Prefrontal activity decline in women under a single dose of diazepam during rule-guided responses: an fMRI study.

Daily life events confront us with new situations demanding responses to usual and unusual rules. Diazepam (DZ), a clinically important drug, facilitates the inhibitory activity of the GABAergic system. Prefrontal cortex, rich in DZ receptors, coordinates necessary resources to direct actions according to rules. The balance between excitatory and inhibitory activity is critical to achieve optimal function of brain systems leading to complex functions. Major sex differences in the physiological mechanisms of the GABAergic system have been reported. However, the differential influence of DZ on men and women in neural activity during behavior directed by frontal lobes remains unexplored. The ability of healthy volunteers to select responses following usual/congruent and novel/incongruent rules, and brain correlates were measured with fMRI under the administration of DZ and a placebo. 10 mg of DZ was enough to decrease the performance in a different manner between men and women. While reaction times increased in both men and women, women committed more errors selecting responses than men under DZ. Men demonstrated increased activity, while women demonstrated decreased activity in frontal regions involved in response selection of rules. These findings could have important consequences in understanding the differential influences of DZ between the sexes in complex daily life situations. More importantly, this study emphasizes the importance of understanding the differential effects on men and women of drugs widely employed by society, thereby achieves better therapeutic results and avoids side effects that the present study revealed to be different between sexes.

Acute effect of callosotomy on cortical temporal coupling in humans: intraoperative electrocorticographic recording.

OBJECTIVE: To investigate the acute role of the corpus callosum in inter- and intrahemispheric temporal coupling. METHODS: Intraoperative electrocorticography (ECoG) makes it possible to investigate the acute role of the corpus callosum in cortical temporal coupling, or synchrony, without additional surgical intervention, thus avoiding the confounding effects of scalp recordings and the long-term reorganization of functional connectivity. ECoGs were recorded in three patients during callosotomies. Bilateral electrode grids were placed over the frontal cortex. ECoGs were recorded immediately before and after performing the anterior two-thirds callosal transection, were digitalized at a sampling rate of 512Hz, inspected for artifacts, and later analyzed offline. Cross-correlation between inter- and intrahemispheric electrode pairs were obtained for 1Hz bins and special broad bands obtained by principal component analysis for each patient pre- and post-callosotomy. RESULTS: A statistically significant change was observed in intrahemispheric temporal coupling between electrode pairs that exceeded the confidence limit of correlation. CONCLUSIONS: Present results show that interrupting the influence of the corpus callosum has an acute effect on intrahemispheric activity by decreasing temporal coupling between cortical areas. SIGNIFICANCE: Intrahemispheric temporal coupling does not depend exclusively on ipsilateral cortico-cortical pathways or on subcortical influences, but also on callosal pathways.

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.