NIHRDataInsights/HRCSData huggingface dataset:
Title: Oxford Centre for Neural Circuits and Behaviour.
Funder: Wellcome Trust

Abstract: Understanding how nerve cells work together to generate intelligent behaviour remains one of the most difficult problems in biology. The use of new genetic tools to label nerve cells and to control their function is poised to make this problem tractable. By observing how neurons communicate, the structure of neural circuits can be worked out and their function inferred. By controlling neurons remotely, hypotheses about function can be tested, making it possible to understand how neuronal activit y underpins behaviour. Our intention is to assemble a team of neuroscientists working in a single building in Oxford to develop and apply the necessary genetic reagents. Key resources in which these tools can be deployed are fruit flies, zebrafish, and mice.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Pursuing a multi-level understanding of memory and motivation.
Funder: Wellcome Trust

Abstract: The ability to appropriately direct behaviour using our memories is something we take for granted. However, in certain disease-states, such as affective disorders and addiction, our motivational control goes awry and behaviour runs amok. We will explore the brain systems encoding memory and motivation and determine how they are integrated to direct behaviour. We wish to understand how memories are represented in the brain and will identify neural networks, neurons within the network and molecule s within those neurons that are involved. We aim to understand the changes that occur when memories are formed and are particularly interested in why some memories last minutes whereas others last for days, or a lifetime. We also wish to understand how motivational states, such as hunger and satiety, are represented in the brain and how that information is integrated with memory systems so that behaviour is controlled in a meaningful way. What brain mechanisms explain why the smell of food is m ore likely to lead to a search for a meal if we are hungry? We will study these conserved processes using the small brain of the fruit fly where current genetic technology allows us to interrogate these biological questions with unrivalled precision.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Importance of mammillary body connections for memory.
Funder: Wellcome Trust

Abstract: The devastating effects of conditions such as Alzheimer s disease underline the importance of our memories. Memory is vital, not only for remembering our past but also learning to adapt to changes in our everyday lives. At the same time, understanding how our brains support memory remains one of the greatest scientific challenges. Studies of patients who have become amnesic i.e. lost the ability to form new memories following brain damage, have led to the identification of potentially important brain structures for memory. These structures include the mammillary bodies. My research will focus on uncovering the contributions of the mammillary bodies to memory formation. The prevailing view is that mammillary bodies principally act as a relay, passing on information from the hippocampus, another well-known memory structure. However, my recent findings suggest that the actual situation is very different, as the mammillary bodies may themselves be necessary for normal hippocampal functio n. My research will use a combination of cutting edge techniques to test models of mammillary body function and to identify the nature of the information that the mammillary bodies supply to the hippocampus.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Working memory and attention in the young-adult and ageing human brain: distractor suppression and cortical-striatal loops
Funder: Wellcome Trust

Abstract: Working memory (WM) and selective attention (SA) are both vital in daily life,and may share common neural components, but the exact nature of their relation is unknown. Top-down control of distractor-filtering in WM, associated with a basal-ganglia/frontal/parietal mechanism, may contribute to an individual's WM capacity (McNab & Klingberg, 2008). Here we will address whether this mechanism is common to both WM and SA, and its generality or specificity across different types of distraction. The basal ganglia are highly innervated with dopamine receptors. Dopamine plays an important role in WM. With dopaminergic drugs we will interrogate the role of dopamine in distractorfiltering, for both WM and SA contexts. Recently we revealed some plasticity in the dopamine system of young adults with WM training (McNab et al., 2009). Here we will test whether specific training of distractor-filtering can offer greater benefit. This will also allow further tests of the association betweenWM and SA. Following reports of age-related distractor-suppression deficits and striatal dopamine changes, I will test our hypothesis that the basal-ganglia/frontal mechanism is specifically affected by ageing, contributing to age-related WM and SA deficits. I shall also test whether distractorfiltering training and/or dopaminergic modulations can ameliorate such normal age-related deficits.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Neural mechanisms of sensory awareness.
Funder: Wellcome Trust

