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Jonathan D. Clayden

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9 papers

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YNIMG Journal 2019 Journal Article

Tractography-based parcellation does not provide strong evidence of anatomical organisation within the thalamus

Jonathan D. Clayden
David L. Thomas
Alexander Kraskov

Connectivity-based parcellation of subcortical structures using diffusion tractography is now a common paradigm in neuroscience. These analyses often imply voxel-level specificity of connectivity, and the formation of compact, spatially coherent clusters is often taken as strong imaging-based evidence for anatomically distinct subnuclei in an individual. In this study, we demonstrate that internal structure in diffusion anisotropy is not necessary for a plausible parcellation to be obtained, by spatially permuting diffusion parameters within the thalami and repeating the parcellation. Moreover, we show that, in a winner-takes-all paradigm, most voxels receive the same label before and after this shuffling process—a finding that is stable across image acquisitions and tractography algorithms. We therefore suggest that such parcellations should be interpreted with caution.

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YNICL Journal 2018 Journal Article

Structural and effective connectivity in focal epilepsy

Christopher S. Parker
Jonathan D. Clayden
M. Jorge Cardoso
Roman Rodionov
John S. Duncan
Catherine Scott
Beate Diehl
Sebastien Ourselin

Patients with medically-refractory focal epilepsy may be candidates for neurosurgery and some may require placement of intracranial EEG electrodes to localise seizure onset. Assessing cerebral responses to single pulse electrical stimulation (SPES) may give diagnostically useful data. SPES produces cortico-cortical evoked potentials (CCEPs), which infer effective brain connectivity. Diffusion-weighted images and tractography may be used to estimate structural brain connectivity. This combination provides the opportunity to observe seizure onset and its propagation throughout the brain, spreading contiguously along the cortex explored with electrodes, or non-contiguously. We analysed CCEPs and diffusion tractography in seven focal epilepsy patients and reconstructed the effective and structural brain networks. We aimed to assess the inter-modal similarity of the networks at a large scale across the cortex, the effective and structural connectivity of the ictal-onset zone, and investigate potential mechanisms of non-contiguous seizure spread. We found a significant overlap between structural and effective networks. Effective network CCEP amplitude, baseline variation, and outward connectivity was higher at ictal-onset zones, while structural connection strength within the ictal-onset zone tended to be higher. These findings support the concept of hyperexcitable cortex being associated with seizure generation. The high prevalence of structural and effective connections from the ictal-onset zone to sites of non-contiguous spread suggests that macroscopic structural and effective connections are plausible routes for non-contiguous seizure spread.

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YNICL Journal 2015 Journal Article

Tract shape modeling detects changes associated with preterm birth and neuroprotective treatment effects

Devasuda Anblagan
Mark E. Bastin
Sarah Sparrow
Chinthika Piyasena
Rozalia Pataky
Emma J. Moore
Ahmed Serag
Alastair Graham Wilkinson

Preterm birth is associated with altered connectivity of neural circuits. We developed a tract segmentation method that provides measures of tract shape and integrity (probabilistic neighborhood tractography, PNT) from diffusion MRI (dMRI) data to test the hypotheses: 1) preterm birth is associated with alterations in tract topology (R), and tract-averaged mean diffusivity (〈D〉) and fractional anisotropy (FA); 2) neural systems are separable based on tract-averaged dMRI parameters; and 3) PNT can detect neuroprotective treatment effects. dMRI data were collected from 87 preterm infants (mean gestational age 29(+1) weeks, range 23(+2) -34(+6)) at term equivalent age and 24 controls (mean gestational age 39(+6) weeks). PNT was used to segment eight major fasciculi, characterize topology, and extract tract-averaged〈D〉and FA. Tract topology was altered by preterm birth in all tracts except the splenium (p < 0.05, false discovery rate [FDR] corrected). After adjustment for age at scan, tract-averaged〈D〉was increased in the genu and splenium, right corticospinal tract (CST) and the left and right inferior longitudinal fasciculi (ILF) in preterm infants compared with controls (p < 0.05, FDR), while tract-averaged FA was decreased in the splenium and left ILF (p < 0.05, FDR). Specific fasciculi were separable based on tract-averaged〈D〉and FA values. There was a modest decrease in tract-averaged〈D〉in the splenium of preterm infants who had been exposed to antenatal MgSO4 for neuroprotection (p = 0.002). Tract topology is a biomarker of preterm brain injury. The data provide proof of concept that tract-averaged dMRI parameters have utility for evaluating tissue effects of perinatal neuroprotective strategies.

