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General discussion
Our environment imposes on us a constant stream of stimuli and potential tasks to engage
in. Dealing with this constantly changing environment requires the ability to flexibly adapt
our behavioural and cognitive programs to changing task demands. In addition, we adapt
our behaviour to changes in potential rewards, which serve both a motivational function,
by invigorating and energizing ongoing behaviour and cognition, as well as a directional
function, biasing behaviour towards one action or another by influencing choice and
learning. In this thesis, I have focused on the motivational function of reward and specifically,
on its role in motivating cognitive control. Previous experimental and anatomical work has
suggested a role for dopamine, the striatum and connections between the striatum and the
prefrontal cortex in motivated cognitive control (
chapters 1 and 2
, (Haber et al., 2000; Haber,
2003; Aarts et al., 2010). Until recently, experimental evidence supporting these hypotheses
was either absent, indirect or did not speak to the specific receptor types involved in the
underlying process (
chapters 1 and 2
).
In this thesis, I aimed to improve our understanding of the role of dopamine and the
corticostriatal network during the integration of reward and flexible cognitive control. More
specifically my work aimed to test
whether the manipulation of dopamine and specific
dopamine receptors
(
chapter 3, 4
), and (prefrontal modulation of) signalling in the striatum
(
chapter 6 and 7
)
can alter motivated cognitive control. In addition, I assessed reward-
cognition integration across the life span, from adolescence to senescence (
chapter 5
) and in
patients with attention deficit hyperactivity disorder (ADHD) (
chapter 4
).
Summary of findings
In
chapter 1
, we provided an overview of the state of the relevant literature up until the start of
my thesis on how motivation can change cognitive control, how the neural signals associated
with these processes may be integrated and how signals in the prefrontal cortex may modulate
striatal processing. In that same chapter we also put forward a working hypothesis, suggesting
an important role for striatal dopamine in motivated cognitive control. However, which
specific dopamine receptor subtype is important for motivated cognitive control had not
been assessed, and experimental work thus far had not directly manipulated the striatum
and the dopamine system. In
chapter 3
, we filled this gap by conducting a pharmacological
study to investigate the causal role of dopamine, specifically the dopamine D2 receptor, in
task switching and in the integration between reward and task switching. In this study, we
replicated the previous observation (Aarts et al., 2010) that inter-individual variation in
the dopamine transporter genotype
(DAT1/SLC6A3)
can modulate the effect of reward on
task-switching behaviour, suggesting -again- a role for striatal dopamine in this interaction.
However, our pharmacological manipulation did not alter motivated cognitive control.
The administration of a dopamine D2 receptor agonist did however change task-switching
behaviour, irrespective of reward. This observation is in line with previous theorizing and
work in humans and rodents implicating the D2 receptor in flexible behaviour (Mehta et