title: Effects of modafinil on neural correlates of response inhibition in alcohol-dependent patients.
abstract: BACKGROUND
  Impaired response inhibition is a key feature of patients with alcohol dependence. Improving impulse control is a promising target for the treatment of alcohol dependence. The pharmacologic agent modafinil enhances cognitive control functions in both healthy subjects and in patients with various psychiatric disorders. However, very little is known about the underlying neural correlates of improvements in response inhibition following modafinil.
  
  
  METHODS
  We conducted a randomized, double-blind, placebo-controlled, crossover study using functional magnetic resonance imaging with a stop signal task to examine effects of a single dose of modafinil (200 mg) on response inhibition and underlying neural correlates in abstinent alcohol-dependent patients (AD) (n = 16) and healthy control subjects (n = 16).
  
  
  RESULTS
  Within the AD group modafinil administration improved response inhibition (reflected by the stop signal reaction time [SSRT]) in subjects with initial poor response inhibition, whereas response inhibition was diminished in better performing subjects. In AD patients with initial poor response inhibition, modafinil-induced SSRT improvement was accompanied by greater activation in the thalamus and supplementary motor area (SMA) and reduced connectivity between the thalamus and the primary motor cortex. In addition, the relationship between baseline response inhibition and modafinil-induced SSRT improvement was mediated by these changes in thalamus and SMA activation.
  
  
  CONCLUSIONS
  These findings indicate that modafinil can improve response inhibition in alcohol-dependent patients through its effect on thalamus and SMA function but only in subjects with poor baseline response inhibition. Therefore, baseline levels of response inhibition should be taken into account when considering treatment with modafinil in AD.
authors.affiliation: Amsterdam Institute for Addiction Research, Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. lianschmaal@gmail.com
authors.forename: Lianne
authors.initials: L
authors.lastname: Schmaal
authors.forename: Leen
authors.initials: L
authors.lastname: Joos
authors.forename: Marte
authors.initials: M
authors.lastname: Koeleman
authors.forename: Dick J
authors.initials: DJ
authors.lastname: Veltman
authors.forename: Wim
authors.initials: W
authors.lastname: van den Brink
authors.forename: Anna E
authors.initials: AE
authors.lastname: Goudriaan
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000503:physiopathology*; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D009415:Nerve Net / Q000187:drug effects / Q000503:physiopathology; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects* / Q000502:physiology
chemical_list: D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D000077408:Modafinil