Theodora Duka - Academia.edu (original) (raw)

Papers by Theodora Duka

Psychopharmacology, Jun 6, 2020

Rational The ability of conditioned stimuli to affect instrumental responding is a robust finding... more Rational The ability of conditioned stimuli to affect instrumental responding is a robust finding from animal as well as human research and is assumed as a key factor regarding the development and maintenance of addictive behaviour. Objectives While it is well known that stress is an important factor for relapse after treatment, little is known about the impact of stress on conditioned substance-associated stimuli and their influence on instrumental responding. Methods We administered in the present study a Pavlovian-to-instrumental transfer (PIT) paradigm with stimuli associated with smoking-and chocolate-related rewards using points in a token economy to light to moderate smokers who also indicated to like eating chocolate. After completion of the first two phases of the PIT paradigm (i.e. Pavlovian training and instrumental trainings), participants were randomly allocated to the socially evaluated cold pressor test or a control condition before the final phase of the PIT paradigm, the transfer phase, was administered. The presentation of a smoking-related stimulus enhanced instrumental responding for a smoking-related reward (i.e. 'smoking-PIT' effect) and presentation of a chocolate-related stimulus for a chocolate-related reward (i.e. 'chocolate-PIT' effect) in participants aware of the experimental contingencies as indicated by expectancy ratings. However, acute stress did not change (i.e. neither enhanced nor attenuated) the 'smoking-PIT' effect or the 'chocolate-PIT' effect, and no overall effect of acute stress on tobacco choice was observed in aware participants. Conclusions The established role of stress in addiction appears not to be driven by an augmenting effect on the ability of drug stimuli to promote drug-seeking.

Learning & Memory, Feb 15, 2019

Stimuli conditioned with a substance can generate drug-approach behaviors due to their acquired m... more Stimuli conditioned with a substance can generate drug-approach behaviors due to their acquired motivational properties. According to implicit theories of addiction, these stimuli can decrease cognitive control automatically. The present study (n = 49) examined whether reward-associated stimuli can interfere with cognitive processes in the absence of knowledge about stimulus-outcome contingencies. Conditioned stimuli (CS) were paired with high-reward (HR) or low-reward (LR) probabilities of monetary reward using a Pavlovian learning task. Participants were categorized as Aware or Unaware of contingencies using a Bayesian analysis. CS were then used as task-irrelevant distractors in modified flanker and N-back tasks. Results show HR CS can generate increased interference in the flanker task for participants Unaware of contingencies, contributing further evidence for the existence of implicit Pavlovian conditioning. For the N-back task, working memory performance was affected by HR CS, albeit only for Aware participants. These results suggest that CS can interfere implicitly with cognitive processes in a similar way to drug-related stimuli. Such an effect could occur in a stimulus-driven fashion, devoid of top-down goal-directedness. These findings have implications for the conceptualization and study of implicit processes in addiction and highlights the necessity to reconsider the measurement of such phenomena.

Interoception and activation in the anterior insula cortex in binge drinkers.

British Journal of Pharmacology, 2021

Existing pharmacotherapies for managing craving, a strong predictor of relapse to automated addic... more Existing pharmacotherapies for managing craving, a strong predictor of relapse to automated addictive behaviours, are limited in efficacy and characterised by increased health risks associated with their pharmacological profile. Preclinical studies have identified oxytocin as a promising pharmacotherapy with anticraving properties for addictive behaviours. Here, we provide the first systematic review of 17 human studies (n = 722; 30% female) investigating the efficacy of intranasal oxytocin to reduce craving or consumption in addictive behaviours. We identify intranasal oxytocin as a method that warrants further investigation regarding its capacity to decrease cue‐induced, acute stress‐induced or withdrawal‐related craving and relapse related to alcohol, cannabis, opioids, cocaine or nicotine, including a potential role as ad hoc medication following exposure to drug‐related cues. Future studies should investigate the role of factors such as treatment regimens and sample characteris...

Pilot and Feasibility Studies, 2021

Background Individuals who are ‘moderately’ or ‘severely’ dependent consume alcohol at levels tha... more Background Individuals who are ‘moderately’ or ‘severely’ dependent consume alcohol at levels that are likely to have a severe impact on their own health and mortality, the health and behaviours of others (family members) and to have economic and social implications. Treatment guidelines suggest that treatment needs to be planned with medically assisted withdrawal (also referred to as detoxification), and aftercare support but outcomes are poor with low proportions engaging in after care and high relapse rates. An approach of structured preparation before alcohol detoxification (SPADe) puts an emphasis on introducing lifestyle changes, development of coping strategies for cravings, stress and emotions as well as introducing changes to the immediate family and social environment in advance of alcohol cessation. Such a pre-habilitation paradigm compliments the established treatment approach. The key research question was: can we design a large scale, randomised controlled trial (RCT) ...

Psychopharmacology, 2019

Rationale: Gambling and alcohol use are recreational behaviours that share substantial commonalit... more Rationale: Gambling and alcohol use are recreational behaviours that share substantial commonalities at a phenomenological, clinical, and neurobiological level. Past studies have shown that alcohol can have a disinhibiting effect on gambling behaviour, in terms of bet size and persistence. Objectives: To characterize how alcohol affects biases in judgment and decision-making that occur during gambling, with a focus on sequential decision-making including the gambler's fallacy. Methods: Sequential biases were elicited via a roulette-based gambling task. Using a standard between-groups alcohol challenge procedure, male participants played the roulette task 20 minutes after receiving an alcoholic (0.8g/kg; n = 22) or placebo (n = 16) beverage. The task measured colour choice decisions (red/black) and bet size, in response to varying lengths of colour runs and winning/losing feedback streaks. Results: Across both groups, a number of established sequential biases were observed. On colour choice, there was an effect of run length in line with the gambler's fallacy, which further varied by previous feedback (wins vs losses). Bet size increased with feedback streaks, especially for losing streaks. Compared to placebo, the alcohol group placed higher bets following losses compared to wins. Conclusions: Increased bet size after losses following alcohol consumption may reflect increased loss chasing that may amplify gambling harms. Our results do not fit a simple pattern of enhanced gambling distortions or reward sensitivity, but help contextualize the effects of alcohol on gambling to research on decision-making biases.

