Cereb Cortex transcription-neuroimaging association analysis reveals the genetic mechanism of resting state functional connectivity in human visual cortex subregions

Written by Zhang Cun, edited by Zhu Jiajia, Wang Sizhen The human visual cortex is composed of multiple sub-regions with different functions.
The processing of information requires the interaction between different brain regions.
Resting-state functional magnetic resonance (resting-state functional magnetic resonance) Imaging (rs-fMRI) can use resting-state functional connectivity (rsFC) to measure the correlation between the blood oxygen levels in different areas of the brain and reflect the interaction between different brain areas
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Using this indicator, previous scholars found that there are differences between the rsFC patterns of visual subregions [1], which further illustrates that differences in brain functions may be affected by differences in connection patterns
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In addition, the functional connection patterns of visual subregions are highly conserved among populations [2], which suggests that there may be a certain genetic mechanism, but this genetic mechanism needs to be further revealed
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 On October 5, 2021, the neuroimaging team of the Radiology Department of the First Affiliated Hospital of Anhui Medical University published a research paper entitled "Genetic architecture underlying differential resting-state functional connectivity of subregions within the human visual cortex" on Cerebral Cortex.
The doctoral student Zhang Cun of the school is the first author of the paper, and the corresponding authors are Professor Yu Yongqiang and Associate Professor Zhu Jiajia
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The study found that different occipital lobe visual subregions rsFC patterns are related to different gene expression patterns, and there are significant differences in the number and functional characteristics of genes related to rsFC in the medial and lateral visual cortex subregions
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These findings help us understand the heterogeneity of visual cortex function from a genetic point of view
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 The human visual cortex is mainly located in the occipital lobe of the brain, and consists of multiple sub-regions that differ in function
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Using rsFC, the researchers found that there are differences between the rsFC patterns of visual subregions, which further illustrates that differences in brain function may be affected by differences in connection patterns
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In addition, the functional connection pattern of visual subregions is highly conserved among populations, suggesting that there may be a certain genetic mechanism, but this genetic mechanism needs to be further revealed
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 Transcriptome-neuroimaging association analysis can combine micro-scale molecular functions such as the Allen Human Brain Atlas (AHBA) [3] with macro-level brain structures such as neuroimaging phenotypes to explore neuroimaging phenotypes.
Genetic mechanism
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Previous studies have used this method to screen out genes whose spatial expression pattern is consistent with the spatial structure of rsFC in healthy people [4-9]
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Nevertheless, the genetic mechanism of rsFC in the visual cortex subregion is still poorly understood
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In addition, the original transcriptome data requires standardized processing procedures to ensure the reliability and repeatability of the results, and the combination of high-dimensional, multi-scale transcriptome data and neuroimaging data also requires reasonable correlation methods
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 In this study, the researchers used the latest transcriptome data standardized processing guidelines [10] to preprocess the AHB data, and obtained multiple rs-fMRI databases (one discovery set and two sources from different scanning instruments, different ethnicities).
The results were verified using the data from the validation set of the transcriptome-neuroimaging space correlation analysis method to explore the molecular mechanism of the human visual subregion rsFC (Figure 1)
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Figure 1 Flow chart of experimental design and analysis (picture quoted from: Cun Zhang, et al.
, Cerebral Cortex, 2021; bhab335) The researchers found that there is a difference between the rsFC pattern of different visual subregions and the expression pattern of different gene sets Associated
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Specifically, compared with the sub-regions of the lateral visual cortex (such as the middle temporal visual area (V5/MT+) and the medial superior occipital gyrus (msOccG)), the rsFC of the medial visual cortex sub-region is related to More gene expression patterns are correlated.
These medial visual cortex subregions include caudal lingual gyrus (cLinG), rostral cuneus gyrus (rCunG), and caudal cuneus (caudal cuneus).
gyrus, cCunG), rostral lingual gyrus (rLinG), and ventromedial parietooccipital sulcus (vmPOS); further functional annotation results show that genes related to the medial visual subregion rsFC are enriched in more Diverse physiological functions and psychiatric diseases (Figure 2), and specifically expressed in a variety of neurons and immune cells, as well as the middle and late stages of cortical development (Figure 3)
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Figure 2 Functional enrichment results of genes related to occipital visual subregion rsFC (picture quoted from: Cun Zhang, et al.
, Cerebral Cortex, 2021; bhab335) Figure 3 Specificity of genes related to occipital visual subregion rsFC Expression analysis results (picture quoted from: Cun Zhang, et al.
, Cerebral Cortex, 2021; bhab335) In order to further study the behavioral meaning of genes related to the visual subregion rsFC, the researchers used Neurosynth to compare gene expression patterns and behavioral items Connect
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The results showed that the genes related to the inner and outer visual subregions (rCunG, rLinG, vmPOS, and msOccG) rsFC are all related to behavioral items such as sensation, language, movement, emotion, and attention; in addition, they are related to the outer visual subregion (msOccG) rsFC Related genes are also related to some high-level cognitive activities such as personality, semantic memory, imagination, and social cognition
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It is worth noting that among all the behavioral items, there is the most significant association between the rsFC-related genes in the visual subregion and the visual-related behaviors, which proves that these genes are mainly involved in the visual-related behavior process (Figure 4)
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Figure 4 The correlation between rsFC-related genes in the visual subregion and the behavioral items in Neurosynth (picture quoted from: Cun Zhang, et al.
