Dr Lee Hogarth
Associate Professor

Research

Research interests

Contributions to Science 

1. Incentive salience theory of addiction in humans

My PhD and early Postdoctoral research tested Robinson and Berridge’s (1993) incentive salience theory of addiction in humans. This account predicts that (a) drug addicts should have their attention captured by drug cues, (b) attentional capture by drug cues should play a causal role in driving drug-seeking behavior, and therefore (c) abolishing the attentional bias should reduce cue-elicited drug-seeking. My first publication was one of the earliest demonstrations that drug cues do in fact capture addicts’ attention, using a reaction time measure of attention(A) and is in the top 10% for citations relative to comparable articles based on Scopus data. My subsequent work demonstrated that this attentional bias could be conditioned to arbitrary stimuli and measured more sensitively by eye tracking(B). However, I later discovered that abolishing the attentional bias did not reduce the ability of drug cues to elicit drug-seeking behavior, suggesting that abolishing the attentional bias will not provide a viable therapeutic intervention for addiction(C,D). This latter paper is in the top 30% for citations despite contradicting a core tenet within addiction theory. My prediction from this pre-clinical work, that attentional bias retraining would not yield therapeutic benefits, has been confirmed by clinical trials.

A. Hogarth LC, Mogg K, Bradley BP, Duka T, Dickinson A. Attentional orienting towards smoking-related stimuli. Behav Pharmacol. 2003 Mar;14(2):153-60. PMID: 12658076.

B. Hogarth L, Dickinson A, Hutton SB, Elbers N, Duka T. Drug expectancy is necessary for stimulus control of human attention, instrumental drug-seeking behaviour and subjective pleasure. Psychopharmacology (Berl). 2006 May;185(4):495-504. PMID: 16547713.

C. Hogarth L, Dickinson A, Janowski M, Nikitina A, Duka T. The role of attentional bias in mediating human drug-seeking behaviour. Psychopharmacology (Berl). 2008 Nov;201(1):29-41. PMID: 18679657.

D. Hogarth L, Dickinson A, Duka T. Detection versus sustained attention to drug cues have dissociable roles in mediating drug seeking behavior. Exp Clin Psychopharmacol. 2009 Feb;17(1):21-30. PMID: 19186931.

 

2. Drug cue-reactivity

Having discovered that attentional bias for drug cues is not a viable target for therapy, I switched to studying the decision mechanisms underpinning drug cue-reactivity. My first aim was to test whether cue elicited drug-seeking is automatic as predicted by implicit accounts, or driven by an expectation of the drug as predicted by decision making accounts. To test these predictions, I was the first person to develop an outcome-specific Pavlovian to instrumental transfer (PIT) procedure for humans with drug reinforcers (a method only previously used in animal behavioural neuroscience). My human procedure demonstrated that a drug stimulus could transfer selective control over a separately trained drug-seeking response, but not over a response trained with a different reinforcer(A) (top 6% cited). To produce this effect, the drug stimulus must have retrieved an expectation of the drug which selectively primed drug-seeking. This effect cannot be explained by automatic, habitual or implicit accounts of drug cue-reactivity.

Paradoxically, I later found that the selective control by a tobacco stimulus over a tobacco-seeking response was not attenuated by nicotine replacement therapy (NRT)(B) (top 7% cited). Furthermore, Dr. Hitsman and I extended this result, finding that that cue-elicited tobacco craving was also not attenuated by varenicline(C) (top 25% cited). The implication of these findings is that drug cues elicit drug-seeking by retrieving an expectation that the drug-seeking response has a higher probability of being reinforced, irrespective of whether the drug outcome currently has low value. I subsequently, confirmed this view experimentally and outlined the implications for cue-retraining therapies(D) (top10% cited).

The crucial observation across all of these studies, however, was that the capacity of drug cues to prime drug-seeking in the PIT procedure was not associated with individual differences in level of dependence(A,B,D). Thus, drug cue-reactivity is not the principal mechanism underpinning risk of dependence, so I turned my research program away from this outcome measure.

