Human drug dependence: Cognitive predisposition and neural mechanisms

Lead Research Organisation: University of Nottingham
Department Name: Sch of Psychology

Abstract

Although a large percentage of the population have tried addictive drugs, only a small percentage become pathologically addicted in that they bring about significant harm to their health and social relationships. Others, by contrast, maintain casual drug use, but ultimately stop before incurring serious damage. Although the risk of becoming addicted largely depends upon whether one has an ?addictive personality?, the exact nature of this personality remains unclear. To improve our understanding of the risk factors for addiction, we plan to test whether addicts, in contrast to casual users, are less able to inhibit drug seeking behaviour in the laboratory in the face of knowledge that this behaviour is no longer rewarding, is actively causing harm, or is inappropriate in the context. Such experimental data would confirm the clinical impression that addiction is caused by an inability to inhibit drug seeking in the face of knowledge of the negative consequences of this behaviour. In addition, the laboratory methods developed in the project could provide a screening instrument for the addictive personality, and the insight gained into addiction would justify funding for treatments that target addicts? perception of drug harm.
The frontal cortex is a brain region that sits just behind the eyes, where options are considered before action judged beneficial is undertaken. It has been suggested that addicts have damage in this area, which reduces the weight given to the negative consequences when considering whether to engage in drug seeking. To test this hypothesis, we will measure activity in the frontal cortex while addicts and casual drug users consider undertaking drug seeking that is potentially harmful. If addicts show a reduced signal for this harm compared to causal users, which predicts the continuation of drug seeking despite the harm, we will be able to conclude that a flaw in the frontal cortex confers a neurobiological risk factor for the addictive personality and addiction. This conclusion would support pharmacological treatments that seek to correct this brain abnormality.
The final part of the project aims to test whether our laboratory measure of the addictive personality provides an accurate screening instrument for adolescents who are at risk of becoming drug addicted. These data would support a prevention strategy that identifies and informs these adolescents of their susceptibility before they become addicted, and in particular, seeks to enhance their understanding of the negative consequences of drug seeking.

Technical Summary

A key diagnostic of human drug dependence is that drug seeking continues despite this behaviour causing medical and social harm. Such perseveration has recently been observed in a sub-population of animals that are unable to inhibit drug seeking when this behaviour is extinguished or punished. The implication is that humans who meet clinical criteria for drug dependence should demonstrate such perseveration under similar conditioning schedules. To test this hypothesis, clinically dependent and non-dependent smokers will be assessed for their perseveration of tobacco and money seeking under extinction, punishment and conditioned inhibition, versus none of these challenges. These experiments will indicate whether dependence related perseveration is general to reward seeking or specific to drug seeking. In addition, comparison of the three paradigms and measurement of visual attention will indicate whether perseveration is mediated by a failure to attend to or to encode the negative consequences of drug seeking, or a failure to apply inhibitory control on the basis of this knowledge. This work would refine the clinical assessment of dependence, and specify treatments that act upon the inhibitory control deficit.
It has been argued that the neurobiological basis of drug dependence is a failure of the orbital frontal cortex (OFC) to encode the expectation of negative consequences that would normally moderate harmful drug seeking. To test this, we will use an MRI scanner to measure the OFC BOLD signal in dependent and non-dependent smokers engaged in punished and non-punished tobacco and money seeking. The finding of a reduced OFC signal for punishment in the dependent group, which is associated with perseveration of tobacco seeking under punishment, would confirm the OFC as an important neurobiological substrate of dependence, strengthening neuropharmacological interventions that act upon this abnormality.
The final aim of the project is to develop a screening instrument for the risk of substance dependence in adolescence. To this end, we will examine whether behavioural perseveration of reward seeking is associated with an established psychometric index of dependence risk in young offenders. This relationship would suggest that behavioural perseveration is a risk factor for dependence rather than the consequence of chronic drug use, and would strengthen interventions that enhance the insight of the high risk cohort into the negative consequences of drug seeking. We hope to follow this work with funding for a prospective design to assess the predictive validity of behavioural perseveration as a screening instrumental for subsequent dependence.

Publications

10 25 50
 
Description Alcohol seeking and consumption: the role of reward valuation and attentional bias
Amount £98,000 (GBP)
Funding ID ES/I024131/1 
Organisation Economic and Social Research Council 
Sector Public
Country United Kingdom
Start 01/2011 
End 01/2012
 
Description Australian Research Council
Amount $96 (AUD)
Funding ID DP130103277 
Organisation Australian Research Council 
Sector Public
Country Australia
Start 01/2013 
End 01/2014
 
Description ESRC Reseach Studentship
Amount £80,000 (GBP)
Organisation Economic and Social Research Council 
Sector Public
Country United Kingdom
Start 09/2014 
End 09/2018
 
Description Neurophysiological correlates of Pavlovian to instrumental transfer in heavy drinkers
Amount £5,000 (GBP)
Organisation Alcohol Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2011 
End 01/2011
 
