23 results on '"Luke Clark"'
Search Results
2. Immersion in Substance-Related and Behavioural Addictions: Neural Systems and Neurochemical Substrates
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Fiza Arshad and Luke Clark
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Behavioral Neuroscience ,Public Health, Environmental and Occupational Health - Published
- 2022
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3. Understanding the Slot Machine Zone
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W. Spencer Murch and Luke Clark
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Dissociation (neuropsychology) ,media_common.quotation_subject ,030227 psychiatry ,03 medical and health sciences ,Psychiatry and Mental health ,Clinical Psychology ,0302 clinical medicine ,Harm ,Slot machine ,Psychology ,Function (engineering) ,030217 neurology & neurosurgery ,Cognitive psychology ,media_common - Abstract
The slot machine zone describes a ‘trance-like’ state of diminished attention to time passing and gambling-irrelevant events during Electronic Gaming Machine (EGM) use. This article summarizes two prominent theoretical accounts of this state and articulates a new account that seeks to integrate them. Zone experiences are correlated with gambling problems and may be amplified by specific features of EGMs and other modern gambling formats. Links with excitement, relaxation, and depression have been found, implicating both positive and negative reinforcement processes. Emerging evidence suggests gamblers in the zone are more focused on EGM use (‘zoned in’). Models rooted in either Flow Theory or dissociation do not fully account for these effects. Integrating earlier models, we propose a continuum of gambling immersion as a function of problem gambling severity. Cognitive studies aimed at clarifying the psychological nature of immersion will help inform programmes that treat and prevent gambling harm.
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- 2021
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4. Serotonin depletion impairs both Pavlovian and instrumental reversal learning in healthy humans
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Annemieke M. Apergis-Schoute, Robyn Yellowlees, Trevor W. Robbins, Molly J. Crockett, Rudolf N. Cardinal, Frederique E. Arntz, Jonathan W. Kanen, Barbara J. Sahakian, David M Christmas, Annabel Price, Luke Clark, Febe E. van der Flier, Kanen, Jonathan W. [0000-0002-4095-5405], Price, Annabel [0000-0002-5505-5231], Cardinal, Rudolf [0000-0002-8751-5167], Christmas, David M [0000-0001-5423-0221], Clark, Luke [0000-0003-1103-2422], Sahakian, Barbara [0000-0001-7352-1745], Robbins, Trevor [0000-0003-0642-5977], Apollo - University of Cambridge Repository, Kanen, Jonathan W [0000-0002-4095-5405], Cardinal, Rudolf N [0000-0002-8751-5167], Sahakian, Barbara J [0000-0001-7352-1745], and Robbins, Trevor W [0000-0003-0642-5977]
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Serotonin ,Punishment (psychology) ,Cognitive flexibility ,Reversal Learning ,030227 psychiatry ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,Neurochemical ,Punishment ,Reward ,Healthy volunteers ,Conditioning, Operant ,Humans ,Psychology ,Neuroscience ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) ,030217 neurology & neurosurgery ,ComputingMilieux_MISCELLANEOUS - Abstract
Funder: Gates Cambridge Trust; doi: https://doi.org/10.13039/501100005370, Funder: DH | National Institute for Health Research (NIHR); doi: https://doi.org/10.13039/501100000272, Serotonin is involved in updating responses to changing environmental circumstances. Optimising behaviour to maximise reward and minimise punishment may require shifting strategies upon encountering new situations. Likewise, autonomic responses to threats are critical for survival yet must be modified as danger shifts from one source to another. Whilst numerous psychiatric disorders are characterised by behavioural and autonomic inflexibility, few studies have examined the contribution of serotonin in humans. We modelled both processes, respectively, in two independent experiments (N = 97). Experiment 1 assessed instrumental (stimulus-response-outcome) reversal learning whereby individuals learned through trial and error which action was most optimal for obtaining reward or avoiding punishment initially, and the contingencies subsequently reversed serially. Experiment 2 examined Pavlovian (stimulus-outcome) reversal learning assessed by the skin conductance response: one innately threatening stimulus predicted receipt of an uncomfortable electric shock and another did not; these contingencies swapped in a reversal phase. Upon depleting the serotonin precursor tryptophan-in a double-blind randomised placebo-controlled design-healthy volunteers showed impairments in updating both actions and autonomic responses to reflect changing contingencies. Reversal deficits in each domain, furthermore, were correlated with the extent of tryptophan depletion. Initial Pavlovian conditioning, moreover, which involved innately threatening stimuli, was potentiated by depletion. These results translate findings in experimental animals to humans and have implications for the neurochemical basis of cognitive inflexibility.
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- 2021
5. The effects of alcohol on sequential decision-making biases during gambling
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Juliette Tobias-Webb, Silvia Vearncombe, Eve H Limbrick-Oldfield, Luke Clark, and Theodora Duka
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Adult ,Male ,Pharmacology ,Roulette ,Alcohol Drinking ,Decision Making ,Pharmacology toxicology ,Alcohol ,Sequential decision ,030227 psychiatry ,Young Adult ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Double-Blind Method ,Reward ,chemistry ,Reward sensitivity ,Gambling ,Humans ,Female ,Psychology ,Alcohol consumption ,Social psychology ,030217 neurology & neurosurgery - Abstract
Rationale: \ud 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. \ud Objectives: \ud 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. \ud Methods: \ud 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.\ud Results: \ud 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. \ud Conclusions: \ud 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.
