Alcohol-Paired Contextual Cues Produce an Immediate and Selective Loss of Goal-directed Action in Rats

We assessed whether the presence of contextual cues paired with alcohol would disrupt rats’ capacity to express appropriate goal-directed action control. Rats were first given differential context conditioning such that one set of contextual cues was paired with the injection of ethanol and a second, distinctive set of cues was paired with the injection of saline. All rats were then trained in a third, neutral context to press one lever for grain pellets and another lever for sucrose pellets. They were then given two extinction tests to evaluate their ability to choose between the two actions in response to the devaluation of one of the two food outcomes with one test conducted in the alcohol-paired context and the other conducted in the control (saline-paired) context. In the control context, rats exhibited goal-directed action control; i.e., they were able selectively to withhold the action that previously earned the now devalued outcome. However, these same rats were impaired when tested in the alcohol-paired context, performing both actions at the same rate regardless of the current value of their respective outcomes. Subsequent testing revealed that the rats were capable of overcoming this impairment if they were giving response-contingent feedback about the current value of the food outcomes. These results provide a clear demonstration of the disruptive influence that alcohol-paired cues can exert on decision-making in general and goal-directed action selection and choice in particular

Goal-directed action transiently depends on action space

Abstract Rats use spatiotemporal features of the environment to navigate to a goal, but whether representations of ‘action space’ are necessary for non-navigational goal-directed actions is unknown. We addressed this question by assessing goal-directed action control across contexts and under hippocampal inactivation and found that such actions do indeed rely on a representation of action space but only immediately after initial acquisition. One Sentence Summary Goal-directed actions depend on a hippocampal representation of action space immediately after initial encoding but not after a delay

Anything You Can Do, You Can Do Better: Neural Substrates of Incentive-Based Performance Enhancement

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

Medial Orbitofrontal Cortex Regulates Instrumental Conditioned Punishment, but not Pavlovian Conditioned Fear

Abstract Bidirectionally aberrant medial orbitofrontal cortical (mOFC) activity has been consistently linked with compulsive disorders and related behaviors. Although rodent studies have established a causal link between mOFC excitation and compulsive-like actions, no such link has been made with mOFC inhibition. Here we use excitotoxic lesions of mOFC to investigate its role in sensitivity to punishment; a core characteristic of many compulsive disorders. In our first experiment, we demonstrated that mOFC lesions prevented rats from learning to avoid a lever that was punished with a stimulus that co-terminated with footshock. Our second experiment demonstrated that retrieval of punishment learning is also somewhat mOFC-dependent, as lesions prevented the extended retrieval of punishment contingencies relative to shams. In contrast, mOFC lesions did not prevent rats from re-acquiring the ability to avoid a punished lever when it was learned prior to lesions being administered. In both experiments, Pavlovian fear conditioning to the stimulus was intact for all animals. Together, these results reveal that the mOFC regulates punishment learning and retrieval in a manner that is separate from any role in Pavlovian fear conditioning. These results imply that aberrant mOFC activity may contribute to the punishment insensitivity that is observed across multiple compulsive disorders.</jats:p

Paradoxical reversal learning enhancement by stress or prefrontal cortical damage: rescue with BDNF.

Stress affects various forms of cognition. We found that moderate stress enhanced late reversal learning in a mouse touchscreen-based choice task. Ventromedial prefrontal cortex (vmPFC) lesions mimicked the effect of stress, whereas orbitofrontal and dorsolateral striatal lesions impaired reversal. Stress facilitation of reversal was prevented by BDNF infusion into the vmPFC. These findings suggest a mechanism by which stress-induced vmPFC dysfunction disinhibits learning by alternate (for example, striatal) systems

Neuroscience in gambling policy and treatment: an interdisciplinary perspective

Neuroscientific explanations of gambling disorder can help people make sense of their experiences and guide the development of psychosocial interventions. However, the societal perceptions and implications of these explanations are not always clear or helpful. Two workshops in 2013 and 2014 brought together multidisciplinary researchers aiming to improve the clinical and policy-related effects of neuroscience research on gambling. The workshops revealed that neuroscience can be used to improve identification of the dangers of products used in gambling. Additionally, there was optimism associated with the diagnostic and prognostic uses of neuroscience in problem gambling and the provision of novel tools (eg, virtual reality) to assess the effectiveness of new policy interventions before their implementation. Other messages from these workshops were that neuroscientific models of decision making could provide a strong rationale for precommitment strategies and that interdisciplinary collaborations are needed to reduce the harms of gambling

