679 research outputs found

    Quantitative MRI provides markers of intra-, inter-regional, and age-related differences in young adult cortical microstructure

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    Measuring the structural composition of the cortex is critical to understanding typical development, yet few investigations in humans have charted markers in vivo that are sensitive to tissue microstructural attributes. Here, we used a well-validated quantitative MR protocol to measure four parameters (R1, MT, R2*, PD*) that differ in their sensitivity to facets of the tissue microstructural environment (R1, MT: myelin, macromolecular content; R2*: myelin, paramagnetic ions, i.e., iron; PD*: free water content). Mapping these parameters across cortical regions in a young adult cohort (18–39 years, N = 93) revealed expected patterns of increased macromolecular content as well as reduced tissue water content in primary and primary adjacent cortical regions. Mapping across cortical depth within regions showed decreased expression of myelin and related processes – but increased tissue water content – when progressing from the grey/white to the grey/pial boundary, in all regions. Charting developmental change in cortical microstructure cross-sectionally, we found that parameters with sensitivity to tissue myelin (R1 & MT) showed linear increases with age across frontal and parietal cortex (change 0.5–1.0% per year). Overlap of robust age effects for both parameters emerged in left inferior frontal, right parietal and bilateral pre-central regions. Our findings afford an improved understanding of ontogeny in early adulthood and offer normative quantitative MR data for inter- and intra-cortical composition, which may be used as benchmarks in further studies

    Extensive Tonotopic Mapping across Auditory Cortex Is recapitulated by spectrally directed attention and systematically related to Cortical Myeloarchitecture

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    Auditory selective attention is vital in natural soundscapes. But, it is unclear how attentional focus on the primary dimension of auditory representation - acoustic frequency - might modulate basic auditory functional topography during active listening. In contrast to visual selective attention, which is supported by motor-mediated optimization of input across saccades and pupil dilation, the primate auditory system has fewer means of differentially sampling the world. This makes spectrally-directed endogenous attention a particularly crucial aspect of auditory attention. Using a novel functional paradigm combined with quantitative MRI, we establish in male and female listeners that human frequency-band-selective attention drives activation in both myeloarchitectonically-estimated auditory core, and across the majority of tonotopically-mapped non-primary auditory cortex. The attentionally-driven best-frequency maps show strong concordance with sensory-driven maps in the same subjects across much of the temporal plane, with poor concordance in areas outside traditional auditory cortex. There is significantly greater activation across most of auditory cortex when best frequency is attended, versus ignored; the same regions do not show this enhancement when attending to the least-preferred frequency band. Finally, the results demonstrate that there is spatial correspondence between the degree of myelination and the strength of the tonotopic signal across a number of regions in auditory cortex. Strong frequency preferences across tonotopically-mapped auditory cortex spatially correlate with R1-estimated myeloarchitecture, indicating shared functional and anatomical organization that may underlie intrinsic auditory regionalization

    Apparent thinning of human visual cortex during childhood is associated with myelination

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    Human cortex appears to thin during childhood development. However, the underlying microstructural mechanisms are unknown. Using functional magnetic resonance imaging (fMRI), quantitative MRI (qMRI), and diffusion MRI (dMRI) in children and adults, we tested what quantitative changes occur to gray and white matter in ventral temporal cortex (VTC) from childhood to adulthood, and how these changes relate to cortical thinning. T1 relaxation time from qMRI and mean diffusivity (MD) from dMRI provide independent and complementary measurements of microstructural properties of gray and white matter tissue. In face- and character-selective regions in lateral VTC, T1 and MD decreased from age 5 to adulthood in mid and deep cortex, as well as in their adjacent white matter. T1 reduction also occurred longitudinally in children’s brain regions. T1 and MD decreases 1) were consistent with tissue growth related to myelination, which we verified with adult histological myelin stains, and 2) were correlated with apparent cortical thinning. In contrast, in place-selective cortex in medial VTC, we found no development of T1 or MD after age 5, and thickness was related to cortical morphology. These findings suggest that lateral VTC likely becomes more myelinated from childhood to adulthood, affecting the contrast of MR images and, in turn, the apparent gray–white boundary. These findings are important because they suggest that VTC does not thin during childhood but instead gets more myelinated. Our data have broad ramifications for understanding both typical and atypical brain development using advanced in vivo quantitative measurements and clinical conditions implicating myelin

