Ignite Creation Date:
2024-05-06 @ 7:24 PM
Last Modification Date:
2024-10-26 @ 3:05 PM
Study NCT ID:
NCT05992272
Status:
RECRUITING
Last Update Posted:
2023-08-15
First Post:
2023-06-30
Brief Title:
Cue Effects in Human Addiction Pavlovian to Instrumental Transfer
Sponsor:
Charite University Berlin Germany
Organization:
Charite University Berlin Germany
Study Overview
Official Title:
Cue Effects in Human Addiction Pavlovian to Instrumental Transfer
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ReCoDe
Brief Summary:
Individuals with substance use disorders SUD have to cope with drug-related cues and contexts which can affect instrumental drug seeking as shown with Pavlovian to instrumental transfer PIT paradigms in animals and humans The investigators aimed to investigate the impact of acute and chronic stress on Pavlovian-to-instrumental transfer PIT how PIT it is associated with cognitive control abilities and whether such effects predict losing vs regaining control in subjects with AUD Moreover the investigators aimed to develop a novel full transfer task that assesses both general and specific PIT to investigate whether specific PIT differs between alcohol use disorder AUD and control subjects
Detailed Description:
This project has four research aims
1 The investigators want to assess the effects of acute as well as repeated stress exposure on PIT and its neuroimaging correlates and the investigators will test whether modulation of PIT by stress predicts losing vs regaining control of drug intake in mild to moderate AUD subjects
2 The investigators will investigate how cognitive control abilities eg interference control and response inhibition are related to the costs of interference between Pavlovian and instrumental control in PIT
3 The investigators will compare PIT its relation to cognitive control and the neural mechanisms between different drugs of abuse by investigating participants with AUD and also smokers
4 The investigators will develop an outcome-specific PIT paradigm with alternative food and drug rewards to compare AUD and healthy controls and the investigators will explore communalities and differences in behavioral and neural processes between general PIT and outcome-specific PIT
Therefore the investigators conduct 3 Experiments with the following Hypotheses
Experiment 1
Here the investigators assess on a behavioral and neural level a general PIT task that consists of four parts
In the instrumental part participants have to learn which shells to collect or leave in order to gain as much money as possible the correct choice is probabilistically rewarded in 80 of all times Absolutely unrelated to this instrumental part during Pavlovian conditioning colorful fractals are presented in the back of the screen which have been passively paired either with monetary gain no change or monetary loss ie they act as positively valued neutral or negatively valued cues These fractals thus act as independent Pavlovian conditioned background stimuli and interact with instrumental behavior in the unrelated third transfer part of the PIT task Also the investigators assess the effects of drug-specific cues in the background on instrumental behavior during this transfer part To avoid further learning the transfer part will be conducted under nominal extinction Finally query trials in which participants will have to choose one of two pictures will to assess the relative cue value
Acute stress will be induced by the Trier Social Stress Test TSST chronic stress will be assessed by questionnaires and hair cortisol
Hypothesis 1a
Acute and chronic stress exposure increase behavioral and neural PIT effects elicited by monetary Pavlovian conditioned stimuli CS and decrease inhibitory effects of alcohol Pavlovian CS Functional correlates of PIT effects will be found in the amygdala and in the ventral striatum
Hypothesis 1b
Following stress exposure high PIT effects elicited by monetary Pavlovian CS and low inhibitory effects elicited by alcohol Pavlovian CS predict higher subsequent alcohol intake in the follow-up period of 6 months
Methods
Between group analysis The investigators will analyze on a behavioral and imaging level how acutely consuming AUD subjects and matched controls differ regarding money- and alcohol-related PIT
Within-group analysis The investigators will analyze how acute stress affects PIT effects This 2x2 design 1 within-group subject factor with two levels STRESS vs NO STRESS and 1 between-group subject factor with two levels AUD vs matched controls will be tested on a behavioral and neural level
Experiment 2
In this experiment the investigators will utilize a 2x3 factorial group design Participants will be categorized into two main groups those with AUD and those without non-AUD Each of these groups will be further divided into three subgroups daily smokers non-daily smokers and non-smokers Each cell individual subgroup will consist of 35 subjects In addition to the PIT task described above the N 210 participants will additionally perform a Counting Stroop task and a No-go Simon task Participants will also perform a stop signal task during functional MRI fMRI
Methods
Interference Costs Interference costs will be calculated based on error rate ER and reaction time RT differences between task conditions eg incongruent vs congruent conditions
Between-group analysis the investigators will examine group differences in the interference PIT effect at both the behavioral and neural levels using a two AUD vs non-AUD by three daily smokers vs non-daily smokers vs non-smokers design In addition the investigators aim to investigate the associations between the interference PIT effect and other continuous measures Alcohol Use Disorders Identification Test AUDIT Fagerström Test for Nicotine Dependence FTND along with quantity-frequency indices
Other analysis In order to gain a better understanding of the mechanisms underlying PIT the investigators will also fit a drift diffusion model to the behavioral data and explore the connectivity within the neural networks during PIT in relation to the connectivity during the stop signal task response inhibition
