Dissociating neuromodulatory effects of diazepam on episodic memory encoding and executive function

Rationale: Diazepam and other benzodiazepines impair episodic memory encodi ng. Deficits in tests of executive function are also reported. In this stud y; we ask whether the latter effects are secondary to mnemonic impairment, or reflect specific and distinct effects of benzodiazepines on executive fu nction. Objectives: Using positron emission tomography in healthy human vol unteers, we examined similarities in the neuroanatomical correlates of the effect of diazepam on performance of executive compared to episodic memory tasks. Close: similarities are proposed to reflect commonalities in the fun ctional effects of the drug. Conversely, any evidence of task-specific regi onal changes in activity is proposed to reflect distinct functional effects of DZP on the two tasks. Methods: Twelve volunteers received placebo or 10 mg diazepam in a between-subjects design. During scanning, subjects perfor med one of four experimental conditions, corresponding to a 2x2 factorial d esign, with memory encoding and executive function ton-line ordering of sti muli) as the two factors. Drug- or task-induced changes in brain activation indexed the neuroanatomical correlates of each condition. Results: Average d across all conditions, and compared to placebo, diazepam decreased activi ty bilaterally in prefrontal and temporal cortices. Within this network of deactivation, left dorsal prefrontal cortex activity was attenuated by diaz epam during memory encoding, while left frontal opercular activity was atte nuated during ordering. Conclusion: This neuroanatomical dissociation refle cts distinct functional effects of diazepam on encoding versus ordering tas ks. Therefore, the effects of diazepam on ordering tasks are not simply sec ondary to diazepam effects on episodic memory, but reflect real and distinc t effects of the drug on executive function.