    Microstructural imaging of human neocortex in vivo

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    The neocortex of the human brain is the seat of higher brain function. Modern imaging techniques, chief among them magnetic resonance imaging (MRI), allow non-invasive imaging of this important structure. Knowledge of the microstructure of the neocortex has classically come from post-mortem histological studies of human tissue, and extrapolations from invasive animal studies. From these studies, we know that the scale of important neocortical structure spans six orders of magnitude, ranging from the size of axonal diameters (microns), to the size of cortical areas responsible for integrating sensory information (centimetres). MRI presents an opportunity to move beyond classical methods, because MRI is non-invasive and MRI contrast is sensitive to neocortical microstructure over all these length scales. MRI thus allows inferences to be made about neocortical microstructure in vivo, i.e. MRI-based in vivo histology. We review recent literature that has applied and developed MRI-based in vivo histology to probe the microstructure of the human neocortex, focusing specifically on myelin, iron, and neuronal fibre mapping. We find that applications such as cortical parcellation (using maps as proxies for myelin content) and investigation of cortical iron deposition with age (using maps) are already contributing to the frontiers of knowledge in neuroscience. Neuronal fibre mapping in the cortex remains challenging in vivo, but recent improvements in diffusion MRI hold promise for exciting applications in the near future. The literature also suggests that utilising multiple complementary quantitative MRI maps could increase the specificity of inferences about neocortical microstructure relative to contemporary techniques, but that further investment in modelling is required to appropriately combine the maps. In vivo histology of human neocortical microstructure is undergoing rapid development. Future developments will improve its specificity, sensitivity, and clinical applicability, granting an ever greater ability to investigate neuroscientific and clinical questions about the human neocortex

    Advances in noninvasive myelin imaging

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    Myelin is important for the normal development and healthy function of the nervous system. Recent developments in MRI acquisition and tissue modeling aim to provide a better characterization and more specific markers for myelin. This allows for specific monitoring of myelination longitudinally and noninvasively in the healthy brain as well as assessment of treatment and intervention efficacy. Here, we offer a nontechnical review of MRI techniques developed to specifically monitor myelin such as magnetization transfer (MT) and myelin water imaging (MWI). We further summarize recent studies that employ these methods to measure myelin in relation to development and aging, learning and experience, and neuropathology and psychiatric disorders

    Relating quantitative 7T MRI across cortical depths to cytoarchitectonics, gene expression and connectomics

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    Ultra‐high field MRI across the depth of the cortex has the potential to provide anatomically precise biomarkers and mechanistic insights into neurodegenerative disease like Huntington's disease that show layer‐selective vulnerability. Here we compare multi‐parametric mapping (MPM) measures across cortical depths for a 7T 500 μm whole brain acquisition to (a) layer‐specific cell measures from the von Economo histology atlas, (b) layer‐specific gene expression, using the Allen Human Brain atlas and (c) white matter connections using high‐fidelity diffusion tractography, at a 1.3 mm isotropic voxel resolution, from a 300mT/m Connectom MRI system. We show that R2*, but not R1, across cortical depths is highly correlated with layer‐specific cell number and layer‐specific gene expression. R1‐ and R2*‐weighted connectivity strength of cortico‐striatal and intra‐hemispheric cortical white matter connections was highly correlated with grey matter R1 and R2* across cortical depths. Limitations of the layer‐specific relationships demonstrated are at least in part related to the high cross‐correlations of von Economo atlas cell counts and layer‐specific gene expression across cortical layers. These findings demonstrate the potential and limitations of combining 7T MPMs, gene expression and white matter connections to provide an anatomically precise framework for tracking neurodegenerative disease

    Relating quantitative 7T MRI across cortical depths to cytoarchitectonics, gene expression and connectomics

