NIHRDataInsights/HRCSData huggingface dataset:
Title: Standing up for Dementia: exchanging knowledge on developing a patient and professional pathway for physical activity and exercise.
Funder: Economic and Social Research Council

Abstract: Dementia is currently a major healthcare problem. As our population ages, the number of people suffering from dementia increases yearly. This comes at both a large human and financial cost. Currently, there is no cure for dementia but medication can help to delay the progress of the disease although this has varying degrees of success - other treatment options which involve the patient more directly in their own care are therefore a necessity. Mild cognitive impairment (MCI - defined as a level of cognitive impairment which although noticeable, does not impact sufficiently on an individual's life to be diagnosed as dementia) is seen a stepping stone in the development of dementia, with large numbers of people diagnosed going on to develop dementia over the coming years. One of the main symptoms of dementia and MCI is the detrimental effect that it has on cognitive processes (for example memory, planning, perception and orientation). Within an elderly age group, research suggests that increasing physical activity can have beneficial effects on cognitive processes in later life and this may also be the case in individuals with MCI. This can also be protective as people who are more physically active in their younger years are at less risk of developing dementia as they get older. Unfortunately, many of the studies carried out so far in groups with MCI have not been performed to a high methodological standard, often with mixed groups of dementia participants with different diagnoses of dementia (it is likely that different types of dementia will respond differently to physical activity, just as they do with medications prescribed), in different care settings and without comparable cognitive assessment tools. This means that there is no current clinical advice for individuals with MCI, their caregivers and healthcare professionals as to what sort of physical activity may be beneficial to them as an alternative to current treatments. We propose to develop a behaviour change program which promotes the use of physical activity to maintain cognitive function and prevent cognitive decline in older adults at risk of dementia (those with MCI). This will aim to change the behaviour of both the individual with MCI and the healthcare professionals responsible for their care with the ultimate aim that physical activity can be offered as a healthcare 'prescription' to individuals.


Research activity codes: 5.7 PHYSICAL
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Enhancing the perception of social facial cues using non-invasive brain stimulation
Funder: Economic and Social Research Council

Abstract: This project will examine whether brain stimulation and perceptual training can help to improve social perception abilities in healthy adults and atypical groups. Even in the most fleeting social interaction, we are confronted with a wide array of social signals several of which are displayed by the face. Our ability to successfully interpret and use these signals is a critical feature of our everyday lives. In recent years we have made large strides in understanding brain mechanisms that we use for a range of our social perception abilities (e.g. emotion perception, person perception). This project builds on this by examining whether increasing neural activity in these brain regions can enhance our social perception abilities. To do this, the project will use novel brain stimulation techniques called transcranial direct current stimulation (tDCS) and transcranial random noise stimulation (tRNS). These techniques involve a small current (1-2milliamps) being passed between two rubber pads that are placed on the scalp. When current flows between the two pads, the brain area underneath them becomes more excitable. This makes the particular brain area more responsive to signals that it processes and it has been shown that if the excitatory stimulation is given while someone is training / learning a new skill (that recruits the brain area being stimulated) then the benefits of learning / training are enhanced and occur more rapidly. The project will use these types to brain stimulation to examine whether we can facilitate face recognition and facial emotion recognition. This will include studies in typical and atypical groups (e.g. in developmental prosopagnosia - where individuals are unable to perceive the facial identities of other people). The project will also build upon recent studies using face-training paradigms to improve facial identity and emotion processing abilities, by stimulating the brain during training. Based upon findings in other domains, it is predicted that increasing excitability in brain areas shown to be involved in each task (i.e. person perception and emotion perception) will enhance specific social perception skills. It is also expected that pairing social perception training paradigms with brain stimulation will lead to training effects being boosted and lasting longer. The findings will therefore provide insights into the mechanisms of the brain that contribute to our social perception abilities and determine whether we can influence them in order facilitate social perception abilities in typical and atypical groups.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Primate medial thalamus: Investigating its functions and interrelated neural systems for memory
Funder: Medical Research Council

