Local vulnerability and global connectivity jointly shape neurodegenerative disease propagation

PLoS Biology, Год журнала: 2019, Номер 17(11), С. e3000495 - e3000495

Опубликована: Ноя. 21, 2019

It is becoming increasingly clear that brain network organization shapes the course and expression of neurodegenerative diseases. Parkinson disease (PD) marked by progressive spread atrophy from midbrain to subcortical structures and, eventually, cerebral cortex. Recent discoveries suggest process involves misfolding prion-like propagation endogenous α-synuclein via axonal projections. However, mechanisms translate local "synucleinopathy" large-scale dysfunction remain unknown. Here, we use an agent-based epidemic spreading model integrate structural connectivity, functional gene predict sequential volume loss due neurodegeneration. The dynamic replicates spatial temporal patterning empirical in PD implicates substantia nigra as epicenter. We reveal a significant role for both connectome topology geometry shaping distribution atrophy. also demonstrates SNCA GBA transcription influence concentration regional vulnerability. Functional coactivation further amplifies set architecture expression. Altogether, these results support theory progression multifactorial depends on cell-to-cell misfolded proteins

Язык: Английский

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The effect of network thresholding and weighting on structural brain networks in the UK Biobank

NeuroImage, Год журнала: 2020, Номер 211, С. 116443 - 116443

Опубликована: Янв. 10, 2020

Whole-brain structural networks can be constructed using diffusion MRI and probabilistic tractography. However, measurement noise the nature of tracking procedure result in an unknown proportion spurious white matter connections. Faithful disentanglement genuine connections is hindered by a lack comprehensive anatomical information at network-level. Therefore, network thresholding methods are widely used to remove ostensibly false connections, but it not yet clear how different strategies affect basic properties their associations with meaningful demographic variables, such as age. In sample 3153 generally healthy volunteers from UK Biobank Imaging Study (aged 44–77 years), we whole-brain applied two principled approaches (consistency proportional thresholding). These were over broad range threshold levels across six alternative weightings (streamline count, fractional anisotropy, mean diffusivity three novel neurite orientation dispersion density imaging) for four common measures (mean edge weight, characteristic path length, efficiency clustering coefficient). We compared against age found that: 1) derived unthresholded matrices yielded weakest age-associations (0.033 ​≤ ​|β| ​0.409); 2) most commonly-used level proportional-thresholding literature (retaining 68.7% all possible connections) significantly weaker (0.070 ​0.406) than consistency-based approach which retained only 30% (0.140 ​0.409). determined that stringency was stronger determinant network-age association choice method identified highly overlapping set (ICC ​= ​0.84), when matched 70% sparsity. Generally, more stringent resulted age-sensitive five weightings, except highest sparsity (>90%), where crucial then removed. At levels, discarded β ​|0.068|) smaller magnitude corresponding ​|0.219|, p ​< ​0.001, uncorrected). Given histological evidence widespread degeneration brain connectivity increasing age, these results indicate may accurate identifying true

Язык: Английский

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Learning function from structure in neuromorphic networks

Nature Machine Intelligence, Год журнала: 2021, Номер 3(9), С. 771 - 786

Опубликована: Авг. 9, 2021

Язык: Английский

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Differences in subcortico-cortical interactions identified from connectome and microcircuit models in autism

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Апрель 13, 2021

Abstract The pathophysiology of autism has been suggested to involve a combination both macroscale connectome miswiring and microcircuit anomalies. Here, we combine connectome-wide manifold learning with biophysical simulation models understand associations between global network perturbations dysfunctions in autism. We studied neuroimaging phenotypic data 47 individuals 37 typically developing controls obtained from the Autism Brain Imaging Data Exchange initiative. Our analysis establishes significant differences structural organization relative controls, strong between-group effects low-level somatosensory regions moderate high-level association cortices. Computational reveal that degree anomalies is related atypical increases recurrent excitation/inhibition, as well subcortical inputs into cortical microcircuits, especially sensory motor areas. Transcriptomic based on postmortem datasets identifies genes expressed thalamic areas childhood young adulthood. Finally, supervised machine finds are associated symptom severity scores Diagnostic Observation Schedule. Together, our analyses suggest subcortico-cortical interactions

Язык: Английский

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Shared vulnerability for connectome alterations across psychiatric and neurological brain disorders

Nature Human Behaviour, Год журнала: 2019, Номер 3(9), С. 988 - 998

Опубликована: Авг. 5, 2019

Язык: Английский

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A multi-scale cortical wiring space links cellular architecture and functional dynamics in the human brain

