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Rationale Prcvious studics havc shown that sclective scrotonin reuptake inhibitors,activators of the cortex,apparently improved language functional recoveiy after brain damage rather than simply affective disorders.Objective Our aim was to determine whether venlafaxine (an agonist of both norcpinephrinc and 5-hydroxytryptamine) could modulate language cortex function.Methods A double-blind.crossover.randomized design was used to compare tw0 7-day treatment sessions with either venlafaxine (75 mg per day) or placebo.A functional magnctic resonanCe imaging cxperiment 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 afier placebo (days 0,7,and 18).Hyper- activation (venlafaxine minus placebo>0) or hypoactivation (placebo minus venlafaxine >0) by venlaxafine was assessed on the basis of the activation-baseline contrast.Results The naming score (P<.O01) and spontaneous lan- guage 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 pos terior 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 temp oro-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.