Abstract: The proposed research will investigate the cognitive processes and neural systems associated with memory processing in the medial thalamus. Strokes and chronic alcoholism are some of the main causes of brain damage in the medial thalamus resulting in memory loss and these conditions are becoming more prevalent as a consequence of our modern lifestyles. Yet relatively little is known about how the medial thalamus contributes to memory as the majority of research has focussed on the medial temporal lobes instead. Current evidence indicates that the medial temporal lobe is no longer a unitary long-term declarative memory system. Thus a shift has occurred into identifying other neural structures in the brain associated with memory. The present proposal will use a multi-faceted approach in primates to determine how various medial thalamic structures may contribute to memory processing and other cognitive abilities, for example, executive function. Within this overall aim there are several main objectives and aims, I will 1. expand the characterisation of cognitive deficits in the macaque model of thalamic amnesia; 2. determine the neural circuits that are critical for medial thalamic involvement in new learning, retrieval and other cognitive processing including executive function; 3. complement the behavioural experiments using immunohistochemistry techniques, specifically immediate-early gene imaging, which will provide information about functional activity in neural circuits involving structures within the medial thalamus during particular types of cognitive challenge. 4. develop expertise in comparative studies of memory processing involving human patients and non-human primates using a combination of neuropsychological testing and functional neuroimaging techniques. To my knowledge I am currently the only researcher in the world who is studying the contribution of the medial thalamus in memory processing using macaques. The primates will participate in a variety of different cognitive memory tasks. Animal models of amnesia continue to provide a valid and reliable methodology for conducting vital experiments and in association with other experimental techniques they complement and advance our understanding of the neural mechanisms of memory processing in the brain. Furthermore the similarity of brain structures and interconnections between humans and Old World macaques will benefit both basic science and clinical practice. The proposed research is highly important as improving our understanding of the medial thalamus can have significant benefits in the longer term for the development of diagnostic tools and methods of rehabilitation for memory loss in both the younger and older population.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Outcome at School Age Following Treatment With Whole Body Hypothermia After Perinatal Asphyxial Encephalopathy
Funder: Medical Research Council

Abstract: We intend to evaluate the neurological, neuropsychological function and educational attainment of participants of the TOBY trial at 6-7 years of age. The study will commence in September 2009 and continue for 48 months. We intend to use a series of neuropsychological tests and a formal neuromotor assessment to assess and classify disabilities. The primary outcome measure will be survival with an intelligence quotient (IQ) 70 or greater. Secondary outcomes will include scores on general cognitive and executive function tests, parent and teacher report behavioural measures, scholastic attainment, patterns of disabilities and the severity and pattern of abnormalities on magnetic resonance imaging (MRI). We will use standard statistical tests to look for significant differences in these measures between children in the cooled and control groups.


Research activity codes: 6.7 PHYSICAL
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: The Centre for Neuropsychiatric Genetics and Genomics
Funder: Medical Research Council

Abstract: The overarching mission of the proposed Centre will be to use genetics and genomics to inform our understanding of the aetiology, pathogenesis and classification of the major psychiatric and neurodegenerative disorders, and to train a cadre of clinical and non-clinical scientists capable of delivering the discovery and translational agenda. Research will focus upon common psychiatric and neurodegenerative disorders. It will be organised around 5 major themes. 1. Psychosis and Major Affective Disorders- schizophrenia, bipolar and unipolar mood disorders; 2. Neurodegenerative Disorders- Alzheimer?s disease, Huntington?s disease, Progressive Supranuclear Palsy, Parkinson?s Disease; 3. Developmental Disorders- dyslexia, ADHD, childhood depression, pre-natal environmental influences on behaviour; 4. Genetic Mouse Models- genetics of impulsive behaviours, familial dementias (Alzheimer?s Disease, FTDP-17), sex chromosome effects on behaviour, genomic imprinting, behavioural epigenetics; 5. Biostatistics and Bioinformatics- this supports research in the above areas. This will be consolidated and developed, particularly in regard to bioinformatics, by institutional and MRC support if Centre status is awarded. Our objectives over the next five years are to deploy the new opportunities afforded by technological advances and large sample sizes to identify new risk genes for psychiatric disorders and to explore the impact of specific genes across diagnostic boundaries and in relation to specific symptoms and dimensions. While much of the Centre?s work will remain focused on the identification of risk genes, we envisage an increasing emphasis on translational work over the next 5 years. The latter will be built upon a number of existing projects as well as several new strategic appointments and collaborations. We request funding in order to: 1) enhance our training capability in particular by establishing a 4 year Centre PhD programme, 2) establish a new senior post in Bioinformatics at Lecturer/Senior Lecturer level in order to enhance our ability to compete in a very data rich environment, and to deliver the added value arising from our synergistic research programmes as well as to our training agenda, 3) establish an innovative public engagement and communications strategy in order to bring the results of our research closer to the patient and to application, 4) develop collaborations allowing us to explore the factors that mediate the effects of risk genes on clinical phenotypes in longitudinal, population-based cohorts.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Cambridge PET Neurochemist Training Programme
Funder: Medical Research Council

