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General discussion
in this region (Sattler and Tymianski, 2001). The loss of neurons in the nucleus accumbens
will disrupt both its input from the cortex, as well as its output to the dorsal striatum (e.g. via
the midbrain). In summary, these results reflect that information transfer from the nucleus
accumbens (disrupted in
chapter 6
) to the dorsal striatum (measured in
chapter 5
) mediates
motivated cognitive control. In addition, the results fit well with those from chapter 7: NMDA
lesions (
chapter 6
) will also disrupt prefrontal input to the striatum, disrupting prefrontal
modulation of striatal processing (
chapter 7
).
It is clear from the literature that dopamine is involved in flexible cognitive control. In
chapter
3
we show a clear and causal role for the dopamine D2 receptor in task switching. Work on
the role for dopamine D1 and D2 receptors in reward processing suggests that concurrent
activation of dopamine D1 and D2 receptors is crucial for reward-related processes (Ikemoto
et al., 1997). Conversely, it was suggested that dopamine D1 –receptor stimulation may be
crucial for reward-related processes (Beninger and Miller, 1998; Meririnne et al., 2001). In
chapter 4
, the administration of methylphenidate in adults with ADHD normalized the
increased signal in the caudate nucleus which was present when the patients had not taken
their medication, possibly by increasing dopamine levels in the striatum (Volkow et al., 2001),
but possibly also (noradrenaline) in the prefrontal cortex (Berridge and Arnsten, 2013).
Although the work in
chapter 3 and 4
strengthened the evidence for a role for dopamine
in motivated cognition, it did not lead to a conclusion about which dopamine receptor is
involved. Future work will have to elucidate which dopamine receptor mediates effects of
reward motivation on cognitive control (
future research
).
Rewarded task switching vs. motivated cognitive control
The work in this thesis focused on one aspect of cognitive control: switching between well-
established task sets. However, as was discussed in
chapter 1
, there are numerous ways to
manipulate and measure motivation and cognitive control and differences between these
paradigms result in the recruitment of different brain regions and potentially opposing effects
of dopamine.
Studies that measure attention, working memory, or forms of flexible control that require new
learning commonly report effects in the prefrontal cortex (Pochon et al., 2002; Locke and
Braver, 2008; Engelmann et al., 2009; Pessoa and Engelmann, 2010), while our form of flexible
‘habit-like’ cognitive control appears to rely more heavily on the striatum than it does on the
cortex (Aarts et al., 2010) (
chapter 1
). However, our work and that of others has shown that
effects of reward motivation on cognitive control are not restricted to the prefrontal cortex and
often both cortical and striatal regions are activated during motivated cognitive control, also
when ‘prefrontal’ paradigms are used. For example, signals in the striatum and inferior frontal
gyrus have been associated with reward effects on response inhibition and attention tasks
(Padmala and Pessoa, 2010; Krebs et al., 2012) and reward reduced conflict-related signalling
in the medial PFC during a Stroop-like task and increased coupling between the ventral