Motivation, reward, and Parkinson’s disease: influence of dopatherapy
Introduction
Motivation is a conscious or unconscious internal state, which incites the subject to act [28]. It influences all stages of behavioural planning: determination of aim, selection and elaboration of responses, and evaluation of consequences of action. Conversely, motivation and planning are affected by the ability to identify the behavioural relevance and the reinforcing value of environmental stimuli and to take into account the difference between the anticipated and the obtained reward. Motivation and sensitivity to reinforcement are therefore central processes for adaptive orientation of behaviour. According to Rolls [40], “computing the reward and punishment value of sensory stimuli, and then using selection between different rewards and avoidance of punishments in a common reward-based currency appears to be the fundamental solution that the brain uses in order to produce appropriate behaviour”.
This computation may be explicit when the rule is clear and the same reward is regularly associated to the same stimulus, as in Stimulus–Reward Learning. When subjects have explicitly learned the stimulus–reward association, the reward contingencies may be unexpectedly reversed (Reversal), or extinguished (Extinction) [41]. The ability to reverse the stimulus–reward–response association suggests a form of “sensitivity to reward” flexibility [11], whereas the ability to withhold a response is related to control of impulsiveness [41].
In real life, however, outcomes in terms of reward or punishment are more uncertain. Bechara et al. [3], [4] designed a task, so called the Gambling task, which resembles the decisions made in real life. The task includes four decks of cards, two of them being disadvantageous (high gains and unpredictable higher penalties), whereas the other two are advantageous (small immediate gains and lower penalties). Normal subjects progressively learn to choose the advantageous decks. This behaviour is largely implicit, since bias toward the selection of advantageous choices occurs before the subject becomes aware of the goodness or badness of his or her choice, and a great proportion of normal controls do not reach awareness [6].
Animal studies implicate limbic structures (amygdala and orbitofrontal cortex) in motivation, reinforcement associated learning, “sensitivity to reward” flexibility, and control of impulsiveness [40], [48]. The ventral striatum, which connects the limbic and frontal executive systems via the “orbitofrontal” and “cingulate” loops, [2] is also involved. In addition, the mesolimbic and the nigrostriatal dopaminergic systems, which modulate the activity of these loops, intervene in signalling changes or errors in the prediction of rewarding events [43]. In humans, reinforcement associated learning, “sensitivity to reward” flexibility, and control of impulsiveness have been shown to be impaired by orbitofrontal lesions [3], [41], whereas apathy or loss of motivation, in the absence of depression, has been observed in cases of lesions of basal ganglia [16], [24], [26]. Is apathy related to decreased sensitivity to reinforcement? Are the striatofrontal loops involved in reinforcement associated learning in humans? Does dopamine intervene in “sensitivity to reward” flexibility? Parkinson’s disease (PD), which alters the mesocorticolimbic dopaminergic system [21], [33] and consequently impairs the function of “orbitofrontal” and “cingulate” loops [1], [10], may help to answer these questions. Indeed, apathy has been observed in PD and might worsen the cognitive and behavioural difficulties of these patients [25], [45].
The aims of the study were to investigate motivation and sensitivity to reinforcement in non-demented and -depressed PD patients and to evaluate the influence of dopaminergic therapy comparing patients in “on” (with l-Dopa) and “off” (without l-Dopa) states.
Section snippets
Subjects
Thirty patients hospitalised in the Neurology Department of the Salpetriere Hospital for therapeutic equilibration or for candidature for subthalamic nucleus deep brain stimulation were recruited for the study. Inclusion criteria were idiopathic PD [20], persistence of a good reactivity to l-Dopa, lack of dementia (score >130 on the Mattis Dementia Rating Scale) [29] or depression (score <20 on the Montgomery and Asberg Depression Rating Scale (MADRS)) [30], ability to be tested not only in the
Motivation
Global ANOVA showed no repetition effect on the Apathy Scale [F(1,48)=0.025; P=0.88], but did show a group effect [F(2,48)=5.65; P=0.006] and an interaction between group and repetition [F(2,48)=8.32; P=0.0008]. Post-hoc analysis of the group effect showed that “On-first” patients (P=0.027) and “Off-first” patients (P<0.0001) differed from controls, but not one from another (P=0.13). Apathy was therefore similar in both groups of patients and more severe in patients than in controls. Post-hoc
Discussion
Several experimental variables were impaired in patients with PD. Their score on the Apathy Scale was higher than in control subjects, confirming that apathy may be observed in PD, even in non-demented and -depressed patients. Apathy was mild, since the mean score for patients was lower than the cut-off pathological score of 14. However, three patients in the “On-first” subgroup and six patients in the “Off-first” subgroup had pathological scores, comprising 39% of patients. This percentage is
Acknowledgements
INSERM and Assistance Publique supported the study. Dr. A. Bechara kindly provided us with the computerised version of his Gambling task. Dr. A.M. Bonnet and the nurses of the Centre d’Investigation Clinique and Federation de Neurologie are thanked for their contribution. Leon Tremblay gave us helpful comments. Nikki Horne revised the English.
References (49)
- et al.
Insensitivity to future consequences following damage to human prefrontal cortex
Cognition
(1994) Differential behavioral effects in frontal lobe disease
Neuropsychologia
(1968)- et al.
Role of the striatum, cerebellum and frontal lobes in the automatization of a repeated visuomotor sequence of movements
Neuropsychologia
(1998) The basal ganglia and chunking of action repertoires
Neurobiology of Learning and Memory
(1998)- et al.
Distinct contribution of the striatum and cerebellum to motor learning
Brain and Cognition
(2001) A modified Card Sorting Test sensitive to frontal lobe defect
Cortex
(1976)- et al.
Delayed response task in basal ganglia lesions in man: further evidence for a striato-frontal cooperation in behavioral adaptation
Neuropsychologia
(1996) - et al.
Memory for spatial location is affected in Parkinson’s disease
Neuropsychologia
(1996) - et al.
Probabilistic learning and reversal deficits in patients with Parkinson’s disease or frontal or temporal lobe lesions: possible effects of dopaminergic medication
Neuropsychologia
(2000) - et al.
Impaired planning but intact decision making in early Huntington’s disease: implications for specific fronto-striatal pathology
Neuropsychologia
(2000)