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Falk Kiefer - One of the best experts on this subject based on the ideXlab platform.
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Plasma calcium concentration during detoxification predicts neural Cue-Reactivity and craving during early abstinence in alcohol-dependent patients
European Archives of Psychiatry and Clinical Neuroscience, 2021Co-Authors: Patrick Bach, Rilana Schuster, Anne Koopmann, Sabine Vollstaedt-klein, Rainer Spanagel, Falk KieferAbstract:Recent studies on the pathophysiology of alcohol dependence suggest a link between peripheral calcium concentrations and alcohol craving. Here, we investigated the association between plasma calcium concentration, Cue-induced brain activation, and alcohol craving. Plasma calcium concentrations were measured at the onset of inpatient detoxification in a sample of N = 115 alcohol-dependent patients. Alcohol Cue-Reactivity was assessed during early abstinence (mean 11.1 days) using a functional magnetic resonance imaging (fMRI) alcohol Cue-Reactivity task. Multiple regression analyses and bivariate correlations between plasma calcium concentrations, clinical craving measures and neural alcohol Cue-Reactivity (CR) were tested. Results show a significant negative correlation between plasma calcium concentrations and compulsive alcohol craving. Higher calcium levels predicted higher alcohol Cue-induced brain response in a cluster of frontal brain areas, including the dorsolateral prefrontal cortex (dlPFC), the anterior prefrontal cortex (alPFC), and the inferior (IFG) and middle frontal gyri (MFG). In addition, functional brain activation in those areas correlated negatively with craving for alcohol during fMRI. Higher peripheral calcium concentrations during withdrawal predicted increased alcohol Cue-induced brain activation in frontal brain areas, which are associated with craving inhibition and cognitive control functions. This might indicate that higher plasma calcium concentrations at onset of detoxification could modulate craving inhibition during early abstinence. Trial registration number : DRKS00003388; date of registration: 14.12.2011.
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effects of leptin and ghrelin on neural Cue Reactivity in alcohol addiction two streams merge to one river
Psychoneuroendocrinology, 2019Co-Authors: Patrick Bach, Sabine Vollstadtklein, Jan Malte Bumb, Rilana Schuster, Iris Reinhard, Marcella Rietschel, Stephanie H Witt, Klaus Wiedemann, Falk Kiefer, Anne KoopmannAbstract:Leptin and ghrelin and a "cross-talk" between both hormones were implicated in the pathophysiology of alcohol dependence, both modulating alcohol craving and drug-seeking. To date, the neurobiological mechanisms underlying those effects are still little-known. We thus investigated the effect of leptin and ghrelin on alcohol Cue-induced brain response, alcohol craving and relapse risk in alcohol-dependent subjects. Seventy abstinent alcohol dependent individuals underwent a functional magnetic resonance imaging (fMRI) alcohol Cue-Reactivity task and patients` alcohol craving was assessed. Plasma levels of leptin, total and acylated, active ghrelin were measured prior to the fMRI session. Additionally, relapse data was collected during a three-month follow-up. Associations between hormone levels, mesolimbic Cue-Reactivity, alcohol craving and relapse risk were tested. Leptin levels showed a significant negative association to alcohol Cue-induced brain response in the striatum and alcohol craving. In addition, there was a significant effect of leptin on time to first heavy relapse in which higher leptin levels predicted longer times to first heavy relapse. Moreover, positive associations between acylated ghrelin and increased Cue-Reactivity in bilateral insulae as well as increased craving for alcohol during the fMRI task were revealed. Leptin and acylated ghrelin show opposing effects on mesolimbic Cue-Reactivity and alcohol craving. We suspect that the reduced striatal Cue-Reactivity might be the neurobiological correlate of leptin's effect on relapse-risk. The reported results further support the relevance of appetite regulating hormones in the pathophysiology of addiction and their potential role as future treatment targets.
