Derek K Jones

The Institute of Mental Health, Cardiff, Wales, United Kingdom

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Publications (78)386.67 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: A comprehensive image-based characterization of white matter should include the ability to quantify myelin and axonal attributes irrespective of the complexity of fibre organization within the voxel. While progress has been made with diffusion MRI-based approaches to measure axonal morphology, to date available myelin metrics simply assign a single scalar value to the voxel, reflecting some form of average of its constituent fibres. Here, a new experimental framework that combines diffusion MRI and relaxometry is introduced. It provides, for the first time, the ability to assign to each unique fibre system within a voxel, a unique value of the longitudinal relaxation time, T1 , which is largely influenced by the myelin content. We demonstrate the method through simulations, in a crossing fibres phantom, in fixed brains and in vivo. The method is capable of recovering unique values of T1 for each fibre population. The ability to extract fibre-specific relaxometry properties will provide enhanced specificity and, therefore, sensitivity to differences in white matter architecture, which will be invaluable in many neuroimaging studies. Further the enhanced specificity should ultimately lead to earlier diagnosis and access to treatment in a range of white matter diseases where axons are affected. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 03/2015; DOI:10.1002/mrm.25644 · 3.40 Impact Factor
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    ABSTRACT: The fornix and hippocampus are critical to recollection in the healthy human brain. Fornix degeneration is a feature of aging and Alzheimer's disease. In the presence of fornix damage in mild cognitive impairment (MCI), a recognized prodrome of Alzheimer's disease, recall shows greater dependence on other tracts, notably the parahippocampal cingulum (PHC). The current aims were to determine whether this shift is adaptive and to probe its relationship to cholinergic signaling, which is also compromised in Alzheimer's disease. Twenty-five human participants with MCI and 20 matched healthy volunteers underwent diffusion MRI, behavioral assessment, and volumetric measurement of the basal forebrain. In a regression model for recall, there was a significant group × fornix interaction, indicating that the association between recall and fornix structure was weaker in patients. The opposite trend was present for the left PHC. To further investigate this pattern, two regression models were generated to account for recall performance: one based on fornix microstructure and the other on both fornix and left PHC. The realignment to PHC was positively correlated with free recall but not non-memory measures, implying a reconfiguration that is beneficial to residual memory. There was a positive relationship between realignment to PHC and basal forebrain gray matter volume despite this region demonstrating atrophy at a group level, i.e., the cognitive realignment to left PHC was most apparent when cholinergic areas were relatively spared. Therefore, cholinergic systems appear to enable adaptation to injury even as they degenerate, which has implications for functional restoration. Copyright © 2015 Ray et al.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 01/2015; 35(2):739-47. DOI:10.1523/JNEUROSCI.3617-14.2015 · 6.75 Impact Factor
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    ABSTRACT: Background White matter microstructure alterations of limbic and reward pathways have been reported repeatedly for depressive episodes in major depressive disorder (MDD) and bipolar disorder (BD). However, findings during remission are equivocal. It was the aim of this study to investigate if white matter microstructure changes during the time course of clinical remission. Methods Fifteen depressed patients (11 MDD, 4 BD) underwent diffusion-weighted MRI both during depression, and during remission following successful antidepressive treatment (average time interval between scans=6 months). Fractional anisotropy (FA) was sampled along reconstructions of the supero-lateral medial forebrain bundle (slMFB), the cingulum bundle (CB), the uncinate fasciculus (UF), the parahippocampal cingulum (PHC) and the fornix. Repeated measures ANCOVAs controlling for the effect of age were calculated for each tract. Results There was a significant main effect of time (inter-scan interval) for mean-FA for the right CB and for the left PHC. For both pathways there was a significant time×age interaction. In the right CB, FA increased in younger patients, while FA decreased in older patients. In the left PHC, a reverse pattern was seen. FA changes in the right CB correlated positively with symptom reductions. Mean-FA of UF, slMFB and fornix did not change between the two time points. Limitations All patients were medicated, sample size, and lack of control group. Conclusions Right CB and left PHC undergo age-dependent plastic changes during the course of remission and may serve as a state marker in depression. UF, slMFB and FO microstructure remains stable.
