Orbitofrontal, dorsal striatum, and habenula functional connectivity in psychiatric patients with substance use...

Substance abuse is commonly defined as the persistence of drug use despite negative consequences. Recent preclinical work has shown that higher input from the orbitofrontal cortex (OFC) to the dorsal striatum was associated with compulsive reward-seeking behavior despite negative effects. It remains unknown whether drug use is associated with the connectivity between the OFC and dorsal striatum in humans. We studied the resting state functional connectivity (RSFC) between the OFC, dorsal striatum, and habenula (and the whole brain in a separate analysis) in psychiatric inpatients with high (PU, problem users) and low (LU, low users) substance use. We matched PU and LU for psychiatric comorbidities. We found that PU showed higher RSFC between the left OFC and the left dorsal striatum than LU. RSFC between the habenula and both OFC and dorsal striatum was also higher in PU, which suggests the habenula may be a part of the same circuit. Finally, higher RSFC between the OFC and insula was also observed in PU. Our data shows that OFC, habenula, dorsal striatum, and insula may play an important role in PU. Furthermore, we postulate that the habenula may link the mesolimbic and cortico-striatal systems, which are altered in PU.