Modelling white matter in gyral blades as a continuous vector field

1AbstractMany brain imaging studies aim to measure structural connectivity with diffusion tractography. However, biases in tractography data, particularly near the boundary between white matter and cortical grey matter can limit the accuracy of such studies. When seeding from the white matter, streamlines tend to travel parallel to the convoluted cortical surface, largely avoiding sulcal fundi and terminating preferentially on gyral crowns. When seeding from the cortical grey matter, streamlines generally run near the cortical surface until reaching deep white matter. These so-called “gyral biases” limit the accuracy and effective resolution of cortical structural connectivity profiles estimated by tractography algorithms, and they do not reflect the expected distributions of axonal densities seen in invasive tracer studies or stains of myelinated fibres. We propose an algorithm that concurrently models fibre density and orientation using a divergence-free vector field within gyral blades to encourage an anatomically-justified streamline density distribution along the cortical white/grey-matter boundary while maintaining alignment with the diffusion MRI estimated fibre orientations. Using in vivo data from the Human Connectome Project, we show that this algorithm reduces tractography biases. We compare the structural connectomes to functional connectomes from resting-state fMRI, showing that our model improves cross-modal agreement. Finally, we find that after parcellation the changes in the structural connectome are very minor with slightly improved interhemispheric connections (i.e, more homotopic connectivity) and slightly worse intrahemispheric connections when compared to tracers.

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Non-Negative Data-Driven Mapping of Structural Connections in the Neonatal Brain

10.1101/2020.03.09.965079 ◽

2020 ◽

Author(s):

E. Thompson ◽

A.R. Mohammadi-Nejad ◽

E.C. Robinson ◽

M.F. Glasser ◽

S. Jbabdi ◽

...

Keyword(s):

White Matter ◽

Grey Matter ◽

Brain Connectivity ◽

Structural Connectivity ◽

Adult Brain ◽

Data Driven ◽

Neonatal Brain ◽

Human Connectome Project ◽

Tractography Data ◽

Matrix Factorisation

AbstractMapping connections in the neonatal brain can provide insight into the crucial early stages of neurodevelopment that shape brain organisation and lay the foundations for cognition and behaviour. Diffusion MRI and tractography provide unique opportunities for such explorations, through estimation of white matter bundles and brain connectivity. Atlas-based tractography protocols, i.e. a priori defined sets of masks and logical operations in a template space, have been commonly used in the adult brain to drive such explorations. However, rapid growth and maturation of the brain during early development make it challenging to ensure correspondence and validity of such atlas-based tractography approaches in the developing brain. An alternative can be provided by data-driven methods, which do not depend on predefined regions of interest. Here, we develop a novel data-driven framework to extract white matter bundles and their associated grey matter networks from neonatal tractography data, based on non-negative matrix factorisation that is inherently suited to the non-negative nature of structural connectivity data. We also develop a non-negative dual regression framework to map group-level components to individual subjects. Using in-silico simulations, we evaluate the accuracy of our approach in extracting connectivity components and compare with an alternative data-driven method, independent component analysis. We apply non-negative matrix factorisation to whole-brain connectivity obtained from publicly available datasets from the Developing Human Connectome Project, yielding grey matter components and their corresponding white matter bundles. We assess the validity and interpretability of these components against traditional tractography results and grey matter networks obtained from resting-state fMRI in the same subjects. We subsequently use them to generate a parcellation of the neonatal cortex using data from 323 new-born babies and we assess the robustness and reproducibility of this connectivity-driven parcellation.

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XTRACT - Standardised protocols for automated tractography in the human and macaque brain

10.1101/804641 ◽

2019 ◽

Cited By ~ 3

Author(s):

S Warrington ◽

KL Bryant ◽

AA Khrapitchev ◽

J Sallet ◽

M Charquero-Ballester ◽

...

Keyword(s):

White Matter ◽

Grey Matter ◽

Ex Vivo ◽

Open Science ◽

Uk Biobank ◽

Comparative Neuroanatomy ◽

Human Connectome Project ◽

Subject Variability ◽

The Uk

AbstractWe present a new software package with a library of standardised tractography protocols devised for the robust automated extraction of white matter tracts both in the human and the macaque brain. Using in vivo data from the Human Connectome Project (HCP) and the UK Biobank and ex vivo data for the macaque brain datasets, we obtain white matter atlases, as well as atlases for tract endpoints on the white-grey matter boundary, for both species. We illustrate that our protocols are robust against data quality, generalisable across two species and reflect the known anatomy. We further demonstrate that they capture inter-subject variability by preserving tract lateralisation in humans and tract similarities stemming from twinship in the HCP cohort. Our results demonstrate that the presented toolbox will be useful for generating imaging-derived features in large cohorts, and in facilitating comparative neuroanatomy studies. The software, tractography protocols, and atlases are publicly released through FSL, allowing users to define their own tractography protocols in a standardised manner, further contributing to open science.

