NIHRDataInsights/HRCSData huggingface dataset:
Title: Responsibility and Morality within Personality Disorder.
Funder: Wellcome Trust

Abstract: Personality disorder carries heavy stigma. It is associated with crime and deviance. People with personality disorder are often shunned, judged, and blamed. Yet these people come from troubled backgrounds, have low self-esteem,and experience great pain and distress. My research develops a philosophical and scientific framework for assessing the extent to which personality disorder is a moral failing for which people can justifiably be held responsible. I argue that responsibility admits of degrees, and reconcile the idea that background conditions carry some exculpating weight with the idea that people with personality disorder are free agents. Relatedly, I assess therole of self-esteem in the capacity for moral, rational, and prudential behaviour. My framework strengthens an effective clinical approach to personality disorder that treats people with compassion and empathy, yet as responsible and capable of change. It raises questions about the respective roles of science and morality within psychiatry. And it also has important policy implications for the prevention and treatment of personality disorder. I intend to publish scholarly articles based on this research in leading philosophy and psychiatry journals and collections. I also intend to communicate it more broadly, both to high-level policymakers and to ground-level fellow clinicians, via consultation, lectures, editorials, media engagement, and training provision.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: MENTAL HEALTH
Title: Neurobiology of speech communication:cognition, plasticity and social interactions
Funder: Wellcome Trust

Abstract: Functional imaging studies (PET and fMRI) have revealed that human speech is processed along distinct (though interacting) streams, in ways that are analogous to the functional and anatomical auditory streams seen in non-human primate studies. I am proposing a series of studies in which aspects of human speech perception and production are investigated, to identify the neural basis of low level and higher-order control of speech perception, the neural basis of production and perception of speech in different masking contexts, and plasticity and individual differences in speech processing. I am particularly interested in how we can apply these results to the understanding of clinical issues (e.g. aphasic stroke and cochlear implantation), and will address the latter with studies of cochlear implant users and simulations. I also aim to extend this work to consider how the importance of social factors, such as how communicative intent affects the neural regions recruited in addition to those involved in the linguistic processing of speech. This is an attempt to integrate the neurobiology of speech perception and production with themes in social neuroscience, and important link to establish, given the central role of speech as a communication tool.


Research activity codes: 1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH
Title: Investigating the sensorimotor networks in speech perception and production.
Funder: Wellcome Trust

Abstract: How do we understand speech when it can be spoken in a multitude of ways by different speakers and with different accents? One influential theory suggests that we do so by detecting the intended movements that the speaker uses to produce it. Our recent work shows that we can affect the way people perceive speech using a technique called transcranial magnetic stimulation (TMS) to temporarily interfere with the function of the motor system used to produce speech. In this project, we will record brain activity to measure the effects of disruption of the speech motor system on the way the brain detects small differences between speech sounds produced with different articulators. For example, the tongue and the lips are used differently to produce da and ba . Using brain scanning, we will also look at which brain areas are used to produce and perceive these small differences in speech. We want to see if these areas are separate or overlapping and whether there are some areas that p rocess both speech production and perception. This work will help our understanding of how the brain processes speech and shed further light on why people may have speech difficulties, particularly after a stroke.


Research activity codes: 1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH
Title: Glutamate and GABA in adults with autism; an in vivo study using magnetic resonance spectroscopy.
Funder: Wellcome Trust

Abstract: The cause of Autism Spectrum Disorder (ASD) is unknown. However, abnormalities in glutamate and GABA may be central. These are (respectively) the major excitatory and inhibitory neurotransmitters in brain; and both affect brain development and functioning. Until recently we could not directly measure the brain concentration of glutamate and GABA in vivo. Proton Magnetic Resonance Spectroscopy (1H MRS) now allows us to do that non invasively; e.g. without using injections, ionising radiati on, or sedation. We reported pilot evidence that adults with ASD have a significant elevation in the combined signal of glutamate and glutamine (Glx) in brain. However, the magnetic field strength of the MRI scanner, and technical methods, then available did not allow assessment of GABA. New 1H MRS developments now make this possible. Hence we wish to extend our work using these new 1H MRS techniques. We will determine if medication na ve young adults with ASD have a significant elevat ion in glutamate and GABA concentration; and if increases in these neurochemicals are associated with clinical symptoms If successful our work will help us understand the cause(s) of abnormal behaviour in people with ASD, and may identify new treatment targets.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: Can the genotype of the human serotonin transporter (SLC6A4) generate differntial epigenetic signatures over the gene in response to exposure to cocaine?
Funder: Wellcome Trust

