Costly habitual avoidance is reduced by concurrent goal-directed approach in a modified devaluation paradigm

Avoidance habits potentially contribute to maintaining maladaptive, costly avoidance behaviors that persist in the absence of threat. However, experimental evidence about costly habitual avoidance is scarce. In two experiments, we tested whether extensively trained avoidance impairs the subsequent goal-directed approach of rewards. Healthy participants were extensively trained to avoid an aversive outcome by performing simple responses to distinct full-screen color stimuli. After the subsequent devaluation of the aversive outcome, participants received monetary rewards for correct responses to neutral object pictures, which were presented on top of the same full-screen colors. These approach responses were either compatible or incompatible with habitual avoidance responses. Notably, the full-screen colors were not relevant to inform approach responses. In Experiment 1, participants were not instructed about post-devaluation stimulus-response-reward contingencies. Accuracy was lower in habit-incompatible than in habit-compatible trials, indicating costly avoidance, whereas reaction times did not differ. In Experiment 2, contingencies were explicitly instructed. Accuracy differences disappeared, but reaction times were slower in habit-incompatible than in habit-compatible trials, indicating low-cost habitual avoidance tendencies. These findings suggest a small but consistent impact of habitual avoidance tendencies on subsequent goal-directed approach. Costly habitual responding could, however, be inhibited when competing goal-directed approach was easily realizable.

Corticostriatal dynamics underlying components of binge-like eating in mice

Binge eating (BE) is a maladaptive repetitive feeding behavior present across nearly all eating disorder diagnoses. BE is associated with poor psychosocial outcomes (e.g., suicidal ideation) and increased risk for obesity. Despite the substantial negative impact of BE, its underlying neural mechanisms are largely unknown. Many other repetitive behavior disorders (e.g., obsessive compulsive disorder) show dysfunction within corticostriatal circuitry. Additionally, previous pre clinical and clinical work has highlighted an imbalance between goal directed and habitual responding in BE. The aim of the current study was to longitudinally examine in vivo neural activity within corticostriatal regions associated with habitual behavior, the infralimbic cortex (IL) and dorsolateral striatum (DLS), using a robust pre clinical model for BE. Female C57BL/6 mice (N = 32) were randomized to receive: 1) intermittent (daily, 2-hour) binge-like access to palatable food (BE mice), or 2) continuous, non-intermittent (24-hour) access to palatable food (non-BE mice). In vivo calcium imaging was performed via fiber photometry at the baseline timepoint and after 4 weeks (chronic timepoint) of engagement in the model for BE. Feeding behaviors (feeding bout onset, offset) during the recordings were captured using contact lickometers which generated TTL outputs for precise alignment of BE behavior to neural data. Results in the IL showed no specific changes in neural activity related to BE. However, BE animals showed decreased DLS activity from the baseline to chronic timepoint at feeding onset and offset. Additionally, BE mice had significantly lower DLS activity at feeding onset and offset during the chronic time point compared to non-BE mice. These results point to a role for DLS hypofunction in chronic BE, highlighting a potential target for future treatment intervention.

Optogenetic stimulation of striatal patches modifies habit formation and inhibits dopamine release

Habits are inflexible behaviors that develop after extensive repetition, and overreliance on habits is a hallmark of many pathological states. The striatum is involved in the transition from flexible to inflexible responding, and interspersed throughout the striatum are patches, or striosomes, which make up ~15% of the volume of the striatum relative to the surrounding matrix compartment. Previous studies have suggested that patches are necessary for normal habit formation, but it remains unknown exactly how patches contribute to habit formation and expression. Here, using optogenetics, we stimulated striatal patches in Sepw1-NP67 mice during variable interval training (VI60), which is used to establish habitual responding. We found that activation of patches at reward retrieval resulted in elevated responding during VI60 training by modifying the pattern of head entry and pressing. Further, this optogenetic manipulation reduced subsequent responding following reinforcer devaluation, suggesting modified habit formation. However, patch stimulation did not generally increase extinction rates during a subsequent extinction probe, but did result in a small ‘extinction burst’, further suggesting goal-directed behavior. On the other hand, this manipulation had no effect in omission trials, where mice had to withhold responses to obtain rewards. Finally, we utilized fast-scan cyclic voltammetry to investigate how patch activation modifies evoked striatal dopamine release and found that optogenetic activation of patch projections to the substantia nigra pars compacta (SNc) is sufficient to suppress dopamine release in the dorsal striatum. Overall, this work provides novel insight into the role of the patch compartment in habit formation, and provides a potential mechanism for how patches modify habitual behavior by exerting control over dopamine signaling.