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Neuron-specific activation of necroptosis signaling in multiple sclerosis cortical grey matter

Acta Neuropathologica ◽

10.1007/s00401-021-02274-7 ◽

2021 ◽

Vol 141 (4) ◽

pp. 585-604 ◽

Cited By ~ 1

Author(s):

Carmen Picon ◽

Anusha Jayaraman ◽

Rachel James ◽

Catriona Beck ◽

Patricia Gallego ◽

...

Keyword(s):

Multiple Sclerosis ◽

Signaling Pathway ◽

Cortical Neurons ◽

Grey Matter ◽

Molecular Mechanisms ◽

Fold Increase ◽

Cell Types ◽

Meningeal Inflammation ◽

Cortical Grey Matter

AbstractSustained exposure to pro-inflammatory cytokines in the leptomeninges is thought to play a major role in the pathogenetic mechanisms leading to cortical pathology in multiple sclerosis (MS). Although the molecular mechanisms underlying neurodegeneration in the grey matter remain unclear, several lines of evidence suggest a prominent role for tumour necrosis factor (TNF). Using cortical grey matter tissue blocks from post-mortem brains from 28 secondary progressive MS subjects and ten non-neurological controls, we describe an increase in expression of multiple steps in the TNF/TNF receptor 1 signaling pathway leading to necroptosis, including the key proteins TNFR1, FADD, RIPK1, RIPK3 and MLKL. Activation of this pathway was indicated by the phosphorylation of RIPK3 and MLKL and the formation of protein oligomers characteristic of necrosomes. In contrast, caspase-8 dependent apoptotic signaling was decreased. Upregulation of necroptotic signaling occurred predominantly in macroneurons in cortical layers II–III, with little expression in other cell types. The presence of activated necroptotic proteins in neurons was increased in MS cases with prominent meningeal inflammation, with a 30-fold increase in phosphoMLKL+ neurons in layers I–III. The density of phosphoMLKL+ neurons correlated inversely with age at death, age at progression and disease duration. In vivo induction of chronically elevated TNF and INFγ levels in the CSF in a rat model via lentiviral transduction in the meninges, triggered inflammation and neurodegeneration in the underlying cortical grey matter that was associated with increased neuronal expression of TNFR1 and activated necroptotic signaling proteins. Exposure of cultured primary rat cortical neurons to TNF induced necroptosis when apoptosis was inhibited. Our data suggest that neurons in the MS cortex are dying via TNF/TNFR1 stimulated necroptosis rather than apoptosis, possibly initiated in part by chronic meningeal inflammation. Neuronal necroptosis represents a pathogenetic mechanism that is amenable to therapeutic intervention at several points in the signaling pathway.

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Exploring the laminar connectome

10.1101/2021.03.17.21253439 ◽

2021 ◽

Author(s):

Ittai Shamir ◽

Omri Tomer ◽

Ronnie Krupnik ◽

Yaniv Assaf

Keyword(s):

White Matter ◽

Grey Matter ◽

Structural Description ◽

Mri Imaging ◽

Healthy Human ◽

Cortical Grey Matter ◽

Cortical Laminar ◽

White Matter Connectivity ◽

Human Brains

The human connectome is the complete structural description of the network of connections and elements that form the wiring diagram of the brain. Because of the current scarcity of information regarding laminar end points of white matter tracts inside cortical grey matter, tractography remains focused on cortical partitioning into regions, while ignoring radial partitioning into laminar components. To overcome this biased representation of the cortex as a single homogenous unit, we use a recent data-derived model of cortical laminar connectivity, which has been further explored and corroborated in the macaque brain by comparison to published studies. The model integrates multimodal MRI imaging datasets regarding both white matter connectivity and grey matter laminar composition into a laminar-level connectome. In this study we model the laminar connectome of healthy human brains (N=20) and explore them via a set of neurobiologically meaningful complex network measures. Our analysis demonstrates a subdivision of network hubs that appear in the standard connectome into each individual component of the laminar connectome, giving a fresh look into the role of laminar components in cortical connectivity and offering new prospects in the fields of both structural and functional connectivity.