Psychopharmacology, 2019

Rationale State-dependent changes in physiological arousal may influence impulsive behaviours. Ob... more Rationale State-dependent changes in physiological arousal may influence impulsive behaviours. Objectives To examine the relationship between arousal and impulsivity, we assessed the effects of yohimbine (an α 2 -adrenergic receptor antagonist, which increases physiological arousal via noradrenaline release) on performance on established laboratorybased impulsivity measures in healthy volunteers. Methods Forty-three participants received a single dose of either yohimbine hydrochloride or placebo before completing a battery of impulsivity measures. Blood pressure and heart rate were monitored throughout the study. Results Participants in the yohimbine group showed higher blood pressure and better response inhibition in the Stop Signal Task, relative to the placebo group. Additionally, individual changes in blood pressure were associated with performance on Delay Discounting and Information Sampling tasks: raised blood pressure following drug ingestion was associated with more farsighted decisions in the Delay Discounting Task (lower temporal impulsivity) yet reduced information gathering in the Information Sampling Task (increased reflection impulsivity). Conclusions These results support the notion that impulsive behaviour is dependent upon state physiological arousal; however, distinct facets of impulsivity are differentially affected by physiological changes.

Social Cognitive and Affective Neuroscience, 2018

Interoception, i.e. the perception and appraisal of internal bodily signals, is related to the ph... more Interoception, i.e. the perception and appraisal of internal bodily signals, is related to the phenomenon of craving, and is reportedly disrupted in alcohol use disorders. The hormone oxytocin influences afferent transmission of bodily signals and, through its potential modulation of craving, is proposed as a possible treatment for alcohol use disorders. However, oxytocin's impact on interoception in alcohol users remains unknown. Healthy alcohol users (n ¼ 32) attended two laboratory sessions to perform tests of interoceptive ability (heartbeat tracking: attending to internal signals and, heartbeat discrimination: integrating internal and external signals) after intranasal administration of oxytocin or placebo. Effects of interoceptive accuracy, oxytocin administration and alcohol intake, were tested using mixed-effects models. On the tracking task, oxytocin reduced interoceptive accuracy, but did not interact with alcohol consumption. On the discrimination task, we found an interaction between oxytocin administration and alcohol intake: Oxytocin, compared with placebo, increased interoceptive accuracy in heavy drinkers, but not in light social drinkers. Our study does not suggest a pure interoceptive impairment in alcohol users but instead potentially highlights reduced flexibility of internal and external attentional resource allocation. Importantly, this impairment seems to be mitigated by oxytocin. This attentional hypothesis needs to be explicitly tested in future research.

Scientific reports, Jan 22, 2018

In clinical populations, olfactory abilities parallel executive function, implicating shared neur... more In clinical populations, olfactory abilities parallel executive function, implicating shared neuroanatomical substrates within the ventral prefrontal cortex. In healthy individuals, the relationship between olfaction and personality traits or certain cognitive and behavioural characteristics remains unexplored. We therefore tested if olfactory function is associated with trait and behavioural impulsivity in nonclinical individuals. Eighty-three healthy volunteers (50 females) underwent quantitative assessment of olfactory function (odour detection threshold, discrimination, and identification). Each participant was rated for trait impulsivity index using the Barratt Impulsiveness Scale and performed a battery of tasks to assess behavioural impulsivity (Stop Signal Task, SST; Information Sampling Task, IST; Delay Discounting). Lower odour discrimination predicted high ratings in non-planning impulsivity (Barratt Non-Planning impulsivity subscale); both, lower odour discrimination and...

Scientific reports, Jan 14, 2018

Motor actions can be facilitated or hindered by psychophysiological states of readiness, to guide... more Motor actions can be facilitated or hindered by psychophysiological states of readiness, to guide rapid adaptive action. Cardiovascular arousal is communicated by cardiac signals conveying the timing and strength of individual heartbeats. Here, we tested how these interoceptive signals facilitate control of motor impulsivity. Participants performed a stop signal task, in which stop cues were delivered at different time points within the cardiac cycle: at systole when the heart contracts (T-wave peak, approximately 300 ms following the R-wave), or at diastole between heartbeats (R-wave peak). Response inhibition was better at systole, indexed by a shorter stop signal reaction time (SSRT), and longer stop signal delay (SSD). Furthermore, parasympathetic control of cardiovascular tone, and subjective sensitivity to interoceptive states, predicted response inhibition efficiency, although these cardiovascular and interoceptive correlations did not survive correction for multiple comparis...

Psychopharmacology, 2018

Previous research has found that the attention of social drinkers is preferentially oriented towa... more Previous research has found that the attention of social drinkers is preferentially oriented towards alcohol-related stimuli (attentional capture). This is argued to play a role in escalating craving for alcohol that can result in hazardous drinking. According to incentive theories of drug addiction, the stimuli associated with the drug reward acquire learned incentive salience and grab attention. However, it is not clear whether the mechanism by which this bias is created is a voluntary or an automatic one, although some evidence suggests a stimulus-driven mechanism. Here, we test for the first time whether this attentional capture could reflect an involuntary consequence of a goal-driven mechanism. Across three experiments, participants were given search goals to detect either an alcoholic or a non-alcoholic object (target) in a stream of briefly presented objects unrelated to the target. Prior to the target, a task-irrelevant parafoveal distractor appeared. This could either be c...

