Increased Resting Brain Entropy in Mild to Moderate Depression was Decreased by Nonpharmacological Treatment

Abstract Entropy indicates systematic irregularity and information capacity. Recent years have seen increasing interest in assessing regional brain entropy (BEN) using fMRI in healthy controls (HCs) and patients with various brain diseases. Depression and anti-depressant related BEN alterations have been reported in several initial studies. Re-examining these effects using independent cohort is crucial given the high complexity of depression. In this study, we used open data from OpenNeuro from 46 mild to moderate depression patients and 20 HCs to examine regional BEN and its changes due to nonpharmacological treatment (14 patients underwent nonpharmacological treatment). Functional connectivity (FC) analysis was performed to assess the inter-regional relationship between the brain regions showing BEN effects and the rest of the brain. Compared to HCs, depression patients showed increased BEN in left DLPFC, precuneus, and limbic system, including the amygdala, parahippocampal gyrus and hippocampus. Increased BEN in DLPFC, precuneus, and amygdala were suppressed by a nonpharmacological treatment in each individual patient. HCs had positive FC between left and right DLPFC and negative FC between left DLPFC and limbic areas, while patients had abnormally lower or negative FC between left and right DLPFC and positive FC between left DLPFC and the limbic area. These left DLPFC seeded FC changes in patients were reverted after nonpharmacological treatment. The findings highlight the left DLPFC and limbic system in depression and the treatment effects, and patients with depression exhibit significant emotion dysregulation, which is effectively addressed by nonpharmacological treatment targeting the top-down emotion regulation functions mediated by the DLPFC-limbic system. Different from existing literature, these results suggest the entropy/irregularity of DLPFC and limbic system as a potential mechanism underlying depression and suggest BEN in left DLPFC as a potential personalized marker for assessing depression and the corresponding nonpharmacological treatment effects.