Modafinil enhances cognitive, but not emotional conflict processing via enhanced inferior frontal gyrus activation and its communication with the dorsomedial prefrontal cortex

Neuropsychopharmacology. 2020 May;45(6):1026-1033. doi: 10.1038/s41386-020-0625-z. Epub 2020 Jan 29.


Cognitive control regulates cognitive and emotional systems to facilitate goal-directed behavior in the context of task-irrelevant distractors. Cognitive control deficits contribute to residual functional impairments across psychiatric disorders and represent a promising novel treatment target. Translational evidence suggests that modafinil may enhance performance in executive functions; however, differential effects on regulatory control in cognitive and emotional domains have not been examined. The present pre-registered randomized-controlled pharmacological fMRI trial examined differential effects of modafinil (single-dose, 200 mg) on cognitive and emotional conflict processing. To further separate objective cognitive enhancing effects from subjective performance perception, a metacognitive paradigm was employed. Results indicated that modafinil specifically enhanced cognitive conflict performance and concomitantly increased activation in the inferior frontal gyrus and its functional communication with the dorsomedial prefrontal cortex. Exploratory analysis further revealed modafinil-enhanced basolateral amygdala reactivity to cognitive conflict, with stronger reactivity being associated with higher cognitive conflict performance. Whereas modafinil enhanced cognitive performance in the metacognitive paradigm, confidence indices remained unaffected. Overall, the present results suggest that modafinil has the potential to enhance cognitive conflict processing while leaving emotional conflict processing unaffected. On the neural level modafinil enhanced the recruitment of a network engaged in general conflict and regulatory control processes, whereas effects on the amygdala may reflect improved arousal-mediated attention processes for conflicting information. The pattern of cognitive enhancing effects in the absence of effects on affective processing suggests a promising potential to enhance cognitive control in clinical populations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cognition*
  • Communication
  • Emotions*
  • Humans
  • Magnetic Resonance Imaging
  • Modafinil
  • Prefrontal Cortex


  • Modafinil