ORCID Profile
0000-0003-2192-378X
Current Organisations
University of Oxford
,
Cambridge Cognition (United Kingdom)
,
Florey Institute Behavioural Neuroscience
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Publisher: Springer Science and Business Media LLC
Date: 08-2009
DOI: 10.3758/PBR.16.4.641
Publisher: Cold Spring Harbor Laboratory
Date: 05-08-2021
DOI: 10.1101/2021.08.03.21261461
Abstract: Stroke survivors are at high risk of dementia, associated with increasing age and vascular burden and with pre-existing cognitive impairment, older age. Brain atrophy patterns are recognised as signatures of neurodegenerative conditions, but the natural history of brain atrophy after stroke remains poorly described. We sought to determine whether stroke survivors who were cognitively normal at time of stroke had greater total brain (TBV) and hippoc al volume (HV) loss over 3 years than controls. We examined whether stroke survivors who were cognitively impaired (CI) at 3 months following their stroke had greater brain volume loss than cognitively normal (CN) stroke participants. Cognition And Neocortical Volume After Stroke (CANVAS) study is a multi-centre cohort study of first-ever or recurrent adult ischaemic stroke participants compared to age- and sex-matched community controls. Participants were followed with MRI and cognitive assessments over 3 years and were free of a history of cognitive impairment or decline at inclusion. Our primary outcome measure was TBV change between 3 months and 3 years secondary outcomes were TBV and HV change comparing CI and CN participants. We investigated associations between group status and brain volume change using a baseline-volume adjusted linear regression model with robust standard error. Ninety-three stroke (26 women, 66.7±12 years) and 39 control participants (15 women, 68.7±7 years) were available at 3 years. TBV loss in stroke patients was greater than controls: stroke mean (M)=20.3cm 3 ±SD14.8cm 3 controls M=14.2cm 3 ±SD13.2cm 3 (adjusted mean difference 7.88 95%CI [2.84,12.91] p-value=0.002). TBV decline was greater in those stroke participants who were cognitively impaired (M=30.7cm 3 SD=14.2cm 3 ) at 3 months (M=19.6cm 3 SD=13.8cm 3 ) (adjusted mean difference 10.42 95%CI [3.04,17.80], p-value=0.006). No statistically significant differences in HV change were observed. Ischaemic stroke survivors exhibit greater neurodegeneration compared to stroke-free controls. Brain atrophy is greater in stroke participants who were cognitively impaired people early after their stroke. Early cognitive impairment may predict greater subsequent atrophy, reflecting the combined impacts of stroke and vascular brain burden. Atrophy rates could serve as a useful biomarker for trials testing interventions to reduce post-stroke cognitive impairment.
Publisher: Cold Spring Harbor Laboratory
Date: 12-06-2020
DOI: 10.1101/2020.06.12.147934
Abstract: 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 distribution of WHMs associated with in idual cerebrovascular risk factors (CVR), controlling for frequently comorbid risk factors, has not been systematically investigated at the population level in a healthy ageing cohort. Furthermore, there is an inconsistent relationship between total white matter hyperintensity load and cognition, which may be due to the confounding of several simultaneous risk factors in models based on smaller cohorts. We examined trends in in idual CVR factors on total WMH burden in 13,680 in iduals (aged 45-80) using data from the UK Biobank. We estimated the spatial distribution of white matter hyperintensities associated with each risk factor and their contribution to explaining total WMH load using voxel-wise probit regression and univariate linear regression. Finally, we explored the impact of CVR-related WMHs on speed of processing using regression and mediation analysis. Contrary to the assumed dominance of hypertension as the biggest predictor of WMH burden, we show associations with a number of risk factors including diabetes, heavy smoking, APOE ε 4/ ε 4 status and high waist-to-hip ratio of similar, or greater magnitude to hypertension. The spatial distribution of WMHs varied considerably with in idual cerebrovascular risk factors. There were independent effects of visceral adiposity, as measured by waist-to-hip ratio, and carriage of the APOE ε 4 allele in terms of the unique spatial distribution of CVR-related WMHs. Importantly, the relationship between total WMH load and speed of processing was mediated by waist-to-hip ratio suggesting cognitive consequences to WMHs associated with excessive visceral fat deposition. Waist-to-hip ratio, diabetes, heavy smoking, hypercholesterolemia and homozygous APOE ε 4 status are important risk factors, beyond hypertension, associated with WMH total burden and warrant careful control across ageing. The spatial distribution associated with different risk factors may provide important clues as to the pathogenesis and cognitive consequences of WMHs. High waist-to-hip ratio is a key risk factor associated with slowing in speed of processing. With global obesity levels rising, focused management of visceral adiposity may present a useful strategy for the mitigation of cognitive decline in ageing.
