Striatal Dopamine and the Interface between Motivation and Cognition.

Abstract

Brain dopamine has long been known to be implicated in the domains of appetitive motivation and cognition. Recent work indicates that dopamine also plays a role in the interaction between appetitive motivation and cognition. Here we review this work. Animal work has revealed an arrangement of spiraling connections between the midbrain and the striatum that subserves a mechanism by which dopamine can direct information flow from ventromedial to more dorsal regions in the striatum. In line with current knowledge about dopamine's effects on cognition, we hypothesize that these striato-nigro-striatal connections provide the basis for functionally specific effects of appetitive motivation on cognition. One implication of this hypothesis is that appetitive motivation can induce cognitive improvement or impairment depending on task demands.

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and motivation, to more dorsal frontostriatal circuits, associated
with cognition and action (Alexander et al., 1986; Haber and
Knutson, 2010; Figure 1).
Although the widely distributed and diffuse nature of its projec-
tion system to large parts of the forebrain concurs with an account
of dopamine in relatively non-specific terms, such as serving activa-
tion or energization, it is also clear that dopamine does not simply
amplify (or suppress) all forebrain activity in a functionally non-
specific manner. Indeed extensive evidence indicates that effects of
dopamine depend on specific task demands and their underlying
neural systems (Robbins, 2000; Cools et al., 2001a; Frank et al.,
2004). In line with these insights, we suggest here that changes in
appetitive motivation, which may result from changes in neuro-
chemical activity, for example, due to stress, fatigue, or neuropsy-
chiatric abnormality, also have functionally selective consequences
for cognition.
More specifically, we put forward the working hypothesis
that appetitive motivation might promote selectively our abil-
ity to switch between different tasks, providing us with some of
the cognitive flexibility that is required in our constantly chang-
ing environment. Conversely, we speculate, based on preliminary
data, that dopamine-mediated appetitive motivation might also
have detrimental consequences for cognition, e.g., by impairing
cognitive focusing and increasing distractibility. The implication
of this speculation is that dopamine-mediated appetitive motiva-
tion might potentiate flexible behavior, albeit not by potentiating
the impact of current goals on behavior. This speculation stems
partly from the recognition that the motivational forces that drive
behavior are not always under goal-direct control and can be mala-
daptive (Dickinson and Balleine, 2002). Moreover dopamine is
well known to play an important role in mediating the detrimental
(i.e., non-goal-directed) consequences of reward (Berridge, 2007;
Robbins and Everitt, 2007).
IntroductIon
The ability to control our behavior requires our actions to be goal-
directed, and our goals to be organized hierarchically. Goals can
be defined at different levels: motivational goals (e.g., rewards),
cognitive goals (e.g., task-sets), and action goals (e.g., stimulus–
response mappings). Thus, goal-directed behavior requires, among
other things, the transformation of information about reward into
abstract cognitive decisions, which in turn need to be translated
into specific actions. The mechanisms underlying this hierarchy of
goal-directed control are not well understood.
