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General discussion
updating of task-sets in the high reward condition (
chapter 6
) or in maintaining the new
strategy after new learning has taken place (after a successful set-shift and the receipts of a
reward).
Rewarded task-switching
In the rewarded task-switching paradigm presented in
chapter 6
, two discrimination tasks
alternate unpredictably on a trial by trial basis and the use of cues is required to determine the
relevant stimulus dimension. This paradigm is the first rodent paradigm that manipulates and
compares reward conditions (i.e. high vs. low reward) and cognitive conditions (i.e. switch vs.
repeat trials). The paradigm parallels the human paradigm (
chapters 3, 4, 5, and 7
; but see
limitations
) and the pattern of results in
chapter 6
is generally congruous with our previous
work: Reward can improve cognitive flexibility both in (a genetically determined subset of)
humans and in rodents. The results from the rodent work (
chapter 6
) also fit remarkably well
with the pattern of results in the aging work (
chapter 5
): A reduction in the reward benefit
on task switching was observed both in older adults and in animals with lesions of the ventral
striatum, strengthening the hypothesis that the age-related effects observed in
chapter 5
were
related to age-related changes in striatal dopamine.
Implications for neuropsychiatry
In
chapter 4 and 5
we tested the hypothesis that cognitive deficits in ADHD and aging may be
grounded in a deficit to use information about potential gains to adequately allocate cognitive
processes. A similar deficit could underlie cognitive deficits observed in other neuropsychiatric
disorders such as schizophrenia, addiction, Parkinson’s disease and obsessive compulsive
disorder (OCD).
For example, both schizophrenia and OCD have been associated with cognitive deficits
(
chapter 2
) and changes in the corticostriatal circuitry (Shepherd, 2013). Cognitive deficits in
schizophrenia are thought to be related to hypoactivity in the mesocortical dopamine system,
whereas positive symptoms (e.g. hallucinations and delusions) are thought to be related
to hyperactivity in the dopaminergic nigro-striatal connections and increased dopamine
D2 receptor signalling (Simpson et al., 2010). In line with the work in this thesis, excessive
dopamine D2 receptor stimulation may induce a flexible state, at the expense of the ability to
maintain stable representations (Barch and Ceaser, 2012) decreasing the ability of patients
with schizophrenia to filter out irrelevant input. The repetitive behaviours typically observed
inOCDon the other hand are thought to originate from increased activity in the corticostriatal
circuitry, in particular hyperactivity in the cortex and hypoactivity in the striatum. Combined
with the potential involvement of (at least) dopamine D1 receptor in OCD (Nordstrom and
Burton, 2002), this underlying pathology may yield excessive maintenance of prefrontal
representations, causing the inflexible, repetitive behaviours observed in OCD. In addition,