Brain Topography

, Volume 31, Issue 3, pp 380–391 | Cite as

Brain Networks are Independently Modulated by Donepezil, Sleep, and Sleep Deprivation

  • Jonathan Wirsich
  • Marc Rey
  • Maxime Guye
  • Christian Bénar
  • Laura Lanteaume
  • Ben Ridley
  • Sylviane Confort-Gouny
  • Catherine Cassé-Perrot
  • Elisabeth Soulier
  • Patrick Viout
  • Franck Rouby
  • Marie-Noëlle Lefebvre
  • Christine Audebert
  • Romain Truillet
  • Elisabeth Jouve
  • Pierre Payoux
  • David Bartrés-Faz
  • Régis Bordet
  • Jill C. Richardson
  • Claudio Babiloni
  • Paolo Maria Rossini
  • Joelle Micallef
  • Olivier Blin
  • Jean-Philippe Ranjeva
  • The Pharmacog Consortium
Original Paper
  • 267 Downloads

Abstract

Resting-state connectivity has been widely studied in the healthy and pathological brain. Less well-characterized are the brain networks altered during pharmacological interventions and their possible interaction with vigilance. In the hopes of finding new biomarkers which can be used to identify cortical activity and cognitive processes linked to the effects of drugs to treat neurodegenerative diseases such as Alzheimer’s disease, the analysis of networks altered by medication would be particularly interesting. Eleven healthy subjects were recruited in the context of the European Innovative Medicines Initiative ‘PharmaCog’. Each underwent five sessions of simultaneous EEG-fMRI in order to investigate the effects of donepezil and memantine before and after sleep deprivation (SD). The SD approach has been previously proposed as a model for cognitive impairment in healthy subjects. By applying network based statistics (NBS), we observed altered brain networks significantly linked to donepezil intake and sleep deprivation. Taking into account the sleep stages extracted from the EEG data we revealed that a network linked to sleep is interacting with sleep deprivation but not with medication intake. We successfully extracted the functional resting-state networks modified by donepezil intake, sleep and SD. We observed donepezil induced whole brain connectivity alterations forming a network separated from the changes induced by sleep and SD, a result which shows the utility of this approach to check for the validity of pharmacological resting-state analysis of the tested medications without the need of taking into account the subject specific vigilance.

Keywords

EEG-fMRI Functional connectivity Sleep Donepezil Memantine 

Notes

Acknowledgements

This research was developed under the ethical requirements complied with the European Community Council Directive (2010/63/UE). The research leading to these results was conducted as part of the PharmaCog consortium funded by the European Community’s Seventh Framework Program for the Innovative Medicine Initiative under Grant Agreement no. 115009. For further information, please refer to http://www.pharmacog.org/.

Compliance with Ethical Standards

Conflict of interest

The authors report no conflicts of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the of the local ethics committee (Comité de Protection des Personnes Sud-Méditerranée 1 Marseille) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

10548_2017_608_MOESM1_ESM.pdf (333 kb)
Supplementary material 1 (PDF 333 KB)
10548_2017_608_MOESM2_ESM.pdf (425 kb)
Supplementary material 2 (PDF 425 KB)
10548_2017_608_MOESM3_ESM.pdf (345 kb)
Supplementary material 3 (PDF 344 KB)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Jonathan Wirsich
    • 1
    • 2
    • 5
  • Marc Rey
    • 3
  • Maxime Guye
    • 1
    • 2
  • Christian Bénar
    • 5
  • Laura Lanteaume
    • 4
  • Ben Ridley
    • 1
    • 2
  • Sylviane Confort-Gouny
    • 1
    • 2
  • Catherine Cassé-Perrot
    • 4
  • Elisabeth Soulier
    • 1
    • 2
  • Patrick Viout
    • 1
    • 2
  • Franck Rouby
    • 4
  • Marie-Noëlle Lefebvre
    • 4
  • Christine Audebert
    • 4
  • Romain Truillet
    • 4
  • Elisabeth Jouve
    • 4
  • Pierre Payoux
    • 6
  • David Bartrés-Faz
    • 7
  • Régis Bordet
    • 8
  • Jill C. Richardson
    • 9
  • Claudio Babiloni
    • 10
  • Paolo Maria Rossini
    • 11
  • Joelle Micallef
    • 4
  • Olivier Blin
    • 4
  • Jean-Philippe Ranjeva
    • 1
    • 2
  • The Pharmacog Consortium
  1. 1.CRMBM UMR AMU CNRS 7339Aix-Marseille UniversitéMarseilleFrance
  2. 2.AP-HM, CHU Timone, Pôle d’ImagerieCEMEREMMarseilleFrance
  3. 3.AP-HM, CHU Timone, Pôle de Neurosciences Cliniques, Service de NeurophysiologieMarseilleFrance
  4. 4.AP-HM, CHU Timone, CIC CPCET, Service de Pharmacologie Clinique et PharmacovigilanceMarseilleFrance
  5. 5.Inserm, UMR_S 1106, INS, Institut de Neurosciences des SystèmesAix-Marseille UniversitéMarseilleFrance
  6. 6.UMR 825 Inserm, Imagerie Cérébrale et Handicaps NeurologiquesUniversité Toulouse III Paul SabatierToulouseFrance
  7. 7.Department of Psychiatry and Clinical Psychobiology, Faculty of MedicineUniversity of Barcelona and Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)BarcelonaSpain
  8. 8.U1171 Inserm, CHU Lille, Degenerative and Vascular Cognitive DisordersUniversity of LilleLilleFrance
  9. 9.Neurosciences Therapeutic Area UnitGlaxoSmithKline R&DStevenageUK
  10. 10.Department of Physiology and PharmacologyUniversity of Rome “Sapienza”RomeItaly
  11. 11.Institute of NeurologyCatholic University of The Sacred HeartRomeItaly

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