Ignite Creation Date:
2024-05-06 @ 12:24 PM
Last Modification Date:
2024-10-26 @ 12:58 PM
Study NCT ID:
NCT03754062
Status:
COMPLETED
Last Update Posted:
2019-10-10
First Post:
2018-10-23
Brief Title:
Pharmacological Modulation of Belief Salience
Sponsor:
Kings College London
Organization:
Kings College London
Study Overview
Official Title:
Pharmacological Modulation of Belief Salience
Status:
COMPLETED
Status Verified Date:
2019-02
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:
MOBS
Brief Summary:
To provide an initial test of the hypothesis that dopamine mediates the motivational salience of stimuli beyond simple stimulus-reinforcement associations the researchers propose to undertake a study of the modulation of a levels of agreement or disagreement with b the perceived self- relevance and c the perceived interest of propositions expressing beliefs and values in healthy male volunteers using Ii a dopamine antagonist the D2-blocker haloperidol and ii a dopamine precursor L-Dopa to increase CNS dopamine transmission
The researchers will also administer the Salience Attribution Task SAT which will allow researchers to assess reward-learning processing of simple stimuli using a reaction-time game This task was utilised by Roiser et al in order to explore whether delusions in medicated patients with schizophrenia were related to impairments in associative learning The authors hypothesised that associative learning was influenced by D2 receptor blockade The researchers extend this approach to examine the effect of dopamine modulation on the SAT as a measure of associative learning a basic neuropsychological process that may be involved in the attribution of salience to beliefs
Finally the researchers will ask participants to perform a within-subjects dictator game to understand the influence of dopaminergic manipulation of the live attribution of harm intention to partners The task has been previously validated online Participants will play against 3 partners in a random order in each drug condition Each partner will play the participant for 6 trials One partner will always be fair one will always be unfair and one will be 50 unfair We aim to understand whether potentiating dopamine has an additive effect on the harm intention attributions toward partners regardless of the behaviour of the partner
The researchers will also administer the Salience Attribution Task SAT which will allow researchers to assess reward-learning processing of simple stimuli using a reaction-time game This task was utilised by Roiser et al in order to explore whether delusions in medicated patients with schizophrenia were related to impairments in associative learning The authors hypothesised that associative learning was influenced by D2 receptor blockade The researchers extend this approach to examine the effect of dopamine modulation on the SAT as a measure of associative learning a basic neuropsychological process that may be involved in the attribution of salience to beliefs
Finally the researchers will ask participants to perform a within-subjects dictator game to understand the influence of dopaminergic manipulation of the live attribution of harm intention to partners The task has been previously validated online Participants will play against 3 partners in a random order in each drug condition Each partner will play the participant for 6 trials One partner will always be fair one will always be unfair and one will be 50 unfair We aim to understand whether potentiating dopamine has an additive effect on the harm intention attributions toward partners regardless of the behaviour of the partner
Detailed Description:
Delusions in psychiatry are viewed as a form of aberrant belief Consequently it is important to understand the cognitive and neural processes involved in beliefs to provide insights into how these processes go awry in the formation of delusions Beliefs have been defined as a disposition to express assent to or otherwise act in accordance with some proposition Some beliefs are widely held within a given society eg the earth revolves around the sun eating humans is wrong whereas others vary in association with subcultural and individual differences eg God created the universe abortion is wrong Similarly the conviction or agreement with which an individuals beliefs and values are held may change over time to the extent that some beliefs and values may be lost and others acquired Also the perceived relevance of beliefs and values to oneself may vary For example beliefs that the earth revolves around the sun and that global warming is occurring may both be held with conviction but the latter may be perceived as having higher relevance to the self in terms of risk and potential life-style changes Hence self-relevance is a dimension of beliefs that is potentially dissociable from the conviction level of agreement with which a belief is held Further some propositions expressing beliefs and values may be regarded as more interesting than others This raises the question of what neurobiological processes contribute to the sense of conviction for and perceived self-relevance and interest of beliefs and values
The mesolimbic dopamine system is a candidate neural system implicated in mediating the motivational salience of perceptions and ideas whereby events and thoughts come to grab attention drive action and influence goal-directed behaviour because of their association with reward or punishment In human studies haloperidol has been used to show that dopamine activity influences action-value estimates represented in the striatum during instrumental conditioning as would be expected from earlier studies of feedback-based learning Still other data suggest that brain regions rich in dopaminergic inputs play a role in processing the salience of rewarding events What is not known is if these dopaminergic rich regions also modulate the motivational salience of more complex stimuli including ideas and beliefs
Main hypothesis
Prediction 1
At a neurobiological level the hypothesis is that the mesolimbic dopamine system is recruited to tag representations ideas and beliefs as motivationally salient Potentiation of dopamine transmission should increase salience of beliefs as indicated by increases in agreement self-relevance and interest toward propositions within science paranormal politics moral and religious themes in the Beliefs and Values Inventory while attenuation of dopamine transmission should be associated with decreased salience Answers of items within themes will be summed to create summary scores that will be split by agreement interest and self-relevance dimensions
Prediction 2
Potentiating dopamine be associated with increased attribution of harmful intent to partners across all trials but trait paranoia will not be associated with variation in attributions of self-interest of a within-subjects dictator game
Prediction 3
Attribution of harmful intent to different dictators will follow a dose-response relationship fair partially fair unfair across all ranges of dopamine potentiation However L-Dopa conditions will have a higher baseline of average harmful intent There will be no interaction between dopamine manipulations and dictator fairness on attribution of harmful intent
