Characterization of striatal dopamine projections across striatal subregions in behavioral flexibility

Behavioral flexibility is key to survival in a dynamic environment. While flexible, goal-directed behaviors are initially dependent on dorsomedial striatum, they become dependent on lateral striatum with extended training as behaviors become inflexible. Similarly, dopamine release shifts from ventromedial to lateral striatum across learning, and impairment of lateral dopamine release disrupts habitual, inflexible responding. This raises the possibility that lateral dopamine release is a causative mechanism in establishing inflexible behaviors late in training, though this has not been directly tested. Here, we utilized optogenetics to activate dopamine terminals in dorsal medial (DMS), dorsal lateral (DLS), and ventral (NAc) striatum in DATcre mice to determine how specific dopamine subpopulations impact behavioral flexibility. Mice performed a reversal task in which they self-stimulated DMS, DLS, or NAc dopamine terminals by pressing one of two levers before action-outcome lever contingencies were reversed. Consistent with presumed ventromedial/lateral striatal function, we found that mice self-stimulating ventromedial dopamine terminals rapidly reversed lever preference following contingency reversal, while mice self-stimulating dopamine terminals in DLS showed impaired reversal learning. These impairments were characterized by more regressive errors and reliance on lose-stay strategies following reversal, suggesting reward insensitivity and overreliance on previously learned actions. This study supports a model of striatal function in which dorsomedial dopamine facilitates goal-directed responding, and dorsolateral dopamine release is a key mechanism in supporting the transition toward inflexible behaviors.

Rule-based generalization of threat without similarity

Threat generalization to novel instances is central to adaptive behavior. Most previous work has investigated threat generalization based on the perceptual sim- ilarity between past and novel stimuli. Few studies have explored generalization based on abstract, non-perceptual relations despite their importance for cognitive flexibility. In order to measure such rule-based generalization of threat without perceptual similarity, we developed a novel paradigm that prevents perceptual features from gaining predictive value. Our results demonstrate that participants responded according to the correct abstract rule and used it to successfully generalize their anticipatory behavioural threat responses (expectancy ratings, sudomotor nerve activity, and heart rate responses). Our results further show that participants flexibly adapted their responses to an unsignaled mid-session contingency reversal. We interpret our results in the context of other rule-based generalization tasks and argue that variations of our paradigm make possible a wide range of investigations into the conceptual aspects of threat generalization.

Human fear conditioning depends on stimulus contingency instructions

Human fear conditioning is often seen as the result of a highly automatic process that is independent of higher cognitive functions and verbal instructions. However, cumulative research findings call this view into question. In the current preregistered study (N = 102), we investigated whether the number of participants who successfully show conditioned fear acquisition depends on the instructions given to them before the fear conditioning phase. Particularly, one third of the participants were instructed about the precise contingency between the conditioned stimulus (CS) and unconditioned stimulus (US). Another third was merely instructed that there would be a contingency. The last third did not get any instructions about the CS-US contingency. We found facilitated fear acquisition rate in the first and second group compared to the third group. Furthermore, contingency reversal instructions following the acquisition phase reversed both conditioned skin conductance and startle responses. These results highlight that researchers should systematically report the instructions given to participants in human fear conditioning studies.

High beta rhythm amplitude in olfactory learning signs a well-consolidated and non-flexible behavioral state

Beta rhythm (15–30 Hz) is a major candidate underlying long-range communication in the brain. In olfactory tasks, beta activity is strongly modulated by learning but its condition of expression and the network(s) responsible for its generation are unclear. Here we analyzed the emergence of beta activity in local field potentials recorded from olfactory, sensorimotor and limbic structures of rats performing an olfactory task. Rats performed successively simple discrimination, rule transfer, memory recall tests and contingency reversal. Beta rhythm amplitude progressively increased over learning in most recorded areas. Beta amplitude reduced to baseline when new odors were introduced, but remained high during memory recall. Intra-session analysis showed that even expert rats required several trials to reach a good performance level, with beta rhythm amplitude increasing in parallel. Notably, at the beginning of the reversal task, beta amplitude remained high while performance was low and, in all tested animals, beta amplitude decreased before rats were able to learn the new contingencies. Connectivity analysis showed that beta activity was highly coherent between all structures where it was expressed. Overall, our results suggest that beta rhythm is expressed in a highly coherent network when context learning - including both odors and reward - is consolidated and signals behavioral inflexibility.

Demonstrating and disrupting well-learned habits

Researchers have exerted tremendous efforts to empirically study how habits form and dominate at the expense of deliberation, yet we know very little about breaking these rigid habits to restore goal-directed control. In a three-experiment study, we first illustrate a novel approach of studying well-learned habits, in order to effectively demonstrate habit disruption. In Experiment 1, we use a Go/NoGo task with familiar color-response associations to demonstrate outcome-insensitivity when compared to novel, more flexible associations. Specifically, subjects perform more accurately when the required mapping is the familiar association of green–Go/red–NoGo than when it is red–Go/green–NoGo, confirming outcome-insensitive, habitual control. As a control condition, subjects show equivalent performance with unfamiliar color-response mappings (using the colors blue and purple mapped to Go and NoGo responses). Next, in Experiments 2 and 3, we test a motivation-based feedback manipulation in varying magnitudes (i.e., performance feedback with and without monetary incentives) to break the well-established habits elicited by our familiar stimuli. We find that although performance feedback prior to the contingency reversal test is insufficient to disrupt outcome-insensitivity in Experiment 2, a combination of performance feedback and monetary incentive is able to restore goal-directed control in Experiment 3, effectively breaking the habits. As the first successful demonstration of well-learned habit disruption in the laboratory, these findings provide new insights into how we execute and modify habits, while fostering new and translational research avenues that may be applicable to treating habit-based pathologies.