NIHRDataInsights/HRCSData huggingface dataset:
Title: Energy filter with direct electron detector for electron cryo tomography
Funder: Biotechnology and Biological Sciences Research Council

Abstract: The field of cryo-EM is increasingly important in molecular and cellular biology, owing to advances in hardware and software that improve image quality and experimental efficiency. Its scope has expanded to include three-dimensional structure determination over a wide range of samples from sections of tissues, to cell regions, isolated organelles, and individual macromolecular assemblies. In particular, new biological insights arise from structure determination of macromolecular machinery in its native cellular context. However, cellular imaging is limited by sample thickness, because inelastic scattering of electrons gives a high background that obscures structural information in the images. This background can be removed using an energy filter. Earlier generations of electron energy filters such as our current model are very slow, and alignment is difficult and unstable, causing a loss of resolution. Here we request a state-of-the-art, high-resolution post column electron energy filter and associated electron detector for our Polara microscope. Since cryo-EM operates at the limits of detection for delicate biological structures, advances in energy filters and detectors make a vast difference to feasibility, resolution and throughput of data collection, and consequently to the biological insights that can be derived from the experiments. We have recently dramatically expanded our research using cellular electron tomography and will continue to increase our activity in this area. Major projects that now require an advanced energy filter include: studies of intracellular pathogens (e.g. Malaria, Chlamydia, Toxoplasma); bacterial secretion systems in intact cells; phage-bacteria interactions; killing of infected and transformed cells at the immune synapse; neuronal migration and intracellular transport; studies of cellular amyloid deposits. Improvements in biological output resulting from improved detection lead to a much more effective use of expensive facilities.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: NEUROLOGICAL;INFLAMMATORY AND IMMUNE SYSTEM;INFECTION
Title: 4 year PhD in clinical neurosciences: Music and dementia: testing the neural prediction paradigm
Funder: Brain Research UK

Abstract: This is a 1 + 3 year studentship, where the student spends one year rotating between different labs before deciding on their PhD project, which commences in year two. Diseases such as Alzheimer’s and frontotemporal dementia often present initially with complex alterations of social and emotional functioning that are difficult to measure and track reliably, precluding early diagnosis and the design of effective treatments. These complex dementia symptoms may reflect a more fundamental problem in making predictions about the world and other people and in reacting appropriately to unexpected events. In this project, the student will probe this fundamental brain process using music: a ubiquitous tool that relies on ‘rules’ we all expect automatically, so that going against expectation (breaking the musical rules) is heard as a ‘duff note’. She will compare the responses of patients with Alzheimer’s disease and frontotemporal dementia when they make decisions and react physiologically to expected and unexpected musical events and will determine where these responses arise in the damaged brain using functional brain scanning. By using music as a model, she will uncover building blocks of complex symptoms in these dementia diseases and identify new markers that could be used in the future to develop treatments.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: NEUROLOGICAL;MENTAL HEALTH
Title: Using economic theory to understand children's risky visuomotor decisions
Funder: Economic and Social Research Council

Abstract: In playgrounds, traffic and around the house, we are at continuous risk of bodily injury. Children are particularly accident-prone, as reflected in the disproportionally high accident-rates of pedestrians aged 15 year and younger. In recent years many researchers, including myself, have made considerable strides in understanding how visuomotor abilities improve across development. Despite these advances in understanding, current approaches do not consider how children adjust for their changing abilities to avoid unnecessary bodily risk during everyday visuomotor decisions. For example, children are less efficient than adults at avoiding incoming traffic when crossing busy roads. Do they account for this correctly by waiting for larger gaps between cars before crossing? Economic decision-making theories will be employed to model children's visuomotor choices. Economists identify the best financial investments by trading-off probabilities of positive and negative monetary outcomes. Likewise, such tactics can identify the best movement strategy (e.g., when to cross) that maximises safety and efficiency (e.g., avoids accidents but utilises safe gaps in traffic). This has proven very effective for modelling mature visuomotor behaviour, showing that adults often choose movements that optimise performance. Recently I pioneered this approach with children, showing that children aged 6 to 11 years make riskier visuomotor choices than adults during manual reaching. To understand and reduce the effects of risky action selection on childhood injury, we must characterise more broadly how visuomotor decision-making develops, and understand which neurocognitive processes drive this change. A combination of precise behavioural tests, mathematical modelling and neuroimaging will be used to address these fundamental questions. This proposal consists of 3 main objectives that each form a necessary step towards understanding children's movements under real risk in real world situations; These are to (1) characterise children's risky visuomotor decisions in realistic circumstances, including whole-body movements and poor eye-sight, (2) identify which basic mental processes underlie children's immature visuomotor choices, and (3) investigate how these might be improved through training. By characterising changes in visuomotor decision-making in detail at the behavioural and neural level, these objectives will significantly advance our understanding of the developing visuomotor system in action and the mechanisms of visuomotor decision-making. Moreover, this project has great translational potential for improving childhood safety and well being in everyday life, by informing educational programs and generating new ideas for interventions to improve safety.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: NEUROLOGICAL;MENTAL HEALTH
Title: Control of Attention by the Motor System: A Motor Bias Theory of Attention
Funder: Economic and Social Research Council