Description PhD scholarship
Amount £30,000 (GBP)
Organisation Alcohol Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2017 
End 08/2020
 
Description Alcohol Pavlovian to instrumental transfer 
Organisation University of Liverpool
Department Institute of Psychology, Health and Society
Country United Kingdom 
Sector Academic/University 
PI Contribution Contributed to grant application and subsequent design, analysis and publication of results.
Collaborator Contribution Intellectual development
Impact Jones A, Hogarth L, Christiansen P, Rose AK, Martinovic J, Field M (2012) Reward expectancy promotes generalised increases in attentional bias for rewarding stimuli. Q J Exp Psychol in press. Field M, Hogarth L, Bleasdale D, Wright P, Fernie G, Christiansen P (2011) Alcohol expectancy moderates attentional bias for alcohol cues in light drinkers. Addiction 106: 1097-1103. Alcohol Education and Research council (AERC). £5k. Neurophysiological correlates of Pavlovian to instrumental transfer in heavy drinkers. Dr. Matt Field (Liverpool) and Dr. Lee Hogarth (co-investigator). April 2011 to Oct 2011.
Start Year 2010
 
Description Alcohol dependence 
Organisation University of Liverpool
Department Institute of Psychology, Health and Society
Country United Kingdom 
Sector Academic/University 
PI Contribution Contributed to grant application and all subsequent research in terms of design, analysis and publishing results.
Collaborator Contribution Intellectual development
Impact ESRC Project Grant (RES-OOO-22-436). £97k. Alcohol seeking and consumption: The role of reward valuation and attentional bias. Dr. Abi Rose (Liverpool) and Dr. Lee Hogarth (co- investigator). March 2011 to 2012. Hogarth L, Field M, Rose AK (in press) Phasic transition from goal-directed to habitual control over drug-seeking produced by conflicting reinforcer expectancy. Addiction Biology.
Start Year 2011
 
Description Alcohol treatment 
Organisation Nottinghamshire Healthcare NHS Trust
Department Substance Misuse Services
Country United Kingdom 
Sector Public 
PI Contribution Contribution to analysis and publication of existing data set, design and analysis of an ongoing experiment with treatment seeking alcoholics.
Collaborator Contribution Access to clinical groups
Impact Craig M, Pennacchia A, Wright NR, Chase HW, Hogarth L (2011) Evaluation of un-medicated, self-paced alcohol withdrawal. PLoS One 6: e22994. One further experiment is in progress. The collaboration is between consultant psychiatrists working within the NHS substance misuse service, and the experimentalists working at University of Nottingham, and so meets the MRC Addiction Research Strategy to translate between the disciplines.
Start Year 2010
 
Description Depression and addiction 
Organisation Northwestern University
Department Feinberg School of Medicine
Country United States 
Sector Academic/University 
PI Contribution Paper writing and grant writing.
Collaborator Contribution Paper writing and grant writing.
Impact Two papers published, one paper under review, and one grant in preparation.
Start Year 2009
 
Description Exeter Drug Project 
Organisation Exeter Drug Project (EDP)
Country United Kingdom 
Sector Public 
PI Contribution Partnership between research on mechanisms of addiction and the drug treatment service providers.
Collaborator Contribution Co-creation of impactfull projects
Impact None as yet
Start Year 2013
 
Description Psychological mechanisms underpinning addiction 
Organisation University of Bristol
Department School of Experimental Psychology
Country United Kingdom 
Sector Academic/University 
PI Contribution Pooling of research capacity and skills
Collaborator Contribution Pooling of research capacity and skills
Impact Hogarth L, Attwood AS, Bate HA, Munafò MR (2012) Acute alcohol impairs human goal-directed action. Biological Psychology 90: 154-160.
Start Year 2010
 
Description Self control in addiction 
Organisation Curtin University
Department School of Psychology and Speech Pathology
Country Australia 
Sector Academic/University 
PI Contribution Grant co-applicant
Collaborator Contribution Grant co-applicant
Impact Australian Research Council Grant (DP130103277). $96k AUD = £63k. Advancing the science of willpower: investigating the mechanisms and processes of self-control. Prof Martin Hagger (PI), Dr. Lee Hogarth (co- investigator). 2013-2014.
Start Year 2012
 
Description Brain awareness week 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Schools
Results and Impact Approximately 50 student attended a 2 day session on popular issues in neuroscience. My presentation was concerned with neural mechanisms underpinning drug dependence.

Feedback from the delegates was very positive
Year(s) Of Engagement Activity 2011
 
Description British Science Festival - From Pavlov to present 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Approximately 30 members of the public attended a 2 hour session with 5 speakers on the topic of Pavlovian conditioning and its impact on modern psychological and clinical science. Hogarth gave a 20 minute presentation of the role of conditioning in human drug dependence. This was followed by a media interview with the BBC in which the MRC funding for this work was mentioned.

There was a lively discussion following the seminar, so I would consider the seminar as having been successful in engaging the audience.
Year(s) Of Engagement Activity 2010