Dissociating neuromodulatory effects of diazepam on episodic memory encoding and executive function.
BACKGROUND
Diazepam and other benzodiazepines impair episodic memory encoding. Deficits in tests of executive function are also reported. In this study, we ask whether the latter effects are secondary to mnemonic impairment, or reflect specific and distinct effects of benzodiazepines on executive function.


OBJECTIVE
Using positron emission tomography in healthy human volunteers, 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 functional effects of the drug. Conversely, any evidence of task-specific regional 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 performed one of four experimental conditions, corresponding to a 2x2 factorial design, with memory encoding and executive function (on-line ordering of stimuli) as the two factors. Drug- or task-induced changes in brain activation indexed the neuroanatomical correlates of each condition.


RESULTS
Averaged across all conditions, and compared to placebo, diazepam decreased activity bilaterally in prefrontal and temporal cortices. Within this network of deactivation, left dorsal prefrontal cortex activity was attenuated by diazepam during memory encoding, while left frontal opercular activity was attenuated during ordering.


CONCLUSIONS
This neuroanatomical dissociation reflects distinct functional effects of diazepam on encoding versus ordering tasks. Therefore, the effects of diazepam on ordering tasks are not simply secondary to diazepam effects on episodic memory, but reflect real and distinct effects of the drug on executive function.
Coull
J T
JT
Wellcome Department of Cognitive Neurology, Institute of Neurology, London, UK. jcoull@fil.ion.ucl.ac.uk
Frith
C D
CD
Dolan
R J
RJ
D000328:Adult; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology*; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology
D014151:Anti-Anxiety Agents; D003975:Diazepam