Aberrant dynamic functional connectivity of thalamocortical circuitry in major depressive disorder

J Zhejiang Univ Sci B. 2024 Feb 24:1-21. doi: 10.1631/jzus.B2300401. Online ahead of print.
[Article in English, Chinese]

Abstract

Thalamocortical circuitry has a substantial impact on emotion and cognition. Previous studies have demonstrated alterations in thalamocortical functional connectivity (FC), characterized by region-dependent hypo- or hyper-connectivity, among individuals with major depressive disorder (MDD). However, the dynamical reconfiguration of the thalamocortical system over time and potential abnormalities in dynamic thalamocortical connectivity associated with MDD remain unclear. Hence, we analyzed dynamic FC (dFC) between ten thalamic subregions and seven cortical subnetworks from resting-state functional magnetic resonance images of 48 patients with MDD and 57 healthy controls (HCs) to investigate time-varying changes in thalamocortical FC in patients with MDD. Moreover, dynamic laterality analysis was conducted to examine the changes in functional lateralization of the thalamocortical system over time. Correlations between the dynamic measures of thalamocortical FC and clinical assessment were also calculated. We identified four dynamic states of thalamocortical circuitry wherein patients with MDD exhibited decreased fractional time and reduced transitions within a negative connectivity state that showed strong correlations with primary cortical networks, compared with the HCs. In addition, MDD patients also exhibited increased fluctuations in functional laterality in the thalamocortical system across the scan duration. The thalamo-subnetwork analysis unveiled abnormal dFC variability involving higher-order cortical networks in the MDD cohort. Significant correlations were found between increased dFC variability with dorsal attention and default mode networks and the severity of symptoms. Our study comprehensively investigated the pattern of alteration of the thalamocortical dFC in MDD patients. The heterogeneous alterations of dFC between the thalamus and both primary and higher-order cortical networks may help characterize the deficits of sensory and cognitive processing in MDD.

丘脑皮层环路对情绪和认知具有重大影响。研究表明,重度抑郁障碍患者存在丘脑皮层功能连接异常,主要表现为区域依赖性的低连接或超连接。然而,重度抑郁障碍患者丘脑皮层环路动态功能连接的潜在异常目前尚不清楚。因此,基于48名重度抑郁障碍患者和57名健康对照的静息态功能磁共振成像数据,本研究评估了10个丘脑亚区和大脑皮层之间的动态功能连接变化,进而探究重度抑郁障碍患者丘脑皮层环路的动态交互模式。利用动态偏侧性分析探究了丘脑皮层系统的功能偏侧性随时间的动态变化。此外,还计算了丘脑皮层环路的动态功能连接特征与临床量表评分之间的相关性。本研究确定了4个反复出现的丘脑皮层功能连接状态。与健康对照组相比,重度抑郁障碍患者在与初级皮层网络具有较强负相关的连接状态下,时间分数和状态转换概率显著降低。此外,重度抑郁障碍患者丘脑皮层系统的功能偏侧性表现出更大的波动。丘脑-子网络分析进一步发现重度抑郁障碍患者中丘脑与高阶皮层网络之间连接的变异性异常增加,并且与背侧注意网络和默认模式网络相关的丘脑皮层功能连接变异性与患者的症状严重程度之间存在显著的相关性。本研究综合探究了重度抑郁障碍患者丘脑皮层环路的动态功能连接变化模式。研究结果表明,丘脑与初级和高阶皮层网络之间动态功能连接的异质性改变可能有助于表征重度抑郁障碍患者的感觉和认知处理缺陷。.

Keywords: Dynamic functional connectivity; Dynamic laterality; Major depressive disorder; Resting-state functional magnetic resonance imaging; Thalamocortical circuitry.