The Motivational Determinants of Human Action, Their Neural Bases and Functional Impact in Adolescents With Obsessive-Compulsive Disorder.

Background: Establishing the motivational influences on human action is essential for understanding choice and decision making in health and disease. Here we used tests of value-based decision making, manipulating both predicted and experienced reward values to assess the motivational control of goal-directed action in healthy adolescents and those with obsessive-compulsive disorder (OCD). Methods: After instrumental training on a two action-two outcome probabilistic task, adolescents (n = 21) underwent Pavlovian conditioning using distinct stimuli predicting either the instrumental outcomes, a third outcome, or nothing. We then assessed functional magnetic resonance imaging during choice tests in which we varied the predicted value, using specific and general Pavlovian-instrumental transfer, and the experienced value, using outcome devaluation. To establish functional significance, we tested a matched cohort of adolescents with OCD (n = 20). Results: In healthy adolescents, both predicted and experienced values influenced the performance of goal-directed actions, mediated by distinct orbitofrontal-striatal circuits involving the lateral orbitofrontal cortex (OFC) and medial OFC, respectively. However, in adolescents with OCD, choice was insensitive to changes in either predicted or experienced values. These impairments were related to hypoactivity in the lateral OFC and hyperactivity in the medial OFC during specific Pavlovian-instrumental transfer and hypoactivity in the anterior prefrontal cortex, caudate nucleus, and their connectivity in the devaluation test. Conclusions: We found that predicted and experienced values exerted a potent influence on the performance of goal-directed actions in adolescents via distinct orbitofrontal- and prefrontal-striatal circuits. Furthermore, the influence of these motivational processes was severely blunted in OCD, as was the functional segregation of circuits involving medial and lateral OFC, producing dysregulated action control.

Determining the effects of training duration on the behavioral expression of habitual control in humans: a multilaboratory investigation.

It has been suggested that there are two distinct and parallel mechanisms for controlling instrumental behavior in mammals: goal-directed actions and habits. To gain an understanding of how these two systems interact to control behavior, it is essential to characterize the mechanisms by which the balance between these systems is influenced by experience. Studies in rodents have shown that the amount of training governs the relative expression of these two systems: Behavior is goal-directed following moderate training, but the more extensively an instrumental action is trained, the more it becomes habitual. It is less clear whether humans exhibit similar training effects on the expression of goal-directed and habitual behavior, as human studies have reported contradictory findings. To tackle these contradictory findings, we formed a consortium, where four laboratories undertook a preregistered experimental induction of habits by manipulating the amount of training. There was no statistical evidence for a main effect of the amount of training on the formation and expression of habits. However, exploratory analyses suggest a moderating effect of the affective component of stress on the impact of training over habit expression. Participants who were lower in affective stress appeared to be initially goal-directed, but became habitual with increased training, whereas participants who were high in affective stress were already habitual even after moderate training, thereby manifesting insensitivity to overtraining effects. Our findings highlight the importance of the role of moderating variables such as individual differences in stress and anxiety when studying the experimental induction of habits in humans.

Intact corticostriatal control of goal-directed action in Alcohol Use Disorder: a Pavlovian-to-instrumental transfer and outcome-devaluation study.

Deficits in instrumental, goal-directed control, combined with the influence of drug-associated Pavlovian-conditioned stimuli, are thought to influence the development and maintenance of addiction. However, direct evidence has mainly come from animal studies. We sought to establish whether alcohol use disorder (AUD) is characterized by behavioral or neurobiological deficits in (i) the integration of Pavlovian and instrumental values and (ii) goal-directed control; and (iii) whether duration or severity of AUD is associated with such deficits. The influence of cues predicting food rewards on instrumental action was assessed in a Pavlovian-to-instrumental transfer (PIT) test, measuring both specific and general PIT, and goal-directed behavior in an outcome-devaluation test. Brain activity was measured using functional MRI in 38 abstinent individuals with AUD and 22 matched healthy control individuals (HCs). We found significant specific and general PIT and outcome-devaluation effects across groups indicating goal-directed control, mediated by distinct corticostriatal signals, but no significant differences between individuals with AUD and healthy controls. Bayesian analyses provided substantial-to-strong evidence for the absence of group differences for these effects, or any relationship with duration or severity of AUD. These results suggest intact ability to integrate action-outcome associations on specific and general PIT and goal-directed learning in AUD during abstinence.

Inhibitory Pavlovian-instrumental transfer in humans.

Although there has been extensive research in both humans and rodents regarding the influence of excitatory predictions on action selection, the influence of inhibitory reward predictions is less well understood. We used a feature-negative conditioned inhibition procedure to generate Pavlovian excitors and inhibitors, predicting the presence or absence of specific outcomes, and assessed their influence on action selection using a Pavlovian-instrumental transfer test. Inhibitors predicting the absence of a specific outcome reversed the bias in action selection elicited by outcome-specific excitors; whereas excitors promoted responding on the action associated with the same outcome as the cue, inhibitors shifted responding away from such actions and toward other actions. Furthermore, the influence of the inhibitors on choice reflected the nature of the inhibitory associations learned by participants; those encoding outcome-specific inhibitory associations showed a strong reversal in the bias elicited by the excitors, selectively biasing performance away from the action associated with the to-be-omitted outcome and toward other actions. In contrast, those encoding only general inhibitory associations did not show any bias during the transfer test and instead reduced their performance of both actions. (PsycINFO Database Record

Stress associated changes in Pavlovian-instrumental transfer in humans.

