Thomas Nichols

Thomas Nichols
University of Oxford | OX · Big Data Institute, Nuffield Department of Population Health

PhD

About

399
Publications
73,830
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51,381
Citations
Additional affiliations
January 2008 - December 2011
Imperial College London
January 2008 - December 2009
January 2006 - December 2010
University of Oxford

Publications

Publications (399)
Article
Full-text available
Alcohol’s impact on telomere length, a proposed marker of biological aging, is unclear. We performed the largest observational study to date (in n = 245,354 UK Biobank participants) and compared findings with Mendelian randomization (MR) estimates. Two-sample MR used data from 472,174 participants in a recent genome-wide association study (GWAS) of...
Article
Full-text available
Background Brain iron deposition has been linked to several neurodegenerative conditions and reported in alcohol dependence. Whether iron accumulation occurs in moderate drinkers is unknown. Our objectives were to investigate evidence in support of causal relationships between alcohol consumption and brain iron levels and to examine whether higher...
Preprint
Neural demyelination and brain damage accumulated in white matter appear as hyperintense areas on MRI scans in the form of lesions. Modeling binary images at the population level, where each voxel represents the existence of a lesion, plays an important role in understanding aging and inflammatory diseases. We propose a scalable hierarchical Bayesi...
Preprint
Existing methods for fitting continuous time Markov models (CTMM) in the presence of covariates suffer from scalability issues due to high computational cost of matrix exponentials calculated for each observation. In this paper we propose an optimization technique for CTMM which uses a stochastic gradient descent algorithm combined with differentia...
Article
While population-scale neuroimaging studies offer the promise of discovery and characterisation of subtle risk factors, massive sample sizes increase the power for both meaningful associations and those attributable to confounds. This motivates the need for causal modelling of observational data that goes beyond statements of association and toward...
Article
Full-text available
Canonical Correlation Analysis (CCA) has been widely applied to study correlations between neuroimaging data and behavioral data. Practical use of CCA typically requires dimensionality reduction with, for example, Principal Components Analysis (PCA), however, this can result in CCA components that are difficult to interpret. In this paper, we intro...
Article
Full-text available
Moderate alcohol consumption is widespread but its impact on brain structure and function is contentious. The relationship between alcohol intake and structural and functional neuroimaging indices, the threshold intake for associations, and whether population subgroups are at higher risk of alcohol-related brain harm remain unclear. 25,378 UK Bioba...
Article
Full-text available
Magnetic resonance imaging (MRI) has transformed our understanding of the human brain through well-replicated mapping of abilities to specific structures (for example, lesion studies) and functions1–3 (for example, task functional MRI (fMRI)). Mental health research and care have yet to realize similar advances from MRI. A primary challenge has bee...
Preprint
While population-scale neuroimaging studies offer the promise of discovery and characterisation of subtle risk factors, massive sample sizes increase the power for both meaningful associations and those attributable to confounds. This motivates the need for causal modelling of observational data that goes beyond statements of association and toward...
Preprint
Brain iron deposition has been linked to several neurodegenerative conditions and reported in alcohol dependence. Whether iron accumulation occurs in moderate drinkers is unknown. Our objectives were to investigate causal relationships between alcohol consumption and brain iron levels and to examine whether higher brain iron represents a potential...
Article
Full-text available
Severe mental illnesses (SMI) including major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia spectrum disorder (SSD) elevate accelerated brain aging risks. Cardio-metabolic disorders (CMD) are common comorbidities in SMI and negatively impact brain health. We validated a linear quantile regression index (QRI) approach against t...
Article
Patients with multiple sclerosis acquire disability either through: (1) Relapse-associated worsening (RAW), or (2) progression independent of relapse activity (PIRA). This study addresses the relative contribution of relapses to disability worsening over the course of the disease, how early progression begins, and the extent to which multiple scler...
Preprint
Full-text available
The analysis of excursion sets in imaging data is essential to a wide range of scientific disciplines such as neuroimaging, climatology and cosmology. Despite growing literature, there is little published concerning the comparison of processes that have been sampled across the same spatial region but which reflect different study conditions. Given...
