title: Modafinil modulation of the default mode network.
abstract: BACKGROUND
  The default mode network (DMN) is a functional network which is implicated in a range of cognitive processes. This network is proposed to consist of hubs located in the ventromedial prefrontal cortex (vmPFC), posterior cingulate/retrosplenial cortex (PCC/rSpl), and inferior parietal lobule (IPL), with other midline cortical and temporal lobe nodes connected to these hubs. How this network is modulated by neurochemical systems during functional brain activity is not yet understood.
  
  
  OBJECTIVE
  In the present study, we used the norepinephrine/dopamine transporter inhibitor modafinil to test the hypothesis that this drug modulates the DMN.
  
  
  METHODS
  Eighteen healthy right-handed adults participated in a double-blind, placebo-controlled study of single oral dose modafinil 200 mg. They performed a simple visual sensorimotor task during slow event-related fMRI. Drug effects were interrogated within the DMN defined by task-induced deactivation (TID) on placebo.
  
  
  RESULTS
  There was a trend toward faster reaction time (RT) on modafinil (Cohen's d = 0.38). Brain regions within the DMN which exhibited significant modafinil-induced augmentation of TID included vmPFC, PCC/rSpl, and left IPL. Across subjects, the modafinil effect on TID in the vmPFC was significantly and specifically associated with drug effects on RT speeding.
  
  
  CONCLUSIONS
  Modafinil augments TID in the DMN to facilitate sensorimotor processing speed, an effect which may be particularly dependent on changes in vmPFC activity. This is consistent with the gain control function of catecholamine systems and may represent an important aspect of the pro-cognitive effects of modafinil.
authors.affiliation: Department of Psychiatry, University of California, Davis School of Medicine, Sacramento, CA, USA. michael.minzenberg@ucdmc.ucdavis.edu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Minzenberg
authors.forename: Jong H
authors.initials: JH
authors.lastname: Yoon
authors.forename: Cameron S
authors.initials: CS
authors.lastname: Carter
mesh_terms: D000328:Adult; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002395:Catecholamines / Q000378:metabolism; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D000077408:Modafinil; D009415:Nerve Net / Q000187:drug effects* / Q000502:physiology; D009483:Neuropsychological Tests; D010296:Parietal Lobe / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D011597:Psychomotor Performance / Q000187:drug effects* / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012146:Rest / Q000502:physiology
chemical_list: D001559:Benzhydryl Compounds; D002395:Catecholamines; D000077408:Modafinil