20 research outputs found

    Longitudinal changes of ADHD symptoms in association with white matter microstructure: A tract-specific fixel-based analysis

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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

    Connectivity gradients on tractography data: Pipeline and example applications

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    Gray matter connectivity can be described in terms of its topographical organization, but the differential role of white matter connections underlying that organization is often unknown. In this study, we propose a method for unveiling principles of organization of both gray and white matter based on white matter connectivity as assessed using diffusion magnetic ressonance imaging (MRI) tractography with spectral embedding gradient mapping. A key feature of the proposed approach is its capacity to project the individual connectivity gradients it reveals back onto its input data in the form of projection images, allowing one to assess the contributions of specific white matter tracts to the observed gradients. We demonstrate the ability of our proposed pipeline to identify connectivity gradients in prefrontal and occipital gray matter. Finally, leveraging the use of tractography, we demonstrate that it is possible to observe gradients within the white matter bundles themselves. Together, the proposed framework presents a generalized way to assess both the topographical organization of structural brain connectivity and the anatomical features driving it

    Overexpression of DosR in Mycobacterium tuberculosis does not affect aerobic replication in vitro or in murine macrophages

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    Mycobacterium tuberculosis H37Rv, constitutively expressing a second copy of the transcriptional regulator DosR (Rv3133c) under control of the hsp60 promoter, was compared to wild-type M. tuberculosis for in vitro expression of the target genes of the DosR dormancy regulon, for its in vitro growth characteristics in liquid 7H9 culture medium, and for its capacity to replicate in murine macrophages. Under aerobic conditions, hsp60-driven DosR significantly induced the expression of 39 out of 44 DosR regulon genes, as assessed by real time qPCR. Increased DosR regulon gene transcription in vitro did not modify the capacity of the strain to grow under axenic conditions nor to infect murine macrophages as compared to unmodified wild-type&nbsp;bacteria.</p

    Principles of temporal association cortex organisation as revealed by connectivity gradients

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    To establish the link between structure and function of any large area of the neocortex, it is helpful to identify its principles of organisation. One way to establish such principles is to investigate how differences in whole-brain connectivity are structured across the area. Here, we use Laplacian eigenmaps on diffusion MRI tractography data to investigate the organisational principles of the human temporal association cortex. We identify three overlapping gradients of connectivity that are, for the large part, consistent across hemispheres: The first gradient reveals an inferior-superior organisation of predominantly longitudinal tracts and separates visual and auditory unimodal and multimodal cortex. The second gradient radiates outward from the posterior middle temporal cortex with the arcuate fascicle as a distinguishing feature with the third gradient being concentrated in the anterior temporal lobe and emanating towards its posterior end. We describe the functional relevance of each of these gradients through meta-analysis of data from the neuroimaging literature. Together, these results unravel the overlapping dimensions of structural organization of the human temporal cortex and provide a framework underlying its functional multiplicit

    Principles of temporal association cortex organisation as revealed by connectivity gradients

    No full text
    Contains fulltext : 219127.pdf (publisher's version ) (Open Access)To establish the link between structure and function of any large area of the neocortex, it is helpful to identify its principles of organisation. One way to establish such principles is to investigate how differences in whole-brain connectivity are structured across the area. Here, we use Laplacian eigenmaps on diffusion MRI tractography data to investigate the organisational principles of the human temporal association cortex. We identify three overlapping gradients of connectivity that are, for the most part, consistent across hemispheres. The first gradient reveals an inferior–superior organisation of predominantly longitudinal tracts and separates visual and auditory unimodal and multimodal cortices. The second gradient radiates outward from the posterior middle temporal cortex with the arcuate fascicle as a distinguishing feature; the third gradient is concentrated in the anterior temporal lobe and emanates towards its posterior end. We describe the functional relevance of each of these gradients through the meta-analysis of data from the neuroimaging literature. Together, these results unravel the overlapping dimensions of structural organization of the human temporal cortex and provide a framework underlying its functional multiplicity.16 p

    Comparing human and chimpanzee temporal lobe neuroanatomy reveals modifications to human language hubs beyond the frontotemporal arcuate fasciculus