Saracatinib Fails to Reduce Alcohol-Seeking and Consumption in Mice and Human Participants

More effective treatments to reduce pathological alcohol drinking are needed. The glutamatergic system and the NMDA receptor (NMDAR), in particular, are implicated in behavioral and molecular consequences of chronic alcohol use, making the NMDAR a promising target for novel pharmacotherapeutics. Ethanol exposure upregulates Fyn, a protein tyrosine kinase that indirectly modulates NMDAR signaling by phosphorylating the NR2B subunit. The Src/Fyn kinase inhibitor saracatinib (AZD0530) reduces ethanol self-administration and enhances extinction of goal-directed ethanol-seeking in mice. However, less is known regarding how saracatinib affects habitual ethanol-seeking. Moreover, no prior studies have assessed the effects of Src/Fyn kinase inhibitors on alcohol-seeking or consumption in human participants. Here, we tested the effects of saracatinib on alcohol consumption and craving/seeking in two species, including the first trial of an Src/Fyn kinase inhibitor to reduce drinking in humans. Eighteen male C57BL/6NCrl mice underwent operant conditioning on a variable interval schedule to induce habitual responding for 10% ethanol/0.1% saccharin. Next, mice received 5 mg/kg saracatinib or vehicle 2 h or 30 min prior to contingency degradation to measure habitual responding. In the human study, 50 non-treatment seeking human participants who drank heavily and met DSM-IV criteria for alcohol abuse or dependence were randomized to receive 125 mg/day saracatinib (n = 33) or placebo (n = 17). Alcohol Drinking Paradigms (ADP) were completed in a controlled research setting: before and after 7–8 days of treatment. Each ADP involved consumption of a priming drink of alcohol (0.03 mg%) followed by ad libitum access (3 h) to 12 additional drinks (0.015 g%); the number of drinks consumed and craving (Alcohol Urge Questionnaire) were recorded. In mice, saracatinib did not affect habitual ethanol seeking or consumption at either time point. In human participants, no significant effects of saracatinib on alcohol craving or consumption were identified. These results in mice and humans suggest that Fyn kinase inhibition using saracatinib, at the doses tested here, may not reduce alcohol consumption or craving/seeking among those habitually consuming alcohol, in contrast to reports of positive effects of saracatinib in individuals that seek ethanol in a goal-directed manner. Nevertheless, future studies should confirm these negative findings using additional doses and schedules of saracatinib administration.

Stress diminishes outcome but enhances response representations during instrumental learning

Stress may shift behavioural control from a goal-directed system that encodes action-outcome relationships to a habit system that learns stimulus-response associations. Although this shift to habits is highly relevant for stress-related psychopathologies, limitations of existing behavioural paradigms hindered previous research to answer the fundamental question of whether the stress-induced bias to habits is due to impaired goal-directed or enhanced habitual processing (or both). Here, we leveraged EEG-based multivariate pattern analysis to decode neural outcome representations, crucial for goal-directed control, and response representations, essential for habitual responding, during instrumental learning. We show that stress reduces outcome representations but enhances response representations, both of which were directly associated with a behavioural index of habitual responding. Further, changes in outcome and response representations were uncorrelated, suggesting that these may reflect distinct processes. Our findings indicate that habit behaviour under stress is the result of both enhanced habitual and diminished goal-directed processing.

