Acute effects of modafinil on brain resting state networks in young healthy subjects

PLoS One. 2013 Jul 25;8(7):e69224. doi: 10.1371/journal.pone.0069224. Print 2013.

Abstract

Background: There is growing debate on the use of drugs that promote cognitive enhancement. Amphetamine-like drugs have been employed as cognitive enhancers, but they show important side effects and induce addiction. In this study, we investigated the use of modafinil which appears to have less side effects compared to other amphetamine-like drugs. We analyzed effects on cognitive performances and brain resting state network activity of 26 healthy young subjects.

Methodology: A single dose (100 mg) of modafinil was administered in a double-blind and placebo-controlled study. Both groups were tested for neuropsychological performances with the Raven's Advanced Progressive Matrices II set (APM) before and three hours after administration of drug or placebo. Resting state functional magnetic resonance (rs-FMRI) was also used, before and after three hours, to investigate changes in the activity of resting state brain networks. Diffusion Tensor Imaging (DTI) was employed to evaluate differences in structural connectivity between the two groups. Protocol ID: Modrest_2011; NCT01684306; http://clinicaltrials.gov/ct2/show/NCT01684306.

Principal findings: Results indicate that a single dose of modafinil improves cognitive performance as assessed by APM. Rs-fMRI showed that the drug produces a statistically significant increased activation of Frontal Parietal Control (FPC; p<0.04) and Dorsal Attention (DAN; p<0.04) networks. No modifications in structural connectivity were observed.

Conclusions and significance: Overall, our findings support the notion that modafinil has cognitive enhancing properties and provide functional connectivity data to support these effects.

Trial registration: ClinicalTrials.gov NCT01684306 http://clinicaltrials.gov/ct2/show/NCT01684306.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Attention / drug effects*
  • Attention / physiology
  • Benzhydryl Compounds / pharmacology*
  • Brain / drug effects*
  • Brain / physiology
  • Brain Mapping
  • Double-Blind Method
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Modafinil
  • Neuropsychological Tests
  • Nootropic Agents / pharmacology*
  • Placebos

Substances

  • Benzhydryl Compounds
  • Nootropic Agents
  • Placebos
  • Modafinil

Associated data

  • ClinicalTrials.gov/NCT01684306

Grants and funding

SLS is supported by funds from the Italian Department of Education [Fondo per gli Investimenti della Ricerca di Base (FIRB) 2003; Programmi di Ricerca di Rilevante Interesse nazionale (PRIN) 2008]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.