Hypothesis 2a
Interference costs ie increased error rate ER in instrumental responses during PIT are associated with interference costs at the stimulus level Stroop task and at the response level No-go Simon task and these costs will also be correlated with the ER during response inhibition No-go Simon task
Hypothesis 2b
The investigators hypothesize that the interference PIT effect will be more pronounced in the AUD group compared to the non-AUD group The investigators also anticipate that the effect will be stronger in the smoker group Furthermore the investigators hypothesize a positive correlation between the PIT effect and AUDIT FTND scores as well as the quantity and frequency of use As the behavioral PIT effect intensifies the investigators expect corresponding neural responses to similarly increase
Experiment 3
The investigators here use a newly-developed full PIT paradigm that introduces primary reinforcers ie alcoholic and soft drinks that the investigators administer on a trial-by-trial basis Furthermore the investigators implemented additional Pavlovian stimuli to examine both general and outcome-specific PIT effects General PIT effects occur when positively valued environmental Pavlovian stimuli enhance instrumental responding regardless of the reinforcer being used Here stimuli that are associated with eg monetary rewards can enhance instrumental responding for alcohol drinks demonstrating a general motivational effect In contrast during outcome-specific PIT this effect is limited for the same stimulus-reward association For instance Pavlovian stimuli associated with a soft drink promote choices for the same soft drink outcome only
Methods
Between-group Analysis The investigators will assess the outcome-specific PIT effects by measuring the change in the proportion of alcohol choices when the alcohol cue is presented versus when the soft drink juice cue is shown On the other hand the investigators will define general PIT effects as the increase in button presses ie slope corresponding to the increased valence of the conditioned monetary cues The investigators plan to examine the differences in both specific and general PIT effects at both the behavioral and neural levels between the AUD group and the non-AUD group controlling for smoking status Additionally the investigators will investigate the relationship between specific and general PIT effects and AUDIT along with quantity-frequency measures Comparison between the two PIT tasks the investigators will explore similarities and differences in PIT effects between the full PIT paradigm and the previously-mentioned single-lever PIT paradigm
Stress the investigators will test whether levels of chronic stress assessed with questionnaires and hair cortisol as for Experiment 1 moderate outcome-specific and full PIT effects
Hypothesis 3a
The investigators expect that both outcome-specific and general PIT effects will be stronger in participants with AUD compared to those without AUD evident at both behavioral and neural levels Additionally the investigators predict positive associations between PIT effects and both AUDIT scores and quantity-frequency measures
Hypothesis 3b
the investigators hypothesize that the PIT effect found in the single-lever PIT task is more strongly associated with the general PIT and less strongly associated with the outcome-specific PIT effect in the full PIT task
Hypothesis 3c
Increased chronic stress will enhance effects of both general and outcome-specific PIT
1 The investigators want to assess the effects of acute as well as repeated stress exposure on PIT and its neuroimaging correlates and the investigators will test whether modulation of PIT by stress predicts losing vs regaining control of drug intake in mild to moderate AUD subjects
2 The investigators will investigate how cognitive control abilities eg interference control and response inhibition are related to the costs of interference between Pavlovian and instrumental control in PIT
3 The investigators will compare PIT its relation to cognitive control and the neural mechanisms between different drugs of abuse by investigating participants with AUD and also smokers
4 The investigators will develop an outcome-specific PIT paradigm with alternative food and drug rewards to compare AUD and healthy controls and the investigators will explore communalities and differences in behavioral and neural processes between general PIT and outcome-specific PIT
Therefore the investigators conduct 3 Experiments with the following Hypotheses
Experiment 1
Here the investigators assess on a behavioral and neural level a general PIT task that consists of four parts
In the instrumental part participants have to learn which shells to collect or leave in order to gain as much money as possible the correct choice is probabilistically rewarded in 80 of all times Absolutely unrelated to this instrumental part during Pavlovian conditioning colorful fractals are presented in the back of the screen which have been passively paired either with monetary gain no change or monetary loss ie they act as positively valued neutral or negatively valued cues These fractals thus act as independent Pavlovian conditioned background stimuli and interact with instrumental behavior in the unrelated third transfer part of the PIT task Also the investigators assess the effects of drug-specific cues in the background on instrumental behavior during this transfer part To avoid further learning the transfer part will be conducted under nominal extinction Finally query trials in which participants will have to choose one of two pictures will to assess the relative cue value
Acute stress will be induced by the Trier Social Stress Test TSST chronic stress will be assessed by questionnaires and hair cortisol
Hypothesis 1a
