Abnormal coupling among spontaneous brain activity metrics and cognitive deficits in major depressive disorder

Background: A variety of functional metrics derived from resting-state functional magnetic resonance imaging (rs-fMRI) have been employed to explore spontaneous brain activity changes in major depressive disorder (MDD) and have enjoyed significant success in unraveling the neurobiological mechanisms underlying this disorder. However, it is unclear whether spatial and temporal coupling relationships among these rs-fMRI metrics are altered in MDD.

Methods: 50 patients with MDD and 36 well-matched healthy controls underwent rs-fMRI scans. A dynamic analysis was applied to compute multiple frequently used metrics including fractional amplitude of low frequency fluctuations, regional homogeneity, voxel-mirrored homotopic connectivity, degree centrality and global signal connectivity. Kendall's W was used to calculate volume-wise (across voxels) and voxel-wise (across time windows) concordance among these metrics. Inter-group differences in the concordance and their associations with clinical and cognitive variables were tested.

Results: Compared to healthy controls, patients with MDD showed decreased whole gray matter volume-wise concordance. Despite similar spatial distributions, quantitative comparison analysis revealed that MDD patients exhibited reduced voxel-wise concordance in multiple cortical and subcortical regions. Moreover, the lower concordance was associated with worse performances in prospective memory and sustained attention in the MDD group.

Limitations: The study design of fairly modest sample size did not allow us to perform a full analysis of the potential effects of medication and illness duration.

Conclusions: Our findings suggest that spatial and temporal decoupling of multiple resting-state brain activity metrics may help elucidate the neural mechanisms of cognitive deficits in depression.