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Chapter 2
any effects dependent on the
DAT1
are associated with the striatum. The previous observation
that motivated cognitive control depends on striatal dopamine signalling (
chapter 1
) was
replicated in
chapter 3
, by showing that the effect of reward on task switching depended on
individual differences in the
DAT1
genotype. Although the administration of bromocriptine
affected task switching, it had no effect on the interaction between reward and task switching.
Thus, the work in
chapter 3
revealed a role for dopamine in motivated cognitive control.
However, evidence for the involvement of dopamine D2 receptors in motivated cognitive
control was not provided. Given previous evidence for a role of dopamine D1 and D2
receptors (Koch et al., 2000), or even combined dopamine D1 and D2 receptor stimulation
(Ikemoto et al., 1997) in reward motivation, we aimed to manipulate the dopamine system
in a more general manner in
chapter 4
. To this end we administered the rewarded task-
switching paradigm in patients with attention deficit hyperactivity disorder (ADHD) after
intake and withdrawal of methylphenidate, a non-selective catecholamine reuptake blocker
(
box 2.2b
), and compared their performance and brain activity to that of a group of subjects
without ADHD.
Clinical relevance: Neuropsychiatric deficits in motivated cognitive con-
trol
ADHD is a neuropsychiatric disorder with symptoms related to hyperactivity, inattention
and/or impulsivity, which start in childhood (American Psychiatric Association, 1994,
2013). ADHD is not exclusively a childhood disorder, but it continues to affect`~2.5% of
adults (Simon et al., 2009). Deficits in flexible, adaptive control have been reported in ADHD
(Sonuga-Barke, 2003; Dibbets et al., 2010), but also in other neuropsychiatric disorders such
as schizophrenia (Ravizza et al., 2010), Parkinson’s disease (Cools et al., 2001a), and obsessive
compulsive disorder (OCD) (Meiran et al., 2011). Interestingly, deficits in these disorders are
not restricted to the cognitive domain, but often extend to reward processing deficits, at least
in ADHD (Plichta and Scheres, 2014), schizophrenia (Strauss et al., 2014) and OCD (Figee
et al., 2010). Combined with the abundance of evidence above showing that motivation can
indeed change cognitive processing, it is conceivable that at least some of these cognitive
deficits may actually stem from deficits in the motivational domain.
Previous work has indeed shown that motivation can improve cognitive control in children
with ADHD (Konrad et al., 2000), but studies on motivated cognitive control are thus far
absent in this group. Previous attempts to elucidate the neural mechanism underlying
aberrant neural processing in ADHD often focused on deficits in dopamine signalling in the
prefrontal cortex, but deficits in reward-related striatal dopamine have also been suggested
in ADHD (Tripp and Wickens, 2009). We hypothesized that ADHD would be accompanied
by aberrant integration of reward and cognitive neural signalling and that
striatal
dopamine
would be involved in this process.
Chapter 4
addresses this issue by assessing, in adults
with ADHD compared with healthy individuals, how reward motivation can alter neural