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Oxytocin Reduces Alcohol Cue-Reactivity in Alcohol-Dependent Rats and Humans
Neuropsychopharmacology, 2018Co-Authors: Anita C Hansson, Anne Koopmann, Stefanie Uhrig, Sina Bühler, Esi Domi, Eva Kiessling, Roberto Ciccocioppo, Robert C Froemke, Valery Grinevich, Falk KieferAbstract:Approved pharmacological treatments for alcohol use disorder are limited in their effectiveness, and new drugs that can easily be translated into the clinic are warranted. One of those candidates is oxytocin because of its interaction with several alcohol-induced effects. Alcohol-dependent rats as well as post-mortem brains of human alcoholics and controls were analyzed for the expression of the oxytocin system by qRT-PCR, in situ hybridization, receptor autoradiography ([^125I]OVTA binding), and immunohistochemistry. Alcohol self-administration and Cue-induced reinstatement behavior was measured after intracerebroventricular injection of 10 nM oxytocin in dependent rats. Here we show a pronounced upregulation of oxytocin receptors in brain tissues of alcohol-dependent rats and deceased alcoholics, primarily in frontal and striatal areas. This upregulation stems most likely from reduced oxytocin expression in hypothalamic nuclei. Pharmacological validation showed that oxytocin reduced Cue-induced reinstatement response in dependent rats—an effect that was not observed in non-dependent rats. Finally, a clinical pilot study (German clinical trial number DRKS00009253) using functional magnetic resonance imaging in heavy social male drinkers showed that intranasal oxytocin (24 IU) decreased neural Cue-Reactivity in brain networks similar to those detected in dependent rats and humans with increased oxytocin receptor expression. These studies suggest that oxytocin might be used as an anticraving medication and thus may positively affect treatment outcomes in alcoholics.
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validating incentive salience with functional magnetic resonance imaging association between mesolimbic Cue Reactivity and attentional bias in alcohol dependent patients
Addiction Biology, 2012Co-Authors: Sabine Vollstadtklein, Karl Mann, Patrick Bach, Martina Kirsch, Sabine Loeber, Anne Richter, Christoph Von Der Goltz, Derik Hermann, Falk KieferAbstract:: Alcohol-associated Cues are able to elicit brain activations in mesocorticolimbic networks that are related to the rewarding properties of the drug. Some authors hypothesize that the activation of the mesocorticolimbic reward system triggers an attention allocation to alcohol-associated Cues. Yet, no functional magnetic resonance imaging (fMRI) studies examining this proposition are available. In this fMRI study we investigate the association between attentional bias and neural Cue Reactivity. Thirty-eight recently abstinent alcohol-dependent patients were examined. fMRI was used to study Cue Reactivity during the presentation of alcohol-related pictures. A modified visual dot-probe task was used to assess attentional bias. Alcohol-dependent patients showed an attentional bias to alcohol-associated Cues as well as Cue-induced fMRI activation in response to alcohol-related stimuli in limbic and reward-related brain regions and visual areas. We found a positive correlation between Cue-induced brain activation and attentional bias score in a network including frontal, temporal and subcortical regions. This study is the first demonstrating that, in line with previous suggestions, Cue induced activation of the mesocorticolimbic reward system triggers focusing attention to substance-associated Cues. However, this association could also be bidirectional with the attentional bias enhancing Cue-induced neural activity.
Patrick Bach - One of the best experts on this subject based on the ideXlab platform.
