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# Improved probabilistic streamlines tractography by 2nd order integration over fibre orientation distributions

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... Track-weighted analysis of juxtacortical WM Ten million streamlines were generated by probabilistic tractography using iFOD2 algorithm 74 and dynamic seeding 53,55 within the anatomically constrained tractography (ACT) framework. 53 Per-streamline cross-section multipliers were optimized using spherical-deconvolution informed filtering of tractograms 2 (SIFT2). ...
... Cortical regions defined by Destrieux parcellation, 74 shown here for left hemisphere (see Supporting Information Figure S6 for results from both hemispheres). The regions corresponding to numeric labels can be found in 74 ...
... Cortical regions defined by Destrieux parcellation, 74 shown here for left hemisphere (see Supporting Information Figure S6 for results from both hemispheres). The regions corresponding to numeric labels can be found in 74 ...
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Purpose: Characterization of cerebral cortex is challenged by the complexity and heterogeneity of its cyto- and myeloarchitecture. This study evaluates quantitative MRI metrics, measured across two cortical depths and in subcortical white matter (WM) adjacent to cortex (juxtacortical WM), indicative of myelin content, neurite density, and diffusion microenvironment, for a comprehensive characterization of cortical microarchitecture. Methods: High-quality structural and diffusion MRI data (N = 30) from the Human Connectome Project were processed to compute myelin index, neurite density index, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity from superficial cortex, deep cortex, and juxtacortical WM. The distributional patterns of these metrics were analyzed individually, correlated to one another, and were compared to established parcellations. Results: Our results supported that myeloarchitectonic and the coexisting cytoarchitectonic structures influence the diffusion properties of water molecules residing in cortex. Full cortical thickness showed myelination patterns similar to those previously observed in humans. Higher myelin indices with similar distributional patterns were observed in deep cortex whereas lower myelin indices were observed in superficial cortex. Neurite density index and other diffusion MRI derived parameters provided complementary information to myelination. Reliable and reproducible correlations were identified among the cortical microarchitectural properties and fiber distributional patterns in proximal WM structures. Conclusion: We demonstrated gradual changes across the cortical sheath by assessing depth-specific cortical micro-architecture using anatomical and diffusion MRI. Mutually independent but coexisting features of cortical layers and juxtacortical WM provided new insights towards structural organizational units and variabilities across cortical regions and through depth.
... These two studies with small sample sizes did not reach consistent conclusions, and the discrete scan timepoints (neonate, 6 months, and 1 year) hindered the continuous characterization of development. In addition, tensorbased tractography used in the previous studies was not ideal for immature infant brain due to difficulties in distinguishing whether the signal reduction was due to immature tissue or crossed fibers within voxels (Descoteaux, 1999), which can be addressed by the probabilistic tractography method based on fiber orientation distribution (FOD; Tournier et al., 2010). ...
... The individual FOD was generated from the preprocessed HARDI data according to the MRtrix3 multi-shell multi-tissue constrained spherical deconvolution (MSMT-CSD) pipeline (Jeurissen et al., 2014), and all individual data were up-sampled to an isotropic voxel of 1 mm. Then, the whole-brain tractography was performed based on individual FOD images utilizing the second-order integration over the FOD method (Tournier et al., 2010), and the tractography profile was as follows: step size = 0.5 mm, minimum/maximum length = 10/250 mm, maximum angle = 90 • , and cutoff = 0.05. Afterward, 10 million streamlines were filtered to 1 million utilizing the sphericaldeconvolution informed filtering of tractograms (SIFT) method (Smith et al., 2013), which selectively removed streamlines such that the streamline density was as close as possible to fiber density. ...
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Exuberant axon growth and competitive pruning lead to dramatic and comprehensive changes in white matter pathways of the infant brain during the first few postnatal months, yet the development of structural configuration in early infancy has not been fully characterized. This study aimed to investigate the developmental trajectory of structural connectivity reflecting relative fiber density in 43 preterm-born infants aged 0–3 months of corrected age without any complications utilizing probabilistic tractography based on fiber orientation distribution and to explore the potential function correlation associated with the network properties based on the Chinese Communication Development of Infant at 10 months of corrected age. The findings revealed significant increases in global efficiency, local efficiency, normalized clustering coefficient, and small-worldness (padj < 0.001 for each), while the normalized characteristic path length showed a non-significant decrease with age (padj = 0.118). Furthermore, those findings were validated by another parcelation strategy. In addition, the early local efficiency was found to be significantly correlated with words understood at 10 months of corrected age. A unique developmental pattern of structural networks with enhancing efficiency and the small-world property was found in early infancy, which was different from those of neonates or toddlers. In addition, this study revealed a significant correlation between local efficiency and late language comprehension, which indicated that enhanced structural connectivity may lay the structural foundation for language specialization.
... After normalizing the FOD to correct for intensity outliers, we use this FOD as the input for either the iFOD2 algorithm for probabilistic tractography or the SD_STREAM algorithm for deterministic tractography. The iFOD2 algorithm conducts second-order integration of estimated fiber orientations to determine principle streamline direction (Tournier et al., 2010). The SD_STREAM algorithm performs Newton optimization to orient streamlines toward local peaks in the fiber orientation . ...
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The anatomic validity of structural connectomes remains a significant uncertainty in neuroimaging. Edge-centric tractography reconstructs streamlines in bundles between each pair of cortical or subcortical regions. Although edge bundles provides a stronger anatomic embedding than traditional connectomes, calculating them for each region-pair requires exponentially greater computation. We observe that major speedup can be achieved by reducing the number of streamlines used by probabilistic tractography algorithms. To ensure this does not degrade connectome quality, we calculate the identifiability of edge-centric connectomes between test and re-test sessions as a proxy for information content. We find that running PROBTRACKX2 with as few as 1 streamline per voxel per region-pair has no significant impact on identifiability. Variation in identifiability caused by streamline count is overshadowed by variation due to subject demographics. This finding even holds true in an entirely different tractography algorithm using MRTrix. Incidentally, we observe that Jaccard similarity is more effective than Pearson correlation in calculating identifiability for our subject population.
... 31 The fibre orientation distribution (FOD) functions were computed using constrained spherical deconvolution. 32 Then, 3 million streamlines were generated using the probabilistic algorithm iFOD2 33 and filtered to keep only those connecting GM ROIs. The resulting tractograms were processed using the Convex Optimization Modelling for Microstructure Informed Tractography (COMMIT). ...
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Central Nervous System involvement in Fabry Disease, a rare systemic X-linked lysosomal storage disorder, is characterized by the presence of heterogeneous but consistent functional and microstructural changes. Nevertheless, knowledge about the degree and extension of macro-scale brain connectivity modifications is to date missing. In this work, we performed connectomic analyses of diffusion and resting-state functional MRI to investigate changes of both structural and functional brain organization in Fabry disease, as well as to explore the relationship between the two and their clinical correlates. In this retrospective cross-sectional study, 46 Fabry disease patients (28F, 42.2 ± 13.2years) and 49 healthy controls (21F, 42.3 ± 16.3years) were included. All subjects underwent an MRI examination including anatomical, diffusion and resting-state functional sequences. Images were processed to obtain quantitative structural and functional connectomes, where the connections between regions of interest were weighted by the total intra-axonal signal contribution of the corresponding bundle and by the correlation between blood-oxygen-level dependent timeseries, respectively. We explored between-group differences in terms of both global network properties, expressed with graph measures, and specific connected subnetworks, identified using a network-based statistics approach. As exploratory analyses, we also investigated the possible association between cognitive performance and structural and functional connectome modifications at both global and subnetwork level in a subgroup of patients (n = 11). Compared to healthy controls, Fabry disease patients showed a significantly reduced global efficiency (p = 0.005) and mean strength (p < 0.001) in structural connectomes, together with an increased modularity (p = 0.005) in functional networks. As for the network-based statistics analysis, a subnetwork with decreased structural connectivity in Fabry disease patients compared to healthy controls emerged, with 8 nodes mainly located at the level of frontal or deep grey matter areas. When probing the relation between altered global network metrics and neuropsychological tests, correlations emerged between the structural and functional disruption with results at verbal and working memory tests, respectively. Furthermore, structural disruption at subnetwork level was associated with worse executive functioning, with a significant moderation effect of functional changes suggesting a compensation mechanism. Taken together, these results further expand the current knowledge about brain involvement in Fabry disease, showing widespread structural disconnection and functional reorganization, primarily sustained by loss in axonal integrity and correlating with cognitive performance.
... A probabilistic tractography algorithm based on the second-order integration over fODFs was used 65 with the anatomically-constrained tractography (ACT) framework in MRTrix 66 (fibre orientation distribution amplitude threshold 0.1, step size 1 mm, 4 samples per step, maximum curvature per step 45°, the cutoff value for terminating tracks 0.06, minimum track length 5 mm, the maximum tract length 300 mm, maximum number of streamlines 10 million). The wholebrain tractography procedure used the grey matter/white matter boundary obtained from Freesurfer as the seed mask. ...