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    The biological foundation for the language-ready brain in the human lineage remains a debated subject. In humans, the arcuate fasciculus (AF) white matter and the posterior portions of the middle temporal gyrus are crucial for language. Compared with other primates, the human AF has been shown to dramatically extend into the posterior temporal lobe, which forms the basis of a number of models of the structural connectivity basis of language. Recent advances in both language research and comparative neuroimaging invite a reassessment of the anatomical differences in language streams between humans and our closest relatives. Here, we show that posterior temporal connectivity via the AF in humans compared with chimpanzees is expanded in terms of its connectivity not just to the ventral frontal cortex but also to the parietal cortex. At the same time, posterior temporal regions connect more strongly to the ventral white matter in chimpanzees as opposed to humans. This pattern is present in both brain hemispheres. Additionally, we show that the anterior temporal lobe harbors a combination of connections present in both species through the inferior fronto-occipital fascicle and human-unique expansions through the uncinate and middle and inferior longitudinal fascicles. These findings elucidate structural changes that are unique to humans and may underlie the anatomical foundations for full-fledged language capacity

    Comparing human and chimpanzee temporal lobe neuroanatomy reveals modifications to human language hubs beyond the frontotemporal arcuate fasciculus

    No full text
    Communication through language is a great achievement of evolution. In humans, the arcuate fasciculus, white matter that extended dramatically during evolution, is known to subserve language. We investigated whether connections through critical language centers in the temporal lobe are uniquely human. We show that connectivity in the posterior temporal lobe via the arcuate fasciculus expanded bilaterally to frontal and parietal cortices in humans compared with chimpanzees. Concomitantly, the ventral tracts connect more strongly to posterior temporal regions in the chimpanzees than in humans. In the anterior temporal lobe, connections shared between both species and uniquely human expansions are present. Changes to human language streams extend beyond the arcuate fasciculus, including a suite of expansions to connectivity within the temporal lobes. The biological foundation for the language-ready brain in the human lineage remains a debated subject. In humans, the arcuate fasciculus (AF) white matter and the posterior portions of the middle temporal gyrus are crucial for language. Compared with other primates, the human AF has been shown to dramatically extend into the posterior temporal lobe, which forms the basis of a number of models of the structural connectivity basis of language. Recent advances in both language research and comparative neuroimaging invite a reassessment of the anatomical differences in language streams between humans and our closest relatives. Here, we show that posterior temporal connectivity via the AF in humans compared with chimpanzees is expanded in terms of its connectivity not just to the ventral frontal cortex but also to the parietal cortex. At the same time, posterior temporal regions connect more strongly to the ventral white matter in chimpanzees as opposed to humans. This pattern is present in both brain hemispheres. Additionally, we show that the anterior temporal lobe harbors a combination of connections present in both species through the inferior fronto-occipital fascicle and human-unique expansions through the uncinate and middle and inferior longitudinal fascicles. These findings elucidate structural changes that are unique to humans and may underlie the anatomical foundations for full-fledged language capacity

    Comparing human and chimpanzee temporal lobe neuroanatomy reveals modifications to human language hubs beyond the fronto-temporal arcuate fascicle

    No full text
    The biological foundation for the language-ready brain in the human lineage remains a debated subject. In humans, the arcuate fasciculus (AF) white matter and the posterior portions of the middle temporal gyrus are crucial for language. Compared with other primates, the human AF has been shown to dramatically extend into the posterior temporal lobe, which forms the basis of a number of models of the structural connectivity basis of language. Recent advances in both language research and comparative neuroimaging invite a reassessment of the anatomical differences in language streams between humans and our closest relatives. Here, we show that posterior temporal connectivity via the AF in humans compared with chimpanzees is expanded in terms of its connectivity not just to the ventral frontal cortex but also to the parietal cortex. At the same time, posterior temporal regions connect more strongly to the ventral white matter in chimpanzees as opposed to humans. This pattern is present in both brain hemispheres. Additionally, we show that the anterior temporal lobe harbors a combination of connections present in both species through the inferior fronto-occipital fascicle and human-unique expansions through the uncinate and middle and inferior longitudinal fascicles. These findings elucidate structural changes that are unique to humans and may underlie the anatomical foundations for full-fledged language capacity

    Longitudinal changes of ADHD symptoms in association with white matter microstructure: A tract-specific fixel-based analysis

    Get PDF
    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) (t(max) = 1.092, standardized effect[SE] = 0.044, p(FWE) = 0.016). Improvement in combined ADHD symptoms over time was associated with more fiber cross-section at follow-up in the lCST (t(max) = 3.775, SE = 0.051, p(FWE) = 0.019). CONCLUSIONS: Aberrant white matter development involves both lCST micro- and macrostructural alterations, and its path may be moderated by preceding symptom trajectory
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