Hao Chen

Pavlovian conditioned stimuli can compromise goal-directed behavior, particularly when they conflict with the required instrumental response. Previous research linked an increased impact of such Pavlovian-to-instrumental transfer (PIT) interference to risky drinking and alcohol dependence. However, it remained unclear whether the observed behavioral and neural alterations generalize to the substantially larger population of non-treatment-seeking individuals with predominantly mild-to-moderate alcohol use disorder (AUD) and to other substances like nicotine. We therefore studied 200 participants from the general population who were stratified by AUD and smoking status before completing a single-lever PIT task during functional imaging. PIT interference was measured as the difference in error rates between incongruent PIT trials, characterized by conflicts of Pavlovian and instrumental stimuli, and congruent trials. Associations with AUD and smoking status, as well as dimensional associations of behavioral PIT interference and neural responses to PIT conflicts with substance-related measures, were examined. As expected, participants with AUD showed greater PIT interference and reduced conflict-related activation in the lateral prefrontal, dorsomedial prefrontal, and anterior cingulate cortex than participants without AUD. The magnitude of these alterations also correlated with higher AUD severity and alcohol consumption, while being independent of smoking status and other smoking-related measures. These findings suggest that enhanced PIT interference generalizes to the broader AUD population but may not extend to other substances like nicotine. They further implicate a reduced recruitment of prefrontal control networks during PIT conflicts as a potential mechanism underlying enhanced PIT interference in AUD and its association with clinically relevant outcome measures.

Background: Pavlovian-to-instrumental transfer (PIT) paradigms assess how environmental cues influence instrumental behaviour. Our previous research linked PIT to alcohol use disorder (AUD) and high-risk drinking using monetary rewards during learning. To better capture alcohol-related cue effects, we developed a PIT paradigm delivering trial-by-trial alcohol and juice rewards alongside monetary rewards, to examine alcohol-specific and general PIT effects in parallel. Methods: Seventy-five participants with AUD and ninety-five controls completed the task during functional magnetic resonance imaging. Alcohol-specific PIT was defined as increased alcohol choices during presentation of alcohol-associated versus juice-associated cues. General PIT was defined as increased response vigor during gain-versus loss-associated cues. Behavioural and neural associations with AUD status and AUDIT scores from baseline through one-year follow-up were examined. Results: Participants with AUD showed stronger alcohol-specific PIT effect than controls. Alcohol-specific PIT was positively associated with baseline AUDIT scores and with AUDIT scores across the one-year follow-up. Alcohol cues elicited stronger anterior insula responses, and region-of-interest analysis showed greater left amygdala responses to alcohol versus juice cues in AUD compared with controls. In contrast, general PIT showed a negative association with AUDIT but no association with AUD status. In the general PIT, no AUD-related neural differences were observed. Conclusions: These findings suggest that alcohol-specific PIT captures a clinically meaningful mechanism of cue-driven alcohol seeking that is distinct from generalized motivational transfer, supporting its potential utility as a mechanistic marker in AUD.

Background: A higher propensity for impulsive and risky choices has often been reported in individuals with addiction, such as alcohol use disorder (AUD). Although domains of choice impulsivity, for example, temporal discounting, have been identified to predispose the development of hazardous alcohol use, research on altered decision making as a consequence of drinking is scarce. These may be particularly pronounced during periods of progressive brain development, such as young adulthood.Methods: This 3‐year prospective study investigated the effects of alcohol use on changes in four decision‐making domains in 18‐year‐old men (N = 130). We assessed temporal changes in discounting of delayed rewards, risk aversion for gains, risk seeking for losses, and loss aversion. By correlating three‐year cumulative alcohol consumption and total binge drinking frequency with respective change scores, we aimed to explore the influences of drinking on altered development in different impulsive choice tendencies.Results: From ages 18 to 21, choice impulsivity in our moderately drinking cohort decreased significantly with respect to temporal discounting and risk aversion for gains, while risk seeking for losses and loss aversion did not change significantly. Importantly, higher cumulative alcohol intake and more binge drinking occasions over 3 years were associated with slower increases in risk aversion for gains, that is, the general trend for lower choice impulsivity was diminished. Such relationships were not found for temporal discounting, risk seeking for losses, or loss aversion.Conclusions: Alcohol consumption in young adulthood is linked to stunted development of risk aversion for gains. Given that risk seeking for gains was previously identified as a risk factor for increasing alcohol intake, this relationship may reinforce a spiral of escalating consumption over time. The absence of similar findings in other decision‐making domains suggests that drinking behavior and modifying factors interact differently across domains, rather than universally enhancing impulsive choice behavior.