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Humans differ from each other in a wide range of biometrics, but to what extent brain connectivity varies between individuals remains largely unknown. By combining diffusion-weighted imaging (DWI) and magnetoencephalography (MEG), this study characterizes the inter-subject variability (ISV) of multimodal brain connectivity. Structural connectivity is characterized by higher ISV in association cortices including the core multiple-demand network and lower ISV in the sensorimotor cortex. MEG ISV exhibits frequency-dependent signatures, and the extent of MEG ISV is consistent with that of structural connectivity ISV in selective macroscopic cortical clusters. Across the cortex, the ISVs of structural connectivity and beta-band MEG functional connectivity are negatively associated with cortical myelin content indexed by the quantitative T1 relaxation rate measured by high-resolution 7 T MRI. Furthermore, MEG ISV from alpha to gamma bands relates to the hindrance and restriction of the white-matter tissue estimated by DWI microstructural models. Our findings depict the inter-relationship between the ISV of brain connectivity from multiple modalities, and highlight the role of tissue microstructure underpinning the ISV.
... It is more accurate than lower degrees and is less affected by noise than higher degrees. Finally, based on the FOD, the improved probabilistic streamlines tractography approach (iFOD2) (Tournier et al., 2010) was used to reconstruct streamlines. The desired number of streamlines was set to 10,000,000 and the step size was 0.5 times the voxel size. ...
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Understanding the laminar brain structure is of great help in further developing our knowledge of the functions of the brain. However, since most layer segmentation methods are invasive, it is difficult to apply them to the human brain in vivo. To systematically explore the human brain's laminar structure noninvasively, the K-means clustering algorithm was used to automatically segment the left hemisphere into two layers, the superficial and deep layers, using a 7 Tesla (T) diffusion magnetic resonance imaging (dMRI)open dataset. The obtained layer thickness was then compared with the layer thickness of the BigBrain reference dataset, which segmented the neocortex into six layers based on the von Economo atlas. The results show a significant correlation not only between our automatically segmented superficial layer thickness and the thickness of layers 1-3 from the reference histological data, but also between our automatically segmented deep layer thickness and the thickness of layers 4-6 from the reference histological data. Second, we constructed the laminar connections between two pairs of unidirectional connected regions, which is consistent with prior research. Finally, we conducted the laminar analysis of the working memory, which was challenging to do in the past, and explained the conclusions of the functional analysis. Our work successfully demonstrates that it is possible to segment the human cortex noninvasively into layers using dMRI data and further explores the mechanisms of the human brain.
... T1 images were obtained using 3D magnetization-prepared rapid gradient echo sequence (MPRAGE) with TR = 2400 (ms), TE = 2.14 (ms), and 0.7 (mm) isotropic voxels. The HCP minimally processed data were further processed using MRtrix3 , including bias-field correction, multi-shell multi-tissue constrained spherical deconvolution with a maximum spherical harmonic degree 8. 10 million probabilistic streamlines were generated for each subject using the 2 nd -order Intergration over Fibre Orientation Distributions algorithm (iFOD2) ( Tournier et al., 2010 ) and anatomicallyconstrained tractography (ACT) (FOD amplitude threshold = 0.06, step size = 0.625 mm). Each streamline was assigned a weight using spherical-deconvolution informed filtering of tractograms (SIFT2) ( Smith et al., 2015 ). ...
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The brain exhibits complex intrinsic dynamics, i.e., spontaneously arising activity patterns without any external inputs or tasks. Such intrinsic dynamics and their alteration are thought to play crucial roles in typical as well as atypical cognitive functioning. Linking the ever-changing intrinsic dynamics to the rather static anatomy is a challenging endeavor. Dynamical systems models are important tools for understanding how structure and function are linked in the brain. Here, we provide a novel modeling framework to examine how functional connectivity depends on structural connectivity in the brain. Existing modeling frameworks typically focus on noise-driven (or stochastic) dynamics near a single attractor. Complementing existing approaches, we examine deterministic features of the distribution of attractors, in particular, how regional states are correlated across all attractors - cross-attractor coordination. We found that cross-attractor coordination between brain regions better predict human functional connectivity than noise-driven single-attractor dynamics. Importantly, cross-attractor coordination better accounts for the nonlinear dependency of functional connectivity on structural connectivity. Our findings suggest that functional connectivity patterns in the brain may reflect transitions between attractors, which impose an energy cost. The framework may be used to predict transitions and energy costs associated with experimental or clinical interventions.
... We performed probabilistic tractography on 7 Tesla preprocessed data using MRtrix3 (https://www.mrtrix.org) iFOD2 algorithm (Tournier et al., 2010) based on constrained spherical deconvolution (Tournier et al., 2007) using the following parameters: 90 maximum angle between successive steps, 0.07 cut-off and 1-mm minimum streamline-length. For each seed-mask, we propagated 100,000 streamlines, and, for each pair of seed-target masks we computed a "structural-connectivity-index" (range: [0 to 1]) equal to the fraction of streamlines propagated from the seed reaching the target mask. ...
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Brainstem nuclei are key participants in the generation and maintenance of arousal, which is a basic function that modulates wakefulness/sleep, autonomic responses, affect, attention, and consciousness. Their mechanism is based on diffuse pathways ascending from the brainstem to the thalamus, hypothalamus, basal forebrain and cortex. Several arousal brainstem nuclei also participate in motor functions that allow humans to respond and interact with the surrounding through a multipathway motor network. Yet, little is known about the structural connectivity of arousal and motor brainstem nuclei in living humans. This is due to the lack of appropriate tools able to accurately visualize brainstem nuclei in conventional imaging. Using a recently developed in vivo probabilistic brainstem nuclei atlas and 7 Tesla diffusion-weighted images (DWI), we built the structural connectome of 18 arousal and motor brainstem nuclei in living humans (n = 19). Furthermore, to investigate the translatability of our findings to standard clinical MRI, we acquired 3 Tesla DWI on the same subjects, and measured the association of the connectome across scanners. For both arousal and motor circuits, our results showed high connectivity within brainstem nuclei, and with expected subcortical and cortical structures based on animal studies. The association between 3 Tesla and 7 Tesla connectivity values was good, especially within the brainstem. The resulting structural connectome might be used as a baseline to better understand arousal and motor functions in health and disease in humans.
... For each FOD template, we performed whole-brain probabilistic tractography (iFOD2) seeded from a whole-brain white matter mask to generate a tractogram of 20 million streamlines and a fixel-fixel connectivity matrix (Tournier et al., 2019, Tournier et al., 2010. To reduce tractography biases in each whole-brain tractogram, we selected a subset of 2 million streamlines that best fit the diffusion signal using the SIFT algorithm (Smith et al., 2013). ...
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Background Variation in the longitudinal course of childhood attention deficit/hyperactivity disorder (ADHD) coincides with neurodevelopmental maturation of brain structure and function. Prior work has attempted to determine how alterations in white matter (WM) relate to changes in symptom severity, but much of that work has been done in smaller cross-sectional samples using voxel-based analyses. Using standard diffusion-weighted imaging (DWI) methods, we previously showed WM alterations were associated with ADHD symptom remission over time in a longitudinal sample of probands, siblings, and unaffected individuals. Here, we extend this work by further assessing the nature of these changes in WM microstructure by including an additional follow-up measurement (aged 18 – 34 years), and using the more physiologically informative fixel-based analysis (FBA). Methods Data were obtained from 139 participants over 3 clinical and 2 follow-up DWI waves, and analyzed using FBA in regions-of-interest based on prior findings. We replicated previously reported significant models and extended them by adding another time-point, testing whether changes in combined ADHD and hyperactivity-impulsivity (HI) continuous symptom scores are associated with fixel metrics at follow-up. Results Clinical improvement in HI symptoms over time was associated with more fiber density at follow-up in the left corticospinal tract (lCST) (tmax = 1.092, standardized effect[SE] = 0.044, pFWE = 0.016). Improvement in combined ADHD symptoms over time was associated with more fiber cross-section at follow-up in the lCST (tmax = 3.775, SE = 0.051, pFWE = 0.019). Conclusions Aberrant white matter development involves both lCST micro- and macrostructural alterations, and its path may be moderated by preceding symptom trajectory.
... We carried out the experiments on pre-processed data [28] of six different subjects from the young adult data set of the Human Connectome Project [29]. The whole-brain tractograms derived from this data were provided by the authors of [30] 1 and computed with the iFOD2 [31] algorithm. Ten million streamlines were created for each subject, restricted to be between 40mm and 250mm in length, with a step size of 0.625mm. ...
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Tractography has become an indispensable part of brain connectivity studies. However, it is currently facing problems with reliability. In particular, a substantial amount of nerve fiber reconstructions (streamlines) in tractograms produced by state-of-the-art tractography methods are anatomically implausible. To address this problem, tractogram filtering methods have been developed to remove faulty connections in a postprocessing step. This study takes a closer look at one such method, \textit{Spherical-deconvolution Informed Filtering of Tractograms} (SIFT), which uses a global optimization approach to improve the agreement between the remaining streamlines after filtering and the underlying diffusion magnetic resonance imaging data. SIFT is not suitable to judge the plausibility of individual streamlines since its results depend on the size and composition of the surrounding tractogram. To tackle this problem, we propose applying SIFT to randomly selected tractogram subsets in order to retrieve multiple assessments for each streamline. This approach makes it possible to identify streamlines with very consistent filtering results, which were used as pseudo ground truths for training classifiers. The trained classifier is able to distinguish the obtained groups of plausible and implausible streamlines with accuracy above 80%. The software code used in the paper and pretrained weights of the classifier are distributed freely via the Github repository https://github.com/djoerch/randomised_filtering.
