Cereb Cortex Li Tao's group reported the abnormality of the cortical myelin covariation network with the deep characteristics of the cerebral cortex in schizophrenia

Author ︱ Wei Wei, edited by Li Tao ︱ Wang Sizhen Myelin sheath is the structural basis for the rapid transmission of nerve signals in the central nervous system.
Past studies have found that it is abnormal in neuropsychiatric diseases (schizophrenia)
.

However, due to the limited technical means, compared with the white matter inner myelin with mature research methods (such as diffusion tensor imaging), there are currently fewer studies on the cortical inner myelin
.

The cadaver brain research has shown that the myelin content is different in different depths of the cerebral cortex, which makes the research on the inner cortex myelin more complicated
.

In recent years, with the development of magnetic resonance technology, a variety of imaging methods (such as T1w/T2w ratio, magnetic susceptibility, etc.
) can be used for the study of cortical myelin; at the same time, principal component analysis or non-negative matrix decomposition and other co-variation The network construction method greatly reduces the complexity of the analysis and increases the interpretability of the results
.

The progress of these technologies and methods has made it possible for researchers to study the depth characteristics of the cortical myelin sheath
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 In September 2021, in the latest paper on Cerebral Cortex with the title "Structural Covariance of Depth-Dependent Intracortical Myelination in the Human Brain and Its Application to Drug-Naïve Schizophrenia: A T1w/T2w MRI Study", Sichuan University Wei Wei from the Mental Health Center of West China Hospital (the first article) and Li Tao from the Mental Health Center Affiliated to Zhejiang University School of Medicine (corresponding author) and others conducted a study on the depth-dependent structural covariance network (dSCN) of the cerebral cortex.
Analyze and study the abnormalities of related networks in patients with schizophrenia who did not take drugs for the first time
.

The study found that dSCN has good repeatability in different independent data, the same cortical brain area may belong to different networks at different depths, and patients with schizophrenia have myelin abnormalities in multiple networks, which is schizophrenia Abnormal structure of the midbrain provides new insights
.

To study the myelin covariation network under the condition of introducing cortical depth characteristics, the following three prerequisites need to be met: 1.
Use the correct imaging method to characterize the inner cortex myelin; 2.
Divide the cortex based on depth; 3 .
Construct a repeatable covariant network through dimensionality reduction
.

The data processing and analysis process used in this research is shown in Figure 1 below: Figure 1 The construction of cerebral cortex stratification and covariation network is the statistical analysis process (Figure quoted from: Wei et al.
, Cerebral Cortex, 2021; 00: 1– 12) The researcher used the T1w/T2w signal ratio method to characterize the myelin content
.

This method was proposed by Glasser et al.
of the Human Connectome Project (HCP) in 2013 [1].
It uses common T1w and T2w images for calculation and has a mature analysis and calculation process.
It has been widely used in recent years.
The study of the characteristics of myelin development, the construction of multi-modal brain templates and the study of cortical microstructure
.

Researchers have previously used this method to find that cortical myelin abnormalities in schizophrenia are deeply specific [2]
.

 After obtaining the T1w/T2w signal ratio image, the researchers used Freesurfer to obtain the white matter-cortical surface and the cortical-pia mater surface, and used Surface tools to divide the space between the two surfaces into 14 layers of equal volume [3] (Note: Cortical stratification based on cell characteristics does not correspond); in order to reduce the interference between cerebrospinal fluid and white matter signals, only the middle 11 layers are used, and the T1w/T2w signal ratio image of each layer is constructed on this basis, and a reserved DKT template is used The 1011 random partition template of the brain area boundary performs data dimensionality reduction and matrix extraction for the next analysis
.

 The researchers chose to use the non-negative matrix factorization (NMF) method for dSCN construction, and used 100 unrelated data sets from HCP for verification
.

NMF can better identify the covariant characteristics of brain structure and avoid the difficulty of explaining the negative values ​​in the load matrix in principal component or independent component analysis [4]
.

 The results show that when the 1011 brain area and the 11 cortical myelin characteristics are decomposed into 18 networks, the balance between repeatability and matrix reconstruction error ratio is optimal, and different data combinations (ie: only healthy control data, or Using the data of healthy controls and schizophrenia patients at the same time), different template choices (HCP multi-modal segmentation template [5]) have little effect on network distribution
.

Using skewness to visualize the distribution of myelin-related covariant network load (that is, the myelin content at the network level) on the cortical depth, we can observe the distribution of different networks and different brain regions in the cortical depth direction.
The difference is shown in Figure 2: Figure 2 The horizontal distribution pattern of dSCNs and the depth distribution pattern reflected by skewness (picture quoted from: Wei et al.
, Cerebral Cortex, 2021; 00: 1–12) Partial least squares correlation is used After analysis (partial least squares correlation), the researchers further found that in patients with schizophrenia, there was a decrease in myelin content in the cortex in the prefrontal lobe, orbitofrontal lobe, that is, the cingulate network (Figure 3), and the language-related network in the perilateral fissure area There is an increase in the content of myelin sheath in the cortex, and the above abnormal network is associated with the clinical symptoms of schizophrenia
.