Striatal Volume Predicts Level of Video Game Skill Acquisition

Video game skills transfer to other tasks, but individual differences in performance and in learning and transfer rates make it difficult to identify the source of transfer benefits. We asked whether variability in initial acquisition and of improvement in performance on a demanding video game, the Space Fortress game, could be predicted by variations in the pretraining volume of either of 2 key brain regions implicated in learning and memory: the striatum, implicated in procedural learning and cognitive flexibility, and the hippocampus, implicated in declarative memory. We found that hippocampal volumes did not predict learning improvement but that striatal volumes did. Moreover, for the striatum, the volumes of the dorsal striatum predicted improvement in performance but the volumes of the ventral striatum did not. Both ventral and dorsal striatal volumes predicted early acquisition rates. Furthermore, this early-stage correlation between striatal volumes and learning held regardless of the cognitive flexibility demands of the game versions, whereas the predictive power of the dorsal striatal volumes held selectively for performance improvements in a game version emphasizing cognitive flexibility. These findings suggest a neuroanatomical basis for the superiority of training strategies that promote cognitive flexibility and transfer to untrained tasks.United States. Office of Naval Research (grant number N00014-07-1-0903

Functional MRI in Awake Unrestrained Dogs

Because of dogs' prolonged evolution with humans, many of the canine cognitive skills are thought to represent a selection of traits that make dogs particularly sensitive to human cues. But how does the dog mind actually work? To develop a methodology to answer this question, we trained two dogs to remain motionless for the duration required to collect quality fMRI images by using positive reinforcement without sedation or physical restraints. The task was designed to determine which brain circuits differentially respond to human hand signals denoting the presence or absence of a food reward. Head motion within trials was less than 1 mm. Consistent with prior reinforcement learning literature, we observed caudate activation in both dogs in response to the hand signal denoting reward versus no-reward

Reward-Related Behavioral Paradigms for Addiction Research in the Mouse: Performance of Common Inbred Strains

The mouse has emerged as a uniquely valuable species for studying the molecular and genetic basis of complex behaviors and modeling neuropsychiatric disease states. While valid and reliable preclinical assays for reward-related behaviors are critical to understanding addiction-related processes, and various behavioral procedures have been developed and characterized in rats and primates, there have been relatively few studies using operant-based addiction-relevant behavioral paradigms in the mouse. Here we describe the performance of the C57BL/6J inbred mouse strain on three major reward-related paradigms, and replicate the same procedures in two other commonly used inbred strains (DBA/2J, BALB/cJ). We examined Pavlovian-instrumental transfer (PIT) by measuring the ability of an auditory cue associated with food reward to promote an instrumental (lever press) response. In a separate experiment, we assessed the acquisition and extinction of a simple stimulus-reward instrumental behavior on a touchscreen-based task. Reinstatement of this behavior was then examined following either continuous exposure to cues (conditioned reinforcers, CRs) associated with reward, brief reward and CR exposure, or brief reward exposure followed by continuous CR exposure. The third paradigm examined sensitivity of an instrumental (lever press) response to devaluation of food reward (a probe for outcome insensitive, habitual behavior) by repeated pairing with malaise. Results showed that C57BL/6J mice displayed robust PIT, as well as clear extinction and reinstatement, but were insensitive to reinforcer devaluation. DBA/2J mice showed good PIT and (rewarded) reinstatement, but were slow to extinguish and did not show reinforcer devaluation or significant CR-reinstatement. BALB/cJ mice also displayed good PIT, extinction and reinstatement, and retained instrumental responding following devaluation, but, unlike the other strains, demonstrated reduced Pavlovian approach behavior (food magazine head entries). Overall, these assays provide robust paradigms for future studies using the mouse to elucidate the neural, molecular and genetic factors underpinning reward-related behaviors relevant to addiction research