... In brief, multishell multitissue constrained spherical deconvolution algorithm from MRtrix was applied to generate fiber orientation distributions [131,132]. Probabilistic streamline tractography based on the generated fiber orientation distributions was used to reconstruct white matter edges [133]. The tract weights were optimized by estimating an appropriate cross-section multiplier for each streamline following the procedure proposed by Smith and colleagues [134]. ...
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Whole-brain neural communication is typically estimated from statistical associations among electromagnetic or haemodynamic time-series. The relationship between functional network architectures recovered from these 2 types of neural activity remains unknown. Here, we map electromagnetic networks (measured using magnetoencephalography (MEG)) to haemodynamic networks (measured using functional magnetic resonance imaging (fMRI)). We find that the relationship between the 2 modalities is regionally heterogeneous and systematically follows the cortical hierarchy, with close correspondence in unimodal cortex and poor correspondence in transmodal cortex. Comparison with the BigBrain histological atlas reveals that electromagnetic–haemodynamic coupling is driven by laminar differentiation and neuron density, suggesting that the mapping between the 2 modalities can be explained by cytoarchitectural variation. Importantly, haemodynamic connectivity cannot be explained by electromagnetic activity in a single frequency band, but rather arises from the mixing of multiple neurophysiological rhythms. Correspondence between the two is largely driven by MEG functional connectivity at the beta (15 to 29 Hz) frequency band. Collectively, these findings demonstrate highly organized but only partly overlapping patterns of connectivity in MEG and fMRI functional networks, opening fundamentally new avenues for studying the relationship between cortical microarchitecture and multimodal connectivity patterns.
... Subsequently, we computed the tractogram by exploiting an Anatomically Constrained Tractography (Smith et al. 2012) approach, using as anatomical constraints a five-tissue-type (5TT) segmented tissue image obtained from the patient's structural T1w image within the MRtrix 5ttgen routine and including as fifth tissue (i.e., the pathological tissue) the manually segmented lesion mask. Individual fibre tracking was performed with a second-order Integration over Fiber Orientation Distributions (FOD) algorithm (Tournier et al. 2010) with streamline termination criteria values set at software defaults (maximum angle q = 45°, FOD amplitude cut-off value of 0.1). The number of generated streamlines for each patient initially amounted to 100 M, which were quantitatively reduced to 10 M via the Spherical-deconvolution Informed Filtering of Tractograms framework (Smith et al. 2013). ...
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Gliomas are amongst the most common primary brain tumours in adults and are often associated with poor prognosis. Understanding the extent of white matter (WM) which is affected outside the tumoral lesion may be of paramount importance to explain cognitive deficits and the clinical progression of the disease. To this end, we explored both direct (i.e., tractography based) and indirect (i.e., atlas-based) approaches to quantifying WM structural disconnections in a cohort of 44 high- and low-grade glioma patients. While these methodologies have recently gained popularity in the context of stroke and other pathologies, to our knowledge, this is the first time they are applied in patients with brain tumours. More specifically, in this work, we present a quantitative comparison of the disconnection maps provided by the two methodologies by applying well-known metrics of spatial similarity, extension, and correlation. Given the important role the oedematous tissue plays in the physiopathology of tumours, we performed these analyses both by including and excluding it in the definition of the tumoral lesion. This was done to investigate possible differences determined by this choice. We found that direct and indirect approaches offer two distinct pictures of structural disconnections in patients affected by brain gliomas, presenting key differences in several regions of the brain. Following the outcomes of our analysis, we eventually discuss the strengths and pitfalls of these two approaches when applied in this critical field.
... To date, bilateral atlases have been constructed for the optic radiation and corticospinal tract. First, the tract is reconstructed in each of a series of healthy training dMRI datasets (n=16) [25] using multi-shell multi-tissue constrained spherical deconvolution [26][27][28] and probabilistic streamline tractography [29,30] and a consistent ROI-based reconstruction protocol. After manual filtering of biologically implausible streamlines, the reconstructions are transformed to MNI space [31]. ...
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Purpose Intraoperative diffusion MRI could provide a means of visualising brain fibre tracts near a neurosurgical target after preoperative images have been invalidated by brain shift. We propose an atlas-based intraoperative tract segmentation method, as the standard preoperative method, streamline tractography, is unsuitable for intraoperative implementation. Methods A tract-specific voxel-wise fibre orientation atlas is constructed from healthy training data. After registration with a target image, a radial tumour deformation model is applied to the orientation atlas to account for displacement caused by lesions. The final tract map is obtained from the inner product of the atlas and target image fibre orientation data derived from intraoperative diffusion MRI. Results The simple tumour model takes only seconds to effectively deform the atlas into alignment with the target image. With minimal processing time and operator effort, maps of surgically relevant tracts can be achieved that are visually and qualitatively comparable with results obtained from streamline tractography. Conclusion Preliminary results demonstrate feasibility of intraoperative streamline-free tract segmentation in challenging neurosurgical cases. Demonstrated results in a small number of representative sample subjects are realistic despite the simplicity of the tumour deformation model employed. Following this proof of concept, future studies will focus on achieving robustness in a wide range of tumour types and clinical scenarios, as well as quantitative validation of segmentations.
... Probabilistic tractography was carried out in MRtrix3 using the Second-order Integration over Fiber Orientation Distributions (iFOD2) algorithm (73) in the upsampled individual subject space. Each subject's FOD . ...
... Next, whole-brain probabilistic fibre tractography on the FOD template was performed (20 million streamlines, termination cut-off 0.6, angle 22.5, max length 250mm, min length 10mm) using the iFOD2 algorithm (Tournier et al., 2010). The tractogram was then filtered to reduce the number of streamlines to 2 million using sphericaldeconvolution informed filtering of tractograms algorithm (SIFT2; (Smith et al., 2013)) to reduce global reconstruction biases. ...
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... [27] We then performed spherical deconvolution on the preprocessed DWI to get direct fiber orientation density function for every voxel. [28] We ran probabilistic tractography [29] and weighted the tractogram with spherical-deconvolution informed filtering of tractograms (SIFT2) for improved biological accuracy of whitematter representation. [30] Finally, we generated the structural connectomes by assigning SIFT2-weighted streamline counts between ROIs (SC connectome), and average fractional anisotropy (FA) between ROIs in the DK segmentation (FA connectome). ...
Article
Objective We sought to augment the presurgical workup of medically refractory temporal lobe epilepsy by creating a supervised machine learning technique that uses diffusion-weighted imaging to classify patient-specific seizure onset laterality and surgical outcome. Methods 151 subjects were included in this analysis: 62 patients (aged 18–68 years, 36 women) and 89 healthy controls (aged 18–71 years, 47 women). We created a supervised machine learning technique that uses diffusion-weighted metrics to classify subject groups. Specifically, we sought to classify patients versus healthy controls, unilateral versus bilateral temporal lobe epilepsy, left versus right temporal lobe epilepsy and seizure-free versus not seizure-free surgical outcome. We then reduced the dimensionality of derived features with community detection for ease of interpretation. Results We classified the subject groups in withheld testing data sets with a cross-fold average testing areas under the receiver operating characteristic curve of 0.745 for patients versus healthy controls, 1.000 for unilateral versus bilateral seizure onset, 0.662 for left versus right seizure onset, 0.800 for left-sided seizure-free vsersu not seizure-free surgical outcome and 0.775 for right-sided seizure-free versus not seizure-free surgical outcome. Conclusions This technique classifies important clinical decisions in the presurgical workup of temporal lobe epilepsy by generating discerning white-matter features. We believe that this work augments existing network connectivity findings in the field by further elucidating important white-matter pathology in temporal lobe epilepsy. We hope that this work contributes to recent efforts aimed at using diffusion imaging as an augmentation to the presurgical workup of this devastating neurological disorder.
... These were then used to estimate FOD based on constrained spherical deconvolution using dwi2fod (Tournier, Calamante, & Connelly, 2007). For fiber tracking, we then used tckgen with the improved second-order integration over fiber orientation distributions (iFOD2) algorithm (Tournier, Calamante, & Connelly, 2010 ...
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Autonomic, pain, limbic, and sensory processes are mainly governed by the central nervous system, with brainstem nuclei as relay centers for these crucial functions. Yet, the structural connectivity of brainstem nuclei in living humans remains understudied. These tiny structures are difficult to locate using conventional in vivo MRI, and ex vivo brainstem nuclei atlases lack precise and automatic transformability to in vivo images. To fill this gap, we mapped our recently developed probabilistic brainstem nuclei atlas developed in living humans to high-spatial resolution (1.7 mm isotropic) and diffusion weighted imaging (DWI) at 7 Tesla in 20 healthy participants. To demonstrate clinical translatability, we also acquired 3 Tesla DWI with conventional resolution (2.5 mm isotropic) in the same participants. Results showed the structural connectome of 15 autonomic, pain, limbic, and sensory (including vestibular) brainstem nuclei/nuclei complex (superior/inferior colliculi, ventral tegmental area-parabrachial pigmented, microcellular tegmental-parabigeminal, lateral/medial parabrachial, vestibular, superior olivary, superior/inferior medullary reticular formation, viscerosensory motor, raphe magnus/pallidus/obscurus, parvicellular reticular nucleus-alpha part), derived from probabilistic tractography computation. Through graph measure analysis, we identified network hubs and demonstrated high intercommunity communication in these nuclei. We found good (r = .5) translational capability of the 7 Tesla connectome to clinical (i.e., 3 Tesla) datasets. Furthermore, we validated the structural connectome by building diagrams of autonomic/pain/limbic connectivity, vestibular connectivity, and their interactions, and by inspecting the presence of specific links based on human and animal literature. These findings offer a baseline for studies of these brainstem nuclei and their functions in health and disease, including autonomic dysfunction, chronic pain, psychiatric, and vestibular disorders.
