NIHRDataInsights/HRCSData huggingface dataset:
Title: Neural dynamics of response inhibition and gambling across the lifespan
Funder: Biotechnology and Biological Sciences Research Council

Abstract: The overarching aim of this research project is to advance understanding of how the human brain controls inhibitory decision-making, with a view toward developing a deeper understanding of ageing, and furthering new interventions in the treatment of pathological gambling and related addictions. Part A will employ concurrent transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) to determine how the prefrontal cortex inhibits actions via connections with key subcortical structures, including the basal ganglia. We will also test how fronto-subcortical interactions are influenced by normal ageing. Part B will explore the neural mechanisms underpinning our recent discovery that inhibitory motor demands can cause a powerful and long-lasting reduction in risk-taking during gambling. In particular, we will employ fMRI, concurrent TMS-fMRI, and magnetic resonance spectroscopy (MRS) - in combination with behavioural tasks that combine motor inhibition and gambling - to uncover the neurophysiological and neurochemical systems that link decision-making at different levels of cognitive control. As in Part A, we will also study the extent to which the relationship between motor inhibition and gambling behaviour differs between younger and older adults. Overall, this project seeks to reveal new insights into neural mechanisms of response inhibition, with implications for understanding the neurobiology of ageing and the development of new therapeutic pathways for addiction.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Environmental enrichment and cognitive function across the lifespan
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Environmental enrichment induces neuronal elaboration and synaptic strengthening, processes thought to underlie the positive aspects of enrichment on age-related cognitive functioning. Whilst brain derived neurotrophic factor (BDNF) has been repeatedly implicated in the changes associated with enrichment, the molecular mechanisms underpinning its effects are not know. Using a mutant mouse that lacks the kinase activity of mitogen- and stress-activated kinase 1 (MSK1), an enzyme downstream of BDNF/TrkB receptors, and which regulates gene transcription via phosphorylation of CREB and histone H3, we have recently shown that MSK1 is necessary to translate sensory experience into enduring changes in neuronal structure and function: MSK1 kinase-dead mice do not display the increase in hippocampal synaptic transmission observed in wild-type mice and display a blunted increase in spine density. Accordingly, MSK1 plays a pivotal role in translating the activation of BDNF TrkB receptors into the gene expression underlying enduring experience-dependent neuronal plasticity. We now wish to extend these observations to establish the extent to which these MSK1-dependent neuronal adaptations influence learning and memory throughout the life-span by testing wild-type and mutant mice, housed under standard and enriched conditions, in tasks of spatial memory (Barnes and Morris mazes). In addition we will establish, using next generation deep sequencing techniques, the MSK1-dependent genes that are regulated by enrichment and which underpin the enhancement of cognitive function. These studies will provide valuable tangible insight into the molecular mechanisms regulating the influence of enrichment on synaptic structure and function, and the ensuing enhancement of cognitive function. Such studies are a fundamental requirement if we are to develop drugs to slow, halt or even potentially reverse cognitive decline in the elderly.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Characterising encoding and retrieval contributions to age-related memory impairment
Funder: Biotechnology and Biological Sciences Research Council

Abstract: The proposed research aims to use novel behavioural manipulations and advanced structural and multivariate functional MRI analysis to explore how variability in the structure and function of the brain influences the degree to which older adults can benefit from encoding and retrieval strategies designed to enhance recollection. There are three main components to the project, each with clearly defined objectives and measurable outcomes. The first component aims to identify the key cognitive and neural mechanisms governing effective encoding strategies that older adults can implement to enable the construction of rich and vivid memory representations. The second component will explore methods to promote the adoption by older adults of controlled retrieval processes that can maximize successful recollection, identify sources of deficits in these abilities, and reveal neural differences that determine the level of retrieval success observed. The third component will use structural MRI, diffusion tensor imaging, and resting state fMRI to assess the degree to which individual differences in structural and functional integrity of key brain regions and networks can predict the effectiveness with which individuals are able to benefit from the encoding and retrieval strategies targeted. The findings of the proposed research will advance understanding of how individual differences in brain structure and function associated with controlled recollection processes can help to predict the efficacy of memory strategies for older adults. These advances will contribute to the development of rehabilitative interventions designed to enhance memory abilities in the elderly, with the potential for providing tangible improvements in quality of life and wellbeing.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Identifying mechanisms regulating central nervous system homeostasis
Funder: Biotechnology and Biological Sciences Research Council