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YNIMG Journal 2013 Journal Article

Functional brain network organisation of children between 2 and 5years derived from reconstructed activity of cortical sources of high-density EEG recordings

Joe Bathelt
Helen O'Reilly
Jonathan D. Clayden
J. Helen Cross
Michelle de Haan

There is increasing interest in applying connectivity analysis to brain measures (Rubinov and Sporns, 2010), but most studies have relied on fMRI, which substantially limits the participant groups and numbers that can be studied. High-density EEG recordings offer a comparatively inexpensive easy-to-use alternative, but require channel-level connectivity analysis which currently lacks a common analytic framework and is very limited in spatial resolution. To address this problem, we have developed a new technique for studies of network development that overcomes the spatial constraint and obtains functional networks of cortical areas by using EEG source reconstruction with age-matched average MRI templates (He et al. , 1999). In contrast to previously reported channel-level analysis, this approach provides information about the cortical areas most likely to be involved in the network as well as their functional relationship (Babiloni et al. , 2005; De Vico Fallani et al. , 2007). In this study, we applied source reconstruction with age-matched templates to task-free high-density EEG recordings in typically-developing children between 2 and 6years of age (O'Reilly, 2012). Graph theory was then applied to the association strengths of 68 cortical regions of interest based on the Desikan–Killiany atlas. We found linear increases of mean node degree, mean clustering coefficient and maximum betweenness centrality between 2years and 6years of age. Characteristic path length was negatively correlated with age. The correlation of the network measures with age indicates network development towards more closely integrated networks similar to reports from other imaging modalities (Fair et al. , 2008; Power et al. , 2010). We also applied eigenvalue decomposition to obtain functional modules (Clayden et al. , 2013). Connection strength within these modules did not change with age, and the modules resembled hub networks previously described for MRI (Hagmann et al. , 2010; Power et al. , 2010). The high temporal resolution of EEG additionally allowed us to distinguish between frequency bands potentially reflecting dynamic coupling between different neural oscillators. Generally, network parameters were similar for networks based on different frequency bands, but frequency band did emerge as a significant factor for clustering coefficient and characteristic path length. In conclusion, the current analysis shows that source reconstruction of high-density EEG recordings with appropriate head models offers a valuable tool for estimating network parameters in studies of brain development. The findings replicate the pattern of closer functional integration over development described for other imaging modalities (Fair et al. , 2008; Power et al. , 2010).

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YNICL Journal 2013 Journal Article

White matter microstructure correlates with autism trait severity in a combined clinical–control sample of high-functioning adults

Clare R. Gibbard
Juejing Ren
Kiran K. Seunarine
Jonathan D. Clayden
David H. Skuse
Chris A. Clark

Diffusion tensor imaging (DTI) studies have demonstrated white matter (WM) abnormalities in tracts involved in emotion processing in autism spectrum disorder (ASD), but little is known regarding the nature and distribution of WM anomalies in relation to ASD trait severity in adults. Increasing evidence suggests that ASD occurs at the extreme of a distribution of social abilities. We aimed to examine WM microstructure as a potential marker for ASD symptom severity in a combined clinical-neurotypical population. SIENAX was used to estimate whole brain volume. Tract-based spatial statistics (TBSS) was used to provide a voxel-wise comparison of WM microstructure in 50 high-functioning young adults: 25 ASD and 25 neurotypical. The severity of ASD traits was measured by autism quotient (AQ); we examined regressions between DTI markers of WM microstructure and ASD trait severity. Cognitive abilities, measured by intelligence quotient, were well-matched between the groups and were controlled in all analyses. There were no significant group differences in whole brain volume. TBSS showed widespread regions of significantly reduced fractional anisotropy (FA) and increased mean diffusivity (MD) and radial diffusivity (RD) in ASD compared with controls. Linear regression analyses in the combined sample showed that average whole WM skeleton FA was negatively influenced by AQ (p = 0.004), whilst MD and RD were positively related to AQ (p = 0.002; p = 0.001). Regression slopes were similar within both groups and strongest for AQ social, communication and attention switching scores. In conclusion, similar regression characteristics were found between WM microstructure and ASD trait severity in a combined sample of ASD and neurotypical adults. WM anomalies were relatively more severe in the clinically diagnosed sample. Both findings suggest that there is a dimensional relationship between WM microstructure and severity of ASD traits from neurotypical subjects through to clinical ASD, with reduced coherence of WM associated with greater ASD symptoms. General cognitive abilities were independent of the relationship between WM indices and ASD traits.

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YNIMG Journal 2010 Journal Article

Quantifying the effects of normal ageing on white matter structure using unsupervised tract shape modelling

Mark E. Bastin
Susana Muñoz Maniega
Karen J. Ferguson
Laura J. Brown
Joanna M. Wardlaw
Alasdair M.J. MacLullich
Jonathan D. Clayden

Quantitative tractography may provide insights into regional heterogeneity of changes in white matter structure in normal ageing. Here we examine how brain atrophy and white matter lesions affect correlations between tract shape, tract integrity and age in a range of frontal and non-frontal tracts in 90 non-demented subjects aged over 65 years using an enhanced version of probabilistic neighbourhood tractography. This novel method for automatic single seed point placement employs unsupervised learning and streamline selection to provide reliable and accurate tract segmentation, whilst also indicating how the shape of an individual tract compares to that of a predefined reference tract. There were significant negative correlations between tract shape similarity to reference tracts derived from a young brain white matter atlas and age in genu and splenium of corpus callosum. Controlling for intracranial and lateral ventricle volume, the latter of which increased significantly with age, attenuated these correlations by 40% and 84%, respectively, indicating that this age-related change in callosal tract topology is significantly mediated by global atrophy and ventricular enlargement. In accordance with the “frontal ageing” hypothesis, there was a significant positive correlation between mean diffusivity (〈D〉) and age, and a significant negative correlation between fractional anisotropy (FA) and age in corpus callosum genu; correlations not seen in splenium. Significant positive correlations were also observed between 〈D〉 and age in bilateral cingulum cingulate gyri, uncinate fasciculi and right corticospinal tract. This pattern of correlations was not, however, reproduced when those subjects with significant white matter lesion load were analyzed separately from those without. These data therefore suggest that brain atrophy and white matter lesions play a significant role in driving regional patterns of age-related changes in white matter tract shape and integrity.

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YNIMG Journal 2009 Journal Article

Reproducibility of tract segmentation between sessions using an unsupervised modelling-based approach

Jonathan D. Clayden
Amos J. Storkey
Susana Muñoz Maniega
Mark E. Bastin

This work describes a reproducibility analysis of scalar water diffusion parameters, measured within white matter tracts segmented using a probabilistic shape modelling method. In common with previously reported neighbourhood tractography (NT) work, the technique optimises seed point placement for fibre tracking by matching the tracts generated using a number of candidate points against a reference tract, which is derived from a white matter atlas in the present study. No direct constraints are applied to the fibre tracking results. An Expectation–Maximisation algorithm is used to fully automate the procedure, and make dramatically more efficient use of data than earlier NT methods. Within-subject and between-subject variances for fractional anisotropy and mean diffusivity within the tracts are then separated using a random effects model. We find test–retest coefficients of variation (CVs) similar to those reported in another study using landmark-guided single seed points; and subject to subject CVs similar to a constraint-based multiple ROI method. We conclude that our approach is at least as effective as other methods for tract segmentation using tractography, whilst also having some additional benefits, such as its provision of a goodness-of-match measure for each segmentation.

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YNIMG Journal 2008 Journal Article

Tract shape modelling provides evidence of topological change in corpus callosum genu during normal ageing

Mark E. Bastin
Jakub P. Piatkowski
Amos J. Storkey
Laura J. Brown
Alasdair M.J. MacLullich
Jonathan D. Clayden

Understanding how ageing affects brain structure is an important challenge for medical science. By allowing segmentation of fasciculi-of-interest from diffusion magnetic resonance imaging (dMRI) data, tractography provides a promising tool for assessing white matter connectivity in old age. However, the output from tractography algorithms is usually strongly dependent on the subjective location of user-specified seed points, with the result that it can be both difficult and time consuming to identify the same tract reliably in cross-sectional studies. Here we investigate whether a novel method for automatic single seed point placement based on tract shape modelling, termed probabilistic model-based neighbourhood tractography (PNT), can reliably segment the same tract from subject to subject in a non-demented cohort aged over 65 years. For the fasciculi investigated (genu and splenium of corpus callosum, cingulum cingulate gyri, corticospinal tracts and uncinate fasciculi), PNT was able to provide anatomically plausible representations of the tract in question in 70 to 90% of subjects compared with 2. 5 to 60% if single seed points were simply transferred directly from standard to native space. In corpus callosum genu there was a significant negative correlation between a PNT-derived measure of tract shape similarity to a young brain reference tract and age, and a trend towards a significant negative correlation between tract-averaged fractional anisotropy and age; results that are consistent with previous dMRI studies of normal ageing. These data show that it is possible automatically to segment comparable tracts in the brains of older subjects using single seed point tractography, if the seed point is carefully chosen.

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YNIMG Journal 2006 Journal Article

Improved segmentation reproducibility in group tractography using a quantitative tract similarity measure

Jonathan D. Clayden
Mark E. Bastin
Amos J. Storkey

The field of tractography is rapidly developing, and many automatic or semiautomatic algorithms have now been devised to segment and visualize neural white matter fasciculi in vivo. However, these algorithms typically need to be given a starting location as input, and their output can be strongly dependent on the exact location of this “seed point”. No robust method has yet been devised for placing these seed points so as to segment a comparable tract in a group of subjects. Here, we develop a measure of tract similarity, based on the shapes and lengths of the two tracts being compared, and apply it to the problem of consistent seed point placement and tract segmentation in group data. We demonstrate that using a single seed point transferred from standard space to each native space produces considerable variability in tractography output between scans. However, by seeding in a group of nearby candidate points and choosing the output with the greatest similarity to a reference tract chosen in advance–a method we refer to as neighborhood tractography–this variability can be significantly reduced.

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