PLoS Biology, Год журнала: 2020, Номер 18(11), С. e3000979 - e3000979

Опубликована: Ноя. 30, 2020

The vast net of fibres within and underneath the cortex is optimised to support convergence different levels brain organisation. Here, we propose a novel coordinate system human based on an advanced model its connectivity. Our approach inspired by seminal, but so far largely neglected models cortico-cortical wiring established postmortem anatomical studies capitalises cutting-edge in vivo neuroimaging machine learning. new expands currently prevailing diffusion magnetic resonance imaging (MRI) tractography incorporation additional features cortical microstructure proximity. Studying several datasets parcellation schemes, could show that our robustly recapitulates sensory-limbic anterior-posterior dimensions A series validation experiments showed space reflects microcircuit (including pyramidal neuron depth glial expression) allowed for competitive simulations functional connectivity dynamics resting-state (rs-fMRI) intracranial electroencephalography (EEG) coherence. results advance understanding how cell-specific neurobiological gradients produce hierarchical scheme concordant with increasing sophistication evaluations demonstrate bridges across scales neural organisation can be easily translated single individuals.

Язык: Английский

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Signal diffusion along connectome gradients and inter-hub routing differentially contribute to dynamic human brain function

NeuroImage, Год журнала: 2020, Номер 224, С. 117429 - 117429

Опубликована: Окт. 7, 2020

Human cognition is dynamic, alternating over time between externally-focused states and more abstract, often self-generated, patterns of thought. Although cognitive neuroscience has documented how networks anchor particular modes brain function, mechanisms that describe transitions distinct functional remain poorly understood. Here, we examined time-varying changes in function emerge within the constraints imposed by macroscale structural network organization. Studying a large cohort healthy adults (n = 326), capitalized on manifold learning techniques identify low dimensional representations connectome organization decomposed neurophysiological activity into their transition using Hidden Markov Models. Structural predicted dynamic anchored sensorimotor systems those transmodal states. Connectome topology analyses revealed involving traversed short intermediary distances adhered strongly to communication diffusion. Conversely, involved spatially distributed hubs increasingly engaged long-range routing. These findings establish structure cortex optimized allow neural freedom vary processing, so provides key insight give rise flexibility human cognition.

Язык: Английский

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The modular organization of brain cortical connectivity across the human lifespan

NeuroImage, Год журнала: 2020, Номер 218, С. 116974 - 116974

Опубликована: Май 22, 2020

The network architecture of the human brain contributes in shaping neural activity, influencing cognitive and behavioral processes. availability neuroimaging data across lifespan allows us to monitor how this reorganizes, influenced by processes like learning, adaptation, maturation, senescence. Changing patterns connectivity can be analyzed with tools science, which used reveal organizational principles such as modular topology. identification modules is fundamental, they parse into coherent sub-systems allow for both functional integration segregation among different areas. In work we examined brain's organization developing an ensemble-based multilayer approach, allowing link changes structural development aging. We show that structure exhibits linear nonlinear age-related trends. early late lifespan, communities are more modular, track origins high modularity two substrates connectivity, linked number weights intra-clusters edges. also demonstrate aging leads a progressive increasing reconfiguration redistribution hemispheres. Finally, identify those regions most contribute remain stable lifespan.

Язык: Английский

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Edges in brain networks: Contributions to models of structure and function

Network Neuroscience, Год журнала: 2021, Номер unknown, С. 1 - 28

Опубликована: Авг. 13, 2021

Abstract Network models describe the brain as sets of nodes and edges that represent its distributed organization. So far, most discoveries in network neuroscience have prioritized insights highlight distinct groupings specialized functional contributions nodes. Importantly, these are determined expressed by web their interrelationships, formed edges. Here, we underscore important made for understanding Different types different relationships, including connectivity similarity among Adopting a specific definition can fundamentally alter how analyze interpret network. Furthermore, associate into collectives higher order arrangements, time series, form edge communities provide topology complementary to traditional node-centric perspective. Focusing on edges, or dynamic information they provide, discloses previously underappreciated aspects structural

Язык: Английский

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An expanding manifold in transmodal regions characterizes adolescent reconfiguration of structural connectome organization

eLife, Год журнала: 2021, Номер 10

Опубликована: Март 31, 2021

Adolescence is a critical time for the continued maturation of brain networks. Here, we assessed structural connectome development in large longitudinal sample ranging from childhood to young adulthood. By projecting high-dimensional connectomes into compact manifold spaces, identified marked expansion connectomes, with strongest effects transmodal regions during adolescence. Findings reflected increased within-module connectivity together segregation, indicating increasing differentiation higher-order association networks rest brain. Projection subcortico-cortical patterns these manifolds showed parallel alterations pathways centered on caudate and thalamus. Connectome findings were contextualized via spatial transcriptome analysis, highlighting genes enriched cortex, thalamus, striatum. Statistical learning cortical subcortical features at baseline their maturational change predicted measures intelligence follow-up. Our demonstrate that can bridge conceptual empirical gaps between macroscale network reconfigurations, microscale processes, cognitive outcomes adolescent development.

Язык: Английский

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