Imbalanced functional architecture of anterior cingulate cortex subregions in unmedicated depression

619 

Abstract Submission 

Zilin Zhou¹, Yingxue Gao¹, Lingxiao Cao¹, Weijie Bao¹, Xinyue Hu¹, Hailong Li¹, Lianqing Zhang¹, Weihong Kuang², Qiyong Gong^1,3, Xiaoqi Huang¹

¹Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan, ²Mental Health Center, Department of Psychiatry, West China Hospital of Sichuan University, Chengdu, Sichuan, ³Department of Radiology, West China Xiamen Hospital of Sichuan University, Xiamen, Fujian

Zilin Zhou  
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Chengdu, Sichuan

Yingxue Gao  
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Chengdu, Sichuan

Lingxiao Cao  
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Chengdu, Sichuan

Weijie Bao  
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Chengdu, Sichuan

Xinyue Hu  
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Chengdu, Sichuan

Hailong Li  
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Chengdu, Sichuan

Lianqing Zhang  
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Chengdu, Sichuan

Weihong Kuang  
Mental Health Center, Department of Psychiatry, West China Hospital of Sichuan University
Chengdu, Sichuan

Qiyong Gong  
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University|Department of Radiology, West China Xiamen Hospital of Sichuan University
Chengdu, Sichuan|Xiamen, Fujian

Xiaoqi Huang  
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Chengdu, Sichuan

Dysconnectivity of anterior cingulate cortex (ACC), a functionally heterogenous region along its ventral-dorsal continuum (Dixon et al., 2017), fulfills a crucial role in major depressive disorder (MDD) (Mulders et al., 2015; Pizzagalli & Roberts, 2022). Most studies on functional connectivity of ACC subregional networks relied on a priori coordinates or anatomical atlas, which may not be optimally aligned with current functional data, potentially introducing bias. The well-developed data-driven connectivity-based parcellation technique (CBP) (Eickhoff et al., 2018) enables a more accurate representation of functional subregions within the ACC by leveraging their functional connectivity properties. Our research utilized ACC subdivisions derived from CBP to precisely delineate the fine-grained ACC subregional functional connectivity alterations in MDD.

We enrolled 168 unmedicated patients with first-episode MDD and 128 healthy controls (HC) matched for age, sex and education level. All subjects were scanned using 3T Siemens MRI scanner with an 8‐channel phased‐array head coil. Resting-state functional MRI and T1-weighted anatomical images were preprocessed through a standardized pipeline in DPABI. The CBPtools (Reuter et al., 2020) implemented in Python3.7 was employed to segment the entire ACC per hemisphere from automated anatomical labeling atlas (AAL2) into distinct subdivisions based on their resting-state functional connectivity (rsFC) with the rest of whole brain. Briefly, k-means clustering was applied to assign the ACC voxels into clusters with similar connectivity profiles at individual level, and group-level clustering incorporated relabeling individual clusters and computing mode of subject-wise relabeled clustering. Optimal cluster number was determined by Silhouette, Calinski-Harabasz and Davies-Bouldin indices. The rsFC maps of each ACC subregion were generated for all participants.
Diagnosis-by-subregion flexible-factorial analysis of variance was performed to evaluate group differences in ACC subregional rsFC patterns, controlling for age, sex and head motion, followed by post-hoc analysis using the simple effects test in SPSS24.0. Moreover, relationships between the rsFC alterations with illness duration and symptom severity in MDD group were explored via partial correlation, with age, sex and head motion as covariates.

Demographic and clinical information of all participants was detailed in Table 1. Two subdivisions of ACC per hemisphere, ventral ACC (vACC) and dorsal ACC (dACC), were identified according to all clustering quality metrics (Fig.1a/b). The ACC subregions obtained by CBP showed a similar spatial extent to those outlined in AAL3 (Fig.1c), and distinct rsFC patterns of vACC and dACC across all subjects were illustrated in Fig.1d.
Flexible-factorial analysis of variance revealed a significant diagnosis-by-subregion interaction in the bilateral posterior cingulate cortex (PCC), manifested by a significant hypoconnectivity of vACC and bilateral PCC and a tendency for hyperconnectivity of dACC and bilateral PCC in MDD relative to HC (Fig.2a). Notably, we observed positive correlations between rsFC of bilateral dACC and bilateral PCC with suicide risk, and between rsFC of right vACC and bilateral PCC with illness insight (Fig.2b). Main effect of diagnosis showed an enhancement in rsFC of left ACC and right orbitofrontal cortex and of right ACC and right opercular part of inferior frontal gyrus in MDD compared to HC (Fig.2a).

A bipartite ventral-dorsal ACC subdivision was identified using data-driven CBP, consistent with the Rolls et al. (2019). We further discovered an imbalanced connectivity pattern between ACC subregions and bilateral PCC in patients with MDD, which was potentially related to illness insight and suicide risk. Our findings underscore functional heterogeneity of the ACC along its ventral-dorsal axis and provide valuable insights into the fine-grained ACC subregional dysfunctions in MDD.

Psychiatric (eg. Depression, Anxiety, Schizophrenia) ¹

Connectivity (eg. functional, effective, structural) ²

ADULTS

FUNCTIONAL MRI

Psychiatric Disorders

Segmentation

Other - anterior cingulate cortex; major depressive disorder