, Cerebral Cortex, 2021; bhab335) Protein-protein interaction network analysis (Protein-protein interaction Analysis, PPI) results show that the four visual subregions (rCunG, rLinG, vmPOS, and msOccG) rsFC-related genes can form a statistically significant PPI network (Figure 5)
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In each PPI network, the genes with the node degree in the top 10% are defined as hub genes
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Therefore, there are 34, 11, 14 and 2 hub genes in the PPI network composed of genes related to rCunG, rLinG, vmPOS and msOccG subregions rsFC (Figure 6)
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The researchers showed the spatiotemporal expression trajectory characteristics of the genes with the highest node degree among these hub genes (Figure 5)
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Figure 5 Protein-protein interaction network analysis results (picture quoted from: Cun Zhang, et al.
, Cerebral Cortex, 2021; bhab335) Figure 6 Circos diagram display of the hub gene in the protein-protein interaction network (picture quoted from: Cun Zhang, et al.
, Cerebral Cortex, 2021; bhab335) article conclusions and discussions, inspiration and prospects.
In summary, the results of this study indicate that different occipital visual subregions rsFC are related to the expression patterns of different genes, and are related to the medial and lateral visual cortex.
There are significant differences in the number and functional characteristics of genes related to rsFC in the region
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These findings help us understand the heterogeneity of visual cortex function from the perspective of genetic mechanism
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 Although the results of this study used transcription-neuroimaging association analysis to find genes related to the spatial pattern of rsFC in the visual cortex subregion, there are still some limitations
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First of all, transcriptomics and neuroimaging data come from different individuals.
The individual-level transcription-neuroimaging association analysis used by researchers focuses on genes that are conservatively expressed in the population, which makes it impossible to further study those that are specific in individuals.
Expressed genes; secondly, the results of correlation analysis cannot explain the causal relationship, and further explanation of this discovery is needed in animal research.
Finally, due to the scarcity of brain specimens, the AHBA database selected in this study only measured six donated brains The gene expression pattern of this time still needs more representative human transcriptome data to verify the results
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1093/cercor/bhab335 Zhang Cun (left, first author), Zhu Jiajia (right, corresponding author) (photo provided from: Neuroimaging Function Laboratory) Selected previous articles [1] Mol Cell︱ Alzheimer's disease New mechanism: Tau protein oligomerization induces nuclear cell transport of RNA-binding protein HNRNPA2B1 and mediates m6A-RNA modification enhancement [2] Cereb Cortex | Li Tao's group reported that the cortical myelin covariant network with deep features of the cerebral cortex is involved in schizophrenia The abnormality in the symptom [3] Cell︱ hold hands, advance and retreat together! The formation of a cellular network between microglia to work together to degrade pathological α-syn [4] lipids and Alzheimer's disease! The lack of sulfatides in the myelin sheath in the central nervous system in adulthood can lead to Alzheimer’s disease-like neuroinflammation and cognitive impairment [5] Brain︱ new method! Plasma soluble TREM2 can be used as a potential detection marker for white matter damage in cerebral small vessel disease [6] EMBO J︱neuron Miro1 protein deletion destroys mitochondrial autophagy and overactivates the integrated stress response [7] Science frontier review interpretation︱nicotinic acetylcholine The regulatory mechanism of receptor-assisted molecules and the application prospects of disease treatment and transformation [8] Cereb Cortex︱ oxytocin can regulate the individualized processing of facial identities and the classification of facial races in the early facial regions of the brain [9] Nat Commun | Qi Xin Project The group revealed the molecular mechanism of the compound CHIR99021 to treat Huntington’s disease by regulating mitochondrial function [10] Neurosci Bull︱ synapse-associated protein Dlg1 improves depression-like behavior in mice by inhibiting microglia activation [11] Brain | For the first time! PAX6 may be a key factor in the pathogenesis of Alzheimer's disease and a new therapeutic target [12] Sci Adv︱ blockbuster! DNA methylation protein DNMT1 mutation can induce neurodegenerative diseases [13] Cereb Cortex︱MET tyrosine kinase signal transduction timing abnormality is a key mechanism affecting the development and behavior of normal cortical neural circuits in mice [14] Nat Biomed Eng︱ The team of academician Ye Yuru develops a new strategy for whole-brain gene editing-mediated treatment of Alzheimer's disease [15] Luo Liqun Science's heavy review System Interpretation ︱ Neural circuit structure-a high-quality scientific research training course recommendation for a system that makes the brain "computer" run at high speed 【1】Data graph help guide! How good is it to learn these software? 【2】Single-cell sequencing data analysis and project design network practical class (October 16-17)【3】JAMA Neurol︱Attention! Young people are more likely to suffer from "Alzheimer's disease"? [4] Patch Clamp and Optogenetics and Calcium Imaging Technology Seminar (October 30-31) References (slide up and down to view) [1] Park BY, Tark KJ, Shim WM, Park H.
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