Motivation determines multiple aspects of behavior, including action selection and energization of behavior. Several components of the underlying neural systems have been examined closely, but the specific role of the different neuromodulatory systems in motivation remains unclear. Here, we compare directly the activity of dopaminergic neurons from the substantia nigra pars compacta and noradrenergic neurons from the locus coeruleus in monkeys performing a task manipulating the reward/effort trade-off. Consistent with previous reports, dopaminergic neurons encoded the expected reward, but we found that they also anticipated the upcoming effort cost in connection with its negative influence on action selection. Conversely, the firing of noradrenergic neurons increased with both pupil dilation and effort production in relation to the energization of behavior. Therefore, this work underlines the contribution of dopamine to effort-based decision making and uncovers a specific role of noradrenaline in energizing behavior to face challenges.

IntroductionWhile several theories have highlighted the importance of the noradrenergic system for behavioral flexibility, a number of recent studies have also shown a role for noradrenaline in motivation, particularly in effort processing. Here, we designed a novel sequential cost/benefit decision task to test the causal influence of noradrenaline on these two functions in rhesus monkeys.MethodsWe manipulated noradrenaline using clonidine, an alpha-2 noradrenergic receptor agonist, which reduces central noradrenaline levels and examined how this manipulation influenced performance on the task. ResultsClonidine had two specific and distinct effects: first, it decreased choice variability, without affecting the cost/benefit trade-off; and second, it reduced force production, without modulating the willingness to work.ConclusionsTogether, these results support an overarching role for noradrenaline in facing challenging situations in two complementary ways: by modulating behavioral volatility, which would facilitate adaptation depending on the lability of the environment, and by modulating the mobilization of resources to face immediate challenges.Electronic supplementary materialThe online version of this article (10.1007/s00213-018-4963-z) contains supplementary material, which is available to authorized users.

To survive in their complex environment, primates must integrate information over time and adjust their actions beyond immediate events. The underlying neurobiological processes, however, remain unclear. Here, we assessed the contribution of the ventromedial prefrontal cortex (VMPFC), a brain region important for value-based decision-making. We recorded single VMPFC neurons in monkeys performing a task where obtaining fluid rewards required squeezing a grip. The willingness to perform the action was modulated not only by visual information about Effort and Reward levels but also by contextual factors such as Trial Number (i.e., fatigue and/or satiety) or behavior in recent trials. A greater fraction of VMPFC neurons encoded contextual information, compared with visual stimuli. Moreover, the dynamics of VMPFC firing was more closely related to slow changes in motivational states driven by these contextual factors rather than rapid responses to individual task events. Thus, the firing of VMPFC neurons continuously integrated contextual information and reliably predicted the monkeys's willingness to perform the task. This function might be critical when animals forage in a complex environment and need to integrate information over time. Its relation with motivational states also resonates with the VMPFC's implication in the "default mode" or in mood disorders.

The two catecholamines, noradrenaline and dopamine, have been shown to play comparable roles in behavior. Both noradrenergic and dopaminergic neurons respond to cues predicting reward availability and novelty. However, even though both are thought to be involved in motivating actions, their roles in motivation have seldom been directly compared. We therefore examined the activity of putative noradrenergic neurons in the locus coeruleus and putative midbrain dopaminergic neurons in monkeys cued to perform effortful actions for rewards. The activity in both regions correlated with engagement with a presented option. By contrast, only noradrenaline neurons were also (i) predictive of engagement in a subsequent trial following a failure to engage and (ii) more strongly activated in nonrepeated trials, when cues indicated a new task condition. This suggests that while both catecholaminergic neurons are involved in promoting action, noradrenergic neurons are sensitive to task state changes, and their influence on behavior extends beyond the immediately rewarded action.

