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Chapter 2
Aging and cognitive control
Aging is accompanied by a range of cognitive deficits and diminished striatal processing which
are, at least partly, due to changes in the dopamine system. These changes in the dopamine
system occur gradually across the life span and start early in adulthood (Backman and Farde,
2001). In
chapter 5
I explored how integration of reward with cognitive control information
changes across the life span, from adolescence to senescence. The results presented in
chapter
5
show that aging is indeed accompanied by diminished integration between reward and task
switching: younger subjects showed a reward-based adaptation of cognitive control, whereas
responding in older adults did not vary with changing reward conditions.
In summary, the
DAT1
-depencency and BOLD fMRI work in
chapters 3 and 4
suggest
that striatal dopamine is involved in motivated cognitive control. In addition, previous
work has shown age-related reductions in striatal dopamine. In chapter 5 I observed age-
related changes in motivation-cognition integration (
chapter 5
). Together these results
suggest a role for the striatum in mediating this interaction. However, changes in BOLD
response (
chapter 4
and
box 2.4
),
DAT1
genotype-dependent effects (
chapter 3 and 4
) or
the correlation between aging and motivated cognitive control (
chapter 5
) do not provide
evidence for a causal role. When one wants to assess whether a region is crucial for a given
function, the consequences of manipulating this region or its associated circuit is required.
To assess whether the striatum was indeed crucial for successful integration of reward and
task-switching signals, I aimed to disrupt processing in the ventral striatum in rodents. One
challenge was the absence of a suitable paradigm to measure this effect in rodents. Paradigms
in rodents often assess whether they can learn to flexibly adapt their behaviour, based on trial-
and-error learning (i.e. without the use of cues) (Ragozzino et al., 1999). Further, although
rewards are generally used to reinforce behaviour, the amount of reward an animal anticipates
is often not directly manipulated, at least not on tasks measuring behavioural flexibility. To
overcome this issue, I first developed a rodent homologue of the rewarded task-switching
paradigm (
chapter 6
). Next, I applied excitotoxic lesions (
box 2.5
) to the rodent striatum
(i.e. the nucleus accumbens core) to assess whether it is crucial for optimal integration of
reward information and cognitive processes (
chapter 6
). The results in
chapter 6
showed
reward-related improvements in cognitive flexibility in animals with an intact striatum, but
not in those with lesions of the striatum. Together the results so far are in line with the role for
striatal dopamine in motivated cognitive control. However, in chapter 1 we hypothesized that
communication between the prefrontal cortex and the striatum may also be important for
motivated cognitive control. More specifically, we hypothesized that signals in the prefrontal
cortex might control activity in the striatum in a top-down manner.