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- 2019
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6. Applying Data Science to Behavioral Analysis of Online Gambling
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Tilman Lesch, Xiaolei Deng, and Luke Clark
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Risk identification ,Psychological intervention ,Online gambling ,Data science ,030227 psychiatry ,Task (project management) ,Behavioral analysis ,03 medical and health sciences ,Psychiatry and Mental health ,Clinical Psychology ,Identification (information) ,0302 clinical medicine ,Harm ,Psychology ,030217 neurology & neurosurgery - Abstract
Gambling operators’ capacity to track gamblers in the online environment may enable identification of those users experiencing gambling harm. This review provides an update on research testing behavioral variables against indicators of disordered gambling. We consider the utility of machine learning algorithms in risk prediction, and challenges to be overcome. Disordered online gambling is associated with a range of behavioral variables, as well as other predictors including demographic and payment-related information. Machine learning is ideally suited to the task of combining these predictors in risk identification, although current research has yielded mixed success. Recent work enhancing the temporal resolution of behavioral analysis to characterize bet-by-bet changes may identify novel predictors of loss chasing. Data science has considerable potential to identify high-risk online gambling, informed by principles of behavioral analysis. Identification may enable targeting of interventions to users who are most at risk.
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- 2019
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7. Role Reversal: The Influence of Slot Machine Gambling on Subsequent Alcohol Consumption
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Nataly Kaufman, Juliette Tobias-Webb, Luke Clark, and Rebecca L. Griggs
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Adult ,Male ,Alcohol Drinking ,Sociology and Political Science ,Slot machines ,030508 substance abuse ,Electronic gaming machines ,Alcohol ,Taste test ,Young Adult ,03 medical and health sciences ,chemistry.chemical_compound ,Ad libitum ,0302 clinical medicine ,Role reversal ,Slot machine ,Surveys and Questionnaires ,Humans ,Computer Simulation ,General Psychology ,Drink alcohol ,Consumption (economics) ,Tobacco and Alcohol ,Behavior, Addictive ,chemistry ,Gambling ,0305 other medical science ,Psychology ,Reinforcement, Psychology ,Alcohol consumption ,030217 neurology & neurosurgery ,Clinical psychology - Abstract
Experimental studies examining the relationship between alcohol use and gambling have focused predominantly on alcohol's influence on gambling behavior. There has been little consideration of the reverse pathway: whether gambling influences subsequent alcohol use. Two experiments examined whether gambling and gambling outcomes (i.e. profits during a gambling session) influenced subsequent alcohol consumption. Experiment 1 (n = 53) used an ad libitum consumption test, in which participants could request beverages during a 30 min window. Experiment 2 (n = 29) used a beer taste test procedure, in which participants were asked to rate a series of beers. In both studies, male regular gamblers were assigned to watch a television show or play a modern slot machine for 30 min, before being provided with access to alcohol. On the ad libitum procedure, gambling significantly increased the number of alcoholic drinks ordered, the volume of alcohol consumed, the participants' speed of drinking, and their intention to drink alcohol. These effects were not corroborated using the taste test procedure. Across both studies, gambling outcomes were not associated with alcohol consumption. In conjunction with prior findings, the observation that gambling can promote alcohol consumption under certain conditions highlights a possible feedback loop whereby gambling and alcohol reinforce one another. However, the divergent results between the ad libitum and taste test experiments point to boundary conditions for the effect and raise methodological considerations for future work measuring alcohol consumption in gambling environments.
