NIHRDataInsights/HRCSData huggingface dataset:
Title: Feasibility assessment of the opportunity for the use of transcranial cranial stimulation for the treatment of brain disorders
Funder: Innovate UK

Abstract: Neuro 360 is developing the first brain stimulator device for personalized home therapy and rehabilitation. Brain stimulation therapeutics address the needs of approximately 550 million people worldwide with the potential to relieve a burden of $620 billion on healthcare systems The company aims to use this TSB grant to identify the best clinical application, develop commercial and IP stratgies and conduct a proof of function experiment.


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: STROKE;MENTAL HEALTH;NEUROLOGICAL
Title: BRAIN UK: accessing NHS tissue archives for neuroscience research
Funder: Medical Research Council

Abstract: BRAIN UK is a virtual brain bank providing access to human tissue from more than 60,000 cases held in 13 NHS regional neuroscience centres across the UK. All ethical and NHS R&D permissions have been granted for blanket use of this tissue for researchers in the UK and overseas, so saving researchers considerable time and effort by removing these bureaucratic barriers to the use of human tissue. Many substantial advances in the understanding of neurological diseases have been made over the past decades from direct observations made on post mortem human tissue and further advances are to be anticipated. Animal models of disease have an important role, but also have their limitations. Types of tissue encompassed by BRAIN UK are the brain and associated components including the spinal cord, nerves, muscle, eye and samples of other organs when relevant to neurological disease. BRAIN UK is not limited to diseases that can attract sufficient funding for dedicated brain banks and is therefore complementary to them. For example, BRAIN UK has many hundreds of cases of head injury, stroke and mental health disorders and also examples of many rare conditions such as Progressive multifocal leucoencephalopathy and Neuromyelitis optica. The work in collecting, processing, categorising and archiving the samples has already been performed within the NHS; in providing a mechanism for access to this tissue for research BRAIN UK provides exceptional added value. With this proposal for continued funding for BRAIN UK we aim to: continue providing access to tissue for researchers, further refine the database for greater precision in access to information and put into place a mechanism to permit inclusion of new cases obtained now and into the future.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: STROKE;MENTAL HEALTH;NEUROLOGICAL
Title: Developing a neuroscience-led basis for diagnosis, prognosis, management and therapy for aphasia post-stroke.
Funder: Medical Research Council

Abstract: There are approximately 100,000 first-time stroke incidents per year in the UK. Of non-communicable diseases, stroke is the second leading cause of disability adjusted life years (DALYs) lost. At least 30% will have language deficits (aphasia) in the acute stage (<6 months), while 20% will experience this chronically. Current diagnosis, prognosis and management is based on behavioural models of language processing, derived from neuropsychology, linguistics, and sociology. In contrast, advances in brain imaging methods have vastly improved our understanding of language within the field of cognitive neuroscience but this has largely focused on intact function, with minimal progress in applying this technology for the benefit of people with deficits after stroke. My goal is to: 1) create the largest and most detailed longitudinal neuropsychological and multimodal neuroimaging database of aphasia recovery in the field; and 2) apply machine learning to the behavioural and neuroimaging data. This will allow me to: (a) improve diagnosis by mapping multimodal MRI (structural and functional) to different language deficits, (b) understand prognosis by investigating how recovery after brain damage changes the way our brain operates, and (c) use machine learning approaches to build and test prognostic models (i.e., use brain scans to determine the severity and type of behavioural problems and likelihood of recovery). Model predictions are able to provide subject-specific estimates; therefore, if successful, it would open up a clinical pathway towards precision medicine. I will collaborate with three world experts to improve my brain-behaviour mapping, machine learning and acute clinical skills. The Fellowship will help: 1) refine our behavioural models and their neural bases, 2) propose neural mechanisms of recovery for different behaviours and how they might interact with neural plasticity, and 3) generate the largest cohort of recovery data in the field.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: STROKE;MENTAL HEALTH;NEUROLOGICAL
Title: Learning and recovery of skilled finger movements.
Funder: Wellcome Trust

Abstract: Strokes often paralyze one side of the body, leaving the victim severely impaired. In many cases, general motor function recovers spontaneously to a certain degree. Nonetheless, the fine control of finger movements involved in skills such as typing, writing, or buttoning a shirt often remain a challenge in patients daily lives. This research aims to understand how skilled finger movements are leaned and represented in the human brain and how these representations change during stroke recovery. We will use non-invasive brain imaging techniques to measure brain activity while volunteers make finger movements. New analysis techniques will allow us to determine the brain regions that encode and learn these movements, and we will be able to track the changes in these areas during normal ageing and in recovery after stroke. Furthermore, we will test whether brain stimulation during the training of skilled finger movements can improve the speed of learning and potentially influence stroke re covery. These results may provide the empirical basis for the development of new treatments to improve recovery of hand function after stroke, a step that would have a major impact on the quality of live for many stroke victims


