Brain circuits for maternal sensitivity and pain involving anterior cingulate cortex among mothers receiving buprenorphine treatment for opioid use disorder.

Opioid-induced deficits in maternal behaviors are well-characterized in rodent models. Amid the current epidemic of opioid use disorder (OUD), prevalence among pregnant women has risen sharply. Yet, the roles of buprenorphine replacement treatment for OUD (BT/OUD) in the brain functions of postpartum mothers are unclear. Using functional magnetic resonance imaging (fMRI), we have developed an evolutionarily conserved maternal behavior neurocircuit (MBN) model to study human maternal care versus defensive/aggressive behaviors critical to mother-child bonding. The anterior cingulate gyrus (ACC) is not only involved in the MBN for mother-child bonding and attachment, but also part of an opioid sensitive "pain-matrix". The literature suggests that prescription opioids produce physical and emotional "analgesic" effects by disrupting specific resting-state functional connectivity (rs-FC) of ACC to regions related to MBN. Thus, in this longitudinal study, we report findings of overlapping MBN and pain matrix circuits, for mothers with chronic exposure of BT/OUD. A total of 32 mothers were studied with 6 min rs-FC at 1 month (T1) and 4 months postpartum (T2), including seven on BT/OUD and 25 non-BT/OUD mothers as a comparison group. We analyzed rs-FC between the insula, putamen, and the dorsal anterior cingulate cortex (DACC) and rostral ACC (RACC), as the regions of interest that mediate opioid analgesia. BT/OUD mothers, as compared to non-BT/OUD mothers, showed less left insula-RACC rs-FC but greater right putamen-DACC rs-FC at T1, with these between-group differences diminished at T2. Some of these rs-FC results were correlated with the scores of postpartum parental bonding questionnaire. We found time-by-treatment interaction effects on DACC and RACC-dependent rs-FC, potentially identifying brain mechanisms for beneficial effects of BT, normalizing dysfunction of maternal brain and behavior over the first four months postpartum. This study complements recent studies to ascertain how BT/OUD affects maternal behaviors, mother-child bonding, and intersubjectivity and reveals potential MBN/pain-matrix targets for novel interventions.