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- 2018
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8. Sex differences in risk-based decision making in adolescents with conduct disorder
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Roberta Riccelli, Justina Sidlauskaite, Harriet Cornwell, Areti Smaragdi, Karen Gonzalez-Madruga, Edmund J.S. Sonuga-Barke, Graeme Fairchild, Molly Batchelor, Luke Clark, and Ignazio Puzzo
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Risk ,Conduct Disorder ,Male ,medicine.medical_specialty ,Adolescent ,Decision Making ,BF ,Antisocial behaviour ,Conduct disorder ,Developmental psychology ,Reward processing ,03 medical and health sciences ,Typically developing ,HV ,Risk-Taking ,0302 clinical medicine ,Reward ,Sex differences ,Developmental and Educational Psychology ,medicine ,Child and adolescent psychiatry ,Humans ,0501 psychology and cognitive sciences ,Child ,Sex Characteristics ,05 social sciences ,Neuropsychology ,General Medicine ,medicine.disease ,Key features ,Control subjects ,Preference ,Psychiatry and Mental health ,Pediatrics, Perinatology and Child Health ,Female ,Psychology ,Decision making ,030217 neurology & neurosurgery ,050104 developmental & child psychology - Abstract
© 2017, The Author(s). Altered decision making processes and excessive risk-seeking behaviours are key features of conduct disorder (CD). Previous studies have provided compelling evidence of abnormally increased preference for risky options, higher sensitivity to rewards, as well as blunted responsiveness to aversive outcomes in adolescents with CD. However, most studies published to date have focused on males only; thus, it is not known whether females with CD show similar alterations in decision making. The current study investigated potential sex differences in decision making and risk-seeking behaviours in adolescents with CD. Forty-nine adolescents with CD (23 females) and 51 control subjects (27 females), aged 11-18 years, performed a computerised task assessing decision making under risk—the Risky Choice Task. Participants made a series of decisions between two gamble options that varied in terms of their expected values and probability of gains and losses. This enabled the participants’ risk preferences to be determined. Taking the sample as a whole, adolescents with CD exhibited increased risk-seeking behaviours compared to healthy controls. However, we found a trend towards a sex-by-group interaction, suggesting that these effects may vary by sex. Follow-up analyses showed that males with CD made significantly more risky choices than their typically developing counterparts, while females with CD did not differ from typically developing females in their risk-seeking behaviours. Our results provide preliminary evidence that sex may moderate the relationship between CD and alterations in risk attitudes and reward processing, indicating that there may be sex differences in the developmental pathways and neuropsychological deficits that lead to CD. European Commission’s Seventh Framework Programme for research, technological development and demonstration (FP7/2007-2013) under Grant Agreement no. 602407 (FemNAT-CD).
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- 2017
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9. Mixed Emotions to Near-Miss Outcomes: A Psychophysiological Study with Facial Electromyography
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Luke Clark and Steve Sharman
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Adult ,Male ,medicine.medical_specialty ,Future studies ,Sociology and Political Science ,030508 substance abuse ,Audiology ,Near miss ,Developmental psychology ,Arousal ,03 medical and health sciences ,Risk-Taking ,0302 clinical medicine ,Reward ,Slot machine ,medicine ,Humans ,Mixed emotions ,Valence (psychology) ,General Psychology ,Electromyography ,Galvanic Skin Response ,C830 Experimental Psychology ,Facial Expression ,Affect ,Behavioral data ,Gambling ,Female ,0305 other medical science ,Psychology ,Facial electromyography ,Photic Stimulation ,030217 neurology & neurosurgery - Abstract
Near-misses occur across many forms of gambling and are rated as unpleasant while simultaneously increasing the motivation to continue playing. On slot machines, the icon position relative to the payline moderates the effects of near-misses, with near-misses before the payline increasing motivation, and near-misses after the payline being rated as aversive. Near-misses are also known to increase physiological arousal compared to full-misses, but physiological measures to date have not been able to dissociate positive and negative emotional responses. The present study measured facial electromyography at the corrugator (brow) and zygomaticus (cheek) sites, as well as electrodermal activity (EDA), following gambling outcomes on a two-reel slot machine simulation in 77 novice gamblers. Behavioral data was collected using trial-by-trial ratings of motivation and valence. Wins were rated as more pleasant and increased motivation to continue playing, compared to non-win outcomes. Wins were also accompanied by increased EDA and zygomaticus activity. Near-misses after the payline were rated as more aversive than other non-wins, and this was accompanied by increased EDA and zygomaticus activity. Near-misses before the payline increased motivation to continue playing, and were accompanied by increased EDA. Thus, both subjective and physiological responses to near-misses differ for events falling either side of the payline. The 'near-miss effect' is not a unitary phenomenon. Facial EMG has differential sensitivity to positive and negative valence and may be a useful measure for future studies of gambling behavior.
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- 2015
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10. Rates of Problematic Gambling in a British Homeless Sample: A Preliminary Study
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Henrietta Bowden-Jones, Steve Sharman, Michael R. F. Aitken, Jenny Dreyer, and Luke Clark
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medicine.medical_specialty ,Sociology and Political Science ,Public health ,Sample (statistics) ,Prevalence survey ,Diagnostic tools ,Social issues ,Risk category ,Risk groups ,medicine ,Vulnerable population ,Psychology ,Psychiatry ,General Psychology ,Clinical psychology - Abstract
Homelessness and problem gambling are two public health concerns in the UK that are rarely considered concurrently, and little is known about the extent of gambling involvement and problematic gambling in the homeless. We recruited 456 individuals attending homelessness services in London, UK. All participants completed a screen for gambling involvement, and where gambling involvement was endorsed, the Problem Gambling Severity Index (PGSI) was administered. The PGSI risk categories were compared against data from the 2010 British Gambling Prevalence Survey (BGPS). PGSI problem gambling was indicated in 11.6 % of the homeless population, compared to 0.7 % in the BGPS. Of participants endorsing any PGSI symptoms, a higher proportion of homeless participants were problem gamblers relative to the low and moderate risk groups, compared to the BGPS data. These results confirm that the homeless constitute a vulnerable population for problem gambling, and that diagnostic tools for gambling involvement should be integrated into homelessness services in the UK.
