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General discussion
carrying the 9R allele, but had no effect in those homozygous for the 10R allele.
These results strengthen the evidence for a causal role for dopamine in motivated cognitive
control and they reveal differences in striatal dopamine signalling between patients with
ADHD and subjects without ADHD during motivated cognitive control.
The effects observed in
chapter 4
seemat odds with those observed in healthy subjects (
chapter
3
and (Aarts et al., 2010)). In healthy young adults who carry the 9R allele, reward previously
increased the task-switch related signal in the caudate nucleus (Aarts et al., 2010). In addition,
reward anticipation had a
beneficial
effect on task switching performance in young healthy
adults (
chapter 3)
. By contrast, in the healthy control group in
chapter 4
, we did not observe
any evidence for an effect of reward on task switching, either in terms of neural signalling
or behaviour. In patients with ADHD who carry the 9R allele of the
DAT1
genotype, we
observed that reward motivation increased the task-switch related signal in the striatum (i.e.
the caudate nucleus), as it previously did in young healthy subjects (Aarts et al., 2010). In
addition, (if anything) reward had a
detrimental
effect on task switching in these patients.
Thus, the neural signal in the ADHD patients was in line with that observed previously in
young healthy subjects, but to our surprise, in the healthy control group in
chapter 4
, we
did not replicate previous work showing that the integration between reward and cognitive
control was associated with a
DAT1
genotype-dependent change in behaviour (
chapter 3
) and
striatal signalling (Aarts et al., 2010). One potential explanation for this discrepancy is related
to the age of the participants: Whereas the subjects in the healthy control group in the ADHD
study were ~38 years old, subjects in the other studies were younger (~22 years old). Striatal
dopamine levels decrease dramatically across the lifespan, starting in early adulthood (from
~20 years onwards) (Volkow et al., 1996a; Bäckman et al., 2000; Backman and Farde, 2001).
If striatal dopamine is indeed crucial for successful motivation-cognition integration, deficits
in motivated cognition should be evident with increasing age. ADHD has been associated
with a developmental delay, resulting from dysfunctional nigrostriatal dopamine projections
(Sagvolden et al., 2005). Such a developmental delay may explain the observation of an effect
of reward on task switching in patients, but not in age-matched healthy controls. The questions
remains however why this increased signalling in the 9R ADHD group is not associated with
beneficial effects on behaviour, and why they – if anything – are even behaviourally impaired
when integrating reward and task-switching signals.
In
chapter 5
we assessed whether any evidence for age-related changes in the motivational
enhancement of cognitive control could be revealed. To this end we analyzed data from
subjects ranging from14 to 69 years oldwho performed the rewarded task-switching paradigm
and we observed that increasing age was indeed associated with less flexible adaptation to
changing task demands. Specifically, the younger group showed reward-related behaviour
that depended on the cognitive condition (i.e. whether a task repetition or a task switch was
required), whereas the older group did not show any reward-related change in cognitive
control. Based on previous imaging work which revealed decreases in dopamine neurons
with increasing age, we speculate that the age-related effects observed in
chapter 5
are due