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Plasma calcium concentration during detoxification predicts neural Cue-Reactivity and craving during early abstinence in alcohol-dependent patients
European Archives of Psychiatry and Clinical Neuroscience, 2021Co-Authors: Patrick Bach, Rilana Schuster, Anne Koopmann, Sabine Vollstaedt-klein, Rainer Spanagel, Falk KieferAbstract:Recent studies on the pathophysiology of alcohol dependence suggest a link between peripheral calcium concentrations and alcohol craving. Here, we investigated the association between plasma calcium concentration, Cue-induced brain activation, and alcohol craving. Plasma calcium concentrations were measured at the onset of inpatient detoxification in a sample of N = 115 alcohol-dependent patients. Alcohol Cue-Reactivity was assessed during early abstinence (mean 11.1 days) using a functional magnetic resonance imaging (fMRI) alcohol Cue-Reactivity task. Multiple regression analyses and bivariate correlations between plasma calcium concentrations, clinical craving measures and neural alcohol Cue-Reactivity (CR) were tested. Results show a significant negative correlation between plasma calcium concentrations and compulsive alcohol craving. Higher calcium levels predicted higher alcohol Cue-induced brain response in a cluster of frontal brain areas, including the dorsolateral prefrontal cortex (dlPFC), the anterior prefrontal cortex (alPFC), and the inferior (IFG) and middle frontal gyri (MFG). In addition, functional brain activation in those areas correlated negatively with craving for alcohol during fMRI. Higher peripheral calcium concentrations during withdrawal predicted increased alcohol Cue-induced brain activation in frontal brain areas, which are associated with craving inhibition and cognitive control functions. This might indicate that higher plasma calcium concentrations at onset of detoxification could modulate craving inhibition during early abstinence. Trial registration number : DRKS00003388; date of registration: 14.12.2011.
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effects of leptin and ghrelin on neural Cue Reactivity in alcohol addiction two streams merge to one river
Psychoneuroendocrinology, 2019Co-Authors: Patrick Bach, Sabine Vollstadtklein, Jan Malte Bumb, Rilana Schuster, Iris Reinhard, Marcella Rietschel, Stephanie H Witt, Klaus Wiedemann, Falk Kiefer, Anne KoopmannAbstract:Leptin and ghrelin and a "cross-talk" between both hormones were implicated in the pathophysiology of alcohol dependence, both modulating alcohol craving and drug-seeking. To date, the neurobiological mechanisms underlying those effects are still little-known. We thus investigated the effect of leptin and ghrelin on alcohol Cue-induced brain response, alcohol craving and relapse risk in alcohol-dependent subjects. Seventy abstinent alcohol dependent individuals underwent a functional magnetic resonance imaging (fMRI) alcohol Cue-Reactivity task and patients` alcohol craving was assessed. Plasma levels of leptin, total and acylated, active ghrelin were measured prior to the fMRI session. Additionally, relapse data was collected during a three-month follow-up. Associations between hormone levels, mesolimbic Cue-Reactivity, alcohol craving and relapse risk were tested. Leptin levels showed a significant negative association to alcohol Cue-induced brain response in the striatum and alcohol craving. In addition, there was a significant effect of leptin on time to first heavy relapse in which higher leptin levels predicted longer times to first heavy relapse. Moreover, positive associations between acylated ghrelin and increased Cue-Reactivity in bilateral insulae as well as increased craving for alcohol during the fMRI task were revealed. Leptin and acylated ghrelin show opposing effects on mesolimbic Cue-Reactivity and alcohol craving. We suspect that the reduced striatal Cue-Reactivity might be the neurobiological correlate of leptin's effect on relapse-risk. The reported results further support the relevance of appetite regulating hormones in the pathophysiology of addiction and their potential role as future treatment targets.