Behavioural brain research, Apr 14, 2017

Classical conditioning theories of addiction suggest that stimuli associated with rewards acquire... more Classical conditioning theories of addiction suggest that stimuli associated with rewards acquire incentive salience, inducing emotional and attentional conditioned responses. It is not clear whether those responses occur without contingency awareness (CA), i.e. are based on explicit or implicit learning processes. Examining implicit aspects of stimulus-reward associations can improve our understanding of addictive behaviours, supporting treatment and prevention strategies. However, the acquisition of conditioned responses without CA has yet to be rigorously demonstrated, as the existing literature shows a lack of methodological agreement regarding the measurement of implicit and explicit processes. The purpose of two experiments presented here was to study the emotional value acquired by CS through implicit emotional and attentional processes, trying to overcome critical methodological issues. Experiment 1 (n = 48) paired two stimuli categories (houses/buildings) with high (HR) or ...

Genes, brain, and behavior, Jan 19, 2016

GABAA receptors form the major class of inhibitory neurotransmitter receptors in the mammalian br... more GABAA receptors form the major class of inhibitory neurotransmitter receptors in the mammalian brain. This review sets out to summarise the evidence that variations in genes encoding GABAA receptor isoforms are associated with aspects of addictive behaviour in humans, while animal models of addictive behaviour also implicate certain subtypes of GABAA receptor. In addition to outlining the evidence for the involvement of specific subtypes in addiction, we summarise the particular contributions of these isoforms in control over the functioning of brain circuits, especially the mesolimbic system, and make a first attempt to bring together evidence from several fields to understanding potential involvement of GABAA Receptor Subtypes in addictive behaviour. While the weight of the published literature is on alcohol dependency, the underlying principles outlined are relevant across a number of different aspects of addictive behaviour.

Addiction biology, Jan 21, 2015

Binge drinking is associated with impaired cognitive functioning, but the relationship of cogniti... more Binge drinking is associated with impaired cognitive functioning, but the relationship of cognitive impairments and white matter integrity is less known. We used diffusion tensor imaging (DTI) to investigate the relationships of binge drinking, whole brain white matter integrity and cognitive performance during young adulthood (18 to 25 years), a period of continued brain development in two sessions 1 year apart. Binge drinkers (n = 20) and non-binge drinkers (n = 20) underwent DTI and completed measures of spatial working memory and motor impulsivity. Fractional anisotropy (FA), a measure derived from DTI, was estimated from whole brain and from five segments of the corpus callosum (CC): prefrontal, premotor/supplementary motor, motor, (SMA) sensory and parietal/temporal/occipital (PTO). FA was lower for binge than for non-binge men but not women at Session 1 and 2 for all measurements except for FA in the motor segment, which was significantly increased from Session 1 to Session 2...

Neuropsychologia, 2003

Facial expression recognition is a central feature of emotional and social behaviour and previous... more Facial expression recognition is a central feature of emotional and social behaviour and previous studies have found that alcoholics are impaired in this skill when presented with single emotions of differing intensities. The aim of this study was to explore biases in alcoholics' recognition of emotions when they were a mixture of two closely related emotions. The amygdala is intimately involved in encoding of emotions, especially those related to fear. In animals an increased number of withdrawals from alcohol leads to increased seizure sensitivity associated with facilitated transmission in the amygdala and related circuits. A further objective therefore was to explore the effect of previous alcohol detoxifications on the recognition of emotional facial expressions. Fourteen alcoholic inpatients were compared with 14 age and sex matched social drinking controls. They were asked to rate how much of each of six emotions (happiness, surprise, fear, sadness, disgust and anger) were present in morphed pictures portraying a mix of two of those emotions. The alcoholic group showed enhanced fear responses to all of the pictures compared to the controls and showed a different pattern of responding on anger and disgust. There were no differences between groups on decoding of sad, happy and surprised expressions. In addition the enhanced fear recognition found in the alcoholic group was related to the number of previous detoxifications. These results provide further evidence for impairment in facial expression recognition present in alcoholic patients. In addition, since the amygdala has been associated with the processing of facial expressions of emotion, particularly those of fear, the present data furthermore suggest that previous detoxifications may be related to changes within the amygdala.

Psychopharmacology, 2011

Rationale Our previous study using memantine in smokers suggests that there may be a differential... more Rationale Our previous study using memantine in smokers suggests that there may be a differential role for N-methyl-D-aspartate (NMDA) receptors in the subjective and cognitive effects of smoking. Objectives This study was designed to investigate if D- cycloserine (DCS) would modulate the subjective and cognitive effects of limited smoking. Methods Forty-eight habitual smokers abstinent for a minimum of 2 h were randomly allocated to receive either placebo or 50 mg DCS (double-blind) and were subsequently required either to smoke half of one cigarette or to remain abstinent. Subjective and physiological effects of DCS were measured at baseline, 90 min postcapsule, and again after the partial-smoking manipulation, while the effects on sustained attention (rapid visual information processing test-RVIP) and cognitive flexibility (intraextra dimensional set-shift test-IED) were evaluated only after the partial-smoking manipulation. Results DCS alone did not produce significant subjective effects other than an increase in ratings of "Stimulated". In combination with partial smoking, however, DCS blocked the smoking-induced increase in "Stimulated" and the decrease in "Relaxed" ratings. Furthermore, in combination with smoking, DCS reduced the number of false alarms during the RVIP test (an index of inhibitory control) and produced a small increase in diastolic blood pressure. DCS failed to modulate IED performance. Conclusions These findings provide further evidence of a role for glutamate release in the subjective effects of smoking but not the effects on attention and cognitive flexibility. Furthermore, our results indicate that glutamate release may also be involved in the effect of smoking on inhibitory control.