... Next, the FOD template was segmented using the JHU Neonate Atlas ( Oishi et al., 2011 ) utilizing a multi-channel registration algorithm with the mean DWI, FA, and MD contrasts ( Djamanakova et al., 2013 ) to obtain regions-of-interest (ROIs) for tracking of the five association fibers (see details in Supplementary material and Fig.S2), including the arcuate fasciculus (AF), cingulum, uncinate fasciculus (UNC), inferior frontooccipital fasciculus (IFO), and inferior longitudinal fasciculus (ILF). Tractography was performed on the FOD template using the secondorder integration over FOD method ( Tournier et al., 2010 ) with the following parameters: step size = 0.5 mm, maximum length = 250 mm, minimum length = 10 mm, maximum angles were set to 75°, and a relatively high FOD cutoff of 0.1 to avoid partial volume effect. The trunk Fig. 1. ...
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Association fibers connect the cortical regions and experience rapid development involving myelination and axonal growth during infancy. Yet, the spatiotemporal patterns of microstructural changes along these tracts, as well as the developmental interaction between the white matter (WM) tracts and the cortical gray matter (cGM) connected to them, are mostly unknown during infancy. In this study, we performed a diffusion MRI-based tractography and microstructure study in a cohort of 89 healthy preterm-born infants with gestational age at birth between 28.1∼36.4 weeks and postmenstrual age at scan between 39.9∼59.9 weeks. Results revealed that several C-shaped fibers, such as the arcuate fasciculus, cingulum, and uncinate fasciculus, demonstrated symmetrical along-tract profiles; and the horizontally oriented running fibers, including the inferior fronto-occipital fasciculus and the inferior longitudinal fasciculus, demonstrated an anterior-posterior developmental gradient. This study characterized the along-tract profiles using fixel-based analysis and revealed that the fiber cross-section (FC) of all five association fibers demonstrated a fluctuating increase with age, while the fiber density (FD) monotonically increase with age. NODDI was utilized to analyze the microstructural development of cGM and indicated cGM connected to the anterior end of the association fibers developed faster than that of the posterior end during 0-5 months. Notably, a mediation analysis was used to explore the relation between the development of WM and associated cGM, and demonstrated a partial mediation effect of FD in WM on the development of intracellular volume (ICV) in cGM and a full mediation effect of ICV on the growth of FD in most fibers, suggesting a predominant mediation of cGM on the WM development. Furthermore, for assessing whether those results were biased by prematurity, we compared preterm- and term-born neonates with matched scan age, gender, and multiple births from the developing human connectome project (dHCP) dataset to assess the effect of preterm-birth, and the results indicated a similar developmental pattern of the association fibers and their attached cGM. These findings presented a comprehensive picture of the major association fibers during early infancy and deciphered the developmental interaction between WM and cGM in this period.
... The white matter fiber orientation distribution (FOD) was then resolved at the voxel-wise level by processing the outermost b-value shell (b=3000s/mm 2 ) using single-shell constrained spherical deconvolution, a technique to separate directional axonal signal from intracellular and extracellular isotropic diffusion 54 . Probabilistic tractography was performed by applying the iFOD2 algorithm which propagates streamlines between voxels based on the direction and amplitude of the underlying FOD 87 . Seeding of streamlines was performed by randomly selecting voxels within a whole brain mask created by co-registering using ANTs each subject's skull-stripped T1 output from Freesurfer 75,88 . ...
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Functional connectivity between the amygdala and the medial prefrontal cortex (mPFC) has been identified as a neural substrate of emotion regulation that undergoes changes throughout development. Amygdala-mPFC connectivity has been well studied in adolescents and adults, with a mature profile typically emerging at 10 years of age. Maternal bonding in childhood has been shown to buffer amygdala reactivity and to influence the trajectory of amygdala-mPFC coupling, which in turn may impact socio-emotional dysfunction later in life. The oxytocinergic system is critical in the development of social behavior and maternal bonding. Early life parental care influences the methylation status of the oxytocin receptor (OXTRm) in animal models and humans, and higher OXTRm is associated with lower amygdala-PFC functional connectivity in adults. Using a neuroimaging-epigenetic approach, we investigated OXTRm as a biological marker of functional connectivity maturation in middle childhood. We find that higher levels of OXTRm are associated with a more adult-like functional connectivity profile. We also find that lower OXTRm blunts the association between amygdala-mPFC connectivity and future internalizing behaviors in early adolescence. These findings implicate OXTRm as a biological marker at the interface of the social environment and amygdala-mPFC coupling in emotional and behavioral regulation. Ultimately, identification of neurobiological markers may lead to earlier detection of children at risk for socio-emotional dysfunction.
... The fiber orientation distributions (FODs) were estimated using constrained spherical deconvolution (CSD) (Tournier et al., 2007) with default parameters. Probabil-185 istic tractography was calculated using the second-order Integration over FODs (iFOD2) (Tournier et al., 2010) (Smith et al., 2013), keeping 3 million of fibers per subject. ...
Article
The study of short association fibers is still an incomplete task due to their higher inter-subject variability and the smaller size of this kind of fibers in comparison to known long association bundles. However, their description is essential to understand human brain dysfunction and better characterize the human brain connectome. In this work, we present a multi-subject atlas of short association fibers, which was computed using a superficial white matter bundle identification method based on fiber clustering. To create the atlas, we used probabilistic tractography from one hundred subjects from the HCP database, aligned with non-linear registration. The method starts with an intra-subject clustering of short fibers (30-85 mm). Based on a cortical atlas, the intra-subject cluster centroids from all subjects are segmented to identify the centroids connecting each region of interest (ROI) of the atlas. To reduce computational load, the centroids from each ROI group are randomly separated into ten subgroups. Then, an inter-subject hierarchical clustering is applied to each centroid subgroup, followed by a second level of clustering to select the most-reproducible clusters across subjects for each ROI group. Finally, the clusters are labeled according to the regions that they connect, and clustered to create the final bundle atlas. The resulting atlas is composed of 525 bundles of superficial short association fibers along the whole brain, with 384 bundles connecting pairs of different ROIs and 141 bundles connecting portions of the same ROI. The reproducibility of the bundles was verified using automatic segmentation on three different tractogram databases. Results for deterministic and probabilistic tractography data show high reproducibility, especially for probabilistic tractography in HCP data. In comparison to previous work, our atlas features a higher number of bundles and greater cortical surface coverage.
... The peaks of the fODF were calculated and input into a software known as TractSeg to obtain tracts and tractending segmentations (Wasserthal et al., 2018(Wasserthal et al., , 2019. Tract orientation mappings were then calculated and tractography generated through probabilistic tracking using iFOD2 and a dilation factor of 2 ( Figure 2A) (Tournier et al., 2010). The corpus callosum was partitioned into seven segments according to the Witelson scheme based on locations of cortical intercepts (Witelson, 1989). ...
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Introduction Disease development in multiple sclerosis (MS) causes dramatic structural changes, but the exact changing patterns are unclear. Our objective is to investigate the differences in brain structure locally and spatially between relapsing-remitting MS (RRMS) and its advanced form, secondary progressive MS (SPMS), through advanced analysis of diffusion magnetic resonance imaging (MRI) and image texture. Methods A total of 20 patients with RRMS and nine patients with SPMS from two datasets underwent 3T anatomical and diffusion tensor imaging (DTI). The DTI was harmonized, augmented, and then modeled, which generated six voxel- and sub-voxel-scale measures. Texture analysis focused on T2 and FLAIR MRI, which produced two phase-based measures, namely, phase congruency and weighted mean phase. Data analysis was 3-fold, i.e., histogram analysis of whole-brain normal appearing white matter (NAWM); region of interest (ROI) analysis of NAWM and lesions within three critical white matter tracts, namely, corpus callosum, corticospinal tract, and optic radiation; and along-tract statistics. Furthermore, by calculating the z-score of core-rim pathology within lesions based on diffusion measures, we developed a novel method to define chronic active lesions and compared them between cohorts. Results Histogram features from diffusion and all but one texture measure differentiated between RRMS and SPMS. Within-tract ROI analysis detected cohort differences in both NAWM and lesions of the corpus callosum body in three measures of neurite orientation and anisotropy. Along-tract statistics detected cohort differences from multiple measures, particularly lesion extent, which increased significantly in SPMS in posterior corpus callosum and optic radiations. The number of chronic active lesions were also significantly higher (by 5–20% over z-scores 0.5 and 1.0) in SPMS than RRMS based on diffusion anisotropy, neurite content, and diameter. Conclusion Advanced diffusion MRI and texture analysis may be promising approaches for thorough understanding of brain structural changes from RRMS to SPMS, thereby providing new insight into disease development mechanisms in MS.
... The intensity of the white matter fibre orientation distributions was normalized (30), and used for anatomically constrained whole-brain tractography (34) (along with the registered 5TT image). The tractography protocols were as follows: 15 million tracks were generated, iFOD2 probabilistic fibre tracking (35), dynamic seeding (36), maximum length 300 mm, backtrack selected and crop at gray-matter-white-matter interface selected. For quantitative analysis, the corresponding weight for each streamline in the tractogram was derived using SIFT2 (36); the streamline weights and tractogram were used to generate a track-density image (TDI) (37). ...