This paper focuses on the degree to which such goal-directed
behavior is controlled by incentive motivation. We have restricted
our discussion to the effects of appetitive motivation, while taking
note of the wealth of evidence indicating that stimuli that acti-
vate the appetitive motivational system have an inhibitory influ-
ence on behavior that is controlled by the aversive motivational
system (Konorsky, 1967; Dickinson and Balleine, 2002). Unlike
aversive motivation, appetitive motivation refers to the state trig-
gered by external stimuli that have rewarding properties and has
been argued to have a general potentiating or enhancing effect on
behavior and cognition (Dickinson and Balleine, 2002; Robbins
and Everitt, 2003; Krawczyk et al., 2007; Pessoa, 2009; Jimura
et al., 2010; Pessoa and Engelmann, 2010; Savine and Braver,
2010). Its effects on behavior and cognition have been associ-
ated with changes in neurochemical activity, such as increases
in dopamine signaling in the striatum (Lyon and Robbins, 1975;
Ikemoto and Panksepp, 1999; Robbins and Everitt, 2003; Berridge,
2007). This observation is generally in keeping with proposals
that dopamine plays an important role in reward-related effort
(Salamone et al., 2007) and generalized activation/energization
of behavior (Robbins and Everitt, 2007). It is also consistent with
data suggesting that dopamine might direct information flow
from ventromedial frontostriatal circuits, implicated in reward
Striatal dopamine and the interface between motivation and
cognition
Esther Aarts1*, Mieke van Holstein2 and Roshan Cools2,3
1 Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA
2 Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
3 Department of Psychiatry, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
Brain dopamine has long been known to be implicated in the domains of appetitive motivation
and cognition. Recent work indicates that dopamine also plays a role in the interaction between
appetitive motivation and cognition. Here we review this work. Animal work has revealed an
arrangement of spiraling connections between the midbrain and the striatum that subserves a
mechanism by which dopamine can direct information flow from ventromedial to more dorsal
regions in the striatum. In line with current knowledge about dopamine’s effects on cognition,
we hypothesize that these striato-nigro-striatal connections provide the basis for functionally
specific effects of appetitive motivation on cognition. One implication of this hypothesis is
that appetitive motivation can induce cognitive improvement or impairment depending on
task demands.
Keywords: dopamine, motivation, cognition, striatum, flexibility, prefrontal cortex, reward, Parkinson’s disease
Edited by:
Wim Notebaert, Ghent University,
Belgium
Reviewed by:
K. Richard Ridderinkhof, University of
Amsterdam, Netherlands
Patrick Santens, Gent University,
Belgium
*Correspondence:
Esther Aarts, Helen Wills Neuroscience
Institute, University of California at
Berkeley, 132 Barker Hall, Berkeley, CA
94720-3190, USA.
e-mail: estheraarts@berkeley.edu
www.frontiersin.org July 2011 | Volume 2 | Article 163 | 1
Review ARticle
published: 14 July 2011
doi: 10.3389/fpsyg.2011.00163

Page 2

Our working hypothesis is grounded in (albeit preliminary)
empirical evidence indicating opposite effects of both dopamin-
ergic and motivational/affective state manipulations on cogni-
tive flexibility and cognitive focusing, which have been argued to
reflect distinct striatal and prefrontal brain regions respectively
(Crofts et al., 2001; Bilder et al., 2004; Dreisbach and Goschke,
2004; Dreisbach, 2006; Hazy et al., 2006; Cools et al., 2007; Rowe
et al., 2007; van Steenbergen et al., 2009; Cools and D’Esposito,
2011). Indeed current models highlight a role for dopamine, par-
ticularly in the striatum, in the flexible updating of current task-
representations (Hazy et al., 2006; Maia and Frank, 2011). The
finding that appetitive motivation is associated with robust changes
in dopamine levels particularly in the striatum, thus concurs with
our hypothesis that appetitive motivation potentiates (at least some
forms of) cognitive flexibility, perhaps even at the expense of cog-
nitive focusing. Such a bias toward cognitive flexibility should be
generally adaptive, given that motivational goals in the real world
are not often readily available, thus requiring preparatory behavior
that is flexible rather than focused (Baldo and Kelley, 2007).
Together these observations suggest that appetitive motivation
acts to enhance cognition in a manner that is functionally specific,
varying as a function of task demands, and that these functionally
specific effects are mediated by dopamine. Clearly, as in the case
of dopamine (Cools and Robbins, 2004; Cools et al., 2009), effects
of appetitive motivation will vary not only as a function of task
demands, but also as a function of the baseline state of the system.
Thus both motivational and neurochemical state changes will have
rather different effects in individuals with low and high baseline
levels of motivation, consistent with the existence of multiple Yerkes
Dodson “inverted U shaped” functions (Yerkes and Dodson, 1908;
Cools and Robbins, 2004).