Neuropsychopharmacology, 2012

Alcoholic patients who have undergone multiple detoxifications/relapses show altered processing o... more Alcoholic patients who have undergone multiple detoxifications/relapses show altered processing of emotional signals. We performed functional magnetic resonance imaging during performance of implicit and explicit versions of a task in which subjects were presented with morphs of fearful facial emotional expressions. Participants were abstaining, multiply detoxified (MDTx; n ¼ 12) or singly detoxified patients (SDTx; n ¼ 17), and social drinker controls (n ¼ 31). Alcoholic patients were less able than controls to recognize fearful expressions, and showed lower activation in prefrontal areas, including orbitofrontal cortex and insula, which mediate emotional processing. The decrease in activation was greater in MDTx patients who also showed decreased connectivity between insula and prefrontal areas, and between amygdala and globus pallidus. In the explicit condition, the strength of connectivity between insula and areas involved in regulation of emotion (inferior frontal cortex and frontal pole) was negatively correlated with both the number of detoxifications and dependency (measured by the severity of alcohol dependency (SADQ) and control over drinking score (Impaired Control questionnaire, ICQ)). In contrast, increased connectivity was found between insula and the colliculus neuronal cluster, and between amygdala and stria terminalis bed nucleus. In the implicit condition, number of detoxifications and ICQ score correlated positively with connectivity between amygdala and prefrontal cortical areas involved in attentional and executive processes. Repeated episodes of detoxification from alcohol are associated with altered function both in fear perception pathways and in cortical modulation of emotions. Such changes may confer increased sensitivity to emotional stress and impaired social competence, contributing to relapse.

Neuropsychopharmacology, 2013

Acute alcohol ingestion increases attentional bias to alcohol-related stimuli; however, the under... more Acute alcohol ingestion increases attentional bias to alcohol-related stimuli; however, the underlying cognitive and brain mechanisms remain unknown. We combined functional magnetic resonance imaging (fMRI) with performance of a dual task that probed attentional distraction by alcohol-related stimuli during 'conflict' processing: the Concurrent Flanker/Alcohol-Attentional bias task (CFAAT). In this task, an Eriksen Flanker task is superimposed on task-unrelated background pictures with alcohol-associated or neutral content. Participants respond to the direction of a central 'target' arrow and ignore adjacent congruent (low cognitive load) or incongruent (high cognitive load) 'flanking' arrows. Using a between-subject design, 40 healthy moderate-to-heavy social drinkers received either no alcohol (placebo), 0.4 g/kg (low dose), or 0.8 g/kg (high dose) of alcohol, and underwent fMRI while performing the CFAAT. The low alcohol dose, relative to placebo, increased response latencies on trials with alcohol-associated backgrounds and, under low cognitive load, increased the activity evoked by these pictures within a medial hypothalamic region. Under high cognitive load, the low alcohol dose, relative to placebo, elicited greater activity within a more lateral hypothalamic region, and reduced activity within frontal motor areas. The high alcohol dose, relative to placebo, did not reliably affect response latencies or neural responses to background images, but reduced overall accuracy under high cognitive load. This effect correlated with changes in reactivity within medial and dorsal prefrontal cortices. These data suggest that alcohol at a low dose primes attentional bias to alcohol-associated stimuli, an effect mediated by activation of subcortical hypothalamic areas implicated in arousal and salience attribution.

Consciousness and Cognition, 2013

One approach to hypnosis suggests that for hypnotic experience to occur frontal lobe activity mus... more One approach to hypnosis suggests that for hypnotic experience to occur frontal lobe activity must be attenuated. For example, cold control theory posits that a lack of awareness of intentions is responsible for the experience of involuntariness and/or the subjective reality of hypnotic suggestions. The mid-dorso-lateral prefrontal cortex and the ACC are candidate regions for such awareness. Alcohol impairs frontal lobe executive function. This study examined whether alcohol affects hypnotisability. We administered 0.8 mg/kg of alcohol or a placebo to 32 medium susceptible participants. They were subsequently hypnotised and given hypnotic suggestions. All participants believed they had received some alcohol. Participants in the alcohol condition were more susceptible to hypnotic suggestions than participants in the placebo condition. Impaired frontal lobe activity facilitates hypnotic responding, which supports theories postulating that attenuation of executive function facilitates hypnotic response, and contradicts theories postulating that hypnotic response involves enhanced inhibitory, attentional or other executive function.

Alcohol and Alcoholism, 2007

It has been proposed that alcohol weakens control processes, which in turn supports the occurrenc... more It has been proposed that alcohol weakens control processes, which in turn supports the occurrence of disinhibited behaviours. Two studies were run, in parallel (both with 32 participants) using a between-subject design to investigate any disinhibiting effects of a moderate dose of alcohol (0.6 g/kg compared to placebo), previously found to trigger increased desire for alcohol. Disinhibiting effects were tested on basic motoric and cognitive control processes, using a go/no-go (GNG) and the Stroop task (ST) respectively. Although a higher proportion of participants wanted more alcohol under the alcohol preload (priming effect), this effect was not found to be significant. In the GNG task, correct response latency (RL) decreased from baseline [P = 0.008] while number of incorrect hits increased [P = 0.030] irrespective of treatment, indicating the formation of a habit-like response and motoric disinhibition. Although error rate did not differ between groups, an interaction occurred with regard to erroneous RL: participants under alcohol became quicker, while those under placebo became slower [P = 0.014]. In the ST, those preloaded with alcohol made significantly more errors [P = 0.021] and were quicker to complete the task [P = 0.044] compared with those preloaded with placebo, indicating a strong alcohol effect on cognitive disinhibition. The data suggest that a moderate dose of alcohol, which induces priming to want more alcohol, had disinhibiting effects both on a basic motoric and a cognitive inhibitory task. Thus the idea that priming may be mediated by the disinhibitory effects of alcohol is supported.

