Aberrant dynamic functional connectivity of the subcortical structures in subthreshold depression

567 

Abstract Submission 

Siying Zhang¹, Qiwen Lin¹, Changyi Kuang¹, Yuanyun He¹, Bingqing Jiao¹, Huiyuan Huang², Lijun Ma¹, Jiabao Lin¹

¹School of Public Health and Management, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, ²Guangzhou University of Chinese medicine, Guangzhou, Guangdong Province

Siying Zhang  
School of Public Health and Management, Guangzhou University of Chinese Medicine
Guangzhou, Guangdong Province

Qiwen Lin  
School of Public Health and Management, Guangzhou University of Chinese Medicine
Guangzhou, Guangdong Province

Changyi Kuang  
School of Public Health and Management, Guangzhou University of Chinese Medicine
Guangzhou, Guangdong Province

Yuanyun He  
School of Public Health and Management, Guangzhou University of Chinese Medicine
Guangzhou, Guangdong Province

Bingqing Jiao  
School of Public Health and Management, Guangzhou University of Chinese Medicine
Guangzhou, Guangdong Province

Huiyuan Huang  
Guangzhou University of Chinese medicine
Guangzhou, Guangdong Province

Lijun Ma  
School of Public Health and Management, Guangzhou University of Chinese Medicine
Guangzhou, Guangdong Province

Jiabao Lin  
School of Public Health and Management, Guangzhou University of Chinese Medicine
Guangzhou, Guangdong Province

Subthreshold depression (StD) could be a significant precursor and a risk factor for major depressive disorder (Zhang et al., 2022). StD individuals generally show mild depressive symptoms in clinical practice, but they do not meet the standardized diagnostic criteria for major depressive disorder (Rodriguez et al., 2012). Previous studies based on functional magnetic resonance imaging (fMRI) have demonstrated that StD appears to be closely correlated with subcortical regions. A study revealed that functional connectivity (FC) was increased between the default mode network and ventral striatum in StD patients compared with healthy controls (Hwang et al., 2016). And Peng et al (2020) found decreased FC between the left amygdala and both the cognitive control network and left insula in individuals with StD. However, these studies mainly focused on static FC but ignored the temporal dynamics of FC. Recent studies have suggested that dynamic FC (dFC) may reveal a great deal of information regarding the brain's time-varying neural activity (Calhoun et al., 2014; Rashid et al., 2016). Therefore, the present study attempted to investigate the differences in the dFC of the subcortical regions between the StD individuals and healthy controls.

In this study, all neuroimaging data used were obtained from the Southwest University Longitudinal Imaging Multimodal (SLIM) Brain Data Repository (Liu et al., 2017) and this study was approved by the Research Ethics Committee of the Brain Imaging Center of Southwest University. Participants with Beck Depression Inventory (BDI) scores between 14-29 were entered into the StD group, and those with BDI scores between 0-6 belonged to the healthy control (HC) group. After screening, there were 50 participants in the StD group and 50 participants in the HC group. The two groups were matched for age, gender, state anxiety score, trait anxiety score, and mean framewise displacement (FD, representing head motion)(Table 1).
Sixteen subcutaneous nuclei were extracted as the regions of interest (ROIs) using the Harvard–Oxford subcortical structural 25% probability atlas. The dFC analysis was carried out using the sliding-window approach (Allen et al., 2014) by DynamicBC toolbox (Liao et al., 2014). For each sliding window, a whole-brain FC map of each ROI was obtained by calculating the Person correlation coefficient between each ROI and each voxel of the whole brain. Then, based on all windows, we computed the variance of each ROI's FC maps (the variance value in each voxel). Finally, between-group comparisons of the variance were performed using the two-sample t-test within DPABI (Yan et al., 2016). These analyses were carried out with multiple comparisons correction using GRF correction (voxel-level p < 0.001, cluster-level p < 0.05).

Compared with the HC group, we found that the StD group showed significantly decreased dFC variance of subcutaneous nuclei with the whole brain. Those brain region pairs include the following: (1) the left caudate with the left median cingulate gyrus (MCG), left cerebellum (CBM), and left superior parietal gyrus (SPG); (2) the right caudate with the right/ left thalamus and left CBM; (3) the left amygdala with the left supramarginal gyrus (SMG) and left MCG; (4) the left brainstem with the right posterior central gyrus (PCG); (5) the right putamen with the left SMG; (6) the right pallidum with the left inferior frontal gyrus (IFG) and left SMG (Table 2 and Figure 1).

In summary, we found the StD group exhibited a significant reduction in temporal variability of dFC in the extensive subcutaneous nucleus compared to the HC group, highlighting an aberrant dFC pattern in StD. Importantly, these dysfunctional regions are particularly involved in the dFC of caudate with MCG and amygdala with MCG, mainly associated with emotional processing functions. Our findings supported and extended the understanding of the subcortical structures in StD.

Psychiatric (eg. Depression, Anxiety, Schizophrenia) ¹

BOLD fMRI ²

MRI

Sub-Cortical

Other - subthreshold depression, dynamic functional connectivity, subcutaneous nuclei