Let us briefly discuss the role of striatal dopamine in the two
separate domains of motivation and cognitive control before
addressing its role in their interaction.
dopamIne and appetItIve motIvatIon
The ventromedial striatum (VMS, including the nucleus accum-
bens) is highly innervated by mesolimbic dopaminergic neurons
and is well known to be implicated in reward and motivation
(Robbins and Everitt, 1992; Berridge and Robinson, 1998; Ikemoto
and Panksepp, 1999; Schultz, 2002; Knutson and Cooper, 2005;
Baldo and Kelley, 2007). Thus dopamine manipulations in the
VMS affect performance on multiple paradigms thought to
measure motivated behavior, including conditioned reinforce-
ment, Pavlovian-instrumental transfer paradigms, effort-based
decision making tasks, and progressive ratio schedules (Taylor
and Robbins, 1984; Dickinson et al., 2000; Wyvell and Berridge,
2000, 2001; Parkinson et al., 2002). These experiments primarily
reveal effects of dopamine on so-called preparatory conditioned
responses, which are thought to reflect activation of a motivational
system (Dickinson and Balleine, 2002), while leaving unaffected,
or if anything, having the opposite effect on the more stereotypic
patterns of consummatory responding (Robbins and Everitt, 1992;
Baldo and Kelley, 2007). Thus administration of the indirect cat-
echolamine enhancer amphetamine in the VMS of hungry rats
potentiated locomotor excitement in the presence of food and
increased lever pressing in response to, or in anticipation of a
reward-predictive cue, while decreasing or leaving unaffected food
intake as well as appetitive hedonic responses like taste reactivity
(Taylor and Robbins, 1984; Bakshi and Kelley, 1991; Pecina et al.,
1997; Wyvell and Berridge, 2000, 2001). Conversely, dopamine
receptor blockade or dopamine lesions in the VMS reduced loco-
motor activity and cue-evoked incentive motivation for reward
(Dickinson et al., 2000; Parkinson et al., 2002), while again leaving
unaffected or even increasing food intake (Koob et al., 1978). These
animal studies emphasize the importance of VMS dopamine in
appetitive motivation and suggest that the hedonic or consumma-
tory aspects of reward are likely mediated by a different, possible
antagonistic system (Floresco et al., 1996; Robbins and Everitt,
1996, 2003; Berridge and Robinson, 1998; Ikemoto and Panksepp,
1999; Baldo and Kelley, 2007; Berridge, 2007; Phillips et al., 2007;
Salamone et al., 2007; for similar suggestions in humans, see Aarts
et al., 2010).
At first sight, this well-established observation provides appar-
ently clear grounds for assuming that dopamine contributes to
optimal reward- or goal-directed behavior. However, psychologists
have also long recognized that there are multiple distinct compo-
nents to the motivation of behavior (Konorsky, 1967; Dickinson
and Balleine, 2002). Thus instrumental behavior is motivated not
only by the goals that we set ourselves, but also by generalized drives
and/or so-called Pavlovian “wanting,” the latter two processes not
necessarily always contributing to adaptive, optimized behavior.
To clarify this point, it may help to consider the operational defi-
nition that psychologists have invoked for distinguishing instru-
mental behavior that is goal-directed from instrumental behavior
that is not goal-directed, i.e., habitual (Dickinson and Balleine,
2002). Following this tradition, behavior is goal-directed only if
it accords to two criteria; first, it has to be driven by knowledge
about the contingency between the action and the outcome (as
measured with contingency degradation tests); second, it has to
be sensitive to changes in the value of the goal (as measured with
outcome devaluation tests, involving for example selective satiety).
