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. 2023 Sep;13(9):e3027.
doi: 10.1002/brb3.3027. Epub 2023 Jul 18.

Abnormality of anxious behaviors and functional connectivity between the amygdala and the frontal lobe in maternally deprived monkeys

Xiao-Li Feng  1   2   3 , Jiao-Jian Wang  4   5 , Jing Wu  1 , Xiao-Feng Ren  1   6 , Hui Zhou  2 , Si-Yu Li  2 , Jie Zhang  7 , Sheng-Hai Wang  7 , Yun Wang  8 , Zheng-Fei Hu  8 , Xin-Tian Hu  1   8   9 , Tian-Zi Jiang  10   11   12
Affiliations

Abnormality of anxious behaviors and functional connectivity between the amygdala and the frontal lobe in maternally deprived monkeys

Xiao-Li Feng et al. Brain Behav. 2023 Sep.

Abstract

Objective: Anxious behaviors often occur in individuals who have experienced early adversity. Anxious behaviors can bring many hazards, such as social withdrawal, eating disorders, negative self-efficacy, self-injurious thoughts and behaviors, anxiety disorders, and even depression. Abnormal behavior are is closely related to changes in corresponding circuit functions in the brain. This study investigated the relationship between brain circuits and anxious behaviors in maternal-deprived rhesus monkey animal model, which mimic early adversity in human.

Methods: Twenty-five rhesus monkeys (Macaca mulatta) were grouped by two different rearing conditions: 11 normal control and mother-reared (MR) monkeys and 14 maternally deprived and peer-reared (MD) monkeys. After obtaining images of the brain areas with significant differences in maternal separation and normal control macaque function, the relationship between functional junction intensity and stereotypical behaviors was determined by correlation analysis.

Results: The correlation analysis revealed that stereotypical behaviors were negatively correlated with the coupling between the left lateral amygdala subregion and the left inferior frontal gyrus in both MD and MR macaques.

Conclusion: This study suggests that early adversity-induced anxious behaviors are associated with changes in the strength of the amygdala-prefrontal connection. The normalization of the regions involved in the functional connection might reverse the behavioral abnormality. It provides a solid foundation for effective intervention in human early adversity.

Significance statement: This study suggests that early adversity-induced anxious behaviors are associated with changes in the strength of the amygdala-prefrontal connection. The higher the amygdala-prefrontal connection strength, the less stereotyped behaviors exhibited by monkeys experiencing early adversity. Thus, in the future, changing the strength of the amygdala-prefrontal connection may reverse the behavioral abnormalities of individuals who experience early adversity. This study provides a solid foundation for effective intervention in humans' early adversity.

Keywords: amygdala-prefrontal connection; anxious behaviors; brain circuits; maternal deprivation; rhesus monkeys.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
The framework of this study. (A) Definition of the bilateral amygdala in rhesus monkeys, (B) mapping the whole brain anatomical connectivity pattern for each voxel in amygdala, (C) calculating the whole brain anatomical connectivity similarity of each pair of voxels in amygdala (D) selecting the number of clusters based on silhouette and overlap degree indices, (E) parcellation results of amygdala, (F) whole brain functional connectivity analysis for each amygdala subregion.
FIGURE 2
FIGURE 2
Comparison of the duration of stereotyped behaviors between the maternally deprived and peer‐reared (MD) monkeys and normal control and mother‐reared monkey (MR) monkeys. Compared to MR monkeys (n = 11, blue dots), the duration of stereotyped behaviors in MD monkeys (n = 14, red triangles) was significantly increased (Mann–Whitney U‐test, U = 26, p = .0039).
FIGURE 3
FIGURE 3
Anatomical connectivity based parcellation of bilateral amygdala. Anatomical connectivity‐based parcellation identified two subregions in left and right amygdala. One cluster is located in the lateral amygdala (red one) and the other one is located in the medial amygdala (green one).
FIGURE 4
FIGURE 4
Whole brain functional connectivity differences of amygdala subregion in MD monkeys. Whole brain functional connectivity analysis identified significantly lower functional connectivity between left lateral subregion of amygdala and the left inferior frontal gyrus (IFG) in MD than MR monkeys. After calculating the mean FC between left lateral amygdala subregion and IFG, compared to MR monkeys (n = 11, blue dots), the functional connectivity in MD monkeys (n = 14, red triangles) was significantly decreased (independent samples t‐test, t = 3.552, p = .0017).
FIGURE 5
FIGURE 5
The correlation between stereotyped behaviors and the connectivity between left lateral amygdala subregion and left IFG in both MD and MR monkeys. Stereotyped behaviors were negatively correlated with the coupling between the left lateral amygdala subregion and the left IFG in both MD (n = 14, red triangles) and MR (n = 11, blue dots) monkeys (Pearson correlation analysis, r = −0.5451, p = .0048).
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