Neural correlates of instrumental responding in the context of alcohol-related cues index disorder severity and relapse risk

Schad, Daniel J.; Garbusow, Maria; Friedel, Eva; Sommer, Christian; Sebold, Miriam; Hägele, Claudia; Bernhardt, Nadine; Nebe, Stephan; Kuitunen‐Paul, Sören; Liu, Shuyan; Eichmann, Uta; Beck, Anne; Wittchen, Hans‐Ulrich; Walter, Henrik; Sterzer, Philipp; Zimmermann, U.; Smolka, Michael N.; Schlagenhauf, Florian; Huys, Quentin J. M.; Heinz, Andreas; Rapp, Michael A.

doi:10.1007/s00406-017-0860-4

Cited by 33 publications

(53 citation statements)

References 67 publications

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“…Also, it has been observed before that NAcc and amygdala seem to hold relevant signal related to PIT in healthy subjects (Prévost et al, 2012) and to increased PIT in addicted subjects (Garbusow et al, 2016). Interestingly, previous studies (Garbusow et al, 2016;Schad et al, 2018) have observed that in recently detoxified treatment-seeking AD patients, images of alcoholic beverages in the background have a suppressing effect on the instrumental task in the foreground. Contrarily, we have seen that gambling cues elicit a stronger gamble acceptance increase in GD than in HC.…”

Section: Discussionmentioning

confidence: 89%

“…There is evidence that the influence of cue-induced emotional states onto value-based decision-making is stronger in GD than HC subjects (Dixon et al, 2006;van Holst, van Holstein, et al, 2012) (Genauck, under review). The influence of cues onto value-based decision-making may be regarded as a form of Pavlovian-to-Instrumental Transfer (PIT), the increase of which has been associated with addictive disorders in general Garbusow et al, 2016;Genauck, Huys, Heinz, & Rapp, 2013;Mitchell, Gao, Hallett, & Voon, 2016;Schad et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Patients suffering from SUDs have displayed increased PIT (Corbit & Janak, 2016;Corbit, Janak, & Balleine, 2007;Corbit, Nie, & Janak, 2012;Garbusow et al, 2016;Schad et al, 2018), however not in all studies (Hogarth & Chase, 2012). Furthermore, the effect seems to scale with the probability of relapse (Garbusow et al, 2016).…”

Section: Introductionmentioning

confidence: 93%

“…A second onset regressor modeled the time when gamble presentation was on (1 vs. 0). This phase was modeled according to the laec model and according to modeling PIT neurally (Garbusow et al, 2016;Schad et al, 2018). Modeling PIT neurally simply entails introducing interaction terms of cue reactivity regressors (e.g.…”

Section: Fmri Datamentioning

confidence: 99%

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Neural correlates of cue-induced changes in decision-making distinguish subjects with gambling disorder from healthy controls

Genauck

Matthis

Andrejević

et al. 2018

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Background:Just as substance use disorders (SUD), gambling disorder (GD) is characterized by an increase in cue-dependent decision-making (Pavlovian-to-instrumental transfer, PIT). PIT, as studied in SUDs and healthy subjects, is associated with altered communication between Nucleus Accumbens (NAcc), amygdala, and orbitofrontal cortex (OFC). However, these neural differences are poorly understood. For example, it is unclear whether they are due to the physiological effects of substance abuse, or rather related to learning processes and/or other etiological factors like innate traits associated with addiction. We have thus investigated whether network activation patterns during a PIT task are also altered in GD, an addictive disorder not involving substance abuse. We have specifically studied which neural PIT patterns were best at distinguishing GD from healthy control (HC) subjects, all to improve our understanding of the neural signatures of GD and of addiction-related PIT in general. Methods:30 GD and 30 HC subjects completed an affective decision-making task in a functional magnetic resonance imaging (fMRI) scanner. Gambling associated and other emotional cues were shown in the background during the task, allowing us to record multivariate neural PIT signatures focusing on a network of NAcc, amygdala and OFC. We built and tested a classifier based on these multivariate neural PIT signatures using cross-validated elastic net regression. Results and Discussion:As expected, GD subjects showed stronger PIT than HC subjects because they showed stronger increase in gamble acceptance when gambling cues were presented in the Alexander Genauck 5 background. Classification based on neural PIT signatures yielded a significant AUC-ROC (0.70, p = 0.013). When inspecting the features of the classifier, we observed that GD showed stronger PIT-related functional connectivity between nucleus accumbens (NAcc) and amygdala elicited by gambling background cues, as well as between amygdala and orbitofrontal cortex (OFC) elicited by negative and positive cues. Conclusion:We propose that GD and HC subjects are distinguishable by PIT-related neural signatures including amygdala-NAcc-OFC functional connectivity. Our findings suggest that neural PIT alterations in addictive disorders might not depend on the physiological effect of a substance of abuse, but on related learning processes or even innate neural traits, also found in behavioral addictions.Alexander Genauck 6