If these hypotheses receive empirical support it would be relevant to understanding the role of the dopamine system in normal cognitive processes involved in expressing or acting in accordance with beliefs It would also be relevant to determining the role of dopamine dysregulation in psychosis in delusion formation Also reduced levels of the meaningfulness of experience following antipsychotic administration as indexed by reduced agreement for and perceived self- relevance and interest of beliefs and values would identify a potential reason for non-compliance with antipsychotic treatment
Supplementary hypotheses
There will be an interaction between condition placebo dopamine blockade dopamine potentiation x dimension agreement self-relevance interest whereby self-relevance and interest are affected more by dopamine modulation than agreement This might explain why patients with delusions who are given antipsychotics will continue to say that they believe x but dont think about it as much and cease to act upon it
Aims
To provide an initial test of the hypothesis that dopamine mediates the motivational salience of stimuli beyond simple stimulus-reinforcement associations we propose to undertake a study of the modulation of a levels of agreement or disagreement with b the perceived self- relevance and c the perceived interest of propositions expressing beliefs and values in healthy male volunteers using i a dopamine antagonist the D2-blocker haloperidol and ii a dopamine precursor L-Dopa to increase CNS dopamine transmission
The researchers will also administer the Salience Attribution Task SAT which will allow the researchers to assess reward-learning processing of simple stimuli using a reaction-time game This task was utilised by Roiser et al in order to explore whether delusions in medicated patients with schizophrenia were related to impairments in associative learning The authors hypothesised that associative learning was influenced by D2 receptor blockade We extend this approach to examine the effect of dopamine modulation on the SAT as a measure of associative learning a basic neuropsychological process that may be involved in the attribution of salience to beliefs
Finally the researchers will ask participants to perform a within-subjects dictator game to understand the influence of dopaminergic manipulation of the Participants will play against 3 partners in a random order in each drug condition Each partner will play the participant for 6 trials One partner will always be fair one will always be unfair and one will be 50 unfair We aim to understand whether potentiating dopamine has an additive effect on the harm intention attributions toward partners regardless of the behaviour of the partner
The mesolimbic dopamine system is a candidate neural system implicated in mediating the motivational salience of perceptions and ideas whereby events and thoughts come to grab attention drive action and influence goal-directed behaviour because of their association with reward or punishment In human studies haloperidol has been used to show that dopamine activity influences action-value estimates represented in the striatum during instrumental conditioning as would be expected from earlier studies of feedback-based learning Still other data suggest that brain regions rich in dopaminergic inputs play a role in processing the salience of rewarding events What is not known is if these dopaminergic rich regions also modulate the motivational salience of more complex stimuli including ideas and beliefs
Main hypothesis
Prediction 1
At a neurobiological level the hypothesis is that the mesolimbic dopamine system is recruited to tag representations ideas and beliefs as motivationally salient Potentiation of dopamine transmission should increase salience of beliefs as indicated by increases in agreement self-relevance and interest toward propositions within science paranormal politics moral and religious themes in the Beliefs and Values Inventory while attenuation of dopamine transmission should be associated with decreased salience Answers of items within themes will be summed to create summary scores that will be split by agreement interest and self-relevance dimensions
Prediction 2
Potentiating dopamine be associated with increased attribution of harmful intent to partners across all trials but trait paranoia will not be associated with variation in attributions of self-interest of a within-subjects dictator game
Prediction 3
Attribution of harmful intent to different dictators will follow a dose-response relationship fair partially fair unfair across all ranges of dopamine potentiation However L-Dopa conditions will have a higher baseline of average harmful intent There will be no interaction between dopamine manipulations and dictator fairness on attribution of harmful intent
If these hypotheses receive empirical support it would be relevant to understanding the role of the dopamine system in normal cognitive processes involved in expressing or acting in accordance with beliefs It would also be relevant to determining the role of dopamine dysregulation in psychosis in delusion formation Also reduced levels of the meaningfulness of experience following antipsychotic administration as indexed by reduced agreement for and perceived self- relevance and interest of beliefs and values would identify a potential reason for non-compliance with antipsychotic treatment
Supplementary hypotheses
There will be an interaction between condition placebo dopamine blockade dopamine potentiation x dimension agreement self-relevance interest whereby self-relevance and interest are affected more by dopamine modulation than agreement This might explain why patients with delusions who are given antipsychotics will continue to say that they believe x but dont think about it as much and cease to act upon it
Aims
To provide an initial test of the hypothesis that dopamine mediates the motivational salience of stimuli beyond simple stimulus-reinforcement associations we propose to undertake a study of the modulation of a levels of agreement or disagreement with b the perceived self- relevance and c the perceived interest of propositions expressing beliefs and values in healthy male volunteers using i a dopamine antagonist the D2-blocker haloperidol and ii a dopamine precursor L-Dopa to increase CNS dopamine transmission
The researchers will also administer the Salience Attribution Task SAT which will allow the researchers to assess reward-learning processing of simple stimuli using a reaction-time game This task was utilised by Roiser et al in order to explore whether delusions in medicated patients with schizophrenia were related to impairments in associative learning The authors hypothesised that associative learning was influenced by D2 receptor blockade We extend this approach to examine the effect of dopamine modulation on the SAT as a measure of associative learning a basic neuropsychological process that may be involved in the attribution of salience to beliefs
Finally the researchers will ask participants to perform a within-subjects dictator game to understand the influence of dopaminergic manipulation of the Participants will play against 3 partners in a random order in each drug condition Each partner will play the participant for 6 trials One partner will always be fair one will always be unfair and one will be 50 unfair We aim to understand whether potentiating dopamine has an additive effect on the harm intention attributions toward partners regardless of the behaviour of the partner
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?:
False
Is an FDA AA801 Violation?:
None