The present results confirm previous observations that the striatum plays a key role in the cognitive planning of a novel action and that the dopaminergic system seems to be involved in this process. To our knowledge, this is the first study showing that striatal dopamine neurotransmission increases significantly during the performance of executive processes. Specifically, striatal dopamine is released during planning of a set-shift (compared with matching according to an ongoing rule). However, we would like to point out that, since the retrieval with shift condition involved a more demanding cognitive processing than the control task, we cannot rule out that other cognitive features of the task, beyond planning and set-shifting, may have played a certain role in modulating the release of dopamine in the striatum. Indeed, while the retrieval with shift condition required that all the features of the cue card (i.e., color, shape, and number) would be stored in short term memory, in the retrieval without shift condition, only one feature needed to be remembered.
These findings of striatal dopamine release during set-shift tasks are consistent with previous studies of dopamine depletion in non-human primates which reported a possible involvement of striatal dopamine in set-shifting tasks (Collins et al., 2000
; Roberts et al., 1994
). Similarly, indirect observations in PD have shown that controlled L-dopa withdrawal resulted in decreased executive functions (Lange et al., 1992
; Lewis et al., 2005
), thus implying a potential role of the dopaminergic substrate for the deficits observed.
Changes in BP were observed in the dorsal part of the caudate nuclei and anterior putamen (). These findings are in accordance both with anatomical and functional imaging studies. Indeed, studies in rhesus monkeys have shown that both these striatal areas receive axonal afferents mainly from the prefrontal cortex and form part of the ‘cognitive’ corticostriatal loop proposed by Alexander et al. (1986)
. Similarly, in our recent fMRI studies, we have reported a co-activation of the ventrolateral and the posterior prefrontal cortex with the caudate nucleus and putamen, respectively, during planning and execution of a set-shift (Monchi et al., 2001
). Thus, we proposed that the caudate nucleus and putamen are likely to play a critical role in the cognitive planning and execution of a self-generated novel action, respectively (Monchi et al., 2006
). It is worth noting that the putamen, unlike the caudate nucleus, has traditionally been associated more with motor-related activities rather than cognitive functions. However, there has been evidence that the role of the putamen may not be directly linked to the movement itself, but rather to the condition under which it is made (Tolkunov et al., 1998
The activation of both the caudate nucleus and putamen observed in our previous event-related fMRI study of the MCST when comparing the retrieval with shift to the retrieval without shift condition (Monchi et al., 2006
) and the striatal dopamine release measured with [11
C] raclopride PET, in the same context of set-shifting and planning, appear to suggest a possible link. However, it should be noted that, unlike our event-related fMRI studies (Monchi et al., 2001
), the block design of [11
C] raclopride PET does not allow us to separate out the different stages and components of the set-shifting task contributing to striatal dopamine release.
The lack of dopamine release in the ventral part of striatum () was consistent with the fact that the task did not contain a reward or penalty component.
The present study does not provide any insight into the relationship between hemispheric laterality and cognitive functions. Previous neuroimaging studies investigating cognitive processes have also provided controversial findings. Indeed, while some fMRI experiments in healthy subjects have reported an activation of only the right caudate nucleus (Huettel et al., 2002
; Monchi et al., 2006
; Rao et al., 1997
), other studies have shown a bilateral caudate activation (Lewis et al., 2004
; Monchi et al., 2001
). In addition, PET studies in PD have demonstrated only a unilateral striatal involvement with significant correlation between the right caudate nucleus and frontal executive tasks (Bruck et al., 2001
; Marie et al., 1999
). These discrepancies, however, are not surprising considering the different parameters measured (e.g. activation, binding potentials, uptake etc.) and study designs (e.g. block, event related, etc.).
Even though the release of dopamine was consistent across all subjects (), the limited number of participants imposes us to be cautious in generalizing this observation and extending our findings to all executive processes.
The present study supports the role of dopaminergic neurotransmission in set-shifting tasks; however, this observation does not rule out the possible contribution of other neuronal networks. In fact, recently, Aalto et al. (2005)
, studying cortical dopamine release
in healthy individuals using [11C]FLB 457
PET, reported decreased binding in the ventrolateral prefrontal cortex and medial temporal cortex during the performance of conditions with similar cognitive requirements as in the MCST such as tracking and retention of events in working memory, but not requiring set-shifting. These observations are in line with later reports proposing that changes in dopamine levels can modulate certain cognitive processes (see review by Cropley et al., 2006
). However, cholinergic and noradrenergic pathways seem also to play an important role in cognitive functioning (Dubois et al., 1983
; Scatton et al., 1983
The finding of spatially restricted dopamine release has implications for models of basal ganglia function. One of these models proposes that, during a task, there is specific enhancement of activity in corticostriatal loops involved in the current task with concomitant suppression of competing motor networks (Mink, 1996
). The neuroanatomical arrangement of the corticostriatal system in a center-surround inhibitory pattern is thought to facilitate this focusing function (Parent and Hazrati, 1993
) and dopamine may play a significant role in this context (Wickens and Kotter, 1995
). There is evidence that dopamine modulates corticostriatal activity by enhancing transmission at active synapses while suppressing it at inactive ones (Wickens and Kotter, 1995
). Therefore, the effect of dopamine release in the vicinity of highly active corticostriatal terminations could be to increase the signal-to-noise ratio by strengthening that synapse while suppressing neighboring ones.
Our study provides preliminary evidence of an increase in dopamine neurotransmission during the performance of set-shifting processes; this may have potential implications for executive function deficits underlying certain neurological disorders associated with dopamine dysfunction, such as PD.