Noradrenergic Modulation of Cognitive Control

his project characterizes molecular mechanisms mediating behavioral flexibility in rats or mice, and examines how atomoxetine (a treatment for Attention Deficit/Hyperactivity Disorder) affects neural circuitry in humans.

We propose that high functioning creativity depends critically upon cognitive and behavioral flexibility, including the ability to rapidly update thoughts and actions when contingencies begin to change. This kind of flexible behavior and cognition falls under the rubric of “cognitive control”. Recent work has highlighted the unique role for monoamine transmitters (dopamine, norepinephrine and serotonin) in prefrontal cortex in the regulation of cognitive control; however, little is yet known about the specific molecular or neural mechanisms by which these transmitters act to permit flexible thought and behavior. To address these issues, the current project will employ pharmaco-fMRI studies in normal humans and pharmacological and genetic studies in rodents to reveal the mechanisms by which increased catecholamine function stimulates cognitive and behavioral flexibility. Based upon preliminary work in the rodent and non-human primate, we will examine the effects of the selective noradrenaline reuptake inhibitor atomoxetine [Strattera] on the ability to inhibit or switch prepotent responses and the ability to hold information in working memory, using convergent measures of these constructs in rodents and humans.  This work has the potential to identify and characterize the ways in which cognitive function may be modulated in normal individual, providing the substrate for more creative (less inflexible) thought and behavior.