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We examined the white matter of patients with and without focal to bilateral tonic-clonic seizures (FBTCS), and control participants. A neural network based tract segmentation model (Tractseg) was used to isolate tract-specific, track-weighted tensor-based measurements from the tracts of interest. We compared the group differences in the track-weighted tensor-based measurements derived from whole and hemispheric tracts. We identified several regions that displayed significantly altered white matter in patients with focal epilepsy compared to controls. Furthermore, patients without FBTCS showed significantly increased white matter disruption in the inferior fronto-occipital fascicle and the striato-occipital tract. In contrast, the track-weighted tensor-based measurements from the FBTCS cohort exhibited a stronger resemblance to the healthy controls (compared to the non-FBTCS group). Our findings revealed marked alterations in a range of subcortical tracts considered critical in the genesis of seizures in focal epilepsy. Our novel application of tract-specific, track-weighted tensor-based measurements to a new clinical dataset aided the elucidation of specific tracts that may act as a predictive biomarker to distinguish patients likely to develop FBTCS.
... The registration was manually checked before inputting the ROIs into the ACT algorithm. Finally, for tracking, we used the tckgen iFOD2 algorithm, which is capable of reconstructing fibers with complex configurations (Tournier et al., 2010). We used the following additional tckgen settings and inputs: step size 0.8 mm, min. ...
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This study aimed to evaluate the use of diffusion kurtosis imaging (DKI) to detect microstructural abnormalities within the temporal pole (TP) and its temporopolar cortex in temporal lobe epilepsy (TLE) patients. DKI quantitative maps were obtained from fourteen lesional TLE and ten non-lesional TLE patients, along with twenty-three healthy controls. Data collected included mean (MK); radial (RK) and axial kurtosis (AK); mean diffusivity (MD) and axonal water fraction (AWF). Automated fiber quantification (AFQ) was used to quantify DKI measurements along the inferior longitudinal (ILF) and uncinate fasciculus (Unc). ILF and Unc tract profiles were compared between groups and tested for correlation with disease duration. To characterize temporopolar cortex microstructure, DKI maps were sampled at varying depths from superficial white matter (WM) towards the pial surface. Patients were separated according to the temporal lobe ipsilateral to seizure onset and their AFQ results were used as input for statistical analyses. Significant differences were observed between lesional TLE and controls, towards the most temporopolar segment of ILF and Unc proximal to the TP within the ipsilateral temporal lobe in left TLE patients for MK, RK, AWF and MD. No significant changes were observed with DKI maps in the non-lesional TLE group. DKI measurements correlated with disease duration, mostly towards the temporopolar segments of the WM bundles. Stronger differences in MK, RK and AWF within the temporopolar cortex were observed in the lesional TLE and noticeable differences (except for MD) in non-lesional TLE groups compared to controls. This study demonstrates that DKI has potential to detect subtle microstructural alterations within the temporopolar segments of the ILF and Unc and the connected temporopolar cortex in TLE patients including non-lesional TLE subjects. This could aid our understanding of the extrahippocampal areas, more specifically the temporal pole role in seizure generation in TLE and might inform surgical planning, leading to better seizure outcomes.
... First, a tractography with 40 million streamlines (default but modifiable, maximum tract length=400, minimum length=10, cutoff=0.06, step=0.5) is generated using the iFOD2 algorithm and 3-tissue anatomically constrained tractography Tournier et al., 2010). A second tract density image (TDI) of the resulting tractography is computed for QC. ...
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Multimodal magnetic resonance imaging (MRI) has accelerated human neuroscience by fostering the analysis of brain microstructure, geometry, function, and connectivity across multiple scales and in living brains. The richness and complexity of multimodal neuroimaging, however, demands processing methods to integrate information across modalities and to consolidate findings across different spatial scales. Here, we present micapipe, an open processing pipeline for multimodal MRI datasets. Based on BIDS-conform input data, micapipe can generate i) structural connectomes derived from diffusion tractography, ii) functional connectomes derived from resting-state signal correlations, iii) geodesic distance matrices that quantify cortico-cortical proximity, and iv) microstructural profile covariance matrices that assess inter-regional similarity in cortical myelin proxies. The above matrices can be automatically generated across established 18 cortical parcellations (100-1000 parcels), in addition to subcortical and cerebellar parcellations, allowing researchers to replicate findings easily across different spatial scales. Results are represented on three different surface spaces (native, conte69, fsaverage5), and outputs are BIDS-conform. Processed outputs can be quality controlled at the individual and group level. micapipe was tested on several datasets and is available at https://github.com/MICA-MNI/micapipe, documented at https://micapipe.readthedocs.io/, and containerized as a BIDS App http://bids-apps.neuroimaging.io/apps/. We hope that micapipe will foster robust and integrative studies of human brain microstructure, morphology, function, cand connectivity.
... All ROIs were transferred to the study-specific FOD template following linear registration of the FSL HCP1065 standard-space fractional anisotropy (FA) image to the study-specific white matter FOD template. Probabilistic streamline tractography between homologous ROIs was performed using the study-specific FOD template and the 2 nd -order integration over FOD algorithm [78]. To restrict streamlines to those passing only through the CC, appropriate CC inclusion and midline exclusion masks were manually drawn on the white matter FOD template. ...
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Aging may be associated with motor decline that is attributed to deteriorating white matter microstructure of the corpus callosum (CC), among other brain-related factors. Similar to motor functioning, executive functioning (EF) typically declines during aging, with age-associated changes in EF likewise being linked to altered white matter connectivity in the CC. Given that both motor and executive functions rely on white matter connectivity via the CC, and that bimanual control is thought to rely on EF, the question arises whether EF can at least party account for the proposed link between CC-connectivity and motor control in older adults. To address this, diffusion magnetic resonance imaging data were obtained from 84 older adults. A fiber-specific approach was used to obtain fiber density (FD), fiber cross-section (FC), and a combination of both metrics in eight transcallosal white matter tracts. Motor control was assessed using a bimanual coordination task. EF was determined by a domain-general latent EF-factor extracted from multiple EF tasks, based on a comprehensive test battery. FD of transcallosal prefrontal fibers was associated with cognitive and motor performance. EF partly accounted for the relationship between FD of prefrontal transcallosal pathways and motor control. Our results underscore the multidimensional interrelations between callosal white matter connectivity (especially in prefrontal brain regions), EF across multiple domains, and motor control in the older population. They also highlight the importance of considering EF when investigating brain-motor behavior associations in older adults.
... This tool can discern crossing fibers and provide more than one direction in each voxel. Next, streamline tractography was performed on the estimated fiber orientation distributions using a probabilistic algorithm (iFOD2; Tournier et al. 2010 ) with the following parameters: step size 1mm, maximum fiber length 200mm, minimum fiber length 20mm, FODs amplitude threshold 0.05, angle threshold 45 degrees. The ROIs used in the streamline tractography are described in Table 1 (please note that the dentatothalamic tract is a cross-hemispheric tract; in the present study we defined the hemisphere of this tract based on the thalamic hemisphere for the convenience of the description). ...
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The “primary” or “first-order relay” nuclei of the thalamus feed the cerebral cortex with information about ongoing activity in the environment or the subcortical motor systems. Because of the small size of these nuclei and the high specificity of their input and output pathways, new imaging protocols are required to investigate thalamocortical interactions in human perception, cognition and language. The goal of the present study was twofold: I) to develop a reconstruction protocol based on in vivo diffusion MRI to extract and measure the axonal fiber tracts that originate or terminate specifically in individual first-order relay nuclei; and, II) to test the reliability of this reconstruction protocol. In left and right hemispheres, we investigated the thalamocortical/corticothalamic axon bundles linking each of the first-order relay nuclei and their main cortical target areas, namely, the lateral geniculate nucleus (optic radiation), the medial geniculate nucleus (acoustic radiation), the ventral posterior nucleus (somatosensory radiation) and the ventral lateral nucleus (motor radiation). In addition, we examined the main subcortical input pathway to the ventral lateral posterior nucleus, which originates in the dentate nucleus of the cerebellum. Our protocol comprised three components: defining regions-of-interest; preprocessing diffusion data; and modeling white-matter tracts and tractometry. We then used computation and test-retest methods to check whether our protocol could reliably reconstruct these tracts of interest and their profiles. Our results demonstrated that the protocol had nearly perfect computational reproducibility and good-to-excellent test-retest reproducibility. This new protocol may be of interest for both basic human brain neuroscience and clinical studies and has been made publicly available to the scientific community.
... (1) tissue segmentation based on T1-weighted structural image; (2) calculation of 4D images with gray matter, white matter, and cerebrospinal fluid using multi-shell, multi-tissue constrained spherical deconvolution [79]; (3) generation of white matter-constrained tractography using second-order integration over fiber orientation distributions (iFOD2), a probabilistic tracking algorithm (1,000,000 streamlines for each participant, max length = 250 mm, cutoff = 0.06) [80]; (4) use of FSL's FNIRT to reverse-register the MMP parcellation to individual space; (5) calculation of FA maps using dtifit of FSL; and (6) measurement of the average FA on all the streamlines connecting any 2 parcels. This process finally resulted in 360 × 360 FA matrices and FN matrices for 99 participants. ...
