Gong Qiyong team iScience: Gray matter network dysfunction in patients with social anxiety disorder|Cell Press paper express

Interdisciplinary

Interdisciplinary

On September 8, 2022, Gong Qiyong's team from the Magnetic Resonance Research Center (HMRRC) of West China Clinical Medical College of Sichuan University published a paper entitled "Large-scale dysfunctional white-matter and grey matter networks in patients with social anxiety" in iScience, an interdisciplinary journal under Cell Press Cell Press Disorder", a cluster analysis of brain network functions in patients with social anxiety disorder (1) constructed eight stable brain gray matter function networks and ten white matter function networks; (2) It revealed that the abnormal functional network connection of patients with social anxiety with the limbic system network as the core was revealed; (3) and found that abnormal functional connectivity is related to the symptoms and course of patients with social anxiety disorder; (4) and provide an
illustration of the application of white matter functional networks in cognitive neuroscience.

Long press the image recognition QR code to read the original article

Relevant background

Social anxiety disorder (SAD) is considered the most common anxiety disorder, which is characterized by persistent and extreme fear, anxiety and avoidance in a social environment, which greatly affects the patient's social interactions, interpersonal relationships and daily affairs, and may be accompanied by alcoholism, high divorce rates and suicide risks, bringing a heavy financial burden
to individuals, families and society.
However, its pathogenesis is unknown
.
A large number of functional magnetic resonance imaging (fMRI) studies provide key information at the brain function level for the neurophysiological mechanism of SAD, and some studies have proposed that SAD patients are characterized by dysfunction of the limbic system-prefrontal circuit, and expand to brain regions such as parietal and occipital lobes, but the current research is mostly based on artificial selection of regions of interest (ROI).
Or the analysis method of brain map template may lead to inconsistent connectivity results between different seed points or brain map division, and ignore the functional connection characteristics of brain regions other than seed points and the interaction between large-scale networks; At the same time, previous studies also used diffusion tensor imaging to study the structural connection pattern of SAD brain interval from the perspective of white matter microstructural integrity, and found that patients with SAD had abnormal
structural connections such as the prefrontal-limbic system and frontal-parietal-temporal pathway.
However, due to the fundamental differences in the signal sources of functional magnetic resonance and diffusion tensor imaging, we cannot explain the abnormal
functional connection of gray matter networks based on the spatial continuity of gray matter and white matter alone.
With the development of mental imaging, it has been found that the white matter has similar neurological activities and network characteristics
to the gray matter.
Therefore, this study aims to analyze the gray matter and white matter networks of SAD at the same time from the aspects of functional characteristics, so as to have a more comprehensive understanding
of the functional role of SAD whole brain network.

Interpretation of results

1.
Eight stable gray matter functional networks were identified

By performing K-means clustering of gray matter voxels and comparing the DICE coefficients of different numbers of clusters, the team obtained eight stable gray matter functional networks (Dice coefficient ≥ 0.
9), and named the networks according to the spatial anatomical position of the functional networks and the classical gray matter functional networks, such as (1) GM1 default mode network; (2) GM2 midbrain cerebellar network; (3) GM3 sensorimotor network; (4) GM4 edge system network; GM5 backside attention network; (6) GM6 Frontal Network; (7) GM7 Vision Network; (8) GM8 dorsal frontal network (Figure 1).

Fig.
1 Gray matter network clustering results and stability

2.
Identified 10 stable white matter functional networks

By performing K-mean clustering of white matter voxels and comparing the DICE coefficients of different numbers of clusters, the team obtained ten stable gray matter functional networks (Dice coefficient ≥ 0.
9), and named the networks according to the spatial anatomical position of the functional networks and the classical gray matter functional networks, such as (1) WM1 radial crown network; (2) WM2 orbitofrontal and medial frontal networks; (3) WM3 deep beam network; (4) WM4 front buckle network; (5) WM5 perceptual motion network; (6) WM6 Frontal Network; (7) Buckle network in WM7; (8) WM8 vision network; (9) WM cerebellar network; (10) WM10 rear cingulate network (Figure 2).

