Altered task modulation of global signal topography in the default-mode network of unmedicated major depressive disorder

Background: Altered global signal (GS) topography features in the resting-state fMRI of major depressive disorder (MDD), showing abnormally strong global signal representation in the default-mode network (DMN). Whether the abnormal local to global change also shapes activity during task states, and how it relates to psychopathological symptoms, e.g., abnormally slow time speed of motor, cognitive, and affective symptoms, remains unknown. Methods: We investigated fMRI-based GS with its topographical representation during task states in unmedicated 51 MDD subjects and 28 healthy subjects. Task-related global signal correlation (GSCORR) was probed by a novel paradigm testing the processing of negative/neutral emotions during different time speeds, i.e., slow and fast. Results: We observed a significant interaction between time speed and emotion of GSCORR in various DMN regions in healthy subjects. Next, we showed that MDD exhibits reduced task-related GSCORR in various DMN regions during specifically the fast processing of negative emotions. Finally, we demonstrated that GSCORR in DMN and other brain regions (motor-related regions, inferior frontal cortex) correlated with the degree of psychomotor retardation especially during the fast emotional stimuli. Limitations: The measurement of interoceptive variables like respiration rate or heart rate were not included in our fMRI acquisition. Conclusion: Together, we demonstrated the functional relevance of GS topography by showing reduced GSCORR in DMN during specifically the fast processing of negative emotions in MDD, suggesting the abnormal slowness, i.e., reduced time speed, to be a key feature of both brain and symptoms in MDD.