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: STROKE;MENTAL HEALTH;NEUROLOGICAL
Title: Understanding the inattentive and impulsive brain.
Funder: Wellcome Trust

Abstract: Inattention and impulsivity are common problems affecting patients across a range of brain disorders, from stroke through to Parkinson's disease (PD) and adults with attention deficit hyperactivity disorder (ADHD). To develop treatments for these behaviours across diseases we need to understand normal mechanisms underlying attention, working (short-term) memory and rapid decision-making under risk, and examine whether they can be altered by drugs. We aim to characterize such mechanisms in h ealthy people and patients with stroke, PD and ADHD by: 1. Establishing whether one type of inattention might be ultra-rapid forgetting of information placed in working memory 2. Determining if one aspect of impulsivity might be hypersensitivity to rewards while conversely apathy might be associated with insensitivity to rewards 3. Defining whether some types of inattention interact with rapid decision-making under risky conditions to contribute to impulsivity or apathy 4. Altering attention and decision-making using drugs that act at the receptor for the neurotransmitter dopamine in healthy people and patients with stroke and PD 5. Testing a new model that we have developed to see if it provides a better way to understand how information is held and protected in working memory.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: STROKE;MENTAL HEALTH;NEUROLOGICAL
Title: Institute of Metabolic Science.
Funder: Wellcome Trust

Abstract: With support from the Wellcome Trust and MRC, we have established an internationally leading Institute for Metabolic Science (IMS) in Cambridge. The world-class investigators we have assembled, combined with the excellent facilities we have established, have brought us within sight of our goal to translate advances in the understanding of basic mechanisms involved in obesity, diabetes and related metabolic diseases into benefits for health. In this proposal, we seek support for: 1. The co nstruction of a dedicated Metabolic Clinical Research Facility (MCRF) and Eating Behaviour Unit (EBU) to support the expansion of translational research programmes and capitalise on local strengths in the basic and clinical neuroscience of appetitive behaviour. 2. A collaborative programme with the Wellcome Trust Sanger Institute in the generation and phenotyping of murine models of metabolic disease. 3. Improved cell imaging and proteomic facilities in collaboration with the Cambridge Ins titute for Medical Research (CIMR). 4. Equipment to update our core Genomics/Transcriptomics laboratory We have been encouraged to submit a complementary bid to the MRC and further support is being provided by the University of Cambridge. If awarded, these additional resources will significantly enhance our abilities to conduct the highest level basic and translational science in metabolism.


Research activity codes: 5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION);3.5 RESOURCES AND INFRASTRUCTURE (PREVENTION);2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: STROKE;METABOLIC AND ENDOCRINE
Title: The molecular aetiology of central obesity: moving from variant to function using large-scale data-driven approaches.
Funder: Wellcome Trust

Abstract: Central obesity is a leading contributing cause of illness and death across the world. Currently available strategies for prevention and treatment of this condition are manifestly inadequate. The research proposed here aims to identify fundamental processes involved in the development of central obesity. I plan to harness the power of human genetics, fused with deep molecular characterisation of the adipocytes to generate novel insights into the biology of central obesity. This ‘multi-omics’ approach will provide the basis for more effective preventative and therapeutic approaches that reduce the burden of central obesity and associated disease.

Lay abstract: Obesity is a result of an inherited tendency for weight gain acting together with environmental factors (excess food intake in combination with lack of exercise). Genetic factors can affect appetite, but also how and where the body stores fat. Fat in the abdomen is associated with far more serious effects than fat deposited elsewhere. My work has shown that there are different biology influencing overall obesity than fat concentrating in the abdomen. It is important to understand differences in the ways in which individuals vary in the amount of fat they accumulate, and where their bodies store this fat. I will test possible explanations for how the fat is distributed over the body and why some people store fat preferentially in the abdomen. By developing a better understanding of causal mechanisms regulating central fat storage we may learn what biological pathways we should target for drug intervention.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: STROKE;METABOLIC AND ENDOCRINE;CARDIOVASCULAR;CANCER AND NEOPLASMS
Title: Economic analysis of health impacts of carbon pricing on transport
Funder: Wellcome Trust