Acute and chronic stress exposure increase behavioral and neural PIT effects elicited by monetary Pavlovian conditioned stimuli CS and decrease inhibitory effects of alcohol Pavlovian CS Functional correlates of PIT effects will be found in the amygdala and in the ventral striatum
Hypothesis 1b
Following stress exposure high PIT effects elicited by monetary Pavlovian CS and low inhibitory effects elicited by alcohol Pavlovian CS predict higher subsequent alcohol intake in the follow-up period of 6 months
Methods
Between group analysis The investigators will analyze on a behavioral and imaging level how acutely consuming AUD subjects and matched controls differ regarding money- and alcohol-related PIT
Within-group analysis The investigators will analyze how acute stress affects PIT effects This 2x2 design 1 within-group subject factor with two levels STRESS vs NO STRESS and 1 between-group subject factor with two levels AUD vs matched controls will be tested on a behavioral and neural level
Experiment 2
In this experiment the investigators will utilize a 2x3 factorial group design Participants will be categorized into two main groups those with AUD and those without non-AUD Each of these groups will be further divided into three subgroups daily smokers non-daily smokers and non-smokers Each cell individual subgroup will consist of 35 subjects In addition to the PIT task described above the N 210 participants will additionally perform a Counting Stroop task and a No-go Simon task Participants will also perform a stop signal task during functional MRI fMRI
Methods
Interference Costs Interference costs will be calculated based on error rate ER and reaction time RT differences between task conditions eg incongruent vs congruent conditions
Between-group analysis the investigators will examine group differences in the interference PIT effect at both the behavioral and neural levels using a two AUD vs non-AUD by three daily smokers vs non-daily smokers vs non-smokers design In addition the investigators aim to investigate the associations between the interference PIT effect and other continuous measures Alcohol Use Disorders Identification Test AUDIT Fagerström Test for Nicotine Dependence FTND along with quantity-frequency indices
Other analysis In order to gain a better understanding of the mechanisms underlying PIT the investigators will also fit a drift diffusion model to the behavioral data and explore the connectivity within the neural networks during PIT in relation to the connectivity during the stop signal task response inhibition
Hypothesis 2a
Interference costs ie increased error rate ER in instrumental responses during PIT are associated with interference costs at the stimulus level Stroop task and at the response level No-go Simon task and these costs will also be correlated with the ER during response inhibition No-go Simon task
Hypothesis 2b
The investigators hypothesize that the interference PIT effect will be more pronounced in the AUD group compared to the non-AUD group The investigators also anticipate that the effect will be stronger in the smoker group Furthermore the investigators hypothesize a positive correlation between the PIT effect and AUDIT FTND scores as well as the quantity and frequency of use As the behavioral PIT effect intensifies the investigators expect corresponding neural responses to similarly increase
Experiment 3
The investigators here use a newly-developed full PIT paradigm that introduces primary reinforcers ie alcoholic and soft drinks that the investigators administer on a trial-by-trial basis Furthermore the investigators implemented additional Pavlovian stimuli to examine both general and outcome-specific PIT effects General PIT effects occur when positively valued environmental Pavlovian stimuli enhance instrumental responding regardless of the reinforcer being used Here stimuli that are associated with eg monetary rewards can enhance instrumental responding for alcohol drinks demonstrating a general motivational effect In contrast during outcome-specific PIT this effect is limited for the same stimulus-reward association For instance Pavlovian stimuli associated with a soft drink promote choices for the same soft drink outcome only
Methods
Between-group Analysis The investigators will assess the outcome-specific PIT effects by measuring the change in the proportion of alcohol choices when the alcohol cue is presented versus when the soft drink juice cue is shown On the other hand the investigators will define general PIT effects as the increase in button presses ie slope corresponding to the increased valence of the conditioned monetary cues The investigators plan to examine the differences in both specific and general PIT effects at both the behavioral and neural levels between the AUD group and the non-AUD group controlling for smoking status Additionally the investigators will investigate the relationship between specific and general PIT effects and AUDIT along with quantity-frequency measures Comparison between the two PIT tasks the investigators will explore similarities and differences in PIT effects between the full PIT paradigm and the previously-mentioned single-lever PIT paradigm
Stress the investigators will test whether levels of chronic stress assessed with questionnaires and hair cortisol as for Experiment 1 moderate outcome-specific and full PIT effects
Hypothesis 3a
The investigators expect that both outcome-specific and general PIT effects will be stronger in participants with AUD compared to those without AUD evident at both behavioral and neural levels Additionally the investigators predict positive associations between PIT effects and both AUDIT scores and quantity-frequency measures
Hypothesis 3b
the investigators hypothesize that the PIT effect found in the single-lever PIT task is more strongly associated with the general PIT and less strongly associated with the outcome-specific PIT effect in the full PIT task
Hypothesis 3c
Increased chronic stress will enhance effects of both general and outcome-specific PIT
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None