Abstract: This project focuses on normal molecular and cellular mechanisms by which neurons maintain homeostasis studying them through the opposing paradigms of neuronal function and dysfunction. Developing and maintaining healthy neurons is of crucial importance to humans and animals and we seek to bring novel approaches to the study of non-pathological cognitive deficits resulting from various stressors. This area is central to the BBSRC strategic priority of bioscience underpinning health. However, since CNS function and wellbeing are inextricably linked to the behaviour and welfare of animals, this area is also central to the BBSRC overarching policies on food security and the health and welfare of managed animals. Healthy CNS homeostasis relies on multiple factors, including regulation of neuronal survival, neuronal protection (eg. by neuropeptides and neurosteroids), cross-talk between neuronal networks and inter-cellular communication (e.g. between glia and neurons via chemokines). We have shown that exposure to stress at various times of life, from the prenatal period through to adulthood, can have detrimental effects on the brain, in particular in neuroendocrine systems that maintain homeostasis and brain circuits regulating social behaviour and cognition. In this theme we will investigate the central mechanisms involved and whether early life stress has detrimental effects on cognitive performance and behavioural outcomes. We will investigate how communication between neurons and glia contribute to neuronal health. Within neurons, various molecules have been identified as potential mediators of neuronal protection and we will determine how neuroprotection from these is manifest at molecular levels.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Randomised Feasibility Study of a Physiotherapy Programme for Patients with Functional Motor Symptoms
Funder: Department of Health (England)

Abstract: Functional (psychogenic) motor symptoms (FMS) are common, cause significant disability and have a large economic cost. Treatment options are limited and prognosis is poor. Most neurologists believe physiotherapy to be an effective treatment, yet when surveyed physiotherapists report low knowledge levels regarding treatment of this patient group, despite them being a significant proportion of their workload. The aim of this research is to develop and assess the feasibility of a physiotherapy intervention for Fms This work will allow us to produce the necessary evidence and knowledge to design and implement a randomised clinical trial of physiotherapy for patients with Fms


Research activity codes: 5.7 PHYSICAL;6.7 PHYSICAL
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Improving access to UK dementia services for the South Asian minority ethnic population: development and pilot of an intervention.
Funder: Department of Health (England)

Abstract: Early diagnosis of dementia is a National Dementia Strategy priority. It can improve outcomes for people with dementia and carers by enabling treatment, support and the opportunity to plan for the future. People from minority ethnic groups access dementia services later than the White UK population and previous research has shown this is likely to be due to cultural differences. I propose carrying out further qualitative research to explore what kind of intervention South Asian community members would find helpful in encouraging earlier help-seeking for dementia. I would then develop and test the intervention in a pilot randomised controlled trial


Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Cognitive outcomes in people with behavioural and brain disorders within UK Biobank
Funder: Chief Scientist Office (Scotland)