Abstract: The proposed economic analysis aims to estimate the extent to which a carbon price on energy could transform road transport, increasing active travel including the use of public transport, bringing benefits to both the climate and health. This extends an analysis underway (Phase 1) assessing the impacts of carbon pricing on the land-use sector on agricultural production, food prices, diets, and health outcomes. The work will comprise modelling the consequences of carbon pricing at two levels: (i) keeping global temperature rise below 2oC above pre-industrial levels; (ii) achieving a rise of less than 1.5oC. The analysis will also consider potential differential effects of carbon pricing across socio-economic groups and between high, medium and low-income countries, as a basis for identifying policy interventions to equitably mitigate harmful outcomes.This analysis will contribute to the goal of The Lancet-Chatham House Commission which is to identify actions that can impact positively across the shared drivers of threats to human and planetary health. Importantly it will provide novel evidence for the ways in which co-benefits and co-costs of interventions might form a significant part of the political and economic cases for intervening at national and international levels and optimising policy design.


Research activity codes: 1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: STROKE;METABOLIC AND ENDOCRINE;GENERIC HEALTH RELEVANCE
Title: Predictive (in silico) Medicine
Funder: Department of Health and Social Care

Abstract: Short-term: 1. Non-invasive quantification of changes over time of the neuromotor condition using gait analysis (GA), dynamometry (DYN), electromyography (EMG), and wearable sensors (WS) in combination with MRI imaging, in Parkinson’s disease, motor neuron disease, multiple sclerosis, stroke, and ataxia patients. Quantitative biomarkers depend on the disease and the scope of the clinical research, and include; joint kinematics and kinetics during different movements; gait spatio-temporal parameters and their variability; balance tests (i.e. stabilometry); muscle activation (surface EMG); force generation in isometric, isotonic, isokinetic, and fatiguing conditions; joint torque, articular forces, muscle forces, and activation patterns during specified movements; wearable sensors for instrumented clinical tests during clinic visits; wearable sensors for life style and physical activity monitoring at home; quantitative efficacy evaluation of assistive devices. 2. Images and signals processing and modelling, to extract derivative quantifications, such as muscle Physiological Cross-Sectional Area, that cannot be obtained directly. Medium-term: 1. Collaborating with the Imaging theme, development of protocols for fMRI and MR spectroscopy, to be used in combination with EMG and dynamometry, to determine the contribution of force generation loss due to sarcopenia, loss of innervation, and pathological neuromotor control. 2. Use of subject-specific whole body neuromusculoskeletal dynamics stochastic models to quantify whole body neuromuscular coordination, to investigate compensation strategies in MND, stroke, and MS patients. Long-term: 1. Translate into experimental medicine studies the use of subject-specific models for patient stratification for multiple interventions available (personalised medicine) and the combination in clinical trials of interventions for rare diseases of actual and predictive patients (in silico-augmented clinical trials).


Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: STROKE;MUSCULOSKELETAL;NEUROLOGICAL
Title: Measuring functional outcome following treatment for leg spasticity.
Funder: Department of Health (England)

Abstract: The importance of measuring the impact of treatments from the perspective of patients and carers has been emphasised in the Department of Health Guidance on Patient Reported Outcome Measures. There is currently no measure of function in the leg for patients with spasticity, ranging from passive caring for the limb in severely disabled patients, to using the limb for mobility. This project builds on previous work, to develop a measure of leg function. The content will be drawn from systematic review findings and analysis of our database of goals for treatment. Measurement properties will be examined in real-life patient care.


Research activity codes: 6.7 PHYSICAL
Health categories: STROKE;NEUROLOGICAL
Title: Facilitating the inclusion of people with acquired communication disorders in decision-making: development and evaluation of a tool to support mental capacity assessment and provision of accessible information.
Funder: Department of Health (England)

Abstract: Healthcare professionals often need to assess hospital patients' mental capacity to make informed decisions about their medical treatment and care. This assessment is challenging, especially when it involves patients with communication difficulties, who need additional support to understand information about decisions. This research will develop and test a tool to help professionals assess capacity more accurately and provide information tailored to patients' individual communication needs. The tool will be developed using best evidence and by consulting hospital staff, patients and carers. The tool will be tested in hospitals with different patients to check that it is valid, reliable and acceptable.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: STROKE;NEUROLOGICAL
Title: Development of clinically viable, calibrated FMRI
Funder: Engineering and Physical Sciences Research Council