Publisher: Wiley
Date: 09-03-2011
DOI: 10.1002/HBM.21219
Publisher: Oxford University Press (OUP)
Date: 08-2021
DOI: 10.1093/GIGASCIENCE/GIAB051
Abstract: As the global health crisis unfolded, many academic conferences moved online in 2020. This move has been hailed as a positive step towards inclusivity in its attenuation of economic, physical, and legal barriers and effectively enabled many in iduals from groups that have traditionally been underrepresented to join and participate. A number of studies have outlined how moving online made it possible to gather a more global community and has increased opportunities for in iduals with various constraints, e.g., caregiving responsibilities. Yet, the mere existence of online conferences is no guarantee that everyone can attend and participate meaningfully. In fact, many elements of an online conference are still significant barriers to truly erse participation: the tools used can be inaccessible for some in iduals the scheduling choices can favour some geographical locations the set-up of the conference can provide more visibility to well-established researchers and reduce opportunities for early-career researchers. While acknowledging the benefits of an online setting, especially for in iduals who have traditionally been underrepresented or excluded, we recognize that fostering social justice requires inclusivity to actively be centered in every aspect of online conference design. Here, we draw from the literature and from our own experiences to identify practices that purposefully encourage a erse community to attend, participate in, and lead online conferences. Reflecting on how to design more inclusive online events is especially important as multiple scientific organizations have announced that they will continue offering an online version of their event when in-person conferences can resume.
Publisher: Cold Spring Harbor Laboratory
Date: 03-11-2016
DOI: 10.1101/085068
Abstract: Recent evidence suggests that visual short-term memory (VSTM) capacity estimated using simple objects, such as colours and oriented bars, may not generalise well to more naturalistic stimuli. More visual detail can be stored in VSTM when complex, recognisable objects are maintained compared to simple objects. It is not yet known if it is recognisability that enhances memory precision, nor whether maintenance of recognisable objects is achieved with the same network of brain regions supporting maintenance of simple objects. We used a novel stimulus generation method to parametrically warp photographic images along a continuum, allowing separate estimation of the precision of memory representations and the number of items retained. The stimulus generation method was also designed to create unrecognisable, though perceptually matched, stimuli, to investigate the impact of recognisability on VSTM. We adapted the widely-used change detection and continuous report paradigms for use with complex, photographic images. Across three functional magnetic resonance imaging (fMRI) experiments, we demonstrated greater precision for recognisable objects in VSTM compared to unrecognisable objects. This clear behavioural advantage was not the result of recruitment of additional brain regions, or of stronger mean activity within the core network. Representational similarity analysis revealed greater variability across item repetitions in the representations of recognisable, compared to unrecognisable complex objects. We therefore propose that a richer range of neural representations support VSTM for complex recognisable objects.
Publisher: Oxford University Press (OUP)
Date: 19-12-2020
DOI: 10.1093/BRAINCOMMS/FCAA219
Abstract: Female sex, age and carriage of the apolipoprotein E e4 allele are the greatest risk factors for sporadic Alzheimer’s disease. The hippoc us has a selective vulnerability to atrophy in ageing that may be accelerated in Alzheimer’s disease, including in those with increased genetic risk of the disease, years before onset. Within the hippoc al complex, subfields represent cytoarchitectonic and connectivity based isions. Variation in global hippoc al and subfield volume associated with sex, age and apolipoprotein E e4 status has the potential to provide a sensitive biomarker of future vulnerability to Alzheimer’s disease. Here, we examined non-linear age, sex and apolipoprotein E effects, and their interactions, on hippoc al and subfield volumes across several decades spanning mid-life to old age in 36 653 healthy ageing in iduals. FMRIB Software Library derived estimates of total hippoc al volume and Freesurfer derived estimates hippoc al subfield volume were estimated. A model-free, sliding-window approach was implemented that does not assume a linear relationship between age and subfield volume. The annualized percentage of subfield volume change was calculated to investigate associations with age, sex and apolipoprotein E e4 homozygosity. Hippoc al volume showed a marked reduction in apolipoprotein E e4/e4 female carriers after age 65. Volume was lower in homozygous e4 in iduals in specific subfields including the presubiculum, subiculum head, cornu ammonis 1 body, cornu ammonis 3 head and cornu ammonis 4. Nearby brain structures in medial temporal and subcortical regions did not show the same age, sex and apolipoprotein E interactions, suggesting selective vulnerability of the hippoc us and its subfields. The findings demonstrate that in healthy ageing, two factors—female sex and apolipoprotein E e4 status—confer selective vulnerability of specific hippoc al subfields to volume loss.