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Anatomical Characterization of the Human Structural Connectivity between the Pedunculopontine Nucleus and Globus Pallidus via Multi-Shell Multi-Tissue Tractography

Medicina ◽

10.3390/medicina56090452 ◽

2020 ◽

Vol 56 (9) ◽

pp. 452

Author(s):

Salvatore Bertino ◽

Gianpaolo Antonio Basile ◽

Giuseppe Anastasi ◽

Alessia Bramanti ◽

Bartolo Fonti ◽

...

Keyword(s):

Globus Pallidus ◽

Spatial Organization ◽

Structural Connectivity ◽

Spatial Relations ◽

Pedunculopontine Nucleus ◽

Anterior Portion ◽

Therapeutic Implications ◽

Efferent Connections ◽

Human Connectome Project

Background and objectives: The internal (GPi) and external segments (GPe) of the globus pallidus represent key nodes in the basal ganglia system. Connections to and from pallidal segments are topographically organized, delineating limbic, associative and sensorimotor territories. The topography of pallidal afferent and efferent connections with brainstem structures has been poorly investigated. In this study we sought to characterize in-vivo connections between the globus pallidus and the pedunculopontine nucleus (PPN) via diffusion tractography. Materials and Methods: We employed structural and diffusion data of 100 subjects from the Human Connectome Project repository in order to reconstruct the connections between the PPN and the globus pallidus, employing higher order tractography techniques. We assessed streamline count of the reconstructed bundles and investigated spatial relations between pallidal voxels connected to the PPN and pallidal limbic, associative and sensorimotor functional territories. Results: We successfully reconstructed pallidotegmental tracts for the GPi and GPe in all subjects. The number of streamlines connecting the PPN with the GPi was greater than the number of those joining it with the GPe. PPN maps within pallidal segments exhibited a distinctive spatial organization, being localized in the ventromedial portion of the GPi and in the ventral-anterior portion in the GPe. Regarding their spatial relations with tractography-derived maps of pallidal functional territories, the highest value of percentage overlap was noticed between PPN maps and the associative territory. Conclusions: We successfully reconstructed the anatomical course of the pallidotegmental pathways and comprehensively characterized their topographical arrangement within both pallidal segments. PPM maps were localized in the ventromedial aspect of the GPi, while they occupied the anterior pole and the most ventral portion of the GPe. A better understanding of the spatial and topographical arrangement of the pallidotegmental pathways may have pathophysiological and therapeutic implications in movement disorders.

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Identification of a distinct association fiber tract “IPS-FG” to connect the intraparietal sulcus areas and fusiform gyrus by white matter dissection and tractography

Scientific Reports ◽

10.1038/s41598-020-72471-z ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Tatsuya Jitsuishi ◽

Atsushi Yamaguchi

Keyword(s):

White Matter ◽

Posterior Parietal Cortex ◽

Structural Connectivity ◽

Temporal Cortex ◽

Fusiform Gyrus ◽

Intraparietal Sulcus ◽

Visuomotor Integration ◽

Fiber Tract ◽

Fiber Tracts ◽

Human Connectome Project

Abstract The intraparietal sulcus (IPS) in the posterior parietal cortex (PPC) is well-known as an interface for sensorimotor integration in visually guided actions. However, our understanding of the human neural network between the IPS and the cortical visual areas has been devoid of anatomical specificity. We here identified a distinctive association fiber tract “IPS-FG” to connect the IPS areas and the fusiform gyrus (FG), a high-level visual region, by white matter dissection and tractography. The major fiber bundles of this tract appeared to arise from the medial bank of IPS, in the superior parietal lobule (SPL), and project to the FG on the ventral temporal cortex (VTC) in post-mortem brains. This tract courses vertically at the temporo-parieto-occipital (TPO) junction where several fiber tracts intersect to connect the dorsal-to-ventral cortical regions, including the vertical occipital fasciculus (VOF). We then analyzed the structural connectivity of this tract with diffusion-MRI (magnetic resonance imaging) tractography. The quantitative tractography analysis revealed the major streamlines of IPS-FG interconnect the posterior IPS areas (e.g., IP1, IPS1) with FG (e.g., TF, FFC, VVC, PHA2, PIT) on the Human Connectome Project multimodal parcellation atlas (HCP MMP 1.0). Since the fronto-parietal network, including the posterior IPS areas, is recruited by multiple cognitive demands, the IPS-FG could play a role in the visuomotor integration as well as the top-down modulation of various cognitive functions reciprocally.