To survive in their complex environment, primates must integrate information over time and adjust their actions beyond immediate events. The underlying neurobiological processes, however, remain unclear. Here, we assessed the contribution of the ventromedial prefrontal cortex (VMPFC), a brain region important for value-based decision making. We recorded single VMPFC neurons in monkeys performing a task where obtaining fluid rewards required squeezing a grip. The willingness to perform the action was modulated not only by visual information about Effort and Reward levels, but also by contextual factors such as Trial Number (i.e fatigue and/or satiety) or behavior in recent trials. A greater fraction of VMPFC neurons encoded contextual information, compared to visual stimuli. Moreover, the dynamics of VMPFC firing was more closely related to slow changes in motivational states driven by these contextual factors rather than rapid responses to individual task events. Thus, the firing of VMPFC neurons continuously integrated contextual information and reliably predicted the monkeys's willingness to perform the task. This function might be critical when animals forage in a complex environment and need to integrate information over time. Its relation with motivational states also resonates with the VMPFC's implication in the 'default mode' or in mood disorders.

16The two catecholamines, noradrenaline and dopamine, have been shown to play 17 comparable roles in behaviour. Both noradrenergic and dopaminergic neurons 18 respond to salient cues predicting reward availability and to stimulus novelty, and 19 shape action selection strategies. However, their roles in motivation have seldom been 20 directly compared. We therefore examined the activity of noradrenergic neurons in the 21 locus coeruleus and putative midbrain dopaminergic neurons in monkeys cued to 22 perform effortful actions for rewards. The activity in both regions correlated with the 23 likelihood of engaging with a presented option. By contrast, only noradrenaline neurons 24 were also (i) predictive of engagement in a subsequent trial following a failure to 25 engage and (ii) sensitive to the task state change, the discovery of the new task 26 condition in unrepeated trials. This indicates that while dopamine is primarily important 27 for the promotion of actions directed towards currently available rewards, 28 noradrenergic neurons play a crucial complementary role in mobilizing resources to 29 promote future engagement. 30 frame, the magnitude of LC responses to sensory stimuli increases when these stimuli 54 are unexpected, and therefore provide information about the state of the world that 55 may be useful to guide subsequent behaviour. By contrast, perfectly expected stimuli 56 provide little information, and so their presentation should not require the updating of 57 behaviour. In other words, such a function could allow the activation of LC neurons to 58 promote the adaptation of behaviour in response to a change in the state of the world 59

15Among neuromodulatory systems, the noradrenergic system remains one of the least 16 understood. Several theories have pointed out its implication in behavioural flexibility 17 and more recently in motivation, with a strong role in effort processing. Here, we 18 designed a sequential cost/benefit decision task to test the causal role of 19 noradrenaline in these two functions. We manipulated noradrenaline using clonidine, 20 an alpha-2 noradrenergic receptor agonist, which reduces central noradrenaline 21 levels. Clonidine had two distinct effects: it decreased choice volatility (without 22 affecting the cost/benefit trade off) and reduced force production. Because the effects 23 were independent, they cannot be accounted for by a non-specific effect on arousal. 24Altogether, these results support the global implication of noradrenaline in facing 25 challenging situations in two complementary ways: by modulating behavioural 26 volatility, which would facilitate adaptation depending on the lability of the 27 environment, and by modulating the mobilization of resources to face immediate 28 challenges.

Behaviour science has been applied for public value by more than 100 government and public purpose organisations worldwide. Much of this work has focused on evidence production through rigorous research design and theories of behaviour change.However, successfully tested interventions are not always scaled up to an entire population of interest, a new setting, or adapted to new target behaviours. Scaling up effective behaviour change interventions is often the true goal and often represents a challenge for government and research end-users working in behavioural science. We conducted a systematic search for an overview of reviews of scholarly evidence on scale up, and 11 practice interviews with behaviour science researchers and practitioners to identify the factors and activities that influence the scale up of behaviour change interventions. This work is aimed not only at uncovering the effectiveness of these activities but also at increasing the reach and impact of behaviour change interventions at scale.