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Stefan Sunaert

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33

YNIMG Journal 2022 Journal Article

An atlas of white matter anatomy, its variability, and reproducibility based on constrained spherical deconvolution of diffusion MRI

  • Ahmed M. Radwan
  • Stefan Sunaert
  • Kurt Schilling
  • Maxime Descoteaux
  • Bennett A. Landman
  • Mathieu Vandenbulcke
  • Tom Theys
  • Patrick Dupont

Virtual dissection of white matter (WM) using diffusion MRI tractography is confounded by its poor reproducibility. Despite the increased adoption of advanced reconstruction models, early region-of-interest driven protocols based on diffusion tensor imaging (DTI) remain the dominant reference for virtual dissection protocols. Here we bridge this gap by providing a comprehensive description of typical WM anatomy reconstructed using a reproducible automated subject-specific parcellation-based approach based on probabilistic constrained-spherical deconvolution (CSD) tractography. We complement this with a WM template in MNI space comprising 68 bundles, including all associated anatomical tract selection labels and associated automated workflows. Additionally, we demonstrate bundle inter- and intra-subject variability using 40 (20 test-retest) datasets from the human connectome project (HCP) and 5 sessions with varying b-values and number of b-shells from the single-subject Multiple Acquisitions for Standardization of Structural Imaging Validation and Evaluation (MASSIVE) dataset. The most reliably reconstructed bundles were the whole pyramidal tracts, primary corticospinal tracts, whole superior longitudinal fasciculi, frontal, parietal and occipital segments of the corpus callosum and middle cerebellar peduncles. More variability was found in less dense bundles, e.g., the fornix, dentato-rubro-thalamic tract (DRTT), and premotor pyramidal tract. Using the DRTT as an example, we show that this variability can be reduced by using a higher number of seeding attempts. Overall inter-session similarity was high for HCP test-retest data (median weighted-dice = 0.963, stdev = 0.201 and IQR = 0.099). Compared to the HCP-template bundles there was a high level of agreement for the HCP test-retest data (median weighted-dice = 0.747, stdev = 0.220 and IQR = 0.277) and for the MASSIVE data (median weighted-dice = 0.767, stdev = 0.255 and IQR = 0.338). In summary, this WM atlas provides an overview of the capabilities and limitations of automated subject-specific probabilistic CSD tractography for mapping white matter fasciculi in healthy adults. It will be most useful in applications requiring a reproducible parcellation-based dissection protocol, and as an educational resource for applied neuroimaging and clinical professionals.

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YNIMG Journal 2021 Journal Article

Tractography dissection variability: What happens when 42 groups dissect 14 white matter bundles on the same dataset?

  • Kurt G. Schilling
  • François Rheault
  • Laurent Petit
  • Colin B. Hansen
  • Vishwesh Nath
  • Fang-Cheng Yeh
  • Gabriel Girard
  • Muhamed Barakovic

White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation. In this study, we aim to evaluate and quantify the variability that arises from different protocols for bundle segmentation. Through an open call to users of fiber tractography, including anatomists, clinicians, and algorithm developers, 42 independent teams were given processed sets of human whole-brain streamlines and asked to segment 14 white matter fascicles on six subjects. In total, we received 57 different bundle segmentation protocols, which enabled detailed volume-based and streamline-based analyses of agreement and disagreement among protocols for each fiber pathway. Results show that even when given the exact same sets of underlying streamlines, the variability across protocols for bundle segmentation is greater than all other sources of variability in the virtual dissection process, including variability within protocols and variability across subjects. In order to foster the use of tractography bundle dissection in routine clinical settings, and as a fundamental analytical tool, future endeavors must aim to resolve and reduce this heterogeneity. Although external validation is needed to verify the anatomical accuracy of bundle dissections, reducing heterogeneity is a step towards reproducible research and may be achieved through the use of standard nomenclature and definitions of white matter bundles and well-chosen constraints and decisions in the dissection process.

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YNIMG Journal 2021 Journal Article

Virtual brain grafting: Enabling whole brain parcellation in the presence of large lesions

  • Ahmed M. Radwan
  • Louise Emsell
  • Jeroen Blommaert
  • Andrey Zhylka
  • Silvia Kovacs
  • Tom Theys
  • Nico Sollmann
  • Patrick Dupont

Brain atlases and templates are at the heart of neuroimaging analyses, for which they facilitate multimodal registration, enable group comparisons and provide anatomical reference. However, as atlas-based approaches rely on correspondence mapping between images they perform poorly in the presence of structural pathology. Whilst several strategies exist to overcome this problem, their performance is often dependent on the type, size and homogeneity of any lesions present. We therefore propose a new solution, referred to as Virtual Brain Grafting (VBG), which is a fully-automated, open-source workflow to reliably parcellate magnetic resonance imaging (MRI) datasets in the presence of a broad spectrum of focal brain pathologies, including large, bilateral, intra- and extra-axial, heterogeneous lesions with and without mass effect. The core of the VBG approach is the generation of a lesion-free T1-weighted image, which enables further image processing operations that would otherwise fail. Here we validated our solution based on Freesurfer recon-all parcellation in a group of 10 patients with heterogeneous gliomatous lesions, and a realistic synthetic cohort of glioma patients (n = 100) derived from healthy control data and patient data. We demonstrate that VBG outperforms a non-VBG approach assessed qualitatively by expert neuroradiologists and Mann-Whitney U tests to compare corresponding parcellations (real patients U(6,6) = 33, z = 2.738, P < .010, synthetic-patients U(48,48) = 2076, z = 7.336, P < .001). Results were also quantitatively evaluated by comparing mean dice scores from the synthetic-patients using one-way ANOVA (unilateral VBG = 0.894, bilateral VBG = 0.903, and non-VBG = 0.617, P < .001). Additionally, we used linear regression to show the influence of lesion volume, lesion overlap with, and distance from the Freesurfer volumes of interest, on labeling accuracy. VBG may benefit the neuroimaging community by enabling automated state-of-the-art MRI analyses in clinical populations using methods such as FreeSurfer, CAT12, SPM, Connectome Workbench, as well as structural and functional connectomics. To fully maximize its availability, VBG is provided as open software under a Mozilla 2.0 license (https://github.com/KUL-Radneuron/KUL_VBG).

