title: Neural substrates of impulsive decision making modulated by modafinil in alcohol-dependent patients.
abstract: BACKGROUND
  Impulsive decision making is a hallmark of frequently occurring addiction disorders including alcohol dependence (AD). Therefore, ameliorating impulsive decision making is a promising target for the treatment of AD. Previous studies have shown that modafinil enhances cognitive control functions in various psychiatric disorders. However, the effects of modafinil on delay discounting and its underlying neural correlates have not been investigated as yet. The aim of the current study was to investigate the effects of modafinil on neural correlates of impulsive decision making in abstinent AD patients and healthy control (HC) subjects.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled, within-subjects cross-over study using functional magnetic resonance imaging (fMRI) was conducted in 14 AD patients and 16 HC subjects. All subjects participated in two fMRI sessions in which they either received a single dose of placebo or 200 mg of modafinil 2 h before the session. During fMRI, subjects completed a delay-discounting task to measure impulsive decision making.
  
  
  RESULTS
  Modafinil improved impulsive decision making in AD pateints, which was accompanied by enhanced recruitment of frontoparietal regions and reduced activation of the ventromedial prefrontal cortex. Moreover, modafinil-induced enhancement of functional connectivity between the superior frontal gyrus and ventral striatum was specifically associated with improvement in impulsive decision making.
  
  
  CONCLUSIONS
  These findings indicate that modafinil can improve impulsive decision making in AD patients through an enhanced coupling of prefrontal control regions and brain regions coding the subjective value of rewards. Therefore, the current study supports the implementation of modafinil in future clinical trials for AD.
authors: Amsterdam Institute for Addiction Research, Department of Psychiatry, Academic Medical Center,University of Amsterdam,Amsterdam,The Netherlands.
authors: L
authors: L
authors: Schmaal
authors: Amsterdam Institute for Addiction Research, Department of Psychiatry, Academic Medical Center,University of Amsterdam,Amsterdam,The Netherlands.
authors: A E
authors: AE
authors: Goudriaan
authors: Collaborative Antwerp Psychiatric Research Institute (CAPRI), Department of Psychiatry,University of Antwerp,Antwerp,Belgium.
authors: L
authors: L
authors: Joos
authors: Collaborative Antwerp Psychiatric Research Institute (CAPRI), Department of Psychiatry,University of Antwerp,Antwerp,Belgium.
authors: G
authors: G
authors: Dom
authors: Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam,VU University Medical Center,Amsterdam,The Netherlands.
authors: T
authors: T
authors: Pattij
authors: Amsterdam Institute for Addiction Research, Department of Psychiatry, Academic Medical Center,University of Amsterdam,Amsterdam,The Netherlands.
authors: W
authors: W
authors: van den Brink
authors: Department of Psychiatry,VU University Medical Center,Amsterdam,The Netherlands.
authors: D J
authors: DJ
authors: Veltman
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000188:drug therapy* / Q000503:physiopathology; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology; D018592:Cross-Over Studies; D065786:Delay Discounting / Q000187:drug effects* / Q000502:physiology; D004311:Double-Blind Method; D006801:Humans; D007175:Impulsive Behavior / Q000187:drug effects* / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D016896:Treatment Outcome; D066328:Ventral Striatum / Q000187:drug effects* / Q000503:physiopathology; D064690:Wakefulness-Promoting Agents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001559:Benzhydryl Compounds; D064690:Wakefulness-Promoting Agents; D000077408:Modafinil