NIHRDataInsights/HRCSData huggingface dataset:
Title: Imaging fast neural activity in the brain with Electrical Impedance Tomography (EIT).
Funder: Wellcome Trust

Abstract: Electrical Impedance Tomography (EIT) is a new medical imaging method which is portable, inexpensive, safe, and rapid; images are produced with electronics about the size of a shoebox, and rings of ECG type electrodes. It has the potential to image fast electrical activity in the brain over milliseconds, by imaging small changes in electrical properties of brain cells known to occur during activity. If successful, this would produce a revolutionary advance in neuroscience technology, as it would allow testing of theories of brain function produced by computer modeling of activity in pathways in the brain. Although the method is sound in principle, the changes are very small and present a technical challenge. Based on modeling studies validated in crab nerve and human scalp recordings, the applicants have just achieved a technical breakthrough by producing accurate EIT images in the anaesthetized rat with a square grid array of electrodes placed directly on the brain during visual, l imb or whisker sensory stimulation. Support is sought over three years to develop this method to imaging such activity throughout the entire brain in the rat, first with brain and then with non-invasive scalp electrodes. If successful, the method would be applied to human subjects.


Research activity codes: 1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING)
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Exploring navigational gudiance systems in the human brain.
Funder: Wellcome Trust

Abstract: Finding our way around is vital for our survival. To navigate, the brain needs to establish where we are, where our goal is located and how we should reach it. Despite decades of research on navigation, we know surprisingly little about how the brain determines our spatial relationship to goals, or guides navigation to them. We will use brain imaging to study the brain activity associated with navigation. Whilst being scanned participants will be required to watch a film of movement through a fa miliar environment and make choices at street junctions about which direction to go in. Analysis of the data will determine: 1) how distance and direction to goals are encoded by the brain during navigation, 2) which brain regions help reassess our path when we hit an unexpected obstruction to the route, 3) how reward associated with goals affects brain activity, 4) whether different rhythmic oscillations in brain activity help brain regions communicate with one another and maintain information about goals. This work will not only help us to understand how we navigate, but also to establish how brain networks track information as we move through the world, and how they support and drive goal-directed behaviour.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Decoding dorsal depth processing in the human brain.
Funder: Wellcome Trust

Abstract: Interpreting 3D structure is an integral part of our daily lives whether we are crossing a road or watching a movie. The brain s task is difficult: it has to arrive at a stable interpretation using ambiguous signals registered by the two eyes. This problem has fascinated artists, philosophers and scientists for centuries, yet we know surprisingly little about the neural circuits that support 3D perception. I will use advanced brain imaging techniques to reveal how the brain organises, interpre ts and combines information about depth provided by a range of depth cues (e.g. binocular disparity, shading, shadows and motion). I aim to show that there are high-level interactions between pathways in the visual cortex that have traditionally been treated as separate hierarchies. In particular, my hypothesis is that depth signals traditionally regarded as being used to control movements are also useful to support our perception of 3D objects. To test these ideas, I will use functional brain i maging, advanced computational analysis, behavioural tests of patients with brain lesions and stimulation techniques that induce temporary, focal disruptions of brain activity in healthy participants. The work will advance our understanding of how the brain combines visual signals to interpret 3D structure.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Development of novel meta-machine learning algorithms for the integration of genomic and neuroimaging data for genetic pathway discovery: application to Parkinson's disease and schizophrenia.
Funder: Wellcome Trust

Abstract: My proposed study is focused on computational approaches to identify genetic risk factors via the fusion of genomic and neuroimaging data on Parkinson's Disease and schizophrenia in order to discover pathways of genetic changes that are associated with increased risk for these diseases and that act directly on neuroimaging intermediate phenotypes associated with each disease. In order to do so, I will develop a novel meta-machine learning algorithm for the integration of these two disparate sources of data to increase the ability to detect pathways impacting on disease and imaging phenotypes.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Neuronal mechanisms of spatial memory.
Funder: Wellcome Trust

