Changes in Spontaneous Alpha—Gamma Coupling in Primary Dysmenorrhea

[[abstract]]Women of reproductive age who experience cyclic menstrual pain without pelvic abnormalities are considered primary dysmenorrhea (PDM). While our earlier research discovered the associations between BDNF Val66Met polymorphism and functional changes in the descending pain modulatory systems in PDM, as well as weakened slow/fast interconnections across the menstrual cycle, there is a lack of understanding of how BDNF Val66Met polymorphism influences neural oscillations across the menstrual cycle. This study aimed to address this gap by investigating the effects of gene polymorphism on resting-state oscillations during and after long-term menstrual discomfort. Resting-state magnetoencephalography (MEG) recordings were evaluated for n:m cross-frequency coupling (CFC) in 50 individuals with PDM and 49 healthy women (CON). Psychological assessments and cross-frequency couplings at each menstruation (MENS) and periovulatory (POV) period were compared between BDNF Val66Met gene polymorphisms. The state-anxiety scale for CON with Met/Met was inversely correlated with alpha/gamma phase-phase coupling in the left superior parietal regions during menstruation. In contrast, PDM with Met/Met showed an inverse pattern of n:m CFC couplings. Altered functional coupling in pain-related regions may arise from the interaction between the BDNF Val66Met genotyping and long-term pain experience, ultimately affecting the perception, emotion, and attention to pain in those experiencing cyclic pain.