Psychopharmacology, Jun 6, 2020

Rational The ability of conditioned stimuli to affect instrumental responding is a robust finding... more Rational The ability of conditioned stimuli to affect instrumental responding is a robust finding from animal as well as human research and is assumed as a key factor regarding the development and maintenance of addictive behaviour. Objectives While it is well known that stress is an important factor for relapse after treatment, little is known about the impact of stress on conditioned substance-associated stimuli and their influence on instrumental responding. Methods We administered in the present study a Pavlovian-to-instrumental transfer (PIT) paradigm with stimuli associated with smoking-and chocolate-related rewards using points in a token economy to light to moderate smokers who also indicated to like eating chocolate. After completion of the first two phases of the PIT paradigm (i.e. Pavlovian training and instrumental trainings), participants were randomly allocated to the socially evaluated cold pressor test or a control condition before the final phase of the PIT paradigm, the transfer phase, was administered. The presentation of a smoking-related stimulus enhanced instrumental responding for a smoking-related reward (i.e. 'smoking-PIT' effect) and presentation of a chocolate-related stimulus for a chocolate-related reward (i.e. 'chocolate-PIT' effect) in participants aware of the experimental contingencies as indicated by expectancy ratings. However, acute stress did not change (i.e. neither enhanced nor attenuated) the 'smoking-PIT' effect or the 'chocolate-PIT' effect, and no overall effect of acute stress on tobacco choice was observed in aware participants. Conclusions The established role of stress in addiction appears not to be driven by an augmenting effect on the ability of drug stimuli to promote drug-seeking.

Learning & Memory, Feb 15, 2019

Stimuli conditioned with a substance can generate drug-approach behaviors due to their acquired m... more Stimuli conditioned with a substance can generate drug-approach behaviors due to their acquired motivational properties. According to implicit theories of addiction, these stimuli can decrease cognitive control automatically. The present study (n = 49) examined whether reward-associated stimuli can interfere with cognitive processes in the absence of knowledge about stimulus-outcome contingencies. Conditioned stimuli (CS) were paired with high-reward (HR) or low-reward (LR) probabilities of monetary reward using a Pavlovian learning task. Participants were categorized as Aware or Unaware of contingencies using a Bayesian analysis. CS were then used as task-irrelevant distractors in modified flanker and N-back tasks. Results show HR CS can generate increased interference in the flanker task for participants Unaware of contingencies, contributing further evidence for the existence of implicit Pavlovian conditioning. For the N-back task, working memory performance was affected by HR CS, albeit only for Aware participants. These results suggest that CS can interfere implicitly with cognitive processes in a similar way to drug-related stimuli. Such an effect could occur in a stimulus-driven fashion, devoid of top-down goal-directedness. These findings have implications for the conceptualization and study of implicit processes in addiction and highlights the necessity to reconsider the measurement of such phenomena.

Interoception and activation in the anterior insula cortex in binge drinkers.

British Journal of Pharmacology, 2021

Existing pharmacotherapies for managing craving, a strong predictor of relapse to automated addic... more Existing pharmacotherapies for managing craving, a strong predictor of relapse to automated addictive behaviours, are limited in efficacy and characterised by increased health risks associated with their pharmacological profile. Preclinical studies have identified oxytocin as a promising pharmacotherapy with anticraving properties for addictive behaviours. Here, we provide the first systematic review of 17 human studies (n = 722; 30% female) investigating the efficacy of intranasal oxytocin to reduce craving or consumption in addictive behaviours. We identify intranasal oxytocin as a method that warrants further investigation regarding its capacity to decrease cue‐induced, acute stress‐induced or withdrawal‐related craving and relapse related to alcohol, cannabis, opioids, cocaine or nicotine, including a potential role as ad hoc medication following exposure to drug‐related cues. Future studies should investigate the role of factors such as treatment regimens and sample characteris...

Pilot and Feasibility Studies, 2021

Background Individuals who are ‘moderately’ or ‘severely’ dependent consume alcohol at levels tha... more Background Individuals who are ‘moderately’ or ‘severely’ dependent consume alcohol at levels that are likely to have a severe impact on their own health and mortality, the health and behaviours of others (family members) and to have economic and social implications. Treatment guidelines suggest that treatment needs to be planned with medically assisted withdrawal (also referred to as detoxification), and aftercare support but outcomes are poor with low proportions engaging in after care and high relapse rates. An approach of structured preparation before alcohol detoxification (SPADe) puts an emphasis on introducing lifestyle changes, development of coping strategies for cravings, stress and emotions as well as introducing changes to the immediate family and social environment in advance of alcohol cessation. Such a pre-habilitation paradigm compliments the established treatment approach. The key research question was: can we design a large scale, randomised controlled trial (RCT) ...

Psychopharmacology, 2019

Rationale: Gambling and alcohol use are recreational behaviours that share substantial commonalit... more Rationale: Gambling and alcohol use are recreational behaviours that share substantial commonalities at a phenomenological, clinical, and neurobiological level. Past studies have shown that alcohol can have a disinhibiting effect on gambling behaviour, in terms of bet size and persistence. Objectives: To characterize how alcohol affects biases in judgment and decision-making that occur during gambling, with a focus on sequential decision-making including the gambler's fallacy. Methods: Sequential biases were elicited via a roulette-based gambling task. Using a standard between-groups alcohol challenge procedure, male participants played the roulette task 20 minutes after receiving an alcoholic (0.8g/kg; n = 22) or placebo (n = 16) beverage. The task measured colour choice decisions (red/black) and bet size, in response to varying lengths of colour runs and winning/losing feedback streaks. Results: Across both groups, a number of established sequential biases were observed. On colour choice, there was an effect of run length in line with the gambler's fallacy, which further varied by previous feedback (wins vs losses). Bet size increased with feedback streaks, especially for losing streaks. Compared to placebo, the alcohol group placed higher bets following losses compared to wins. Conclusions: Increased bet size after losses following alcohol consumption may reflect increased loss chasing that may amplify gambling harms. Our results do not fit a simple pattern of enhanced gambling distortions or reward sensitivity, but help contextualize the effects of alcohol on gambling to research on decision-making biases.

