NIHRDataInsights/HRCSData huggingface dataset:
Title: Developing a patient-centred evidence-based intervention to address distress in the context of chronic MSK pain
Funder: Versus Arthritis

Abstract: People with chronic musculoskeletal pain are often diagnosed with co-morbid depression, and commonly prescribed antidepressants. However, there is strong evidence to suggest that distress in the context of pain is qualitatively different from clinical depression, and that patients may not want, and do not respond well, to psychopharmacological interventions. For primary care professionals (particularly general practitioners, GPs) this poses a dilemma on how best to manage patients’ psychological distress within their own care, and who to refer to. We therefore plan a body of research in three stages: Stage 1) A qualitative study, conducting semi-structured interviews with patients and general practitioners which will enable and exploration of how both these groups understand pain-related distress in contrast to ‘depression’, how patients and practitioners negotiate and make decisions about diagnosis, management, and referral pathways, and which interventions patients have found most useful and acceptable. Stage 2) A cross sectional questionnaire study of people with chronic MSK pain and people with clinical depression will use a latent profile analysis approach to identify items that characterise pain-related distress and distinguish it from clinical depression. The identification of a set of reduced questions that predict pain- related distress will be used to inform eligibility and an education content in stage 3. Stage 3) We will develop a new framework of pain-related distress from the results of these studies, and then develop, and carry out proof-of-concept testing of, a new patient-centred intervention to reduce pain-related distress. We will design an intervention, informed by stages 1 and 2, developed in partnership with our patient advisory group (PAG). We will test our intervention for acceptability and proof of concept with 20 patients recruited from NHS settings, including primary care and physiotherapy clinics. The final output of this project will be an acceptable, patient-centred and patient-led intervention that is likely to include an on-going interactive bespoke website, combined with personalised and individual advice and support in social reactivation and managing pain and mood.


Research activity codes: 5.6 PSYCHOLOGICAL AND BEHAVIOURAL;6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH;MUSCULOSKELETAL
Title: MS news &amp; research
Funder: Multiple Sclerosis Society

Abstract: What is the project about? Some people with MS leave their jobs earlier than people who donâ€™t have MS. This could be for many different reasons. MS comes with uncertainties and can be unpredictable which could make managing a job and symptoms difficult. Dr Ford has already led research in this area to develop a tool which helps to show when someoneâ€™s job may be coming under threat. This three-year project will explore what can be done to help people with MS stay in work._x000D_ _x000D_ 200 people with MS who are working will take part in the project. They will complete a set of questionnaires four times over two and a half years to explore how many people leave their job in this time and what the people who stay in work have in common._x000D_ _x000D_ How will it help people with MS?_x000D_ _x000D_ This work could lead to a better understanding of why some people with MS leave their jobs early and could lead to better ways of supporting them to remain in work.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: The role of Dkk1 in Amyloid-beta mediated effects on dendritic spines and long-term depression
Funder: Alzheimer's Research UK

Abstract: Brain function depends on the formation of functional neuronal circuits created by connecting nerve cells together through specific junctions, called synapses. Loss or dysfunction of synapses contributes to diverse neurological disorders. Recent studies have revealed that synapse loss occurs at early stages of Alzheimer’s disease (AD) and that this process might contribute to cognitive and memory deficits in AD. Our research group studies the function of Wnts, proteins that promote the formation, growth and maintenance of synapses. We discovered that a secreted Wnt antagonist, Dkk1, induces synaptic loss and deficits in long-term memory in mice expressing high levels of Dkk1. Dkk1 is elevated in AD brain and in mouse models of AD. Importantly, we found that Amyloid ß (Aß) rapidly increases Dkk1 levels and that Dkk1 blockade suppresses the synaptic effects of Aß. Thus, Dkk1 is necessary for Aß-induced synapse loss and therefore Dkk1 may contribute to cognitive decline in AD. In this proposal, we will investigate the contribution of Dkk1 to Aß-mediated synaptic changes in the hippocampus, a brain area important for learning and memory. We will also screen for small molecules that modulate Wnt signalling with the aim to identify new therapeutic avenues for the treatment of AD.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Using network analysis to understand why patients with small vessel disease suffer cognitive impairment.
Funder: Alzheimer's Research UK

