NIHRDataInsights/HRCSData huggingface dataset:
Title: Imaging the functional anatomy of fascicles in the mammalian vagus nerve with neural tracers, electrophysiology and Electrical Impedance Tomography.
Funder: Biotechnology and Biological Sciences Research Council

Abstract: The fascicular organisation of the cervical vagus nerve is almost completely unknown. The aim of this proposal is to investigate the functional anatomy of fascicles in the mammalian cervical vagus nerve which supply autonomic innervation to the stomach, heart, lungs and other visceral organs. Fascicle functional anatomy will be defined using AAV5 or other neural tracers and computerised fascicle tracing, and functional physiology with multielectrode arrays and electrophysiology, and the new method of fast neural imaging with Electrical Impedance Tomography (EIT). Initial studies will be in rat and rabbit sciatic nerve to enable technical integration of the methods. The refined methods will then be used in a defining dataset in anaesthetised pigs, and then a human study based on these findings using a non-penetrating nerve cuff with fast neural EIT; this is the only method which is non-invasive and so justifiable ethically for human studies. This will be performed for 30 minutes during an operation to insert a vagal nerve stimulator for treatment of epilepsy. It will deliver images of internal nerve activation in response to activity such as respiration or the ECG. The deliverables from this work will be : 1) A detailed anatomical atlas of the functional anatomy of fascicles in the cervical vagus nerve in the pig. 2) The first ever images of localised function in human vagus using fast neural EIT. This will be a novel resource for the autonomic community and inform the avoidance of off-target effects in "Electroceutical" autonomic nerve selective stimulation. The work will be led by an internationally leading consortium with expertise in bioengineering, computer science, autonomic physiology, large animal veterinary surgery, and a neurosurgeon who implants vagal nerve stimulators for epilepsy. The PI, David Holder, is a clinical neurophysiologist and engineer who has pioneered the development of fast neural EIT. 3) Refined method suite for future similar studies


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.4 METHODOLOGIES AND MEASUREMENTS
Health categories: NEUROLOGICAL
Title: 4 year PhD in Clinical Neurosciences: Attentional and inhibitory mechanisms in Tourette's syndrome
Funder: Brain Research UK

Abstract: This is a 1 + 3 year studentship, where the student spends one year rotating between different labs before deciding on their PhD project, which commences in year two. This project investigates the role of attentional control of tic inhibition in subgroups of Tourette syndrome patients according to comorbidity and treatment response. Additionally, the excitability of corticospinal output during inhibition of action and tics will be examined using TMS as part of a collaboration. Subsequently by investigating the attentional control and cortical neurophysiology of tic inhibition in Tourette’s syndrome patients, the efficacy of attentional distraction therapies for tic management will be assessed.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL
Title: A pilot study of sensory mapping of lumbar facet joint pain
Funder: British Journal of Anaesthesia

Abstract: Low back pain is highly prevalent in today’s society and has severe effects on physical and mental health. Roughly half of lower back pain is due to lumbar facet joint issues. One of many approaches to managing the pain is to use radiofrequency (RF) nerve ablation, currently done in two steps. First a diagnostic anaesthetic block is delivered to verify lumbar facet joint issues, then at a second appointment nerve ablation is undertaken. The current study would like to use RF stimulation diagnostically prior to the RF ablation during the same theatre session and avoid prior anaesthetic blocks.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: NEUROLOGICAL
Title: Do anti dementia drugs reduce mortality in the population with dementia aged 65 and over admitted to an acute hospital?
Funder: Chief Scientist Office, Scotland

Abstract: People with dementia experience poor outcomes following acute hospital admission, with mortality being particularly high. There is no cure for dementia; anti-dementia drugs can temporarily alleviate symptoms, but their effect on mortality in real-world settings is little known. We propose to conduct a retrospective cohort study to investigate the effect of anti-dementia drugs on mortality in an unselected population of older people with dementia from Tayside and Fife, following an acute admission between 2010 and 2015. The study will use anonymised routine healthcare data, which will be provided in the Health Informatics Centre’s safe haven at the University of Dundee.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: NEUROLOGICAL
Title: Consensus methodology to define key elements of a Complex Intervention to improve the outcomes of people with confusion admitted acutely to the general hospital
Funder: Chief Scientist Office, Scotland

