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BackgroundAnorexia nervosa (AN) is a chronic and disabling psychiatric condition characterized by low hedonic drive towards food, and is thought to be inclusive of altered dimensions of reward processing. Whether there exists a fundamental aberrancy in the capacity to acquire and maintain de novo hedonic associations-a critical component of hedonic responding-has never been studied in AN.MethodsThis multi-modal study will employ a 2-day Pavlovian appetitive conditioning paradigm to interrogate the (1) acquisition, (2) extinction, (3) spontaneous recovery and (4) reinstatement of appetitive learning in adolescents and young adults with AN. Participants will be 30 currently ill, underweight individuals with AN; 30 weight-restored individuals with AN; and 30 age-matched healthy controls, all aged 12-22 years. All subjects will undergo clinical assessment, followed by the 2-day appetitive conditioning task during which fMRI, pupillometry, heart rate deceleration, and subjective ratings will be acquired.DiscussionThis study will be the first to interrogate appetitive conditioning in AN-a disorder characterized by altered hedonic responding to food. Results will help establish objective biomarkers of appetitive conditioning in AN and lay the groundwork for developing novel lines of treatment for AN and other psychiatric disorders involving diminished ability to experience pleasure and reward.Trial registrationPending.Intended registryClinicaltrials.gov.

Obsessions and compulsions are central components of obsessive-compulsive disorder (OCD) and obsessive-compulsive related disorders such as body dysmorphic disorder (BDD). Compulsive behaviours may result from an imbalance of habitual and goal-directed decision-making strategies. The relationship between these symptoms and the neural circuitry underlying habitual and goal-directed decision-making, and the arbitration between these strategies, remains unknown. This study examined resting state effective connectivity between nodes of these systems in two cohorts with obsessions and compulsions, each compared with their own corresponding healthy controls: OCD (nOCD = 43; nhealthy = 24) and BDD (nBDD = 21; nhealthy = 16). In individuals with OCD, the left ventrolateral prefrontal cortex, a node of the arbitration system, exhibited more inhibitory causal influence over the left posterolateral putamen, a node of the habitual system, compared with controls. Inhibitory causal influence in this connection showed a trend for a similar pattern in individuals with BDD compared with controls. Those with stronger negative connectivity had lower obsession and compulsion severity in both those with OCD and those with BDD. These relationships were not evident within the habitual or goal-directed circuits, nor were they associated with depressive or anxious symptomatology. These results suggest that abnormalities in the arbitration system may represent a shared neural phenotype across these two related disorders that is specific to obsessive-compulsive symptoms. In addition to nosological implications, these results identify potential targets for novel, circuit-specific treatments.

Diminished motivation to pursue and obtain primary and secondary rewards has been demonstrated in anorexia nervosa (AN). However, the neurobehavioral mechanisms underlying the behavioral activation component of aberrant reward motivation remains incompletely understood. This work aims to explore this underexplored facet of reward motivation in AN. We recruited female adolescents with AN, restricting type (n = 32) and a healthy control group (n = 28). All participants underwent functional magnetic resonance imaging (fMRI) while performing a monetary reward task. Diffusion MRI data was also collected to examine the reward motivation circuit's structural connectivity. Behavioral results demonstrated slower speed of reward-seeking behavior in those with AN compared with controls. Accompanying this was lower functional connectivity and reduced white matter structural integrity of the connection between the ventral tegmental area/substantia nigra pars compacta and the nucleus accumbens within the mesolimbic circuit. Further, there was evidence of neurobehavioral decoupling in AN between reward-seeking behavior and mesolimbic regional activation and functional connectivity. Aberrant activity of the bed nucleus of the stria terminalis (BNST) and its connectivity with the mesolimbic system was also evident in AN during the reward motivation period. Our findings suggest functional and structural dysconnectivity within a mesolimbic reward circuit, neurofunctional decoupling from reward-seeking behavior, and abnormal BNST function and circuit interaction with the mesolimbic system. These results show behavioral indicators of aberrant reward motivation in AN, particularly in its activational component. This is mediated neuronally by mesolimbic reward circuit functional and structural dysconnectivity as well as neurobehavioral decoupling. Based on these findings, we suggest a novel circuit-based mechanism of impaired reward processing in AN, with the potential for translation to developing more targeted and effective treatments in this difficult-to-treat psychiatric condition.