Abstract: Small Vessel Disease (SVD) damages small brain blood vessels and is the most common cause of vascular dementia making it a huge health problem. We don’t fully understand why patients with SVD develop cognitive impairment. One theory is that damage to brain pathways (white matter tracts) disrupts complex circuits connecting different brain regions (brain “networks’) resulting in different regions not able to function together in an organised fashion. Advanced MRI techniques allow us to study brain damage in SVD, particularly a sensitive technique called DTI which allows us to see which pathways are damaged. Recently a new analysis technique has become available (network analysis) which allows us to directly determine whether ‘brain networks’ are disrupted. We will apply this technique to patients with SVD and look at whether disruption of networks occurs in the disease and whether this causes disrupted brain function. This project will provide information on how patients with SVD develop cognitive decline which could help us develop better treatment approaches. In addition MRI with network analysis provides a promising technique which can be used to monitor change in SVD patients and study the effects of therapeutic interventions.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Emergence of cognitive impairment in an Alzheimer's Disease mouse model: the role of NMDA receptor currents.
Funder: Alzheimer's Research UK

Abstract: Current evidence suggests that memory loss in early Alzheimer’s disease (AD) starts when amyloid-beta (Ab) and tau proteins interfere with the capacity of neurons to modify the strength of their connections (synaptic plasticity), an indispensable brain function for storing new memories. However, the events that set off the disease process are not well understood and available treatments are only modeslty effective. To understand the earliest mechanisms of AD, we will use a mouse model in which overproduction of Aβ can be switched on and off. The student will use a combination of behavioural and physiological experiments to link adult-onset memory impairment with synaptic function. The focus will be on glutamate receptors of the NMDA subtype (NRs), which are essential for many forms of learning and memory and known targets of Aβ. Furthermore, the student will investigate whether (early and late) NR changes and memory impairment are reversible, by switching off Aβ production. The results of this work will highlight the timing and relevance of NR modifications to the onset of cognitive impairment. A better understanding of their role in memory loss will allow us to target them more effectively in the search for drugs that modify AD symptoms or progression.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Systems Cognitive Neuroscience of Healthy Ageing: Population-Representative Studies of Functional Plasticity and Neural Change
Funder: Biotechnology and Biological Sciences Research Council