Abstract: Cognitive impairment is a core feature of many different behavioural and brain disorders, contributing to the significant burden of disease attributed to these conditions. In addition to rising dementia prevalence in the ageing population, cognitive dysfunction is a major cause of disability for a large number of working age adults living with chronic conditions such as major depression, bipolar disorder and multiple sclerosis. Among those affected, there is considerable individual-level variation in severity and persistence of cognitive impairment; the reasons for this are not fully understood. Complex models are needed that take account of a range of genetic, demographic, environmental, lifestyle and disease-related risk factors, which are likely to be exerting relatively small effects and operating in an interactive manner. Such relationships cannot be reliably detected in small samples, typical of clinical studies. The UK Biobank cohort of more than 500,000 British residents provides an unprecedented opportunity to investigate multivariate predictors of cognitive performance in health and disease. The proposed project will comprise a series of cross-sectional studies of baseline cognitive data from the UK Biobank resource. Multivariate regression and structural equation modelling will be used to estimate the magnitude of effect of independent variables (e.g. disease status or genotype) on cognitive outcomes, and to explore the mediating and moderating influence of covariates. The potential healthcare applications of this work include enhancing our understanding of risk factors for cognitive dysfunction, some of which may be modifiable, as well as furthering the drive towards stratified and targeted treatment development.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Synthetic Cognitive Systems
Funder: Engineering and Physical Sciences Research Council

Abstract: The brain can be viewed as an immensely sophisticated computational system, the understanding of which presents us with a very challenging problem. Whilst much progress has been made in understanding how the brain functions, a fundamental question that remains to be resolved is how the brain encodes and processes information as spatiotemporal patterns of neural activity. This proposal will establish a core team of interdisciplinary researchers and the facilities required in order to address this important question. The key aim of the group's research program is to produce a synthetic system, incorporating living neurons, which is capable of cognition at a highly simplified, elemental, level. The system will incorporate a continuous, closed-loop, flow of information between the network and its environment analogous to that in a real organism and will ensure the system has some relevance to neural processing. It will result in a tool that will overcome current limitations; allowing a close correspondence between the experimental system and the mathematical models. This experimental tool will be made available to the neuroscience community at large and will enable researchers to develop the beginnings of a theory of neural processing. The initial system will undergo continual development; incorporating technical innovations and improvements to construct neural systems of ever increasing complexity and relevance.This proposal will provide an investment in the core activities of a new interdisciplinary facility that will provide an experimental platform for neuroscientists both from the UK and abroad. The expertise of the facility will be both in the development and production of synthetic cognitive systems as well as their application to fundamental, curiosity-driven, neuroscience research. The majority of output from this facility will come from funding attracted by the collaborative projects that arise both during the development and the application of this tool.The relatively simple initial system will undergo continual development; incorporating technical innovations and improvements. For example, larger networks will be produced, more sophisticated methods of monitoring and controlling biochemical pathways will be incorporated and networks of interacting networks will be produced to construct neural systems of ever increasing complexity and relevance.Ultimately these systems will allow us to develop models of information processing in the more complex networks found in living brains. These models may lead to treatments to correct the instabilities that underlie many brain diseases and disorders and may lead to advances in artificial intelligence.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: BABEL
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Recent advances in behavioural and computational neuroscience, in cognitive robotics, and in the hardware implementation of large-scale neural networks, provide the opportunity for an accelerated understanding of brain functions and for the design of interactive robotic systems based on brain-inspired control systems This is especially the case in the domain of action and language learning, given the significant scientific and technological developments in this field. This project aims at advancing the understanding of neural and behavioural mechanisms in word learning, the validation of these principles in neuroanatomically grounded models, and real-time implementations of brain language models within the SpiNNaker neuromorphic architecture that will support comparisons with neuroimaging experiments. The scientific hypotheses and cortical language model will also be validated by implementing a model of embodied active language learning on the humanoid robot iCub. Specifically, in the project we will develop, based on neuroscientific principles, a theory of language learning at the neural circuit level and build a neurocomputational model of the language cortex that implements the learning of words used to speak about objects and actions in large-scale neuronal circuits. This theoretical work will be supported by novel, hypothesis-driven brain imaging investigations using MEG, EEG and fMRI to identify the neural correlates and mechanisms of the learning of words for objects and actions. Imaging results will inform the improvement of the large-scale neuroanatomical models. These models will be implemented on the SpiNNaker software and hardware infrastructure, to implement a scaled-up real-time model of the language cortex using more realistic spiking activity. Finally, the project will translationally apply these neuro-anatomical models and SpiNNaker system as controllers for language and action learning simulations with the humanoid robot iCub, within the embodied and active learning context where the semantics of the language is directly driven by the context of object manipulation tasks. This is a highly interdisciplinary project that integrates essential expertise and methodologies from neuromorphic engineering, computational and experimental neuroscience, and cognitive robotics. The project is based around the unique and strategic partnership of applicants with an international track record in these areas of expertise and with previous collaborative experience. Furthermore, the project will benefit from an International Advisory Board, with both academic and industrial advisors, to foster the international dimension and impact of the project.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Robust graph analysis of brain connectivity
Funder: Engineering and Physical Sciences Research Council