Using these operational definitions, Dickinson and Balleine (2002)
have established that Pavlovian conditioned stimuli that induce
so-called “wanting” can modify instrumental behavior without
accessing action–outcome representations, that is, in a manner
that is not goal-directed. This is illustrated most clearly by the
role of reward-predictive stimuli in compulsive craving for drugs of
abuse or other targets of addiction, which of course almost always
implicates dopamine dysfunction (Berridge and Robinson, 1998;
Everitt and Robbins, 2005; Volkow et al., 2009). In keeping with
this observation are suggestions that motivational influences on
instrumental behavior by Pavlovian stimulus reinforcer contingen-
cies might reflect modulation of well-established habits rather than
of goal-directed behavior (Dickinson and Balleine, 2002). Data
showing that dopamine D1/D2 receptor antagonists attenuated
Pavlovian-instrumental transfer without affecting instrumen-
tal incentive learning (Dickinson et al., 2000) indeed suggested
that dopamine might act through Pavlovian processes rather than
through modifying action–outcome representations (Dickinson
and Balleine, 2002).
In this context, it is perhaps not surprising that the effects of
appetitive motivation on cognition that are mediated by dopa-
mine are functionally specific, leading to cognitive improvement
Aarts et al. Dopamine and the motivation–cognition interface
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paradigm demonstrating that effects of dopamine D1/D2 receptor
agonist administration to healthy young volunteers on flexibility
(task-switching) and focusing (distractor–resistance) were accom-
panied by drug effects on the striatum and the PFC respectively
(Cools et al., 2007).
In sum, dopamine’s effects on cognition are known to be func-
tionally specific rather than global, with opposite effects on cogni-
tive flexibility and cognitive focusing. These opposite effects have
been proposed to reflect modulation of distinct brain regions, with
dopamine in the striatum playing a prominent role in a form of
flexibility that involves shifting to well-established, i.e., “habitized”
stimulus–response sets.
dopamIne and the motIvatIon–cognItIon
InteractIon
So far we have seen that striatal dopamine’s effect on motivated
behavior is most prominent in terms of its preparatory component
and that such preparatory effects can be maladaptive. This observa-
tion that dopamine’s effect on motivation might have maladaptive
consequences for behavior concurs with observations that effects
of dopamine in the cognitive domain depend on task demands
and associated neural systems, so that dopaminergic drugs can
have detrimental as well as beneficial consequences for cognition.
Together these insights have led to the speculation that incentive
motivation might act to enhance cognitive performance by poten-
tiating dopamine in the striatum in a manner that is functionally
specific, i.e., restricted to a form of cognitive flexibility that involves
shifting to well-established habits, and not extending to, or even at
the expense of cognitive focusing. Below we review empirical evi-
dence that address the different aspects of this working hypothesis.
evIdence from neuroanatomIcal studIes
Motivation–cognition interactions have long been proposed to
reflect dopamine-dependent interfacing between different paral-
lel frontostriatal circuits associated with motivation and cognition
(Figure 1). For example, neuroanatomical studies in rats from the
1970s have suggested that activity in the dorsal striatum is modu-
lated by activity in the ventral striatum via the dopaminergic cells
in the substantia nigra (Nauta et al., 1978). Tracer experiments
in non-human primates have revived this notion by revealing an
arrangement of spiraling striato-nigro-striatal (SNS) connections
between the dopaminergic cells in the midbrain and striatal regions
that were defined on the basis of their frontal cortical input (Haber
et al., 2000; Haber, 2003). Similar connections have been found in
rodents (Ikemoto, 2007). The SNS connections are thought to direct
information flow in a feed-forward manner via stepwise disinhi-
bition of the ascending dopaminergic projections from the VMS
(including the nucleus accumbens), via the dorsomedial striatum
(DMS, caudate nucleus), to the dorsolateral striatum (DLS, puta-
men). The resulting information flow from ventromedial to dorso-
lateral striatal regions provides a hierarchical (or heterarchical, see
Haruno and Kawato, 2006) mechanism by which motivational goals
can influence cognitive and subsequent motor control processes.