Abstract: A population-based cohort of 3000 adults will be recruited with demographic and basic cognitive assessments (LoLa3000 cohort). Of these, 700 will be selected for the Virtual Brain and Behaviour Bank (LoLa700 cohort) comprising structural and functional neuroimaging (MRI & MEG), standardised neuropsychological tests, and specialised cognitive tests. From the multi-faceted neuroimaging data, several measures of neural structure and function will be derived, using a broad array of analysis tools, techniques and expertise. Structural MRI data will be analysed using SPM8 and the Dartel toolbox; FMRI using SPM8; DTI using FSLs probabilistic tractography; connectivity with PPI & DCM; and custom Matlab. MEG data will be analysed using tools from Elekta Neuromag, SPM8 (including DCM), Fieldtrip; and custom Matlab. Our 'automatic analysis' parallel processing tools will be used to facilitate rapid processing of the large quantities of MRI and MEG data. We will measure both local neural integrity and neural integration across cortical regions taking care to control for factors that are not related to neural function but which influence neuroimaging, such as changes in neuro-vascular coupling. The derived neural measures will be related to age and performance, and to current models from cognitive neuroscience. On a subset of 280 adults (LoLa280 cohort) further investigations of neuro-cognitive functions will use FMRI, MEG/EEG and further behavioural testing. These will allow investigation of the effect of ageing on the specific cognitive domains of Attention, Language, Motor & Learning, Memory, Emotion, and the relationship between these different domains. Formal statistical models will be used to examine the changes that occur with healthy ageing, and the reorganisation in terms of strategies and structures invoked to compensate for them. This approach offers hypothesis-driven insights into healthy ageing that are relevant to the general population.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: The effect of D-alanine and a prebiotic on rat brain N-methyl-D-aspartate (NMDA) receptors and executive function
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Brain N-methyl-D-aspartate receptors (NMDARs) are integral to the neural circuitry underpinning memory and cognition. D-alanine, an NMDAR co-agonist, is thought to arise from the natural breakdown of bacteria in the mammalian gut. Brain levels of D-alanine are low compared to the major NMDAR co-agonist D-serine. A repeated administration of D-alanine results in its stable accumulation in the cerebral cortex. This build up of brain D-alanine may lead to long-term augmentation of NMDAR activity, and possibly, improvement in executive brain functions mediated by the frontal cortex. Thus, D-alanine intake may be beneficial in some situations, such as aging, where NMDAR function progressively declines. In preliminary experiments we observed elevated levels of phosphorylated NR1, NR2B, but not NR2A, NMDAR subunits in the rat frontal cortex after a 2 week administration of D-alanine, or the prebiotic fructo-oligisaccharide (FOS), which promotes lactobacilli growth in the gut. We know plan to examine the functional consequences of elevated NMDAR subunit phosphorylation by D-alanine and FOS at the level of electrophysiology and behaviour. Our proposed research will: 1) Test if rats fed for 2 and 8 weeks with D-alanine and FOS show improvements in the attentional set-shift task which is a measure of medial prefrontal cortex function; 2) measure rat brain NMDAR phosphorylation after behavioural tasks; 3) confirm if FOS administration leads to increased levels of gut bacteria and brain D-alanine; 4) evaluate NMDAR activity in the frontal cortex of experimental and control rats with in vivo electrophysiology; 5) explore in cell cultures the direct effects of D-alanine on the expression of NMDARs and the signalling pathways (ERK-MAP kinases, CREB) which are modulated by NMDAR activation. If successful, the study will provide novel insights into NMDAR modulation, and may reveal the utility of D-alanine and prebiotics in the maintenance of healthy cognitive function.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;3.3 NUTRITION AND CHEMOPREVENTION
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Emotion regulation and well-being as we age: Implications of cognitive decline and prefrontal atrophy for corticolimbic function
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Ageing is associated with age-related brain atrophy, affecting regions such as the prefrontal cortex (PFC), involved in executive function (EF), more strongly than other cortical regions of the brain. A lateral PFC network similar to that involved in EF has been identified in emotion regulation whilst individual differences in recruitment of medial parts of the PFC have been associated with wellbeing. This suggests that neural loss in the PFC should impact emotion regulatory ability and wellbeing. However, some studies suggest sustained emotion regulatory ability with ageing, although it is unknown the extent to which older adults in these studies experienced neural tissue loss and/or cognitive decline. We propose to study 70 adults aged 55-85, 35 of whom have experienced cognitive decline, as well as 20 younger adults. We will collect structural and functional MRI augmented with psychophysiological measures of regulatory success, whilst participants perform an emotion regulation task. Behavioural performance on cognitive tasks will be assessed, and salivary cortisol provided over the course of 3 days, and self-reported wellbeing will also be obtained. We will test whether functional plasticity, characterised by the recruitment of a different, more medially located, PFC network, underlies a maintained ability to regulate emotions in older adults, even those experiencing cognitive decline and lateral PFC atrophy. A lateral-medial shift in PFC recruitment is predicted to be more marked with increasing atrophy in individuals whose wellbeing is maintained. Given the paucity of data on cognitive decline and emotion regulation, we will consider the alternative scenario that individuals experiencing cognitive decline and PFC atrophy have a compromised emotion regulatory ability. The findings are expected to advance our understanding of factors impacting older adults' ability to adapt to cortical atrophy and to inform intervention programmes to promote successful ageing.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Cognitive and Motor Skills: Adapation over the Lifespan, Neural Signatures, and Transfer from Lab to Field
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Sensory information is used for motor control not only for 'online' guidance, but is also used to construct representations that are used in the skilful, feedforward and automatic execution of movements on the basis of prior experience. While most work in this area has focussed on learning the kinematics of action, there is comparatively little work on the automation of the rules that guide actions. Saccadic eye movements serve as excellent models with which to investigate the automation of action selection and action kinematics under stringent experimental control, and the variation of these abilities across the lifespan. The ability to select eye movements appropriately is relatively poor in children. In older people, the increasingly inefficient mechanics of the oculomotor apparatus render it prone to kinematic error. However, some motor skills are acquired and retained more effectively by elite sportspeople. Here, I propose to use unskilled individuals and elite cricketers across the age span to investigate the effects of aging and training on the selection and execution of eye movements. I will use saccadic adaptation and conditional, rule-guided eye movements in both the laboratory and the field, and the cerebellar basis of such learning will be investigated using functional MRI. Here, this project builds on previous work to achieve three main goals: (i) We aim to understand how the ability to learn rules that govern eye movements to automatic performance levels changes from childhood through to old age, and whether a history sporting activity that exercises eye-movement skills contributes to performance advantages in later life; (ii) We also aim to relate performance to haemodynamic signatures of cerebellar plasticity, and (iii) To study the eye movement strategies that are automatically implemented by highly skilled batsmen, and determine whether gaze-contingent feedback training of the same skills in unskilled individuals can raise performance.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Understanding age-related changes in processing facial emotion
Funder: Biotechnology and Biological Sciences Research Council