Abstract: To address one of the major restrictions on the use of the molecular imaging technique of positron emission tomography (PET) for neuroscience research at Cambridge, the lack of trained PET chemists to design and prepare the required brain imaging probes, proposed is an integrated programme of training and research. In partnership with PET centres, academic and industrial, in the US and Europe we have constructed a training programme designed to train a post-doctoral scientist with a PhD background in chemistry to group leader capability within four yours. Integrated with this training, is the development of probes for the 5-HT2a receptors and beta-amyloid plaques and in the second phase of the programme collaboration with Siemens in the development of novel imaging probes for neurofibrillary tangles, one of the main neuropathological features of Alzheimer s disease (AD) and other dementias. The tracers will then be applied to PET imaging projects in the area of neuropsychiatric and neurodegenerative disorders, with a focus on 1) preclinical studies that have significant translational aspects and 2) human research projects targeted toward understanding the mechanisms of neurological diseases and thereby identifying potential therapeutics. The proposed projects include; i) studies on impulsivity based on imaging 5-HT2a receptors on rats with this behavioural trait; ii) imaging serotonergic modulation in marmosets to investigate mechanistic components common to various neuropsychiatric disorders such of schizophrenia, depression and obsessive compulsive disorder; iii) the role of 5-HT2a in frontotemporal dementia and iv) evaluation of the novel beta-amyloid tracer in AD and MCI patients and normal control subjects, coupled with autoradiographic experiments on brain tissue.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Neurobiological and Neurochemical mechanisms underlying emotional regulation
Funder: Medical Research Council

Abstract: Emotions are highly adaptive and complex states, simultaneously engaging psychological, physiological and behavioral responses that are triggered by the appraisal of external events. However, our immediate reactions to emotive stimuli are not always beneficial, and therefore, an important element of emotion is the ability to appropriately adapt and rapidly modify emotional responses on a moment-by-moment basis. That such regulation is essential for the physiological, psychological and social health of the individual is clearly illustrated by the range of neuropsychiatric disorders in which emotional dysregulation is a core feature, including anxiety, depression, schizophrenia, autism and sociopathy. In all of these disorders there is neuropathology or neurochemical imbalances in neural circuitry that includes the amygdala and orbitofrontal cortex (OFC). Defining the underlying mechanisms by which this orbitofrontal-amygdala circuit contributes to distinct aspects of affective processing will help us to understand the underlying behavioural and social deficits in these disorders. It will also help us to develop new treatments and target current treatments more effectively. This Programme will investigate the neural and neurochemical substrates of emotional regulation focussing on the OFC and the amygdala and their modulation by the neurotransmitter, serotonin. Major components of emotions are the physiological responses that accompany behaviour including autonomic, neuroendocrine and somatic. These changes in the internal state of the body anticipate, facilitate and accommodate the consequences of our actions. Thus, key cardiovascular variables, namely heart rate and blood pressure will be monitored alongside behaviour. We hypothesise that distinct elements of the orbitofrontal-amygdala circuit are involved in regulating our emotional reactions to cues in the environment that predict appetitive and aversive stimuli, as well as in regulating our instrumental actions, guided by those cues, to obtain or avoid such stimuli. We will assess the role of distinct sub-regions of the OFC in these different aspects of regulation and determine whether such processing is independent, or not, of affective valence. We will also identify the key role played by serotonin, both at the level of the OFC and at the level of the amygdala, in modulating these different aspects of regulation in both the appetitive and the aversive domain. Particular attention will be paid to how dysfunction within the orbitofrontal-amygdala circuit contributes to anxiety and whether changes in serotonergic modulation of this circuit underlie individual differences in anxiety.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Behavioural and Clinical Neuroscience Institute (BCNI)
Funder: Medical Research Council