Publisher: Springer Nature Singapore
Date: 2022
Publisher: Oxford University Press (OUP)
Date: 18-03-2021
Abstract: Patients with small vessel cerebrovascular disease frequently suffer from apathy, a debilitating neuropsychiatric syndrome, the underlying mechanisms of which remain to be established. Here we investigated the hypothesis that apathy is associated with disrupted decision making in effort-based decision making, and that these alterations are associated with abnormalities in the white matter network connecting brain regions that underpin such decisions. Eighty-two patients with MRI evidence of small vessel disease were assessed using a behavioural paradigm as well as diffusion weighted MRI. The decision-making task involved accepting or rejecting monetary rewards in return for performing different levels of physical effort (hand grip force). Choice data and reaction times were integrated into a drift diffusion model that framed decisions to accept or reject offers as stochastic processes approaching a decision boundary with a particular drift rate. Tract-based spatial statistics were used to assess the relationship between white matter tract integrity and apathy, while accounting for depression. Overall, patients with apathy accepted significantly fewer offers on this decision-making task. Notably, while apathetic patients were less responsive to low rewards, they were also significantly averse to investing in high effort. Significant reductions in white matter integrity were observed to be specifically related to apathy, but not to depression. These included pathways connecting brain regions previously implicated in effort-based decision making in healthy people. The drift rate to decision parameter was significantly associated with both apathy and altered white matter tracts, suggesting that both brain and behavioural changes in apathy are associated with this single parameter. On the other hand, depression was associated with an increase in the decision boundary, consistent with an increase in the amount of evidence required prior to making a decision. These findings demonstrate altered effort-based decision making for reward in apathy, and also highlight dissociable mechanisms underlying apathy and depression in small vessel disease. They provide clear potential brain and behavioural targets for future therapeutic interventions, as well as modelling parameters that can be used to measure the effects of treatment at the behavioural level.
Publisher: Wiley
Date: 02-12-2014
DOI: 10.1002/HBM.22711
Publisher: Informa UK Limited
Date: 04-07-2017
DOI: 10.1080/13554794.2017.1364775
Abstract: We present a patient with reading inexpertise and right hemianopia following left posterior cerebral artery (PCA) stroke. We examine the extent of disruption to reading performance and the extent of white matter tract damage relative to a patient with more limited PCA infarction and isolated right hemianopia. We show white matter disconnection of the temporal occipital fusiform cortex in our pure alexia patient. Connectivity-based laterality indices revealed right hemisphere laterality in the alexia patient this was not associated with improved reading function. We speculate that the degree of premorbid laterality may be a critical factor affecting the extent of reading dysfunction in alexia.
Publisher: MDPI AG
Date: 10-11-2017
Publisher: Cold Spring Harbor Laboratory
Date: 04-02-2020
DOI: 10.1101/2020.02.03.20020131
Abstract: Executive dysfunction affects 40% of stroke patients and is associated with poor quality of life. Stroke severity and lesion volume rarely predict whether a patient will have executive dysfunction. Stroke typically occurs on a background of cerebrovascular burden, which impacts cognition and brain network structural integrity. We investigated whether measures of white matter microstructural integrity and cerebrovascular risk factors better explain executive dysfunction than markers of stroke severity. We used structural equation modelling to examine multivariate relationships between cerebrovascular risk, white matter microstructural integrity (fractional anisotropy and mean diffusivity), stroke characteristics and executive dysfunction in 126 stroke patients (mean age 68.4 years), three months post-stroke, and compared to 40 age- and sex-matched control participants. Executive function was measured using the Trail Making Tests, Clock Drawing task and Rey Complex Figure copy task. Microstructural integrity was estimated using a standard pipeline to process diffusion weighted images. Executive function was below what would be expected for age and education level in stroke patients (t-test compared to controls t(79)=5.75, p .001). A multivariate structural equation model illustrated the complex relationship between executive function, white matter integrity, stroke characteristics and cerebrovascular risk. Pearson’s correlations confirmed a stronger relationship between executive dysfunction and white matter integrity, than executive dysfunction and stroke severity. Mediation analysis showed the relationship between executive function and white matter integrity is mediated by cerebrovascular burden. White matter microstructural degeneration of the superior longitudinal fasciculus in the executive control network better explains executive dysfunction than markers of stroke severity.
