Geraint Rees

Geraint Rees
University College London | UCL · Institute of Cognitive Neuroscience

PhD

About

536
Publications
91,945
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34,736
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Additional affiliations
January 2001 - December 2013
University College London

Publications

Publications (536)
Chapter
Deep generative models have emerged as promising tools for detecting arbitrary anomalies in data, dispensing with the necessity for manual labelling. Recently, autoregressive transformers have achieved state-of-the-art performance for anomaly detection in medical imaging. Nonetheless, these models still have some intrinsic weaknesses, such as requi...
Conference Paper
Background Conventional 3-Tesla MRI shows volume loss in the motor cortex (M1) up to 15 years before motor onset. Post-mortem data, typically at the end stage of Huntington's disease, suggests selective pyramidal cell loss of layers 3 and 5 in M1. However, the extent and patterns of cortical layer specific M1 pathology in the premanifest stage are...
Conference Paper
Background The HD Young Adult Study provided deep phenotyping of the earliest cohort of adult HD mutation carriers to date. We previously reported elevated levels of neurofilament light protein, suggestive of early neurodegenerative change. Putaminal volumes were also significantly reduced in HD mutation carriers. However, there was no evidence of...
Article
Full-text available
Recent advances in regenerative therapy have placed the treatment of previously incurable eye diseases within arms’ reach. Achromatopsia is a severe monogenic heritable retinal disease that disrupts cone function from birth, leaving patients with complete colour blindness, low acuity, photosensitivity and nystagmus. While successful gene-replacemen...
Preprint
Correctly estimating the influence of uncertainty on our decisions is a critical metacognitive faculty. However, the relationship between sensory uncertainty (or its inverse, precision), decision accuracy, and subjective confidence is currently unclear. Although some findings indicate that healthy adults exhibit an illusion of over-confidence, unde...
Preprint
Full-text available
Equity is widely held to be fundamental to the ethics of healthcare. In the context of clinical decision-making, it rests on the comparative fidelity of the intelligence -- evidence-based or intuitive -- guiding the management of each individual patient. Though brought to recent attention by the individuating power of contemporary machine learning,...
Article
Upregulation of functional network connectivity in the presence of structural degeneration is seen in the premanifest stages of Huntington’s disease (preHD) 10-15 years from clinical diagnosis. However, whether widespread network connectivity changes are seen in gene-carriers much further from onset has yet to be explored. We characterised function...
Preprint
Full-text available
Data used in image segmentation are not always defined on the same grid. This is particularly true for medical images, where the resolution, field-of-view and orientation can differ across channels and subjects. Images and labels are therefore commonly resampled onto the same grid, as a pre-processing step. However, the resampling operation introdu...
Preprint
Full-text available
Deep generative models have emerged as promising tools for detecting arbitrary anomalies in data, dispensing with the necessity for manual labelling. Recently, autoregressive transformers have achieved state-of-the-art performance for anomaly detection in medical imaging. Nonetheless, these models still have some intrinsic weaknesses, such as requi...
Article
Visual hallucinations are common in Parkinson’s (PD) and associated with worse outcomes. ¹ Neuroim- aging shows widespread but non-specific grey matter atrophy in PD-hallucinations ¹ ; white matter (WM) loss may be an earlier, more sensitive marker. To detect WM changes in PD-hallucinations we performed diffusion-weighted imaging in 105 patients wi...
Article
Visual hallucinations are common in Parkinson’s (PD) and associated with poorer prognosis. Imaging studies have shown white matter and functional changes in PD-hallucinations 1 2 but the biological factors underlying selective vulnerability of brain regions are unknown. We performed diffusion-weighted imaging in 100 PD patients (81 without hallucin...
Article
Full-text available
Pathological brain appearances may be so heterogeneous as to be intelligible only as anomalies, defined by their deviation from normality rather than any specific set of pathological features. Amongst the hardest tasks in medical imaging, detecting such anomalies requires models of the normal brain that combine compactness with the expressivity of...
Preprint
An important step towards the development of treatments for cognitive impairment in ageing and neurodegenerative diseases is to identify genetic and environmental modifiers of cognitive function and understand the mechanism by which they exert an effect. In Huntington's disease, the most common autosomal dominant dementia, a small number of studies...
Preprint
Full-text available
The characteristics and determinants of health and disease are often organised in space, reflecting our spatially extended nature. Understanding the influence of such factors requires models capable of capturing spatial relations. Though a mature discipline, spatial analysis is comparatively rare in medicine, arguably a consequence of the complexit...