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YNICL Journal 2020 Journal Article

Ventral stream hierarchy underlying perceptual organization in adolescents with autism

  • Laurie-Anne Sapey-Triomphe
  • Bart Boets
  • Lien Van Eylen
  • Ilse Noens
  • Stefan Sunaert
  • Jean Steyaert
  • Johan Wagemans

Object recognition relies on a hierarchically organized ventral visual stream, with both bottom-up and top-down processes. Here, we aimed at investigating the neural underpinnings of perceptual organization along the ventral visual stream in Autism Spectrum Disorders (ASD), and at determining whether this would be associated with decreased top-down processing in ASD. Nineteen typically developing (TD) adolescents and sixteen adolescents with ASD participated in an fMRI study where they had to detect visual objects. Five conditions displayed Gabor patterns (defined by texture and/or contour) with increasing levels of perceptual organization. In each condition, both groups showed similar abilities. In line with the expected cortical hierarchy, brain activity patterns revealed a progressive involvement of regions, from low-level occipital regions to higher-level frontal regions, when stimuli became more and more organized. The brain patterns were generally similar in both groups, but the ASD group showed greater activation than TD participants in the middle occipital gyrus and lateral occipital complex when perceiving fully organized everyday objects. Effective connectivity analyses suggested that top-down functional connections between the lower levels of the cortical hierarchy were less influenced by the meaning carried by the stimuli in the ASD group than in the TD group. We hypothesize that adolescents with ASD may have been less influenced by top-down processing when perceiving recognizable objects.

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YNIMG Journal 2019 Journal Article

Sensorimotor cortex neurometabolite levels as correlate of motor performance in normal aging: evidence from a 1H-MRS study

  • Oron Levin
  • Akila Weerasekera
  • Bradley R. King
  • Kirstin F. Heise
  • Diana M. Sima
  • Sima Chalavi
  • Celine Maes
  • Ronald Peeters

Aging is associated with gradual alterations in the neurochemical characteristics of the brain, which can be assessed in-vivo with proton-magnetic resonance spectroscopy (1H-MRS). However, the impact of these age-related neurochemical changes on functional motor behavior is still poorly understood. Here, we address this knowledge gap and specifically focus on the neurochemical integrity of the left sensorimotor cortex (SM1) and the occipital lobe (OCC), as both regions are main nodes of the visuomotor network underlying bimanual control. 1H-MRS data and performance on a set of bimanual tasks were collected from a lifespan (20–75 years) sample of 86 healthy adults. Results indicated that aging was accompanied by decreased levels of N-acetylaspartate (NAA), glutamate-glutamine (Glx), creatine ​+ ​phosphocreatine (Cr) and myo-inositol (mI) in both regions, and decreased Choline (Cho) in the OCC region. Lower NAA and Glx levels in the SM1 and lower NAA levels in the OCC were related to poorer performance on a visuomotor bimanual coordination task, suggesting that NAA could serve as a potential biomarker for the integrity of the motor system supporting bimanual control. In addition, lower NAA, Glx, and mI levels in the SM1 were found to be correlates of poorer dexterous performance on a bimanual dexterity task. These findings highlight the role for 1H-MRS to study neurochemical correlates of motor performance across the adult lifespan.

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YNICL Journal 2017 Journal Article

Altered functional brain connectivity in patients with visually induced dizziness

  • Angelique Van Ombergen
  • Lizette Heine
  • Steven Jillings
  • R. Edward Roberts
  • Ben Jeurissen
  • Vincent Van Rompaey
  • Viviana Mucci
  • Stefanie Vanhecke

BACKGROUND: Vestibular patients occasionally report aggravation or triggering of their symptoms by visual stimuli, which is called visually induced dizziness (VID). These patients therefore experience dizziness, discomfort, disorientation and postural unsteadiness. The underlying pathophysiology of VID is still poorly understood. OBJECTIVE: The aim of the current explorative study was to gain a first insight in the underlying neural aspects of VID. METHODS: We included 10 VID patients and 10 healthy matched controls, all of which underwent a resting state fMRI scan session. Changes in functional connectivity were explored by means of the intrinsic connectivity contrast (ICC). Seed-based analysis was subsequently performed in visual and vestibular seeds. RESULTS: We found a decreased functional connectivity in the right central operculum (superior temporal gyrus), as well as increased functional connectivity in the occipital pole in VID patients as compared to controls in a hypothesis-free analysis. A weaker functional connectivity between the thalamus and most of the right putamen was measured in VID patients in comparison to controls in a seed-based analysis. Furthermore, also by means of a seed-based analysis, a decreased functional connectivity between the visual associative area and the left parahippocampal gyrus was found in VID patients. Additionally, we found increased functional connectivity between thalamus and occipital and cerebellar areas in the VID patients, as well as between the associative visual cortex and both middle frontal gyrus and precuneus. CONCLUSIONS: We found alterations in the visual and vestibular cortical network in VID patients that could underlie the typical VID symptoms such as a worsening of their vestibular symptoms when being exposed to challenging visual stimuli. These preliminary findings provide the first insights into the underlying functional brain connectivity in VID patients. Future studies should extend these findings by employing larger sample sizes, by investigating specific task-based paradigms in these patients and by exploring the implications for treatment.