Psychopharmacology, 2019

Rationale State-dependent changes in physiological arousal may influence impulsive behaviours. Ob... more Rationale State-dependent changes in physiological arousal may influence impulsive behaviours. Objectives To examine the relationship between arousal and impulsivity, we assessed the effects of yohimbine (an α 2 -adrenergic receptor antagonist, which increases physiological arousal via noradrenaline release) on performance on established laboratorybased impulsivity measures in healthy volunteers. Methods Forty-three participants received a single dose of either yohimbine hydrochloride or placebo before completing a battery of impulsivity measures. Blood pressure and heart rate were monitored throughout the study. Results Participants in the yohimbine group showed higher blood pressure and better response inhibition in the Stop Signal Task, relative to the placebo group. Additionally, individual changes in blood pressure were associated with performance on Delay Discounting and Information Sampling tasks: raised blood pressure following drug ingestion was associated with more farsighted decisions in the Delay Discounting Task (lower temporal impulsivity) yet reduced information gathering in the Information Sampling Task (increased reflection impulsivity). Conclusions These results support the notion that impulsive behaviour is dependent upon state physiological arousal; however, distinct facets of impulsivity are differentially affected by physiological changes.

Social Cognitive and Affective Neuroscience, 2018

Interoception, i.e. the perception and appraisal of internal bodily signals, is related to the ph... more Interoception, i.e. the perception and appraisal of internal bodily signals, is related to the phenomenon of craving, and is reportedly disrupted in alcohol use disorders. The hormone oxytocin influences afferent transmission of bodily signals and, through its potential modulation of craving, is proposed as a possible treatment for alcohol use disorders. However, oxytocin's impact on interoception in alcohol users remains unknown. Healthy alcohol users (n ¼ 32) attended two laboratory sessions to perform tests of interoceptive ability (heartbeat tracking: attending to internal signals and, heartbeat discrimination: integrating internal and external signals) after intranasal administration of oxytocin or placebo. Effects of interoceptive accuracy, oxytocin administration and alcohol intake, were tested using mixed-effects models. On the tracking task, oxytocin reduced interoceptive accuracy, but did not interact with alcohol consumption. On the discrimination task, we found an interaction between oxytocin administration and alcohol intake: Oxytocin, compared with placebo, increased interoceptive accuracy in heavy drinkers, but not in light social drinkers. Our study does not suggest a pure interoceptive impairment in alcohol users but instead potentially highlights reduced flexibility of internal and external attentional resource allocation. Importantly, this impairment seems to be mitigated by oxytocin. This attentional hypothesis needs to be explicitly tested in future research.

Scientific reports, Jan 22, 2018

In clinical populations, olfactory abilities parallel executive function, implicating shared neur... more In clinical populations, olfactory abilities parallel executive function, implicating shared neuroanatomical substrates within the ventral prefrontal cortex. In healthy individuals, the relationship between olfaction and personality traits or certain cognitive and behavioural characteristics remains unexplored. We therefore tested if olfactory function is associated with trait and behavioural impulsivity in nonclinical individuals. Eighty-three healthy volunteers (50 females) underwent quantitative assessment of olfactory function (odour detection threshold, discrimination, and identification). Each participant was rated for trait impulsivity index using the Barratt Impulsiveness Scale and performed a battery of tasks to assess behavioural impulsivity (Stop Signal Task, SST; Information Sampling Task, IST; Delay Discounting). Lower odour discrimination predicted high ratings in non-planning impulsivity (Barratt Non-Planning impulsivity subscale); both, lower odour discrimination and...

Scientific reports, Jan 14, 2018

Motor actions can be facilitated or hindered by psychophysiological states of readiness, to guide... more Motor actions can be facilitated or hindered by psychophysiological states of readiness, to guide rapid adaptive action. Cardiovascular arousal is communicated by cardiac signals conveying the timing and strength of individual heartbeats. Here, we tested how these interoceptive signals facilitate control of motor impulsivity. Participants performed a stop signal task, in which stop cues were delivered at different time points within the cardiac cycle: at systole when the heart contracts (T-wave peak, approximately 300 ms following the R-wave), or at diastole between heartbeats (R-wave peak). Response inhibition was better at systole, indexed by a shorter stop signal reaction time (SSRT), and longer stop signal delay (SSD). Furthermore, parasympathetic control of cardiovascular tone, and subjective sensitivity to interoceptive states, predicted response inhibition efficiency, although these cardiovascular and interoceptive correlations did not survive correction for multiple comparis...

Psychopharmacology, 2018

Previous research has found that the attention of social drinkers is preferentially oriented towa... more Previous research has found that the attention of social drinkers is preferentially oriented towards alcohol-related stimuli (attentional capture). This is argued to play a role in escalating craving for alcohol that can result in hazardous drinking. According to incentive theories of drug addiction, the stimuli associated with the drug reward acquire learned incentive salience and grab attention. However, it is not clear whether the mechanism by which this bias is created is a voluntary or an automatic one, although some evidence suggests a stimulus-driven mechanism. Here, we test for the first time whether this attentional capture could reflect an involuntary consequence of a goal-driven mechanism. Across three experiments, participants were given search goals to detect either an alcoholic or a non-alcoholic object (target) in a stream of briefly presented objects unrelated to the target. Prior to the target, a task-irrelevant parafoveal distractor appeared. This could either be c...