Article
The characteristics and determinants of health and disease are often organised in space, reflecting our spatially extended nature. Understanding the influence of such factors requires models capable of capturing spatial relations. Though a mature discipline, spatial analysis is comparatively rare in medicine, arguably a consequence of the complexit...
Article
Full-text available
Objectives To investigate the timeframe prior to symptom onset when cortico-basal ganglia white matter (white matter) loss begins in premanifest Huntington’s disease (preHD), and which striatal and thalamic sub-region white matter tracts are most vulnerable. Methods We performed fixel-based analysis, which allows resolution of crossing white matte...
Article
Healthcare should be judged by its equity as well as its quality. Both aspects depend not only on the characteristics of service delivery but also on the research and innovation that ultimately shape them. Conducting a fully-inclusive evaluation of the relationship between enrolment in primary research studies at University College London Hospitals...
Preprint
Full-text available
We describe Countersynth, a conditional generative model of diffeomorphic deformations that induce label-driven, biologically plausible changes in volumetric brain images. The model is intended to synthesise counterfactual training data augmentations for downstream discriminative modelling tasks where fidelity is limited by data imbalance, distribu...
Article
Full-text available
Cognitive and behavioural outcomes in stroke reflect the interaction between two complex anatomically-distributed patterns: the functional organization of the brain and the structural distribution of ischaemic injury. Conventional outcome models—for individual prediction or population-level inference—commonly ignore this complexity, discarding anat...
Conference Paper
Objectives Cognitive flexibility, which is key for adaptive decision-making, engages prefrontal cortex (PFC)-striatal circuitry and is impaired in both manifest and premanifest HD (pre-HD). The aim of this study was to examine cognitive flexibility in a far from onset pre-HD cohort to determine whether an early impairment exists and if so, whether...
Conference Paper
Background Disease-modifying treatments are in development for Huntington’s disease (HD); crucial to their success in delaying or preventing onset is to identify a timepoint when there is a measurable biomarker of early neurodegeneration while clinical function is still intact. Aims We aimed to identify the earliest HD changes and the most promisi...
Article
Background The gating of movement in humans is thought to depend on activity within the cortico-striato-thalamic loops. Within these loops, emerging from the cells of the striatum, run two opponent pathways the direct and indirect pathway. Both are complex and polysynaptic but the overall effect of activity within these pathways is to encourage and...
Article
Full-text available
Ultra‐high field MRI across the depth of the cortex has the potential to provide anatomically precise biomarkers and mechanistic insights into neurodegenerative disease like Huntington's disease that show layer‐selective vulnerability. Here we compare multi‐parametric mapping (MPM) measures across cortical depths for a 7T 500 μm whole brain acquisi...
Article
Full-text available
Background Over half a million individuals are diagnosed with head and neck cancer each year globally. Radiotherapy is an important curative treatment for this disease, but it requires manual time to delineate radiosensitive organs at risk. This planning process can delay treatment while also introducing interoperator variability, resulting in down...
Preprint
Full-text available
The gating of movement depends on activity within the cortico-striato-thalamic loops. Within these loops, emerging from the cells of the striatum, run two opponent pathways - the direct and indirect basal ganglia pathway. Both are complex and polysynaptic but the overall effect of activity within these pathways is thought to encourage and inhibit m...
Article
Early prediction of patient outcomes is important for targeting preventive care. This protocol describes a practical workflow for developing deep-learning risk models that can predict various clinical and operational outcomes from structured electronic health record (EHR) data. The protocol comprises five main stages: formal problem definition, dat...
Article
Full-text available
Background Pathological processes in Huntington's disease (HD) begin many years prior to symptom onset. Recently we demonstrated that in a premanifest cohort approximately 24 years from predicted disease onset, despite intact function, there was evidence of subtle neurodegeneration. Here, we use novel imaging techniques to determine whether macro-...
Preprint
Full-text available
Objectives To investigate the timeframe prior to symptom onset when cortico-basal ganglia white matter (WM) loss begins in premanifest Huntington’s disease (preHD), and which striatal and thalamic sub-region WM tracts are most vulnerable. Methods We performed fixel-based analysis, which allows resolution of crossing WM fibres at the voxel level, o...
Article
Background The composite Unified Huntington's Disease Rating Scale (cUHDRS) is a multidimensional measure of progression in Huntington's disease (HD) being used as a primary outcome in clinical trials investigating potentially disease‐modifying huntingtin‐lowering therapies. Objective Evaluating volumetric and structural connectivity correlates of...
