Glutamate levels in the ventromedial prefrontal cortex and resting-state functional connectivity within reward circuits in alcohol-dependent patients.

Great progress has been made in understanding the neural mechanisms associated with alcohol-dependent (AD) patients. However, the interactions within the reward circuits of the patients need further exploration. Glutamatergic projections from the prefrontal cortex to some brain regions are present in the reward circuit. However, little is known about the potential implications of glutamate levels in the prefrontal cortex on abnormal interactions within reward circuits in AD patients. To determine the potential roles of reward circuits in drinking, we investigated differences in resting-state functional connectivity (RSFC) and multivariate Granger causality analysis between 20 AD patients and 20 healthy controls (HC). The neuroimaging findings were then correlated with clinical variables (alcohol use disorder identification test). The ventromedial prefrontal cortex (VmPFC) is believed to play a critical role in addiction disorders, and glutamatergic projections from the prefrontal cortex to several regions of the brain are present in reward circuits. Proton magnetic resonance spectroscopy was also performed to assess the difference in glutamate levels in VmPFC between AD patients and HC. The results showed that the strength of functional connectivity in the reward circuit was generally attenuated in AD patients, and the reciprocal enhancement of activity between the right insula, left thalamus and VmPFC was found to be significantly greater in AD patients. It is worth noting that although glutamate levels in the VmPFC did not show significant differences between the two groups, the level of glutamate in the VmPFC was significantly correlated with RSFC. We hope that the current findings will help us to develop new intervention models based on the important role of the VmPFC in AD.

Reduced resting-state functional connectivity and sleep impairment in abstinent male alcohol-dependent patients.

Alcohol dependence is associated with poor sleep quality, which has both been implicated with thalamocortical circuits function. To identify the possible roles of these circuits in the alcohol-sleep association, we investigated the volume of both left and right thalamus and corresponding resting-state functional connectivity (RSFC) differences between 15 alcohol-dependent patients (AD) and 15 healthy controls (HC) male participants. The neuroimaging findings were then correlated with clinical variables, that is, Alcohol Use Disorders Identification Test (AUDIT) and Pittsburgh Sleep Quality Index (PSQI). Additionally, mediation analysis was carried out to test whether the thalamocortical RSFC mediates the relationship between drinking behavior and sleep impairments in AD when applicable. We observed a significant positive correlation between AUDIT score and PSQI score in AD. Compared with HC, AD showed reduced RSFC between the left thalamus and medial prefrontal cortex (mPFC), orbitofrontal cortex, anterior cingulate cortex (ACC), and right caudate. We also observed a negative correlation between RSFC of the left thalamus-mPFC and PSQI score in AD. More importantly, the left thalamus-mPFC RSFC strength mediated the relationship between AUDIT score and PSQI score in AD. No significant difference was detected in the normalized volume of both left and right thalamus, and volumes were not significantly correlated with clinical variables. Our results demonstrate that AD show abnormal interactions within thalamocortical circuits in association with drinking behaviors and sleep impairments. It is hoped that our study focusing on thalamocortical circuits could provide new information on potential novel therapeutic targets for treatment of sleep impairment in alcohol-dependent patients.