Modulatory Effects of Modafinil on Neural Circuits Regulating Emotion and Cognition
Open accessAbstract
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.
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In healthy adults, modafinil decreases amygdala activation during the viewing of fearful stimuli and boosts prefrontal cortical activation during executive functions.
“In healthy adults, modafinil decreases amygdala activation during the viewing of fearful stimuli and boosts prefrontal cortical activation during executive functions (132).”
From Emotion Dysregulation in Attention Deficit Hyperactivity Disorder (2014) · cites this paper as [132]
The Results (Neuroimaging Data) support the claim that modafinil lowered amygdala activation during processing of fearful and angry faces. But the Abstract and Discussion report reduced, not boosted, prefrontal activation during executive-cognition tasks. The second half of the attributed claim reverses the paper’s finding. (LLM, conf=0.92)
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Cites
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“…by catecholaminergic neurons and is similar to the results of numerous neuroimaging studies in the literature involving catecholaminergic effects (eg, Apud et al, 2007; Cools et al, 2002; Cools and Robbins, 2004; Gibbs and D’Esposito, 2005, 2006; Mattay et al, 2002, 2003; Mehta et al, 2000).”
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- Authors
- Rasetti, R., Mattay, V. S., Stankevich, B., Skjei, K., Blasi, G., Sambataro, F., Arrillaga-Romany, I. C., Goldberg, T. E., Callicott, J. H., Apud, J. A., & Weinberger, D. R.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Weinberger, Daniel R
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2010-06-16
- Volume
- 35
- Issue
- 10
- Pages
- 2101-2109
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3013347
- OpenAlex
- W2093959215
- Cited by
- 83
- References
- 5
- Citations by year
- 2025: 5 · 2024: 1 · 2023: 5 · 2021: 2 · 2020: 5 · 2019: 3 · 2018: 3 · 2017: 13 · 2016: 2 · 2015: 9 · 2014: 6 · 2013: 13 · 2012: 8
- FWCI
- 3.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System (University of Udine) (submittedVersion)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (Z01MH002905)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neuroethics, Human Enhancement, Biomedical Innovations
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- modafinil, nootropic drugs, amygdala reactivity, fear processing, working memory, attentional control, prefrontal cortex, anterior cingulate cortex, anxiety, mood, arousal, executive function, neural circuits
- MeSH terms
- Modafinil, Adult, Benzhydryl Compounds, Brain, Brain Mapping, Cognition, Dose-Response Relationship, Drug, Double-Blind Method, Emotions, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Oxygen, Statistics as Topic, Cross-Over Studies, Neuroprotective Agents
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