Article
Full-text available
Parkinson’s dementia is characterised by changes in perception and thought, and preceded by visual dysfunction, making this a useful surrogate for dementia risk. Structural and functional connectivity changes are seen in humans with Parkinson’s disease, but the organisational principles are not known. We used resting-state fMRI and diffusion-weight...
Article
Full-text available
Background In this study, we asked whether differences in striatal activity during a reinforcement learning (RL) task, with gain and loss domains, could be one of the earliest functional imaging features associated with carrying the Huntington’s Disease (HD) gene. Based on previous work, we hypothesised that HD gene carriers would show either a neu...
Preprint
Background: Apathy, a disabling and poorly understood neuropsychiatric symptom, is characterised by impaired self-initiated behaviour. Although the computational mechanisms that determine self-initiation are poorly understood, it has been hypothesised that the opportunity cost of time (OCT) may be a key variable linking self-initiated behaviour wit...
Preprint
Full-text available
Achromatopsia (ACHM) is an inherited retinal disease characterised by complete loss of cone photoreceptor function from birth. In recent years, gene therapies have successfully been used to induce signal processing in dormant cones in animal models of ACHM, with greater functional benefits for younger animals. With several completed or on-going cli...
Preprint
BACKGROUND Over half a million individuals are diagnosed with head and neck cancer each year globally. Radiotherapy is an important curative treatment for this disease, but it requires manual time to delineate radiosensitive organs at risk. This planning process can delay treatment while also introducing interoperator variability, resulting in down...
Article
BACKGROUND: Characterizing changing brain structure in neurodegeneration is fundamental to understanding longterm effects of pathology and ultimately providing therapeutic targets. It is well established that Huntington’s disease (HD) gene carriers undergo progressive brain changes during the course of disease, yet the long-term trajectory of corti...
Article
Full-text available
The ability to represent and respond to uncertainty is fundamental to human cognition and decision-making. Noradrenaline (NA) is hypothesized to play a key role in coordinating the sensory, learning, and physiological states necessary to adapt to a changing world, but direct evidence for this is lacking in humans. Here, we tested the effects of att...
Article
Full-text available
Background Characterizing changing brain structure in neurodegeneration is fundamental to understanding long-term effects of pathology and ultimately providing therapeutic targets. It is well-established that Huntington’s disease (HD) gene-carriers undergo progressive brain changes during the course of disease, yet the long-term trajectory of corti...
Article
Full-text available
Objectives Cognitive flexibility, which is key for adaptive decision-making, engages prefrontal cortex (PFC)-striatal circuitry and is impaired in both manifest and premanifest Huntington’s disease (pre-HD). The aim of this study was to examine cognitive flexibility in a far from onset pre-HD cohort to determine whether an early impairment exists a...
Article
Full-text available
Visual hallucinations are common in Parkinson's disease and are associated with poorer prognosis. Imaging studies show white matter loss and functional connectivity changes with Parkinson's visual hallucinations, but the biological factors underlying selective vulnerability of affected parts of the brain network are unknown. Recent models for Parki...
Article
Huntington’s disease (HD) is a monogenic disorder with 100% penetrance. With the advent of genetic testing in adults, disease-related, structural brain changes can be investigated from the earliest, premorbid stages of HD. While examining macrostructural change characterises global neuronal damage, investigating microstructural alterations provides...
Article
BACKGROUND: In this study, we asked whether differences in striatal activity during a reinforcement learning (RL) task with gain and loss domains could be one of the earliest functional imaging features associated with carrying the Huntington's disease (HD) gene. Based on previous work, we hypothesized that HD gene carriers would show either neural...
Article
Full-text available
Progression to exudative ‘wet’ age-related macular degeneration (exAMD) is a major cause of visual deterioration. In patients diagnosed with exAMD in one eye, we introduce an artificial intelligence (AI) system to predict progression to exAMD in the second eye. By combining models based on three-dimensional (3D) optical coherence tomography images...
Article
Full-text available
Background Disease-modifying treatments are in development for Huntington's disease; crucial to their success is to identify a timepoint in a patient's life when there is a measurable biomarker of early neurodegeneration while clinical function is still intact. We aimed to identify this timepoint in a novel cohort of young adult premanifest Hunting...
Article
The human motor cortex comprises a microcircuit of five interconnected layers with different cell types. In this Review, we use a layer-specific and cell-specific approach to integrate physiological accounts of this motor cortex microcircuit with the pathophysiology of neurodegenerative diseases affecting motor functions. In doing so we can begin t...
Article
Full-text available
Background Structural brain MRI measures are frequently examined in both healthy and clinical groups, so an understanding of how these measures vary over time is desirable. Purpose To test the stability of structural brain MRI measures over time. Population In all, 112 healthy volunteers across four sites. Study Type Retrospective analysis of pr...
