Dopamine Stimulation Modulates the Balance Between Ignoring and Updating Information

Post by Flora Moujaes

What's the science?

Deficits in working memory are a common feature of numerous psychiatric disorders, however, are not effectively treated by available therapies. Working memory deficits have often been attributed to altered dopaminergic signalling, but dopamine’s specific role has not been clearly defined. For example, dopamine has been shown to be integral to the ability to ignore distracting stimuli, but less research has been done on how this may relate to flexibility and the ability to update working memory representations. Furthermore, how individual differences affect dopamine’s modulation of working memory is unclear. Research has indicated that the ability to gate the contents of working memory is linked to both the balance between D1 and D2 dopamine receptors and tonic dopamine levels (i.e. the ‘sustained’ background dopamine release). Although it is difficult to measure tonic dopamine levels in the human brain, it may be possible to use baseline working memory performance as a proxy. This week in Journal of Psychopharmacology, Fallon and colleagues from Masud Husain’s lab at the University of Oxford explore how dopamine D2 receptor stimulation modulates both working memory and cognitive control, and how this relates to individual differences in baseline working memory performance.

How did they do it?

Researchers manipulated dopamine in 26 healthy older adults. Older adults were chosen as, like Parkinson’s patients, they show a depletion of dopaminergic functioning. However, without the progressive neuronal pathology seen in Parkinson’s they provide a clearer window into the effect dopamine has on cognitive functioning. Participants completed two sessions following either the administration of a single dose of cabergoline (1 mg), a relatively selective D2 dopamine agonist, or placebo. The order in which they received the dopamine agonist or placebo was counterbalanced to avoid order effects. Each session consisted of three tasks. The first was the Ignore/Update working memory Task, designed to assess the ability to ignore or update information in working memory. In this task, participants were shown two differently coloured arrows and required to encode their orientations. They then saw a second pair of arrows that they either had to disregard in the ignore condition, or use to replace the previous orientation information held in working memory in the update condition. The second task was the Baseline working memory Task, which provided a baseline measure of working memory ability as participants merely had to remember the orientation of an arrow after a delay. The third task was the Response Conflict (Simon) Task, which was used to obtain a relatively working memory-free measure of cognitive control. In this task, participants had to indicate which way an arrow was pointing, and the arrow’s location on the screen was either congruent or incongruent to its direction.

What did they find?

Baseline working memory ability modulates the direction of dopamine’s effect on ignoring vs. updating: Researchers found that dopamine D2 receptor stimulation did not influence overall working memory recall, but did modulate the balance between ignoring and updating in divergent ways according to baseline working memory performance. High-working memory individuals were relatively better at ignoring compared to updating after drug administration, whereas the opposite occurred in low-working memory individuals. This indicates that increased dopamine can enhance the robustness of mental representations in high-working memory individuals, but makes representations less stable and flexible in low-working memory individuals. Dopamine has common, but antagonistic, effects on ignoring and overcoming response conflict: The ability to overcome response conflict was not affected by drug administration, but the researchers did find a negative relationship between the effect the drug had on response conflict performance and ignoring. This indicates that both response conflict, a working memory free measure of cognitive control, and ignoring, a sub-process of working memory, are coupled to dopaminergic stimulation levels.
What's the impact?

What’s the impact?

Overall, this study provides a clearer window into the effect dopamine has on cognitive functioning, which may have wider implications for disorders such as Parkinson’s. Furthermore, these findings highlight the importance both of accounting for individual differences and decomposing working memory into its subcomponents when assessing the effects of dopaminergic drugs. This study also suggests that dopamine-altering cognitive enhancers may be of minimal benefit, as augmenting D2 stimulation acts as a double-edged sword: improving one cognitive function at the expense of another. Future studies would benefit by examining the effects of both dopamine agonists and antagonists in the same sample, in order to more closely examine how the balance between D1 and D2 dopamine receptors relates to working memory.

Fallon et al. Dopamine D2 receptor stimulation modulates the balance between ignoring and updating according to baseline working memory ability. Journal of Psychopharmacology (2019). Access the original scientific publication here.