Imaging Transcriptomics of Brain Disorders DOI Creative Commons
Aurina Arnatkevičiūtė, Ben Fulcher, Mark A. Bellgrove

et al.

Biological Psychiatry Global Open Science, Journal Year: 2021, Volume and Issue: 2(4), P. 319 - 331

Published: Oct. 22, 2021

Noninvasive neuroimaging is a powerful tool for quantifying diverse aspects of brain structure and function in vivo, it has been used extensively to map the neural changes associated with various disorders. However, most techniques offer only indirect measures underlying pathological mechanisms. The recent development anatomically comprehensive gene expression atlases opened new opportunities studying transcriptional correlates noninvasively measured phenotypes, offering rich framework evaluating pathophysiological hypotheses putative Here, we provide an overview some fundamental methods imaging transcriptomics outline their application understanding disorders neurodevelopment, adulthood, neurodegeneration. Converging evidence indicates that spatial variations are linked normative during age-related maturation neurodegeneration part cell-specific markers expression. Transcriptional disorder-related phenotypes also transcriptionally dysregulated genes identified ex vivo analyses patient brains. Modeling studies demonstrate patterns involved regional vulnerability spread disease across brain. This growing body work supports utility testing about molecular mechanism driving disease-related macroscopic phenotypes.

Language: Английский

Spread of pathological tau proteins through communicating neurons in human Alzheimer’s disease DOI Creative Commons
Jacob W. Vogel, Yasser Iturria‐Medina,

Olof Strandberg

et al.

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: May 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.

Language: Английский

Citations

392
The ENIGMA Toolbox: multiscale neural contextualization of multisite neuroimaging datasets DOI
Sara Larivière, Casey Paquola, Bo‐yong Park

et al.

Nature Methods, Journal Year: 2021, Volume and Issue: 18(7), P. 698 - 700

Published: June 30, 2021

Language: Английский

Citations

170
Standardizing workflows in imaging transcriptomics with the abagen toolbox DOI Creative Commons
Ross D. Markello, Aurina Arnatkevičiūtė, Jean‐Baptiste Poline

et al.

eLife, Journal Year: 2021, Volume and Issue: 10

Published: Nov. 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

Language: Английский

Citations

143
Null models in network neuroscience DOI
František Váša, Bratislav Mišić

Nature reviews. Neuroscience, Journal Year: 2022, Volume and Issue: 23(8), P. 493 - 504

Published: May 31, 2022

Language: Английский

Citations

137
Brain network communication: concepts, models and applications DOI
Caio Seguin, Olaf Sporns, Andrew Zalesky

et al.

Nature reviews. Neuroscience, Journal Year: 2023, Volume and Issue: 24(9), P. 557 - 574

Published: July 12, 2023

Language: Английский

Citations

130
Local structure-function relationships in human brain networks across the lifespan DOI Creative Commons
Farnaz Zamani Esfahlani, Joshua Faskowitz,

Jonah Slack

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: April 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

Language: Английский

Citations

116
Connectome-based modelling of neurodegenerative diseases: towards precision medicine and mechanistic insight DOI
Jacob W. Vogel, Nick Corriveau‐Lecavalier, Nicolai Franzmeier

et al.

Nature reviews. Neuroscience, Journal Year: 2023, Volume and Issue: 24(10), P. 620 - 639

Published: Aug. 24, 2023

Language: Английский

Citations

77
Local molecular and global connectomic contributions to cross-disorder cortical abnormalities DOI Creative Commons
Justine Y. Hansen, Golia Shafiei, Jacob W. Vogel

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Aug. 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.

Language: Английский

Citations

70
Connectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study DOI Creative Commons
Foivos Georgiadis, Sara Larivière, David C. Glahn

et al.

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(6), P. 1869 - 1881

Published: Feb. 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-

Language: Английский

Citations

20
Frontotemporal dementia. How to deal with its diagnostic complexity? DOI Creative Commons
Annibale Antonioni,

Emanuela Maria Raho,

Enrico Granieri

et al.

Expert Review of Neurotherapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 6, 2025

Frontotemporal dementia (FTD) encompasses a group of heterogeneous neurodegenerative disorders. Aside from genetic cases, its diagnosis is challenging, particularly in the early stages when symptoms are ambiguous, and structural neuroimaging does not reveal characteristic patterns. The authors performed comprehensive literature search through MEDLINE, Scopus, Web Science databases to gather evidence aid diagnostic process for suspected FTD patients, phases, even sporadic ranging established promising tools. Blood-based biomarkers might help identify very neuropathological guide further evaluations. Subsequently, neurophysiological measures reflecting functional changes cortical excitatory/inhibitory circuits, along with assessing brain network, connectivity, metabolism, perfusion alterations, could detect specific associated decades before symptom onset. As advances, cognitive-behavioral profiles atrophy patterns emerge, distinguishing subtypes. Emerging disease-modifying therapies require patient enrollment. Therefore, paradigm shift needed - relying on typical cognitive advanced cases widely applicable biomarkers, primarily fluid and, subsequently, where appropriate. Additionally, exploring subjective complaints behavioral detected by home-based technologies be crucial diagnosis.

Language: Английский

Citations

2