Article
Big Data neuroimaging collaborations including Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) integrated worldwide data to identify regional brain deficits in major depressive disorder (MDD). We evaluated the sensitivity of translating ENIGMA-defined MDD deficit patterns to the individual level. We treated ENIGMA MDD deficit patter...
Article
Full-text available
Background Novartis and the University of Oxford’s Big Data Institute (BDI) have established a research alliance with the aim to improve health care and drug development by making it more efficient and targeted. Using a combination of the latest statistical machine learning technology with an innovative IT platform developed to manage large volumes...
Preprint
Motivated by a brain lesion application, we introduce penalized generalized estimating equations for relative risk regression for modelling correlated binary data. Brain lesions can have varying incidence across the brain and result in both rare and high incidence outcomes. As a result, odds ratios estimated from generalized estimating equations wi...
Article
Full-text available
Imaging genetics analyses use neuroimaging traits as intermediate phenotypes to infer the degree of genetic contribution to brain structure and function in health and/or illness. Coefficients of relatedness (CR) summarize the degree of genetic similarity among subjects and are used to estimate the heritability - the proportion of phenotypic varianc...
Conference Paper
Full-text available
Background Existing work, using indirect health measures, suggests independent links between brain and heart health within disease cohorts. We studied the links between MRI-derived heart and brain structure and function in the UK Biobank population-based cohort. Methods Image acquisition and analysis was according to pre-defined protocols. We incl...
Preprint
Full-text available
Background Magnetic resonance imaging (MRI) of the brain could be a key diagnostic and research tool for understanding the neuropsychiatric complications of COVID-19. For maximum impact, multi-modal MRI protocols will be needed to measure the effects of SARS-CoV2 infection on the brain by diverse potentially pathogenic mechanisms, and with high rel...
Article
Full-text available
Tobacco smoking is an addictive behavior that supports nicotine dependence and is an independent risk factor for cancer and other illnesses. Its neurogenetic mechanisms are not fully understood but may act through alterations in the cerebral white matter (WM). We hypothesized that the vertical pleiotropic pathways, where genetic variants influence...
Article
Several studies have established specific relationships between White Matter (WM) and behaviour. However, these studies have typically focussed on fractional anisotropy (FA), a neuroimaging metric that is sensitive to multiple tissue properties, making it difficult to identify what biological aspects of WM may drive such relationships. Here, we car...
Preprint
Full-text available
Big Data neuroimaging collaborations including Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) integrated worldwide data to identify regional brain deficits in major depressive disorder (MDD). We evaluated the sensitivity of translating ENIGMA-defined MDD deficit patterns to the individual level. We treated ENIGMA MDD deficit patter...
Preprint
Full-text available
Alcohols impact on telomere length, a proposed marker of biological age, is unclear. We performed the largest observational study to date and compared findings with Mendelian randomization (MR) estimates. Two-sample MR used data from a recent genome-wide association study (GWAS) of telomere length. Genetic variants were selected on the basis of ass...
Article
Full-text available
The analysis of longitudinal, heterogeneous or unbalanced clustered data is of primary importance to a wide range of applications. The linear mixed model (LMM) is a popular and flexible extension of the linear model specifically designed for such purposes. Historically, a large proportion of material published on the LMM concerns the application of...
Preprint
Full-text available
While the development of analytical tools and techniques has broadened our horizons for comprehending the complexities of the human brain, a growing body of research in the neuroimaging literature has highlighted the pitfalls of such methodological plurality. In a recent study, we found that the choice of software package used to run the analysis p...
Preprint
Full-text available
The Adolescent Brain Cognitive Development Study (ABCD), a 10 year longitudinal neuroimaging study of the largest population based and demographically distributed cohort of 9-10 year olds (N=11,877), was designed to overcome reproducibility limitations of prior child mental health studies. Besides the fantastic wealth of research opportunities, the...
Preprint
Full-text available
Background Pulmonary rehabilitation is the best treatment for chronic breathlessness in COPD but there remains an unmet need to improve efficacy. Pulmonary rehabilitation has strong parallels with exposure-based cognitive behavioural therapies (CBT), both clinically and in terms of brain activity patterns. The partial NMDA-receptor agonist, D-cyclo...