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- 2014
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11. Serotonin Modulates the Effects of Pavlovian Aversive Predictions on Response Vigor
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Sharon Morein-Zamir, Annemieke M. Apergis-Schoute, Molly J. Crockett, Luke Clark, and Trevor W. Robbins
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Adult ,Male ,Serotonin ,Punishment (psychology) ,Psychopharmacology ,Conditioning, Classical ,Context (language use) ,Choice Behavior ,behavioral disciplines and activities ,Developmental psychology ,03 medical and health sciences ,Cognition ,0302 clinical medicine ,Punishment ,Reward ,Reaction Time ,aversion ,Humans ,Pavlovian ,Behavioral inhibition ,Set (psychology) ,030304 developmental biology ,Pharmacology ,Motivation ,0303 health sciences ,Tryptophan ,Response bias ,instrumental ,inhibition ,Inhibition, Psychological ,Psychiatry and Mental health ,Behavioral Science ,behavior and behavior mechanisms ,Conditioning ,Original Article ,Female ,Psychology ,Neuroscience ,psychological phenomena and processes ,030217 neurology & neurosurgery - Abstract
Updated theoretical accounts of the role of serotonin (5-HT) in motivation propose that 5-HT operates at the intersection of aversion and inhibition, promoting withdrawal in the face of aversive predictions. However, the specific cognitive mechanisms through which 5-HT modulates withdrawal behavior remain poorly understood. Behavioral inhibition in response to punishments reflects at least two concurrent processes: instrumental aversive predictions linking stimuli, responses, and punishments, and Pavlovian aversive predictions linking stimuli and punishments irrespective of response. In the current study, we examined to what extent 5-HT modulates the impact of instrumental vs Pavlovian aversive predictions on behavioral inhibition. We used acute tryptophan depletion to lower central 5-HT levels in healthy volunteers, and observed behavior in a novel task designed to measure the influence of Pavlovian and instrumental aversive predictions on choice (response bias) and response vigor (response latencies). After placebo treatment, participants were biased against responding on the button that led to punishment, and they were slower to respond in a punished context, relative to a non-punished context. Specifically, participants slowed their responses in the presence of stimuli predictive of punishments. Tryptophan depletion removed the bias against responding on the punished button, and abolished slowing in the presence of punished stimuli, irrespective of response. We suggest that this set of results can be explained by a role for 5-HT in Pavlovian aversive predictions. These findings suggest additional specificity for the influence of 5-HT on aversively motivated behavioral inhibition and extend recent models of the role of 5-HT in aversive predictions.
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- 2012
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12. Gut feelings and the reaction to perceived inequity: The interplay between bodily responses, regulation, and perception shapes the rejection of unfair offers on the ultimatum game
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Luke Clark, Barnaby D. Dunn, Davy Evans, Josh White, and Dasha Makarova
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Adult ,Male ,Economic decision making ,Adolescent ,Cognitive Neuroscience ,media_common.quotation_subject ,Decision Making ,Article ,Behavioral Neuroscience ,Cognition ,Heart Rate ,Perception ,Emotional reaction ,Humans ,Aged ,media_common ,Emotion ,Ultimatum game ,Galvanic Skin Response ,Middle Aged ,Self Concept ,Embodied cognition ,Games, Experimental ,Feeling ,Trait ,Interoception ,Female ,Rejection, Psychology ,Psychology ,Social psychology ,Decision-making ,Cognitive psychology - Abstract
It has been robustly demonstrated using the ultimatum game (UG) that individuals frequently reject unfair financial offers even if this results in a personal cost. One influential hypothesis for these rejections is that they reflect an emotional reaction to unfairness that overrides purely economic decision processes. In the present study, we examined whether the interplay between bodily responses, bodily regulation, and bodily perception (“interoception”) contributes to emotionally driven rejection behavior on the UG. Offering support for bodily feedback theories, interoceptive accuracy moderated the relationship between changes in electrodermal activity to proposals and the behavioral rejection of such offers. Larger electrodermal responses to rejected relative to accepted offers predicted greater rejection in those with accurate interoception but were unrelated to rejection in those with poor interoception. Although cardiovascular responses during the offer period were unrelated to rejection rates, greater resting heart rate variability (linked to trait emotion regulation capacity) predicted reduced rejection rates of offers. These findings help clarify individual differences in reactions to perceived unfairness, support previous emotion regulation deficit accounts of rejection behavior, and suggest that the perception and regulation of bodily based emotional biasing signals (“gut feelings”) partly shape financial decision making on the UG.