Introduction: The emergence of Pavlovian-to-instrumental transfer (PIT) research in the human neurobehavioral domain has been met with increased interest over the past two decades. A variety of PIT tasks were developed during this time; while successful in demonstrating transfer phenomena, existing tasks have limitations that should be addressed. Herein, we introduce two PIT paradigms designed to assess outcome-specific and general PIT within the context of addiction. Materials and Methods: The single-lever PIT task, based on an established paradigm, replaced button presses with joystick motion to better assess avoidance behavior. The full transfer task uses alcohol and nonalcohol rewards associated with Pavlovian cues and instrumental responses, along with other gustatory and monetary rewards. We constructed mixed-effects models with the addition of other statistical analyses as needed to interpret various behavioral measures. Results: Single-lever PIT: both versions were successful in eliciting a PIT effect (joystick: p < 0.001, η_p² = 0.36, button-box: p < 0.001, η_p² = 0.30). Full transfer task: it was determined that the alcohol and nonalcoholic reward cues selectively primed their respective reward-associated responses (gustatory version: p < 0.001, r = 0.59, and monetary version: p < 0.001, r = 0.84). The appetitive/aversive cues resulted in a general transfer effect (gustatory: p < 0.001, η_p² = 0.09, and monetary: p < 0.001, η_p² = 0.17). Discussion/Conclusion: Single-lever PIT: PIT was observed in both task versions. We posit that the use of a joystick is more advantageous for the analysis of avoidance behavior. It evenly distributes movement between approach and avoid trials, which is relevant to analyzing fMRI data. Full transfer task: While gustatory conditioning has been used in the past to elicit transfer effects, we present the first paradigm that successfully elicits both specific and general transfers in humans with gustatory alcohol rewards.

A mechanism known as Pavlovian-to-instrumental transfer (PIT) describes a phenomenon by which the values of environmental cues acquired through Pavlovian conditioning can motivate instrumental behavior. PIT may be one basic mechanism of action control that can characterize mental disorders on a dimensional level beyond current classification systems. Therefore, we review human PIT studies investigating subclinical and clinical mental syndromes. The literature prevails an inhomogeneous picture concerning PIT. While enhanced PIT effects seem to be present in non-substance-related disorders, overweight people, and most studies with AUD patients, no altered PIT effects were reported in tobacco use disorder and obesity. Regarding AUD and relapsing alcohol-dependent patients, there is mixed evidence of enhanced or no PIT effects. Additionally, there is evidence for aberrant corticostriatal activation and genetic risk, e.g., in association with high-risk alcohol consumption and relapse after alcohol detoxification. In patients with anorexia nervosa, stronger PIT effects elicited by low caloric stimuli were associated with increased disease severity. In patients with depression, enhanced aversive PIT effects and a loss of action-specificity associated with poorer treatment outcomes were reported. Schizophrenic patients showed disrupted specific but intact general PIT effects. Patients with chronic back pain showed reduced PIT effects. We provide possible reasons to understand heterogeneity in PIT effects within and across mental disorders. Further, we strengthen the importance of reliable experimental tasks and provide test-retest data of a PIT task showing moderate to good reliability. Finally, we point toward stress as a possible underlying factor that may explain stronger PIT effects in mental disorders, as there is some evidence that stress per se interacts with the impact of environmental cues on behavior by selectively increasing cue-triggered wanting. To conclude, we discuss the results of the literature review in the light of Research Domain Criteria, suggesting future studies that comprehensively assess PIT across psychopathological dimensions.

Pavlovian‐to‐instrumental transfer (PIT) tasks examine the influence of Pavlovian stimuli on ongoing instrumental behaviour. Previous studies reported associations between a strong PIT effect, high‐risk drinking and alcohol use disorder. This study investigated whether susceptibility to interference between Pavlovian and instrumental control is linked to risky alcohol use in a community sample of 18‐year‐old male adults. Participants (N = 191) were instructed to ‘collect good shells’ and ‘leave bad shells’ during the presentation of appetitive (monetary reward), aversive (monetary loss) or neutral Pavlovian stimuli. We compared instrumental error rates (ER) and functional magnetic resonance imaging (fMRI) brain responses between the congruent and incongruent conditions, as well as among high‐risk and low‐risk drinking groups. On average, individuals showed a substantial PIT effect, that is, increased ER when Pavlovian cues and instrumental stimuli were in conflict compared with congruent trials. Neural PIT correlates were found in the ventral striatum and the dorsomedial and lateral prefrontal cortices (lPFC). Importantly, high‐risk drinking was associated with a stronger behavioural PIT effect, a decreased lPFC response and an increased neural response in the ventral striatum on the trend level. Moreover, high‐risk drinkers showed weaker connectivity from the ventral striatum to the lPFC during incongruent trials. Our study links interference during PIT to drinking behaviour in healthy, young adults. High‐risk drinkers showed higher susceptibility to Pavlovian cues, especially when they conflicted with instrumental behaviour, indicating lower interference control abilities. Increased activity in the ventral striatum (bottom‐up), decreased lPFC response (top‐down), and their altered interplay may contribute to poor interference control in the high‐risk drinkers.