Mapping neurotransmitter systems to the structural and functional organization of the human neocortex

Nature Neuroscience, Journal Year: 2022, Volume and Issue: 25(11), P. 1569 - 1581

Published: Oct. 27, 2022

Abstract Neurotransmitter receptors support the propagation of signals in human brain. How receptor systems are situated within macro-scale neuroanatomy and how they shape emergent function remain poorly understood, there exists no comprehensive atlas receptors. Here we collate positron emission tomography data from more than 1,200 healthy individuals to construct a whole-brain three-dimensional normative 19 transporters across nine different neurotransmitter systems. We found that profiles align with structural connectivity mediate function, including neurophysiological oscillatory dynamics resting-state hemodynamic functional connectivity. Using Neurosynth cognitive atlas, uncovered topographic gradient overlapping distributions separates extrinsic intrinsic psychological processes. Finally, both expected novel associations between cortical abnormality patterns 13 disorders. replicated all findings an independently collected autoradiography dataset. This work demonstrates chemoarchitecture shapes brain structure providing new direction for studying multi-scale organization.

Language: Английский

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Standardizing workflows in imaging transcriptomics with the abagen toolbox

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

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Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa: A Coordinated Analysis by the ENIGMA Eating Disorders Working Group

Biological Psychiatry, Journal Year: 2022, Volume and Issue: 92(9), P. 730 - 738

Published: June 1, 2022

Language: Английский

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BrainStat: A toolbox for brain-wide statistics and multimodal feature associations

NeuroImage, Journal Year: 2022, Volume and Issue: 266, P. 119807 - 119807

Published: Dec. 10, 2022

Analysis and interpretation of neuroimaging datasets has become a multidisciplinary endeavor, relying not only on statistical methods, but increasingly associations with respect to other brain-derived features such as gene expression, histological data, functional well cognitive architectures. Here, we introduce BrainStat - toolbox for (i) univariate multivariate linear models in volumetric surface-based brain imaging datasets, (ii) multidomain feature association results spatial maps post-mortem expression histology, task-based fMRI meta-analysis, resting-state motifs across several common surface templates. The combination statistics into turnkey streamlines analytical processes accelerates cross-modal research. is implemented both Python MATLAB, two widely used programming languages the neuroinformatics communities. openly available complemented by an expandable documentation.

Language: Английский

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Coordinated cortical thickness alterations across six neurodevelopmental and psychiatric disorders

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

Published: Nov. 11, 2022

Abstract Neuropsychiatric disorders are increasingly conceptualized as overlapping spectra sharing multi-level neurobiological alterations. However, whether transdiagnostic cortical alterations covary in a biologically meaningful way is currently unknown. Here, we studied co-alteration networks across six neurodevelopmental and psychiatric disorders, reflecting pathological structural covariance. In 12,024 patients 18,969 controls from the ENIGMA consortium, observed that patterns followed normative connectome organization were anchored to prefrontal temporal disease epicenters. Manifold learning revealed frontal-to-temporal sensory/limbic-to-occipitoparietal gradients, differentiating shared illness effects on thickness along these axes. The principal gradient aligned with covariance established transcriptomic link cortico-cerebello-thalamic circuits. Moreover, gradients segregated functional involved basic sensory, attentional/perceptual, domain-general cognitive processes, distinguished between regional cytoarchitectonic profiles. Together, our findings indicate occur synchronized fashion multiple levels of hierarchical organization.

Language: Английский

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

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

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Robust estimation of cortical similarity networks from brain MRI

Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(8), P. 1461 - 1471

Published: July 17, 2023

Abstract Structural similarity is a growing focus for magnetic resonance imaging (MRI) of connectomes. Here we propose Morphometric INverse Divergence (MIND), new method to estimate within-subject between cortical areas based on the divergence their multivariate distributions multiple MRI features. Compared prior approach morphometric networks (MSNs) n > 11,000 scans spanning three human datasets and one macaque dataset, MIND were more reliable, consistent with cytoarchitectonics symmetry correlated tract-tracing measures axonal connectivity. derived from T1-weighted sensitive age-related changes than MSNs or by tractography diffusion-weighted MRI. Gene co-expression was strongly coupled tractography. network phenotypes also heritable, especially edges structurally differentiated areas. analysis provides biologically validated lens connectomics using readily available data.

Language: Английский

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Systematic evaluation of fMRI data-processing pipelines for consistent functional connectomics

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 4, 2024

Abstract Functional interactions between brain regions can be viewed as a network, enabling neuroscientists to investigate function through network science. Here, we systematically evaluate 768 data-processing pipelines for reconstruction from resting-state functional MRI, evaluating the effect of parcellation, connectivity definition, and global signal regression. Our criteria seek that minimise motion confounds spurious test-retest discrepancies topology, while being sensitive both inter-subject differences experimental effects interest. We reveal vast systematic variability across pipelines’ suitability connectomics. Inappropriate choice pipeline produce results are not only misleading, but so, with majority failing at least one criterion. However, set optimal consistently satisfy all different datasets, spanning minutes, weeks, months. provide full breakdown each pipeline’s performance inform future best practices in

Language: Английский

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

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

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Regional brain iron correlates with transcriptional and cellular signatures in Alzheimer's disease

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(1)

Published: Jan. 1, 2025

The link between overload brain iron and transcriptional/cellular signatures in Alzheimer's disease (AD) remains inconclusive. Iron deposition 41 cortical subcortical regions of 30 AD patients 26 healthy controls (HCs) was measured using quantitative susceptibility mapping (QSM). expression 15,633 genes estimated the same transcriptomic data from Allen Human Brain Atlas (AHBA). Partial least square (PLS) regression used to identify association gene transcription aberrant regional QSM signal AD. biological processes cell types associated with linked were evaluated. Gene ontological analyses showed that first PLS component (PLS1) enriched for relating "protein phosphorylation" "metal ion transport". Additionally, these expressed microglia (MG) glutamatergic neurons (GLUs). Our findings provide mechanistic insights transcriptional cellular into accumulation by Spatial patterns changes correlate spatial subjects. identified profile underlies related predominantly MG GLUs.

Language: Английский

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