Paroxetine-induced modulation of cortical activity supporting language representations of action

Previous studies have shown that paroxetine, a selective serotonin reuptake inhibitor, affects brain motor pathway activity in healthy subjects using simple motor tasks. In this study, we explored the effects of paroxetine on the activity of cortical areas implicated in higher-order representations of goal-directed movements, i.e., action-related language processing.

A double-blind, crossover, randomized paradigm was used to compare two 1-month treatment phases with either paroxetine (20 mg per day) or placebo. A functional magnetic resonance imaging experiment on 12 healthy subjects, conducted at the end of each treatment phase, comprised a single list of verbs and three tasks that consisted in repeating the verbs aloud, generating verbs depicting actions aloud, and mentally simulating the corresponding actions. The effects of the drug, i.e., paroxetine-placebo>0 (hyperactivation) and placebo-paroxetine >0 (hypoactivation) were assessed on the basis of the activation-rest contrast for each task.

For both verb generation and mental simulation of action which both engaged higher-order representations of action, we observed hypoactivation in the left-sided prefrontal and right-sided medial premotor cortex. By contrast, we observed hyperactivation in the right-sided Brodmann's area 6 for the less demanding verb repetition task.

Chronic treatment with paroxetine may modulate the cerebral activities elicited by action-related language tasks depending on the cognitive components involved in such tasks.