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YNIMG Journal 2017 Journal Article

Convexity-constrained and nonnegativity-constrained spherical factorization in diffusion-weighted imaging

  • Daan Christiaens
  • Stefan Sunaert
  • Paul Suetens
  • Frederik Maes

Diffusion-weighted imaging (DWI) facilitates probing neural tissue structure non-invasively by measuring its hindrance to water diffusion. Analysis of DWI is typically based on generative signal models for given tissue geometry and microstructural properties. In this work, we generalize multi-tissue spherical deconvolution to a blind source separation problem under convexity and nonnegativity constraints. This spherical factorization approach decomposes multi-shell DWI data, represented in the basis of spherical harmonics, into tissue-specific orientation distribution functions and corresponding response functions, without assuming the latter as known thus fully unsupervised. In healthy human brain data, the resulting components are associated with white matter fibres, grey matter, and cerebrospinal fluid. The factorization results are on par with state-of-the-art supervised methods, as demonstrated also in Monte-Carlo simulations evaluating accuracy and precision of the estimated response functions and orientation distribution functions of each component. In animal data and in the presence of oedema, the proposed factorization is able to recover unseen tissue structure, solely relying on DWI. As such, our method broadens the applicability of spherical deconvolution techniques to exploratory analysis of tissue structure in data where priors are uncertain or hard to define.

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YNICL Journal 2016 Journal Article

Face shape and face identity processing in behavioral variant fronto-temporal dementia: A specific deficit for familiarity and name recognition of famous faces

  • François-Laurent De Winter
  • Dorien Timmers
  • Beatrice de Gelder
  • Marc Van Orshoven
  • Marleen Vieren
  • Miriam Bouckaert
  • Gert Cypers
  • Jo Caekebeke

Deficits in face processing have been described in the behavioral variant of fronto-temporal dementia (bvFTD), primarily regarding the recognition of facial expressions. Less is known about face shape and face identity processing. Here we used a hierarchical strategy targeting face shape and face identity recognition in bvFTD and matched healthy controls. Participants performed 3 psychophysical experiments targeting face shape detection (Experiment 1), unfamiliar face identity matching (Experiment 2), familiarity categorization and famous face-name matching (Experiment 3). The results revealed group differences only in Experiment 3, with a deficit in the bvFTD group for both familiarity categorization and famous face-name matching. Voxel-based morphometry regression analyses in the bvFTD group revealed an association between grey matter volume of the left ventral anterior temporal lobe and familiarity recognition, while face-name matching correlated with grey matter volume of the bilateral ventral anterior temporal lobes. Subsequently, we quantified familiarity-specific and name-specific recognition deficits as the sum of the celebrities of which respectively only the name or only the familiarity was accurately recognized. Both indices were associated with grey matter volume of the bilateral anterior temporal cortices. These findings extent previous results by documenting the involvement of the left anterior temporal lobe (ATL) in familiarity detection and the right ATL in name recognition deficits in fronto-temporal lobar degeneration.

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YNICL Journal 2016 Journal Article

Voxel-based lesion-symptom mapping of stroke lesions underlying somatosensory deficits

  • Sarah Meyer
  • Simon S. Kessner
  • Bastian Cheng
  • Marlene Bönstrup
  • Robert Schulz
  • Friedhelm C. Hummel
  • Nele De Bruyn
  • Andre Peeters

The aim of this study was to investigate the relationship between stroke lesion location and the resulting somatosensory deficit. We studied exteroceptive and proprioceptive somatosensory symptoms and stroke lesions in 38 patients with first-ever acute stroke. The Erasmus modified Nottingham Sensory Assessment was used to clinically evaluate somatosensory functioning in the arm and hand within the first week after stroke onset. Additionally, more objective measures such as the perceptual threshold of touch and somatosensory evoked potentials were recorded. Non-parametric voxel-based lesion-symptom mapping was performed to investigate lesion contribution to different somatosensory deficits in the upper limb. Additionally, structural connectivity of brain areas that demonstrated the strongest association with somatosensory symptoms was determined, using probabilistic fiber tracking based on diffusion tensor imaging data from a healthy age-matched sample. Voxels with a significant association to somatosensory deficits were clustered in two core brain regions: the central parietal white matter, also referred to as the sensory component of the superior thalamic radiation, and the parietal operculum close to the insular cortex, representing the secondary somatosensory cortex. Our objective recordings confirmed findings from clinical assessments. Probabilistic tracking connected the first region to thalamus, internal capsule, brain stem, postcentral gyrus, cerebellum, and frontal pathways, while the second region demonstrated structural connections to thalamus, insular and primary somatosensory cortex. This study reveals that stroke lesions in the sensory fibers of the superior thalamocortical radiation and the parietal operculum are significantly associated with multiple exteroceptive and proprioceptive deficits in the arm and hand.

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YNIMG Journal 2015 Journal Article

Global tractography of multi-shell diffusion-weighted imaging data using a multi-tissue model

  • Daan Christiaens
  • Marco Reisert
  • Thijs Dhollander
  • Stefan Sunaert
  • Paul Suetens
  • Frederik Maes

Diffusion-weighted imaging and tractography provide a unique, non-invasive technique to study the macroscopic structure and connectivity of brain white matter in vivo. Global tractography methods aim at reconstructing the full-brain fiber configuration that best explains the measured data, based on a generative signal model. In this work, we incorporate a multi-shell multi-tissue model based on spherical convolution, into a global tractography framework, which allows to deal with partial volume effects. The required tissue response functions can be estimated from and hence calibrated to the data. The resulting track reconstruction is quantitatively related to the apparent fiber density in the data. In addition, the fiber orientation distribution for white matter and the volume fractions of gray matter and cerebrospinal fluid are produced as ancillary results. Validation results on simulated data demonstrate that this data-driven approach improves over state-of-the-art streamline and global tracking methods, particularly in the valid connection rate. Results in human brain data correspond to known white matter anatomy and show improved modeling of partial voluming. This work is an important step toward detecting and quantifying white matter changes and connectivity in healthy subjects and patients.