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    ABSTRACT: Transection of the nonhuman primate fornix has been shown to impair learning of configurations of spatial features and object-in-scene memory. Although damage to the human fornix also results in memory impairment, it is not known whether there is a preferential involvement of this white-matter tract in spatial learning, as implied by animal studies. Diffusion-weighted MR images were obtained from healthy participants who had completed versions of a task in which they made rapid same/different discriminations to two categories of highly visually similar stimuli: (1) virtual reality scene pairs; and (2) face pairs. Diffusion-MRI measures of white-matter microstructure [fractional anisotropy (FA) and mean diffusivity (MD)] and macrostructure (tissue volume fraction, f) were then extracted from the fornix of each participant, which had been reconstructed using a deterministic tractography protocol. Fornix MD and f measures correlated with scene, but not face, discrimination accuracy in both discrimination tasks. A complementary voxelwise analysis using tract-based spatial statistics suggested the crus of the fornix as a focus for this relationship. These findings extend previous reports of spatial learning impairments after fornix transection in nonhuman primates, critically highlighting the fornix as a source of interindividual variation in scene discrimination in humans.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 09/2014; 34(36):12121-6. DOI:10.1523/JNEUROSCI.0026-14.2014 · 6.75 Impact Factor
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    ABSTRACT: White matter microstructure alterations of limbic and reward pathways have been reported repeatedly for depressive episodes in major depressive disorder (MDD) and bipolar disorder (BD). However, findings during remission are equivocal. It was the aim of this study to investigate if white matter microstructure changes during the time course of clinical remission.
    Journal of Affective Disorders 08/2014; 170C:143-149. DOI:10.1016/j.jad.2014.08.031 · 3.71 Impact Factor
  • Alzheimer's and Dementia 07/2014; 10(4):P384. DOI:10.1016/j.jalz.2014.05.457 · 17.47 Impact Factor
  • Proceedings of the International Society for Magnetic Resonance in Medicine, Milan, Italy; 05/2014
  • Schizophrenia Research 04/2014; 153:S207. DOI:10.1016/S0920-9964(14)70600-0 · 4.43 Impact Factor
  • Proceedings of the International Society for Magnetic Resonance in Medicine, Milan, Italy; 04/2014
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    ABSTRACT: Diffusion MRI is used widely to probe microstructural alterations in neurological and psychiatric disease. However, ageing and neurodegeneration are also associated with atrophy, which leads to artefacts through partial volume effects due to cerebrospinal-fluid contamination (CSFC). The aim of this study was to explore the influence of CSFC on apparent microstructural changes in mild cognitive impairment (MCI) at several spatial levels: individually reconstructed tracts; at the level of a whole white matter skeleton (tract-based spatial statistics); and histograms derived from all white matter. 25 individuals with MCI and 20 matched controls underwent diffusion MRI. We corrected for CSFC using a post-acquisition voxel-by-voxel approach of free-water elimination. Tracts varied in their susceptibility to CSFC. The apparent pattern of tract involvement in disease shifted when correction was applied. Both spurious group differences, driven by CSFC, and masking of true differences were observed. Tract-based spatial statistics were found to be robust across much of the skeleton but with some localised CSFC effects. Diffusivity measures were affected disproportionately in MCI, and group differences in fornix microstructure were exaggerated. Group differences in white matter histogram measures were also partly driven by CSFC. For diffusivity measures, up to two thirds of observed group differences were due to CSFC. Our results demonstrate that CSFC has an impact on quantitative differences between MCI and controls. Furthermore, it affects the apparent spatial pattern of white matter involvement. Free-water elimination provides a step towards disentangling intrinsic and volumetric alterations in individuals prone to atrophy.
    NeuroImage 02/2014; DOI:10.1016/j.neuroimage.2014.01.031 · 6.13 Impact Factor
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  • Proceedings of the International Society for Magnetic Resonance in Medicine, Milan, Italy; 01/2014
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    ABSTRACT: Huntington's disease (HD) is an autosominal dominant neurodegenerative condition that leads to progressive loss of motor and cognitive functions. Early symptoms in HD include subtle executive dysfunction related to white and grey matter loss in cortico-striatal-thalamic loops. There is no cure for HD and hence a significant need for early intervention with the potential to delay the clinical onset of the disease.
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    ABSTRACT: Fundamental to increasing our understanding of the role of white matter microstructure in normal/abnormal function in the living human is the development of MR-based metrics that provide increased specificity to distinct attributes of the white matter(e.g., local fibre architecture, axon morphology, myelin content). In recent years, different approaches have been developed to enhance this specificity, and the Tractometry framework was introduced to combine the resulting multi-parametricdata for a comprehensive assessment of white matter properties. The present work exploits that framework to characterize the statistical properties, specifically the variance and covariance, of these advanced microstructural indices across the major white matter pathways, blackwith the aim of giving clear indications on the preferred metric(s) given the specific research question. A cohort of healthy subjects was scanned with a protocol that combined multi-component relaxometry with conventional and advanced diffusion MRI acquisitions to build the first comprehensive MRI atlas of white matter microstructure. The mean and standard deviation of the different metrics were analysed in order to understand how they vary across different brain regions/individuals and the correlation between them. Characterizing the fibre architectural complexity (in terms of number of fibre populations in a voxel) provides clear insights into correlation/lack of correlation between the different metrics and explains why DT-MRI is a good model for white matter only some of the time. The study also identifies the metrics that account for the largest inter-subject variability and reports the minimal sample size required to detect differences in means, blackshowing that, on the other hand, conventional DT-MRI indices might still be the safest choice in many contexts.