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

Section: Fmri Datamentioning

confidence: 99%

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Neural correlates of cue-induced changes in decision-making distinguish subjects with gambling disorder from healthy controls

Genauck

Matthis

Andrejević

et al. 2018

Preprint

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“…In animal experiments, effects of appetitive classical conditioning are studied using primary rewards, such as food, which elicits innate, reflexive responses (Corbit and Balleine, 2011). Providing primary rewards repeatedly in experiments with human subjects can be challenging and deprivation prior to an experiment (e.g., hunger or thirst) may be required to ensure reward saliency (Freeman et al, 2015;Manglani et al, 2017;Schad et al, 2018).…”

mentioning

confidence: 99%

Development of Pavlovian-to-instrumental transfer (PIT) task to examine the effects of reward-predicting cues on behavioral activation in young adults

Costa

Furukawa

Hoefle

et al. 2019

Preprint

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There is a growing recognition that much of human behavior is governed by the presence of classically conditioned cues. The Pavlovian-to-Instrumental Transfer (PIT) paradigm offers a way to measure the effects of classically conditioned stimuli on behavior. In the current study, a novel PIT paradigm was developed for use in conjunction with an fMRI classical conditioning task. This could allow for a measurement of BOLD responses to anticipated rewards, unconfounded by operant responses, while providing a behavioral measure of conditioning effects. Twenty-four healthy young adults completed 1) instrumental training, 2) Pavlovian conditioning, and 3) Transfer test. During instrumental training, participants learned to apply force on a handgrip to win money from slot machines pictured on a computer screen. During Pavlovian conditioning, slot machines appeared with one of two abstract symbols (cues), one symbol was predictive of monetary reward. During the Transfer test, participants again applied force on a handgrip to win more money. This time, slot machines were presented with the Pavlovian cues, but with the outcomes hidden. The results indicated increased effort on the instrumental task, i.e., higher response frequency and greater force, in the presence of a reward-predicting cue. Our findings add to a growing number of studies demonstrating PIT effects in humans. This paradigm was proved to be useful in measuring the effects of a conditioned stimulus on behavioral activation.

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The Dopamine System in Mediating Alcohol Effects in Humans

Beck

Ebrahimi

Rosenthal

et al. 2023

Current Topics in Behavioral Neurosciences

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Neural correlates of instrumental responding in the context of alcohol-related cues index disorder severity and relapse risk

Abstract: LeAD study, http://www.lead-studie.de , NCT01679145.

Cited by 33 publications

References 67 publications

Neural correlates of cue-induced changes in decision-making distinguish subjects with gambling disorder from healthy controls

Neural correlates of cue-induced changes in decision-making distinguish subjects with gambling disorder from healthy controls

Development of Pavlovian-to-instrumental transfer (PIT) task to examine the effects of reward-predicting cues on behavioral activation in young adults

The Dopamine System in Mediating Alcohol Effects in Humans

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