Abstract: How does the genotype of the human serotonin transporter alter our behaviour in response to pharmaceutical challenge? In addition to altering the function of the serotonin transporter protein, drugs, such as cocaine, antidepressants and lithium alter actual SLC6A4 gene expression itself. Such regulatory changes may be crucial for medium and long term responses of an individual after drug exposure. Data from the Quinn group suggests these epigenetic changes are potentially differential and based on genotype. This variation could help explain why repeated exposure to cocaine for example, can lead to cumulative-effects that outlast drug exposure and may be considered irreversible


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: Probing visual short-term memory representations with dynamically adaptive imaging.
Funder: Wellcome Trust

Abstract: Four experiments will investigate how the brain stores images of real-world objects in Visual Short-Term Memory (VSTM). These will use a new imaging technique (DAI) that uses brain activity measured in real-time to modify which items are presented to the participant. Visual objects can be characterised by various sensory (e.g. colour, shape) and semantic (e.g. animate) features. We will explore which combinations of these features are represented in different areas of the brain that are known to be important in VSTM. Secondly, we will investigate which features are held in VSTM for different kinds of visual objects, and whether all objects are represented in memory using similar attributes. To do this we will analyse which objects generate similar activity patterns in the brain and how this is related to the features that characterise them. We will also investigate how the brain manages to simultaneously hold information about several different objects in VSTM. Since peopl e differ in their ability to maintain information in VSTM, we will examine how differences in memory capacity relate to differences in brain activity. Finally, we will look at how the brain s code changes and which aspects of the memory are lost when we forget visual information.


Research activity codes: 1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH
Title: Neurobiological factors underlying the onset of psychosis.
Funder: Wellcome Trust

Abstract: Psychotic illnesses, such as schizophrenia, are common, devastating conditions. Although their causes are unknown, research shows that patients with psychosis have increased levels of the chemical messenger, dopamine, in the brain. Other research indicates that psychosis is associated with changes in the structure and function in the medial temporal lobe of the brain. Until now, these two factors have mainly been studied separately. A key aim of this project is to put information on dopamine an d medial temporal lobe function together and discover how they affect each other. We will do this by using different brain scanning techniques to measure dopaminergic and medial temporal activity in people who have a very high risk of developing psychosis in the near future. After scanning these subjects, we will follow them up to find out which of them goes on to develop a psychotic illness. This will allow us to determine which brain factors predict whether someone will later become psychotic. This may ultimately help doctors to identify the people who are most vulnerable to later illness.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: Mechanisms for human auditory cognition
Funder: Wellcome Trust

Abstract: The enhanced work contains three elements that are not funded in the current fellowship (see progress summary in this application and my 2012 annual report). In summary, the proposed enhanced work extends an approach to human auditory cognition (perception and memory) based on stochastic' stimuli governed by statistical rules applied to frequency-time space.


Research activity codes: 1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH
Title: The Management of Alcohol Dependence Syndrome: Autonomy, Compulsion and Ulysses Contracts.
Funder: Wellcome Trust

Abstract: RESEARCH QUESTION ABSTRACT ONLY Alcohol Dependence Syndrome (ADS - sometimes called 'alcoholism') is a very damaging condition. This study aims to find out more about whether people with ADS are capable of mak


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;7.3 MANAGEMENT AND DECISION MAKING
Health categories: MENTAL HEALTH
Title: PREMIUM: A program for effective mental health interventions in under-resourced health systems
Funder: Wellcome Trust

Abstract: The proposed program (?PREMIUM?) aims to define a systematic methodology for the development and evaluation of psychological treatments for delivery by Community and Lay Health Workers and to test this methodology for two mental disorders of global health significance, viz., Depressive Disorder and Alcohol Use Disorders. In the first phase, the program will implement the systematic methodology for development of treatments, derived from three distinct sources of experience and knowledge, to answer two key questions: what are the components of the treatment and how should it be delivered. This phase will comprise a number of sequential steps: synthesis of global and local evidence through systematic reviews and search of the gray literature; determining components of the treatment through consultations with diverse stakeholders; determining an acceptable and feasible delivery model for the treatment through formative research case studies; and testing the intervention in the real world in pilot trials. In the second phase, the clinical and cost-effectiveness of the treatments developed will be evaluated in parallel group randomized controlled trials with primary health care attenders. In the final phase, the findings will be disseminated and a framework for increasing access to these treatments within routine health care programs developed.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL;8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: MENTAL HEALTH
Title: The historical intersection of psychiatry and 'sexual deviation' between 1949-1992: exploring the role of nurses and the experience of former patients.
Funder: Wellcome Trust

