TY - JOUR
T1 - Modulatory effects of modafinil on neural circuits regulating emotion and cognition
AU - Rasetti, Roberta
AU - Mattay, Venkata S.
AU - Stankevich, Beth
AU - Skjei, Kelsey
AU - Blasi, Giuseppe
AU - Sambataro, Fabio
AU - Arrillaga-Romany, Isabel C.
AU - Goldberg, Terry E.
AU - Callicott, Joseph H.
AU - Apud, José A.
AU - Weinberger, Daniel R.
N1 - Funding Information:
This research was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health. We thank Saumitra Das, MA, Guilna Alce, BS, Ajay Premkumar, Alan Lazerow, BA, and Natkai Akbar, BS, for their invaluable research assistance. We thank Steven H Gorman, BS, and Alexander Kogan, BS, Cephalon, Inc., for information related to measurement of plasma modafinil levels, and Cephalon, Inc., for the measurement of plasma modafinil levels.
PY - 2010/9
Y1 - 2010/9
N2 - 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.
AB - 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.
KW - Modafinil
KW - amygdala
KW - cognitive processing
KW - emotion
KW - fMRI
KW - healthy volunteers
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U2 - 10.1038/npp.2010.83
DO - 10.1038/npp.2010.83
M3 - Article
C2 - 20555311
AN - SCOPUS:77955715528
SN - 0893-133X
VL - 35
SP - 2101
EP - 2109
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 10
ER -