Abstract: Our senses supply us with a huge amount of information. One of the main tasks of the human brain is the selection of information that is currently relevant for behaviour. Why is the same task-relevant sensory information sometimes perceived and sometimes not perceived? This can be of critical importance in many situations (e.g. driving a car) and jobs (e.g. air traffic controller, pilot, surgeon). What are the factors determining the fate of sensory information in the brain? Recent research su ggests that rhythmic fluctuations in brain activity (brain oscillations) play a role in gating sensory information. Our project is designed to test this hypothesis with a series of five experiments. We aim at establishing a clear understanding of how information processing in the brain is reflected in changes of brain oscillations and test the hypothesis that brain oscillations are predictive of conscious perception of stimuli.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Automatic and analytical altruism: Neurobiological foundations of human prosocial behaviour.
Funder: Wellcome Trust

Abstract: Economic theories of social preferences implicitly assume that prosocial behaviour is goal-directed- that is, intentional and guided by expected outcomes. However, recent advances in neuroscience have revealed that motivated behaviours are multiply determined- in different conditions the same behaviours can arise from reflexes or habits instead of goals. Thus, prosocial behaviour may be goal-directed only in certain circumstances. I aim to demonstrate behaviourally that prosocial behaviour ca n arise from multiple decision-making systems (reflexes, habits and goals); to understand some of the internal and external conditions that promote the dominance of one system over another; and to define the neural mechanisms comprising the underlying structure of social preferences, in order to predict the characteristics of prosocial behaviour in different contexts. I will achieve this by combining sophisticated behavioural methods from animal learning theory and economics with advanced tech niques in cognitive neuroscience including model-based fMRI, psychopharmacology and patient studies. My goal is to develop an updated account of human social preferences that considers reflexive and habitual, as well as goal-directed, contributions to prosocial behaviour.


Research activity codes: 1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Role of temporal silencing in the circadian clock.
Funder: Wellcome Trust

Abstract: Every day we awaken and go to sleep at roughly the same time. This is not just because of regular change in the levels of daylight, but because we have in our brain a master clock whose neurons send wake up and sleep messages to the rest of the brain and body. This clock is synchronized by the environmental light-dark cycle. The 'clock genes' that form the basis for this clock are known, but we do not yet understand how they alter the properties of the neurones in which they are contained. A gre ater understanding of how clock cells listen to their internal molecular clock and how they communicate and share clock information will help in developing better therapies for sleep disorders and the debilitating effects on health of shift work schedules. Recently we made an important discovery that the neurones making a key clock gene, period1, have unexpected and unusual electrical characteristics not seen in cells that do not contain period1. Subsequent investigations suggest that these char acteristics may be pivotal in determining how clock cells talk to one another as well as if, when, and how they respond to inputs from the eye and other parts of the brain.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: 4 year PhD in Neuroscience - The role of endogenous brain rhythms in linking memory and perception
Funder: Wellcome Trust

Abstract: Maintaining multiple objects in short-term memory (STM) achieves two ends. It retains information about those objects in an activated state over a number of seconds, and it keeps information about different objects distinct. STM maintenance also has been linked to the synchronization of slow, 4-8 Hz (theta) oscillations in the frontal cortex and hippocampus, which may help in achieving those two goals. Synchronization of activity in this frequency range has been proposed to regulate the excitability of specific neural pools involved in maintaining single objects (Lisman & Idiart, 1995). In this framework, neurons representing one object fire at a specific phase in the theta cycle, helping to integrate information about that object and keeping it separate from information about other objects, which is reactivated at other phases in the theta cycle. Whether this synchronization extends to more posterior visual processing areas when STM is updated using ongoing visual perception is not known. Interestingly, theta oscillations have also been linked to the encoding of information into long-term memory. The possibility that both forms of memory rely on a similar mechanism based on theta-band synchronization has not been explored extensively. In this project, we aim to measure neural oscillations using magnetoencephalography (MEG) and disrupt them using combined TMS-EEG to investigate whether slow frequency synchronization is a possible neural mechanism linking visual perception to visual memories at different time scales.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Before 'Translational Medicine': Bench-Clinic Relations since 1950.
Funder: Wellcome Trust