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- 2012
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13. Place your bets: psychophysiological correlates of decision-making under risk
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Luke Clark and Bettina Studer
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Adult ,Male ,Risk ,Feedback, Psychological ,Cognitive Neuroscience ,media_common.quotation_subject ,Decision Making ,Individuality ,Poison control ,Context (language use) ,Article ,050105 experimental psychology ,Arousal ,Developmental psychology ,03 medical and health sciences ,Behavioral Neuroscience ,Risk-Taking ,0302 clinical medicine ,Heart Rate ,Injury prevention ,Humans ,Personality ,0501 psychology and cognitive sciences ,media_common ,Emotion ,05 social sciences ,Human factors and ergonomics ,Galvanic Skin Response ,Psychophysiology ,Gambling ,Impulsive Behavior ,Female ,Psychology ,Skin conductance ,030217 neurology & neurosurgery ,Decision-making - Abstract
Emotions and their psychophysiological correlates are thought to play an important role in decision-making under risk. We used a novel gambling task to measure psychophysiological responses during selection of explicitly presented risky options and feedback processing. Active-choice trials, in which the participant had to select the size of bet, were compared to fixed-bet, no-choice trials. We further tested how the chances of winning and bet size affected choice behavior and psychophysiological arousal. Individual differences in impulsive and risk-taking traits were assessed. The behavioral results showed sensitivity to the choice requirement and to the chances of winning: Participants were faster to make a response on no-choice trials and when the chances of winning were high. In active-choice trials, electrodermal activity (EDA) increased with bet size during both selection and processing of losses. Cardiac responses were sensitive to choice uncertainty: Stronger selection-related heart rate (HR) decelerations were observed in trials with lower chances of winning, particularly on active-choice trials. Finally, betting behavior and psychophysiological responsiveness were moderately correlated with self-reported impulsivity-related traits. In conclusion, we demonstrate that psychophysiological arousal covaries with risk-sensitive decision-making outside of a learning context. Our results further highlight the differential sensitivities of EDA and HR to psychological features of the decision scenario.
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- 2011
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14. Reply to Griffiths: The Relationship Between Gambling and Homelessness
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Luke Clark, Steve Sharman, and Michael R. F. Aitken
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Sociology and Political Science ,Criminology ,Psychology ,General Psychology - Published
- 2014
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15. Striatal sensitivity to personal responsibility in a regret-based decision-making task
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Valentino Antonio Pironti, Trevor W. Robbins, Luke Clark, Chris M. Dodds, N. Camille, and Michael R. F. Aitken
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Adult ,Male ,Counterfactual thinking ,Cognitive Neuroscience ,Decision Making ,Emotions ,Functional Laterality ,Young Adult ,Behavioral Neuroscience ,Interpersonal relationship ,Agency (sociology) ,Image Processing, Computer-Assisted ,medicine ,Humans ,Interpersonal Relations ,Moral responsibility ,Aged ,Analysis of Variance ,Brain Mapping ,Disappointment ,Sense of agency ,Regret ,Middle Aged ,Magnetic Resonance Imaging ,Corpus Striatum ,Oxygen ,Gambling ,Female ,Orbitofrontal cortex ,medicine.symptom ,Psychology ,Social psychology ,Cognitive psychology - Abstract
Regret and relief are complex emotional states associated with the counterfactual processing of nonobtained outcomes in a decision-making situation. In the "actor effect," a sense of agency and personal responsibility is thought to heighten these emotions. Using fMRI, we scanned volunteers (n = 22) as they played a task involving choices between two wheel-of-fortune gambles. We examined how neural responses to counterfactual outcomes were modulated by giving subjects the opportunity to change their minds, as a manipulation of personal responsibility. Satisfaction ratings to the outcomes were highly sensitive to the difference between the obtained and nonobtained outcome, and ratings following losses were lower on trials with the opportunity to change one's mind. Outcome-related activity in the striatum and orbitofrontal cortex was positively related to the satisfaction ratings. The striatal response was modulated by the agency manipulation: Following losses, the striatal signal was significantly lower when the subject had the opportunity to change his/her mind. These results support the involvement of frontostriatal mechanisms in counterfactual thinking and highlight the sensitivity of the striatum to the effects of personal responsibility.
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- 2010
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16. Substantia nigra/ventral tegmental reward prediction error disruption in psychosis
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Philip R. Corlett, Paul C. Fletcher, Luke Clark, Graham K. Murray, Trevor W. Robbins, Edward T. Bullmore, Mathias Pessiglione, Andrew D. Blackwell, Garry D. Honey, and Peter B. Jones
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Adult ,Male ,Psychosis ,Adolescent ,Striatum ,Models, Psychological ,Neuropsychological Tests ,Choice Behavior ,Article ,Cellular and Molecular Neuroscience ,Reward system ,Reward ,Dopamine ,Image Processing, Computer-Assisted ,medicine ,Humans ,Molecular Biology ,Psychiatric Status Rating Scales ,Analysis of Variance ,Ventral Tegmental Area ,Dopaminergic ,medicine.disease ,Magnetic Resonance Imaging ,Oxygen ,Substantia Nigra ,Ventral tegmental area ,Psychiatry and Mental health ,medicine.anatomical_structure ,Psychotic Disorders ,Schizophrenia ,Case-Control Studies ,Incentive salience ,Female ,Psychology ,Neuroscience ,Photic Stimulation ,medicine.drug - Abstract
While dopamine systems have been implicated in the pathophysiology of schizophrenia and psychosis for many years, how dopamine dysfunction generates psychotic symptoms remains unknown. Recent theoretical interest has been directed at relating the known role of midbrain dopamine neurons in reinforcement learning, motivational salience and prediction error to explain the abnormal mental experience of psychosis. However, this theoretical model has yet to be explored empirically. To examine a link between psychotic experience, reward learning and dysfunction of the dopaminergic midbrain and associated target regions, we asked a group of first episode psychosis patients suffering from active positive symptoms and a group of healthy control participants to perform an instrumental reward conditioning experiment. We characterized neural responses using functional magnetic resonance imaging. We observed that patients with psychosis exhibit abnormal physiological responses associated with reward prediction error in the dopaminergic midbrain, striatum and limbic system, and we demonstrated subtle abnormalities in the ability of psychosis patients to discriminate between motivationally salient and neutral stimuli. This study provides the first evidence linking abnormal mesolimbic activity, reward learning and psychosis.
