Midbrain dopamine system triggers shifting of context representations in dorsolateral prefrontal cortex

Shifting quickly and flexibly between different goals that one is pursuing is one of the most amazing of human cognitive skills. For example, running into a friend in the midst of shopping groceries for one’s family in a local store one is able to recall what one had intended to relate to him/her upon seeing that friend. Following lively discussion for several minutes, getting back to the goal of shopping the groceries is flexible and effortless. At the same while that there is this amazing flexibility, one is perseverant and not distracted from pursuing one’s goals by other stimuli and events that are irrelevant to the behavioral goals at hand. It has been proposed that the midbrain dopaminergic system and prefrontal cortical areas underlie this capability to shift between goal directed behaviors, but empirical demonstrations have not been unequivocal.

In their recent study, D’Ardenne et al. (2012) combined transcranial magnetic stimulation and functional magnetic resonance imaging to study the interplay between phasic signals produced by the brain stem dopaminergic system and context representations (aka “cognitive set”) maintained by the prefrontal cortex. The authors observed that transcranial magnetic stimulation of especially the right dorsolateral prefrontal cortex, timed around the presentation of the task context, impaired context-dependent responses more than context-independent responses. Functional magnetic resonance imaging of the ventral tegmental area and substantia nigra further disclosed phasic signals that co-occurred with context shifting events and correlated with phasic signals that were observed in dorsolateral prefrontal cortex.

Together, these experiments provide robust support for the model where phasic (presumably dopaminergic) signals produced by ventral tegmental area and substantia nigra trigger shifting of context representation in the (especially the right) dorsolateral prefrontal cortex. This study also provides a nice example of how transcranial magnetic stimulation can be combined with functional magnetic resonance imaging and behavioral task designs to gain insight into the neural basis of human goal directed behavior.

Reference: D’Ardenne K, Eshel N, Luka J, Lenartowicz A, Nystrom LE, Cohen JD. Role of prefrontal cortex and the midbrain dopamine system in working memory updating. Proc Natl Acad Sci USA (2012) e-publication ahead of print. http://dx.doi.org/10.1073/pnas.1116727109