Abstract: In the last decade the government, drug companies and patient groups have all emphasised the need to improve the speed and efficiency with which new remedies move from biomedical research, through evaluation, to the clinical application and the development of practice guidelines. The major response of the medical profession has been the creation of the new specialism of Translational Medicine, which is attracting considerable attention and investment in research labs, universities and hospitals . While the term Translational Medicine is recent, the goal of developing productive and efficient links between research laboratory and bedside are far from new, and they have been central to biomedicine for decades. In this project we will explore how and why relations between laboratory and clinic changed since 1950 and identify the lessons for policies in the new Translational Medicine. Our research will mainly focus on conditions affecting the brain: mental disorders, dementia and stro ke, plus studies of the impact of molecular biology on medicine. Our PhD students will look at the work of the Medical Research Council, imaging technologies, and evidence-based medicine. As well as engaging with the public in a variety of activities, we will run events with and for researchers and clinicians.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;6.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Mechanisms and plasticity of dendritic temporal sequence processing.
Funder: Wellcome Trust

Abstract: The mechanism by which neurons detect, organize and process numerous chemical and electrical signals is a fundamental problem in modern neuroscience. For example, the ability to discriminate spatiotemporal sequences of synaptic input has been suggested to be important for generating efficient coding schemes, and input sequence detection in general is a computation essential for animal behaviour. Previous work showed that dendrites could be responsive to the "direction" of temporally spaced inputs due to their cable filtering properties, suggesting that single neurons could act as basic sequence detectors. This "passive" direction selectivity was confirmed experimentally by Branco and colleagues, who also discovered that "active" NMDA receptor conductance recruitment dramatically enhances the direction sensitivity of somatic responses. In addition, Branco et al. 3 found that dendrites could discriminate not only directional sequences, bu1 also a wide range of spatiotemporal patterns. However, the role and impact of dendritic sequence processing is unknown for computation in different cortical areas and under different conditions. I plan to concentrate on two broad questions addressing how dendritic mechanisms can optimally discriminate sequences and potentially store selected input patterns. First, I will concentrate on the types of spatiotemporal patterns that can be distinguished from each other. Second, I will investigate whether specific input sequences can be stored, by probing plasticity processes triggered by different input patterns. Optimal conditions for dendritic pattern recognition. What is the optimal spatial distribution of inputs? What is the "optimal dendrite"? Interaction of patterns on the dendrite. The interaction of backpropagating action potential and patterned inputs. Influence of background noise. Sources of calcium ? pharmacology. Tthe effects of neuromodulation. Plasticity triggered.by patterned input. Plasticity induction readouts. Plasticity induction protocols - repetition of the same input pattern and pattern and action-potential combination Effect of neuromodulation in regulating of pattern-induced plasticity.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Systems neuroscience: From networks to behaviour - Modulation of prefrontal cortex circuits in vivo and in vitro in normal animals and rodent models of schizophrenia.
Funder: Wellcome Trust

Abstract: The prefrontal cortex (PFC) is involved in many higher cognitive functions including working memory, attention and planning. Neuromodulators, such as the monoamines dopamine and serotonin play a key role in regulating these functions and are also central to many diseases associated with PFC dysfunction, including addiction and schizophrenia. In addition, the neuromodulator systems are also the targets of treatment for these conditions. Despite this key role the mechanisms of how the different neuromodulator systems alter PFC circuit function are still unclear and this proposal aims to further our understanding of the role of these key neuromodulators in the PFC.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Neuropharmacological basis of short and long-range neuronal synchronization in cognition.
Funder: Wellcome Trust