Behavioural brain research, Apr 14, 2017

Classical conditioning theories of addiction suggest that stimuli associated with rewards acquire... more Classical conditioning theories of addiction suggest that stimuli associated with rewards acquire incentive salience, inducing emotional and attentional conditioned responses. It is not clear whether those responses occur without contingency awareness (CA), i.e. are based on explicit or implicit learning processes. Examining implicit aspects of stimulus-reward associations can improve our understanding of addictive behaviours, supporting treatment and prevention strategies. However, the acquisition of conditioned responses without CA has yet to be rigorously demonstrated, as the existing literature shows a lack of methodological agreement regarding the measurement of implicit and explicit processes. The purpose of two experiments presented here was to study the emotional value acquired by CS through implicit emotional and attentional processes, trying to overcome critical methodological issues. Experiment 1 (n = 48) paired two stimuli categories (houses/buildings) with high (HR) or ...

Genes, brain, and behavior, Jan 19, 2016

GABAA receptors form the major class of inhibitory neurotransmitter receptors in the mammalian br... more GABAA receptors form the major class of inhibitory neurotransmitter receptors in the mammalian brain. This review sets out to summarise the evidence that variations in genes encoding GABAA receptor isoforms are associated with aspects of addictive behaviour in humans, while animal models of addictive behaviour also implicate certain subtypes of GABAA receptor. In addition to outlining the evidence for the involvement of specific subtypes in addiction, we summarise the particular contributions of these isoforms in control over the functioning of brain circuits, especially the mesolimbic system, and make a first attempt to bring together evidence from several fields to understanding potential involvement of GABAA Receptor Subtypes in addictive behaviour. While the weight of the published literature is on alcohol dependency, the underlying principles outlined are relevant across a number of different aspects of addictive behaviour.

Addiction biology, Jan 21, 2015

Binge drinking is associated with impaired cognitive functioning, but the relationship of cogniti... more Binge drinking is associated with impaired cognitive functioning, but the relationship of cognitive impairments and white matter integrity is less known. We used diffusion tensor imaging (DTI) to investigate the relationships of binge drinking, whole brain white matter integrity and cognitive performance during young adulthood (18 to 25 years), a period of continued brain development in two sessions 1 year apart. Binge drinkers (n = 20) and non-binge drinkers (n = 20) underwent DTI and completed measures of spatial working memory and motor impulsivity. Fractional anisotropy (FA), a measure derived from DTI, was estimated from whole brain and from five segments of the corpus callosum (CC): prefrontal, premotor/supplementary motor, motor, (SMA) sensory and parietal/temporal/occipital (PTO). FA was lower for binge than for non-binge men but not women at Session 1 and 2 for all measurements except for FA in the motor segment, which was significantly increased from Session 1 to Session 2...

Neuropsychologia, 2003

Facial expression recognition is a central feature of emotional and social behaviour and previous... more Facial expression recognition is a central feature of emotional and social behaviour and previous studies have found that alcoholics are impaired in this skill when presented with single emotions of differing intensities. The aim of this study was to explore biases in alcoholics' recognition of emotions when they were a mixture of two closely related emotions. The amygdala is intimately involved in encoding of emotions, especially those related to fear. In animals an increased number of withdrawals from alcohol leads to increased seizure sensitivity associated with facilitated transmission in the amygdala and related circuits. A further objective therefore was to explore the effect of previous alcohol detoxifications on the recognition of emotional facial expressions. Fourteen alcoholic inpatients were compared with 14 age and sex matched social drinking controls. They were asked to rate how much of each of six emotions (happiness, surprise, fear, sadness, disgust and anger) were present in morphed pictures portraying a mix of two of those emotions. The alcoholic group showed enhanced fear responses to all of the pictures compared to the controls and showed a different pattern of responding on anger and disgust. There were no differences between groups on decoding of sad, happy and surprised expressions. In addition the enhanced fear recognition found in the alcoholic group was related to the number of previous detoxifications. These results provide further evidence for impairment in facial expression recognition present in alcoholic patients. In addition, since the amygdala has been associated with the processing of facial expressions of emotion, particularly those of fear, the present data furthermore suggest that previous detoxifications may be related to changes within the amygdala.

Psychopharmacology, 2011

Rationale Our previous study using memantine in smokers suggests that there may be a differential... more Rationale Our previous study using memantine in smokers suggests that there may be a differential role for N-methyl-D-aspartate (NMDA) receptors in the subjective and cognitive effects of smoking. Objectives This study was designed to investigate if D- cycloserine (DCS) would modulate the subjective and cognitive effects of limited smoking. Methods Forty-eight habitual smokers abstinent for a minimum of 2 h were randomly allocated to receive either placebo or 50 mg DCS (double-blind) and were subsequently required either to smoke half of one cigarette or to remain abstinent. Subjective and physiological effects of DCS were measured at baseline, 90 min postcapsule, and again after the partial-smoking manipulation, while the effects on sustained attention (rapid visual information processing test-RVIP) and cognitive flexibility (intraextra dimensional set-shift test-IED) were evaluated only after the partial-smoking manipulation. Results DCS alone did not produce significant subjective effects other than an increase in ratings of "Stimulated". In combination with partial smoking, however, DCS blocked the smoking-induced increase in "Stimulated" and the decrease in "Relaxed" ratings. Furthermore, in combination with smoking, DCS reduced the number of false alarms during the RVIP test (an index of inhibitory control) and produced a small increase in diastolic blood pressure. DCS failed to modulate IED performance. Conclusions These findings provide further evidence of a role for glutamate release in the subjective effects of smoking but not the effects on attention and cognitive flexibility. Furthermore, our results indicate that glutamate release may also be involved in the effect of smoking on inhibitory control.

