Abnormal dynamic functional connectivity of hippocampal subregions associated with working memory impairment in melancholic depression

Abstract

Background Previous studies have demonstrated structural and functional changes of the hippocampus in patients with major depressive disorder (MDD). However, no studies have analyzed the dynamic functional connectivity (dFC) of hippocampal subregions in melancholic MDD. We aimed to reveal the patterns for dFC variability in hippocampus subregions – including the bilateral rostral and caudal areas and its associations with cognitive impairment in melancholic MDD. Methods Forty-two treatment-naive MDD patients with melancholic features and 55 demographically matched healthy controls were included. The sliding-window analysis was used to evaluate whole-brain dFC for each hippocampal subregions seed. We assessed between-group differences in the dFC variability values of each hippocampal subregion in the whole brain and cognitive performance on the MATRICS Consensus Cognitive Battery (MCCB). Finally, association analysis was conducted to investigate their relationships. Results Patients with melancholic MDD showed decreased dFC variability between the left rostral hippocampus and left anterior lobe of cerebellum compared with healthy controls (voxel p < 0.005, cluster p < 0.0125, GRF corrected), and poorer cognitive scores in working memory, verbal learning, visual learning, and social cognition (all p < 0.05). Association analysis showed that working memory was positively correlated with the dFC variability values of the left rostral hippocampus-left anterior lobe of the cerebellum (r = 0.338, p = 0.029) in melancholic MDD. Conclusions These findings confirmed the distinct dynamic functional pathway of hippocampal subregions in patients with melancholic MDD, and suggested that the dysfunction of hippocampus-cerebellum connectivity may be underlying the neural substrate of working memory impairment in melancholic MDD.

Reduced hippocampal gray matter volume is a common feature of patients with major depression, bipolar disorder, and schizophrenia spectrum disorders

“…While previous studies had linked verbal memory to hippocampal volume, our findings show associations with working memory/executive function, which has also been documented in several previous studies (e.g [80,[82][83][84]). However, our results go beyond these findings, as we demonstrated that these effects are not related to the traditional, descriptive diagnoses, but apply to all patients and healthy controls on a dimensional level.…”

Abnormal degree centrality values as a potential imaging biomarker for major depressive disorder: A resting-state functional magnetic resonance imaging study and support vector machine analysis

“…The hippocampus is an important region involved in memory and cognitive function ( 32 ), composed of different subregions interacting with varying areas of the brain, resulting in a neuro-anatomical network of emotion regulation and cognitive processing ( 33 ). For instance, the hippocampal volume of patients with MDD depreciated substantially ( 34 , 35 ) and elevated after electroconvulsive therapy (ECT) relative to HCs ( 36 ).…”

Shared and specific dynamics of brain activity and connectivity in amnestic and nonamnestic mild cognitive impairment

“…Previous studies provided the range of the appropriate window length as 10–75 TR, step = 1 TR, and a moderate sliding window length may maximize the statistical power, because it may be an optimal balance between capturing rapidly shifting dynamic relationships (with shorter windows) and achieving reliable estimates of the correlations between regions (with longer windows) 2,64 . Additionally, a sliding window size of 50 TR and a window step of 1 TR has been repeatedly used in previous studies, and they were able to capture the dynamics 65–68 . Therefore, the present study applied a sliding window size of 50 TR and a window step of 1 TR to calculate the dReHo and dFC.…”

“…2,64 Additionally, a sliding window size of 50 TR and a window step of 1 TR has been repeatedly used in previous studies, and they were able to capture the dynamics. [65][66][67][68] Therefore, the present study applied…”