Learning-induced neuroplastic changes, modulated by content and setting, are reflected in brain functional connectivity (FC). Selective serotonin reuptake inhibitors (SSRIs) facilitate neuroplasticity in animal models, particularly during emotional relearning, such as fear extinction, which may translate to clinical improvements in patients. 

A recent study investigated a comparable modulation of neuroplasticity in humans by enrolling 99 healthy subjects who underwent three weeks of emotional (matching faces) or non-emotional learning (matching Chinese characters to unrelated German nouns). They subsequently relearned shuffled pairings of the original content for the same time. During relearning, subjects received either a daily dose of the SSRI escitalopram or a placebo. 

The study performed Resting-state functional magnetic resonance imaging of the patients before and after the (re-)learning phases. 

The study found that Escitalopram intake modulated FC changes in a network comprising Brocas area, the medial prefrontal cortex, and the right inferior temporal and left lingual gyrus. Precisely, it increased the bidirectional connectivity between the medial prefrontal cortex and lingual gyrus for non-emotional and the connectivity from the medial prefrontal cortex to Brocas area for emotional relearning. 

Together with behavioral correlations, these effects suggest that SSRIs like escitalopram improve neuroplasticity rather than psychiatric symptoms only, in clinical practice.

Klöbl M, Seiger R, Vanicek T, et al. escitalopram modulates learning content-specific neuroplasticity of functional brain networks. NeuroImage. 2022;247. https://doi.org/10.1016/j.neuroimage.2021.118829.