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Chapter 6
2001a) whereas prefrontal regions and prefrontal dopamine D2 receptor stimulation plays a
more prominent role in ED shifting (Floresco et al., 2006b; Robbins, 2007). Future work will
need to elucidate the differences between the neural mechanisms underlying these different
forms of behavioral flexibility.
This study was not without limitations and future work should aim to address these. Although
the current design parallels the paradigm we use in our work with human subjects, a number
of differences between the rodent and human version should be noted. First, in human subjects
we manipulated the amount of reward on a trial-by-trial basis (Aarts et al., 2010), instead of in
blocks, as is done in the rodent version. However, blocked designs have been proven effective
in revealing reward-related effects on cognition in studies with human subjects (Kouneiher
et al., 2009; Jimura et al., 2010). Second, the paradigm in humans presents a large number of
trials in a fast succession. It is well documented that increased preparation times reduce the
switch cost (Monsell, 2003). The current experimental design was based on previous work in
which conflict adaptation was successfully achieved in rodents (Haddon and Killcross, 2006),
and a first step was to expand this to the task-switching domain. The long presentation of task
cues in the current paradigmmay explain the absence of a main effect of task-switching in the
current study. An obvious next step would be to see if the trial duration can be reduced, by
increasing the number of trials, reducing the duration of the task cues and/or training animals
to perform one action per trial.
Nevertheless, we show for the first time that a complex, cue-driven task-switching task can
translate across species from humans to rodents. Also, we provide the first direct, causal
evidence that performance on this task relies on the AcbC, as we would expect from previous
neuroimaging work in humans (Pessoa, 2009; Aarts et al., 2010). This novel paradigmprovides
important new opportunities for assessing the neural basis of a range of neuropsychiatric
disorders which have been associated with deficits in the functioning of the AcbC and/or
corticostriatal circuits (e.g. schizophrenia, attention deficit hyperactivity disorder, addiction
and obsessive compulsive disorder (Graybiel and Rauch, 2000; Belin and Everitt, 2008;
Shepherd, 2013; Aarts et al., 2015; Morris et al., 2015).