Tract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data

Oxford University Centre for Functional MRI of the Brain (FMRIB), Dept. Clinical Neurology, University of Oxford, UK.
NeuroImage (Impact Factor: 6.36). 08/2006; 31(4):1487-505. DOI: 10.1016/j.neuroimage.2006.02.024
Source: PubMed


There has been much recent interest in using magnetic resonance diffusion imaging to provide information about anatomical connectivity in the brain, by measuring the anisotropic diffusion of water in white matter tracts. One of the measures most commonly derived from diffusion data is fractional anisotropy (FA), which quantifies how strongly directional the local tract structure is. Many imaging studies are starting to use FA images in voxelwise statistical analyses, in order to localise brain changes related to development, degeneration and disease. However, optimal analysis is compromised by the use of standard registration algorithms; there has not to date been a satisfactory solution to the question of how to align FA images from multiple subjects in a way that allows for valid conclusions to be drawn from the subsequent voxelwise analysis. Furthermore, the arbitrariness of the choice of spatial smoothing extent has not yet been resolved. In this paper, we present a new method that aims to solve these issues via (a) carefully tuned non-linear registration, followed by (b) projection onto an alignment-invariant tract representation (the "mean FA skeleton"). We refer to this new approach as Tract-Based Spatial Statistics (TBSS). TBSS aims to improve the sensitivity, objectivity and interpretability of analysis of multi-subject diffusion imaging studies. We describe TBSS in detail and present example TBSS results from several diffusion imaging studies.

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    • "Subsequently, maps of fractional anisotropy (FA) were worked out for each subject using the function FDT (FMRIB's Diffusion Toolbox) package, with the diffusion tensor being obtained for each voxel. TBSS (Tract-Based Spatial Statistics ) [37] was then applied and individual whole-brain FA data was aligned via non-linear registration with the most representative subjects brain space and then affine-aligned into specific template according to this study (children's study template). All the subjects were then registered in a common space, and a mean FA image was generated and thinned to create a mean FA skeleton representing the centres of all common tracts for all the subjects, with a threshold set at FA = 0.20. "
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    ABSTRACT: Non-invasive quantitative MRI methods, such as Diffusion Tensor Imaging (DTI) can offer insights into diverse developmental brain disorders such as dyslexia, the most prevalent reading disorder in childhood. In this article, we quantified the microstructural attributes of the main fascicles of both hemispheres related to the reading network in three groups of Spanish children: typically developing readers (TDR or controls), dyslexic readers (DXR) and readers with monocular vision due to ocular motility disorders (MVR), to assess whether the dyslexic children neuronal network for reading shares similarities with the neuronal network for reading in children with impaired binocular vision due to ocular motility disorders or not. Diffusion anisotropy, and mean, radial and axial diffusivity of cross-sectional subregions of the main fascicles studied were computed using a validated DTI methodology. Our results reveal differences in fractional anisotropy (FA) values between the DXR and the non-dyslexic readers, with a decreased FA for the DXR and no significant differences between TDR and MVR groups in the left Arcuate fasciculus, and a tendency to higher FA values in the DXR group compared to the other two groups in the genu of the Corpus Callosum (CC). In the splenium of the CC a trend towards higher FA values was observed in the DXR and MVR groups versus the TDR. This study reveals a different brain connectivity pattern for reading in Spanish children with dyslexia from those with impaired binocular vision due to ocular motility disorders, which would support the hypothesis that ocular motility disorders are not a causal factor of dyslexia.
    Biomedical Signal Processing and Control 01/2016; 23:19-27. DOI:10.1016/j.bspc.2015.07.009 · 1.42 Impact Factor
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    • "All subjects' images were then aligned into the Montreal Neurological Institute (MNI) space. Statistical analysis of tractography images was carried out using Tract-Based Spatial Statistics (threshold 0.2) (Smith et al., 2006). "
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    ABSTRACT: Tics are sometimes described as voluntary movements performed in an automatic or habitual way. Here, we addressed the question of balance between goal-directed and habitual behavioural control in Gilles de la Tourette syndrome and formally tested the hypothesis of enhanced habit formation in these patients. To this aim, we administered a three-stage instrumental learning paradigm to 17 unmedicated and 17 antipsychotic-medicated patients with Gilles de la Tourette syndrome and matched controls. In the first stage of the task, participants learned stimulus-response-outcome associations. The subsequent outcome devaluation and 'slip-of-action' tests allowed evaluation of the participants' capacity to flexibly adjust their behaviour to changes in action outcome value. In this task, unmedicated patients relied predominantly on habitual, outcome-insensitive behavioural control. Moreover, in these patients, the engagement in habitual responses correlated with more severe tics. Medicated patients performed at an intermediate level between unmedicated patients and controls. Using diffusion tensor imaging on a subset of patients, we also addressed whether the engagement in habitual responding was related to structural connectivity within cortico-striatal networks. We showed that engagement in habitual behaviour in patients with Gilles de la Tourette syndrome correlated with greater structural connectivity within the right motor cortico-striatal network. In unmedicated patients, stronger structural connectivity of the supplementary motor cortex with the sensorimotor putamen predicted more severe tics. Overall, our results indicate enhanced habit formation in unmedicated patients with Gilles de la Tourette syndrome. Aberrant reinforcement signals to the sensorimotor striatum may be fundamental for the formation of stimulus-response associations and may contribute to the habitual behaviour and tics of this syndrome.
    Brain 11/2015; DOI:10.1093/brain/awv307 · 9.20 Impact Factor
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    • "Each participant ' s FA image was co - registered to the FMRIB58_FA 1 mm standard space template using tract - based spatial statistics ( TBSS ; Smith et al . , 2006 ) , as described in detail in our previous work ( Johnson et al . , 2012 ) . Briefly , non - linear voxel - wise registration was used to transform images into MNI space , where FA images were averaged to generate a mean FA image . The mean FA image was subsequently used to create a common WM tract skeleton . This skeleton was threshold"
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    ABSTRACT: Task-induced deactivations within the brain's default mode network (DMN) are thought to reflect suppression of endogenous thought processes to support exogenous goal-directed task processes. Older adults are known to show reductions in deactivation of the DMN compared to younger adults. However, little is understood about the mechanisms contributing to functional dysregulation of the DMN in aging. Here, we explored the relationships between functional modulation of the DMN and age, task performance and white matter (WM) microstructure. Participants were 117 adults ranging from 25 to 83 years old who completed an fMRI task switching paradigm, including easy (single) and difficult (mixed) conditions, and underwent diffusion tensor imaging (DTI). The fMRI results revealed an age by condition interaction (β = -0.13, t = -3.16, p = 0.002) such that increasing age affected deactivation magnitude during the mixed condition (β = -0.29, t = -3.24 p = 0.002) but not the single condition (p = 0.58). Additionally, there was a WM by condition interaction (β = 0.10, t = 2.33, p = 0.02) such that decreasing WM microstructure affected deactivation magnitude during the mixed condition (β = 0.30, t = 3.42 p = 0.001) but not the single condition (p = 0.17). Critically, mediation analyses indicated that age-related reductions in WM microstructure accounted for the relationship between age and DMN deactivation in the more difficult mixed condition. These findings suggest that age-related declines in anatomical connectivity between DMN regions contribute to functional dysregulation within the DMN in older adults.
    Frontiers in Aging Neuroscience 10/2015; 7:194. DOI:10.3389/fnagi.2015.00194 · 4.00 Impact Factor
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