Indeed, the VMS has long been hypothesized to provide the basis
for the interface between motivation and action on the basis of its
major inputs from limbic areas like the amygdala, hippocampus and
the anterior cingulate cortex (ACC) and output to the motor areas
or cognitive impairment depending on the specific task demands
under study. An important implication of this observation is that
effects of dopamine on interactions between motivation and cog-
nitive control that appear to be mediated by a modification of
motivational influences on cognitively mediated, goal-directed
behavior may in fact reflect modification of motivational influ-
ences on habitual behavior.
dopamIne and cognItIon
Accumulating evidence in the domain of cognition indicates
that manipulations of dopamine can have contrasting effects as
a function of task demands. For example, opposite effects have
been observed in terms of cognitive flexibility and cognitive
focusing (Crofts et al., 2001; Bilder et al., 2004; Cools et al., 2007;
Durstewitz and Seamans, 2008; Durstewitz et al., 2010; Cools and
D’Esposito, 2011). Mehta et al. (2004) have shown that dopamine
D2 receptor blockade after acute administration of the antagonist
sulpiride impaired cognitive flexibility (measured in terms of task-
switching), but improved cognitive focusing (measured in terms
of delayed response performance with task-irrelevant distractors).
Similar contrasting effects on cognitive flexibility and focusing have
been reported after dopamine lesions in non-human primates
(Roberts et al., 1994; Collins et al., 2000; Crofts et al., 2001), after
dopaminergic medication withdrawal in patients with Parkinson’s
disease (PD; Cools et al., 2001a, 2003, 2010a) and as a function of
genetic variation in human dopamine genes (Bilder et al., 2004;
Colzato et al., 2010). Evidence from functional neuroimaging and
computational modeling work has suggested that these opposite
effects might reflect modulation of distinct brain regions, with the
striatum mediating effects on at least some forms of cognitive flexi-
bility, but the prefrontal cortex (PFC) mediating effects on cognitive
focusing (Hazy et al., 2006; Cools et al., 2007; Cools and D’Esposito,
2011). This hypothesis likely reflects an oversimplified view of
dopamine’s complex effects on cognition, with different forms of
cognitive flexibility implicating distinct neural and neurochemical
systems (Robbins and Arnsten, 2009; Kehagia et al., 2010; Floresco
and Jentsch, 2011). In particular, the striatum seems implicated
predominantly in a form of cognitive flexibility that involves shift-
ing to well-established (“habitized”) stimulus–response sets, that
does not require new learning or working memory. For example
6-OHDA lesions in the striatum of marmosets impaired set-shifting
to an already established set, but left unaffected set-shifting to a
new, to-be-learned set (Collins et al., 2000). This finding paralleled
the beneficial effects of dopaminergic medication in PD, which
implicates primarily the striatum. These effects were restricted to
task-set switching between well-established sets, and did not extend
to set shifting to new, to-be-learned sets (Cools et al., 2001b; Lewis
et al., 2005; Slabosz et al., 2006). The PFC might well be implicated
in higher-order forms of set shifting that do involve new learning
and/or working memory (Monchi et al., 2004; Floresco and Magyar,
2006; Cools et al., 2010b; Kehagia et al., 2010). Interestingly, the
beneficial effects of dopaminergic medication in PD on this striatal
form of well-established, habit-like task-set switching were accom-
panied by detrimental effects on cognitive focusing, as measured in
terms of distractor–resistance during the performance of a delayed
response task (Cools et al., 2010a). These findings paralleled phar-
macological neuroimaging work with the same delayed response
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sensitivity of neuronal firing in the DMS as well as midbrain dopa-
mine neurons to appetitive motivation. In this task, one of four
directions was randomly assigned as the target location by a cue
that also signaled the anticipation of reward. Subsequently, the
monkey had to make a saccade to the remembered location. It was
found that cues that predicted reward resulted in earlier and faster
saccades relative to cues that predicted no reward. Firing patterns in
caudate nucleus (DMS) neurons correlated with the change in sac-
cade behavior, changing their preferred direction to the rewarded
direction (Kawagoe et al., 1998). In a follow-up study, the authors
observed that reward-predictive cues resulted in increased firing
of dopaminergic neurons in the midbrain, as well as in neurons of
the caudate nucleus (DMS; Kawagoe et al., 2004). Together, these
findings demonstrate that effects of reward anticipation on DMS
activity and associated motor-planning behavior were accompanied
by changes in dopamine activity.
