Time related effects on functional brain connectivity after serotonergic and cholinergic neuromodulation.
Psychopharmacological research, if properly designed, may offer insight into both timing and area of effect, increasing our understanding of the brain's neurotransmitter systems. For that purpose, the acute influence of the selective serotonin reuptake inhibitor citalopram (30 mg) and the acetylcholinesterase inhibitor galantamine (8 mg) was repeatedly measured in 12 healthy young volunteers with resting state functional magnetic resonance imaging (RS-fMRI). Eighteen RS-fMRI scans were acquired per subject during this randomized, double blind, placebo-controlled, crossover study. Within-group comparisons of voxelwise functional connectivity with 10 functional networks were examined (P < 0.05, FWE-corrected) using a non-parametric multivariate approach with cerebrospinal fluid, white matter, heart rate, and baseline measurements as covariates. Although both compounds did not change cognitive performance on several tests, significant effects were found on connectivity with multiple resting state networks. Serotonergic stimulation primarily reduced connectivity with the sensorimotor network and structures that are related to self-referential mechanisms, whereas galantamine affected networks and regions that are more involved in learning, memory, and visual perception and processing. These results are consistent with the serotonergic and cholinergic trajectories and their functional relevance. In addition, this study demonstrates the power of using repeated measures after drug administration, which offers the chance to explore both combined and time specific effects. Hum Brain Mapp 38:308-325, 2017. © 2016 Wiley Periodicals, Inc.
Leiden University, Institute of Psychology, Leiden, the Netherlands.|Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.|Leiden University, Leiden Institute for Brain and Cognition, Leiden, the Netherlands.|Centre for Human Drug Research, Leiden, the Netherlands.
Bernadet L
BL
Klaassens
Leiden University, Institute of Psychology, Leiden, the Netherlands.|Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.|Leiden University, Leiden Institute for Brain and Cognition, Leiden, the Netherlands.
Serge A R B
SA
Rombouts
Oxford Centre for Functional MRI of the Brain, Oxford University, Oxford, United Kingdom.
Anderson M
0000-0002-4169-9781
AM
Winkler
Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.|Leiden University, Leiden Institute for Brain and Cognition, Leiden, the Netherlands.|Centre for Human Drug Research, Leiden, the Netherlands.
Helene C
HC
van Gorsel
Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
Jeroen
J
van der Grond
Centre for Human Drug Research, Leiden, the Netherlands.
Joop M A
JM
van Gerven
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology*; D001931:Brain Mapping; D018678:Cholinergic Agents / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000097:blood / Q000494:pharmacology; D015283:Citalopram / Q000097:blood / Q000494:pharmacology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005702:Galantamine / Q000097:blood / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007091:Image Processing, Computer-Assisted; D008297:Male; D008959:Models, Neurological; D010100:Oxygen / Q000097:blood; D011388:Prolactin / Q000097:blood; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000494:pharmacology; D055815:Young Adult
D018678:Cholinergic Agents; D002800:Cholinesterase Inhibitors; D015283:Citalopram; D005702:Galantamine; D006854:Hydrocortisone; D010100:Oxygen; D011388:Prolactin; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors
AChEI; SSRI; acetylcholine; citalopram; functional connectivity; galantamine; psychopharmacology; resting state fMRI; resting state network; serotonin