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Hemispheric lateralization constitutes a core architectural principle of human brain organization underlying cognition, often argued to represent a stable, trait-like feature. However, emerging evidence underlines the inherently dynamic nature of brain networks, in which time-resolved alterations in functional lateralization remain uncharted. Integrating dynamic network approaches with the concept of hemispheric laterality, we map the spatiotemporal architecture of whole-brain lateralization in a large sample of high-quality resting-state fMRI data ( N = 991, Human Connectome Project). We reveal distinct laterality dynamics across lower-order sensorimotor systems and higher-order associative networks. Specifically, we expose 2 aspects of the laterality dynamics: laterality fluctuations (LF), defined as the standard deviation of laterality time series, and laterality reversal (LR), referring to the number of zero crossings in laterality time series. These 2 measures are associated with moderate and extreme changes in laterality over time, respectively. While LF depict positive association with language function and cognitive flexibility, LR shows a negative association with the same cognitive abilities. These opposing interactions indicate a dynamic balance between intra and interhemispheric communication, i.e., segregation and integration of information across hemispheres. Furthermore, in their time-resolved laterality index, the default mode and language networks correlate negatively with visual/sensorimotor and attention networks, which are linked to better cognitive abilities. Finally, the laterality dynamics are associated with functional connectivity changes of higher-order brain networks and correlate with regional metabolism and structural connectivity. Our results provide insights into the adaptive nature of the lateralized brain and new perspectives for future studies of human cognition, genetics, and brain disorders.
... More specifically, fibre orientation distributions were generated using the multi-shell multi-tissue constrained spherical deconvolution algorithm from MRtrix 107,108 . White-matter edges were then reconstructed using probabilistic streamline tractography based on the generated fibre orientation distributions 109 . The tract weights were then optimised by estimating an appropriate cross-section multiplier for each streamline following the procedure proposed by Smith et al. 110 and a connectivity matrix was built for each participant using the 68-region Deskian-Killiany parcellation 40,41 . ...
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Numerous brain disorders demonstrate structural brain abnormalities, which are thought to arise from molecular perturbations or connectome miswiring. The unique and shared contributions of these molecular and connectomic vulnerabilities to brain disorders remain unknown, and has yet to be studied in a single multi-disorder framework. Using MRI morphometry from the ENIGMA consortium, we construct maps of cortical abnormalities for thirteen neurodevelopmental, neurological, and psychiatric disorders from N = 21,000 participants and N = 26,000 controls, collected using a harmonised processing protocol. We systematically compare cortical maps to multiple micro-architectural measures, including gene expression, neurotransmitter density, metabolism, and myelination (molecular vulnerability), as well as global connectomic measures including number of connections, centrality, and connection diversity (connectomic vulnerability). We find a relationship between molecular vulnerability and white-matter architecture that drives cortical disorder profiles. Local attributes, particularly neurotransmitter receptor profiles, constitute the best predictors of both disorder-specific cortical morphology and cross-disorder similarity. Finally, we find that cross-disorder abnormalities are consistently subtended by a small subset of network epicentres in bilateral sensory-motor, inferior temporal lobe, precuneus, and superior parietal cortex. Collectively, our results highlight how local molecular attributes and global connectivity jointly shape cross-disorder cortical abnormalities. Changes to structural and functional connectivity can give rise to neurodegeneration and neurodevelopmental diseases. Here the authors investigate molecular and connectomic patterns in 13 different neurological, psychiatric and neurodevelopmental diseases from the ENIGMA consortium.
... For each voxel the fiber orientation distribution function was computed using a constrained spherical deconvolution (CSD) model (Tournier et al., 2007). A final tracking step was carried out using a seed-based probabilistic strategy (Tournier et al., 2010) with a step size of 1.0 mm, maximum length 250 mm, and minimum length 10 mm. The fiber orientation distribution function (fODF) amplitude cut-off was set to 0.1, and the maximum angle of curvature to 30 • . ...
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Phonemic and semantic fluency are neuropsychological tests widely used to assess patients’ language and executive abilities and are highly sensitive tests in detecting language deficits in glioma patients. However, the networks that are involved in these tasks could be distinct and suggesting either a frontal (phonemic) or temporal (semantic) involvement. 42 right-handed patients (26 male, mean age=52.5 years, SD=±13.3) were included in this retrospective study. Patients underwent awake (54.8%) or asleep (45.2%) surgery for low-grade (16.7%) or high-grade-glioma (83.3%) in the frontal (64.3%) or temporal lobe (35.7%) of the left (50%) or right (50%) hemisphere. Pre-operative tractography was reconstructed for each patient, with segmentation of the inferior fronto-occipital fasciculus (IFOF), arcuate fasciculus (AF), uncinate fasciculus (UF), inferior longitudinal fasciculus (ILF), third branch of the superior longitudinal fasciculus (SLF-III), frontal aslant tract (FAT), and cortico-spinal tract (CST). Post-operative percentage of damage and disconnection of each tract, based on the patients’ surgical cavities, were correlated with verbal fluencies’ scores at one week and one month after surgery. Analyses of differences between fluency scores at these timepoints (before surgery, one week and one month after surgery) were performed; lesion-symptom mapping was used to identify the correlation between cortical areas and post-operative scores. Immediately after surgery, a transient impairment of verbal fluency was observed, that improved within a month. Left hemisphere lesions were related to a worse verbal fluency performance, being a damage to the left superior frontal or temporal gyri associated with phonemic or semantic fluency deficit, respectively. At a subcortical level, disconnection analyses revealed that fluency scores were associated to the involvement of the left FAT and the left frontal part of the IFOF for phonemic fluency, and the association was still present one month after surgery. For semantic fluency, the correlation between post-surgery performance emerged for the left AF, UF, ILF and the temporal part of the IFOF, but disappeared at the follow-up. This approach based on the patients’ pre-operative tractography, allowed to trace for the first time a dissociation between white matter pathways integrity and verbal fluency after surgery for glioma resection. Our results confirm the involvement of a frontal anterior pathway for phonemic fluency and a ventral temporal pathway for semantic fluency. Finally, our longitudinal results suggest that the frontal executive pathway requires a longer interval to recover compared to the semantic one.
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The human auditory cortex around Heschl’s gyrus (HG) exhibits diverging patterns across individuals owing to the heterogeneity of its substructures. In this study, we investigated the subregions of the human auditory cortex using data-driven machine-learning techniques at the individual level and assessed their structural and functional profiles. We studied an openly accessible large dataset of the Human Connectome Project and identified the subregions of the HG in humans using data-driven clustering techniques with individually calculated imaging features of cortical folding and structural connectivity information obtained via diffusion magnetic resonance imaging tractography. We characterized the structural and functional profiles of each HG subregion according to the cortical morphology, microstructure, and functional connectivity at rest. We found three subregions. The first subregion (HG1) occupied the central portion of HG, the second subregion (HG2) occupied the medial-posterior-superior part of HG, and the third subregion (HG3) occupied the lateral-anterior-inferior part of HG. The HG3 exhibited strong structural and functional connectivity to the association and paralimbic areas, and the HG1 exhibited a higher myelin density and larger cortical thickness than other subregions. A functional gradient analysis revealed a gradual axis expanding from the HG2 to the HG3. Our findings clarify the individually varying structural and functional organization of human HG subregions and provide insights into the substructures of the human auditory cortex.
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Complex cognitive abilities are thought to arise from the ability of the brain to adaptively reconfigure its internal network structure as a function of task demands. Recent work has suggested that this inherent flexibility may in part be conferred by the widespread projections of the ascending arousal systems. While the different components of the ascending arousal system are often studied in isolation, there are anatomical connections between neuromodulatory hubs that we hypothesize are crucial for mediating key features of adaptive network dynamics, such as the balance between integration and segregation. To test this hypothesis, we estimated the strength of structural connectivity between key hubs of the noradrenergic and cholinergic arousal systems (the locus coeruleus [LC] and nucleus basalis of Meynert [nbM], respectively). We then asked whether the strength of structural LC and nbM inter-connectivity was related to individual differences in the emergent, dynamical signatures of functional integration measured from resting state fMRI data, such as network and attractor topography. We observed a significant positive relationship between the strength of white-matter connections between the LC and nbM and the extent of network-level integration following BOLD signal peaks in LC relative to nbM activity. In addition, individuals with denser white-matter streamlines interconnecting neuromodulatory hubs also demonstrated a heightened ability to shift to novel brain states. These results suggest that individuals with stronger structural connectivity between the noradrenergic and cholinergic systems have a greater capacity to mediate the flexible network dynamics required to support complex, adaptive behaviour. Furthermore, our results highlight the underlying static features of the neuromodulatory hubs can impose some constraints on the dynamic features of the brain.
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Major depression is a leading cause of disability due to its trend to recurrence and treatment resistance. Currently, there are no biomarkers which could potentially identify patients with risk of treatment resistance. In this original paper, we propose a two-level shape analysis of the white matter bundles based on the Large Diffeomorphic Deformation Metric Mapping framework, to study treatment resistant depression. Fiber bundles are characterised via the deformation of their center line from a centroid shape. We developed two statistical analyses at a global and a local level to identify the most relevant bundles related to treatment resistant depression. Using a prospective longitudinal cohort including 63 patients. We applied this approach at baseline on 50 white matter fiber-tracts, to predict the clinical improvement at 6 months. Our results show a strong association between three bundles and the clinical improvement 6 months after. More precisely, the right-sided thalamo-occipital fascicle and optic radiations are the most robust followed by the splenium. The present study shows the interest in considering white matter shape in the context of depression, contributing to improve our understanding of neurobiological process of treatment resistance depression.
