Abstract

Evidence suggests that selective serotonin reuptake inhibitors (SSRIs) reorganize neural networks via a transient window of neuroplasticity. While previous findings support an effect of SSRIs on intrinsic functional connectivity, little is known regarding the influence of SSRI-administration on connectivity during sequence motor learning. To investigate this, we administered 20 mg escitalopram or placebo for 1-week to 60 healthy female participants undergoing concurrent functional magnetic resonance imaging and sequence motor training in a double-blind randomized controlled design. We assessed task-modulated functional connectivity with a psycho-physiological interaction (PPI) analysis in the thalamus, putamen, cerebellum, dorsal premotor, primary motor, supplementary motor, and dorsolateral prefrontal cortices. Comparing an implicit sequence learning condition to a control learning condition, we observed decreased connectivity between the thalamus and bilateral motor regions after 7 days of escitalopram intake. Additionally, we observed a negative correlation between plasma escitalopram levels and PPI connectivity changes, with higher escitalopram levels being associated with greater thalamo-cortico decreases. Our results suggest that escitalopram enhances network-level processing efficiency during sequence motor learning, despite no changes in behaviour. Future studies in more diverse samples, however, with quantitative imaging of neurochemical markers of excitation and inhibition, are necessary to further assess neural responses to escitalopram.

Highlights

  • Evidence suggests that selective serotonin reuptake inhibitors (SSRIs) reorganize neural networks via a transient window of neuroplasticity

  • Plasma escitalopram levels are within the expected range[34]

  • We employed psycho-physiological interaction (PPI) analysis to assess the effects of 1-week escitalopram-intake on functional brain connectivity during implicit sequence motor learning

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Summary

Introduction

Evidence suggests that selective serotonin reuptake inhibitors (SSRIs) reorganize neural networks via a transient window of neuroplasticity. Motor learning is an anatomically diverse process, drawing on contributions from the primary, supplementary, premotor, prefrontal cortices, and c­ erebellum[1,2]. Interactions between these regions are dynamic, and both functional and structural motor connectivity can be strengthened by p­ ractice[3] or altered by d­ isease[4]. Previous conceptual models propose that selective serotonin reuptake inhibitors (SSRIs), anti-depressant and anxiolytic medications that increase extracellular s­ erotonin[5], act by reorganizing neural networks via a transient window of ­neuroplasticity[6,7].

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