Functional connectivity associations with menstrual pain characteristics in adolescents: an investigation of the triple network model

Abstract Menstrual pain is associated with deficits in central pain processing, yet neuroimaging studies to date have all been limited by focusing on group comparisons of adult women with vs without menstrual pain. This study aimed to investigate the role of the triple network model (TNM) of brain networks in adolescent girls with varied menstrual pain severity ratings. One hundred participants (ages 13-19 years) completed a 6-min resting state functional magnetic resonance imaging (fMRI) scan and rated menstrual pain severity, menstrual pain interference, and cumulative menstrual pain exposure. Imaging analyses included age and gynecological age (years since menarche) as covariates. Menstrual pain severity was positively associated with functional connectivity between the cingulo-opercular salience network (cSN) and the sensory processing regions, limbic regions, and insula, and was also positively associated with connectivity between the left central executive network (CEN) and posterior regions. Menstrual pain interference was positively associated with connectivity between the cSN and widespread brain areas. In addition, menstrual pain interference was positively associated with connectivity within the left CEN, whereas connectivity both within the right CEN and between the right CEN and cortical areas outside the network (including the insula) were negatively associated with menstrual pain interference. Cumulative menstrual pain exposure shared a strong negative association with connectivity between the default mode network and other widespread regions associated with large-scale brain networks. These findings support a key role for the involvement of TNM brain networks in menstrual pain characteristics and suggest that alterations in pain processing exist in adolescents with varying levels of menstrual pain.