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Tractography combined with regions of interest (ROIs) has been used to non-invasively study the structural connectivity of the cortex as well as to assess the reliability of these connections. However, the subcortical connectome (subcortex to subcortex) has not been comprehensively examined, in part due to the difficulty of performing tractography in this complex and compact region. In this study, we performed an in vivo investigation using tractography to assess the feasibility and reliability of mapping known connections between structures of the subcortex using the test-retest dataset from the Human Connectome Project (HCP). We further validated our observations using a separate unrelated subjects dataset from the HCP. Quantitative assessment was performed by computing tract densities and spatial overlap of identified connections between subcortical ROIs. Further, known connections between structures of the basal ganglia and thalamus were identified and visually inspected, comparing tractography reconstructed trajectories with descriptions from tract-tracing studies. Our observations demonstrate both the feasibility and reliability of using a data-driven tractography-based approach to map the subcortical connectome in vivo.
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Preterm birth is closely associated with diffuse white matter dysmaturation inferred from diffusion MRI and neurocognitive impairment in childhood. Diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) are distinct dMRI modalities, yet metrics derived from these two methods share variance across tracts. This raises the hypothesis that dimensionality reduction approaches may provide efficient whole-brain estimates of white matter microstructure that capture (dys)maturational processes. To investigate the optimal model for accurate classification of generalised white matter dysmaturation in preterm infants we assessed variation in DTI and NODDI metrics across 16 major white matter tracts using principal component analysis and structural equation modelling, in 79 term and 141 preterm infants at term equivalent age. We used logistic regression models to evaluate performances of single-metric and multimodality general factor frameworks for efficient classification of preterm infants based on variation in white matter microstructure. Single-metric general factors from DTI and NODDI capture substantial shared variance (41.8-72.5%) across 16 white matter tracts, and two multimodality factors captured 93.9% of variance shared between DTI and NODDI metrics themselves. General factors associate with preterm birth and a single model that includes all seven DTI and NODDI metrics provides the most accurate prediction of microstructural variations associated with preterm birth. This suggests that despite global covariance of dMRI metrics in neonates, each metric represents information about specific (and additive) aspects of the underlying microstructure that differ in preterm compared to term subjects.
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Tractography is a powerful tool for the investigation of the complex organization of the brain in vivo, as it allows inferring the macroscopic pathways of the major fiber bundles of the white matter based on non-invasive diffusion-weighted magnetic resonance imaging acquisitions. Despite this unique and compelling ability, some studies have exposed the poor anatomical accuracy of the reconstructions obtained with this technique and challenged its effectiveness for studying brain connectivity. In this work, we describe a novel method to readdress tractography reconstruction problem in a global manner by combining the strengths of so-called generative and discriminative strategies. Starting from an input tractogram, we parameterize the connections between brain regions following a bundle-based representation that allows to drastically reducing the number of parameters needed to model groups of fascicles. The parameters space is explored following an MCMC generative approach, while a discrimininative method is exploited to globally evaluate the set of connections which is updated according to Bayes’ rule. Our results on both synthetic and real brain data show that the proposed solution, called bundle-o-graphy, allows improving the anatomical accuracy of the reconstructions while keeping the computational complexity similar to other state-of-the-art methods.
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Diffu0sion-weighted magnetic resonance imaging (dMRI) is a non-invasive imaging technique that provides information about the barriers to the diffusion of water molecules in tissue. In the brain, this information can be used in several important ways, including to examine tissue abnormalities associated with brain disorders and to infer anatomical connectivity and the organization of white matter bundles through the use of tractography algorithms. However, dMRI also presents certain challenges. For example, historically, the biological validation of tractography models has shown only moderate correlations with anatomical connectivity as determined through invasive tract-tracing studies. Some of the factors contributing to such issues are low spatial resolution, low signal-to-noise ratios, and long scan times required for high-quality data, along with modeling challenges like complex fiber crossing patterns. Leveraging the capabilities provided by an ultra-high field scanner combined with denoising, we have acquired whole-brain, 0.58 mm isotropic resolution dMRI with a 2D-single shot echo planar imaging sequence on a 10.5 Tesla scanner in anesthetized macaques. These data produced high-quality tractograms and maps of scalar diffusion metrics in white matter. This work demonstrates the feasibility and motivation for in-vivo dMRI studies seeking to benefit from ultra-high fields.
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Understanding brain structure and function often requires combining data across different modalities and scales to link microscale cellular structures to macroscale features of whole brain organisation. Here we introduce the BigMac dataset, a resource combining in vivo MRI, extensive postmortem MRI and multi-contrast microscopy for multimodal characterisation of a single whole macaque brain. The data spans modalities (MRI and microscopy), tissue states (in vivo and postmortem), and four orders of spatial magnitude, from microscopy images with micrometre or sub-micrometre resolution, to MRI signals on the order of millimetres. Crucially, the MRI and microscopy images are carefully co-registered together to facilitate quantitative multimodal analyses. Here we detail the acquisition, curation, and first release of the data, that together make BigMac a unique, openly-disseminated resource available to researchers worldwide. Further, we demonstrate example analyses and opportunities afforded by the data, including improvement of connectivity estimates from ultra-high angular resolution diffusion MRI, neuroanatomical insight provided by polarised light imaging and myelin-stained histology, and the joint analysis of MRI and microscopy data for reconstruction of the microscopy-inspired connectome. All data and code are made openly available.
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Network control theory provides a framework by which neurophysiological dynamics of the brain can be modelled as a function of the structural connectome constructed from diffusion MRI. Average controllability describes the ability of a region to drive the brain to easy-to-reach neurophysiological states whilst modal controllability describes the ability of a region to drive the brain to difficult-to-reach states. In this study, we identify increases in mean average and modal controllability in children with drug-resistant epilepsy compared to healthy controls. Using simulations, we purport that these changes may be a result of increased thalamocortical connectivity. At the node level, we demonstrate decreased modal controllability in the thalamus and posterior cingulate regions. In those undergoing resective surgery, we also demonstrate increased modal controllability of the resected parcels, a finding specific to patients who were rendered seizure free following surgery. Changes in controllability are a manifestation of brain network dysfunction in epilepsy and may be a useful construct to understand the pathophysiology of this archetypical network disease. Understanding the mechanisms underlying these controllability changes may also facilitate the design of network-focussed interventions that seek to normalise network structure and function. Children with drug-resistant epilepsy exhibit distinct structural connectomes and changes in network controllability from healthy controls, providing further insight into the pathophysiology of this disease.
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Alzheimer’s disease (AD) phenotypes might result from differences in selective vulnerability. Evidence from preclinical models suggests that tau pathology has cell-to-cell propagation properties. Therefore, here, we tested the cell-to-cell propagation framework in the amnestic, visuospatial, language, and behavioral/dysexecutive phenotypes of AD. We report that each AD phenotype is associated with a distinct network-specific pattern of tau aggregation, where tau aggregation is concentrated in brain network hubs. In all AD phenotypes, regional tau load could be predicted by connectivity patterns of the human brain. Furthermore, regions with greater connectivity displayed similar rates of longitudinal tau accumulation in an independent cohort. Connectivity-based tau deposition was not restricted to a specific vulnerable network but was rather a general property of brain organization, linking selective vulnerability and transneuronal spreading models of neurodegeneration. Together, this study indicates that intrinsic brain connectivity provides a framework for tau aggregation across diverse phenotypic manifestations of AD.
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Adolescence is a time of profound changes in the physical wiring and function of the brain. Here, we analyzed structural and functional brain network development in an accelerated longitudinal cohort spanning 14 to 25 y ( n = 199). Core to our work was an advanced in vivo model of cortical wiring incorporating MRI features of corticocortical proximity, microstructural similarity, and white matter tractography. Longitudinal analyses assessing age-related changes in cortical wiring identified a continued differentiation of multiple corticocortical structural networks in youth. We then assessed structure–function coupling using resting-state functional MRI measures in the same participants both via cross-sectional analysis at baseline and by studying longitudinal change between baseline and follow-up scans. At baseline, regions with more similar structural wiring were more likely to be functionally coupled. Moreover, correlating longitudinal structural wiring changes with longitudinal functional connectivity reconfigurations, we found that increased structural differentiation, particularly between sensory/unimodal and default mode networks, was reflected by reduced functional interactions. These findings provide insights into adolescent development of human brain structure and function, illustrating how structural wiring interacts with the maturation of macroscale functional hierarchies.
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Structural and functional brain networks are modular. Canonical functional systems, such as the default mode network, are well-known modules of the human brain and have been implicated in a large number of cognitive, behavioral and clinical processes. However, modules delineated in structural brain networks inferred from tractography generally do not recapitulate canonical functional systems. Neuroimaging evidence suggests that functional connectivity between regions in the same systems is not always underpinned by anatomical connections. As such, direct structural connectivity alone would be insufficient to characterize the functional modular organization of the brain. Here, we demonstrate that augmenting structural brain networks with models of indirect (polysynaptic) communication unveils a modular network architecture that more closely resembles the brain’s established functional systems. We find that diffusion models of polysynaptic connectivity, particularly communicability, narrow the gap between the modular organization of structural and functional brain networks by 20–60%, whereas routing models based on single efficient paths do not improve mesoscopic structure-function correspondence. This suggests that functional modules emerge from the constraints imposed by local network structure that facilitates diffusive neural communication. Our work establishes the importance of modeling polysynaptic communication to understand the structural basis of functional systems.
