title: Modulatory effects of modafinil on neural circuits regulating emotion and cognition.
abstract: Modafinil differs from other arousal-enhancing agents in chemical structure, neurochemical profile, and behavioral effects. Most functional neuroimaging studies to date examined the effect of modafinil only on information processing underlying executive cognition, but cognitive enhancers in general have been shown to have pronounced effects on emotional behavior, too. We examined the effect of modafinil on neural circuits underlying affective processing and cognitive functions. Healthy volunteers were enrolled in this double-blinded placebo-controlled trial (100 mg/day for 7 days). They underwent BOLD fMRI while performing an emotion information-processing task that activates the amygdala and two prefrontally dependent cognitive tasks-a working memory (WM) task and a variable attentional control (VAC) task. A clinical assessment that included measurement of blood pressure, heart rate, the Hamilton anxiety scale, and the profile of mood state (POMS) questionnaire was also performed on each test day. BOLD fMRI revealed significantly decreased amygdala reactivity to fearful stimuli on modafinil compared with the placebo condition. During executive cognition tasks, a WM task and a VAC task, modafinil reduced BOLD signal in the prefrontal cortex and anterior cingulate. Although not statistically significant, there were trends for reduced anxiety, for decreased fatigue-inertia and increased vigor-activity, as well as decreased anger-hostility on modafinil. Modafinil in low doses has a unique physiologic profile compared with stimulant drugs: it enhances the efficiency of prefrontal cortical cognitive information processing, while dampening reactivity to threatening stimuli in the amygdala, a brain region implicated in anxiety.
authors.affiliation: Clinical Brain Disorders Branch: Genes, Cognition, and Psychosis Program, NIMH, NIH, Bethesda, MD 20892, USA.
authors.forename: Roberta
authors.initials: R
authors.lastname: Rasetti
authors.forename: Venkata S
authors.initials: VS
authors.lastname: Mattay
authors.forename: Beth
authors.initials: B
authors.lastname: Stankevich
authors.forename: Kelsey
authors.initials: K
authors.lastname: Skjei
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Blasi
authors.forename: Fabio
authors.initials: F
authors.lastname: Sambataro
authors.forename: Isabel C
authors.initials: IC
authors.lastname: Arrillaga-Romany
authors.forename: Terry E
authors.initials: TE
authors.lastname: Goldberg
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Callicott
authors.forename: José A
authors.initials: JA
authors.lastname: Apud
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Weinberger
mesh_terms: D000328:Adult; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D001921:Brain / Q000098:blood supply / Q000187:drug effects*; D001931:Brain Mapping; D003071:Cognition / Q000187:drug effects*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004644:Emotions / Q000187:drug effects*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D000077408:Modafinil; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D013223:Statistics as Topic
chemical_list: D001559:Benzhydryl Compounds; D018696:Neuroprotective Agents; D000077408:Modafinil; D010100:Oxygen