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- 2007
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17. Stop signal response inhibition is not modulated by tryptophan depletion or the serotonin transporter polymorphism in healthy volunteers: implications for the 5-HT theory of impulsivity
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Jonathan P. Roiser, David C. Rubinsztein, Barbara J. Sahakian, Luke Clark, Trevor W. Robbins, and Roshan Cools
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Adult ,Male ,Serotonin ,medicine.medical_specialty ,Adolescent ,Neuropsychological Tests ,Neurotransmission ,Stop signal ,Impulsivity ,chemistry.chemical_compound ,Double-Blind Method ,Internal medicine ,Diet, Protein-Restricted ,Reaction Time ,medicine ,Humans ,Neurotransmitter ,5-HT receptor ,Serotonin transporter ,Serotonin Plasma Membrane Transport Proteins ,Pharmacology ,Analysis of Variance ,Cross-Over Studies ,Polymorphism, Genetic ,biology ,5-Hydroxyindoleacetic acid ,Tryptophan ,Middle Aged ,Inhibition, Psychological ,Endocrinology ,chemistry ,Biochemistry ,Impulsive Behavior ,biology.protein ,Female ,medicine.symptom ,Psychology ,medicine.drug - Abstract
Reduced serotonin neurotransmission is implicated in disorders of impulse control, but the involvement of serotonin in inhibitory processes in healthy human subjects remains unclear.To investigate the effects of an acute manipulation of serotonin and genotype at a functional polymorphism in a gene coding for the serotonin transporter (5-HTT) on an established measure of response inhibition.Serotonin function was reduced by the acute tryptophan depletion (ATD) procedure in a double-blind, crossover design in 42 healthy subjects. The Stop Signal Task (SST) was administered 5-7 h after drink administration. The influences of 5-HTT polymorphism, gender and trait impulsivity were investigated.ATD was associated with significant depletion of plasma tryptophan levels but did not increase the stop signal reaction time in comparison to the balanced (placebo) amino acid mixture. Subjects possessing the short allele of the 5-HTT polymorphism were not more impulsive on the SST than subjects homozygous for the long allele under placebo conditions and were not disproportionately sensitive to the effects of ATD. There was no effect of gender or trait impulsivity on ATD-induced change.We find no support for the involvement of brain serotonin neurotransmission in this form of inhibitory control in healthy human subjects.
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- 2005
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18. Methylphenidate (‘Ritalin’) can Ameliorate Abnormal Risk-Taking Behavior in the Frontal Variant of Frontotemporal Dementia
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Barbara J. Sahakian, Shibley Rahman, Trevor W. Robbins, Luke Clark, John R. Hodges, Mitul A. Mehta, and Peter J. Nestor
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Male ,medicine.medical_specialty ,Prefrontal Cortex ,Neuropsychological Tests ,Audiology ,Article ,Cognition ,Risk-Taking ,Double-Blind Method ,Reward ,medicine ,Humans ,Learning ,Dementia ,Prefrontal cortex ,Aged ,Pharmacology ,Working memory ,Methylphenidate ,Hemodynamics ,Middle Aged ,medicine.disease ,Psychiatry and Mental health ,Memory, Short-Term ,Pattern Recognition, Visual ,Gambling ,Central Nervous System Stimulants ,Female ,Orbitofrontal cortex ,Psychology ,Somatic marker hypothesis ,Neuroscience ,Frontotemporal dementia ,medicine.drug - Abstract
The frontal variant of frontotemporal dementia is a significant neurological condition worldwide. There exist few treatments available for the cognitive and behavioural sequelae of fvFTD. Previous research has shown that these patients display risky decision-making, and numerous studies have now demonstrated pathology affecting the orbitofrontal cortex. The present study uses a within-subjects, double-blind, placebo-controlled procedure to investigate the effects of a single dose of methylphenidate (40 mg) upon a range of different cognitive processes including those assessing prefrontal cortex integrity. Methylphenidate was effective in ‘normalizing’ the decision-making behavior of patients, such that they became less risk taking on medication, although there were no significant effects on other aspects of cognitive function, including working memory, attentional set shifting, and reversal learning. Moreover, there was an absence of the normal subjective and autonomic responses to methylphenidate seen in elderly subjects. The results are discussed in terms of the ‘somatic marker’ hypothesis of impaired decision-making following orbitofrontal dysfunction.