Abstract: It is estimated that, by 2060, one quarter of the British population will be over 65, many of whom will still be working. Over a lifetime, the brain ages as dramatically as the body (Grady, 2008), manifesting itself in the decline of the basic and essential task of interpreting social signals. Research has established that ageing adults show specific differences in the emotional interpretation of facial expressions, particularly anger. We will study how oscillatory networks in the ageing brain extract and further process visual information to recognize facial expressions of emotion at different intensities. Specifically, we will quantify changes in the information processing parameters of naturalistic, dynamic expressive faces, in groups of younger (20-35 years), middle-aged (40-55) and older (60-75 years) adults. To this achieve this aim, we will combine a state-of-the-art framework blending a unique Glasgow-based platform that precisely controls the photo-realistic biological motion of faces with other developments in applications of information theoretic mathematics to analyses of brain signals (i.e. Mutual Information; Transfer Entropy, Schyns et al., 2011). We will apply the information theoretic measures to behavioural variables (e.g. emotion classification responses and reaction times) and to the nodes of cortical networks reconstructed from oscillatory MEG sources (guided by spatially resolved fMRI). We will seek to further our understanding of the dynamic face information required to classify facial expressions and of the brain regions recruited to process this critical information, and how these brain regions process and transfer information between stimulus onset and categorization response in cortical networks. This focus on information processing will directly test the dedifferentiation hypothesis-i.e. the idea that an initially differentiated brain progressively recruits other regions as a compensation strategy to counteract the effects of aging.


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 Multi-innervated Dendritic Spines in Memory Formation in Ageing
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Hippocampal ageing is associated with impairments in long-term potentiation (LTP). However, despite LTP deficits, aged rodents can form memory, raising the question as to which mechanism could be responsible? Our recently published study proposes a hypothesis for this. We have shown that in a knock-in mutant mouse lacking the autophosphorylation of alphaCaMKII that hippocampus-dependent memory can be formed despite fully blocked LTP and that this memory formation depends on the generation of multi-innervated dendritic spines (MIS), a particular type of synapse where a dendritic spine receives more than one presynaptic input. Further, we found that MIS-dependent memory is less flexible than memory relying on intact LTP. Here, we will test the hypothesis that in old age memory formation depends on MIS generation. We will train young adult and aged C57BL/6 mice in contextual fear conditioning and the Morris watermaze task. This will be followed by a quantitative 3D electron microscopic analysis of synapses and dendritic spines in hippocampal area CA1 and the dentate gyrus. Further, we will manipulate MIS generation by manipulating PSD-95, SAP97 and Kvbeta1.1 expression and to study the behavioural impact. PSD-95 and SAP97 overexpression will be used to increase MIS generation and PSD-95 as well as Kvbeta1.1 knock-down will reduce MIS generation. These molecular biological manipulations will be completed by pharmacological epxeriments that either enhance (NO donors) or reduce (rapamycin) MIS generation. Finally, we will study whether reconsolidation of hippocampus-dependent memory is impaired in old age as predicted by our hypothesis.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Visual motion perception in healthy ageing
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Healthy aging diminishes performance in visual motion perception. Low-level motion perception decreases especially dramatically. The perception of more familiar high-level dynamic stimuli remains relatively intact, although older adults have difficulties integrating local motion and global form as efficiently as younger adults. A potential reason that high-level motion perception is less affected by ageing than low-level motion is that higher-level visual processes compensate for decreased functioning of lower-level visual processes. Plasticity of the functional organization of cognitive and cortical processes occurs throughout life and functional networks that underlie visual perception still undergo reorganization during aging. The goal of the proposed research is to elucidate the perceptual and functional changes underlying visual motion perception in healthy ageing. We will study the relationship between decreased low-level motion perception and high-level motion perception in ageing by correlating performance in low-level visual tasks such as motion detection and direction discrimination with performance in higher-level visual tasks, such as the discrimination of point-light walkers. Further, we will elucidate age-related constraints on high-level motion mechanisms and investigate to what extent local motion and global form information contribute to the perception of high-level visual motion perception. Last, we will explore the underlying neural mechanisms of high-level visual motion processing in ageing and ascertain the brain areas that contribute to high- and low-level motion perception in ageing and their functional connections. The proposed research will combine psychophysical methods and fMRI. In the long run, results from the proposed project will help us to understand the mechanisms underlying motion perception in healthy ageing and lead to a more complete model of the processes underlying visual motion perception in general.


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