The modulation of venlafaxine on cortical activation of language area in healthy subjects with fMRI study

Previous studies have shown that selective serotonin reuptake inhibitors, activators of the cortex, apparently improved language functional recovery after brain damage rather than simply affective disorders. Our aim was to determine whether venlafaxine (an agonist of both norepinephrine and 5-hydroxytryptamine) could modulate language cortex function. A double-blind, crossover, randomized design was used to compare two 7-day treatment sessions with either venlafaxine (75 mg per day) or placebo. A functional magnetic resonance imaging experiment and two language function tests were performed on eight healthy males (mean age, 28.25 +/- 3.15 years) at the end of each session, i.e., study entry, after venlafaxine, and after placebo (days 0, 7, and 18). Hyperactivation (venlafaxine minus placebo > 0) or hypoactivation (placebo minus venlafaxine > 0) by venlaxafine was assessed on the basis of the activation-baseline contrast. The naming score (P < .001) and spontaneous language fluency (P < .001) were significantly higher after venlafaxine than after placebo. Functional magnetic resonance imaging (fMRI) showed that (1) picture naming activated the left posterior gyrus frontalis medius and the bilateral fusiform gyrus and the bilateral outer occipital lobes, (2) hyperactivation was observed in the adjoining area of posterior upper Broca area and premotor area in the dominant hemisphere in venlafaxine session (after venlafaxine), (3) the hyperactivation of the left gyrus frontalis medius on fMRI and the increase in naming test score were positively correlated, and (4) by contrast, we observed hypoactivation in the temporo-parieto-occipital region in venlafaxine session (after venlafaxine). This improvement may be related to increased phonics-related output in the frontal language cortex of the dominant hemisphere.