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- 2005
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19. Punishment Induces Risky Decision-Making in Methadone-Maintained Opiate Users but not in Heroin Users or Healthy Volunteers
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Jonathan P. Roiser, Luke Clark, Karen D. Ersche, M. London, Trevor W. Robbins, and Barbara J. Sahakian
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Adult ,Male ,Narcotics ,Risk ,medicine.medical_specialty ,Methadone maintenance ,media_common.quotation_subject ,Decision Making ,Neuropsychological Tests ,Article ,Heroin ,Punishment ,mental disorders ,Reaction Time ,medicine ,Humans ,Drug Interactions ,Psychiatry ,Amphetamine ,media_common ,Pharmacology ,Chi-Square Distribution ,Substance dependence ,Addiction ,Middle Aged ,medicine.disease ,Behavior, Addictive ,Substance abuse ,Psychiatry and Mental health ,Case-Control Studies ,Female ,Opiate ,Psychology ,Methadone ,medicine.drug - Abstract
Reinforcing properties of psychoactive substances are considered to be critically involved in the development and maintenance of substance dependence. While accumulating evidence suggests that the sensitivity to reinforcement values may generally be altered in chronic substance users, relatively little is known about the influence reinforcing feedback exerts on ongoing decision-making in these individuals. Decision-making was investigated using the Cambridge Risk Task, in which there is a conflict between an unlikely large reward option and a likely small reward option. Responses on a given trial were analyzed with respect to the outcome on the previous trial, providing a measure of the impact of prior feedback in modulating behavior. Five different groups were compared: (i) chronic amphetamine users, (ii) chronic opiate users in methadone maintenance treatment (MMT), (iii) chronic users of illicit heroin, (iv) ex-drug users who had been long-term amphetamine / opiate users but were abstinent from all drugs of abuse for at least 1 year and (v) matched controls without a history of illicit substance use. Contrary to our predictions, choice preference was modified in response to feedback only in opiate users enrolled in MMT. Following a loss, the MMT opiate group chose the likely small reward option significantly less frequently than controls and heroin users. Our results suggest that different opiates are associated with distinctive behavioral responses to feedback. These findings are discussed with respect to the different mechanisms of action of heroin and methadone. Neuropsychopharmacology (2005) 30, 2115-2124. doi:10.1038/sj.npp.1300812; published online 6 July 2005.
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- 2005
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20. Relative lack of cognitive effects of methylphenidate in elderly male volunteers
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Luke Clark, Danielle C. Turner, Adam R. Aron, Jonathan H. Dowson, Barbara J. Sahakian, and Trevor W. Robbins
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Central Nervous System ,Male ,medicine.medical_specialty ,Administration, Oral ,Neuropsychological Tests ,law.invention ,Cardiovascular Physiological Phenomena ,Cognition ,Randomized controlled trial ,Risk Factors ,law ,Monoaminergic ,Reaction Time ,medicine ,Humans ,Psychiatry ,Aged ,Pain Measurement ,Pharmacology ,Dose-Response Relationship, Drug ,Methylphenidate ,Working memory ,Dopaminergic ,Age Factors ,Middle Aged ,Reuptake inhibitor ,Psychology ,medicine.drug ,Clinical psychology ,Executive dysfunction - Abstract
Methylphenidate, a dopaminergic and noradrenergic reuptake inhibitor, has been shown in young, healthy adult volunteers to produce pronounced effects on working memory and sustained attention. We were interested in assessing whether similar improvements could be conferred upon elderly volunteers in order to gain a more complete understanding of the effects of age on monoaminergic manipulations of working memory and attention, as well as to explore the potential for pharmacological intervention in attention and executive dysfunction disorders in this age group.The main aim of the study was to characterise the dose-related effects of methylphenidate on a range of neuropsychological functions in elderly healthy volunteers.Sixty healthy elderly adult male volunteers received either a single oral dose of placebo, 20 mg or 40 mg methylphenidate prior to performing a variety of tasks designed to assess memory, attention and executive function. A randomised double-blind, between-subjects design was used.Methylphenidate had significant cardiovascular and subjective effects. However, unlike in younger volunteers, no significant effects of drug on working memory (spatial span and spatial working memory), response inhibition (stop-signal) or sustained attention (rapid visual information processing) were seen. Subtle effects on latency similar to those in younger volunteers were identified: both doses of methylphenidate resulted in a slowing in response time during set-shifting and decision-making.The results of this study demonstrate that, in elderly subjects, the cognitive effects of methylphenidate are grossly attenuated and distinct from the profile previously described in younger volunteers. It is suggested that methylphenidate may not be appropriate as a pharmacological intervention in elderly patient groups, such as those reporting age-related cognitive decline.