In humans, a role for dopamine in the effects of motivation on
cognition has so far been addressed only in the domain of long-term
memory associated with the hippocampus (Wittmann et al., 2005;
Adcock et al., 2006; Schott et al., 2006; for a review, see Shohamy
and Adcock, 2010). This relatively young field suggests that dopa-
mine may well play a role in the long-term plasticity-enhancing
effects of motivation. In the next section, we address studies that
focus on dopamine-dependent effects of motivation on shorter
term plasticity, involving the striatum.
evIdence from human studIes: motIvatIon and cognItIve
flexIbIlIty
Data from two recent studies support the hypothesis that dopa-
mine is critical for interactions between motivation and cognition.
Specifically, these studies highlight an important role for dopamine
in the modification by appetitive motivation of switching between
well-established habits. The set-shifting paradigm involved cued
task-switching between well-learnt task-sets, minimizing learn-
ing and working memory processes (Rogers and Monsell, 1995).
Subjects switched between responding according to the direction
of the arrow (task A) and responding according to the direction
indicated by the word (task B) of a series of arrow-word targets
(consisting of the words “left” or “right” in a left or right pointing
arrow; Figure 2A). Repetitions or switches of task-set were pseudo-
randomly preceded by high or low reward cues. In the first study,
young healthy adults performed the task in the magnetic resonance
scanner and both behavioral and neural responses were assessed as
a function of inter-individual variability in dopamine genes (Aarts
et al., 2010). In particular, we focused on a common variable num-
ber of tandem repeats (VNTR) polymorphism in the dopamine
transporter gene (DAT1), expressed predominantly in the striatum.
Relative to the 10R homozygotes, the 9R carriers – with presumably
increased striatal dopamine levels – exhibited significant reward
benefits in terms of overall performance and increased reward-
related BOLD responses in VMS. However, most critically, they also
demonstrated significant reward benefits in terms of task-switching
(i.e., reduced switch costs in the high versus low reward condition).
This effect was accompanied by a potentiation of switch-related
BOLD responses in DMS (caudate nucleus) in the high reward
versus the low reward condition (Figures 2B,C). Importantly, the
reward-related activity in VMS correlated positively with the effects
via the globus pallidus (Mogenson et al., 1980; Groenewegen et al.,
1996). However, rather than a direct limbic-motor connection, the
SNS connections provide a more physiologically and psychologi-
cally plausible mechanism by which motivational goals exert their
influence on action (Haber et al., 2000).
evIdence from psychopharmacologIcal studIes In anImals
Rodent research on drug addiction has provided evidence for the
functional importance of dopamine-mediated interactions between
ventral and dorsal parts of the striatum. For example, Belin and
Everitt (2008) have adopted an intrastriatal disconnection proce-
dure in rats to investigate the necessity of the SNS connections in
the transition of reward-directed drug-seeking behavior to habitual
behavior associated with the DLS. The authors lesioned the VMS
selectively on one side of the rat brain and, concomitantly, blocked
dopaminergic input from the substantia nigra in the DLS with a
receptor antagonist on the contralateral side of the brain. Thus,
they functionally disconnected the VMS and DLS on both sides of
the brain, while leaving unilateral VMS and DLS on opposite sites
intact. This functional disconnection between VMS and DLS greatly
reduced the transition of VMS-associated to DLS-associated habit-
ual behavior, whereas the unilateral manipulations were ineffective
in isolation (Belin and Everitt, 2008). These data show the functional
importance of the spiraling SNS connections in VMS control over
dorsal striatal functioning in addiction (Belin et al., 2009).
