Role of dopamine in modulating the relationship between working memory, reward and punishment

Dopamine has been implicated in facilitating both working memory and
reward-related processes. However, there is relatively little work integrating
reward-related processes into models of cognitive control. This study aims to
test the hypothesis suggested by n influential neurocognitive model (Frank,
2005), that unexpected reward could facilitate the updating of working memory
representations, while rendering these representations more vulnerable to
distracting input. Conversely, unexpected punishment might prevent the updating
of working memory representations, while rendering these representations more
robust to distracting input. Our hypothesis is that these effects influenced by
dopamine, and are dependent on baseline levels of dopamine as determined by
interindividual genetic variation.

Examine how unexpected reward and unexpected punishment affect working memory,
that is, the ability to maintain information across time, update task-relevant
information and ignore task-irrelevant information.

Determine the extent to which methylphenidate (Ritalin) modulates the
relationship between reward, punishment and working memory.

Assess whether these effects of methylphenidate, which blocks the dopamine
transporter (DAT) depend on individual genetic differences in the efficacy of
the DAT.

Assess the neural locus of the effects of methylphenidate on working memory as
a function of reward and punishment using functional magnetic resonance imaging
(fMRI).

Examine whether unexpected reward and punishment have the same effects on
working memory as they have on learning.

Participants will have a functional magnetic resonance scan when taking
methylphenidate and placebo.A within-subject, double-blind, placebo-controlled,
cross-over design will be employed. In the scanner participants will have to
perform a working memory task that requires them to ignore or attend to newly
presented information. The effficacy with which participants can do this after
unexpected reward or punishment will be examined.

Subjects will have to lie in an fMRI scanner and perform a working memory task,
which requires the viewing and memorizing of abstract visual patterns. This
task will have to be performed twice: once after administration of a placebo
substance and once after administration of 20mg methylphenidate. On the day
preceding each drug session, subjects will have to adhere to some simple
restrictions with respect to medication, alcohol and drug intake. Also, on the
morning of each scanning session, subjects will also have to refrain from
smoking and stimulant containing drinks.. The most common side effect of taking
repeated doses of methylphenidate is a headache (occurring in over 10% of
people who take the drug). Other, less common, side effects include feeling
dizzy, nauseous or anxious. However, our prior experience with administering
methylphenidate has found that these side effects are well tolerated by
subjects.