Predictive learning is known to influence instrumental responding for reward. Cues associated with an instrumental outcome can influence performance in two ways: (a) by selectively promoting actions associated with the outcome predicted by the cue (specific transfer), and (b) by increasing motivation and the vigour of instrumental responding (general transfer). To examine these two distinct processes in humans we developed a novel behavioural task in which participants were able to liberate junk-food snacks from a virtual vending machine. Additionally, the relationship between stress and cue-driven reward seeking was examined using participant scores on the Depression Anxiety and Stress Scale (DASS). Reward-paired cues were found to separately bias action selection and influence the rate of responding for rewards. Furthermore, the effects of reward-paired cues on the rate of responding for reward was influenced by increased stress and anxiety. Increased levels of stress and anxiety were associated particularly with changes in cue-driven response vigour; whereas high levels of stress and anxiety were associated with elevated responding above baseline in the presence of a cue associated with a non-rewarding outcome, participants with low levels of anxiety and stress showed appropriate suppression of responding during this cue. These differences in performance between high and low anxiety and stress participants provides initial evidence that, as has been demonstrated in rodents, stress affects the influence of cue-driven response vigour in humans.

Motor Performance is Impaired Following Vestibular Stimulation in Ageing Mice.

UNLABELLED: Balance and maintaining postural equilibrium are important during stationary and dynamic movements to prevent falls, particularly in older adults. While our sense of balance is influenced by vestibular, proprioceptive, and visual information, this study focuses primarily on the vestibular component and its age-related effects on balance. C57Bl/6J mice of ages 1, 5-6, 8-9 and 27-28 months were tested using a combination of standard (such as grip strength and rotarod) and newly-developed behavioral tests (including balance beam and walking trajectory tests with a vestibular stimulus). In the current study, we confirm a decline in fore-limb grip strength and gross motor coordination as age increases. We also show that a vestibular stimulus of low frequency (2-3 Hz) and duration can lead to age-dependent changes in balance beam performance, which was evident by increases in latency to begin walking on the beam as well as the number of times hind-feet slip (FS) from the beam. Furthermore, aged mice (27-28 months) that received continuous access to a running wheel for 4 weeks did not improve when retested. Mice of ages 1, 10, 13 and 27-28 months were also tested for changes in walking trajectory as a result of the vestibular stimulus. While no linear relationship was observed between the changes in trajectory and age, 1-month-old mice were considerably less affected than mice of ages 10, 13 and 27-28 months. CONCLUSION: this study confirms there are age-related declines in grip strength and gross motor coordination. We also demonstrate age-dependent changes to finer motor abilities as a result of a low frequency and duration vestibular stimulus. These changes showed that while the ability to perform the balance beam task remained intact across all ages tested, behavioral changes in task performance were observed.

Corticostriatal control of goal-directed action is impaired in schizophrenia.

BACKGROUND: Goal-directed actions depend on our capacity to integrate the anticipated consequences of an action with the value of those consequences, with the latter derived from direct experience or inferred from predictive stimuli. Schizophrenia is associated with poor goal-directed performance, but whether this reflects a deficit in experienced or predicted value or in integrating these values with action-outcome information is unknown, as is the locus of any associated neuropathology. METHODS: We assessed the contribution of these sources of value to goal-directed actions in people with schizophrenia (SZ) (n = 18) and healthy adults (n = 18). Participants learned to use specific actions to liberate snack foods from a vending machine. They also learned about the reward value of the foods, changes in reward value, and the relationship between various predictive stimuli and food delivery. We then evaluated the ability of subjects to use experienced or predicted value to guide goal-directed actions while undergoing functional magnetic resonance imaging. RESULTS: Acquisition and sensitivity to experienced changes in outcome value did not differ in SZ and healthy adults. The SZ were, however, deficient in their ability to integrate action-outcome learning with outcome values to guide choice, more so when actions were guided by experienced than by predicted values. These effects were differentially associated with reductions in activity in caudate and limbic structures, respectively. CONCLUSIONS: This novel assessment of goal-directed learning revealed dysfunction in corticostriatal control associated with a profound deficit in integrating changes in experienced value with the action-outcome association in schizophrenia.

Behavioral assessment of the aging mouse vestibular system.

Age related decline in balance performance is associated with deteriorating muscle strength, motor coordination and vestibular function. While a number of studies show changes in balance phenotype with age in rodents, very few isolate the vestibular contribution to balance under either normal conditions or during senescence. We use two standard behavioral tests to characterize the balance performance of mice at defined age points over the lifespan: the rotarod test and the inclined balance beam test. Importantly though, a custom built rotator is also used to stimulate the vestibular system of mice (without inducing overt signs of motion sickness). These two tests have been used to show that changes in vestibular mediated-balance performance are present over the murine lifespan. Preliminary results show that both the rotarod test and the modified balance beam test can be used to identify changes in balance performance during aging as an alternative to more difficult and invasive techniques such as vestibulo-ocular (VOR) measurements.