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YNICL Journal 2015 Journal Article

Training-induced improvements in postural control are accompanied by alterations in cerebellar white matter in brain injured patients

  • David Drijkoningen
  • Karen Caeyenberghs
  • Inge Leunissen
  • Catharine Vander Linden
  • Alexander Leemans
  • Stefan Sunaert
  • Jacques Duysens
  • Stephan P. Swinnen

We investigated whether balance control in young TBI patients can be promoted by an 8-week balance training program and whether this is associated with neuroplastic alterations in brain structure. The cerebellum and cerebellar peduncles were selected as regions of interest because of their importance in postural control as well as their vulnerability to brain injury. Young patients with moderate to severe TBI and typically developing (TD) subjects participated in balance training using PC-based portable balancers with storage of training data and real-time visual feedback. An additional control group of TD subjects did not attend balance training. Mean diffusivity and fractional anisotropy were determined with diffusion MRI scans and were acquired before, during (4 weeks) and at completion of training (8 weeks) together with balance assessments on the EquiTest® System (NeuroCom) which included the Sensory Organization Test, Rhythmic Weight Shift and Limits of Stability protocols. Following training, TBI patients showed significant improvements on all EquiTest protocols, as well as a significant increase in mean diffusivity in the inferior cerebellar peduncle. Moreover, in both training groups, diffusion metrics in the cerebellum and/or cerebellar peduncles at baseline were predictive of the amount of performance increase after training. Finally, amount of training-induced improvement on the Rhythmic Weight Shift test in TBI patients was positively correlated with amount of change in fractional anisotropy in the inferior cerebellar peduncle. This suggests that training-induced plastic changes in balance control are associated with alterations in the cerebellar white matter microstructure in TBI patients.

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YNICL Journal 2014 Journal Article

Altered functional connectivity of the language network in ASD: Role of classical language areas and cerebellum

  • Marjolein Verly
  • Judith Verhoeven
  • Inge Zink
  • Dante Mantini
  • Ronald Peeters
  • Sabine Deprez
  • Louise Emsell
  • Bart Boets

The development of language, social interaction and communicative skills is remarkably different in the child with autism spectrum disorder (ASD). Atypical brain connectivity has frequently been reported in this patient population. However, the neural correlates underlying their disrupted language development and functioning are still poorly understood. Using resting state fMRI, we investigated the functional connectivity properties of the language network in a group of ASD patients with clear comorbid language impairment (ASD-LI; N = 19) and compared them to the language related connectivity properties of 23 age-matched typically developing children. A verb generation task was used to determine language components commonly active in both groups. Eight joint language components were identified and subsequently used as seeds in a resting state analysis. Interestingly, both the interregional and the seed-based whole brain connectivity analysis showed preserved connectivity between the classical intrahemispheric language centers, Wernicke's and Broca's areas. In contrast however, a marked loss of functional connectivity was found between the right cerebellar region and the supratentorial regulatory language areas. Also, the connectivity between the interhemispheric Broca regions and modulatory control dorsolateral prefrontal region was found to be decreased. This disruption of normal modulatory control and automation function by the cerebellum may underlie the abnormal language function in children with ASD-LI.

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YNICL Journal 2014 Journal Article

Characterizing the microstructural basis of “unidentified bright objects” in neurofibromatosis type 1: A combined in vivo multicomponent T2 relaxation and multi-shell diffusion MRI analysis

  • Thibo Billiet
  • Burkhard Mädler
  • Felice D'Arco
  • Ronald Peeters
  • Sabine Deprez
  • Ellen Plasschaert
  • Alexander Leemans
  • Hui Zhang

INTRODUCTION: The histopathological basis of "unidentified bright objects" (UBOs) (hyperintense regions seen on T2-weighted magnetic resonance (MR) brain scans in neurofibromatosis-1 (NF1)) remains unclear. New in vivo MRI-based techniques (multi-exponential T2 relaxation (MET2) and diffusion MR imaging (dMRI)) provide measures relating to microstructural change. We combined these methods and present previously unreported data on in vivo UBO microstructure in NF1. METHODS: 3-Tesla dMRI data were acquired on 17 NF1 patients, covering 30 white matter UBOs. Diffusion tensor, kurtosis and neurite orientation and dispersion density imaging parameters were calculated within UBO sites and in contralateral normal appearing white matter (cNAWM). Analysis of MET2 parameters was performed on 24 UBO-cNAWM pairs. RESULTS: No significant alterations in the myelin water fraction and intra- and extracellular (IE) water fraction were found. Mean T2 time of IE water was significantly higher in UBOs. UBOs furthermore showed increased axial, radial and mean diffusivity, and decreased fractional anisotropy, mean kurtosis and neurite density index compared to cNAWM. Neurite orientation dispersion and isotropic fluid fraction were unaltered. CONCLUSION: Our results suggest that demyelination and axonal degeneration are unlikely to be present in UBOs, which appear to be mainly caused by a shift towards a higher T2-value of the intra- and extracellular water pool. This may arise from altered microstructural compartmentalization, and an increase in 'extracellular-like', intracellular water, possibly due to intramyelinic edema. These findings confirm the added value of combining dMRI and MET2 to characterize the microstructural basis of T2 hyperintensities in vivo.

