Pavlovian-to-Instrumental Transfer of Nicotine and Food Cues in Deprived Cigarette Smokers.

INTRODUCTION: Smoking-related cues can promote drug-seeking behavior and curtail attempts to quit. One way to understand the potential impact of such cues is to compare cue-elicited behaviors for smoking and other reinforcers (eg, food) using the Pavlovian-to-instrumental transfer paradigm, which measures how much control cues can exert over reward-seeking responses. METHODS: We tested the influence of appetitive cues on smokers' behavior following 12 hours of abstinence from smoking and eating. First, we equated the value of cigarette and food by assessing a Willingness-to-Pay measure for each reinforcer. Second, we evaluated behavioral differences between cues with Pavlovian-to-instrumental transfer. In two phases, participants learned (1) the association between distinct stimuli and cigarette or food outcomes and, (2) specific instrumental responses that yielded such outcomes. Motivated behavior was probed under extinction in a subsequent transfer test assessing instrumental responding in the presence of the cues. RESULTS: Participants showed an increase in specific responding (eg, instrumental response associated with cigarette) when faced with the corresponding appetitive cue (eg, stimulus associated with cigarette) despite absence of outcome. Notably, they made more cigarette-seeking than food-seeking instrumental responses, suggesting that cues representative of cigarette outcomes exert stronger influences on behavior than non-drug (food) cues. Using a measure of subjective preference, we also observed that greater preference for cigarette-compared to food-cues correlated with increased cigarette-seeking behavior in the test phase. CONCLUSION: Taken together, these results highlight how drug and non-drug cues differentially influence reward-seeking behaviors during deprivation, which has implications for smoking cessation treatment and relapse. IMPLICATIONS: This study examines the motivational influence of both drug and non-drug cues within a single sample of cigarette smokers. Our results demonstrate that the motivational properties of smoking cues differ from cues relating to other types of reward, such as food. This research informs smoking cessation programs to target the salience of nicotine cues and the maladaptive drug-seeking behaviors prompted by them.

The effects of acute stress exposure on striatal activity during Pavlovian conditioning with monetary gains and losses.

Pavlovian conditioning involves the association of an inherently neutral stimulus with an appetitive or aversive outcome, such that the neutral stimulus itself acquires reinforcing properties. Across species, this type of learning has been shown to involve subcortical brain regions such as the striatum and the amygdala. It is less clear, however, how the neural circuitry involved in the acquisition of Pavlovian contingencies in humans, particularly in the striatum, is affected by acute stress. In the current study, we investigate the effect of acute stress exposure on Pavlovian conditioning using monetary reinforcers. Participants underwent a partial reinforcement conditioning procedure in which neutral stimuli were paired with high and low magnitude monetary gains and losses. A between-subjects design was used, such that half of the participants were exposed to cold stress while the remaining participants were exposed to a no stress control procedure. Cortisol measurements and subjective ratings were used as measures of stress. We observed an interaction between stress, valence, and magnitude in the ventral striatum, with the peak in the putamen. More specifically, the stress group exhibited an increased sensitivity to magnitude in the gain domain. This effect was driven by those participants who experienced a larger increase in circulating cortisol levels in response to the stress manipulation. Taken together, these results suggest that acute stress can lead to individual differences in circulating cortisol levels which influence the striatum during Pavlovian conditioning with monetary reinforcers.

Avoidance-based human Pavlovian-to-instrumental transfer.

The Pavlovian-to-instrumental transfer (PIT) paradigm probes the influence of Pavlovian cues over instrumentally learned behavior. The paradigm has been used extensively to probe basic cognitive and motivational processes in studies of animal learning. More recently, PIT and its underlying neural basis have been extended to investigations in humans. These initial neuroimaging studies of PIT have focused on the influence of appetitively conditioned stimuli on instrumental responses maintained by positive reinforcement, and highlight the involvement of the striatum. In the current study, we sought to understand the neural correlates of PIT in an aversive Pavlovian learning situation when instrumental responding was maintained through negative reinforcement. Participants exhibited specific PIT, wherein selective increases in instrumental responding to conditioned stimuli occurred when the stimulus signaled a specific aversive outcome whose omission negatively reinforced the instrumental response. Additionally, a general PIT effect was observed such that when a stimulus was associated with a different aversive outcome than was used to negatively reinforce instrumental behavior, the presence of that stimulus caused a non-selective increase in overall instrumental responding. Both specific and general PIT behavioral effects correlated with increased activation in corticostriatal circuitry, particularly in the striatum, a region involved in cognitive and motivational processes. These results suggest that avoidance-based PIT utilizes a similar neural mechanism to that seen with PIT in an appetitive context, which has implications for understanding mechanisms of drug-seeking behavior during addiction and relapse.

Acute stress influences neural circuits of reward processing.

People often make decisions under aversive conditions such as acute stress. Yet, less is known about the process in which acute stress can influence decision-making. A growing body of research has established that reward-related information associated with the outcomes of decisions exerts a powerful influence over the choices people make and that an extensive network of brain regions, prominently featuring the striatum, is involved in the processing of this reward-related information. Thus, an important step in research on the nature of acute stress' influence over decision-making is to examine how it may modulate responses to rewards and punishments within reward processing neural circuitry. In the current experiment, we employed a simple reward processing paradigm - where participants received monetary rewards and punishments - known to evoke robust striatal responses. Immediately prior to performing each of two task runs, participants were exposed to acute stress (i.e., cold pressor) or a no stress control procedure in a between-subjects fashion. No stress group participants exhibited a pattern of activity within the dorsal striatum and orbitofrontal cortex (OFC) consistent with past research on outcome processing - specifically, differential responses for monetary rewards over punishments. In contrast, acute stress group participants' dorsal striatum and OFC demonstrated decreased sensitivity to monetary outcomes and a lack of differential activity. These findings provide insight into how neural circuits may process rewards and punishments associated with simple decisions under acutely stressful conditions.