Abstract: Our memories define who we are. Memory problems feature in many neurological and psychiatric conditions, including dementia, with extreme implications for the well-being of both patient and carer. Despite recent advances knowledge regarding the molecules, neurons and synapses which form our brains, we do not know how they collectively encode, store, maintain and retrieve our memories. This gap prevents direct application of our knowledge of how disease, genetic factors or medicines affect neuron s and synapses to how they will impact upon day-to-day memory and the symptoms we use to monitor neurological diseases. I will focus on spatial memory, which is affected early in Alzheimer s disease, and which can be studied similarly in humans and rodent models. I will investigate how spatial memory results from the actions of populations of neurons, making use of new techniques such as virtual reality and sophisticated methods to monitor brain activity. With this data, I will make a precise model of how the activity and dynamics of neuronal populations represent, store and retrieve information concerning our spatial environment and the events occurring within it. The model will also address how these processes can go wrong in dementia, epilepsy and post-traumatic stress disorder.


Research activity codes: 1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Cellular and synaptic mechanisms of learning in cortical circuits.
Funder: Wellcome Trust

Abstract: Our ability to learn depends on modifications in our brain, and likely occurs due to changes in connections between nerve cells, which are called synapses. Because of the complexity of the brain consisting of 100 billion nerve cells, each receiving thousands of synapses it has been difficult to study how changes in connectivity might mediate learning and memory formation. Recent advances in high-resolution microscopy and genetic methods enable me tovisualize neurons, their activity and their synapses in the intact brain, and follow howthey change while an animal is learning. I will use these powerful new methods, some of which I have pioneered, to study the mechanisms of learning in the visual cortex - the part of our brain which computes visual information and enables us to see. I will test how the formation of new synapses between nerve cells contributes to the changes observed in their function while an animal learns or encounters new visual experiences, and if such modification of synapses provides a way to store new information in the brain. Obtaining insight into mechanisms of learning is also necessary for understanding how they become disruptedin devastating diseases such as Alzheimer's and mental retardation.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Development of function in asymmetric brain circuits.
Funder: Wellcome Trust

Abstract: It has been known for a long time now that the brain is not completely left-right symmetric and, indeed, neuroanatomical asymmetries are present in all animals. These asymmetries enable the brain to perform specific activities more efficiently. For example, language and dominant handedness are usually localised to the left hemisphere leaving the right free to perform other tasks. The extent of brain functions shown to be lateralized is continuously increasing, and several neuropatholgies and dis orders have also been associated with altered asymmetry. Despite the importance of these neuroanatomical and functional asymmetries, we do not know how they develop or how they lead to the formation of complex cognitive processes and behaviours. The zebrafish is the best vertebrate model to study the formation of brain asymmetries as well as to gain insight into lateralised behavioural and cognitive processes. In this project, I will use imaging techniques to visualize how neuronal activity in asymmetric brain circuitry develops, how it contributes to the final organization of lateralized structures, and how it is modified when normal asymmetry is altered. Furthermore, I will perform assays to establish how lateralized activity leads to the development of specific behaviours.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: The role of CNTNAP2 in the Cerebellum
Funder: Wellcome Trust

Abstract: The cerebellum is increasingly implicated in higher cognitive function and cerebellar dysfunction has been linked to several diseases. Recently, there has been accumulating evidence for the involvement of the cerebellum in autism. Cntnap2 -/- mice have been described as a model of autism. In this project, I aim to investigate Cntnap2 function in the cerebellum. I will analyse its cerebellar expression patterns during development and aim to elucidate its role at the synapse of parallel fibres. I will test whether Cntnap2 -/- mice also display a cerebellar behavioural phenotype in addition to the previously described autism-like phenotype. Finally, I aim to rescue Cntnap2 expression in cerebellar granule cells by crossing the Cntnap2 knockout mice with Math1-Cntnap2 transgenic mice and asses motor and autism-like behaviour


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Contributions of COMT and DAT to dopaminergic regulation of reward-guided behaviour
Funder: Wellcome Trust