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increased mesolimbic Cue Reactivity in carriers of the mu opioid receptor gene oprm1 a118g polymorphism predicts drinking outcome a functional imaging study in alcohol dependent subjects
European Neuropsychopharmacology, 2015Co-Authors: Patrick Bach, Andreas Heinz, Sabine Vollsta Dtklein, Martina Kirsch, Sabine Hoffmann, Anne Jorde, Josef Frank, Katrin Charlet, Anne Beck, Henrik WalterAbstract:The endogenous opioid system is involved in the pathophysiology of alcohol-use disorders. Genetic variants of the opioid system alter neural and behavioral responses to alcohol. In particular, a single nucleotide polymorphism rs1799971 (A118G) in the mu-opioid receptor gene (OPRM1) is suggested to modulate alcohol-related phenotypes and neural response in the mesocorticolimbic dopaminergic system. Little is known about the clinical implications of these changes. The current study investigated the relationship of genotype effects on subjective and neural responses to alcohol Cues and relapse in a sample of abstinent alcohol-dependent patients. Functional magnetic resonance imaging (fMRI) was used to investigate alcohol Cue-Reactivity and drinking outcome of 81 abstinent alcohol-dependent patients. G-allele carriers displayed increased fMRI Cue-Reactivity in the left dorsal striatum and bilateral insulae. Neural responses to alcohol Cues in these brain regions correlated positively with subjective craving for alcohol and positive expectations of alcohol׳s effects. Moreover, alcohol Cue-Reactivity in the left dorsal striatum predicted time to first severe relapse. Current results show that alcohol-dependent G-allele carriers׳ increased Cue-Reactivity is associated with an increased relapse risk. This suggests that genotype effects on Cue-Reactivity might link the OPRM1 A118G risk allele with an increased relapse risk that was reported in earlier studies. From a clinical perspective, risk-allele carriers might benefit from treatments, such as neuro-feedback or extinction-based therapy that are suggested to reduce mesolimbic Reactivity.
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validating incentive salience with functional magnetic resonance imaging association between mesolimbic Cue Reactivity and attentional bias in alcohol dependent patients
Addiction Biology, 2012Co-Authors: Sabine Vollstadtklein, Karl Mann, Patrick Bach, Martina Kirsch, Sabine Loeber, Anne Richter, Christoph Von Der Goltz, Derik Hermann, Falk KieferAbstract:: Alcohol-associated Cues are able to elicit brain activations in mesocorticolimbic networks that are related to the rewarding properties of the drug. Some authors hypothesize that the activation of the mesocorticolimbic reward system triggers an attention allocation to alcohol-associated Cues. Yet, no functional magnetic resonance imaging (fMRI) studies examining this proposition are available. In this fMRI study we investigate the association between attentional bias and neural Cue Reactivity. Thirty-eight recently abstinent alcohol-dependent patients were examined. fMRI was used to study Cue Reactivity during the presentation of alcohol-related pictures. A modified visual dot-probe task was used to assess attentional bias. Alcohol-dependent patients showed an attentional bias to alcohol-associated Cues as well as Cue-induced fMRI activation in response to alcohol-related stimuli in limbic and reward-related brain regions and visual areas. We found a positive correlation between Cue-induced brain activation and attentional bias score in a network including frontal, temporal and subcortical regions. This study is the first demonstrating that, in line with previous suggestions, Cue induced activation of the mesocorticolimbic reward system triggers focusing attention to substance-associated Cues. However, this association could also be bidirectional with the attentional bias enhancing Cue-induced neural activity.
Reinout W. Wiers - One of the best experts on this subject based on the ideXlab platform.
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striatal alcohol Cue Reactivity is stronger in male than female problem drinkers
European Journal of Neuroscience, 2019Co-Authors: Anne Marije Kaag, Reinout W. Wiers, Taco J De Vries, Tommy Pattij, Anna E GoudriaanAbstract:Despite apparent sex differences in the development and treatment of alcohol use disorder, relatively little is known about the underlying neural mechanisms. In this study, we therefore investigated neural Cue-Reactivity in a sample of male (n = 28) and female (n = 27) problem drinkers (matched on age and alcohol use severity) with an average alcohol use disorder identification test score of 12 which is indicative of a likely alcohol use disorder. Neural Cue-Reactivity data were extracted from four regions of interest: the ventral and dorsal striatum and the ventral and dorsal anterior cingulate cortex, with a significance level set at p < 0.05. While the Cue-Reactivity paradigm induced similar levels of self-reported craving in men and women, visual alcohol Cues induced significantly stronger striatal activation in men compared to drinkers. While sex differences in ventral striatal Cue-Reactivity were partly explained by sex differences in alcohol intake, cannabis use, negative affect and anxiety, this was not the case for sex differences in dorsal striatal Cue-Reactivity. These results suggest that alcohol Cues are differentially processed by men and women and that the neurobiological mechanisms behind Cue-Reactivity differ between the sexes. Consequently, paradigms using alcohol-related pictures may not be optimal to induce Cue-Reactivity in female drinkers and may not be optimal to measure neurobiological markers of alcohol use severity and relapse. Future alcohol Cue-Reactivity studies should, in addition to including both men and women, include different types of Cues (e.g., stressors and imagery in addition to pictures) to assess sex differences in alcohol Cue-Reactivity.
