Modafinil modulates resting-state functional network connectivity and cognitive control in alcohol-dependent patients

Chronic alcohol abuse is associated with deficits in cognitive control functions. Cognitive control is likely to be mediated through the interaction between intrinsic large-scale brain networks involved in externally oriented executive functioning and internally focused thought processing. Improving the interaction between these functional brain networks could be an important target for treatment. Therefore, the current study aimed to investigate the effects of the cognitive enhancer modafinil on within-network and between-network resting-state functional connectivity and cognitive control functions in alcohol-dependent patients. In a double-blind, placebo-controlled cross-over design, resting-state functional magnetic resonance imaging and a Stroop task were employed in alcohol-dependent patients (n = 15) and healthy control subjects (n = 16). Within-network and between-network functional connectivity was calculated using a combination of independent component analysis and functional network connectivity analysis. Modafinil significantly increased the negative coupling between executive networks and the default mode network, which was associated with modafinil-induced improvement in cognitive control in alcohol-dependent patients. These findings demonstrate that modafinil at least partly exerts its effects by targeting intrinsic functional relationships between large-scale brain systems underlying cognitive control. The current study therefore provides a neurobiological rationale for implementing modafinil as an adjunct in the treatment of alcohol dependence, although clinical studies are needed to substantiate this promise