NIHRDataInsights/HRCSData huggingface dataset:
Title: Co-ordination Of UK Network Of Brain Banks
Funder: Medical Research Council

Abstract: This application seeks to secure support for the co-ordinating centre for the MRC Network of Brain Banks in the UK. This MRC initiative is designed to facilitate research into human neurological and psychiatric diseases by ensuring uniformly high standards of operation and the collection of samples fit for the purposes of 21st century science. The Network will also address the current shortage of control brain tissue samples, initially by facilitating exchange and use of current samples, and later by seeking to develop additional means of collection. The Network will develop a database and web site; the database will contain data from existing UK brain banks in order to allow researchers to identify whether samples required for their research are available and to quickly locate the most appropriate source. This data are very large (thousands of tissue samples) and complex in terms of information on clinical and pathological features, the anatomical regions of the brain sampled and the formats for storage. The construction of a searchable database that will include this complex data will require substantial input from a full time database manager, with additional programming support. The website will also contain information for potential donors and will facilitate donation by directing potential donors to the most appropriate banks for further information and registration. The Network Director runs the co-ordinating centre and will be responsible for the work of the support staff - a database manager and a part-time personal assistant, essential for supporting the Director and acing as Network co-ordinator. The activities of the Network will be overseen by a Steering Group, and work of the Network will be informed by a scientific users group to ensure that the material collected and stored is suitable for the diverse scientific needs of researchers. A Management Group comprising the principal investigators from each bank will function as an operational body to agree and develop standards of operation on tissue sampling, storage, analysis and labelling, and ethics and governance mechanisms. The Network will support research in the UK funded not only by the MRC, but by other funding bodies and charities, in order to advance understanding of common neurodegenerative disorders and neuropsychiatric diseases that place an enormous burden on patients, their carers and the National Health Service. The co-ordinating centre is a key component of the Network and will act as a focal contact point for scientists, media and the public alike.


Research activity codes: 1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING)
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Neural Mechanisms Underlying Memory Control
Funder: Medical Research Council

Abstract: This project seeks to understand the cognitive and neural mechanisms that enable people to control unwanted memories. Recent work by Anderson has found that when people confront a reminder to an experience that they would prefer not to think about, they engage executive control mechanisms often recruited to override prepotent motor responses to suppress retrieval. This work has led to a theoretical perspective in which memory control is accomplished by an attention system that interacts with memory and that is governed by principles and components isomorphic to those involved in perceptual orienting of attention. A key process is attentional inhibition, which is triggered by conflict between the goal-directed focus of attention and the focus demanded by reflexive orienting to abrupt onsets in mnemonic space. Attentional inhibition is conceptualized as a flexible component of task set that can be recruited when conflict is expected or present, to override reflexive memorial orienting. The current project aims to evaluate key hypotheses, including (a) the hippocampal modulation hypothesis, according to which memory control is affected by down-regulating mnemonic activity in the hippocampus, (b) the mnemonic attention hypothesis, in which memory intrusions constitute cases of mnemonic reflexive orienting that build on the same neural mechanisms engaged to reflexively orient attention to events in the perceptual world, (c) the response override hypothesis, in which mnemonic control is accomplished by brain mechanisms involved in overriding prepotent motor actions, and (d) the motivated forgetting hypothesis, in which memory control mechanisms lead to selective forgetting of unwanted events. The approach to this question will combine traditional cognitive methods, developed by Anderson, a new approach to measuring intrusions, as well as fMRI and EEG. If correct, this view stands to forge a highly specific connection between research on attention and long-term memory that will move beyond the simple observation that attention can be directed to memory to the nature of mnemonic attention system itself. This work will specify a rich framework in which to understand how people control unwanted memories of the past. Such insights are not merely of theoretical significance, but of potentially profound practical importance in understanding and ameliorating the conditions of those suffering from intrusive memories.