Abstract: People who have confusion when admitted to hospital experience poor outcomes (length of stay, mortality, re-admission). Confusion may be due to dementia, delirium, delirium superimposed on dementia or unspecified cognitive impairment. We plan to develop and test a complex intervention to improve the outcomes of people with confusion who are admitted to the general hospital. In this project we will use consensus methodology informed by a systematic literature review to identify the essential elements of such a complex intervention. Experts on the consensus panel will include carers of people who have had first-hand experience of an acute hospital admission.


Research activity codes: 5.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: NEUROLOGICAL
Title: Spatial Trancriptomic and Metabolomic Profiling of Multiple Sclerosis Lesions
Funder: Chief Scientist Office, Scotland

Abstract: Scotland has the highest rate of multiple sclerosis (MS) in the world. Doctors are now good at treating early MS, but there are no therapies at all for the later stages. In later MS, the nerves in the brain die, and we want to stop this by improving brain repair. The human brain tries to repair damage, but with variable success between different people with MS, and between different MS lesions in one person. This project will study this variability by using cutting-edge molecular biology techniques to look at single molecules in single brain cells and small areas of post mortem MS brain. We hope this will help us find better treatments to improve brain repair.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL
Title: Oligosaccharides as new therapeutic for CNS repair
Funder: Chief Scientist Office, Scotland

Abstract: The damage to the central nervous system (CNS) after injury or disease is largely permanent, mainly due to the limited capacity for repair, and represents a major area of unmet clinical need. We have developed a moderate throughput assay to model spinal cord injury (SCI). It comprises of mixed rat neural cells that over time develop into many myelinated fibres with correctly formed nodes of Ranvier. When cut they exhibit feature of SCI including astrocytosis, demyelination and a neurite free area resembling a lesion(1-3). Using these cultures we have validated the model by showing similar repair potential of drugs used in animal models of SCI. We have identified the level of sulphation around a lesion as a potential therapeutic strategy and now arm to test various drugs developed by Glycomar for the clinic that can modulate sulphation for other diseases in our model to establish their novel use in the clinic for CNS repair.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: NEUROLOGICAL
Title: Circuit-level pathophysiology and amelioration of NMDAR-channelopathies in two new rat models
Funder: Chief Scientist Office, Scotland

Abstract: The N-methyl-D-aspartate receptor (NMDAR) is an important protein in the brain that helps to transmit chemical signals between brain cells. Some people with brain disorders like intellectual disability, autism and epilepsy, have mutations in their genetic code for these receptors. Some of these mutations have been shown to alter the function of NMDARs, and the brain cells they are found in. It is therefore probable that these mutations are at least part of the cause of the disorders with which they are associated. However, it isn’t known exactly how the changes in receptor and cell functioning might lead to a change in brain function. NMDARs help brain cells fire together, so it is likely that changes in NMDAR function would alter this. The aim of this proposal is thus to assess whether NMDAR mutations lead to changes in how groups of brain cells coordinate their activity. This will be done using animal models where two types of mutations have been purposefully introduced into rats’ genetic code. One is a mutation which alters the receptor’s normal properties. One is a mutation which prevents one of the receptor genes being expressed. Regions of brain from rats carrying these mutations will be examined for coordinated brain cell activity by making recordings simultaneously from a large grid of electrodes. If further funding becomes available, electroencephalograms can be made, combined with video monitoring. If abnormalities are found using either of these techniques, there are some chemicals available which can be used to try to reverse the changes. In summary, I aim to use innovative electrophysiological techniques to make the first assessment of brain function at the circuit level in two new rat models of epilepsy and intellectual disability, with the aim of improving understanding and future treatments for these and related disorders.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL
Title: Improving predictions of prognosis in Parkinson’s: moving from intensive small-scale studies to large and reliable routinely-collected datasets
Funder: Chief Scientist Office, Scotland