Preprint
Full-text available
Large scale neuroimaging datasets present unique challenges for automated processing pipelines. Motivated by a large-scale clinical trials dataset of Multiple Sclerosis (MS) with over 235,000 magnetic resonance imaging (MRI) scans, we consider the challenge of defacing - anonymisation to remove identifying features on the face and the ears. The def...
Preprint
There is strong evidence for brain-related abnormalities in COVID-19 1-13 . It remains unknown however whether the impact of SARS-CoV-2 infection can be detected in milder cases, and whether this can reveal possible mechanisms contributing to brain pathology. Here, we investigated brain changes in 785 UK Biobank participants (aged 51-81) imaged twi...
Article
Full-text available
The Adolescent Brain Cognitive Development (ABCD) Study is the largest single-cohort prospective longitudinal study of neurodevelopment and children's health in the United States. A cohort of n= 11,880 children aged 9-10 years (and their parents/guardians) were recruited across 22 sites and are being followed with in-person visits on an annual basi...
Preprint
Full-text available
Objectives To estimate the relationship between moderate alcohol consumption and brain health, determining the threshold intake for harm and identifying whether population subgroups are at differential risk. Design Observational cohort study. Alcohol consumption was determined at baseline assessment visit using touchscreen questionnaire (2016-10)....
Article
Full-text available
Objectives White matter lesions are a very common finding on MRI in older adults and their presence increases the risk of stroke and dementia. Accurate and computationally efficient modelling methods are necessary to map the association of lesion incidence with risk factors, such as hypertension. However, there is no consensus in the brain mapping...
Article
Full-text available
Background Physical activity (PA) may positively stimulate the brain, cognition and mental health during adolescence, a period of dynamic neurobiological development. High-intensity interval training (HIIT) or vigorous PA interventions are time-efficient, scalable and can be easily implemented in existing school curricula, yet their effects on cogn...
Preprint
Full-text available
Background Novartis and the University of Oxford's Big Data Institute (BDI) have established a research alliance with the aim to improve health care and drug development by making it more efficient and targeted. Using a combination of the latest statistical machine learning technology with an innovative IT platform developed to manage large volumes...
Preprint
Full-text available
The analysis of longitudinal, heterogeneous or unbalanced clustered data is of primary importance to a wide range of applications. The Linear Mixed Model (LMM) is a popular and flexible extension of the linear model specifically designed for such purposes. Historically, a large proportion of material published on the LMM concerns the application of...
Article
Full-text available
Current statistical inference methods for task-fMRI suffer from two fundamental limitations. First, the focus is solely on detection of non-zero signal or signal change, a problem that is exacerbated for large scale studies (e.g. UK Biobank, N=40,000+) where the ‘null hypothesis fallacy’ causes even trivial effects to be determined as significant....
Article
Full-text available
Background The Oxford Big Data Institute, multiple sclerosis (MS) physicians and Novartis aim to address unresolved questions in MS with a novel comprehensive clinical trial data set. Objective The objective of this study is to describe the Novartis–Oxford MS (NO.MS) data set and to explore the relationships between age, disease activity and disea...
Article
Full-text available
Neurological and psychiatric illnesses are associated with regional brain deficit patterns that bear unique signatures and capture illness-specific characteristics. The Regional Vulnerability Index (RVI) was developed to quantify brain similarity by comparing individual white matter microstructure, cortical gray matter thickness and subcortical gra...
Article
The World Health Organization promotes physical exercise and a healthy lifestyle as means to improve youth development. However, relationships between physical lifestyle and human brain development are not fully understood. Here, we asked whether a human brain-physical latent mode of covariation underpins the relationship between physical activity,...
Preprint
Full-text available
Objectives: White matter lesions are a very common finding on MRI in older adults and their presence increases the risk of stroke and dementia. Accurate and computationally efficient modelling methods are necessary to map the association of lesion incidence with risk factors, such as hypertension. However, there is no consensus in the brain mapping...
Preprint
Full-text available
Several studies have established specific relationships between White Matter (WM) and behaviour. However, these studies have typically focussed on fractional anisotropy (FA), a neuroimaging metric that is sensitive to multiple tissue properties, making it difficult to identify what biological aspects of WM may drive such relationships. Here, we car...
Article
Full-text available
When unoccupied by an explicit external task, humans engage in a wide range of different types of self-generated thinking. These are often unrelated to the immediate environment and have unique psychological features. Although contemporary perspectives on ongoing thought recognise the heterogeneity of these self-generated states, we lack both a cle...