Research activity codes: 1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: The interplay between short-term memory and long-term memory.
Funder: Medical Research Council

Abstract: The primary function of memory is not simply to remember the past, but to construct representations that can guide our actions in the future. Our perceptual and cognitive processes are always influenced by our prior experience. This programme investigates the way experience (information in long-term memory (LTM)) influences short-term memory (STM), and the way in which new experiences are combined to construct effective representations of prior knowledge in LTM. Although long-and short-term memory are neurally and cognitively separate short- and long-term memory systems, the two necessarily operate in concert. How does this interaction occur? From a theoretical standpoint most of the work takes place within a Bayesian framework. Long term knowledge can be viewed as a set of priors which must be continually updated in the light of new information. In turn, these priors influence the interpretation of new information arriving in STM. We investigate this by means of a combination of behavioural experiments, neuroimaging, and computational modelling. We conduct behavioural studies of sequence learning and of the way in which ’chunks’ of information in long term memory help short-term recall. For example, this addresses the classic issue of how chunking influences the capacity of STM. Our computational modelling work focusses on the challenging task of modelling the learning of representations of sequences. The target data-set for most of this work is an extensive body of literature on the Hebb repetition task. We also model the development of chunks in LTM and how this interacts with STM, and have developed a novel Bayesian model of recency effects in visual STM. In order to understand the neural mechanisms underlying the interaction between STM and LTM conduct a complementary series of neuroimaging studies. These examine the neural representation of serial order in short-term memory and how those representations develop and are transferred into long-term memory. The programme also encompasses research on training working memory conducted in collaboration with S. Gathercole, and a further strand on visual word recognition in collaboration with S. Kinoshita of Macquarie University.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: EP5: Understanding and enhancing executive networks in childhood
Funder: Medical Research Council

Abstract: Our research programme was established in 2012, supporting the Unit’s new strategic priority of understanding cognition and the brain in typical and atypical development, and reflecting the MRC’s emphasis on developmental and lifespan approaches to health and disorder. Our focus has been on understanding cognitive control. Performing poorly on tasks that tax these control processes is a very substantial risk factor for both educational underachievement and clinical diagnosis in childhood. Across the programme our goal is to understand the dynamic neural systems that afford cognitive control in different contexts, the mechanisms that regulate these systems, how they develop, how they vary according to educational and clinical outcome, and the prospects for their enhancement. A hallmark of our work has been the use of new analysis methods for EEG, MEG, and MRI data. These techniques have been applied to children recruited from mainstream education, clinicians, specialist panels, and in many cases via a research clinic founded with Gathercole, J. Holmes and Manly (MRC CBU).


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Adaptive processing of spoken language
Funder: Medical Research Council

Abstract: Human listeners easily comprehend spoken language despite wide variation in the form and content of speech. This suggests that neural systems for speech perception and comprehension possess impressive capabilities for adjusting to variable and ambiguous speech. These processes are called on in everyday situations in which we understand speech that is presented in background noise or acoustically degraded, spoken in a novel accent, that includes unfamiliar words or phrases or in resolving transient ambiguities created by words with multiple meanings (e.g. bark). The ability of the comprehension system to adjust to incoming speech plays a critical role in supporting effective spoken language comprehension for post-lingually deafened individuals that receive a cochlear implant, in acquiring and maintaining the form and meaning of spoken words, as well as in supporting educational achievements that depend on spoken language (such as literacy and second-language acquisition). In our research we conduct behavioural studies in which participants learn to understand artificially-manipulated speech (e.g. vocoded speech, or syllables containing ambiguous phonemes), novel words or novel word sequences and meanings. We explore the role of external feedback (e.g. presentation of non-distorted speech, or spoken/written context) in supporting initial learning. We also compare performance on learned and novel items in practiced or novel tasks at various delays after initial exposure in order to assess the role of offline, possibly sleep-associated consolidation processes in supporting language learning and generalisation. By combining these methods with multimodal functional brain imaging (primarily fMRI and E/MEG) and brain stimulation we can study the neural systems that support these various forms of learning and adaptation. In this way we can uncover the functional and neural mechanisms that are critical for successful comprehension of spoken language in healthy volunteers, and that contribute to successful learning and rehabilitation in educational and clinical settings.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Cooperating brain systems in attention and control
Funder: Medical Research Council