Instrumental and Pavlovian Mechanisms in Alcohol Use Disorder

Purpose of Review Current theories of alcohol use disorders (AUD) highlight the importance of Pavlovian and instrumental learning processes mainly based on preclinical animal studies. Here, we summarize available evidence for alterations of those processes in human participants with AUD with a focus on habitual versus goal-directed instrumental learning, Pavlovian conditioning, and Pavlovian-to-instrumental transfer (PIT) paradigms. Recent Findings The balance between habitual and goal-directed control in AUD participants has been studied using outcome devaluation or sequential decision-making procedures, which have found some evidence of reduced goal-directed/model-based control, but little evidence for stronger habitual responding. The employed Pavlovian learning and PIT paradigms have shown considerable differences regarding experimental procedures, e.g., alcohol-related or conventional reinforcers or stimuli. Summary While studies of basic learning processes in human participants with AUD support a role of Pavlovian and instrumental learning mechanisms in the development and maintenance of drug addiction, current studies are characterized by large variability regarding methodology, sample characteristics, and results, and translation from animal paradigms to human research remains challenging. Longitudinal approaches with reliable and ecologically valid paradigms of Pavlovian and instrumental processes, including alcohol-related cues and outcomes, are warranted and should be combined with state-of-the-art imaging techniques, computational approaches, and ecological momentary assessment methods.

Balancing Between Goal-Directed and Habitual Responding Following Acute Stress

Instrumental learning is regulated by two memory systems: a relatively rigid but efficient habit system and a flexible but resource-demanding goal-directed system. Previous work has demonstrated that exposure to acute stress may shift the balance between these systems toward the habitual system. In the current study, we used a 2-day outcome devaluation paradigm with a 75% reward contingency rate and altered food reward categories to replicate and extend our previous findings. Participants learned neutral stimulus–response–reward associations on the first day. On the second day, rewards were devalued by eating to satiety. Subsequently, acute stress was induced in half of the participants using the Maastricht Acute Stress Test, while the other half engaged in a nonstressful control task. Finally, relative goal-directed versus habitual behavior was evaluated in a slips-of-action phase, where more slips-of-action indicate a shift toward the habitual system. Results showed that participants successfully acquired the stimulus–response–reward associations, that devaluation was effective, and that stressed participants displayed significant increases in cortisol and blood pressure. Stress led participants to commit more slips-of-action compared with nonstressed controls. The current study extends previous work, showing that the employed paradigm and outcome devaluation procedure are boundary conditions to the stress-induced shift in instrumental responding.

Learning Habits: Does Overtraining Lead to Resistance to New Learning?

We explore the development of habitual responding within the colour-word contingency learning paradigm, in which participants respond to the colour of neutral words. Each word is most often presented in one colour. Learning is indicated by faster responses to the colour when the word is presented in the expected rather than in the unexpected colour. In Experiment 1, participants took part in two sessions, separated by one day. Critically, one set of words was trained across both days, and other new sets of words were introduced at various time points. Overall performance was faster on trials with overtrained words. Additionally, contingency effects were larger for overtrained words than for words introduced on Day 2. Removing the contingency had a similar impact on the learning effect for overtrained and new words. However, during a counterconditioning phase, where the words were made predictive of new colours, the previous contingency continued to influence performance for overtrained words but not for more recently introduced words. Relatedly, the new contingency was not acquired for the overtrained words. The reverse pattern was observed for recently-introduced words, with the newly-introduced contingency rapidly acquired and the influence of the old contingency quickly extinguished. In Experiments 2 and 3, however, both new and old learning effects were observed for both overtrained and recently-acquired contingencies. The net results suggest that while contingency learning effects are highly pliable during initial and subsequent learning, early-acquired contingency knowledge is maintained after removal of the contingency. Implications for models of learning are discussed.