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Cue Reactivity and its relation to craving and relapse in alcohol dependence: a combined laboratory and field study
Psychopharmacology, 2015Co-Authors: Jurriaan Witteman, Hans Post, Mika Tarvainen, Avalon Bruijn, Elizabeth De Sousa Fernandes Perna, Johannes G. Ramaekers, Reinout W. WiersAbstract:The present study investigated the nature of physiological Cue Reactivity and craving in response to alcohol Cues among alcohol-dependent patients ( N = 80) who were enrolled in detoxification treatment. Further, the predictive value with regard to future drinking of both the magnitude of the physiological and craving response to alcohol Cues while in treatment and the degree of alcohol-Cue exposure in patients’ natural environment was assessed. Physiological Reactivity and craving in response to experimental exposure to alcohol and soft drink advertisements were measured during detoxification treatment using heart rate variability and subjective rating of craving. Following discharge, patients monitored exposure to alcohol advertisements for five consecutive weeks with a diary and were followed up with an assessment of relapse at 5 weeks and 3 months post-discharge. The results indicated that the presence of alcohol Cues such as the portrayal of the drug and drinking behaviour induced physiological Cue Reactivity and craving. Additionally, Cue Reactivity and craving were positively correlated, and Cue Reactivity was larger for patients with shorter histories of alcohol dependence. Further, patients reported a substantial daily exposure to alcohol Cues. The magnitude of Cue Reactivity and the craving response to alcohol Cues at baseline and degree of exposure to alcohol Cues in patients’ natural environment did not predict relapse. It is concluded that the presence of alcohol Cues such as portrayal of alcoholic beverages and drinking behaviour induces Cue Reactivity and craving in alcohol dependence through a conditioned appetitive response.
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effects of cognitive bias modification training on neural alcohol Cue Reactivity in alcohol dependence
American Journal of Psychiatry, 2015Co-Authors: Corinde E. Wiers, Steffen Pawelczack, Thomas E. Gladwin, Christiane K. Gawron, Heiner Stuke, Soyoung Q. Park, Christine Stelzel, Andreas Heinz, Reinout W. Wiers, Mike RinckAbstract:Objective:In alcohol-dependent patients, alcohol Cues evoke increased activation in mesolimbic brain areas, such as the nucleus accumbens and the amygdala. Moreover, patients show an alcohol approach bias, a tendency to more quickly approach than avoid alcohol Cues. Cognitive bias modification training, which aims to retrain approach biases, has been shown to reduce alcohol craving and relapse rates. The authors investigated effects of this training on Cue Reactivity in alcohol-dependent patients.Method:In a double-blind randomized design, 32 abstinent alcohol-dependent patients received either bias modification training or sham training. Both trainings consisted of six sessions of the joystick approach-avoidance task; the bias modification training entailed pushing away 90% of alcohol Cues and 10% of soft drink Cues, whereas this ratio was 50/50 in the sham training. Alcohol Cue Reactivity was measured with functional MRI before and after training.Results:Before training, alcohol Cue-evoked activation wa...
