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

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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.

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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

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Correspondence to Jonathan Wirsich.

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The authors report no conflicts of interest.

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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.

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

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Wirsich, J., Rey, M., Guye, M. et al. Brain Networks are Independently Modulated by Donepezil, Sleep, and Sleep Deprivation. Brain Topogr 31, 380–391 (2018).

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