Multiscale neural modeling of resting-state fMRI reveals executive-limbic malfunction as a core mechanism in major depressive disorder

NeuroImage: Clinical

卷:31

Danian Li¹  Pew-Thian Yap¹  Ye Wu²  Ying Cui²  Yaoping Chen³  Yanting Zheng³  Han Zhang⁴  Xinyu Liang⁵  Yujie Liu⁵  Guoshi Li⁵  Shijun Qiu⁵  Dinggang Shen⁶ 

[1] Department of Radiology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China;

[2] Department of Radiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China;

[3] The First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China;

[4] Cerebropathy Center, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China;

[5] Department of Radiology and BRIC, University of North Carolina at Chapel Hill, Chapel Hill, NC USA;

关键词: Neural mass model;    Effective connectivity;    Resting-state fMRI;    Major depressive disorder;    Genetic algorithm;    Brain networks;   

DOI  :  

来源: DOAJ

【 摘 要 】

Major depressive disorder (MDD) represents a grand challenge to human health and society, but the underlying pathophysiological mechanisms remain elusive. Previous neuroimaging studies have suggested that MDD is associated with abnormal interactions and dynamics in two major neural systems including the default mode - salience (DMN-SAL) network and the executive - limbic (EXE-LIM) network, but it is not clear which network plays a central role and which network plays a subordinate role in MDD pathophysiology. To address this question, we refined a newly developed Multiscale Neural Model Inversion (MNMI) framework and applied it to test whether MDD is more affected by impaired circuit interactions in the DMN-SAL network or the EXE-LIM network. The model estimates the directed connection strengths between different neural populations both within and between brain regions based on resting-state fMRI data collected from normal healthy subjects and patients with MDD. Results show that MDD is primarily characterized by abnormal circuit interactions in the EXE-LIM network rather than the DMN-SAL network. Specifically, we observe reduced frontoparietal effective connectivity that potentially contributes to hypoactivity in the dorsolateral prefrontal cortex (dlPFC), and decreased intrinsic inhibition combined with increased excitation from the superior parietal cortex (SPC) that potentially lead to amygdala hyperactivity, together resulting in activation imbalance in the PFC-amygdala circuit that pervades in MDD. Moreover, the model reveals reduced PFC-to-hippocampus excitation but decreased SPC-to-thalamus inhibition in MDD population that potentially lead to hypoactivity in the hippocampus and hyperactivity in the thalamus, consistent with previous experimental data. Overall, our findings provide strong support for the long-standing limbic-cortical dysregulation model in major depression but also offer novel insights into the multiscale pathophysiology of this debilitating disease.

【 授权许可】

Unknown