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neural responses associated with Cue Reactivity in frequent cannabis users
Addiction Biology, 2013Co-Authors: Janna Cousijn, Anna E Goudriaan, Wim Van Den Brink, Dick J Veltman, Richard K Ridderinkhof, Reinout W. WiersAbstract:Cue-Reactivity reflects enhanced motivational processing underlying continued substance use and relapse in substance use disorders. Substance use disorders are associated with greater Cue-Reactivity in orbitofrontal cortex, anterior cingulate cortex, striatum, ventral tegmental area and amygdala. Here we examine whether this also holds for frequent cannabis users. Using functional magnetic resonance imaging (fMRI), neural responses to neutral and cannabis-related Cues were compared between frequent cannabis users (n = 31), sporadic cannabis users (n = 20) and cannabis-naive controls (n = 21). In addition, fMRI findings were correlated with the level of cannabis use, problem severity and craving. In frequent users compared with sporadic users and controls, cannabis images engendered higher activation than control images in the ventral tegmental area. Activation of the orbitofrontal cortex, anterior cingulate cortex and striatum was only higher in a subgroup of frequent users with high compared with low-problem severity. Activity in the right putamen and right dorsolateral prefrontal cortex correlated negatively with subjective craving in frequent users. Activity was not correlated with level of cannabis use. These findings indicate that cannabis Cues activate areas associated with addiction pathology in frequent cannabis users compared with sporadic users and controls. However, among frequent users, Cue-Reactivity seems to be primarily associated with problem severity, not with amount of cannabis use. These findings imply neural Cue-Reactivity as a tool in assessing problem severity of cannabis use.
Dick J Veltman - One of the best experts on this subject based on the ideXlab platform.
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Cue Reactivity is associated with duration and severity of alcohol dependence an fmri study
PLOS ONE, 2014Co-Authors: Zsuzsika Sjoerds, Wim Van Den Brink, Aartjan T F Beekman, Brenda W J H Penninx, Dick J VeltmanAbstract:Introduction: With the progression of substance dependence, drug Cue-related brain activation is thought to shift from motivational towards habit pathways. However, a direct association between Cue-induced brain activation and dependence duration has not yet been shown. We therefore examined the relationship between alcohol Cue-Reactivity in the brain, Cue-induced subjective craving and alcohol dependence duration and severity. Since alcohol dependence is highly comorbid with depression/anxiety, which may modulate brain responses to alcohol Cues, we also examined the relation between comorbid depression/anxiety and Cue-Reactivity. Methods: We compared 30 alcohol dependent patients with 15 healthy controls and 15 depression/anxiety patients during a visual alcohol Cue-Reactivity task using functional magnetic resonance imaging blood oxygenated level-dependent responses and subjective craving as outcomes. Within the alcohol dependent group we correlated Cue-Reactivity with alcohol dependence severity and duration, with Cue-induced craving and with depression/anxiety levels. Results: Alcohol dependent patients showed greater Cue-Reactivity in motivational brain pathways and stronger subjective craving than depression/anxiety patients and healthy controls. Depression/anxiety was not associated with Cue-Reactivity, but depression severity in alcohol dependent patients was positively associated with craving. Within alcohol dependence, longer duration of alcohol dependence was associated with stronger Cue-related activation of the posterior putamen, a structure involved in habits, whereas higher alcohol dependence severity was associated with lower Cue-Reactivity in the anterior putamen, an area implicated in goal-directed behavior preceding habit formation. Conclusion: Cue-Reactivity in alcohol dependence is not modulated by comorbid depression or anxiety. More importantly, the current data confirm the hypothesis of a ventral to dorsal striatal shift of learning processes with longer dependence duration, which could underlie increasingly habitual substance use with progressing substance dependence.