Abstract: A broad range of neurological diseases and disorders have been linked with pathological alterations in the connectivity of the brain. However, robust methods for identifying and characterising abnormalities in connectivity, their evolution over time and response to treatments, are lacking; and addressing this omission represents a pressing clinical need. In this proposal we aim to meet this need using novel methods based on medical imaging and graph theory, a well-established mathematical framework with which to describe and characterise interconnected systems To establish a clear baseline, we will characterise the typical "normal" connectivity network, and model statistically its variability in a healthy population. We will also investigate approaches to classifying graphs into groups, and identify common factors underlying structural and functional connectivity, to be used as new biomarkers. We will use magnetic resonance imaging (MRI) and electroencephalography (EEG) to obtain connectivity information in the living brain; and childhood epilepsy and autism spectrum disorders will be investigated as neurological disorders which can display altered brain connectivity. Our developments will also be applicable to other data which can be represented graphically. This work will provide major novel tools for graph analysis of brain connectivity, thereby driving connectivity network methods towards reliable and routine clinical application. Through our close links with clinical colleagues we will ensure that our developments are well positioned for wide-ranging applicability, elucidating connectivity failures in disease and their recovery with treatment.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: SAMS - Software Architecture for Mental health Self management
Funder: Engineering and Physical Sciences Research Council

Abstract: SAMS is a proposed 3-year project to that will investigate the potential for novel data and text mining techniques for detecting subtle signs of Cognitive Dysfunction that may indicate the early stages of Alzheimer's disease. Promoting self-awareness of c


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: SLEEP DISTURBANCES AND MILD COGNITIVE IMPAIRMENT IN THE ENGLISH LONGITUDINAL STUDY OF AGEING
Funder: Economic and Social Research Council

Abstract: Recent scientific developments clearly indicate that sleep has an important effect on brain behaviour and function. In particular, it has very important effects on memory, co-ordination and executive functions. Furthermore, it is now known that there is a relationship between the severity of sleep disturbance and these functions of the brain in a number of different clinical conditions and it has been suggested that sleep disturbance may be an important early marker of progressive brain disorders such as Alzheimer's disease. As sleep disorders determine the severity and type of cognitive (brain) impairment in various brain-related disorders their diagnosis and treatment may slow disease progression. It is possible that sleep disorders may, therefore, be present and treatable in individuals with mild brain impairment. This is important as treatment may delay further progression from mild brain impairment to dementia, for example. It is therefore essential to develop tools to easily and accurately detect these individuals who are at greater risk. Our proposed study will assess the evidence for links between two types of mild brain impairments using data which has already been collected on a large group (N~10,000) of men and women over the age of 50 years from the English Longitudinal Study of Ageing (ELSA) who self-report any sleep disturbances. The specific aims of our project are to explore the links between the quantity (i.e. duration) and quality of sleep in relation to the different types of mild brain impairment in individuals from the ELSA study. We will also explore which different social, behavioural and biochemical factors have an effect on these links. This will establish the baseline for future analyses of the causes of further decline in cognitive (brain) function that may occur in subsequent years and as individuals get older.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: MENTAL HEALTH;NEUROLOGICAL