Spread of pathological tau proteins through communicating neurons in human Alzheimer’s disease

Nature Communications, Год журнала: 2020, Номер 11(1)

Опубликована: Май 26, 2020

Tau is a hallmark pathology of Alzheimer's disease, and animal models have suggested that tau spreads from cell to through neuronal connections, facilitated by β-amyloid (Aβ). We test this hypothesis in humans using an epidemic spreading model (ESM) simulate spread, compare these simulations observed patterns measured tau-PET 312 individuals along disease continuum. Up 70% the variance overall spatial pattern can be explained our model. Surprisingly, ESM predicts irrespective whether brain Aβ present, but regions with greater burden show than predicted connectivity patterns, suggesting role accelerating spread. Altogether, results provide evidence communication pathways even normal aging, process accelerated presence Aβ.

Язык: Английский

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The ENIGMA Toolbox: multiscale neural contextualization of multisite neuroimaging datasets

Nature Methods, Год журнала: 2021, Номер 18(7), С. 698 - 700

Опубликована: Июнь 30, 2021

Язык: Английский

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Standardizing workflows in imaging transcriptomics with the abagen toolbox

eLife, Год журнала: 2021, Номер 10

Опубликована: Ноя. 16, 2021

Gene expression fundamentally shapes the structural and functional architecture of human brain. Open-access transcriptomic datasets like Allen Human Brain Atlas provide an unprecedented ability to examine these mechanisms in vivo; however, a lack standardization across research groups has given rise myriad processing pipelines for using data. Here, we develop abagen toolbox, open-access software package working with data, use it how methodological variability influences outcomes Atlas. Applying three prototypical analyses outputs 750,000 unique pipelines, find that choice pipeline large impact on findings, parameters commonly varied literature influencing correlations between derived gene other imaging phenotypes by as much ρ ≥ 1.0. Our results further reveal ordering parameter importance, steps influence normalization yielding greatest downstream statistical inferences conclusions. The presented work development toolbox lay foundation more standardized systematic transcriptomics, will help advance future understanding

Язык: Английский

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Null models in network neuroscience

Nature reviews. Neuroscience, Год журнала: 2022, Номер 23(8), С. 493 - 504

Опубликована: Май 31, 2022

Язык: Английский

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Brain network communication: concepts, models and applications

Nature reviews. Neuroscience, Год журнала: 2023, Номер 24(9), С. 557 - 574

Опубликована: Июль 12, 2023

Язык: Английский

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Local structure-function relationships in human brain networks across the lifespan

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Апрель 19, 2022

Abstract A growing number of studies have used stylized network models communication to predict brain function from structure. Most focused on a small set applied globally. Here, we compare large at both global and regional levels. We find that globally most predictors perform poorly. At the level, performance improves but heterogeneously, in terms variance explained optimal model. Next, expose synergies among by using pairs jointly FC. Finally, assess age-related differences coupling across human lifespan. decreases magnitude structure-function with age. these are driven reduced sensorimotor regions, while higher-order cognitive systems preserve local Our results describe patterns cortex how this may change

Язык: Английский

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Connectome-based modelling of neurodegenerative diseases: towards precision medicine and mechanistic insight

Nature reviews. Neuroscience, Год журнала: 2023, Номер 24(10), С. 620 - 639

Опубликована: Авг. 24, 2023

Язык: Английский

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Local molecular and global connectomic contributions to cross-disorder cortical abnormalities

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Авг. 10, 2022

Abstract Numerous brain disorders demonstrate structural abnormalities, which are thought to arise from molecular perturbations or connectome miswiring. The unique and shared contributions of these connectomic vulnerabilities remain unknown, has yet be studied in a single multi-disorder framework. Using MRI morphometry the ENIGMA consortium, we construct maps cortical abnormalities for thirteen neurodevelopmental, neurological, psychiatric N = 21,000 participants 26,000 controls, collected using harmonised processing protocol. We systematically compare multiple micro-architectural measures, including gene expression, neurotransmitter density, metabolism, myelination (molecular vulnerability), as well global measures number connections, centrality, connection diversity (connectomic vulnerability). find relationship between vulnerability white-matter architecture that drives disorder profiles. Local attributes, particularly receptor profiles, constitute best predictors both disorder-specific morphology cross-disorder similarity. Finally, consistently subtended by small subset network epicentres bilateral sensory-motor, inferior temporal lobe, precuneus, superior parietal cortex. Collectively, our results highlight how local attributes connectivity jointly shape abnormalities.

Язык: Английский

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Connectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study

Molecular Psychiatry, Год журнала: 2024, Номер 29(6), С. 1869 - 1881

Опубликована: Фев. 9, 2024

Abstract Schizophrenia is a prototypical network disorder with widespread brain-morphological alterations, yet it remains unclear whether these distributed alterations robustly reflect the underlying layout. We tested large-scale structural in schizophrenia relate to normative and functional connectome architecture, systematically evaluated robustness generalizability of network-level alterations. Leveraging anatomical MRI scans from 2439 adults 2867 healthy controls 26 ENIGMA sites data Human Connectome Project ( n = 207), we against two susceptibility models: (i) hub vulnerability, which examines associations between regional centrality magnitude disease-related alterations; (ii) epicenter mapping, identifies regions whose typical connectivity profile most closely resembles morphological To assess specificity, contextualized influence site, disease stages, individual clinical factors compared that found affective disorders. Our findings show schizophrenia-related cortical thinning spatially associated hubs, suggesting highly interconnected are more vulnerable Predominantly temporo-paralimbic frontal emerged as epicenters profiles linked schizophrenia’s alteration patterns. Findings were robust across sites, related symptoms. Moreover, transdiagnostic comparisons revealed overlapping bipolar, but not major depressive disorder, suggestive pathophysiological continuity within schizophrenia-bipolar-spectrum. In sum, over course follow brain emphasizing marked temporo-frontal at both level group individual. Subtle variations stages suggest interacting pathological processes, while patient-specific symptoms support additional inter-individual variability vulnerability schizophrenia. work outlines potential pathways better understand macroscale inter-

Язык: Английский

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Topographic gradients of intrinsic dynamics across neocortex

eLife, Год журнала: 2020, Номер 9

Опубликована: Дек. 17, 2020

The intrinsic dynamics of neuronal populations are shaped by both microscale attributes and macroscale connectome architecture. Here we comprehensively characterize the rich temporal patterns neural activity throughout human brain. Applying massive feature extraction to regional haemodynamic activity, systematically estimate over 6000 statistical properties individual brain regions' time-series across neocortex. We identify two robust spatial gradients dynamics, one spanning a ventromedial-dorsolateral axis dominated measures signal autocorrelation, other unimodal-transmodal dynamic range. These reflect gene expression, intracortical myelin cortical thickness, as well structural functional network embedding. Importantly, these correlated with meta-analytic activation, differentiating cognitive versus affective processing sensory higher-order processing. Altogether, findings demonstrate link between architecture, cognition.

Язык: Английский

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