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- 2003
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21. Cognitive enhancing effects of modafinil in healthy volunteers
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Barbara J. Sahakian, Trevor W. Robbins, Adam R. Aron, Danielle C. Turner, Jonathan H. Dowson, and Luke Clark
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Adult ,Male ,medicine.medical_specialty ,Decision Making ,Blood Pressure ,Modafinil ,Audiology ,Spatial memory ,Cognition ,Double-Blind Method ,Heart Rate ,Memory ,medicine ,Memory span ,Humans ,Attention deficit hyperactivity disorder ,Benzhydryl Compounds ,Pain Measurement ,Pharmacology ,Psychological Tests ,Dose-Response Relationship, Drug ,Methylphenidate ,Working memory ,Memoria ,medicine.disease ,Neuroprotective Agents ,Pattern Recognition, Visual ,Psychology ,medicine.drug ,Cognitive psychology - Abstract
Rationale. Modafinil, a novel wake-promoting agent, has been shown to have a similar clinical profile to that of conventional stimulants such as methylphenidate. We were therefore interested in assessing whether modafinil, with its unique pharmacological mode of action, might offer similar potential as a cognitive enhancer, without the side effects commonly experienced with amphetamine-like drugs. Objectives. The main aim of this study was to evaluate the cognitive enhancing potential of this novel agent using a comprehensive battery of neuropsychological tests. Methods. Sixty healthy young adult male volunteers received either a single oral dose of placebo, or 100 mg or 200 mg modafinil prior to performing a variety of tasks designed to test memory and attention. A randomised double-blind, between-subjects design was used. Results. Modafinil significantly enhanced performance on tests of digit span, visual pattern recognition memory, spatial planning and stop-signal reaction time. These performance improvements were complemented by a slowing in latency on three tests: delayed matching to sample, a decision-making task and the spatial planning task. Subjects reported feeling more alert, attentive and energetic on drug. The effects were not clearly dose dependent, except for those seen with the stop-signal paradigm. In contrast to previous findings with methylphenidate, there were no significant effects of drug on spatial memory span, spatial working memory, rapid visual information processing or attentional set-shifting. Additionally, no effects on paired associates learning were identified. Conclusions. These data indicate that modafinil selectively improves neuropsychological task performance. This improvement may be attributable to an enhanced ability to inhibit pre-potent responses. This effect appears to reduce impulsive responding, suggesting that modafinil may be of benefit in the treatment of attention deficit hyperactivity disorder.
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- 2003
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22. Methylphenidate improves response inhibition but not reflection–impulsivity in children with attention deficit hyperactivity disorder (ADHD)
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Barbara J. Sahakian, Michael R. F. Aitken, Anna Maria Dezsery, Luke Clark, Andrew D. Blackwell, Lindsey Kent, Danielle C. Turner, and Elise E. DeVito
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Male ,Child Behavior ,Stop signal ,Neuropsychological Tests ,Disinhibition ,0302 clinical medicine ,Cognition ,Surveys and Questionnaires ,Child ,Response inhibition ,Original Investigation ,Cross-Over Studies ,Methylphenidate ,05 social sciences ,Inhibition, Psychological ,Treatment Outcome ,Research Design ,medicine.symptom ,Psychology ,Cognitive enhancement ,medicine.drug ,Clinical psychology ,medicine.medical_specialty ,Impulsivity ,Reflection–impulsivity ,Adolescent ,Decision Making ,Pharmacology toxicology ,050105 experimental psychology ,03 medical and health sciences ,Double-Blind Method ,mental disorders ,medicine ,ADHD ,Humans ,Attention deficit hyperactivity disorder ,0501 psychology and cognitive sciences ,Psychiatry ,Reflection (computer graphics) ,Pharmacology ,Motor planning ,business.industry ,medicine.disease ,Attention Deficit Disorder with Hyperactivity ,Impulsive Behavior ,Central Nervous System Stimulants ,business ,030217 neurology & neurosurgery ,Psychomotor Performance ,Decision-making - Abstract
Rationale Impulsivity is a cardinal feature of attention deficit hyperactivity disorder (ADHD), which is thought to underlie many of the cognitive and behavioural symptoms associated with the disorder. Impairments on some measures of impulsivity have been shown to be responsive to pharmacotherapy. However, impulsivity is a multi-factorial construct and the degree to which different forms of impulsivity contribute to impairments in ADHD or respond to pharmacological treatments remains unclear. Objectives The aims of the study were to assess the effects of methylphenidate (MPH) on the performance of children with ADHD on measures of reflection–impulsivity and response inhibition and to compare with the performance of healthy volunteers. Methods Twenty-one boys (aged 7–13 years) diagnosed with ADHD underwent a double-blind, placebo-controlled trial of MPH (0.5 mg/kg) during which they performed the Information Sampling Task (IST) and the Stop Signal Task. A healthy age- and education-matched control group was tested on the same measures without medication. Results Children with ADHD were impaired on measures of response inhibition, but did not demonstrate reflection–impulsivity on the IST. However, despite sampling a similar amount of information as their peers, the ADHD group made more poor decisions. MPH improved performance on measures of response inhibition and variability of response, but did not affect measures of reflection–impulsivity or quality of decision-making. Conclusions MPH differentially affected two forms of impulsivity in children with ADHD and failed to ameliorate their poor decision-making on the information sampling test.
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- 2009
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23. Erratum: Serotonin Transporter Polymorphism Mediates Vulnerability to Loss of Incentive Motivation Following Acute Tryptophan Depletion
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Jonathan P Roiser, Andrew D Blackwell, Roshan Cools, Luke Clark, David C Rubinsztein, Trevor W Robbins, and Barbara J Sahakian
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Pharmacology ,Psychiatry and Mental health - Published
- 2006
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