Abstract: Humans must process an overwhelming amount of visual information with limited cognitive resources. Spatial attention allows us to select the relevant information. A metaphor for attention is that of a spotlight; only things within the 'beam' of attention are processed. A widely held view is that control of the spotlight is implemented by the motor system. If we wish to attend to something, we plan (but don't necessarily execute) an action that would orient the eyes or hands to that thing. This 'Premotor' theory of attention has been very influential, but does not explain the full range of empirical data. This project will test a new Motor Bias theory of attention which offers a new explanation of the relationship between motor control and attention. Specifically, it is argued that movement preparation influences attention in a stochastic fashion, such that attention is more likely to be allocated to movement goals when (a) the same goal is being selected by more than one effector system, (b) the movement is close to being initiated and (c) the organism is confident that the movement will reliably acquire the desired target. The project aims to precisely characterise the interaction between attention and the motor system by testing these principles. Understanding the psychology of attention will also inform the development of novel rehabilitation techniques for patients with neuropsychological deficits of attention.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: NEUROLOGICAL;MENTAL HEALTH
Title: Listening effort and multilingual speech communication: Neural measures of auditory and lexical processing by adults and older children
Funder: Economic and Social Research Council

Abstract: People feel like they need to "listen harder" when communicating in a second language, but it isn't clear how this effort changes the brain processes involved in recognising speech. Our initial research has produced a surprising finding; we tested people who were trying to listen to a talker in a noisy background (i.e., a distracting talker), and found that auditory areas of the brain are better at picking out the target talker when people are listening to a second language than their first language. We did this by recording neural activity (electroencephalography; EEG) and measuring how it becomes entrained to the acoustics of speech. Although people would normally be expected to perform better when listening to their first language, we think that second-language listeners had more selective auditory processing because of their additional listening effort. We found related effects for neural measures of word recognition in the same task, and think that we've found mechanisms that allow second-language learners to partially compensate for their speech recognition difficulties. In this grant project, we will expand our investigation in a series of studies that manipulate the acoustics of speech, and compare how speech is recognised in first and second languages by speakers of English and Korean. Furthermore, we will test adults who learned both languages at the same time when they were young children, adults who learned their second language later in life, and older children who are in the process of learning both languages. Our goals are to understand how people can use listening effort to compensate for their difficulties with second-language speech, and examine how this ability develops and relates to proficiency. This work is important for understanding how people apply their processes and structures for language during everyday speech communication, and is relevant to a wide range of difficult listening conditions (e.g., hearing impairment). The work will also advance our scientific understanding of how new measures of neural entrainment for speech relate to practical aspects of speech recognition.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: NEUROLOGICAL;MENTAL HEALTH
Title: Awareness of the bodily self in vicarious perception
Funder: Economic and Social Research Council