Abstract: I will investigate which brain chemicals contribute to cognitive function. This will provide insight into the neuronal mechanisms of cognition. The brain is hierarchically organized, whereby different brain areas have different roles in cognition. Likewise the influence of different brain chemicals on these areas differs. A key goal is to determine which brain chemicals are involved in cognition at different stage of the processing hierarchy (i.e. in different cortical areas), and which recepto rs mediate these functions. I will determine whether different brain chemicals are involved when cognitive demands change, e.g. by comparing attention to working memory. Investigation of the brain chemicals (and their respective receptors) will focus on the NMDA receptor, the cholinergic and the dopaminergic systems The above listed brain chemicals could enable cognition by two different mechanisms Either, they could solely influence the activity levels of individual neurons. The combined i ndividual activity levels would then be the critical determinant of cognitive function. Alternatively, the precise orchestration of neuronal activity (timing of neuronal activity) might be the critical determinant. The proposed study allows to investigate both, as careful manipulation of the neurochemical environment affects these two mechanisms independently, and thus their contribution to an animal s performance is possible.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Epstein-Barr virus induced T cell responses and the pathogenesis of multiple sclerosis.
Funder: Wellcome Trust

Abstract: Multiple Sclerosis (MS) is thought to be caused by the body s immune system mounting an attack on the central nervous system (CNS). One possible explanation for such autoimmune behaviour is that infection with a virus induces strong immune responses which recognise not only the virus but also, by chance, normal components of the CNS. Accumulating evidence suggests that one candidate virus is Epstein-Barr virus (EBV). This is a common virus that almost all people acquire either in infancy or la ter in adolescence and that is then carried for life, usually with no adverse effect. Recent evidence suggests that the immune response to this virus in MS patients differs from that in healthy individuals. Furthermore, parts of this response appear to cross-react with components of the central nervous system. We shall determine whether or not the immune response to EBV in MS patients really does contain cells that, when isolated and studied in the laboratory, are reactive against CNS compon ents. If the answer is yes and such cells are detectable in MS patients blood, then we shall look for more direct evidence that the same types of cells are active at the sites of actual disease in the CNS.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: The elements of cerebellar computation.
Funder: Wellcome Trust

Abstract: A central mission of neuroscience is to understand how patterns of activity in neural circuits represent and store information and give rise to behaviour. This is highly challenging, given the complexity of neural circuits and the speed and distributed nature of their patterns of signalling. This proposal will link the structure of a neural circuit to its function in order to understand a key neural circuit in the brain, the cerebellum, which plays a crucial role in the coordination and learning of voluntary movements. Disruption of cerebellar function, in neurological disorders such as ataxia, is debilitating and prevents execution of smooth, precise, rapid movements. Understanding cerebellar function is therefore likely to improve our understanding of brain function and lead to new treatments for cerebellar disorders. We aim to identify connectivity motifs within cerebellar microcircuits and to show how these patterns define cerebellar network activity during sensation and generation of movements. We will demonstrate where in this network changes take place that may be associated with learning of movements, and we also take advantage of new tools for light-activated control of neural circuits to manipulate such plasticity and thus correct erroneous patterns of activity in mouse models of cerebellar disease.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Bayesian inference using a norm based face coding scheme in humans
Funder: Wellcome Trust

Abstract: Face recognition is a very difficult task, as those who have tried to program a computer to simulate this function will attest, yet the human brain does it almost effortlessly. Recently it has been suggested that the brain encodes faces by recording how a face differs from an average face. Also it has been shown that when the brain tackles problems like face recognition it often usesthe most optimal probabilistic method physically possible to do so. This involves using prior knowledge as well as present sensory evidence to produce an optimal estimate, of face identity for example. This proposal aims to provide evidence for this theory of face encoding in the brain, and to show that this is in fact an example of the optimal use of prior and current knowledge. It would also make sense if the brain split the problem of face recognition into two problems, face detection and face identification. We hypothesise thatpart of the brain, the inferotemporal cortex (aIT), acts as a face identifier,while another part of the brain, the fusiform face area (FFA), acts as a face detector. Therefore we expect to find different responses to different faces in aIT and similar responses to all faces in FFA.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL