scholarly journals Correspondence between gene expression and neurotransmitter receptor and transporter density in the human brain

2021 ◽  
Author(s):  
Justine Y Hansen ◽  
Ross D Markello ◽  
Lauri Tuominen ◽  
Martin Norgaard ◽  
Elena Kuzmin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Present Report ◽  
Neurotransmitter Receptors ◽  
Metabotropic Receptors ◽  
Microarray Gene Expression ◽  
Neurotransmitter Receptor ◽  
Neurotransmitter Systems ◽  
Brain Structure And Function ◽  
And Function ◽  
Direct Measures

Neurotransmitter receptors modulate the signaling between neurons. Thus, neurotransmitter receptors and transporters play a key role in shaping brain function. Due to the lack of comprehensive neurotransmitter receptor/transporter density datasets, microarray gene expression is often used as a proxy for receptor densities. In the present report, we comprehensively test the expression-density association for a total of 27 neurotransmitter receptors, receptor binding-sites, and transporters across 9 different neurotransmitter systems, using both PET and autoradiography imaging modalities. We find poor spatial correspondences between gene expression and density for all neurotransmitter receptors and transporters except four single-protein metabotropic receptors (5-HT1A, D2, CB1, and MOR). These expression-density associations are related to population variance and change across different classes of laminar differentiation. Altogether, we recommend using direct measures of receptor and transporter density when relating neurotransmitter systems to brain structure and function.

scholarly journals Imaging transcriptomics of brain disorders

2021 ◽  
Author(s):  
Aurina Arnatkeviciute ◽  
Ben Fulcher ◽  
Mark Bellgrove ◽  
Alex Fornito
Keyword(s):  
Gene Expression ◽  
Brain Structure ◽  
Ex Vivo ◽  
Specific Gene ◽  
Brain Disorders ◽  
Spatiotemporal Resolution ◽  
Indirect Measures ◽  
Regional Vulnerability ◽  
Brain Structure And Function ◽  
And Function

Non-invasive neuroimaging is a powerful tool for quantifying diverse aspects of brain structure and function invivo and has been used extensively to map the neural changes associated with different brain disorders. However,most neuroimaging techniques have limited spatiotemporal resolution and offer only indirect measures ofunderlying pathological mechanisms. The recent development of anatomically comprehensive gene-expressionatlases has opened new opportunities for studying the transcriptional correlates of non-invasively measured neuralphenotypes, offering a rich framework for evaluating pathophysiological hypotheses and putative mechanisms.Here, we overview some fundamental methods in imaging transcriptomics and outline their application tounderstanding brain disorders of neurodevelopment, adulthood, and neurodegeneration. Converging evidenceindicates that spatial variations in gene expression are linked to normative changes in brain structure during agerelatedmaturation and neurodegeneration that are in part associated with cell-specific gene expression markersof gene expression. Transcriptional correlates of disorder-related neuroimaging phenotypes are also linked totranscriptionally dysregulated genes identified in ex vivo analyses of patient brains. Modeling studies demonstratethat spatial patterns of gene expression are involved in regional vulnerability to neurodegeneration and the spreadof disease across the brain. This growing body of work supports the utility of transcriptional atlases in testinghypotheses about the molecular mechanism driving disease-related changes in macroscopic neuroimagingphenotypes.

scholarly journals Gradients of structure–function tethering across neocortex

2019 ◽  
Vol 116 (42) ◽  
pp. 21219-21227 ◽  
Author(s):  
Bertha Vázquez-Rodríguez ◽  
Laura E. Suárez ◽  
Ross D. Markello ◽  
Golia Shafiei ◽  
Casey Paquola ◽  
...  
Keyword(s):  
Structure Function ◽  
Present Report ◽  
Brain Regions ◽  
Structure And Function ◽  
Spatial Proximity ◽  
Functional Networks ◽  
Functional Connection ◽  
Brain Structure And Function ◽  
And Function ◽  
The Brain

The white matter architecture of the brain imparts a distinct signature on neuronal coactivation patterns. Interregional projections promote synchrony among distant neuronal populations, giving rise to richly patterned functional networks. A variety of statistical, communication, and biophysical models have been proposed to study the relationship between brain structure and function, but the link is not yet known. In the present report we seek to relate the structural and functional connection profiles of individual brain areas. We apply a simple multilinear model that incorporates information about spatial proximity, routing, and diffusion between brain regions to predict their functional connectivity. We find that structure–function relationships vary markedly across the neocortex. Structure and function correspond closely in unimodal, primary sensory, and motor regions, but diverge in transmodal cortex, particularly the default mode and salience networks. The divergence between structure and function systematically follows functional and cytoarchitectonic hierarchies. Altogether, the present results demonstrate that structural and functional networks do not align uniformly across the brain, but gradually uncouple in higher-order polysensory areas.