A. Hogarth L, Dickinson A, Wright A, Kouvaraki M, Duka T. The role of drug expectancy in the control of human drug seeking. J Exp Psychol Anim Behav Process. 2007 Oct;33(4):484-96. PMID: 17924795.

B. Hogarth L. Goal-directed and transfer-cue-elicited drug-seeking are dissociated by pharmacotherapy: evidence for independent additive controllers. J  Exp Psychol Anim Behav Process. 2012 Jul;38(3):266-78. PMID: 22823420.

C. Hitsman B, Hogarth L, Tseng LJ, Teige JC, Shadel WG, DiBenedetti DB, Danto S, Lee TC, Price LH, Niaura R. Dissociable effect of acute varenicline on tonic versus cue-provoked craving in non-treatment-motivated heavy smokers. Drug Alcohol Depend. 2013 Jun 1;130(1-3):135-41. PubMed PMID: 23201174.

D. Hogarth L, Retzler C, Munafò MR, Tran DM, Troisi JR 2nd, Rose AK, Jones A, Field M. Extinction of cue-evoked drug-seeking relies on degrading hierarchical instrumental expectancies. Behav Res Ther. 2014 Aug;59:61-70. PMID: 25011113.

 

3. Habit learning theory of addiction in humans

My PhD supervisor, Anthony Dickinson, had previously developed the habit learning theory of addiction in animals, and this account has since become a popular account of addiction in humans. On this view, drug-seeking is at first goal-directed (driven by the expected value of the drug), and progressively becomes habitual through practice (automatically elicited by drug related contexts without forethought for the consequences). Individual differences in vulnerability to dependence is driven by a propensity for drug-seeking to shift from being goal-directed to habitual, making the behaviour less amenable to cognitive regulation. To test this prediction, I was the first person to develop an outcome devaluation protocol for humans with drug reinforcers based on the animal model (A,B) (top 5% and 6% cited respectively). This work revealed that although drug-seeking could be rendered habitual under conditions of acute alcohol intoxication(C) (top 9% cited) or cognitive load (D) (top 20% cited), under normal conditions, drug-seeking is goal-directed rather than habitual. Furthermore, more dependent individuals were not more susceptible to drug-seeking becoming habitual(A,B,C,D). Instead, they engage in higher frequency of goal-directed drug-seeking, suggesting dependence is driven by greater expected reward value of the drug (consistent with behavioural-economic accounts). I have concluded from these findings that the evidence for habitual drug-seeking in animals is a product of the invariant nature of their laboratory experience, and that habit theory does not account for addiction in human.

A. Hogarth L, Chase HW. Parallel goal-directed and habitual control of human drug-seeking: implications for dependence vulnerability. J Exp Psychol Anim Behav Process. 2011 Jul;37(3):261-76. PMID: 21500933.

B. Hogarth L. Goal-directed and transfer-cue-elicited drug-seeking are dissociated by pharmacotherapy: evidence for independent additive controllers. J Exp Psychol Anim Behav Process. 2012 Jul;38(3):266-78. PMID: 22823420.

C. Hogarth L, Attwood AS, Bate HA, Munafò MR. Acute alcohol impairs human goal-directed action. Biol Psychol. 2012 May;90(2):154-60. PMID: 22406757.

D. Hogarth L, Field M, Rose AK. Phasic transition from goal-directed to habitual control over drug-seeking produced by conflicting reinforcer expectancy. Addict Biol. 2013 Jan;18(1):88-97. PMID: 23167442.

 