Abstract: Dopamine (DA) is cleared from the synapse by two mechanisms: degradation by the enzyme COMT, and recycling via the transporter pump DAT. Both mechanisms contribute to regulation of DAergic transmission in the striatum and thus likely influence striatally-mediated reward-guided behaviours. However, the relative contributions of COMT and DAT have not been described. I will characterize the roles of COMT and DAT in striatal DA regulation and modulation of reward-guided behaviour. Transgenic mice modelling a human polymorphism in the COMT gene will be used, along with pharmacological agents,to manipulate the activity levels of COMT and DAT while mice perform rewarded operant tasks. In addition, fast-scan cyclic voltammetry will be used to monitor striatal DA levels during behaviour and to determine how DA representsvarious aspects of reward, such as reward magnitude and probability, and how COMT and DAT affect this representation. Molecular studies of COMT and DAT expression levels in mice and humans will complement these in vivo investigations. This study will clarify how different DA clearance mechanismscontribute to the regulation of striatal DA levels and, in turn, to reward-guided behaviour.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Action costs and competition costs in reward-guided decision making
Funder: Wellcome Trust

Abstract: I propose to use functional magnetic resonance imaging in combination with computational modelling to investigate questions of learning and decision making. The proposed project aims to understand how the brain processes action-related and social information to minimise decision costs. More specifically, it is intended to examine whether there are brain mechanisms underlying learning and decision making that do not relate specific occurrences of stimuli to specific occurrences of outcomes, as commonly thought, but which instead are based on the rate of reward received over time and the rate of action that is emitted. In some other contexts, where more than one individual is present then it may be the case that an agent will alsocompare their action-reward rates with those that appear to be experienced by other competing agents. From a foraging perspective both sets of information, although seemingly disparate in nature, can be understood as key parameters determining decision costs. In investigating the brain mechanisms underlying the inclusion of these costs in decision making, the research project particularly aims to understand the roles of various frontal cortical regions, especially the cingulate cortex


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Investigating the roles of dopamine and the basal ganglia in reinforcement learning, memory and decision making
Funder: Wellcome Trust

Abstract: The aims of this PhD are to investigate the role of the Basal Ganglia (BG) in reinforcement learning (RL), decision making (OM) and memory. Additionally, the effects of Parkinson's Disease (PO) on these processes will be studied, and as the major effects of PO are due to dopamine deficiency, the role of dopamine will also be examined. Work done during the 4 month project, and that will be continued during the PhD, was based on findings that PO patients off their dopaminergic medications showed learning and memory deficits compared with patients on medications (Coulthard et al., in press; Frank, Seeberger, & O'reilly, 2004; Shiner et al., 2012). I will first increase the sample size of the experiments on Parkinson's Disease (PO) patients I conducted during the 4 month rotation, and examine the data for the effects I did not have time to investigate during the rotation. Different models will also be fit to the data to see if they can explain the effects more accurately than than the ones used previously. The next experiment I will run will investigate whether the changes in beta oscillation power found during decision making originates in the subthalamic nucleus - globus pallidus external segment (STN-GPe) loop. This will be tested using EEG recordings from PD patients undergoing deep brain stimulation (DBS). The STN-GPe model and Basal Ganglia Decision Making model will also be combined. The decision making model will be extended to include a negative reinforcement pathway and the effects of this will be tested experimentally. Effects of levodopa on beta oscillations during decision making will also be investigated with the EEG paradigm, and the effects on consolidation tested more explicitly.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: The neural circuit of perceptual decision-making
Funder: Wellcome Trust

Abstract: We have developed a new automated behavioural task whereby rats take differentroutes in a maze based on an auditory cue. We intend to record with tetrodes from the prefrontal cortex, hippocampus and dorsal striatum in behaving rats during this task in order to investigate the neural circuit of perceptual decision making during a spatial task and secondly the mechanism of planning and evaluating consequences of actions in this circuit. We intend to test the following hypotheses: Are integrators for noisy stimuli in prefrontal cortex? Does virtual 'preplay' experience of locations correlate with activity from other regions which are active during local experience? Does preplay coincide with the decision making process?


