A5022468115- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Functional Brain Connectivity Studies
- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Advanced Neuroimaging Techniques and Applications
- Advanced MRI Techniques and Applications
- Dementia and Cognitive Impairment Research
- Epilepsy research and treatment
- Medical Imaging Techniques and Applications
- Neural dynamics and brain function
- Genetic Neurodegenerative Diseases
- Neuroscience and Neural Engineering
- Botulinum Toxin and Related Neurological Disorders
- EEG and Brain-Computer Interfaces
- Visual perception and processing mechanisms
- Neurological Disease Mechanisms and Treatments
- Glioma Diagnosis and Treatment
- Medical Imaging and Analysis
- Fractal and DNA sequence analysis
- Facial Nerve Paralysis Treatment and Research
- Vestibular and auditory disorders
- Muscle Physiology and Disorders
- Bioinformatics and Genomic Networks
- Meningioma and schwannoma management
Cambridge University Hospitals NHS Foundation Trust
2019-2025
University of Cambridge
2019-2025
National Health Service
2022
California State University, Northridge
2020
University of Lethbridge
2020
Association of British Neurologists
2019-2020
MRC Cognition and Brain Sciences Unit
2019
Medical Research Council
2019
University of Nottingham
1983
Queen's Medical Centre
1983
Atypical parkinsonian syndromes (APS), including progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy (MSA), may be difficult to distinguish in early stages are often misdiagnosed as Parkinson disease (PD). The diagnostic criteria for PSP have been updated encompass a range of clinical subtypes but not prospectively studied.To define the distinguishing features CBS assess their usefulness facilitating diagnosis separation from PD.This cohort study...
Abstract Background Synaptic loss is a prominent and early feature of many neurodegenerative diseases. Objectives We tested the hypothesis that synaptic density reduced in primary tauopathies progressive supranuclear palsy (PSP) (Richardson’s syndrome) amyloid‐negative corticobasal syndrome (CBS). Methods Forty‐four participants (15 CBS, 14 PSP, 15 age‐/sex‐/education‐matched controls) underwent PET with radioligand [ 11 C]UCB‐J, which binds to vesicle glycoprotein 2A, marker density; also...
Cognitive decline is a common feature of Parkinson's disease, and many these cognitive deficits fail to respond dopaminergic therapy. Therefore, targeting other neuromodulatory systems represents an important therapeutic strategy. Among these, the locus coeruleus-noradrenaline system has been extensively implicated in response inhibition deficits. Restoring noradrenaline levels using noradrenergic reuptake inhibitor atomoxetine can improve some patients with but there considerable...
Abstract Background Neurodegeneration in the locus coeruleus (LC) contributes to neuropsychiatric symptoms both Parkinson's disease (PD) and progressive supranuclear palsy (PSP). Spatial precision of LC imaging is improved with ultrahigh field 7 T magnetic resonance imaging. Objectives This study aimed characterize spatial patterns pathological change PD PSP transdiagnostic relationship between signals symptoms. Methods Twenty‐five people idiopathic PD, 14 probable PSP‐Richardson's syndrome,...
Apathy is a debilitating feature of many neuropsychiatric diseases, that typically described as reduction goal-directed behaviour. Despite its prevalence and prognostic importance, the mechanisms underlying apathy remain controversial. Degeneration locus coeruleus-noradrenaline system known to contribute motivational deficits, including apathy. In healthy people, noradrenaline has been implicated in signalling uncertainty expectations about environment. We proposed noradrenergic deficits by...
The clinical syndromes caused by frontotemporal lobar degeneration are heterogeneous, including the behavioural variant dementia (bvFTD) and progressive supranuclear palsy. Although pathologically distinct, they share many behavioural, cognitive physiological features, which may in part arise from common deficits of major neurotransmitters such as γ-aminobutyric acid (GABA). Here, we quantify GABAergic impairment its restoration with dynamic causal modelling a double-blind placebo-controlled...
Abstract Synaptic loss is an early and clinically relevant feature of many neurodegenerative diseases. Here we assess three adults at risk frontotemporal dementia from C9orf72 mutation, using [ 11 C]UCB‐J PET to quantify synaptic density in comparison with 19 healthy controls one symptomatic patient behavioural variant dementia. The pre‐symptomatic carriers showed reduced the thalamus compared controls, there was additional extensive regions patient. may facilitate early, assessment,...
Objective Synaptic loss is an early feature of neurodegenerative disease models, and severe in post mortem clinical studies, including frontotemporal dementia. Positron emission tomography (PET) with radiotracers that bind to synaptic vesicle glycoprotein 2A enables quantification density vivo. This study used [ 11 C]UCB‐J PET participants behavioral variant dementia (bvFTD), testing the hypothesis related severity. Methods Eleven clinically probable bvFTD 25 age‐ sex‐matched healthy...
Abstract Background Synaptic loss is characteristic of many neurodegenerative diseases; it occurs early and strongly related to functional deficits. Objective In this longitudinal observational study, we determine the rate at which synaptic density reduced in primary tauopathies progressive supranuclear palsy (PSP) corticobasal degeneration (CBD), test relationship with disease progression. Methods Our cross‐sectional cohort included 32 participants probable PSP 16 CBD (all amyloid‐negative...