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    Ultra-high field MRI across the depth of the cortex has the potential to provide ana- tomically precise biomarkers and mechanistic insights into neurodegenerative disease like Huntington's disease that show layer-selective vulnerability. Here we compare multi-parametric mapping (MPM) measures across cortical depths for a 7T 500 m whole brain acquisition to (a) layer-specific cell measures from the von Economo his- tology atlas, (b) layer-specific gene expression, using the Allen Human Brain atlas and (c) white matter connections using high-fidelity diffusion tractography, at a 1.3 mm isotropic voxel resolution, from a 300mT/m Connectom MRI system. We show that R2*, but not R1, across cortical depths is highly correlated with layer-specific cell number and layer-specific gene expression. R1- and R2*-weighted connectivity strength of cortico-striatal and intra-hemispheric cortical white matter connections was highly correlated with grey matter R1 and R2* across cortical depths. Limitations of the layer-specific relationships demonstrated are at least in part related to the high cross-correlations of von Economo atlas cell counts and layer-specific gene expres- sion across cortical layers. These findings demonstrate the potential and limitations of combining 7T MPMs, gene expression and white matter connections to provide an anatomically precise framework for tracking neurodegenerative disease

    Neurobiological origin of spurious brain morphological changes: A quantitative MRI study.

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    The high gray-white matter contrast and spatial resolution provided by T1-weighted magnetic resonance imaging (MRI) has made it a widely used imaging protocol for computational anatomy studies of the brain. While the image intensity in T1-weighted images is predominantly driven by T1, other MRI parameters affect the image contrast, and hence brain morphological measures derived from the data. Because MRI parameters are correlates of different histological properties of brain tissue, this mixed contribution hampers the neurobiological interpretation of morphometry findings, an issue which remains largely ignored in the community. We acquired quantitative maps of the MRI parameters that determine signal intensities in T1-weighted images (R1 (=1/T1), R2 *, and PD) in a large cohort of healthy subjects (n = 120, aged 18-87 years). Synthetic T1-weighted images were calculated from these quantitative maps and used to extract morphometry features-gray matter volume and cortical thickness. We observed significant variations in morphometry measures obtained from synthetic images derived from different subsets of MRI parameters. We also detected a modulation of these variations by age. Our findings highlight the impact of microstructural properties of brain tissue-myelination, iron, and water content-on automated measures of brain morphology and show that microstructural tissue changes might lead to the detection of spurious morphological changes in computational anatomy studies. They motivate a review of previous morphological results obtained from standard anatomical MRI images and highlight the value of quantitative MRI data for the inference of microscopic tissue changes in the healthy and diseased brain. Hum Brain Mapp 37:1801-1815, 2016. © 2016 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc

    Volumetric, relaxometric and diffusometric correlates of psychotic experiences in a non-clinical sample of young adults

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    Background Grey matter (GM) abnormalities are robust features of schizophrenia and of people at ultra high-risk for psychosis. However the extent to which neuroanatomical alterations are evident in non-clinical subjects with isolated psychotic experiences is less clear. Methods Individuals (mean age 20 years) with (n = 123) or without (n = 125) psychotic experiences (PEs) were identified from a population-based cohort. All underwent T1-weighted structural, diffusion and quantitative T1 relaxometry MRI, to characterise GM macrostructure, microstructure and myelination respectively. Differences in quantitative GM structure were assessed using voxel-based morphometry (VBM). Binary and ordinal models of PEs were tested. Correlations between socioeconomic and other risk factors for psychosis with cortical GM measures were also computed. Results GM volume in the left supra-marginal gyrus was reduced in individuals with PEs relative to those with no PEs. The greater the severity of PEs, the greater the reduction in T1 relaxation rate (R1) across left temporoparietal and right pre-frontal cortices. In these regions, R1 was positively correlated with maternal education and inversely correlated with general psychopathology. Conclusions PEs in non-clinical subjects were associated with regional reductions in grey-matter volume reduction and T1 relaxation rate. The alterations in T1 relaxation rate were also linked to the level of general psychopathology. Follow up of these subjects should clarify whether these alterations predict the later development of an ultra high-risk state or a psychotic disorder
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