Publisher: Springer Science and Business Media LLC
Date: 07-09-2020
DOI: 10.1038/S41467-020-18201-5
Abstract: 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 that cognitive abilities of healthy in iduals (N = 22,059) in this s le are detrimentally affected by cerebrovascular risk factors. Structural equation modelling revealed that cerebrovascular risk is associated with reduced cerebral grey matter and white matter integrity within a fronto-parietal brain network underlying executive function. Notably, higher systolic blood pressure was associated with worse executive cognitive function in mid-life (44–69 years), but not in late-life ( years). During mid-life this association did not occur in the systolic range of 110–140 mmHg. These findings suggest cerebrovascular risk factors impact on brain structure and cognitive function in healthy people.
Publisher: Wiley
Date: 20-01-2019
DOI: 10.1111/EJN.14320
Abstract: Mentorship facilitates personal growth through pairing trainees with mentors who can share their expertise. In times of global integration, geographical proximity between mentors and mentees is relevant to a lesser degree. This has led to popularization of online mentoring programs. In this editorial, we introduce the history and architecture of the International Online Mentoring Programme organized by the Student and Postdoc Special Interest Group of the Organization for Human Brain Mapping.
Publisher: Research Square Platform LLC
Date: 14-08-2020
DOI: 10.21203/RS.3.RS-53754/V1
Abstract: Female sex, age and carriage of the APOE e4 allele are the greatest risk factors for sporadic Alzheimer's disease (AD). The hippoc us has a selective vulnerability to atrophy in ageing that may be accelerated in AD, including in those with increased genetic risk of AD. Within the hippoc al complex, subfields represent cytoarchitectonic and connectivity based isions. The change in global hippoc al and subfield volume associated with sex, age and APOE e4 status in healthy ageing have not yet been established despite their potential to provide a sensitive biomarker of future vulnerability to AD. Here, we examined non-linear age, sex and APOE effects, and their interactions, on hippoc al and subfield volumes across several decades spanning mid-life to old age in 36 653 healthy ageing in iduals. Hippoc al volume showed a marked reduction in APOE e4/e4 female carriers after age 65. Volume was lower in homozygous e4 in iduals in specific subfields including the presubiculum, subiculum head, CA1 body, CA3 head and CA4. The findings demonstrate that in healthy ageing, two factors - female sex and APOE e4 status - confer selective vulnerability of specific hippoc al subfields to volume loss.
Publisher: Wiley
Date: 10-08-2023
DOI: 10.1002/ALZ.13412
Abstract: Artificial intelligence (AI) and neuroimaging offer new opportunities for diagnosis and prognosis of dementia. We systematically reviewed studies reporting AI for neuroimaging in diagnosis and/or prognosis of cognitive neurodegenerative diseases. A total of 255 studies were identified. Most studies relied on the Alzheimer's Disease Neuroimaging Initiative dataset. Algorithmic classifiers were the most commonly used AI method (48%) and discriminative models performed best for differentiating Alzheimer's disease from controls. The accuracy of algorithms varied with the patient cohort, imaging modalities, and stratifiers used. Few studies performed validation in an independent cohort. The literature has several methodological limitations including lack of sufficient algorithm development descriptions and standard definitions. We make recommendations to improve model validation including addressing key clinical questions, providing sufficient description of AI methods and validating findings in independent datasets. Collaborative approaches between experts in AI and medicine will help achieve the promising potential of AI tools in practice. There has been a rapid expansion in the use of machine learning for diagnosis and prognosis in neurodegenerative disease Most studies (71%) relied on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset with no other in idual dataset used more than five times There has been a recent rise in the use of more complex discriminative models (e.g., neural networks) that performed better than other classifiers for classification of AD vs healthy controls We make recommendations to address methodological considerations, addressing key clinical questions, and validation We also make recommendations for the field more broadly to standardize outcome measures, address gaps in the literature, and monitor sources of bias
Publisher: Springer Science and Business Media LLC
Date: 21-12-2022
DOI: 10.1038/S41467-022-35321-2
Abstract: Medical imaging provides numerous insights into the subclinical changes that precede serious diseases such as heart disease and dementia. However, most imaging research either describes a single organ system or draws on clinical cohorts with small s le sizes. In this study, we use state-of-the-art multi-organ magnetic resonance imaging phenotypes to investigate cross-sectional relationships across the heart-brain-liver axis in 30,444 UK Biobank participants. Despite controlling for an extensive range of demographic and clinical covariates, we find significant associations between imaging-derived phenotypes of the heart (left ventricular structure, function and aortic distensibility), brain (brain volumes, white matter hyperintensities and white matter microstructure), and liver (liver fat, liver iron and fibroinflammation). Simultaneous three-organ modelling identifies differentially important pathways across the heart-brain-liver axis with evidence of both direct and indirect associations. This study describes a potentially cumulative burden of multiple-organ dysfunction and provides essential insight into multi-organ disease prevention.
