Multimodal imaging reveals a complex pattern of dysfunction in corticolimbic pathways in major depressive disorder

Abstract

Major depressive disorder (MDD) is highly prevalent and associated with considerable morbidity, yet its pathophysiology remains only partially understood. While numerous studies have investigated the neurobiological correlates of MDD, most have used only a single neuroimaging modality. In particular, diffusion tensor imaging (DTI) studies have failed to yield uniform results. In this context, examining key tracts and using information from multiple neuroimaging modalities may better characterize potential abnormalities in the MDD brain. This study analyzed data from 30 participants with MDD and 26 healthy participants who underwent DTI, magnetic resonance spectroscopy (MRS), resting‐state functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG). Tracts connecting the subgenual anterior cingulate cortex (sgACC) and the left and right amygdala, as well as connections to the left and right hippocampus and thalamus, were examined as target areas. Reduced fractional anisotropy (FA) was observed in the studied tracts. Significant differences in the correlation between medial prefrontal glutamate concentrations and FA were also observed between MDD and healthy participants along tracts connecting the sgACC and right amygdala; healthy participants exhibited a strong correlation but MDD participants showed no such relationship. In the same tract, a correlation was observed between FA and subsequent antidepressant response to ketamine infusion in MDD participants. Exploratory models also suggested group differences in the relationship between DTI, fMRI, and MEG measures. This study is the first to combine MRS, DTI, fMRI, and MEG data to obtain multimodal indices of MDD and antidepressant response and may lay the foundation for similar future analyses.

Evaluating global brain connectivity as an imaging marker for depression: influence of preprocessing strategies and placebo-controlled ketamine treatment

“…All participants provided written informed consent after oral explanation of study procedures, which were approved by the NIH Combined Central Nervous System Institutional Review Board. Independent analyses and results from these studies have previously been published [6,[21][22][23][24].…”

Studying pre-treatment and ketamine-induced changes in white matter microstructure in the context of ketamine’s antidepressant effects

“…Whereas structural MRI is used to examine macroscopic structural properties of the brain (e.g., volume or cortical thickness), diffusion MRI (dMRI) is able to better characterize properties of tissue microstructure, most notably white matter (WM) microstructure 13 . Previous research has demonstrated that WM structure can be an important factor associated with clinical response to typical antidepressant medications 14,15 , yet only two studies to date have used dMRI to investigate the role of WM in patient response to ketamine treatment 16,17 .…”

Advances in multimodal data fusion in neuroimaging: Overview, challenges, and novel orientation

“…A study employed DTI, magnetic resonance spectroscopy (MRS), rs-fMRI, and magnetoencephalography (MEG) and revealed patterns of abnormalities of patients with major depressive disorders. These patterns included factors in the neurotransmitters (glutamate concentration), white matter fibers (fractional anisotropy), and functional excitations (fMRI) [157] . A multimodal MRI study involves structural MRI and ASL to assess grey matter volume and regional cerebral blood flow in MDD patients.…”