Bristol Neuroscience

Age-associated dementias are neuropathologically characterized by the identification of hallmark intracellular and extracellular deposition of proteins, i.e., hyperphosphorylated-tau, amyloid-β, and α-synuclein, or cerebrovascular lesions. The neuropathological assessment and staging of these pathologies allows for a diagnosis of a distinct disease, e.g., amyloid-β plaques and hyperphosphorylated tau pathology in Alzheimer's disease. Neuropathological assessment in large scale cohorts, such as the UK’s Brains for Dementia Research (BDR) programme, has made it increasingly clear that the ageing brain is characterized by the presence of multiple age-associated pathologies rather than just the ‘pure’ hallmark lesion as commonly perceived. These additional pathologies can range from low/intermediate levels, that are assumed to have little if any clinical significance, to a full-blown mixed disease where there is the presence of two distinct diseases. In our recent paper (McAleese et al. 2021 Concomitant neurodegenerative pathologies contribute to the transition from mild cognitive impairment to dementia, https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.12291, Alzheimer's & Dementia), using the BDR cohort, we investigated the frequency of multimorbidity and specifically investigated the impact of additional low-level pathology on cognition. In this study, of 670 donated post-mortem brains, we found that almost 70% of cases exhibited multimorbidity and only 22% were considered a pure diagnosis. Importantly, no case of Lewy Body dementia or vascular dementia was considered pure. A key finding is that the presence of low levels of additional pathology increased the likelihood of having mild dementia vs mild cognitive impairment by almost 20-fold, indicating low levels of additional pathology do impact the clinical progression of a distinct disease. Given the high prevalence and the potential clinical impact, cerebral multimorbidity should be at the forefront of consideration in dementia research.

In urban environments, social boundaries are the areas that emerge from processes of economic inequality and social segregation. These boundaries are important, as they serve both as areas of interaction and conflict. By applying geographical thinking to classic methods in data science, we can better understand where these boundaries emerge and how they delineate communities. In this talk, I’ll explain a bit about the basics of “boundary detection” in urban analytics. I’ll present a new method, the “geosilhouette,” that builds on previous methods of identifying the boundaries between clusters. And, finally, I’ll show how this can change our understanding of urban community.

Candy will provide an overview of Bristol Health Partners' Chronic Pain Health Integration Team which brings together clinicians, academics, patients and carers to focus on improving the lives of those with chronic pain and supporting those who provide chronic pain services or care. Tony will describe recent and ongoing studies that have been forward and reverse translating pain neuroscience from animal to human including functional imaging in patients, microneurography, industrial partnerships and trials of novel preventative approaches that are benefitting from the people, expertise and facilities available in Bristol and GW4.

Reliable and validated measures of emotion in animals are of great import; they are crucial to better understanding and developing treatments for human mood disorders, and they are necessary for ensuring good animal welfare. We have developed a novel measure of emotion in animals that is grounded in theory and psychological research – decision-making under ambiguity. Specifically, we consider that more ‘optimistic’ decisions about ambiguous stimuli reflect more positive emotional states, while the opposite is true for more ‘pessimistic’ decisions. In this talk, we will outline the background behind and implementation of this measure, meta-analyses that have been conducted to validate the measure, and discuss how computational modelling has been used to further understand the cognitive processes underlying ‘optimistic’ and ‘pessimistic’ decision-making as an indicator of animal emotion and welfare.

Meg was awarded funding to look into how the coronavirus pandemic has affected children's mental health and wellbeing.

The speakers will outline how neurologists in Bristol have been research-active during the COVID-19 pandemic including our contribution to national and international surveillance programmes as well as initiating research studies such as an evaluation of the impact of COVID anxiety on sleep and neurodegeneration and determining whether vascular changes in the eye predict COVID-19 severity.

Christophe Mulle is a cellular neurobiologist with expertise in electrophysiology of synaptic transmission and an international leader in studies on glutamate receptors and hippocampal synaptic plasticity. He was among the first to identify and characterize functional nicotinic receptors in the mammalian brain while working in the laboratory of Jean-Pierre Changeux at the Pasteur Institute. He then generated knock-out mice for KAR subunits at the Salk Institute in the laboratory of Steve Heinemann, which have proven to be instrumental for understanding the function of these elusive glutamate receptors in synaptic function and plasticity.

Prof Caswell Barry, Professorial Research Fellow, Cell & Developmental Biology, Division of Biosciences, University College London. He and his team are trying to understand how the brain works - how it creates that experience of being human, and more specifically, how the brain creates, stores, and updates memories for places and events. They are trying to answer this is by studying areas of the brain linked to memory, the hippocampus and associated sections of cortex – by recording the activity of neurons in these areas we can visualise and hopefully understand the processes the trigger memory formation and retrieval.