    NeuroImage 12/2013; DOI:10.1016/j.neuroimage.2013.12.003 · 6.13 Impact Factor
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    ABSTRACT: In recent years, diffusion MRI has become an extremely important tool for studying the morphology of living brain tissue, as it provides unique insights into both its macrostructure and microstructure. Recent applications of diffusion MRI aimed to characterize the structural connectome using tractography to infer connectivity between brain regions. In parallel to the development of tractography, additional diffusion MRI based frameworks (CHARMED, AxCaliber, ActiveAx) were developed enabling the extraction of a multitude of micro-structural parameters (axon diameter distribution, mean axonal diameter and axonal density). This unique insight into both tissue microstructure and connectivity has enormous potential value in understanding the structure and organisation of the brain as well as providing unique insights to abnormalities that underpin disease states The CONNECT (Consortium Of Neuroimagers for the Non-invasive Exploration of brain Connectivity and Tracts) project aimed to combine tractography and micro-structural measures of the living human brain in order to obtain a better estimate of the connectome, while also striving to extend validation of these measurements. This paper summarizes the project and describes the perspective of using micro-structural measures to study the connectome.
    NeuroImage 05/2013; DOI:10.1016/j.neuroimage.2013.05.055 · 6.13 Impact Factor
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    ABSTRACT: The prevalence of obesity and associated health conditions is increasing in the developed world. Obesity is related to atrophy and dysfunction of the hippocampus and hippocampal lesions may lead to increased appetite and weight gain. The hippocampus is connected via the fornix tract to the hypothalamus, orbitofrontal cortex, and the nucleus accumbens, all key structures for homeostatic and reward related control of food intake. The present study employed diffusion MRI tractography to investigate the relationship between microstructural properties of the fornix and variation in Body Mass Index (BMI), within normal and overweight ranges, in a group of community-dwelling older adults (53-93 years old). Larger BMI was associated with larger axial and mean diffusivity in the fornix (r = 0.64 and r = 0.55 respectively), relationships that were most pronounced in overweight individuals. Moreover, controlling for age, education, cognitive performance, blood pressure and global brain volume increased these correlations. Similar associations were not found in the parahippocampal cingulum, a comparison temporal association pathway. Thus, microstructural changes in fornix white matter were observed in older adults with increasing BMI levels from within normal to overweight ranges, so are not exclusively related to obesity. We propose that hippocampal-hypothalamic-prefrontal interactions, mediated by the fornix, contribute to the healthy functioning of networks involved in food intake control. The fornix, in turn, may display alterations in microstructure that reflect weight gain.
    PLoS ONE 03/2013; 8(3):e59849. DOI:10.1371/journal.pone.0059849 · 3.53 Impact Factor
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    ABSTRACT: Cognitive control, an important facet of human cognition, provides flexibility in response to varying behavioral demands. Previous work has focused on the role of prefrontal cortex, notably the anterior cingulate cortex. However, it is now clear that this is one node of a distributed cognitive network. In this emerging network view, structural connections are inherent elements, but their role has not been emphasized. Furthermore, lesion and functional imaging studies have contributed little knowledge about anatomical segregation, functional specialization, and behavioral importance of white matter connections. The relationship between cognitive control and microstructure of connections within the cingulum, a major white matter tract and conduit of projections to prefrontal sites, was probed in vivo in humans with diffusion MRI. Twenty healthy controls and 25 individuals with amnestic mild cognitive impairment (MCI), an early stage of age-associated cognitive deterioration, underwent cognitive testing, including several measures of cognitive control. For each individual, the anterior, middle, posterior, and parahippocampal portions of the cingulum bundle were reconstructed separately using deterministic tractography and anatomical landmarks. Microstructural variation in the left anterior cingulum was closely related to interindividual control based on verbal or symbolic rules. Errors in a task that involved maintenance of spatial rules were largely restricted to patients with MCI and were related, additionally, to right anterior cingulum microstructure. Cognitive control in MCI was also independently related to posterior parahippocampal connections. These results show how specific subpopulations of connections are critical in cognitive control and illustrate fine-grained anatomical specializations in the white matter infrastructure of this network.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 12/2012; 32(49):17612-17619. DOI:10.1523/JNEUROSCI.3299-12.2012 · 6.75 Impact Factor
