Contribution of catecholamines to visual working memory in the macaque monkey

Abstract

Working memory is the ability to store relevant information temporarily to guide future thought and behavior. It is a basic cognitive function instrumental to processes such as learning, reasoning, comprehension and mental arithmetic. Central to mental disorders, such as attention deficit hyperactivity disorder (ADHD), are impairments in cognition including working memory. It is essential to understand working memory, if we want to understand human cognition and mental disorders. A neural correlate of working memory has been identified as selective persistent activity during the retention intervals of tasks that probe working memory. The signal-to-noise ratio of persistent activity can be modulated by catecholamines, neuromodulators that are depleted in many mental disorders, including ADHD. Such modulations should be evident at the level of behavior, particularly as the demands imposed on working memory are increased. To test the contribution of catecholamines to working memory, we opted to administer methylphenidate to three female macaque monkeys. Methylphenidate is a dopamine and norepinephrine reuptake inhibitor that effectively increases their availability in the brain. By having monkeys perform a visual sequential comparison task, which allows the systematic manipulation of working memory load, we tested the hypothesis that increased catecholamine levels modulate task performance in a dose- and memory load-dependent way. Systematic administration of a wide range of doses of methylphenidate (0.1 – 9 mg/kg) did not affect performance on the visual sequential comparison task in either a dose- or memory load-dependent manner. Given these results, we further tested the effects of methylphenidate on overt attention in a visual search task. Again, we did not observe a dose-dependent effect on performance. Nevertheless, methylphenidate was found to generally increase the monkeys’ motivation. We suggest that the positive effect on motivation, elicited by an increased level of catecholamines, might have led to changes in performance observed in previous literature, but not to changes in the ability of retaining visual information per se. These findings question the previously suggested influence that catecholamines exert on cognition, and suggest that the role of catecholamines in working memory should be reevaluated.