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Regional brain volumes, microstructure and neurodevelopment in moderate–late preterm children

Archives of Disease in Childhood - Fetal and Neonatal Edition ◽

10.1136/archdischild-2019-317941 ◽

2020 ◽

Vol 105 (6) ◽

pp. 593-599 ◽

Cited By ~ 1

Author(s):

Claire E Kelly ◽

Deanne K Thompson ◽

Alicia J Spittle ◽

Jian Chen ◽

Marc L Seal ◽

...

Keyword(s):

White Matter ◽

Grey Matter ◽

Diffusion Tensor ◽

Brain Mri ◽

Developmental Outcomes ◽

Late Preterm ◽

Brain Volumes ◽

Regional Brain ◽

White Matter Microstructure ◽

Cortical Grey Matter

ObjectiveTo explore whether regional brain volume and white matter microstructure at term-equivalent age (TEA) are associated with development at 2 years of age in children born moderate–late preterm (MLPT).Study designA cohort of MLPT infants had brain MRI at approximately TEA (38–44 weeks’ postmenstrual age) and had a developmental assessment (Bayley Scales of Infant and Toddler Development and Infant Toddler Social Emotional Assessment) at 2 years’ corrected age. Relationships between cortical grey matter and white matter volumes and 2-year developmental outcomes were explored using voxel-based morphometry. Relationships between diffusion tensor measures of white matter microstructure (fractional anisotropy (FA) and axial (AD), radial (RD) and mean (MD) diffusivities) and 2-year developmental outcomes were explored using tract-based spatial statistics.Results189 MLPT children had data from at least one MRI modality (volumetric or diffusion) and data for at least one developmental domain. Larger cortical grey and white matter volumes in many brain regions, and higher FA and lower AD, RD and MD in several major white matter regions, were associated with better cognitive and language scores. There was little evidence that cortical grey matter and white matter volumes and white matter microstructure were associated with motor and behavioural outcomes.ConclusionsRegional cortical grey matter and white matter volumes and white matter microstructure are associated with cognitive and language development at 2 years of age in MLPT children. Thus, early alterations to brain volumes and microstructure may contribute to some of the developmental deficits described in MLPT children.

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Increased and Decreased Superficial White Matter Structural Connectivity in Schizophrenia and Bipolar Disorder

Schizophrenia Bulletin ◽

10.1093/schbul/sbz015 ◽

2019 ◽

Vol 45 (6) ◽

pp. 1367-1378 ◽

Cited By ~ 7

Author(s):

Ellen Ji ◽

Pamela Guevara ◽

Miguel Guevara ◽

Antoine Grigis ◽

Nicole Labra ◽

...

Keyword(s):

Bipolar Disorder ◽

White Matter ◽

Language Processing ◽

Structural Connectivity ◽

Anterior Cingulate ◽

Precentral Gyrus ◽

Psychiatric Illnesses ◽

And Function ◽

Post Hoc

Abstract Schizophrenia (SZ) and bipolar disorder (BD) are often conceptualized as “disconnection syndromes,” with substantial evidence of abnormalities in deep white matter tracts, forming the substrates of long-range connectivity, seen in both disorders. However, the study of superficial white matter (SWM) U-shaped short-range tracts remained challenging until recently, although findings from postmortem studies suggest they are likely integral components of SZ and BD neuropathology. This diffusion weighted imaging (DWI) study aimed to investigate SWM microstructure in vivo in both SZ and BD for the first time. We performed whole brain tractography in 31 people with SZ, 32 people with BD and 54 controls using BrainVISA and Connectomist 2.0. Segmentation and labeling of SWM tracts were performed using a novel, comprehensive U-fiber atlas. Analysis of covariances yielded significant generalized fractional anisotropy (gFA) differences for 17 SWM bundles in frontal, parietal, and temporal cortices. Post hoc analyses showed gFA reductions in both patient groups as compared with controls in bundles connecting regions involved in language processing, mood regulation, working memory, and motor function (pars opercularis, insula, anterior cingulate, precentral gyrus). We also found increased gFA in SZ patients in areas overlapping the default mode network (inferior parietal, middle temporal, precuneus), supporting functional hyperconnectivity of this network evidenced in SZ. We thus illustrate that short U-fibers are vulnerable to the pathological processes in major psychiatric illnesses, encouraging improved understanding of their anatomy and function.

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