EEG microstate as a biomarker of personalized transcranial magnetic stimulation treatment on anhedonia in depression

Anhedonia, a core feature of major depressive disorder (MDD), presents significant treatment challenges with conventional methods. Circuit-targeted, personalized repetitive transcranial magnetic stimulation (rTMS) has shown potentiation by focusing on disruptions in specific networks related to anhedonia. However, how rTMS modulates brain network dynamics in anhedonia is not yet fully understood. This research sought to explore these effects using EEG microstate analysis. In this double-blind, randomized, sham-controlled study, resting-state functional MRI was employed to pinpoint the left dorsolateral prefrontal cortex (DLPFC) region that exhibited the strongest functional connectivity to the nucleus accumbens (NAcc), used as the target for rTMS stimulation. Rest-state EEG data from 49 depressive patients with anhedonia(active=26, sham=23) were analyzed both at baseline and after treatment. In addition, a group of 15 healthy participants was included to serve as baseline controls. Resting-state EEG data were collected at baseline and post-treatment. Using polarity-insensitive k-means clustering, EEG microstates were segmented into five categories (A-E). Circuit-targeted rTMS significantly alleviated symptoms of anhedonia and depression. Compared to healthy controls, patients with anhedonia showed reduced microstate B and C occurrence, along with increased microstate D duration. After rTMS targeting the DLPFC-NAcc pathway, the active treatment group exhibited normalization of microstate C occurrence and a reduction in microstate E duration. Notably, the increase in microstate C was significantly correlated with improvements in anticipatory anhedonia, and these changes were observed specifically in treatment responders. The findings suggest that microstate C is linked to anhedonia and could serve as a reliable biomarker for personalized rTMS treatment. These results provide insights into the neural mechanisms underlying rTMS for anhedonia and highlight the potential of EEG microstate analysis in guiding personalized treatment strategies for depression.