Abstract: One of the most exciting scientific developments of the last two decades is our increased understanding of how higher mental functions such as perception, language and memory arise from the neural activity of the brain. One central topic is how humans pay attention to important information in the world around them, constructing coherent and effective thought and behaviour. Although a complex mental function, involving interaction of higher sensory processing with current goals and task demands, the basic process of selective attention and cognitive control is probably similar across different species, allowing productive interaction of work in humans and other animals. In this project, attention and control are studied at multiple levels, including measurements of normal human behaviour, impairment after brain damage, local cerebral activity during different kinds of mental activity using functional brain imaging, and neural activity at the cellular level. By understanding these basic neural mechanisms underlying attention and control, we hope to improve diagnosis and management of crippling attentional impairments following stroke and other brain diseases.


Research activity codes: 1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: EP1: Working memory and executive functions in development and disorder
Funder: Medical Research Council

Abstract: This programme investigates the mechanisms that underpin working memory and executive functions with the aim of developing theoretical understanding of typical cognition, and also how these mechanisms may be disrupted and may be ameliorated in developmental disorders. There are two main components to the programme. The first component focuses on the cognitive and neural mechanisms of working memory in typical adults, with a particular focus on how intensive training can modify these mechanisms. Current projects compare different kinds of training in short-term and working memory with the aim of discovering the processes underpinning transfer to untrained tasks. Methods including brain simulation and neuroimaging are being employed to illuminate the neurological processes underpinning any training-related changes in behaviour. The second component is a cross-programme collaboration with Astle and Manly investigating the cognitive and neural mechanisms of developmental difficulties of attention, learning and memory. Recruitment takes place through a new research clinic established at the Centre for Attention, Learning and Memory (CALM), which aims to discover the core dimensions of impairment common to children with multiple developmental problems including ADHD, dyslexia and dyscalculia. MRI testing and DNA collection provides the basis for neuroimaging and genetic analysis of these children, who are also recruited for participation in intervention studies designed to improve learning outcomes.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: MP2: Systems Neuroscience of Human Memory and its Disorders
Funder: Medical Research Council

Abstract: One of the most important developments during the last two decades of cognitive neuroscience has been the realisation that human memory is not a monolithic entity, but is best viewed as a collection of distinct types. This realisation was originally based on the memory impairments following brain damage or dementia, in which some types of memory are impaired while others are spared, suggesting that these different types of memory are supported by different neural systems. More recently, this evidence has been bolstered by dissociable patterns of activity found in the brains of healthy volunteers while they perform various memory tasks, as measured by functional magnetic resonance imaging (fMRI) or electro- or magneto-encephalography (E/MEG). These data not only inform us about the neural bases of memory, but also help characterise further the theoretical distinctions between each type of memory. Our research programme uses fMRI and E/MEG, in conjunction with computational modelling, to investigate further the theoretical and neural distinctions between two types of conscious memory (recollection and familiarity), and between conscious and unconscious memory (priming), in healthy volunteers. The better theoretical understanding of normal memory that is provided by this research is not only vital for understanding the memory problems associated with brain damage or disease, and their rehabilitation, but also those problems associated with normal ageing of the healthy brain.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Networks of neural dynamics: Knowledge-discovery for experimental neuroscience
Funder: Medical Research Council