Anorexia nervosa (AN) is a difficult to treat, pernicious psychiatric disorder that has been linked to decision-making abnormalities. We examined the structural characteristics of habitual and goal-directed decision-making circuits and their connecting white matter tracts in 32 AN and 43 healthy controls across two independent data sets of adults and adolescents as an explanatory sub-study. Total bilateral premotor/supplementary motor area-putamen tracts in the habit circuit had a significantly higher volume in adults with AN, relative to controls. Positive correlations were found between both the number of tracts and white matter volume (WMV) in the habit circuit, and the severity of ritualistic/compulsive behaviors in adults and adolescents with AN. Moreover, we found a significant influence of the habit circuit WMV on AN ritualistic/compulsive symptom severity, depending on the preoccupations symptom severity levels. These findings suggest that AN is associated with white matter plasticity alterations in the habit circuit. The association between characteristics of habit circuit white matter tracts and AN behavioral symptoms provides support for a circuit based neurobiological model of AN, and identifies the habit circuit as a focus for further investigation to aid in development of novel and more effective treatments based on brain-behavior relationships.

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.

Considerable behavioral data indicate that operant actions can become habitual, as demonstrated by insensitivity to changes in the action-outcome contingency and in subjective outcome values. Notably, although several studies have investigated the neural substrates of habits, none has clearly differentiated the areas of the human brain that support habit formation from those that implement habitual control. We scanned participants with functional magnetic resonance imaging as they learned and performed an operant task in which the conditional structure of the environment encouraged either goal-directed encoding of the consequences of actions, or a habit-like mapping of actions to antecedent cues. Participants were also scanned during a subsequent assessment of insensitivity to outcome devaluation. We identified dissociable roles of the cerebellum and ventral striatum, across learning and test performance, in behavioral insensitivity to outcome devaluation. We also showed that the inferior parietal lobule (an area previously implicated in several aspects of goal-directed action selection, including the attribution of intent and awareness of agency) predicted sensitivity to outcome devaluation. Finally, we revealed a potential functional homology between the human subgenual cortex and rodent infralimbic cortex in the implementation of habitual control. In summary, our findings suggested a broad systems division, at the cortical and subcortical levels, between brain areas mediating the encoding and expression of action-outcome and stimulus-response associations.

While there is accumulating evidence for the existence of distinct neural systems supporting goal-directed and habitual action selection in the mammalian brain, much less is known about the nature of the information being processed in these different brain regions. Associative learning theory predicts that brain systems involved in habitual control, such as the dorsolateral striatum, should contain stimulus and response information only, but not outcome information, while regions involved in goal-directed action, such as ventromedial and dorsolateral prefrontal cortex and dorsomedial striatum, should be involved in processing information about outcomes as well as stimuli and responses. To test this prediction, human participants underwent fMRI while engaging in a binary choice task designed to enable the separate identification of these different representations with a multivariate classification analysis approach. Consistent with our predictions, the dorsolateral striatum contained information about responses but not outcomes at the time of an initial stimulus, while the regions implicated in goal-directed action selection contained information about both responses and outcomes. These findings suggest that differential contributions of these regions to habitual and goal-directed behavioral control may depend in part on basic differences in the type of information that these regions have access to at the time of decision making.

If someone causes you harm, your affective reaction to that person might be profoundly influenced by your inferences about the intentionality of their actions. In the present study, we aimed to understand how affective responses to a biologically salient aversive outcome administered by others are modulated by the extent to which a given individual is judged to have deliberately or inadvertently delivered the outcome. Using fMRI, we examined how neural responses to anticipation and receipt of an aversive stimulus are modulated by this fundamental social judgment. We found that affective evaluations about an individual whose actions led to either noxious or neutral consequences for the subject did indeed depend on the perceived intentions of that individual. At the neural level, activity in the anterior insula correlated with the interaction between perceived intentionality and anticipated outcome valence, suggesting that this region reflects the influence of mental state attribution on aversive expectations.

Evaluating the abilities of others is fundamental for successful economic and social behavior. We investigated the computational and neurobiological basis of ability tracking by designing an fMRI task that required participants to use and update estimates of both people and algorithms' expertise through observation of their predictions. Behaviorally, we find a model-based algorithm characterized subject predictions better than several alternative models. Notably, when the agent's prediction was concordant rather than discordant with the subject's own likely prediction, participants credited people more than algorithms for correct predictions and penalized them less for incorrect predictions. Neurally, many components of the mentalizing network-medial prefrontal cortex, anterior cingulate gyrus, temporoparietal junction, and precuneus-represented or updated expertise beliefs about both people and algorithms. Moreover, activity in lateral orbitofrontal and medial prefrontal cortex reflected behavioral differences in learning about people and algorithms. These findings provide basic insights into the neural basis of social learning.

Performance-based pay schemes in many organizations share the fundamental assumption that the performance level for a given task will increase as a function of the amount of incentive provided. Consistent with this notion, psychological studies have demonstrated that expectations of reward can improve performance on a plethora of different cognitive and physical tasks, ranging from problem solving to the voluntary regulation of heart rate. However, much less is understood about the neural mechanisms of incentivized performance enhancement. In particular, it is still an open question how brain areas that encode expectations about reward are able to translate incentives into improved performance across fundamentally different cognitive and physical task requirements.