences Research Council

Abstract: This proposed project will utilise novel synchrotron x-ray techniques to investigate the origin and role of nanoscale biologically derived iron minerals together with peptide aggregates in Alzheimer's disease (AD). Recent research suggests that the formation of iron mineral deposits and the aggregation of the amyloid-beta peptide could be intimately linked with the development of the disease. Further, the development of magnetic iron minerals may help to provide early diagnosis due to their affect on magnetic resonance images (MRI). The project will build on some recent successful experiments performed by the applicants at the Swiss Light Source and Canadian Light Source facilities, and will utilise the strong track record of the applicants in the application of synchrotron techniques to the analysis of magnetic materials and biominerals. As the facilities required for these experiments do not yet exist within the UK, funding is requested for overseas travel for the principle investigator. This will enable him to perform further experiments, build collaborations with scientists at international synchrotron laboratories, and provide crucial on-site training for a PhD student involved in the project. Further to this, the expertise and technical achievements attained in the project could be translated to planned facilities that will become available at the Diamond Light Source laboratory in the next 3-4 years.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL
Title: iPROBE: in-vivo Platform for the Real-time Observation of Brain Extracellular activity
Funder: Engineering and Physical Sciences Research Council

Abstract: Understanding how the trillions of action potentials of the brain's billions of neurons produce our thoughts, perceptions, and actions is one of the greatest challenges of 21st century science. Similarly, understanding how this activity is disrupted by ne


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.4 METHODOLOGIES AND MEASUREMENTS
Health categories: NEUROLOGICAL
Title: Ultrasound in a Needle: Minimally-invasive High Resolution Imaging for Neurosurgery
Funder: Engineering and Physical Sciences Research Council

Abstract: The research challenge we will tackle is to realise real-time visualisation of tissue in the brain with a needle capable of minimally-invasive, real-time, high resolution ultrasound imaging. This will, for the first time, enable the neurosurgeon to obtain immediate information about lesions and the location of critical structures in the brain intraoperatively, and thus to provide treatment with less morbidity and better patient outcomes. Our specific engineering challenge is to create a needle carrying an integrated, miniature ultrasound array for high-resolution (~100 um) neurological imaging and to demonstrate feasibility for future translation into clinical practice. Previous EPSRC-funded collaboration by the Universities of Birmingham and Dundee has shown that piezocomposite material with microscale features can be realised with net-shape micromoulding techniques. Single element transducers based on these materials have been evaluated already and exploratory studies with Heriot-Watt University have demonstrated the capability to bond dense interconnects onto the new materials at low temperature and pressure to connect kerfless imaging arrays to external imaging electronics. The research we now propose will extend and integrate this technical work with neurosurgery to determine basic capabilities using brain tissue in soft-embalmed cadavers and to explore potential surgical benefits and applications. As well as the three university partners, the work will benefit from support from four companies, covering all aspects of the technology as well as its translation into clinical practice.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;5.4 SURGERY
Health categories: NEUROLOGICAL
Title: Modelling Human Brain Development
Funder: Engineering and Physical Sciences Research Council

Abstract: The neural network of the human brain is arguably the most complex biological pattern; however, the mechanisms forming such neural systems are unclear. Neural systems show structurally emergent properties in terms of their topology and functionally emergent properties concerning information processing. Structural properties are the rise of modular and hierarchical connectivity, of long-distance connections, and of highly connected nodes. Functional properties are the distribution and integration of information, the formation of specialized modules dealing with different tasks, and a rapid reaction time due to parallel processing. Recent advances in neuroimaging, using diffusion tensor imaging, allow us to observe how the human brain network differs over ages ranging from the embryonic to the adult stage (age of 20 years). This project will analyse how the human brain network arises during development by combining data analysis with simulations of brain development. Objectives are to develop a simulation of human brain development, to analyse network features of human brains at different developmental stages, and to compare simulations with real data to discover the underlying mechanisms for brain network development. Simulations are crucial to study the role of different developmental parameters on the final brain network as well as on intermediate networks during development. Understanding how parameters lead to (adult) network features will help to evaluate the contribution of these parameters to healthy and pathological development. Once understanding the time course of development, we should also be able to predict the probabilities of future stages of development. This will be crucial for giving a prognosis for the progression of developmental diseases. In addition to understanding the formation of human cognitive systems, these results will inform the design and update of artificial information processing systems Identifying these key developmental mechanisms will greatly improve our understanding of emergence in biological systems In addition, it might lead to several predictions about the rise of brain disorders such as schizophrenia, epilepsy, and autism that often originate during development and are linked to changes in hub organization. Beyond biological pattern formation, such 'algorithms' for human brain development could inform us how to build artificial intelligent systems Rather than constructing artificial brains in a top-down manner, applying identified mechanisms for neural network development will allow the emergence of intelligent information processing systems leading to systems that are more adaptable. In summary, the formation of human brains is a fundamental question that touches on the emergence of natural and man-made information processing systems


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: NEUROLOGICAL
Title: Anatomy-Driven Brain Connectivity Mapping
Funder: Engineering and Physical Sciences Research Council

Abstract: The connectome, the comprehensive map of neural connections in the human brain, is unique in every individual. Even identical twins differ at the level of neural connectivity. Mapping the human connectome and its variability across individuals is esse


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: NEUROLOGICAL
Title: The fast without the spurious: developing a system for robust and rapid simultaneous EEG-fMRI measurements
Funder: Engineering and Physical Sciences Research Council

Abstract: To increase our understanding of how the brain works and how it goes wrong in people with neurological conditions such as epilepsy we need to develop better systems for making measurements of brain activity. Electroencephalography (EEG) is an important modality in clinical and experimental neuroscience capable of measuring electrical changes occurring with sub-millisecond temporal resolution and a spatial resolution of centimetres while functional Magnetic Resonance Imaging (fMRI) can map haemodynamic changes over the entire the brain at a time-scale of seconds and spatial resolution of a few millimetres or better. Therefore together they can perform measurements across a greater range of brain activity occurring either at faster temporal or smaller spatial scales. However, during simultaneous EEG-fMRI acquisitions these both methods signal are degraded by noise related to motion, thereby significantly limiting the sensitivity of this type of study so far. The purpose of this application is to build a robust system that can perform these simultaneous EEG and fMRI measurements of brain activity. To achieve this goal we will integrate new fast fMRI pulse sequences because images obtained in shorter time intervals are intrinsically less motion sensitive (like a faster shutter speed on a camera). Also better modelling of motion will be possible if we obtain more images per unit time because we can better separate and model the different sources of signal and noise that occur in different frequency ranges. In addition, we will optimise motion detection and prospective motion correction (PMC) using a camera system that tracks the subject's motion and updates the image acquisition process so that patient motion is supressed. When using these improvements to fMRI data acquisition we will need to develop novel EEG artefact correction methods for simultaneous in-scanner EEG recording which currently rely on the repetitive nature of the artefact in time. Both motion and PMC are likely to make the artefact more variable and so will require the development of novel correction methods. Once we have developed this system we will apply it to ten patients with hard to treat epilepsy from Great Ormond Street Hospital who are being assessed for epilepsy surgery. This assessment aims to identify the epileptic brain regions and EEG-fMRI is a tool to help obtain this information. We will compare our current standard EEG-fMRI protocol which often suffers from degradation due to motion (particularly in young children) to our new robust EEG-fMRI incorporating PMC, fast fMRI and improved EEG artefact correction.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: NEUROLOGICAL