Abstract The advent of clinical trials disease-modifying agents for neurodegenerative disease highlights the need evidence-based end point selection. Here we report longitudinal PROSPECT-M-UK study progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), multiple system atrophy (MSA) and related disorders, to compare candidate trial points. In this multicentre UK study, participants were assessed with serial questionnaires, motor examination, neuropsychiatric MRI assessments at...
Although widespread cortical asymmetries have been identified in Alzheimer's disease (AD), thalamic and their relevance to clinical severity AD remain unclear.Lateralization indices were computed for individual subnuclei of 65 participants (33 healthy controls, 14 amyloid-positive patients with mild cognitive impairment, 18 dementia). We compared lateralization across diagnostic groups correlated them measures.Although overall asymmetry the thalamus did not differ between groups, greater...
Abstract The relationship between in vivo synaptic density and molecular pathology primary tauopathies is key to understanding the impact of tauopathy on functional decline informing new early therapeutic strategies. In this cross-sectional observational study, we determine progressive supranuclear palsy corticobasal degeneration as a function disease severity. Twenty-three patients with 12 syndrome were recruited from tertiary referral centre. Nineteen education-, sex- gender-matched...
Idiopathic Bell's palsy can lead to a serious and, sometimes permanently, disfiguring and emotionally challenging facial palsy. Early diagnosis treatment with corticosteroids are important, as they significantly improve recovery rates. is benign condition that should be diagnosed managed in primary care. Patients who self-present the emergency department discharged without needing admission. We reviewed all patients referred urgently our hospital weakness of palsy, explore whether clinicians...
Understanding the cellular underpinnings of neurodegeneration remains a challenge; loss synapses and dendritic arborization are characteristic can be quantified in vivo, with [11C]UCB-J PET MRI-based Orientation Dispersion Imaging (ODI), respectively. We aimed to assess how both measures correlated, 4R-tauopathies progressive supranuclear palsy - Richardson's Syndrome (PSP-RS; n = 22) amyloid-negative (determined by [11C]PiB PET) Corticobasal (Cortiobasal degeneration, CBD; =14), as...
Abstract A fundamental question in neuroscience is how brain organisation gives rise to humans’ unique cognitive abilities. Although complex cognition widely assumed rely on frontal and parietal regions, the underlying mechanisms remain elusive: current approaches are unable disentangle different forms of information processing brain. Here, we introduce a powerful framework identify synergistic redundant contributions neural cognition. Leveraging multimodal data including functional MRI,...
Abstract Objective Dementia with Lewy bodies (DLB) is a common cause of dementia, but atrophy mild compared to Alzheimer’s disease. We propose that DLB associated instead severe synaptic loss, and we test this hypothesis in vivo using positron emission tomography (PET) imaging 11 C-UCB-J, ligand for presynaptic vesicle protein 2A (SV2A), membrane ubiquitously expressed synapses. Methods performed C-UCB-J PET two patients (an amyloid-negative male an amyloid-positive female their 70s) 10...
Abstract INTRODUCTION We examined how abnormal prefrontal neurophysiology and changes in gamma‐aminobutyric acid‐ergic (GABAergic) neurotransmission contribute to behavioral impairments disorders associated with frontotemporal lobar degeneration (FTLD). METHODS recorded magnetoencephalography during an adaptive visuomotor task from 11 people behavioral‐variant dementia, progressive supranuclear palsy, 20 age‐matched controls. used tiagabine, a acid (GABA) re‐uptake inhibitor, as...
Alzheimer's disease (AD) pathology is frequently observed as a comorbidity in people with dementia Lewy bodies (DLB). Here, we evaluated the vivo distribution of tau burden and its influence on clinical phenotype DLB. Tau deposition was quantified using [18F]-AV1451 positron emission tomography DLB (n = 10), AD 27), healthy controls 14). A subset patients body diseases 4) also underwent [11C]-PK11195 to estimate microglial activation. BPND lower than across widespread regions. The medial...
Synaptic loss occurs early in many neurodegenerative diseases and contributes to cognitive impairment even the absence of gross atrophy. Currently, for human disease there are few formal models explain how cortical networks underlying cognition affected by synaptic loss. We advocate that biophysical neurophysiology offer both a bridge from preclinical clinical pathology quantitative assays experimental medicine. Such can also disclose hidden neuronal dynamics generating neurophysiological...
Abstract There is extensive synaptic loss from frontotemporal lobar degeneration, in preclinical models and human vivo post mortem studies. Understanding the consequences of for network function important to support translational guide future therapeutic strategies. To examine this relationship, we recruited 55 participants with syndromes associated degeneration 24 healthy controls. We measured density positron emission tomography using radioligand [ 11 C]UCB-J, which binds presynaptic...
Parkinson's disease (PD) and progressive supranuclear palsy (PSP) both impair response inhibition, exacerbating impulsivity. Inhibitory control deficits vary across individuals are linked with worse prognosis, lack improvement on dopaminergic therapy. Motor cognitive associated noradrenergic innervation of the cortex, arising from locus coeruleus (LC) system. Here we test hypothesis that structural variation LC explains inhibition in PSP PD. Twenty-four people idiopathic PD, 14...
<title>Abstract</title> Noradrenaline plays an integral role in learning, by optimising behavioural strategies and facilitating choice execution. Testing the noradrenergic framework of learning context human diseases offers a test bed for current normative neuroscience theories may also indicate therapeutic potential. Parkinson's disease is often considered as model dopamine deficits, including dopamine’s reinforcement learning. However, function severely impaired disease, contributing to...