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YNIMG Journal 2014 Journal Article

The dynamics of contour integration: A simultaneous EEG–fMRI study

  • Bogdan Mijović
  • Maarten De Vos
  • Katrien Vanderperren
  • Bart Machilsen
  • Stefan Sunaert
  • Sabine Van Huffel
  • Johan Wagemans

To study the dynamics of contour integration in the human brain, we simultaneously acquired EEG and fMRI data while participants were engaged in a passive viewing task. The stimuli were Gabor arrays with some Gabor elements positioned on the contour of an embedded shape, in three conditions: with local and global structure (perfect contour alignment), with global structure only (orthogonal orientations interrupting the alignment), or without contour. By applying JointICA to the EEG and fMRI responses of the subjects, new insights could be obtained that cannot be derived from unimodal recordings. In particular, only in the global structure condition, an ERP peak around 300ms was identified that involved a loop from LOC to the early visual areas. This component can be interpreted as being related to the verification of the consistency of the different local elements with the globally defined shape, which is necessary when perfect local-to-global alignment is absent. By modifying JointICA, a quantitative comparison of brain regions and the time-course of their interplay were obtained between different conditions. More generally, we provide additional support for the presence of feedback loops from higher areas to lower level sensory regions.

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YNIMG Journal 2014 Journal Article

Track Orientation Density Imaging (TODI) and Track Orientation Distribution (TOD) based tractography

  • Thijs Dhollander
  • Louise Emsell
  • Wim Van Hecke
  • Frederik Maes
  • Stefan Sunaert
  • Paul Suetens

Ever since the introduction of the concept of fiber tractography, methods to generate better and more plausible tractograms have become available. Many modern methods can handle complex fiber architecture and take on a probabilistic approach to account for different sources of uncertainty. The resulting tractogram from any such method typically represents a finite random sample from a complex distribution of possible tracks. Generating a higher amount of tracks allows for a more accurate depiction of the underlying distribution. The recently proposed method of track-density imaging (TDI) allows to capture the spatial distribution of a tractogram. In this work, we propose an extension of TDI towards the 5D spatio-angular domain, which we name track orientation density imaging (TODI). The proposed method aims to capture the full track orientation distribution (TOD). Just as the TDI map, the TOD is amenable to spatial super-resolution (or even sub-resolution), but in addition also to angular super-resolution. Through experiments on in vivo human subject data, an in silico numerical phantom and a challenging tractography phantom, we found that the TOD presents an increased amount of regional spatio-angular consistency, as compared to the fiber orientation distribution (FOD) from constrained spherical deconvolution (CSD). Furthermore, we explain how the amplitude of the TOD of a short-tracks distribution (i. e. where the track length is limited) can be interpreted as a measure of track-like local support (TLS). This in turn motivated us to explore the idea of TOD-based fiber tractography. In such a setting, the short-tracks TOD is able to guide a track along directions that are more likely to correspond to continuous structure over a longer distance. This powerful concept is shown to greatly robustify targeted as well as whole-brain tractography. We conclude that the TOD is a versatile tool that can be cast in many different roles and scenarios in the expanding domain of fiber tractography based methods and their applications.

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YNIMG Journal 2013 Journal Article

Weighted linear least squares estimation of diffusion MRI parameters: Strengths, limitations, and pitfalls

  • Jelle Veraart
  • Jan Sijbers
  • Stefan Sunaert
  • Alexander Leemans
  • Ben Jeurissen

Purpose Linear least squares estimators are widely used in diffusion MRI for the estimation of diffusion parameters. Although adding proper weights is necessary to increase the precision of these linear estimators, there is no consensus on how to practically define them. In this study, the impact of the commonly used weighting strategies on the accuracy and precision of linear diffusion parameter estimators is evaluated and compared with the nonlinear least squares estimation approach. Methods Simulation and real data experiments were done to study the performance of the weighted linear least squares estimators with weights defined by (a) the squares of the respective noisy diffusion-weighted signals; and (b) the squares of the predicted signals, which are reconstructed from a previous estimate of the diffusion model parameters. Results The negative effect of weighting strategy (a) on the accuracy of the estimator was surprisingly high. Multi-step weighting strategies yield better performance and, in some cases, even outperformed the nonlinear least squares estimator. Conclusion If proper weighting strategies are applied, the weighted linear least squares approach shows high performance characteristics in terms of accuracy/precision and may even be preferred over nonlinear estimation methods.

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YNIMG Journal 2012 Journal Article

The “why” and “how” of JointICA: Results from a visual detection task

  • Bogdan Mijović
  • Katrien Vanderperren
  • Nikolay Novitskiy
  • Bart Vanrumste
  • Peter Stiers
  • Bea Van den Bergh
  • Lieven Lagae
  • Stefan Sunaert

Since several years, neuroscience research started to focus on multimodal approaches. One such multimodal approach is the combination of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). However, no standard integration procedure has been established so far. One promising data-driven approach consists of a joint decomposition of event-related potentials (ERPs) and fMRI maps derived from the response to a particular stimulus. Such an algorithm (joint independent component analysis or JointICA) has recently been proposed by Calhoun et al. (2006). This method provides sources with both a fine spatial and temporal resolution, and has shown to provide meaningful results. However, the algorithm's performance has not been fully characterized yet, and no procedure has been proposed to assess the quality of the decomposition. In this paper, we therefore try to answer why and how JointICA works. We show the performance of the algorithm on data obtained in a visual detection task, and compare the performance for EEG recorded simultaneously with fMRI data and for EEG recorded in a separate session (outside the scanner room). We perform several analyses in order to set the necessary conditions that lead to a sound decomposition, and to give additional insights for exploration in future studies. In that respect, we show how the algorithm behaves when different EEG electrodes are used and we test the robustness with respect to the number of subjects in the study. The performance of the algorithm in all the experiments is validated based on results from previous studies.