Abstract: People with mirror-touch or mirror-pain synaesthesia literally feel a sensation of touch or pain on their own body when watching somebody else being touched or in pain. While unconscious vicarious perception occurs in most healthy adults (observed as neural and bodily responses to others' experiences), these types of synaesthesia represent an extreme case of conscious vicarious perception. Mirror-touch and mirror-pain synaesthesia have previously been linked with heightened empathy and social perception abilities, and therefore provide a unique opportunity for insight into the mechanisms underlying social processes in everyone, and provide implications for interventions where there may be impairments in this domain. These individual differences in vicarious perception raise a further question: if we represent the experiences of other people (through changes in brain activity, heart rate, emotion, etc.) as well as our own, then how do we maintain a coherent sense of self? Work conducted during my PhD addressed this problem, with a focus on processes related to awareness of one's own body. This work revealed significantly increased depersonalisation (the sense of detachment from the bodily self) and interoception (awareness of one's own internal bodily states) in mirror-pain synaesthetes compared with controls. The findings have important implications for the role of bodily self-awareness in social interaction in typical adults. For instance, since mirror-touch and mirror-pain synaesthesia are associated with heightened empathy, atypical bodily self-awareness in these individuals implicates embodied processes underlying empathic understanding in all of us. This fellowship will ensure that these research findings are disseminated to academic and public audiences in order to further the field of research, and so that the findings can impact on future decisions in industry. This will be achieved through academic and non-academic publications, and a larger public engagement event, which will reach individuals unfamiliar with the field of research. Significant findings from the PhD thesis will be followed up in pilot studies investigating bodily self-awareness in vicarious perception. While data from the PhD thesis indicates greater self-reported interoception in a group of mirror-pain synaesthetes compared with controls, it remains to be seen whether this difference will be found on objective measures. A second experiment will use EEG methods to explore whether impairments in self-other distinction shown by individuals with high depersonalisation are seen in mirror-touch and mirror-pain synaesthesia. This research project will facilitate planning and pilot data for a future grant application, which will allow this line of research to be continued.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: NEUROLOGICAL;MENTAL HEALTH
Title: Infant play and the development of executive function: Implications for policy and practice
Funder: Economic and Social Research Council

Abstract: My fellowship will be focused around assessing the theoretical and practical implications of the findings from my PhD research, and disseminating those findings to policy makers and the public. A primary aim of my fellowship will be to achieve impact through the dissemination of findings from my PhD, regarding the importance of mother-infant play. I will present my findings to the public through events such as The Festival of Ideas and The Science Festival, and through an online blog and/or an article in a magazine aimed at a general audience. I will present my findings to politicians and policy makers through one or more briefing events and contributions to written parliamentary briefings. In 2015, I undertook a 3-month fellowship at The Parliamentary Office of Science and Technology in Westminster, and I will liaise with people I worked with there to determine the best way of communicating my findings to MPs and policy makers, and to arrange at least one briefing event in London. I will measure the impact of my activities through feedback forms at events, data on distribution of magazines and written briefings, and blog view counts. I will complete the writing up of the findings from my PhD for publication in peer-reviewed academic journals. Specifically, an article describing my main findings will be submitted to a special issue of Metacognition & Learning on preschool children's development, and a review article about the role of play in development will be submitted to Educational Psychologist or Educational Research Review. The review article will also be used to inform and develop a funding application to the ESRC New Investigators Scheme. A small portion of the time (approximately 15%) will be spent completing the analysis of some additional data collected during my PhD, which was not included in my thesis. This additional data involves mother-infant play during book reading, and the analysis could strengthen my main PhD findings and provide enhanced guidance for parents and politicians. Finally, I will engage in a small amount of teaching during the fellowship. This will improve my career prospects as a university lecturer, and develop my public speaking and presentation skills.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: NEUROLOGICAL;MENTAL HEALTH
Title: Feasibility demonstration of temporal interference stimulation for non-invasive deep brain stimulation therapy
Funder: Wellcome Trust

Abstract: Brain stimulation technologies can help millions of people around the world who suffer from psychiatric and neurological disorders. Those technologies that target deep brain regions require to insert electrodes into the brain and hence are limited by the high risk to the patients. Dr. Nir Grossman and colleagues in Imperial College and MIT have developed a new brain stimulation strategy, called temporal interference (TI) stimulation, that can target deep brain structures non-invasively. The non-invasive strategy has the potential to change the risk-benefit profile of deep brain stimulation therapy and since it does require chemical or genetic manipulation of the brain it may be rapidly adopted to clinical use. This pathfinder project will use both modelling and physics experiments to characterize the brain targets that can be best addressed by the temporal interference stimulation. https://www.newscientist.com/article/2112921-electric-fields-can-stimulate-deep-in-your-brain-without-surgery/