Article
Full-text available
Non-invasive methods, such as neurofeedback training, could support cognitive symptom management in Huntington’s disease by targeting brain regions whose function is impaired. The aim of our single-blind, sham-controlled study was to collect rigorous evidence regarding the feasibility of neurofeedback training in Huntington’s disease by examining t...
Article
Full-text available
Research and innovation in biomedicine and health care increasingly depend on electronic data. The emergence of data-driven technologies and associated digital transformations has focused attention on the value of such data. Despite the broad consensus of the value of health data, there is less consensus on the basis for that value; thus, the natur...
Article
Full-text available
Objective To investigate the microstructural and macrostructural white matter changes that accompany visual hallucinations and low visual performance in Parkinson disease, a risk factor for Parkinson dementia. Methods We performed fixel-based analysis, a novel technique that provides metrics of specific fiber-bundle populations within a voxel (or...
Preprint
Full-text available
Cortical layer-specific ultra-high field MRI has the potential to provide anatomically precise biomarkers and mechanistic insights into neurodegenerative disease. Here we compare cortical layer-specificity for a 7T multi-parametric mapping (MPM) microns whole brain acquisition to the von Economo and Big Brain post-mortem histology atlases. We also...
Article
Full-text available
Parkinson’s dementia is a common and devastating part of Parkinson’s disease. Whilst timing and severity vary, dementia in Parkinson’s is often preceded by visual dysfunction. White matter changes, representing axonal loss, occur early in the disease process. Clarifying which white matter connections are affected in Parkinson’s with visual dysfunct...
Article
Background: No sensory stimulus is an island entire of itself, the processing of visual inputs is highly influenced by surrounding spatial context. Some accounts of Autism Spectrum Disorder have suggested that the sensory difficulties reported in the condition could arise from differences in contextual modulation of sensory stimuli, specifically pr...
Article
Full-text available
Failure to attend scheduled hospital appointments disrupts clinical management and consumes resource estimated at £1 billion annually in the United Kingdom National Health Service alone. Accurate stratification of absence risk can maximize the yield of preventative interventions. The wide multiplicity of potential causes, and the poor performance o...
Article
Full-text available
We developed a digitally enabled care pathway for acute kidney injury (AKI) management incorporating a mobile detection application, specialist clinical response team and care protocol. Clinical outcome data were collected from adults with AKI on emergency admission before (May 2016 to January 2017) and after (May to September 2017) deployment at t...
Article
Full-text available
Introduction All medicine was innovation, once. Yet the contemporary notion of medical research is remarkably narrow. While every clinician is encouraged to be aware of the latest advances, only a few are expected to contribute to them. Anyone may be a patient, yet clinical practice is determined by the minority included in research studies. The ai...
Article
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Background: Investigating early white matter (WM) change in Huntington's disease (HD) can improve our understanding of the way in which disease spreads from the striatum. Objectives: We provide a detailed characterization of pathology-related WM change in HD. We first examined WM microstructure using diffusion-weighted imaging and then investiga...
Article
Objective A sensorimotor network structural phenotype predicted motor task performance in a previous study in Huntington’s disease (HD) gene carriers. We investigated in the visual network whether structure – function – behaviour relationship patterns, and the effects of the HD mutation, extended beyond the sensorimotor network. Methods We used mul...
Article
Full-text available
The early prediction of deterioration could have an important role in supporting healthcare professionals, as an estimated 11% of deaths in hospital follow a failure to promptly recognize and treat deteriorating patients¹. To achieve this goal requires predictions of patient risk that are continuously updated and accurate, and delivered at an indiv...
Article
Objective: A sensorimotor network structural phenotype predicted motor task performance in a previous study in Huntington's disease (HD) gene carriers. We investigated in the visual network whether structure - function - behaviour relationship patterns, and the effects of the HD mutation, extended beyond the sensorimotor network. Methods: We use...
Article
We developed a digitally enabled care pathway for acute kidney injury (AKI) management incorporating a mobile detection application, specialist clinical response team and care protocol. Clinical outcome data were collected from adults with AKI on emergency admission before (May 2016 to January 2017) and after (May to September 2017) deployment at t...
Article
Full-text available
Hallucinations are a common and distressing feature of many psychiatric and neurodegenerative conditions. In Lewy Body Disease, visual hallucinations are a defining feature, associated with worse outcomes; yet their mechanisms remain unclear and treatment options are limited. Here, we show that hallucinations in Lewy Body Disease are associated wit...