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Mentalizing and social conformity: Pharmacological manipulations and underlying mechanisms
Funder: Wellcome Trust

Abstract: The proposed research project focuses on the neurobiology of social behaviour.Neuroimaging experiments will be combined with pharmacological manipulations to better understand the mechanisms and computations underlying social information processing. We recently developed a paradigm to modulate participant's preferences in an intertemporal choice task (Garvert et al., in preparation). This paradigm is apotentially powerful tool for conceptualizing and quantifying the implicit effects mentalizing exerts on decision making. l aim to use this task to studythe biological mechanisms underlying behaviour of individuals placed in socialsituations by investigating the brain regions that support task performance and the effect played by neuromodulators known to be involved in social behaviour (e.g. oxytocin). Furthermore, it will be investigated whether a similar social conformity effect can be observed in other areas of decision making. Elucidating these mechanisms is highly relevant for understanding psychiatric disorders associated with social dysfunction, such as autism. In


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Hearing the Voice.
Funder: Wellcome Trust

Abstract: Hearing the voice of another person in the absence of any speaker is an important feature of human experience, and one which is associated with considerable social, human and economic costs. Comprising the first major interdisciplinary study of the phenomenon, this five-year medical humanities project consists of five interdependent programmes of research in the fields of phenomenology, cognitive neuroscience, hermeneutics, therapeutic practice and medical humanities methodology. Our starting point is a holistic view of voice-hearing which attempts to integrate scientific and humanities approachesto the phenomenon. Building on our demonstrated strengths across these fields,the first aim of the project is to attain a fuller understanding than has previously been possible of the phenomenon of voice-hearing, including how it relates to typical inner experience, how it is underpinned by specific cognitive and neural mechanisms, how it is interpreted personally, culturally and historically, and how it should be managed. Our second aim is to develop atransferrable methodology for interdisciplinary research into human experiencethat can be applied to other topics of inquiry. We will achieve these aims by assembling a world-class research team, capable of addressing research questions from multiple interdisciplinary perspectives.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Bridging microscopic and macroscopic measures of reward-guided decision making.
Funder: Wellcome Trust

Abstract: RESEARCH QUESTION ABSTRACT ONLY Can microscopic (single-neuron) and macroscopic (neuroimaging) measures of prefrontal cortex activity be understood in a common mechanistic framework when examining their role in rewardguided choice? Do biophysically realistic neural network models explain neural responses in prefrontal cortex? Is it possible to isolate the role of ventromedial prefrontal cortex from other prefrontal regions, using both microscopic and macroscopic measurements? Can we provide a mechanistic understanding of inter-regional communication between prefrontal regions, and of the heterogeneity of neural responses in these regions? Do causal manipulations ofprefrontal neural activity elicit changes in behaviour in paradigms of reward-guided decision-making?


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Neural representations of timing for skilled movements.
Funder: Wellcome Trust

Abstract: In our daily life, we effortlessly produce highly skilled movements: We coordinate our lips, vocal chords and tongue to utter a sentence, our arm and hand to throw a ball to a target and our fingers to play a melody on a piano. In addition to what muscles to move, knowing when to move is necessary to achieve the desired goal. However, how the nervous system acquires and stores representations of movement timing is unknown. I will combine neuroimaging in humans and neurophysiology in mice to addr ess this question. Advanced brain imaging in humans will reveal local patterns of neural activity across the brain that carry information about movement timing and elucidate how these activity patterns progressively change with learning. To test whether these local representations are indispensable for timing accuracy, I will temporarily and non-invasively interfere with these regions and assess whether patients with local brain degeneration are affected. Finally, neurophysiology in rodents will reveal how individual neurons and neuronal populations ensure accurate timing in a series of movements. My results will advance our knowledge of how motor timing is stored in the brain. I believe that, ultimately, this knowledge will improve the rehabilitation of individuals with movement coordination.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: An investigation of synaptic and molecular mechanisms for neural representation of space.
Funder: Wellcome Trust

Abstract: A sense of space is crucial for navigation and planning future actions. Our brains keep track of our location to create neural representations of space. The importance of such brain functions becomes particularly noticeable in cases when we become disoriented and confused, and more dramatically in people with Alzheimer's disease. The neural processing underlying spatial cognition involves a brain area called the entorhinal cortex which is considered the brains distance calculator. Intriguingl y, calculations appear to be carried out simultaneously for low- and high-resolution estimates of distance. I plan to investigate the types of information (e.g. speed of movement, vision, proprioception) that cells in the entorhinal cortex receive from other brain regions and how this information is transformed into spatial maps with different resolutions. I will focus in particular on the anatomical arrangements for computations that mediate perception of space at different resolutions. I w ill also define molecular properties of entorhinal neurons with the aim of generating new tools for further investigation of cognitive functions and related disease states that involve our brains ability to keep track of location.


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