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It is estimated that in the human brain, short association fibres (SAF) represent more than half of the total white matter volume and their involvement has been implicated in a range of neurological and psychiatric conditions. This population of fibres, however, remains relatively understudied in the neuroimaging literature. Some of the challenges pertinent to the mapping of SAF include their variable anatomical course and proximity to the cortical mantle, leading to partial volume effects and potentially affecting streamline trajectory estimation. This work considers the impact of seeding and filtering strategies and choice of scanner, acquisition, data resampling to propose a whole-brain, surface-based short (≤30-40 mm) SAF tractography approach. The framework is shown to produce longer streamlines with a predilection for connecting gyri as well as high cortical coverage. We further demonstrate that certain areas of subcortical white matter become disproportionally underrepresented in diffusion-weighted MRI data with lower angular and spatial resolution and weaker diffusion weighting; however, collecting data with stronger gradients than are usually available clinically has minimal impact, making our framework translatable to data collected on commonly available hardware. Finally, the tractograms are examined using voxel- and surface-based measures of consistency, demonstrating moderate reliability, low repeatability and high between-subject variability, urging caution when streamline count-based analyses of SAF are performed.
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In recent years, multiple data-driven fiber orientation distribution function (fODF) estimation algorithms and automatic tractography pipelines have been proposed to address the limitations of traditional methods. However, these approaches lack precision and generalizability. To tackle these shortcomings, we introduce CTtrack, a CNN+Transformer-based pipeline to estimate fODFs and perform tractography. In this approach, a convolutional neural network (CNN) module is employed to project the resampled diffusion-weighted magnetic resonance imaging (DW-MRI) data to a lower dimension. Then, a transformer model estimates the fiber orientation distribution functions using the projected data within a local block around each voxel. The proposed model represents the extracted fODFs by spherical harmonics coefficients. The predicted fiber ODFs can be used for both deterministic and probabilistic tractography. Our pipeline was tested in terms of the precision and robustness in estimating fODFs and performing tractography using both simulated and real diffusion data. The Tractometer tool was employed to compare our method with the classical and data-driven tractography approaches. The qualitative and quantitative assessments illustrate the competitive performance of our framework compared to other available algorithms.
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Objectives Diffusion-weighted MRI can assist preoperative planning by reconstructing the trajectory of eloquent fiber pathways, such as the corticospinal tract (CST). However, accurate reconstruction of the full extent of the CST remains challenging with existing tractography methods. We suggest a novel tractography algorithm exploiting unused fiber orientations to produce more complete and reliable results. Methods Our novel approach, referred to as multi-level fiber tractography (MLFT), reconstructs fiber pathways by progressively considering previously unused fiber orientations at multiple levels of tract propagation. Anatomical priors are used to minimize the number of false-positive pathways. The MLFT method was evaluated on synthetic data and in vivo data by reconstructing the CST while compared to conventional tractography approaches. Results The radial extent of MLFT reconstructions is comparable to that of probabilistic reconstruction: $$p=0.21$$ p = 0.21 for the left and $$p=0.53$$ p = 0.53 for the right hemisphere according to Wilcoxon test, while achieving significantly higher topography preservation compared to probabilistic tractography: $$p<0.01$$ p < 0.01 . Discussion MLFT provides a novel way to reconstruct fiber pathways by adding the capability of including branching pathways in fiber tractography. Thanks to its robustness, feasible reconstruction extent and topography preservation, our approach may assist in clinical practice as well as in virtual dissection studies.
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In children, higher general intelligence corresponds with better processing speed ability. However, the relationship between structural brain connectivity and processing speed in the context of intelligence is unclear. Furthermore, the impact of brain injury on this relationship is also unknown. Structural networks were constructed for 36 brain tumor patients (mean age: 13.45 ± 2.73, 58% males) and 35 typically developing children (13.30 ± 2.86, 51% males). Processing speed and general intelligence scores were acquired using standard batteries. The relationship between network properties, processing speed, and intelligence was assessed using a partial least squares analysis. Results indicated that structural networks in brain-injured children were less integrated (β = −.38, p = 0.001) and more segregated (β = 0.4, p = 0.0005) compared to typically developing children. There was an indirect effect of network segregation on general intelligence via processing speed, where greater network segregation predicted slower processing speed which in turn predicted worse general intelligence (GoF = 0.37). These findings provide the first evidence of relations between structural connectivity, processing speed, and intelligence in children. Injury-related disruption to the structural network may result in worse intelligence through impacts on information processing. Our findings are discussed in the context of a network approach to understanding brain-behavior relationships.
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The contribution of structural connectivity to functional connectivity dynamics is still far from being fully elucidated. Herein, we applied track-weighted dynamic functional connectivity (tw-dFC), a model integrating structural, functional, and dynamic connectivity, on high quality diffusion weighted imaging and resting-state fMRI data from two independent repositories. The tw-dFC maps were analyzed using independent component analysis, aiming at identifying spatially independent white matter components which support dynamic changes in functional connectivity. Each component consisted of a spatial map of white matter bundles that show consistent fluctuations in functional connectivity at their endpoints, and a time course representative of such functional activity. These components show high intra-subject, inter-subject, and inter-cohort reproducibility. We provided also converging evidence that functional information about white matter activity derived by this method can capture biologically meaningful features of brain connectivity organization, as well as predict higher-order cognitive performance.
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Recent mechanistic models argue for a key role of rhythm processing in both speech production and speech perception. Patients with the non-fluent variant (NFV) of primary progressive aphasia (PPA) with apraxia of speech (AOS) represent a specific study population in which this link can be examined. Previously, we observed impaired rhythm processing in NFV with AOS. We hypothesized that a shared neurocomputational mechanism structures auditory input (sound and speech) and output (speech production) in time, a “temporal scaffolding” mechanism. Since considerable white matter damage is observed in NFV, we test here whether white matter changes are related to impaired rhythm processing. Forty-seven participants performed a psychoacoustic test battery: 12 patients with NFV and AOS, 11 patients with the semantic variant of PPA and 24 cognitively intact age- and education-matched controls. Deformation-based morphometry was used to test whether white matter volume correlated to rhythmic abilities. In 34 participants, we also obtained tract-based metrics of the left Aslant tract, which is typically damaged in patients with NFV. Nine out of twelve patients with NFV displayed impaired rhythmic processing. Left frontal white matter atrophy adjacent to the supplementary motor area (SMA) correlated with poorer rhythmic abilities. The structural integrity of the left Aslant tract also correlated with rhythmic abilities. A colocalized and perhaps shared white matter substrate adjacent to the SMA is associated with impaired rhythmic processing and motor speech impairment. Our results support the existence of a temporal scaffolding mechanism structuring perceptual input and speech output.
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Neurobiological research on anxiety has shown that trait-anxious individuals may be characterized by weaker structural connectivity of the amygdala-prefrontal circuitry, representing a reduced capacity for efficient communication between the two brain regions. However, comparison of available studies has been inconsistent, possibly related to factors such as aging that influences both trait anxiety and structural connectivity of the brain. To help clarify the nature of brain-anxiety relationship, we applied a connectome-based predictive modeling framework on 148 diffusion-weighted imaging data from the Leipzig Study for Mind-Body Emotion Interactions dataset and identified multivariate patterns of whole-brain structural connectivity that predicted trait anxiety. Results showed that networks predictive of trait anxiety differed across age groups. Specifically, an isolated negative network, which shared overlapping features with the amygdala-prefrontal circuitry, was found in younger adults (20–30 years of age), whereas a widespread positive network highlighted by frontotemporal and frontolimbic connectivity was identified when both younger and older adults (20–80 years of age) were examined. No predictive network was observed when only older adults (30–80 years of age) were considered. Our findings highlight an important age-dependent effect on the structural connectome-based prediction of trait anxiety, supporting ongoing efforts to develop potential neural biomarkers of anxiety.
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Along tract statistics enables white matter characterization using various diffusion MRI (dMRI) metrics. These diffusion models reveal detailed insights into white matter microstructural changes with development, pathology, and function. Here, we aim at assessing the clinical utility of dMRI metrics along the corticospinal tract, investigating whether motor glioma patients can be classified with respect to their motor status. We retrospectively included 116 brain tumor patients suffering from either left or right supratentorial, unilateral World Health Organization (WHO) grade II, III & IV gliomas with a mean age of 53.51 ± 16.32 years. 37% of patients presented with preoperative motor function deficits according to the Medical Research Council scale. At group level comparison, the highest non-overlapping dMRI differences were detected in the superior portion of the tracts’ profiles. Fractional anisotropy and fiber density decrease, apparent diffusion coefficient axial diffusivity and radial diffusivity increase. To predict motor deficits, we developed a method based on a support vector machine using histogram-based features of dMRI tract profiles (e.g., mean, standard deviation, kurtosis, and skewness), following a recursive feature elimination method. Our model achieved high performance (74% sensitivity, 75% specificity, 74% overall accuracy, and 77% area under the curve. We found that apparent diffusion coefficient, fractional anisotropy, and radial diffusivity contributed more than other features to the model. Incorporating the patient demographics and clinical features such as age, tumor WHO grade, tumor location, gender, and resting motor threshold did not affect the model’s performance, revealing that these features were not as effective as microstructural measures. These results shed light on the potential patterns of tumor-related microstructural white matter changes in the prediction of functional deficits.
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