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

2021 ◽  
Author(s):  
Justine Y Hansen ◽  
Golia Shafiei ◽  
Ross D Markello ◽  
Kelly Smart ◽  
Sylvia ML Cox ◽  
...  
Keyword(s):  
Functional Organization ◽  
Structural Connectivity ◽  
Brain Organization ◽  
Neurotransmitter Systems ◽  
Oscillatory Dynamics ◽  
Multi Scale ◽  
Positron Emission ◽  
Brain Structure And Function ◽  
And Function ◽  
Novel Associations

Neurotransmitter receptors support the propagation of signals in the human brain. How receptor systems are situated within macroscale neuroanatomy and how they shape emergent function remains poorly understood, and there exists no comprehensive atlas of receptors. Here we collate positron emission tomography scans in >1,200 healthy individuals to construct a whole-brain 3-D normative atlas of 18 receptors and transporters across 9 different neurotransmitter systems. We find that receptor profiles align with structural connectivity and mediate function, including neurophysiological oscillatory dynamics and resting state hemodynamic functional connectivity. Using the Neurosynth cognitive atlas, we uncover a topographic gradient of overlapping receptor distributions that separates extrinsic and intrinsic psychological processes. Finally, we find both expected and novel associations between receptor distributions and cortical thinning patterns across 13 disorders. We replicate all findings in an independently collected autoradiography dataset. This work demonstrates how chemoarchitecture shapes brain structure and function, providing a new direction for studying multi-scale brain organization.

scholarly journals A practical guide to linking brain-wide gene expression and neuroimaging data

2018 ◽  
Author(s):  
Aurina Arnatkevičiūtė ◽  
Ben D. Fulcher ◽  
Alex Fornito
Keyword(s):  
Gene Expression ◽  
Brain Atlas ◽  
Expression Data ◽  
Analysis Pipeline ◽  
Atlas Data ◽  
Processing Pipeline ◽  
Neuroimaging Data ◽  
Brain Structure And Function ◽  
Expression Atlas ◽  
And Function

AbstractThe recent availability of comprehensive, brain-wide gene expression atlases such as the Allen Human Brain Atlas (AHBA) has opened new opportunities for understanding how spatial variations on the molecular scale relate to the macroscopic neuroimaging phenotypes. A rapidly growing body of literature is demonstrating relationships between gene expression and diverse properties of brain structure and function, but approaches for combining expression atlas data with neuroimaging are highly inconsistent, with substantial variations in how the expression data are processed. The degree to which these methodological variations affect findings is unclear. Here, we outline a seven-step analysis pipeline for relating brain-wide transcriptomic and neuroimaging data and compare how different processing choices influence the resulting data. We suggest that studies using AHBA should work towards a unified data processing pipeline to ensure consistent and reproducible results in this burgeoning field.

scholarly journals Overcoming bias in gene-set enrichment analyses of brain-wide transcriptomic data

2020 ◽  
Author(s):  
Ben D. Fulcher ◽  
Aurina Arnatkevičiūtė ◽  
Alex Fornito
Keyword(s):  
Gene Expression ◽  
Brain Structure ◽  
False Positive ◽  
Structure And Function ◽  
Gene Set Enrichment Analysis ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Transcriptomic Data ◽  
Brain Structure And Function ◽  
And Function

The recent availability of whole-brain atlases of gene expression, which quantify the transcriptional activity of thousands of genes across many different brain regions, has opened new opportunities to understand how gene-expression patterns relate to spatially varying properties of brain structure and function. To aid interpretation of a given neural phenotype, gene-set enrichment analysis (GSEA) has become a standard statistical methodology to identify functionally related groups of genes, annotated using systems such as the Gene Ontology (GO), that are associated with a given phenotype. While GSEA has identified groups of genes related to diverse aspects of brain structure and function in mouse and human, here we show that these results are affected by substantial statistical biases. Quantifying the falsepositive rates of individual GO categories across an ensemble of random phenotypic maps, we found an average 875-fold inflation of significant findings relative to expectation in mouse, and a 582-fold inflation in human, with some categories being judged as significant for over 20% of random phenotypes. Concerningly, the probability of a GO category being reported as significant in the extant literature increases with its estimated false-positive rate, suggesting that published reports are strongly affected by the reporting of false-positive bias. We show that the bias is primarily driven by within-category gene–gene coexpression and spatial autocorrelation, which are not accounted for in conventional GSEA nulls, and we introduce flexible ensemble-based null models that can account for these effects. Testing a range of structural connectivity and cell density phenotypes in mouse and human, we demonstrate that many GO categories that would conventionally be judged as highly significant are in fact consistent with ensembles of random phenotypes. Our results highlight major pitfalls with applying standard GSEA to brain-wide transcriptomic data and outline solutions to this pervasive problem, which is made available as an open toolbox.