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YNIMG Journal 2011 Journal Article

The effect of template selection on diffusion tensor voxel-based analysis results

  • Wim Van Hecke
  • Alexander Leemans
  • Caroline A. Sage
  • Louise Emsell
  • Jelle Veraart
  • Jan Sijbers
  • Stefan Sunaert
  • Paul M. Parizel

Diffusion tensor imaging (DTI) is increasingly being used to study white matter (WM) degeneration in patients with psychiatric and neurological disorders. In order to compare diffusion measures across subjects in an automated way, voxel-based analysis (VBA) methods were introduced. In VBA, all DTI data are transformed to a template, after which the diffusion measures of control subjects and patients are compared quantitatively in each voxel. Although VBA has many advantages compared to other post-processing approaches, such as region of interest analysis or tractography, VBA results need to be interpreted cautiously, since it has been demonstrated that they depend on the different parameter settings that are applied in the VBA processing pipeline. In this paper, we examine the effect of the template selection on the VBA results of DTI data. We hypothesized that the choice of template to which all data are transformed would also affect the VBA results. To this end, simulated DTI data sets as well as DTI data from control subjects and multiple sclerosis patients were aligned to (i) a population-specific DTI template, (ii) a subject-based DTI atlas in MNI space, and (iii) the ICBM-81 DTI atlas. Our results suggest that the highest sensitivity and specificity to detect WM abnormalities in a VBA setting was achieved using the population-specific DTI atlas, presumably due to the better spatial image alignment to this template.

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YNIMG Journal 2010 Journal Article

Distributed task coding throughout the multiple demand network of the human frontal–insular cortex

  • Peter Stiers
  • Maarten Mennes
  • Stefan Sunaert

The large variety of tasks that humans can perform is governed by a small number of key frontal–insular regions that are commonly active during task performance. Little is known about how this network distinguishes different tasks. We report on fMRI data in twelve participants while they performed four cognitive tasks. Of 20 commonly active frontal–insular regions in each hemisphere, five showed a BOLD response increase with increased task demands, regardless of the task. Although active in all tasks, each task invoked a unique response pattern across the voxels in each area that proved reliable in split-half multi-voxel correlation analysis. Consequently, voxels differed in their preference for one or more of the tasks. Voxel-based functional connectivity analyses revealed that same preference voxels distributed across all areas of the network constituted functional sub-networks that characterized the task being executed.

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YNIMG Journal 2010 Journal Article

Removal of BCG artifacts from EEG recordings inside the MR scanner: A comparison of methodological and validation-related aspects

  • Katrien Vanderperren
  • Maarten De Vos
  • Jennifer R. Ramautar
  • Nikolay Novitskiy
  • Maarten Mennes
  • Sara Assecondi
  • Bart Vanrumste
  • Peter Stiers

Multimodal approaches are of growing interest in the study of neural processes. To this end much attention has been paid to the integration of electroencephalographic (EEG) and functional magnetic resonance imaging (fMRI) data because of their complementary properties. However, the simultaneous acquisition of both types of data causes serious artifacts in the EEG, with amplitudes that may be much larger than those of EEG signals themselves. The most challenging of these artifacts is the ballistocardiogram (BCG) artifact, caused by pulse-related electrode movements inside the magnetic field. Despite numerous efforts to find a suitable approach to remove this artifact, still a considerable discrepancy exists between current EEG-fMRI studies. This paper attempts to clarify several methodological issues regarding the different approaches with an extensive validation based on event-related potentials (ERPs). More specifically, Optimal Basis Set (OBS) and Independent Component Analysis (ICA) based methods were investigated. Their validation was not only performed with measures known from previous studies on the average ERPs, but most attention was focused on task-related measures, including their use on trial-to-trial information. These more detailed validation criteria enabled us to find a clearer distinction between the most widely used cleaning methods. Both OBS and ICA proved to be able to yield equally good results. However, ICA methods needed more parameter tuning, thereby making OBS more robust and easy to use. Moreover, applying OBS prior to ICA can optimize the data quality even more, but caution is recommended since the effect of the additional ICA step may be strongly subject-dependent.

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YNIMG Journal 2007 Journal Article

Quantitative diffusion tensor imaging in amyotrophic lateral sclerosis

  • Caroline A. Sage
  • Ronald R. Peeters
  • Astrid Görner
  • Wim Robberecht
  • Stefan Sunaert

Objective Aim of present study was to evaluate changes in diffusion tensor imaging (DTI) parameters in the whole brain of 28 patients with amyotrophic lateral sclerosis (ALS) compared to 26 healthy controls. Methods In both fibertracking and voxel-based analysis, quantitative comparisons of the diffusion parameters between ALS patients and controls were performed. Correlation analyses of diffusion parameters and disease duration and disease severity were performed. A second DTI examination was acquired, allowing the evaluation of the effect of disease progression on the diffusion parameters. Results Fibertracking analysis revealed that especially the precentral part of the corticospinal tract (CST) was impaired. In the voxel-based analysis, it was shown that changes of diffusion parameters occurred throughout the brain, including frontal, temporal and parietal lobes. Disease severity was inversely correlated with the fractional anisotropy (FA). In the follow-up examination, a further decline of FA over time could be demonstrated in the CST as well as in the whole brain white matter. Interpretation This study provides support for the view of ALS as being a multisystem degenerative disease, in which abnormalities of extra-motor areas play an important role in the in vivo physiopathology.

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YNIMG Journal 2006 Journal Article

Lateralization of brain activity during lower limb joints movement. An fMRI study

  • Eleni Kapreli
  • Spyros Athanasopoulos
  • Matilda Papathanasiou
  • Paul Van Hecke
  • Nikolaos Strimpakos
  • Athanasios Gouliamos
  • Ronald Peeters
  • Stefan Sunaert

Studies of unilateral finger movement in right-handed subjects have shown asymmetrical patterns of activation in primary motor cortex and subcortical regions. In order to investigate the existence of an analogous pattern during lower limb joints movements, functional magnetic resonance imaging (fMRI) was used. Eighteen healthy, right leg dominant volunteers participated in a motor block design study, performing unilateral right and left repetitive knee, ankle and toes flexion/extension movements. Aiming to relate lower limb joints activation to the well-described patterns of finger movement, serial finger-to-thumb opposition was also assessed. All movements were auditory paced at 72 beats/min (1. 2 Hz). Brain activation during movement of the nondominant joints was more bilateral than during the same movement performed with the dominant joints. Finger movement had a stronger lateralized pattern of activation in comparison with lower limb joints, implying a different functional specialization. Differences were also evident between the joints of the lower limb. Ankle and toes movements elicited the same extend of MR signal change in the majority of the examined brain regions, whereas knee joint movement was associated with a different pattern. Finally, lateralization index in primary sensorimotor cortex and basal ganglia was significantly affected by the main effect of dominance, whereas the lateralization index in cerebellum was significantly affected by the joint main effect, demonstrating a lateralization index increase from proximal to distal joints.

