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Chapter 8
humans (
chapter 3 and 4
) is related to the baseline-dependency of these effects. Whereas the
effect of reward on task switching in humans were only revealed when taking into account
a baseline measure of dopamine signalling, in rodents the effects were revealed without
accounting for individual differences. This discrepancy is possibly explained by the absence
of genetic variation in rodents, caused by the inbred nature of laboratory animals.
In
chapter 7
we assessed the role of prefrontal modulation of striatal processing during
motivated cognitive control and subsequent action selection. However, the effects of prefrontal
stimulation on the processing of information about motivated cognitive control (without
taking into account response switching) did not reach significance. One potential explanation
for the effect may be related to the nature of the spiralling dopamine connections between the
striatum and the midbrain (Ikeda et al., 2013). The striatum sends inhibitory (GABA-ergic)
projections to the midbrain. These GABA-ergic connections inhibit the dopamine neurons
that project back to the (‘next’ region) in the striatum (
figure 2.1
). If we assume that distinct
SNS projections originate from the ventral striatum, the anterior caudate nucleus, posterior
caudate nucleus and putamen (
figure 2.1
), then I would speculate that the inhibition caused
by stimulation of the anterior prefrontal cortex (reflected by the decrease in reward-related
BOLD response after prefrontal stimulation observed in
chapter 7
), decreased the inhibition
of the projection from the anterior caudate nucleus to the section of the midbrain it projects
to. This part of the midbrain (which in turn projects to the posterior caudate nucleus) will
cause an increase in dopamine signalling in the posterior caudate nucleus (i.e. attenuating
the inhibitory effect of TMS, masking any direct prefrontal modulation of the prefrontal
stimulation). Crucially then, this increased signalling in the posterior caudate will increase
the inhibition on the midbrain and will subsequently decrease dopamine release from the
midbrain to the putamen (reflected by a decrease in BOLD response in the putamen during
the integration of motivation, cognition and action in
chapter 7
). However, this idea is highly
speculative and evidence to substantiate the projections assumed above is currently absent
(
future research
).
Future research
Based on the combined evidence presented in
chapter 3, 4, and 5
we propose a role for striatal
dopamine in mediating motivated cognitive control. This claim can be assessed in a number
of ways. First, direct measurements of dopamine signalling in the striatum, for example
using voltammetry or microdialysis in rodents, should reveal increases in striatal dopamine
signalling during motivated cognitive control. Second, age-related dopamine cell loss in
the striatum, measured using molecular imaging (e.g. single photon emission computed
tomography; SPECT) should be related to age-related changes in motivated cognitive control.
This latter approach would parallel the way in which the relationship between motivated
cognitive control and dopamine was previously established in Parkinson’s disease (
chapter 1:
figure 1.2f
(Aarts et al., 2012). Third, in addition to the results of NMDA lesions in
chapter