Abstract: The aim of this Doctor of Philosophy (PhD) study is to examine the meanings that patients and nurses attached to the 'treatments' to change 'sexual deviation' in Britain from 1949 to 1992, to explore why people received such treatments, how they experienced them, how they affected their lives, and their aftermath. Further, it will focus on a hitherto neglected area by looking in detail at nurses' perspectives on providing these treatments.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: MENTAL HEALTH
Title: The role of the KIAA0319 protein in neurodevelopment .
Funder: Wellcome Trust

Abstract: KIAA0319 is one of the most replicated candidate genes for reading disability (dyslexia). Previous results indicate that the risk haplotype associated with dyslexia leads to a reduction of the expression levels of this gene, and knockdown by RNAi impairs neuronal migration. The KIAA0319 protein is a plasma membrane protein with domains that have been previously described as involved in cell adhesion. Our hypothesis is that this protein mediates neuronal migration through interaction with other p roteins at the cell surface. We propose to further analyse the function of KIAA0319 in neuronal migration and to study its putative role in other processes during neurodevelopment. We will identify interacting proteins, analyse the neuroanatomical effects caused by disruption/blocking of expression of the Kiaa0319 gene in animal models, and study the phenotype of a number of knockout mice, with a special focus on the behavioural effects. Our aim is to understand the different roles that the KIAA 0319 protein has in neurodevelopment and to identify which functions, when altered, may increase susceptibility to reading disability. This information will be useful for diagnostic and therapeutic purposes, and will also contribute to increasing our knowledge about the mechanisms involved in the acquisition of language and reading skills.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: Cellular substrates supporting the mnemonic functions of Papez' circuit.
Funder: Wellcome Trust

Abstract: Anterograde amnesia is the failure to learn new day-to-day information. Damage to two brain regions, the medial temporal lobe and the medial diencephalon, is most consistently associated with this amnesia. Within these regions, it is now thought that the hippocampal formation (temporal lobe) and the anterior thalamic nuclei (diencephalon) are the key structures. Considerable evidence has emerged to suppose that these two structures normally function together to support memory. The proposed r esearch will, therefore, examine the anatomical, electrophysiological and functional properties of hippocampal anterior thalamic interactions in the rat. The starting premise is that these interactions are supported by three, parallel circuits each with different tasks. Anatomical studies will compare the sources of information to the three circuits to test their degree of independence. Behavioural studies will examine the impact of jointly disconnecting all three circuits (postcommissural fornix lesion) and then mapping the effects of selective lesions within the individual circuits against functional predictions derived from our models. Complementary electrophysiological studies will examine how the neuronal activity in the investigated structures determines activity and contributes to memory formation in each region. This research will advance our understanding of brain learning mechanisms and produce more complete explanations of amnesia.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: Franco Basaglia and Mental Health Reform in Italy,1960-2009.
Funder: Wellcome Trust

Abstract: In the 1960s and 1970s a movement developed in Italy in favour of radical mental health care reform. It was led by the psychiatrist Franco Basaglia. The Basaglia movement was particularly critical of large asylums, which they compared to concentration camps. The movement argued that these asylums should be closed. So successful was Basaglia in mobilising support that a law was passed in 1978 which shut down all existing asylums and prevented others from being constructed. Despite the fact that t his was a state law, the reform's impact was very different between regions and cities. Local mental health policies were closely linked to political and social factors, and the local strength of the Basaglia movement. This project aims to write an overall history of this movement (for the first time) but also to examine the legacy of these reforms By looking at individual asylum sites and the ways in which they were transformed, changed or abandoned, the project will look to map out the eff ects of the movement after the 1960s and the 1970s and the 1978 law. Finally, this research is interested in memory - that of patients, doctors and volunteers - and that linked to the physical sites themselves.