Abstract: The delicate balance of co-ordinated neuron activity within and between brain regions is essential for normal brain function. Disrupting this co-ordination leads to dysfunction, like the excessive synchrony underlying epileptic seizures, or the loss of synchrony underlying loss of recall in dementia. Consequently, our best understanding of both neural function and dysfunction will be achieved when we can record, control, and analyse system-wide neural activity resolved to the level of co-ordination between each neuron. Large-scale recording technology and system-wide control via optogenetics are becoming routine - but we lack system-wide analyses. I will develop data-mining methods that are able to solve the problems of finding when cells are co-active, which groups they belong to, and what form that co-ordinated activity takes, whether it be simultaneous, in sequences, or something more complex. I will develop a methodological framework based on network theory, modelling the interactions between neurons as links in a network. We will create network-dividing algorithms that automatically determine the size and number of groups of interacting neurons. These algorithms will be capable of data-mining the direction and type of interaction through analysing their delay, sign, and causality. Establishing this systems approach to neurophysiology will enable knowledge-discovery of novel hypotheses for neural coding, neural computation, and their disruption. These algorithms will be used for collaborative analysis of large-scale neural activity data, to discover: the key factors in the healthy development of the striatum (with C. Hammond, INMED, Marseille); how dynamic re-organisation of neuron populations across the prefrontal cortex-hippocampal system underpins learning and decision-making (with S. Wiener, College de France, Paris); and how sensory information is coded by neuron populations in the whisker-related thalamus (with R. Petersen, University of Manchester)


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.4 METHODOLOGIES AND MEASUREMENTS
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Neural mechanisms for inhibitory control over attention and working memory
Funder: Medical Research Council

Abstract: This research explores the brain mechanisms that bias perception and working memory according to behavioural relevance. Previous research has mainly focused on the mechanisms that facilitate processing of behaviourally relevant sensory input. However, inhibition is an important counterpoint to facilitation: very often it may be equally important to inhibit distracting input as it is to enhance processing of behaviourally relevant input. This programme will explore the control mechanisms for selective inhibition, directly contrasting putative neural systems against the well-established architecture for selective facilitation. Core issues will be addressed using a range of complementary neuroscientific methods to measure and perturb brain function with high spatial and temporal precision. The results of these experiments will provide new insights into how the brain processes perceptual information to construct an internal world model that is optimised for guiding purposeful action. A better understanding of the brain mechanism for high-level cognitive control will also provide a solid foundation for new research directions integrating cognitive neuroscientific and psychiatric research. As a first step toward future translational studies, this research will explore how individual differences in selective inhibition relate to mood disorders. The brain mechanisms for inhibitory control are especially likely to be important for understanding the brain bases for negative ruminations in depression, automatic orienting to aversive stimuli in mood disordered patients. The proposed exploratory study will lay the foundation for a more thorough investigation of the neuro-cognitive basis of depression/anxiety, and potential treatment strategies.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Neurosteroids and GABA-A receptors and their roles in neuropsychiatric disorders
Funder: Medical Research Council

Abstract: We will examine how neurosteroids exert their effects via specific GABA-AR isoforms and the consequences for neuropsychiatric disease when this becomes dysfunctional. Our aim is to better understand some of the mechanisms that precipitate mental illness and to provide new approaches for its prevention and treatment by exploiting our knowledge of the neurosteroid modulatory site on GABA-ARs. A combination of cellular, molecular and genetic techniques will examine the roles of neurosteroids using recombinant GABA-ARs in expression systems and native GABA-ARs in cell cultures or brain slices. Whole-cell patch clamp recording methods will measure GABA synaptic and tonic inhibition and associated kinetic parameters. Biochemical (Western blots, phosphorylation) and immunocytochemical techniques (antibody labelling, phosphorylation-specific antibodies, Tirf microscopy) will measure changes to GABA-AR composition, and single particle tracking with quantum dots and the bungarotoxin binding site will monitor GABA-AR mobility. New transgenic animals will help to explore the interactions between GABA-AR phosphorylation and neurosteroid modulation with regard to synaptic and tonic inhibition. Behavioural techniques will examine how neurosteroids affect intact brain function and the consequences that follow when this becomes dysfunctional. We will use structure-function approaches to probe the neurosteroid binding site and transplant it into other receptors to gain valuable information on key structural determinants. We will design (collab. with UCL Chemistry and Industry) new neurosteroid molecules that could be therapeutically beneficial by targeting specific isoforms of the GABA-AR. Our research programme will contribute to our understanding of brain function. It will help us to understand how neurological diseases can be precipitated by dysfunctional neurosteroid signalling, as well as providing new insight into novel therapeutic strategies for mental health.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;NEUROLOGICAL