Figure 3 Patients with schizophrenia have myelin sheath abnormalities in multiple covariant networks (picture quoted from: Wei et al.
, Cerebral Cortex, 2021; 00: 1-12) Conclusion and discussion of the article, inspiration and prospects The structure developed in this research The covariation network method introduces the deep-related characteristics of the cortical inner myelin sheath, and on the basis of constructing a reproducible dSCN, explores the abnormalities of the cortical inner myelin sheath in schizophrenia at the network level, as well as the correlation between related abnormalities and disease symptoms
.

 Due to the limitations of research methods and high analysis complexity, a large number of previous studies have considered the brain structure of different depths in a brain area as a whole for analysis.
The source and the goal of sending nerve signals are not the same [6], and the types of nerve cells at different depths are also different [7]
.

Therefore, the introduction of cortical depth information in myelin correlation analysis is beneficial to improve the sensitivity and specificity of the analysis results
.

 This study also has certain shortcomings.
First, due to the limited signal-to-noise ratio and resolution of the current magnetic resonance imaging technology, it is difficult to distinguish the cortical layer in an anatomical sense from conventional image data.
Isometric stratification is performed, and each layer does not correspond to the anatomical cortex one-to-one
.

Secondly, the use of T1w/T2w ratio method to characterize the cortical inner myelin is also controversial, and more head-to-head studies are needed for comparison and verification in the future
.

 In general, this study proposes to introduce depth information into the study of cortical myelin sheath, and use the method of structural covariation for network recognition and analysis, which provides a new perspective for the imaging study of brain abnormalities in schizophrenia
.

Original link: https://doi.
org/10.
1093/cercor/bhab337 Wei Wei (left), first author, postdoctoral fellow in Mental Health Center/Psychiatric Research Office of West China Hospital, Sichuan University; Li Tao (right), corresponding author, Zhejiang University Medicine Dean of the Mental Health Center (Hangzhou Seventh People's Hospital), Professor of Zhejiang University School of Medicine and West China Hospital of Sichuan University (Photo provided by: Li Tao Laboratory) Laboratory introduction: Professor Li Tao is the Mental Health Center of Zhejiang University School of Medicine Dean, Professor of Zhejiang University, winner of the National Outstanding Youth Fund, winner of the special government allowance of the State Council, distinguished professor of Yangtze River Scholars of the Ministry of Education, and host of national and international cooperation projects such as key projects of the National Natural Science Foundation of China.
Clinical research and basic clinical research on schizophrenia, bipolar disorder, depression, etc.
, comprehensively analyze the etiology and pathogenesis of common mental disorders from brain structure, function, and multiple levels (levels) such as genetics, biochemistry, and metabolism, and promote innovation R&D and clinical transformation of new drugs and clinical technologies
.


.

A series of research results have been achieved, and more than 300 research papers have been published.
Research papers are mainly published in first-class journals in this field
.

We sincerely invite students, postdoctoral fellows and researchers who are interested in clinical research and basic research of mental illness to join us
.

Contact: litaozjusc@zju.
edu.
cn
.

Selected articles from previous issues [1] Cell︱ hold hands, advance and retreat together! The formation of a cellular network between microglia and work together to degrade pathological α-syn [2] lipids and Alzheimer's disease! The lack of myelin in the central nervous system in adulthood can lead to Alzheimer’s disease-like neuroinflammation and cognitive impairment [3] eLife︱ sorting protein SNX27 regulates AMPA receptor transport through synaptic adhesion protein LRFN2 Mechanism [4] Brain︱ new method! Plasma soluble TREM2 can be used as a potential detection marker for white matter damage in cerebral small vessel disease [5] EMBO J︱ neuronal Miro1 protein deletion destroys mitochondrial autophagy and overactivates the integrated stress response [6] Science Frontier Review Interpretation︱ Nicotinic Acetylcholine The regulatory mechanism of receptor-assisted molecules and the application prospects of disease treatment and transformation [7] Cereb Cortex︱ oxytocin can regulate the individualized processing of facial identities and the classification of facial races in early facial regions of the brain [8] Nat Commun | Qi Xin Project The group revealed the molecular mechanism of the compound CHIR99021 in the treatment of Huntington’s disease by regulating mitochondrial function [9] Cereb Cortex︱ Ku Yixuan’s team revealed the ipsilateral sensory cortex representation pattern of working memory [10] Neurosci Bull︱ synapse-associated protein Dlg1 through inhibition Activation of microglia improves depression-like behavior in mice [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 practice 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] Glasser