Dissociation of reward and effort sensitivity in methcathinone‐induced Parkinsonism

Abstract

Methcathinone‐induced Parkinsonism is a recently described extrapyramidal syndrome characterized by globus pallidus and substantia nigra lesions, which provides a unique model of basal ganglia dysfunction. We assessed motivated behaviour in this condition using a novel cost‐benefit decision‐making task, in which participants decided whether it was worth investing effort for reward. Patients showed a dissociation between reward and effort sensitivity, such that pallidonigral complex dysfunction caused them to become less sensitive to rewards, while normal sensitivity to effort costs was maintained.

What Is the Relationship between Dopamine and Effort?

“…What is remarkable is that such a consistent picture emerges despite differences in species, task, technique, and dopamine subsystem (nigrostriatal dopamine neurons versus mesolimbic dopamine release) ( Box 3 for discussion of homogeneity and diversity of dopamine). Moreover, these results align with several other studies implicating dopamine more strongly in reward than in effort processing 37 , 38 , 39 , 40 . Thus, we believe that this feature is neither anecdotal nor due to an experimental artifact.…”

“…One subtle distinction is that, even if dopamine can promote energy expenditure, it only does so as a function of the upcoming reward, and not as a function of the upcoming (energy) cost itself. Crucially, the few recent experiments that examined the influence of dopamine treatments in tasks where efforts costs and reward benefits were dissociated, also found a stronger influence on reward-based over effort-based decisions 37 , 40 . Therefore, even if these manipulations lack the temporal and anatomical precision of recording studies, they reinforce the idea that the dopamine system as a whole is much more sensitive to potential benefits than to potential effort costs, and demonstrate the generality of this relation, as well as its causal nature.…”

Dissociable Motivational Deficits in Pre-manifest Huntington’s Disease

“… 33 , 43 , 44 , 45 , 46 A recent approach to investigating motivation has been through effort-discounting paradigms, which quantify the amount of effort individuals are willing to exert in return for reward. 15 , 18 , 21 , 47 Such paradigms provide a platform to test a critical assumption of prevailing multidimensional theories of apathy—that motivational deficits should be dissociable across separate domains of effort. Here, we provide strong evidence in favor of such theories by demonstrating a selective involvement of cognitive over physical motivation in pre-manifest HD.…”

“…To date, however, no clinical study—in HD or any other patient group—has directly addressed the domain specificity of effort-based decisions. The majority of patient studies have focused on motivation in the physical domain alone, 15 , 16 , 17 , 18 , 19 with fewer examining motivation in the cognitive domain 20 , 21 and none comparing motivation across both domains within the same individuals. Furthermore, interpreting differences in motivation between patient groups relative to healthy controls can in general be challenging, given that clinical populations are likely to have comorbid motor, cognitive, or psychiatric symptoms that may confound any such differences.…”

Pharmacological evidence for the implication of noradrenaline in effort

“…For example, in recent experiments measuring dopaminergic activity using either single-unit recordings or voltammetry, it was much more sensitive to the amount of expected reward than to the level of effort [29][30][31][32][33]. Similarly, when effort, force, and reward could be dissociated, dopaminergic manipulation had little effect on effort processing compared with its effect on reward processing, as measured using choices [34][35][36][37]. Again, we do not question the strong implication of dopamine in energizing behavior and cognition [38,39], but here, our goal is to examine the possibility that energy for action can rely upon a complementary motivational process, which is critical when the action is not directly rewarded and which we will refer to as effort.…”