Time related effects on functional brain connectivity after serotonergic and cholinergic neuromodulation

Abstract

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.

Acute tryptophan loading decreases functional connectivity between the default mode network and emotion‐related brain regions

“…We used a template-based approach, which has been validated by previous studies (Klaassens et al, 2015(Klaassens et al, , 2016 and reliably provides spatial maps of established large-scale brain networks. Briefly, we used the 10 templates from Study design.…”

“…The voxel-wise regression coefficients contained in the resulting spatial maps represent the synchronization between BOLD temporal dynamics at a given voxel and the mean BOLD time courses of a specific network. The strength of the voxel-to-network connectivity is given by the value of these coefficients (Klaassens et al, 2015(Klaassens et al, , 2016. Only the spatial maps representing the DMN were used in the higher-level analysis (85 subjects × 3 interventions = 255 DMN maps).…”

“…Serotonergic ascending fibers from the dorsal raphe nucleus project onto the lateral cerebral cortex and the hypothalamus, the basal forebrain, and the amygdala. Presumably as a result of this innervation, changes in the functional coherence of the DMN following serotonergic medication were observed, especially in brain regions involved in mood and attention regulation (Klaassens et al, 2016(Klaassens et al, , 2015Posner et al, 2013;Van de Ven, Wingen, Kuypers, Ramaekers, & Formisano, 2013). Presumably as a result of this innervation, changes in the functional coherence of the DMN following serotonergic medication were observed, especially in brain regions involved in mood and attention regulation (Klaassens et al, 2016(Klaassens et al, , 2015Posner et al, 2013;Van de Ven, Wingen, Kuypers, Ramaekers, & Formisano, 2013).…”

“…showing both increases and decreases in connectivity after either SSRIs (Klaassens et al, 2015(Klaassens et al, , 2016 or tryptophan manipulations Kunisato et al, 2011). Hence, further investigations are still necessary in order to understand how different brain 5-HT levels affect the functional coherence of the DMN.…”

The M1/M4 agonist xanomeline modulates functional connectivity and NMDAR antagonist-induced changes in the mouse brain

“…It is however unclear whether the net resulting effect of scopolamine is functional silencing of activation of cortical cholinergic tone, given the complex pre-and post-synaptic distribution of muscarinic receptors. We also note that oral administration of galantamine, an acetyl cholinesterase inhibitor, produced mostly decreased functional activity in human testing, with areas of functional increase appearing only at a late timepoint (6 hrs post-administration), and mostly in visual regions (Klaassens et al, 2016).…”