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YNIMG Journal 2006 Journal Article

Mapping multiple visual areas in the human brain with a short fMRI sequence

  • Peter Stiers
  • Ronald Peeters
  • Lieven Lagae
  • Paul Van Hecke
  • Stefan Sunaert

It is a fundamental insight of neuroscience that the cerebral cortex is divided into spatially separated and functionally distinct areas. In this study, we tried to map a large number of visual areas in individual subjects passively viewing a simple stimulus sequence during functional magnetic resonance imaging (fMRI) at 1. 5 T. The blocked stimulus sequence contrasted static object photographs with video takes of movement through natural indoor and outdoor scenes, alternated with a control fixation task. Two runs of the 5-min sequence sufficed to invoke 29 distinguishable activations, 16 (13 bilateral) of which were observed in all 10 participants. At the ventral side, object responsive activations were organized along the lateral occipital–temporal surface and near the collateral and occipital–temporal sulci. The latter activations, corresponding to the lateral occipital complex, showed a different activation profile from those near the collateral sulcus, most likely corresponding to the color constancy areas V4/V8–V4α. A potentially new fusiform object area was seen in 6 subjects, even more anterior than the parahippocampal place area. At the dorsal side, consistent activations were mainly related to motion stimuli and included the well-known areas V3a, VIPS, POIPS, hV5+, STS and the cingulate sulcus. There was consistent activation in the parietal–occipital sulcus, containing the areas V6a and V6. In addition, all subjects showed activation in the superior–anterior precuneus. Thus, the short stimulus sequence robustly invoked multiple visual areas and can be used to map the organization of the visual system in normal and brain-damaged individuals.

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YNIMG Journal 2003 Journal Article

Internal vs external generation of movements: differential neural pathways involved in bimanual coordination performed in the presence or absence of augmented visual feedback

  • Filiep Debaere
  • Nicole Wenderoth
  • Stefan Sunaert
  • Paul Van Hecke
  • Stephan P Swinnen

It is commonly agreed that a functional dissociation with respect to the internal vs external control of movements exists for several brain regions. This has, however, only been tested in relation to the timing and preparation of motor responses, but not to ongoing movement control. Using functional magnetic resonance imaging (fMRI), the present study addressed the neuroanatomical substrate of the internal–external control hypothesis by comparing regional brain activation for cyclical bimanual movements performed in the presence or absence of augmented visual feedback. Subjects performed a bimanual movement pattern, either with the help of on-line visual feedback of the movements (externally guided coordination) or with the eyes closed on the basis of an internal representation of the movement pattern (internally generated coordination). Visual control and baseline rest conditions were also added. Results showed a clear functional dissociation within the network involved in movement coordination. The hMT/V5+, the superior parietal cortex, the premotor cortex, the thalamus, and cerebellar lobule VI showed higher activation levels when movements were guided by visual feedback. Conversely, the basal ganglia, the supplementary motor area, cingulate motor cortex, the inferior parietal, frontal operculum, and cerebellar lobule IV-V/dentate nucleus showed higher involvement when movements were internally generated. Consequently, the present findings suggest the existence of distinct cortico-cortical and subcortico-cortical neural pathways for externally (augmented feedback) and internally guided cyclical bimanual movements. This provides a neurophysiological account for the beneficial effect of providing augmented visual feedback to optimize movements in normal and motor disordered patients.

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YNIMG Journal 2003 Journal Article

Involvement of multiple functionally distinct cerebellar regions in visual discrimination: a human functional imaging study

  • Kristl G Claeys
  • Guy A Orban
  • Patrick Dupont
  • Stefan Sunaert
  • Paul Van Hecke
  • Erik De Schutter

We investigated the contribution of the human cerebellum to cerebral function during visual discrimination using PET and fMRI. The cognitive task was a successive discrimination of shades of brown with a parametric variation of the stimulus presentation rate and a constant task difficulty. The successive color discrimination task was contrasted to a dimming detection control task, with identical retinal input but with double the number of motor responses. Three sets of activated cerebellar and cerebral regions were observed: rate-dependent and rate-independent color discrimination networks and a motor-and-detection network. The rate-dependent color discrimination network included both an anterior and a posterior activation site in lobule-VI of the two lateral cerebellar hemispheres, whereas the rate-independent network involved a bilateral activation site in lateral Crus-I. Cerebellar sites of the motor-and-detection network were located in medial lobule-V bilaterally, in the vermis, and in posterior left Crus-I and right Crus-II. An additional fMRI study was performed to control for differences in motor output and response timing between the tasks. In this control study, the cerebellar activation sites of the rate-dependent and rate-independent color discrimination networks remained unaltered. The motor-and-detection network included cerebellar activations in posterior left Crus-I and right Crus-II, but none in lobule-V or the vermis. Thus, cerebellar activation sites of the motor-and-detection network could be subdivided into those related to a motor network and those belonging to a dimming detection network. We conclude that successive color discrimination activates multiple, functionally distinct cerebellar regions.