Neuropsychopharmacology, 2012

Alcoholic patients who have undergone multiple detoxifications/relapses show altered processing o... more Alcoholic patients who have undergone multiple detoxifications/relapses show altered processing of emotional signals. We performed functional magnetic resonance imaging during performance of implicit and explicit versions of a task in which subjects were presented with morphs of fearful facial emotional expressions. Participants were abstaining, multiply detoxified (MDTx; n ¼ 12) or singly detoxified patients (SDTx; n ¼ 17), and social drinker controls (n ¼ 31). Alcoholic patients were less able than controls to recognize fearful expressions, and showed lower activation in prefrontal areas, including orbitofrontal cortex and insula, which mediate emotional processing. The decrease in activation was greater in MDTx patients who also showed decreased connectivity between insula and prefrontal areas, and between amygdala and globus pallidus. In the explicit condition, the strength of connectivity between insula and areas involved in regulation of emotion (inferior frontal cortex and frontal pole) was negatively correlated with both the number of detoxifications and dependency (measured by the severity of alcohol dependency (SADQ) and control over drinking score (Impaired Control questionnaire, ICQ)). In contrast, increased connectivity was found between insula and the colliculus neuronal cluster, and between amygdala and stria terminalis bed nucleus. In the implicit condition, number of detoxifications and ICQ score correlated positively with connectivity between amygdala and prefrontal cortical areas involved in attentional and executive processes. Repeated episodes of detoxification from alcohol are associated with altered function both in fear perception pathways and in cortical modulation of emotions. Such changes may confer increased sensitivity to emotional stress and impaired social competence, contributing to relapse.

Neuropsychopharmacology, 2013

Acute alcohol ingestion increases attentional bias to alcohol-related stimuli; however, the under... more Acute alcohol ingestion increases attentional bias to alcohol-related stimuli; however, the underlying cognitive and brain mechanisms remain unknown. We combined functional magnetic resonance imaging (fMRI) with performance of a dual task that probed attentional distraction by alcohol-related stimuli during 'conflict' processing: the Concurrent Flanker/Alcohol-Attentional bias task (CFAAT). In this task, an Eriksen Flanker task is superimposed on task-unrelated background pictures with alcohol-associated or neutral content. Participants respond to the direction of a central 'target' arrow and ignore adjacent congruent (low cognitive load) or incongruent (high cognitive load) 'flanking' arrows. Using a between-subject design, 40 healthy moderate-to-heavy social drinkers received either no alcohol (placebo), 0.4 g/kg (low dose), or 0.8 g/kg (high dose) of alcohol, and underwent fMRI while performing the CFAAT. The low alcohol dose, relative to placebo, increased response latencies on trials with alcohol-associated backgrounds and, under low cognitive load, increased the activity evoked by these pictures within a medial hypothalamic region. Under high cognitive load, the low alcohol dose, relative to placebo, elicited greater activity within a more lateral hypothalamic region, and reduced activity within frontal motor areas. The high alcohol dose, relative to placebo, did not reliably affect response latencies or neural responses to background images, but reduced overall accuracy under high cognitive load. This effect correlated with changes in reactivity within medial and dorsal prefrontal cortices. These data suggest that alcohol at a low dose primes attentional bias to alcohol-associated stimuli, an effect mediated by activation of subcortical hypothalamic areas implicated in arousal and salience attribution.

Consciousness and Cognition, 2013

One approach to hypnosis suggests that for hypnotic experience to occur frontal lobe activity mus... more One approach to hypnosis suggests that for hypnotic experience to occur frontal lobe activity must be attenuated. For example, cold control theory posits that a lack of awareness of intentions is responsible for the experience of involuntariness and/or the subjective reality of hypnotic suggestions. The mid-dorso-lateral prefrontal cortex and the ACC are candidate regions for such awareness. Alcohol impairs frontal lobe executive function. This study examined whether alcohol affects hypnotisability. We administered 0.8 mg/kg of alcohol or a placebo to 32 medium susceptible participants. They were subsequently hypnotised and given hypnotic suggestions. All participants believed they had received some alcohol. Participants in the alcohol condition were more susceptible to hypnotic suggestions than participants in the placebo condition. Impaired frontal lobe activity facilitates hypnotic responding, which supports theories postulating that attenuation of executive function facilitates hypnotic response, and contradicts theories postulating that hypnotic response involves enhanced inhibitory, attentional or other executive function.

Alcohol and Alcoholism, 2007

It has been proposed that alcohol weakens control processes, which in turn supports the occurrenc... more It has been proposed that alcohol weakens control processes, which in turn supports the occurrence of disinhibited behaviours. Two studies were run, in parallel (both with 32 participants) using a between-subject design to investigate any disinhibiting effects of a moderate dose of alcohol (0.6 g/kg compared to placebo), previously found to trigger increased desire for alcohol. Disinhibiting effects were tested on basic motoric and cognitive control processes, using a go/no-go (GNG) and the Stroop task (ST) respectively. Although a higher proportion of participants wanted more alcohol under the alcohol preload (priming effect), this effect was not found to be significant. In the GNG task, correct response latency (RL) decreased from baseline [P = 0.008] while number of incorrect hits increased [P = 0.030] irrespective of treatment, indicating the formation of a habit-like response and motoric disinhibition. Although error rate did not differ between groups, an interaction occurred with regard to erroneous RL: participants under alcohol became quicker, while those under placebo became slower [P = 0.014]. In the ST, those preloaded with alcohol made significantly more errors [P = 0.021] and were quicker to complete the task [P = 0.044] compared with those preloaded with placebo, indicating a strong alcohol effect on cognitive disinhibition. The data suggest that a moderate dose of alcohol, which induces priming to want more alcohol, had disinhibiting effects both on a basic motoric and a cognitive inhibitory task. Thus the idea that priming may be mediated by the disinhibitory effects of alcohol is supported.