Abstract: Magnetic resonance imaging (MRI) can be used to view the brain working; this is called functional MRI (or FMRI). By imaging the brain during its normal baseline state and then comparing that with images obtained during an active state (such as during a task like tapping your fingers or viewing flashing lights) we can see regional changes in blood flow and oxygen use which correspond to the areas which have increased metabolism during any given activity. Currently the images produced by this method tend to give locations which are statistically likely to be used, but they provide no information about the underlying metabolic activity which causes these changes in blood flow. Recently, models have been developed which try to extrapolate from what we can measure to estimate an actual metabolic rate of oxygen consumption. To accurately measure the severity and extent of acquired brain injuries such as stroke we mean to develop improved models and measurements of cerebral metabolism based on MRI data obtained from healthy human subjects. We wish to create a MRI-based method of measuring metabolic activity in the brain which is simple, fast and easy to use so that it can be employed in hospitals and emergency rooms throughout the country.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: STROKE;NEUROLOGICAL
Title: Cerebral amyloid angiopathy and intracerebral haemorrhage: community-based cohort study, biobank, and record linkage
Funder: Medical Research Council

Abstract: Background: Spontaneous intracerebral haemorrhage (ICH) affects ~1.5 million adults in the world each year. Unlike ischaemic stroke, the incidence of ICH is not declining and does not have specific treatments. Most ICH occurs in people aged ?70 years, and ICH incidence is likely to rise in ageing societies. Deposition of amyloid in cerebral vessel walls, known as cerebral amyloid angiopathy (CAA), is more common with age and in people with dementia. CAA is often inferred to be the cause of ICH in the brain‘s lobes, but the strength of the association between CAA and lobar ICH, the causal pathway(s), accuracy of diagnostic criteria for ICH due to CAA, and best preventive strategies are unclear. Aim: To better understand how CAA causes ICH, develop diagnostic criteria to identify patients who have CAA underlying ICH, and determine factors influencing prognosis. This stratified medicine approach will inform the design of secondary prevention trials. The objective is to promote healthy ageing (an MRC research priority theme). Design: Community-based ICH biobank, nested within a population-based study. Methods: (1) Using multiple, overlapping sources of case ascertainment I will find incident cases of ICH in a community-based cohort study, and create a biobank of clinical and radiographic data and brain tissue (44% consented to donation so far). I will investigate the association between CAA and lobar ICH in case-control comparisons with the community-based MRC Cognitive Function and Ageing Study (CFAS). I will determine the accuracy of different diagnostic criteria for CAA associated with lobar ICH in my community-based ICH study, using blinded comparisons of clinical criteria, imaging, and cerebrospinal fluid biomarkers to an autopsy reference standard. (2) I will establish two novel record linkages, from a Scottish population-based ICH dataset to national prescribing data and digital brain images, to perform multivariable analyses of clinical, imaging, and therapeutic influences on prognosis after ICH. Estimates of treatment effect and potential recruitment rates will help design trials to improve ICH outcome. Scientific and medical opportunities: Unique ability to link population-wide clinical, brain imaging and prescribing data. Efficient and cost-effective methods using existing NHS data and international collaborations. Expertise in my institution in stroke medicine, brain banking, brain imaging, epidemiological methods, trials methodology research, and nurturing and training clinical academics. Promising recruitment and tissue donation rates to my community-based ICH biobank. Data and tissue collected will enable me to take a stratified approach to deep ICH.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: STROKE;NEUROLOGICAL
Title: Genomic analysis of spontaneous intracerebral haemorrhage; providing new insights into vascular and neurodegenerative mechanisms of dementia
Funder: Dunhill Medical Trust

Abstract: Spontaneous intracerebral haemorrhage (ICH) is the most devastating form of stroke with high mortality in the elderly population. Our understanding of the aetiology is poor and no treatments exist. Survivors have a high rate of dementia (>30%), likely due to widespread deposition of beta-amyloid in vessel walls (cerebral amyloid angiopathy; CAA). We hypothesise that identification of novel common and rare genetic variants associated with ICH will reveal insights into the risk and disease pathways that cause vessel rupture, CAA and dementia. We collected clinical, imaging and DNA on a UK-based series of 1063 ICH patients including 104 ICH multiplex families. We propose to initially focus on known dementia/vascular genetic risk-factors and then conduct a pilot genome-wide-association-study (GWAS) to identify novel common variants. This will be combined with exome sequencing of familial-ICH to identify overlapping, highly penetrant rare variants, likely revealing genetic pathways that lead to amyloid deposition and vessel rupture


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: STROKE;NEUROLOGICAL