4. Negative reinforcement theory of drug dependence

My previous work had suggested that individual differences in sub-clinical dependence is driven by the greater expected reward value of the drug driving higher rates of goal-directed drug-seeking. The suspicion, however, was that a second process contributed to clinical addiction. According to negative reinforcement theories, negative states such as depression, anxiety, withdrawal, cognitive deficits etc., powerfully motivate drug-seeking to acutely mitigate those states. Dr. Hitsman and myself hypothesized that individual sensitivity to such negative triggers motivating goal-directed drug-seeking would be the crucial process underpinning clinical dependence. In testing this hypothesis, we adapted the outcome-devaluation procedure to demonstrate that acute negative mood can powerfully motivate drug-seeking behavior, fully countermanding the capacity of drug satiety to reduce goal-directed drug-seeking(A). We then demonstrated that smokers with current major depression are more sensitive to negative mood and withdrawal induced motivation of tobacco-seeking(B) and young adult drinkers with depression symptoms are more sensitive to negative mood-induced increases in alcohol-seeking(C). We have also synthesized this goal-directed account of drug dependence vulnerability in a high profile review article(D). Overall, we argue that individual differences in sub-clinical dependence are driven by the greater expected reward value of the drug driving higher rates of goal-directed drug-seeking. This process is amplified by negative motivational states in groups with comorbid psychiatric symptoms, which powerfully promote goal-directed drug-seeking producing the pathological character of clinical addiction. Our current work focuses on hypersensitivity to negative triggers for drug use in groups with comorbid psychiatric illness, to inform understanding of mechanisms, as well as treatment and prevention strategies for vulnerable drug user groups.

A. Hogarth, L., He, Z., Chase, H. W., Wills, A. J., Troisi, J., II, Leventhal, A. M., (…), Hitsman, B. (2015). Negative mood reverses devaluation of goal-directed drug-seeking favouring an incentive learning account of drug dependence. Psychopharmacology, 232(17), 3235-3247.  PMID: 26041336.

B. Hogarth, L., Mathew, A. R., & Hitsman, B. (2017). Current major depression is associated with greater sensitivity to the motivational effect of both negative mood induction and abstinence on tobacco-seeking behavior. Drug and Alcohol Dependence, 176, 1-6. PMID: 28460322

C. Hogarth, L., Hardy, L., Mathew, A. R., & Hitsman, B. (in press) Negative mood-induced alcohol-seeking is greater in young adults who report depression symptoms, drinking to cope, and subjective reactivity. Experimental and Clinical Psychopharmacology.

D. Mathew, A. R., Hogarth, L., Leventhal, A. M., Cook, J. W., & Hitsman, B. (2017). Cigarette smoking and depression comorbidity: systematic review and proposed theoretical model. Addiction, 112(3), 401-412. PMID: 27628300.

 

Research projects

Exeter Translational Addiction Partnership (ETAP)
Exeter Translational Addiction Partnership seeks to bridge between research on substance dependence at University of Exeter and the therapeutic services delivered by the charity EDP Drug & Alcohol Services to the community and prison population.

Grants/Funding:

2017 Alcohol Research Council grant: The therapeutic effect of Brief Adaptive Coping Training (BACT) on relapse to alcohol provoked by negative emotional experience.

2013 Australian Research Council Grant: Advancing the science of willpower - investigating the mechanisms and processes of self-control. With Prof. Martin Hagger, Curtin University, Western Australia.

2012 ESRC Project Grant: Alcohol seeking and consumption - the role of reward valuation and attentional bias. With Dr. Abigail Rose, University of Liverpool.

2011 MRC Project Grant: Human drug dependence - cognitive predisposition and neural mechanisms.

2011 Alcohol Education and Research council grant: Neurophysiological correlates of Pavlovian to instrumental transfer in heavy drinkers. With Dr. Matt Field, University of Liverpool.

2007 BBSRC Project Grant: Attentional mediation of conditioned appetitive behaviour in humans. With Prof. Theodora Duka, University of Sussex, and Prof. Anthony Dickinson, University of Cambridge.

Research networks

Dr. Brian Hitsman at Northwestern University and Dr. Robert Schnoll at University of Pennsylvania: Clinical evaluation of smoking cessation pharmacotherapy.

Prof. Marcus Munafò and Dr. Angela Attwood at Bristol University: Pre-clinical pharmacological and behavioural approaches to attenuating human drug-seeking.

Prof. Matt Field and Dr. Abigail Rose at Liverpool University: Behavioural approaches to understand and treat alcohol dependence.

Prof. Martin Hagger at Curtin University, Western Australia: Protective effects of glucose against relapse induced by loss of cognitive control.

Dr. Mohammed Shoaib at Newcastle University: Animal models of drug dependence vulnerability.

Dr. Lynne Dawkins at University of East London: Transfer of dependence to e-cigarettes.

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