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    ABSTRACT: OBJECTIVE: To examine the pattern of association between microstructure of temporal lobe connections and the breakdown of episodic memory that is a core feature of mild cognitive impairment (MCI). METHODS: Twenty-five individuals with MCI and 20 matched controls underwent diffusion MRI and cognitive assessment. Three temporal pathways were reconstructed by tractography: fornix, parahippocampal cingulum (PHC), and uncinate fasciculus. Tissue volume fraction-a tract-specific measure of atrophy-and microstructural measures were derived for each tract. To test specificity of associations, a comparison tract (corticospinal tract) and control cognitive domains were also examined. RESULTS: In MCI, tissue volume fraction was reduced in the fornix. Axial and radial diffusivity were increased in uncinate and PHC implying more subtle microstructural change. In controls, tissue volume fraction in the fornix was the predominant correlate of free recall. In contrast, in MCI, the strongest relationship was with left PHC. Microstructure of uncinate and PHC also correlated with recognition memory, and recognition confidence, in MCI. CONCLUSIONS: Episodic memory in MCI is related to the structure of multiple temporal association pathways. These associations are not confined to the fornix, as they are in healthy young and older adults. In MCI, because of a compromised fornix, alternative pathways may contribute disproportionally to episodic memory performance.
    Neurology 11/2012; 79(23). DOI:10.1212/WNL.0b013e31827689e8 · 8.30 Impact Factor
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    ABSTRACT: The development of therapeutic strategies that promote functional recovery is a major goal of multiple sclerosis (MS) research. Neuroscientific and methodological advances have improved our understanding of the brain's recovery from damage, generating novel hypotheses about potential targets and modes of intervention, and laying the foundation for development of scientifically informed recovery-promoting strategies in interventional studies. This Review aims to encourage the transition from characterization of recovery mechanisms to development of strategies that promote recovery in MS. We discuss current evidence for functional reorganization that underlies recovery and its implications for development of new recovery-oriented strategies in MS. Promotion of functional recovery requires an improved understanding of recovery mechanisms that can be modulated by interventions and the development of robust measurements of therapeutic effects. As imaging methods can be used to measure functional and structural alterations associated with recovery, this Review discusses their use to obtain reliable markers of the effects of interventions.
    Nature Reviews Neurology 09/2012; DOI:10.1038/nrneurol.2012.179 · 15.52 Impact Factor
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    ABSTRACT: Diffusion-weighted MRI (DW-MRI) has been increasingly used in imaging neuroscience over the last decade. An early form of this technique, diffusion tensor imaging (DTI) was rapidly implemented by major MRI scanner companies as a scanner selling point. Due to the ease of use of such implementations, and the plausibility of some of their results, DTI was leapt on by imaging neuroscientists who saw it as a powerful and unique new tool for exploring the structural connectivity of human brain. However, DTI is a rather approximate technique, and its results have frequently been given implausible interpretations that have escaped proper critique and have appeared misleadingly in journals of high reputation. In order to encourage the use of improved DW-MRI methods, which have a better chance of characterizing the actual fiber structure of white matter, and to warn against the misuse and misinterpretation of DTI, we review the physics of DW-MRI, indicate currently preferred methodology, and explain the limits of interpretation of its results. We conclude with a list of 'Do's and Don'ts' which define good practice in this expanding area of imaging neuroscience.
    NeuroImage 07/2012; DOI:10.1016/j.neuroimage.2012.06.081 · 6.13 Impact Factor

Publication Stats

8k Citations
386.67 Total Impact Points


  • 2015
    • The Institute of Mental Health
      Cardiff, Wales, United Kingdom
  • 2007–2015
    • Cardiff University
      • School of Psychology
      Cardiff, Wales, United Kingdom
  • 2013
    • University of Bristol
      • School of Experimental Psychology
      Bristol, England, United Kingdom
  • 2009
    • University of South Wales
      Понтиприте, Wales, United Kingdom
  • 2000–2007
    • King's College London
      • • Department of Clinical Neuroscience
      • • Institute of Psychiatry
      Londinium, England, United Kingdom
  • 2006
    • National Institutes of Health
      • Section on Tissue Biophysics and Biomimetics
      Maryland, United States
  • 2004–2005
    • National Institute of Child Health and Human Development
      Maryland, United States
  • 1999
    • University of Leicester
      Leiscester, England, United Kingdom