Fig.
2 Clustering results and stability of white matter network

3.
Build a brain network matrix

The average time series of each functional network of each participant was extracted from the clustering results (obtained by averaging the fMRI time series of all voxels in each network); Pearson correlation was used to analyze the functional connections between networks and construct a matrix of correlation coefficient functional networks (between gray and gray matter networks, between white matter and white matter functional networks, and between white matter and gray matter networks).

Apply the Fisher's z transformation to satisfy the normality of the correlation coefficients for subsequent statistical analysis (Figure 3).

Fig.
3 Connection matrix diagram of SAD patients and HC functions

4.
Patients with SAD have abnormal network connections with the limbic system network as the core

Patients with SAD (1) have reduced functional connectivity of the limbic system-dorsal prefrontal network (GM4-GM8); (2) Reduced functional connectivity of the edge system network-temporal lobe network (GM4-WM6); (3) The edge system network-sensorimotor network-vision network (GM4-GM3, WM5-WM8, and GM7) function connection is reduced (Figure 3).

。 The limbic system is an important network for emotional processing, and the reduced connectivity of the limbic system-dorsal prefrontal network may reflect the reduction in the regulation of the limbic system network by the prefrontal network, explaining the insufficient control of excessive emotional responses in patients with SAD; Patients with SAD have a wrong understanding of negative expressions, and show excessive vigilance and avoidance, the temporal lobe is involved in visual processing and object recognition, and responds to facial expression tasks, and the functional connection between the gray matter limbic system network and the adjacent white matter temporal lobe network is reduced, suggesting that the coordination between gray and white matter is weakened, which may be one of the mechanisms of SAD facial expression processing defects; The limbic system-sensorimotor network loop is involved in the regulation of fear response patterns to threat-related information, and the loss of connectivity between the limbic system network and the sensorimotor network may be related to decreased emotional regulation, while the reduced functional connectivity of the visual network and the sensorimotor network may reflect a perceived impairment
of social stimuli.

Fig.
4 Comparison results between SAD patients and healthy control brain network functional connection groups

5.
The severity and course of clinical symptoms of SAD are correlated with network functional connectivity

By extracting the functional connections and functional activities of the brain network in the SAD group with differences between groups, and performing Pearson correlation analysis with clinical symptoms and disease course, it was found that (1) the functional connections of the limbic system-prefrontal network and the limbic system-perceptual-motor network were negatively correlated with the HAMAD score, which provided further evidence for emotional regulation disorders in patients with SAD; (2) With the prolongation of the course of the disease, the weaker the interaction between the sensorimotor network and the visual network, indicating that there is a progressive abnormality in the functional integration between the above networks (Fig.
5).

Figure 5 Correlation analysis diagram

6.
There was no difference between groups in subgroup analysis between the functional connection of undrugged SAD and drug-administered SAD

To examine the potential effects of the drug, the team performed a subgroup analysis between undrugged and non-drugged patients and found no significant change in functional connectivity between drug-taking and non-drugged patients after Bonferroni correction (Figure 6).

Fig.
6 Subgroup analysis results

summary

Based on K-means clustering technology, this study explored the interaction between large-scale brain networks in patients with SAD, and revealed abnormal functional network connections with limbic system networks as the core, in which the loss of limbic system network-prefrontal network is considered to be the core neurophysiological change of SAD, which is related to abnormal emotional regulation of SAD, and the reduction of functional connections of limbic system networks-perception networks may be the basis of SAD perception abnormalities, and this study uses white matter function technology.
The discovery of white matter and gray matter dysfunction in patients with SAD based on limbic system networks and sensory network circuits has expanded our understanding of large-scale brain network dysfunction in SAD and revealed the potential role
of white matter functional networks in the neuropathological mechanism of SAD.

Related paper information

The research results are published in the iScience journal of Cell Press, click "Read More" or scan the QR code below to view the paper
.

▌Papers:

Large-scale dysfunctional white matter and grey matter networks in patients with social anxiety disorder

▌Paper URL:

style="white-space: normal;box-sizing: border-box;" _msthash="251167" _msttexthash="10239255">▌ DOI：

https://doi.
org/10.
1016/j.
isci.
2022.
105094

Long press the image recognition QR code to read the original article

In 1974, we published our first flagship journal, Cell
.
Today, CellPress has developed into an international cutting-edge academic publishing
house in the field of science with more than 50 journals.
We firmly believe that the power of science will always benefit mankind
.

CellPress Cell Press