Publisher: Oxford University Press (OUP)
Date: 04-2020
Abstract: This scientific commentary refers to ‘Network localization of clinical, cognitive, and neuropsychiatric symptoms in Alzheimer’s disease’, by Tetreault etal. (doi:10.1093/brain/awaa058).
Publisher: Public Library of Science (PLoS)
Date: 15-12-2022
DOI: 10.1371/JOURNAL.PCBI.1010538
Abstract: Failure is an integral part of life and by extension academia. At the same time, failure is often ignored, with potentially negative consequences both for the science and the scientists involved. This article provides several strategies for learning from and dealing with failure instead of ignoring it. Hopefully, our recommendations are widely applicable, while still taking into account in idual differences between academics. These simple rules allow academics to further develop their own strategies for failing successfully in academia.
Publisher: Research Square Platform LLC
Date: 09-07-2020
DOI: 10.21203/RS.3.RS-36274/V1
Abstract: One third of ischemic stroke patients develop cognitive impairment. It is not known whether topographical secondary neurodegeneration within distributed brain structural covariance networks (SCNs) underlies this cognitive decline. We examined longitudinal changes in SCNs and their relationship to domain-specific cognitive decline in 73 ischemic stroke patients. Patients were scanned with magnetic resonance imaging (MRI) and assessed on five cognitive domains at subacute (3-months) and chronic (1-year) timepoints. In idual-level SCN scores of major cognitive networks were derived from MRI data at each timepoint. We found that distributed degeneration in higher-order cognitive networks was associated with cognitive impairment in subacute stroke. Importantly, faster degradation in these major cognitive SCNs over time was associated with greater decline in attention, memory, and language domains. Our findings suggest that subacute ischemic stroke is associated with degeneration of higher-order structural brain networks and degradation of these networks contribute to in idual trajectories of longitudinal domain-specific cognitive dysfunction.
Publisher: Cold Spring Harbor Laboratory
Date: 03-11-2021
DOI: 10.1101/2021.11.01.466751
Abstract: 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 with logistic regression structures are not necessarily directly interpretable as relative risks. On the other hand, use of log-link regression structures with the binomial variance function may lead to estimation instabilities when event probabilities are close to 1. To circumvent such issues, we use generalized estimating equations with log-link regression structures with identity variance function and unknown dispersion parameter. Even in this setting, parameter estimates can be infinite, which we address by penalizing the generalized estimating functions with the gradient of the Jeffreys prior. Our findings from extensive simulation studies show significant improvement over the standard log-link generalized estimating equations by providing finite estimates and achieving convergence when boundary estimates occur. The real data application on UK Biobank brain lesion maps further reveals the instabilities of the standard log-link generalized estimating equations for a large-scale data set and demonstrates the clear interpretation of relative risk in clinical applications.
Publisher: Elsevier BV
Date: 2019
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.NEUROBIOLAGING.2017.07.011
Abstract: Disruptions to functional connectivity in subsystems of the default mode network are evident in Alzheimer's disease (AD). Functional connectivity estimates correlations in the time course of low-frequency activity. Much less is known about other potential perturbations to this activity, such as changes in the litude of oscillations and how this relates to cognition. We examined the litude of low-frequency fluctuations in 44 AD patients and 128 cognitively normal participants and related this to episodic memory, the core deficit in AD. We show higher litudes of low-frequency oscillations in AD patients. Rather than being compensatory, this appears to be maladaptive, with greater litude in the ventral default mode subnetwork associated with poorer episodic memory. Perturbations to default mode subnetworks in AD are evident in the litude of low-frequency oscillations in the resting brain. These disruptions are associated with episodic memory demonstrating their behavioral and clinical relevance in AD.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2021
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Michele Veldsman.