Abstract: Some people with Parkinson’s disease become disabled and develop dementia in a few years whereas others survive for many years with good quality of life. With this project I will be able to make more accurate predictions of how people fare over time. This will have many benefits: it means that health professionals can give better information about how people might be affected by their disease, it opens up possibilities for doctors to tailor treatments to particular individuals, and it can also be used to design better trials of whether new treatments are effective. I will firstly combine data from the highest-quality studies (six studies, about 1000 participants) that are currently available (those which have tried to identify everybody with newly-diagnosed Parkinson’s in a certain area). I will combine information from these six studies about the characteristics of people with Parkinson’s to identify how people of different ages with Parkinson’s will fare over time in terms of needing help with basic daily activities, developing dementia, going into a nursing home, or survival. I will then work out what characteristics influence whether someone with Parkinson’s will develop these problems, and develop statistical tools to make specific predictions about how individuals will do over time – in a more precise way than has been previously possible. I will then develop new ways to anonymously gather information about characteristics of people at the time of their diagnosis by automatic computer screening of clinical letters. This will allow us to study prognosis in people with Parkinson’s using data which is routinely collected in the health service, which is an efficient and cost-effective way to do research without creating the additional burdens of participation in research studies.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: NEUROLOGICAL
Title: Preventing dementia by targeting risk factors for cerebrovascular disease
Funder: Chief Scientist Office, Scotland

Abstract: About 40% of people with dementia have problems with the small brain blood vessels that contribute in partly or wholly to their dementia. People with higher levels of blood pressure, LDL cholesterol or diabetes ('vascular risk factors') in their middle years have a higher risk of dementia. This may because these risk factors lead to symptomatic or asymptomatic strokes, due to damage the small brain blood vessels, or an effect on brain damage due to Alzheimer's disease. If we could show that lowering vascular risk factors reduced the risk of dementia this would be important for public health. To show this, the best study design would be a 'randomised controlled trial'. The trial would randomly allocate one group of patients to lowering of vascular risk factors, and a second group to a placebo or control treatment. Because dementia takes a long time to develop, both groups would need to be followed for ten to twenty years to see which group had the lowest dementia risk. In this fellowship, I will use a cost-effective method to replicate this best study design. Randomised trials of vascular risk lowering were performed ten to twenty years ago, but they measured the risk of dementia with only five years follow up - not long enough to show any difference in risk. I will extend the length of follow up of these trials for ten or twenty years, and find out which trial participants develop dementia with national health records in UK, Sweden and Canada. The result of this work will be to determine whether lowering vascular risk factors (like blood pressure, cholesterol and diabetes) in the middle years lowers the risk of dementia. This will be important for public health, and has implications on who should be treated and at what age. Damage to the small blood vessels can be detected on brain scans. These findings are called 'cerebral small vessel disease', and might identify those patients who are at highest risk of dementia due to vascular risk factors. In order to test treatments in patients with 'cerebral small vessel disease' it is important to be able to identify them. On promising source of data are reports of brain scans performed in routine clinical practice. I have developed a method to identify these patients using reports of brain imaging in Scotland, and I plan to extend this work during this fellowship to brain scans across the whole country. In this study, I will measure the risk these patients have of dementia, stroke and death in the long term. This method will make it possible to identify patients with cerebral small vessel disease for new large clinical studies at low cost.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;6.1 PHARMACEUTICALS
Health categories: NEUROLOGICAL
Title: ApplTree: Personalised digital reminding to support memory impairment after brain injury
Funder: Chief Scientist Office, Scotland

Abstract: People with brain injury commonly experience difficulties with memory, concentration, attention and judgement, meaning that important everyday actions and tasks are not carried out or not completed, limiting the ability to live independently. Technology-based solutions, including smartphone applications, can help by providing prompts about intended actions at the correct time. However, memory and attention impairments mean people forget to set reminders or fail to set them accurately (e.g. setting the wrong time/date for events). Using co-design methods with prospective users, we developed ApplTree, a smartphone reminding application with design features that can be personalised to individuals. ApplTree prompts reminder setting, supports reminder entry to improve accuracy, and delivers users with prompts at the appropriate times. In this study we will first examine the features of ApplTree that suit participants with different needs based on cognitive ability. Then a pilot randomised controlled trial will be conducted to provide crucial information to inform a future larger scale efficacy trial of ApplTree as an intervention to support memory in people with acquired brain injury.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: NEUROLOGICAL
Title: Protein glycation in Alzheimer's disease: implications for dementia diagnosis, prognosis and therapy
Funder: Dunhill Medical Trust