Research activity codes: 8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health categories: MENTAL HEALTH
Title: 4 year PhD in Neuroscience - Assessing and modelling the effects of antidepressant medication on the learning of emotional and non-emotional information
Funder: Wellcome Trust

Abstract: This project will use behavioural and neuroimaging techniques to test two competing models of the time lag in clinical effects of antidepressant drugs. Both these accounts predict improvements in learning with antidepressant treatment but critically expect a different balance of effects on emotional versus non-emotional learning processes. A series of studies will use behavioural and neural markers of learning and plasticity in healthy volunteers to explore the effects of drug treatments relevant to depression and anxiety. Ultimately, the aim of the project is to improve our understanding of the mechanisms of action of antidepressant medication with a view to using this knowledge to inform the early-stage development of novel treatment regimes.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH
Title: Defining circuits of the basal ganglia circuits for human action selection and instrumental learning.
Funder: Wellcome Trust

Abstract: An unanswered question in human cognition is the precise role of the basal ganglia (BG) will much recent emphasis on reward processing and reward learning. In recent work we have shown that a disposition to act is strongly encoded in BG. Given these findings it is opportune to re examine the precise role of the basal ganglia in action selection and instrumental learning. 1. Effective connectivity in the direct and indirect pathway is enhanced and reduced, respectively, when an action is required compared to when there is no requirement for action. 2. Increased reward enhances activity the direct pathway for Go trials, and enhances activity in the indirect pathway for NoGo trials. 3. Instrumental reinforcement learning involves changes in effective connectivity in these pathways.


Research activity codes: 1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH
Title: Systems neuroscience: From networks to behaviour - Impact of maternal deprivation on cortical gamma oscillations.
Funder: Wellcome Trust

Abstract: Using a rodent model of early life stress, the ability of cortical circuits to generate neuronal oscillations implicated in cognitive function will be examined. Specific aims to be addressed in cortical slices from control and maternally deprived rats are: 1) What si the impact of maternal deprivation for maternal oscillation generating circuits in a number of critical cortical regions? 2) Can differences between gamma oscillations in control and MD cortical circuits be explained by a reduction in the expression of specific interneuron subclasses? 3) assess the longitudinal impact across lifespan of MD for cortical gamma oscillations.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: MENTAL HEALTH
Title: Reward prediction in health and disease.
Funder: Wellcome Trust

Abstract: Learning occurs in response to errors in our predictions. When we make a prediction that turns out to be wrong we can use this information to guide future behaviour. Schizophrenia is a common and disabling condition in which people suffer from odd beliefs and perceptions. This makes it hard to understand the environment and to make decisions and select actions appropriately There is evidence that disturbances in one of the brain s key messenger chemicals (dopamine) are important in producing th e symptoms of schizophrenia. This same chemical is involved in prediction error signalling, leading to hypotheses that predictions may be disturbed in schizophrenia. Initial studies have produced evidence in favour of this view. Our aim is to explore this hypothesis in a way that is informed by more recent ideas about the nature and complexity of predictions . We propose to explore two important features of reward prediction the adaptability of the prediction error and the sensitivity of predi ction to background environment in people with schizophrenia and in healthy participants in whom we have produced temporary changes in dopamine transmission. The results from these brain and behaviour studies will give us important information about the disturbances underlying schizophrenia.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: MENTAL HEALTH
Title: Mapping and remapping of visual space.
Funder: Wellcome Trust

Abstract: How do we recognise shapes in the outside world? It is tempting to study this with interesting shapes like faces, but Science often advances by studying simple problems first sometimes so simple that they are taken for granted.. Our ability to analyse shapes is underpinned by some very basic processes that we do take for granted, for example extrapolation finding the Pole Star from the pointers of the Plough. True, there are 2D maps in the brain, but these are so distorted that they woul d be useless for plotting purposes, even if we had such a thing as a ruler in the head to put against them. There is one known and reliable Map, however: the one that allows us to move our eyes rapidly between points in space.. The brain thus has a method of determining a Vector between points, that is, a virtual line with angle and length. Could these vectors be the means whereby we carry out simple geometrical operations like extrapolation? Our working hypothesis is that they are. To test our theory we want to look for similarities and differences between eye movements and perceptual geometry using perceptual tests and functional brain imaging


Research activity codes: 1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH