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Biomedical subjects

Keith J Worsley

Publications and source records attributed to Keith J Worsley.

10 recordsLinked to original sources

Focal cortical atrophy in multiple sclerosis: relation to lesion load and disability.

Multiple sclerosis (MS) is thought to predominantly affect white matter (WM). Recently, however, loss of cortical gray matter has also been described. Little is known about the cause of cortical atrophy in MS, whether it occurs early in the disease course, and whether it affects all cortical regions equally or if there is a preferential pattern of focal cortical atrophy. An automated method was used to compute the thickness at every vertex of the cortical surface of the brains of 425 early relapsing-remitting MS patients. We correlated cortical thickness with the WM lesion load and the Expanded Disability Status Scale score. Mean cortical thickness correlated with WM lesion load and disability. The correlations of cortical thickness with total lesion load and disability were most significant in cingulate gyrus, insula, and associative cortical regions. Conversely, primary sensory, visual, and motor areas showed a less significant relationship. The highest amount of atrophy per lesion volume or disability scale unit was in the anterior cingulate cortex. This study confirms the relation between cortical atrophy, WM lesion load, and disability in MS, and suggests that cortical atrophy occurs even in MS patients with only mild disability. Most interestingly, we show a specific regional pattern of focal atrophy in MS that is distinctively different from the one in normal aging. The predilection of the atrophic process for areas that are heavily inter-connected with other brain regions suggests that interruption of WM tracts by MS plaques contributes, at least in part, to the development of cortical atrophy.

Aged↗

Functional role of the basal ganglia in the planning and execution of actions.

OBJECTIVE: Recent studies of functional brain imaging have shown the involvement of the basal ganglia in executive processes such as planning and set-shifting. However, the specific contributions of the striatum in those processes remain unknown. This study aimed to test the hypothesis that the caudate nucleus is primarily involved in the preparation of a novel action and not in set-shifting per se. METHODS: In the present event-related functional magnetic resonance imaging (fMRI) study, a new task was developed that permitted, for the first time, to distinguish between shifts in classification when the rule is implicitly given by the task from shifts that require cognitive comparison and planning. RESULTS: Significantly increased activity in the caudate nucleus and the putamen was observed only in conditions in which cognitive planning was required to perform a set-shift, whereas significant activation was seen in the subthalamic nucleus (another region of the basal ganglia) in all shifting conditions whether or not planning was required. INTERPRETATION: We suggest that the caudate nucleus and the putamen are particularly important, respectively, in the planning and the execution of a self-generated novel action, whereas the subthalamic nucleus may be required when a new motor program is solicited independently of the choice of strategy.

Adolescent↗

Accurate statistical tests for smooth classification images.

Despite an obvious demand for a variety of statistical tests adapted to classification images, few have been proposed. We argue that two statistical tests based on random field theory (RFT) satisfy this need for smooth classification images. We illustrate these tests on classification images representative of the literature from F. Gosselin and P. G. Schyns (2001) and from A. B. Sekuler, C. M. Gaspar, J. M. Gold, and P. J. Bennett (2004). The necessary computations are performed using the Stat4Ci Matlab toolbox.

Classification↗

Comparing functional connectivity via thresholding correlations and singular value decomposition.

We compare two common methods for detecting functional connectivity: thresholding correlations and singular value decomposition (SVD). We find that thresholding correlations are better at detecting focal regions of correlated voxels, whereas SVD is better at detecting extensive regions of correlated voxels. We apply these results to resting state networks in an fMRI dataset to look for connectivity in cortical thickness.

Brain↗

Changes in white matter in long-term survivors of severe non-missile traumatic brain injury: a computational analysis of magnetic resonance images.

The aim of this study was to investigate long-term consequences of severe non-missile traumatic brain injury (nmTBI) in patients without macroscopic focal brain lesions (>1.6 cm(3)) on regional white-matter density (WMd), and possible correlations with days of coma and memory performances. T1-weighted magnetic-resonance images (MRI) were acquired in 19 nmTBI patients, 3-113 months following the injury, and in 19 control subjects matched for age and gender. In addition, nmTBI patients underwent a battery of standardised memory tests. The MRIs were processed in a fully automatic system using voxel-by-voxel methods. Corpus callosum, fornix, anterior limb of the internal capsule, superior frontal gyrus, para-hippocampal gyrus, optic radiation and chiasma showed significant WMd reduction in nmTBI when compared to control subjects. None of the correlations between days of coma and memory performance scores with nmTBI voxels value that showed WMd reduction reached significance, with the exception of a significant negative correlation between WMd in the mid body of corpus callosum and short-story delayed recall. We detected reductions in WM density in several brain locations similar to those described in previous post mortem investigations. In addition, we observed WMd reduction in the optic chiasma and in the optic radiations; this finding may reflect transneural degeneration along the visual pathway. The weak correlations between specific anatomical sites of the reduced WMd and behavior may reflect the diffuse nature of the brain damage and/or the different time of onset between behavioral manifestations and neuropathological modifications occurring in nmTBI.

Adolescent↗

Nonstationary cluster-size inference with random field and permutation methods.

Because of their increased sensitivity to spatially extended signals, cluster-size tests are widely used to detect changes and activations in brain images. However, when images are nonstationary, the cluster-size distribution varies depending on local smoothness. Clusters tend to be large in smooth regions, resulting in increased false positives, while in rough regions, clusters tend to be small, resulting in decreased sensitivity. Worsley et al. proposed a random field theory (RFT) method that adjusts cluster sizes according to local roughness of images [Worsley, K.J., 2002. Nonstationary FWHM and its effect on statistical inference of fMRI data. Presented at the 8th International Conference on Functional Mapping of the Human Brain, June 2-6, 2002, Sendai, Japan. Available on CD-ROM in NeuroImage 16 (2) 779-780; Hum. Brain Mapp. 8 (1999) 98]. In this paper, we implement this method in a permutation test framework, which requires very few assumptions, is known to be exact [J. Cereb. Blood Flow Metab. 16 (1996) 7] and is robust [NeuroImage 20 (2003) 2343]. We compared our method to stationary permutation, stationary RFT, and nonstationary RFT methods. Using simulated data, we found that our permutation test performs well under any setting examined, whereas the nonstationary RFT test performs well only for smooth images under high df. We also found that the stationary RFT test becomes anticonservative under nonstationarity, while both nonstationary RFT and permutation tests remain valid under nonstationarity. On a real PET data set we found that, though the nonstationary tests have reduced sensitivity due to smoothness estimation variability, these tests have better sensitivity for clusters in rough regions compared to stationary cluster-size tests. We include a detailed and consolidated description of Worsley nonstationary RFT cluster-size test.

Brain↗

Unified univariate and multivariate random field theory.

We report new random field theory P values for peaks of canonical correlation SPMs for detecting multiple contrasts in a linear model for multivariate image data. This completes results for all types of univariate and multivariate image data analysis. All other known univariate and multivariate random field theory results are now special cases, so these new results present a true unification of all currently known results. As an illustration, we use these results in a deformation-based morphometry (DBM) analysis to look for regions of the brain where vector deformations of nonmissile trauma patients are related to several verbal memory scores, to detect regions of changes in anatomical effective connectivity between the trauma patients and a group of age- and sex-matched controls, and to look for anatomical connectivity in cortical thickness.

Adult↗

Deformation-based surface morphometry applied to gray matter deformation.

We present a unified statistical approach to deformation-based morphometry applied to the cortical surface. The cerebral cortex has the topology of a 2D highly convoluted sheet. As the brain develops over time, the cortical surface area, thickness, curvature, and total gray matter volume change. It is highly likely that such age-related surface changes are not uniform. By measuring how such surface metrics change over time, the regions of the most rapid structural changes can be localized. We avoided using surface flattening, which distorts the inherent geometry of the cortex in our analysis and it is only used in visualization. To increase the signal to noise ratio, diffusion smoothing, which generalizes Gaussian kernel smoothing to an arbitrary curved cortical surface, has been developed and applied to surface data. Afterward, statistical inference on the cortical surface will be performed via random fields theory. As an illustration, we demonstrate how this new surface-based morphometry can be applied in localizing the cortical regions of the gray matter tissue growth and loss in the brain images longitudinally collected in the group of children and adolescents.

Adolescent↗

Statistical mapping analysis of lesion location and neurological disability in multiple sclerosis: application to 452 patient data sets.

In multiple sclerosis (MS), the correlation between disability and the volume of white matter lesions on magnetic resonance imaging (MRI) is usually weak. This may be because lesion location also influences the extent and type of functional disability. We applied an automatic lesion-detection algorithm to 452 MRI scans of patients with relapsing-remitting MS to identify the regions preferentially responsible for different types of clinical deficits. Statistical parametric maps were generated by performing voxel-wise linear regressions between lesion probability and different clinical disability scores. There was a clear distinction between lesion locations causing physical and cognitive disability. Lesion likelihood correlated with the Expanded Disability Status Scale (EDSS) in the left internal capsule and in periventricular white matter mostly in the left hemisphere. Pyramidal deficits correlated with only one area in the left internal capsule that was also present in the EDSS correlation. Cognitive dysfunction correlated with lesion location at the grey-white junction of associative, limbic, and prefrontal cortex. Coordination impairment correlated with areas in interhemispheric and pyramidal periventricular white matter tracts, and in the inferior and superior longitudinal fascicles. Bowel and bladder scores correlated with lesions in the medial frontal lobes, cerebellum, insula, dorsal midbrain, and pons, areas known to be involved in the control of micturition. This study demonstrates for the first time a relationship between the site of lesions and the type of disability in large scale MRI data set in MS.

Adult↗

Multivariate model specification for fMRI data.

We present a general method-denoted MoDef-to help specify (or define) the model used to analyze brain imaging data. This method is based on the use of the multivariate linear model on a training data set. We show that when the a priori knowledge about the expected brain response is not too precise, the method allows for the specification of a model that yields a better sensitivity in the statistical results. This obviously relies on the validity of the a priori information, in our case the representativity of the training set, an issue addressed using a cross-validation technique. We propose a fast implementation that allows the use of the method on large data sets as found with functional Magnetic Resonance Images. An example of application is given on an experimental fMRI data set that includes nine subjects who performed a mental computation task. Results show that the method increases the statistical sensitivity of fMRI analyses.

Brain↗