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YNIMG Journal 2001 Journal Article

Brain Areas Involved in Interlimb Coordination: A Distributed Network

  • Filiep Debaere
  • Stephan P. Swinnen
  • Erik Béatse
  • Stefan Sunaert
  • Paul Van Hecke
  • Jacques Duysens

Whereas behavioral studies have made significant contributions toward the identification of the principles governing the coordination of limb movements, little is known about the role of higher brain areas that are involved in interlimb coordination. Functional magnetic resonance imaging (fMRI) was used to reveal the brain areas activated during the cyclical coordination of ipsilateral wrist and foot movements. Six normal subjects performed five different tasks that were presented in a random order, i. e. , isolated flexion-extension movements of the right wrist (WRIST) and right foot (FOOT), cyclical coordination of wrist and foot according to the isodirectional (ISODIR) and nonisodirectional (NON-ISODIR) mode, and rest (REST). All movements were auditory paced at 66 beats/min. During the coordination of both limb segments, a distributed network was identified showing activation levels in the supplementary motor area (SMA), cingulate motor cortex (CMC), premotor cortex (PMC), primary sensorimotor cortex (M1/S1), and cerebellum that exceeded the sum of the activations observed during the isolated limb movements. In addition, coordination of the limb movements in different directions was associated with extra activation of the SMA as compared to movements in the same direction. It is therefore concluded that the SMA is substantially involved in the coordination of the nonhomologous limbs as part of a distributed motor network. Accordingly, the long-standing exclusive association that has been made between this medial frontal area and bimanual (homologous) coordination needs to be abandoned and extended towards other forms of interlimb coordination (nonhomologous).

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YNIMG Journal 2000 Journal Article

Attention to Speed of Motion, Speed Discrimination, and Task Difficulty: An fMRI Study

  • Stefan Sunaert
  • Paul Van Hecke
  • Guy Marchal
  • Guy A. Orban

We studied the functional neuroanatomy of attention to speed of motion using functional magnetic resonance imaging in eight healthy subjects, who performed a speed discrimination (SID) task using a random textured pattern moving at a reference speed of 6 deg/s. During the control condition (DIM), with retinal stimulation identical to that during SID, subjects detected the dimming of the central fixation point. Attention to speed (SID compared to DIM) activated mainly ventral V3 and V4, dorsal V3 and V3A. Compared to a fixation control condition, speed discrimination recruited a large visuomotor network, including hMT/V5+. However, hMT/V5+ was only marginally more active during speed discrimination than during dimming detection. Thus hMT/V5+ is involved in speed discrimination, in line with the speed discrimination impairments following hMT/V5+ lesions, but our results suggest that this activity simply reflects the processing of motion rather than attention to speed. Manipulating the difficulty of the speed discrimination task over a large range of the psychometric curve revealed that increasing difficulty linearly increases activity in right frontal regions, as well as in lateral occipital and dorsal parietal regions. A weak effect of difficulty was also observed in dorsal V3.

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YNIMG Journal 2000 Journal Article

The Representation of Shape in the Context of Visual Object Categorization Tasks

  • Hans Op de Beeck
  • Erik Béatse
  • Johan Wagemans
  • Stefan Sunaert
  • Paul Van Hecke

To investigate the role of human fusiform gyrus in shape processing, we determined the effect of shape degradation on BOLD contrast in this region with fMRI during three tasks requiring subjects to determine either whether two successively presented nonsense shapes had the same global orientation (OR task); whether two successively presented meaningful objects belonged to the same basic level category (CAT task); or whether two successively presented objects represented the same exemplar of a category (EX task). On the behavioral level, shape degradation by locally shifting the pixels constituting the lines of stimuli had no effect on performance in the OR task, while it was detrimental to performance in the CAT and EX tasks. In comparison to the OR task, both the CAT and EX tasks were associated with activations in the occipitotemporal and parietal cortex. When shape degradation was applied, activation in the middle fusiform gyrus was reduced in all tasks. The occurrence of this effect in the OR task indicates that it is independent of memory representations. The persistence of the effect in both tasks that showed a behavioral effect of degradation suggests that it does not reflect the amount of shape processing performed on the stimuli, but rather the specificity of the final perceptual representation that can be built from the shape information that is available. Other studies have shown effects of stimulus familiarity and task requirements in the fusiform gyrus, suggesting that there is no need to assume different modules for perceptual representation and representation in memory.

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YNIMG Journal 1997 Journal Article

FMRI Studies of the Supplementary Motor Area and the Premotor Cortex

  • Sylvie Van Oostende
  • Paul Van Hecke
  • Stefan Sunaert
  • Bart Nuttin
  • Guy Marchal

Brain activation patterns associated with three motor tasks, differing in the mode of movement selection, were studied in seven right-handed subjects, using functional magnetic resonance imaging (fMRI). The tasks consisted of sequences of finger movements in which the next finger was selected (i) according to a fixed sequence (FIX), (ii) in response to an external sensory cue (RAND), or (iii) on the basis of free, internal selection (SELF). Periods of hand relaxation (REST) alternating with the tasks served as a control. Functional maps resulting from comparison of the motor tasks with REST reveal activation in primary sensorimotor cortex, medial and lateral premotor areas, cingulate cortex, and parietal cortex. The task activation level, defined as the percentage MR signal increase for each task relative to REST, and the differential activation, defined as the percentage MR signal increase for RAND and SELF relative to FIX, were calculated in each area. All areas showed a higher activation level for RAND and SELF than for FIX. A significant difference in activation level or differential activation between SELF and RAND was found in the posterior part of the superior frontal sulcus, in a part of the premotor cortex on the lateral brain surface, in the anterior cingulate motor cortex, and in the posterior part of the superior parietal cortex. The high-resolution and single-subject approach, provided by fMRI, allowed the distinguishing of multiple foci in medial frontal areas, premotor cortex, and parietal cortex, reflecting the functional heterogeneity of these areas suggested by previous studies.

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v2026.09.13