Abstract: Age-related modifications of proteins, such as glycation, have been implicated in the pathology of Alzheimer’s disease (AD) but have been largely overlooked as potential biomarkers. We have developed a new technology using fluorescent boronic acid-based ligands to detect glycated proteins and have identified a number of novel modified proteins in post-mortem brain that would support a role for the immune system in the pathology of AD. Our proposal aims to 1) extend these post-mortem human studies to include additional forms and stages of dementia (with Brains for Dementia Research, London), 2) assess the potential use of identified markers in blood and saliva samples from dementia patients (with Research Institute for the Care of Older People, Bath) and 3) use glycated macrophage migration inhibitory factor (MMIF), discovered in our pilot analyses, for detailed investigations into the hitherto unexplored molecular links between impaired glucose handling, immunity, inflammation and dementia.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: NEUROLOGICAL
Title: Exploring the feasibility of a client-centred electronic prompting tool for supporting everyday activities in individuals with mild to moderate dementia
Funder: Dunhill Medical Trust

Abstract: We have previously used sequential audio and text-based messages to enable a person with early dementia to complete simple tasks. This project will develop a practical computer-based prompting system, for independent use by a carer, to enable a person with the early dementia to complete simple tasks in their own home. The work will: help carers to identify where they could use prompting, teach them to break everyday tasks down into a sequence of steps, develop computer-based technology that will allow carers to load prompting sequences for their chosen tasks, determine whether people with dementia are be able to learn to use prompting technology to initiate and complete tasks, and what clinical or environmental factors predict successful adoption of the technology. Finally, we will investigate whether external prompts can be used to help initiate use of the prompting technology and, if so, how these prompts should best be delivered.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: NEUROLOGICAL
Title: Optimising diagnosis and prediction of outcome of spinal decompression surgery in older people
Funder: Dunhill Medical Trust

Abstract: Spinal stenosis is the most common indication for spinal surgery in people over 65 years of age. The expanding elderly population will therefore be associated with a rise in spinal decompression surgery rates. The outcome of spinal decompression surgery is highly variable with recently published data suggesting ~56% of patients improve and ~44% show no improvement or worsening of the condition. Although enhancements have been made in other surgical specialties (e.g. 3D printed implants, robotic-assisted surgery), these have largely not been mirrored by improvements in diagnostic techniques upon which the surgical decision-making process is based. The aims of this project are to use in-house developed software for MRI analysis to quantify spinal stenosis and develop the scanning protocol for diffusion tensor imaging (DTI) to improve detection of lumbar nerve damage, to correlate these to functional neurophysiology (integrity of neural pathways) and to improve prediction of surgical outcome


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: NEUROLOGICAL
Title: Development of novel gene delivery systems for brain targeting by intravenous administration
Funder: Dunhill Medical Trust

Abstract: The possibility of using gene therapy for the treatment of brain diseases such as Alzheimer’s and Parkinson’s diseases is currently hampered by the lack of safe and efficacious gene delivery systems able to specifically deliver DNA to the brain following intravenous administration. On the basis that iron can effectively reach the brain by using transferrin receptors overexpressed on the blood-brain barrier, we demonstrated that an intravenously administered transferrin-bearing dendrimer led to gene expression in the brain, while decreasing non-specific expression in the lung. Building on these promising results, the proposed project aims to develop new dendrimer-based delivery systems able to specifically deliver DNA to the brain after intravenous administration. The brain delivery and gene expression of these systems will be evaluated on laboratory models, in vitro and in vivo.


Research activity codes: 5.1 PHARMACEUTICALS;5.2 CELLULAR AND GENE THERAPIES
Health categories: NEUROLOGICAL