Functional evidence for a role of dopamine in interactions
between motivation and DMS-associated functions has also been
established in non-human primates. For example, neurophysio-
logical recordings by Hikosaka and colleagues during the perfor-
mance of a memory-guided saccadic eye-movement task revealed
Figure 1 | Ventromedial to dorsolateral direction of information flow
through frontostriatal-nigral circuitry. Interactions between the different
frontostriatal loops involved in motivational control (red), cognitive control
(yellow), and motor control (blue) can take place at the level of the SNS
connections (bend arrows) or at the level of the frontostriatal connections
(straight arrows). The direction of information flow is always from ventromedial
to dorsolateral regions in the frontostriatal circuitry. SNS, striato-nigral-striatal;
N. Acc, nucleus accumbens (ventromedial striatum); Caud, caudate nucleus
(dorsomedial striatum); Put, putamen (dorsolateral striatum); OFC,
orbitofrontal cortex; ACC, anterior cingulate cortex; DLPFC, dorsolateral
prefrontal cortex; PMC, premotor cortex.
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with the degree of dopamine depletion in different striatal sub-
regions as measured with 123I-FP-CIT single photon emission com-
puted tomography (SPECT). First, we replicated previous studies
by demonstrating a switch deficit in PD relative to healthy controls.
Interestingly, this deficit was restricted to certain conditions of the
task, revealing a disproportionate difficulty with switching to the
best established, most dominant “arrow” task. Additionally, the
SPECT measurements showed that this switch deficit in PD was
associated with dopamine cell loss in the most affected striatal
sub-region (posterior putamen, Figure 2E), thus demonstrating
the involvement of striatal dopamine in this particular “habit-like”
of reward on subsequent switch-related activity during the targets
in DMS, with high dopamine subjects demonstrating high activ-
ity in both striatal regions (Figure 2D; Aarts et al., 2010). These
dopamine-mediated motivation–cognition interaction effects
were recently replicated in an independent dataset (van Holstein
et al., 2011) and strengthened our working hypothesis that striatal
dopamine mediates motivational modification of certain cognitive
functions in humans.
In a second study, we investigated the effect of appetitive moti-
vation on cognitive flexibility in patients with PD using the same
paradigm (Figure 2A). Effects within the PD group were associated
Figure 2 | experimental evidence for the beneficial effect of motivation on
cognitive flexibility in humans. (A) The rewarded set-shifting paradigm used in
our studies to investigate the motivation–cognition interface. (B) In our genetic
imaging study (Aarts et al., 2010), participants with genetically determined high
striatal dopamine levels benefited more from reward anticipation in terms of
set-shifting than participants with low dopamine levels. (C) In our genetic
imaging study (Aarts et al., 2010), reward cues elicited activity in VMS (in red),
whereas the dopamine-dependent effect of reward prediction on set shifting
was observed in DMS (in yellow). (D) Activity in these striatal sub-regions [see
(C)] was positively correlated, with high striatal dopamine subjects showing high
activity in both VMS and DMS during reward anticipation and rewarded
set-shifting respectively. (e) In our SPECT study in Parkinson’s disease (Aarts
et al., under review), patients showed the most marked dopamine depletion in
dorsolateral striatum (posterior putamen), whereas ventromedial striatum (n.
accumbens) was least affected. (F) Patients with the greatest dopamine
depletion (i.e., least dopamine cell integrity) showed the greatest effects of
anticipated reward in reducing the switch cost in the dominant arrow task
[(switch-repeat)low − (switch-repeat)high]; presumably by increased reward-
induced dopamine release in the relatively intact neurons in ventromedial
striatum.
Aarts et al. Dopamine and the motivation–cognition interface
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