Abstract: The Behavioural & Clinical Neuroscience Institute is an interdisciplinary group of neuroscientists in the University of Cambridge working together to understand the behavioural, cognitive and neurobiological basis of psychiatric and neurological disorders with a view to improving treatment of these disorders in the medium term. The proposed research is described in relation to four guiding themes: translation, traits, treatments and training. Translation means combining pre-clinical studies of rodent and primate disease models with experimental medicine studies in healthy volunteers and carefully characterised patients to delineate clear conceptual connections from animal models to clinical syndromes. Traits denotes our intention to identify behavioural and neurobiological markers of disease that may cut across traditional diagnostic boundaries and/or mediate genetic risk for disorders (endophenotypes). It also highlights our focus on mathematical analysis of complex networks (connectomes) in animal and human brain systems Treatments indicates our long-term scientific focus on neuropsychopharmacology and our growing success in working with industrial partners to evaluate drug mechanisms of action or to apply innovative experimental techniques in the preclinical and early clinical development of new compounds for CNS disorders. Training refers to our plan to build on a strong track record of student achievement in the prior period by creating a distinctive PhD and MPhil training programme in translational neuroscience. Bibliometric and other outcome analysis indicates that the BCNI has already achieved significant international impact in relation to these objectives. In the next 5 years, we are seeking support to foster and enrich the strong inter-disciplinary research culture of the BCNI, and to build on our underpinning capabilities in relation to PET, animal neurophysiology and MRI, computational neurobiology and neurocognitive genetics. We are requesting direct costs for key administrative, technical and scientific support posts; for 3 PhD studentships per year; and for consumable costs related to the marmoset breeding colony and animal and human neuroimaging. The University of Cambridge is committed strategically to the mission and sustainability of the BCNI and this is reflected both by several major infrastructural investments in the previous period and by a substantial financial contribution to the next period of funding. On this basis, we anticipate making a meaningful difference to the understanding and treatment of a wide range of mental health and brain disorders, including addiction, ADHD, neurodegenerative disorders, OCD, depression and psychosis.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Neuronal- and systems-level understanding of spatial and episodic memory.
Funder: Medical Research Council

Abstract: Our memories are critical to who we are, and depend on the hippocampal formation (HF) and its interactions with other areas. Damage or dysfunction in this system in dementia, epilepsy, stroke, or posttraumatic stress disorder (PTSD) can cause debilitating mnemonic impairments. The precise neuronal and systems-neuroscience mechanisms supporting memory are unknown, leaving a gap between molecular and physiological knowledge of neurons and synapses and behavioural, structural and electrophysiological measures in human health and disease. To bridge this gap, I propose a convergent series of behavioural, neuropsychological, functional neuroimaging and electrophysiological experiments in healthy volunteers, neurological patients and behaving rodents, integrated via computational modelling. I will use spatial memory as a model system, using similar tasks in humans and rodents, to begin to understand the neural mechanisms of episodic memory and how they fail in conditions such as dementia and PTSD. I aim to build a quantitative computational understanding of: i) The neuronal representations underlying memory for environmental spatial locations; ii) The dynamics of these representations, focussing on rhythmicity in the theta band; iii) How novelty affects the neuronal mechanisms of memory, including the creation of new representations; iv) How the mechanisms of spatial memory extend to episodic memory, including the effects of traumatic content or neurological damage. Proposed research includes: 1) Electrophysiological recording and 2-photon microscopic calcium imaging of the activity of place cells and grid cells in rodents navigating in open environments and in head-fixed virtual reality; 2) Testing my computational model of how place cells and grid cells represent environmental locations, and developing it to include the effects of novelty, development and reconsolidation; 3) Extending the model to human spatial memory and the effects upon it of novelty, neurological damage and Alzheimer?s dementia, using fMRI and studies in neurological patients; 4) Understanding the role of theta-band rhythmicity in neural computation and the coordination of processing across brain regions, using magnetoencephalography in healthy volunteers and intracranial recording in epilepsy patients; 5) Extending the model to include the role of the HF in episodic memory: using fMRI to whether the HF supports recall by providing: attractor dynamics for recall; conjunctive codes for binding together the disparate elements of an event; pre-existing contextual associations for the formation of new memories. 6) Understanding the interaction of the HF with the amygdala and sensory systems in supporting memory for context and content of traumatic /fearful memories, and how this fails in PTSD.


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