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

2022 ◽  
Author(s):  
Justine Hansen ◽  
Golia Shafiei ◽  
Ross Markello ◽  
Kelly Smart ◽  
Sylvia Cox ◽  
...  
Keyword(s):  
Functional Organization ◽  
Structural Connectivity ◽  
Brain Organization ◽  
Neurotransmitter Systems ◽  
Oscillatory Dynamics ◽  
Multi Scale ◽  
Positron Emission ◽  
Brain Structure And Function ◽  
And Function ◽  
Novel Associations

Abstract Neurotransmitter receptors support the propagation of signals in the human brain. How receptor systems are situated within macroscale neuroanatomy and how they shape emergent function remains poorly understood, and there exists no comprehensive atlas of receptors. Here we collate positron emission tomography scans in >1,200 healthy individuals to construct a whole-brain 3-D normative atlas of 18 receptors and transporters across 9 different neurotransmitter systems. We find that receptor profiles align with structural connectivity and mediate function, including neurophysiological oscillatory dynamics and resting state hemodynamic functional connectivity. Using the Neurosynth cognitive atlas, we uncover a topographic gradient of overlapping receptor distributions that separates extrinsic and intrinsic psychological processes. Finally, we find both expected and novel associations between receptor distributions and cortical thinning patterns across 13 disorders. We replicate all findings in an independently collected autoradiography dataset. This work demonstrates how chemoarchitecture shapes brain structure and function, providing a new direction for studying multi-scale brain organization.

scholarly journals Gradients of structure-function tethering across neocortex

2019 ◽  
Author(s):  
Bertha Vázquez-Rodríguez ◽  
Laura E. Suárez ◽  
Golia Shafiei ◽  
Ross D. Markello ◽  
Casey Paquola ◽  
...  
Keyword(s):  
Structure Function ◽  
Present Report ◽  
Brain Regions ◽  
Structure And Function ◽  
Spatial Proximity ◽  
Functional Networks ◽  
Functional Connection ◽  
Neuronal Populations ◽  
Brain Structure And Function ◽  
And Function

The white matter architecture of brain networks imparts a distinct signature on neuronal co-activation patterns. Inter-regional projections promote synchrony among distant neuronal populations, giving rise to richly patterned functional networks. A variety of statistical, communication and biophysical models have been proposed to study the relationship between brain structure and function, but the link is not yet known. In the present report we seek to relate the structural and functional connection profiles of individual brain areas. We apply a simple multilinear model that incorporates information about spatial proximity, routing and diffusion between brain regions to predict their functional connectivity. We find that structure-function relationships vary markedly across the neocortex. Structure and function correspond closely in unimodal, primary sensory and motor regions, but diverge in transmodal cortex, corresponding to the default mode and salience networks. The divergence between structure and function systematically follows functional and cytoarchitectonic hierarchies. Altogether, the present results demonstrate that structural and functional networks do not align uniformly across the brain, but gradually uncouple in higher-order polysensory areas.

scholarly journals From molecules to mind

2001 ◽  
Vol 7 (3) ◽  
pp. 363-366
Author(s):  
L. Eisenberg
Keyword(s):  
Gene Expression ◽  
Environmental Factors ◽  
Brain Structure ◽  
Molecular Level ◽  
Structure And Function ◽  
External Factors ◽  
Brain Structure And Function ◽  
Organ Level ◽  
And Function ◽  
The Brain

Thispaper describes the relation between genes at the molecular level and the brain at the organ level, and biological, social and environmental factors. The malleability of the brain and the effect of external factors and experience on influencing gene expression and brain structure and function are discussed.

scholarly journals Imaging brain structure and function, infection and gene expression in the body using light

1997 ◽  
Vol 352 (1354) ◽  
pp. 755-761 ◽  
Author(s):  
David A. Benaron ◽  
Pamela R. Contag ◽  
Christopher H. Contag
Keyword(s):  
Gene Expression ◽  
Brain Function ◽  
The Body ◽  
Low Light ◽  
Non Invasive ◽  
Positron Emission ◽  
Brain Structure And Function ◽  
Imaging Of Infection ◽  
And Function

Light can be used to probe the function and structure of human tissues. We have been exploring two distinct methods: (i) externally emitting light into tissue and measuring the transmitted light to characterize a region through which the light has passed, and (ii) internally generating light within tissue and using the radiated light as a quantitative homing beacon. The emitted–light approach falls within the domain of spectroscopy, and has allowed for imaging of intracranial haemorrhage in newborns and of brain function in adults. The generated–light approach is conceptually parallel to positron emission tomography (PET) or nuclear medicine scanning, and has allowed for real–time, non–invasive monitoring and imaging of infection and gene expression in vivo using low–light cameras and ordinary lenses. In this paper, we discuss recent results and speculate on the applications of such techniques.

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