Behavioural and neural effects of diazepam on a rule-guided response selection task.

Diazepam (DZ), a clinically important drug, reduces alertness and can interfere with complex cognitive processes. The effect of DZ on the behavioural and neural correlates of rule-guided response selection has not been directly investigated. We studied DZ effects, compared to placebo (PL), on performance and brain responses, using fMRI, during rule implementation, when arbitrary stimulus-specific rules were involved. BOLD activity was measured in eighteen healthy volunteers during rule-guided response selection with DZ or PL administered in two counterbalanced sessions. A 10mg dose of DZ was sufficient to increase reaction times and to reduce accuracy in a rule-guided task but not in a motor task containing the same stimuli. With PL, implementing arbitrary rules activated right anterior cingulate/middle frontal gyri. Under DZ more brain areas were recruited during the task compared to PL, especially occipito-parietal cortices, as well as the left temporal lobe. For the congruent trials rules, more activity was observed in the right retrosplenial cortex when participants had taken DZ. These findings indicate that DZ might disrupt the neural activity necessary to implement novel rules, supporting the notion that DZ influence on behaviour goes beyond perceptual and motor processes that can potentially compromise complex cognitive functions.