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Neuroplastic effects of a selective serotonin reuptake inhibitor in relearning and retrieval

Animal studies using selective serotonin reuptake inhibitors (SSRIs) and learning paradigms have demonstrated that serotonin is important for flexibility in executive functions and learning. SSRIs might facilitate relearning through neuroplastic processes and thus exert their clinical effects in psy...

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Published in:NeuroImage (Orlando, Fla.) Fla.), 2021-08, Vol.236, p.118039-118039, Article 118039
Main Authors: Reed, M.B., Vanicek, T., Seiger, R., Klöbl, M., Spurny, B., Handschuh, P., Ritter, V., Unterholzner, J., Godbersen, G.M., Gryglewski, G., Kraus, C., Winkler, D., Hahn, A., Lanzenberger, R.
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container_issue
container_start_page 118039
container_title NeuroImage (Orlando, Fla.)
container_volume 236
creator Reed, M.B.
Vanicek, T.
Seiger, R.
Klöbl, M.
Spurny, B.
Handschuh, P.
Ritter, V.
Unterholzner, J.
Godbersen, G.M.
Gryglewski, G.
Kraus, C.
Winkler, D.
Hahn, A.
Lanzenberger, R.
description Animal studies using selective serotonin reuptake inhibitors (SSRIs) and learning paradigms have demonstrated that serotonin is important for flexibility in executive functions and learning. SSRIs might facilitate relearning through neuroplastic processes and thus exert their clinical effects in psychiatric diseases where cognitive functioning is affected. However, translation of these mechanisms to humans is missing. In this randomized placebo-controlled trial, we assessed functional brain activation during learning and memory retrieval in healthy volunteers performing associative learning tasks aiming to translate facilitated relearning by SSRIs. To this extent, seventy-six participants underwent three MRI scanning sessions: (1) at baseline, (2) after three weeks of daily associative learning and subsequent retrieval (face-matching or Chinese character–noun matching) and (3) after three weeks of relearning under escitalopram (10 mg/day) or placebo. Associative learning and retrieval tasks were performed during each functional MRI (fMRI) session. Statistical modeling was done using a repeated-measures ANOVA, to test for content-by-treatment-by-time interaction effects. During the learning task, a significant substance-by-time interaction was found in the right insula showing a greater deactivation in the SSRI cohort after 21 days of relearning compared to the learning phase. In the retrieval task, there was a significant content-by-time interaction in the left angular gyrus (AG) with an increased activation in face-matching compared to Chinese-character matching for both learning and relearning phases. A further substance-by-time interaction was found in task performance after 21 days of relearning, indicating a greater decrease of performance in the placebo group. Our findings that escitalopram modulate insula activation demonstrates successful translation of relearning as a mechanism of SSRIs in human. Furthermore, we show that the left AG is an active component of correct memory retrieval, which coincides with previous literature. We extend the function of this region by demonstrating its activation is not only stimulus dependent but also time constrained. Finally, we were able to show that escitalopram aids in relearning, irrespective of content.
doi_str_mv 10.1016/j.neuroimage.2021.118039
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1095-9572
language eng
recordid cdi_doaj_primary_oai_doaj_org_article_ae289921062b478f97d9ef105eb44449
source Elsevier
subjects Adult
Angular gyrus
Antidepressants
Association Learning - drug effects
Associative learning
Brain Mapping
Cerebral Cortex - diagnostic imaging
Cerebral Cortex - drug effects
Cerebral Cortex - physiology
Citalopram
Citalopram - administration & dosage
Citalopram - pharmacology
Cognitive ability
Deactivation
DNA methylation
Double-Blind Method
Female
fMRI
Functional magnetic resonance imaging
Humans
Insula
Investigations
Learning
Longitudinal Studies
Magnetic Resonance Imaging
Male
Mathematical models
Memory
Mental disorders
Mental Recall - drug effects
Neuronal Plasticity - drug effects
Neuroplasticity
Parietal Lobe - diagnostic imaging
Parietal Lobe - drug effects
Parietal Lobe - physiology
Participation
Pattern Recognition, Visual - physiology
Placebos
Relearning
Serotonin
Serotonin uptake inhibitors
Serotonin Uptake Inhibitors - administration & dosage
Serotonin Uptake Inhibitors - pharmacology
SSRI
Translation
Young Adult
title Neuroplastic effects of a selective serotonin reuptake inhibitor in relearning and retrieval
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