Article
Full-text available
Background Imaging research has not yet delivered reliable psychiatric biomarkers. One challenge, particularly among youth, is high comorbidity. This challenge might be met through canonical correlation analysis (CCA) designed to model mutual dependencies between symptom dimensions and neural measures. We map the multivariate associations that intr...
Article
Full-text available
Metadata are what makes databases searchable. Without them, researchers would have difficulty finding data with features they are interested in. Brain imaging genetics is at the intersection of two disciplines, each with dedicated dictionaries and ontologies facilitating data search and analysis. Here, we present the genetics Brain Imaging Data Str...
Article
Full-text available
Objectives To examine relationships between fitness, physical activity and psychosocial problems among English secondary school pupils and to explore how components of physically active lifestyles are associated with mental health and well-being. Methods A total of 7385 participants aged 11–13 took a fitness test and completed self-reported measur...
Article
Studies exploring age-related brain and cognitive change have identified substantial heterogeneity among individuals, but the underlying reasons for the differential trajectories remain largely unknown. We investigated cross-sectional and longitudinal associations between brain-imaging phenotypes (IDPs) and cognitive ability, and how these relation...
Article
Full-text available
Healthy cognitive ageing is a societal and public health priority. Cerebrovascular risk factors increase the likelihood of dementia in older people but their impact on cognitive ageing in younger, healthy brains is less clear. The UK Biobank provides cognition and brain imaging measures in the largest population cohort studied to date. Here we show...
Preprint
Full-text available
The World Health Organization (WHO) promotes physical exercise and a healthy lifestyle as means to improve youth development. However, relationships between physical lifestyle and brain development are not fully understood. Here, we asked whether a brain – physical latent mode of covariation underpins the relationship between physical activity, fit...
Article
Full-text available
Objectives White matter hyperintensities (WMHs) are considered macroscale markers of cerebrovascular burden and are associated with increased risk of vascular cognitive impairment and dementia. However, the spatial location of WMHs has typically been considered in broad categories of periventricular versus deep white matter. The spatial distributio...
Article
Full-text available
Coordinate‐based meta‐analyses (CBMA) allow researchers to combine the results from multiple fMRI experiments with the goal of obtaining results that are more likely to generalise. However, the interpretation of CBMA findings can be impaired by the file drawer problem, a type of publications bias that refers to experiments that are carried out but...
Preprint
Full-text available
Objectives White matter hyperintensities (WMHs) are considered macroscale markers of cerebrovascular burden and are associated with increased risk of vascular cognitive impairment and dementia. However, the spatial location of WMHs has typically been considered in broad categories of periventricular versus deep white matter. The spatial distributio...
Article
Full-text available
Dealing with confounds is an essential step in large cohort studies to address problems such as unexplained variance and spurious correlations. UK Biobank is a powerful resource for studying associations between imaging and non-imaging measures such as lifestyle factors and health outcomes, in part because of the large subject numbers. However, the...
Article
Full-text available
Prediction of subject age from brain anatomical MRI has the potential to provide a sensitive summary of brain changes, indicative of different neurodegenerative diseases. However, existing studies typically neglect the uncertainty of these predictions. In this work we take into account this uncertainty by applying methods of functional data analysi...
Article
Full-text available
Recently, there has been a renewed interest in the class of Stochastic Blockmodels (SBM) and their applications to multi‐subject brain networks. In our most recent work, we have considered an extension of the classical SBM, termed Heterogeneous SBM (Het‐SBM), that models subject variability in the cluster‐connectivity profiles through the addition...
Article
Full-text available
Canonical correlation analysis (CCA) has become a key tool for population neuroimaging, allowing investigation of associations between many imaging and non-imaging measurements. As age, sex and other variables are often a source of variability not of direct interest, previous work has used CCA on residuals from a model that removes these effects, t...
Preprint
Full-text available
Current statistical inference methods for task-fMRI suffer from two fundamental limitations. First, the focus is solely on detection of non-zero signal or signal change, a problem that is exasperated for large scale studies (e.g. UK Biobank, N = 40,000+) where the 'null hypothesis fallacy' causes even trivial effects to be determined as significant...