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: NEUROLOGICAL;MENTAL HEALTH
Title: HEalth And Dementia outcomes following Traumatic Brain Injury (HEAD-TBI).
Funder: Chief Scientist Office, Scotland

Abstract: There is growing recognition that traumatic brain injury can lead to a lifelong impact on health, including a higher risk of dementia. Indeed, it is estimated that around 3% of dementia cases in the community are due to brain injury. Notably, poor health outcomes after brain injury include not only dementia. A wide range of conditions are observed in brain injury survivors, many of which also increase dementia risk. As such, our theory is that the increased dementia risk associated with brain injury may be due to both the direct effect of the injury on the brain and the indirect effects of wider, poor health outcomes after brain injury which, in turn, increase dementia risk. To test this theory we propose a series of interlinked studies titled “HEalth And Dementia outcomes following Traumatic Brain Injury (HEAD-TBI)“. These studies are designed to compare differences in health between people with and without a history of brain injury and how these might contribute to dementia risk. This will give us a better understanding of the link between traumatic brain injury and dementia, which will help us identify ways that we might act to reduce this risk. The aims of HEAD-TBI, therefore, are to:  Analyse risk of dementia and other neurodegenerative diseases in those with a history of traumatic brain injury compared to uninjured individuals from the general population.  Analyse common causes of death and common health issues, including mental health, in those with a history of traumatic brain injury compared to uninjured individuals from the general population.  Analyse brain scans to look for changes that may help us understand who is most at risk of dementia following a traumatic brain injury. We will use unique, comprehensive digital health records and death certificate data, together with diagnostic brain scans available for research. Patients with a history of brain injury will be identified from a search of available health records. The lifelong health outcomes and brain scans in these individuals will then be compared to people from the wider population without a history of brain injury, matched to our brain injured patients by year of birth, sex and degree of social deprivation. As results emerge these will be presented at appropriate multi-disciplinary research conferences and made available as draft manuscripts through open access platforms before formal, peer-reviewed journal publication. We anticipate HEAD-TBI will have wide interest and, when appropriate, we will leverage news and social media communications and participate in broad public engagement events


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: NEUROLOGICAL;MENTAL HEALTH
Title: The experience of patients with Parkinson’s Disease Psychosis: A Qualitative Study.
Funder: Barts Charity

Abstract: Introduction: Parkinson?s disease (PD) was long thought to be primarily a movement disorder and as such, research has focused on symptoms arising from difficulties with movement and treatment for these. However, PD can equally be thought of as a chronic neuropsychiatric condition with a myriad of psychiatric symptoms associated with its progression. There has never been any qualitative research into PD patients? experiences of PD psychosis. Aims: To explore the experiences of patients with PD psychosis in a subset of the patients enrolled in the East London Parkinson?s Disease (ELPD) project using qualitative methods. Methods: Patients will be identified from those who are already enrolled in the ELPD project. The number of patients to be recruited will be determined by data saturation as experienced by the interviewer, however, we are expecting to recruit between 10-15 patients based on comparable published literature. The study will intentionally recruit patients from diverse socioeconomic and cultural backgrounds to ensure a representative sample from the East London population. The sampling frame will identify patients who are experiencing symptoms of PD psychosis as per Ravina et al, (2007) which includes illusions, false senses of presence, hallucinations, and delusions. A clinician will review the medical notes to confirm appropriate chronology and duration of the symptoms. Patients with other causes of psychotic symptoms will be excluded. The interview will be steered by a pre-defined topic guide, intended to highlight patients? experiences of the symptoms included in the diagnostic criteria for PD psychosis. Intended Analysis: The anonymised interviews will be professionally transcribed and exported into Nvivo. The data will be analysed using a reflexive thematic analysis approach (Braun & Clarke, 2019). This will involve the established stages of familiarising oneself with the data, ?coding? the data, identifying themes and analysing the themes to draw inferences.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: NEUROLOGICAL;MENTAL HEALTH