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neural responses associated with Cue Reactivity in frequent cannabis users
Addiction Biology, 2013Co-Authors: Janna Cousijn, Anna E Goudriaan, Wim Van Den Brink, Dick J Veltman, Richard K Ridderinkhof, Reinout W. WiersAbstract:Cue-Reactivity reflects enhanced motivational processing underlying continued substance use and relapse in substance use disorders. Substance use disorders are associated with greater Cue-Reactivity in orbitofrontal cortex, anterior cingulate cortex, striatum, ventral tegmental area and amygdala. Here we examine whether this also holds for frequent cannabis users. Using functional magnetic resonance imaging (fMRI), neural responses to neutral and cannabis-related Cues were compared between frequent cannabis users (n = 31), sporadic cannabis users (n = 20) and cannabis-naive controls (n = 21). In addition, fMRI findings were correlated with the level of cannabis use, problem severity and craving. In frequent users compared with sporadic users and controls, cannabis images engendered higher activation than control images in the ventral tegmental area. Activation of the orbitofrontal cortex, anterior cingulate cortex and striatum was only higher in a subgroup of frequent users with high compared with low-problem severity. Activity in the right putamen and right dorsolateral prefrontal cortex correlated negatively with subjective craving in frequent users. Activity was not correlated with level of cannabis use. These findings indicate that cannabis Cues activate areas associated with addiction pathology in frequent cannabis users compared with sporadic users and controls. However, among frequent users, Cue-Reactivity seems to be primarily associated with problem severity, not with amount of cannabis use. These findings imply neural Cue-Reactivity as a tool in assessing problem severity of cannabis use.
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brain activation patterns associated with Cue Reactivity and craving in abstinent problem gamblers heavy smokers and healthy controls an fmri study
Addiction Biology, 2010Co-Authors: Anna E Goudriaan, Wim Van Den Brink, Dick J Veltman, Michiel B De Ruiter, Jaap OosterlaanAbstract:Abnormal Cue Reactivity is a central characteristic of addiction, associated with increased activity in motivation, attention and memory related brain circuits. In this neuroimaging study, Cue Reactivity in problem gamblers (PRG) was compared with Cue Reactivity in heavy smokers (HSM) and healthy controls (HC). A functional magnetic resonance imaging event-related Cue Reactivity paradigm, consisting of gambling, smoking-related and neutral pictures, was employed in 17 treatment-seeking non-smoking PRG, 18 non-gambling HSM, and 17 non-gambling and non-smoking HC. Watching gambling pictures (relative to neutral pictures) was associated with higher brain activation in occipitotemporal areas, posterior cingulate cortex, parahippocampal gyrus and amygdala in PRG compared with HC and HSM. Subjective craving in PRG correlated positively with brain activation in left ventrolateral prefrontal cortex and left insula. When comparing the HSM group with the two other groups, no significant differences in brain activity induced by smoking Cues were found. In a stratified analysis, the HSM subgroup with higher Fagerstrom Test for Nicotine Dependence scores (FTND M = 5.4) showed higher brain activation in ventromedial prefrontal cortex, rostral anterior cingulate cortex, insula and middle/superior temporal gyrus while watching smoking-related pictures (relative to neutral pictures) than the HSM subgroup with lower FTND scores (FTND M = 2.9) and than non-smoking HC. Nicotine craving correlated with activation in left prefrontal and left amygdala when viewing smoking-related pictures in HSM. Increased regional responsiveness to gambling pictures in brain regions linked to motivation and visual processing is present in PRG, similar to neural mechanisms underlying Cue Reactivity in substance dependence. Increased brain activation in related fronto-limbic brain areas was present in HSM with higher FTND scores compared with HSM with lower FTND scores.
Lara A Ray - One of the best experts on this subject based on the ideXlab platform.
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an examination of motivation to change and neural alcohol Cue Reactivity following a brief intervention
Frontiers in Psychiatry, 2019Co-Authors: Erica N Grodin, Aaron C Lim, James Mackillop, Mitchell P Karno, Lara A RayAbstract:Background: Brief interventions represent a promising psychological intervention targeting individuals with heavy alcohol use. Motivation to change represents an individual's openness to engage in a behavior change strategy and is thought to be a crucial component of brief interventions. Neuroimaging techniques provide a translational tool to investigate the neurobiological mechanisms underlying potential mediators of treatment response, including motivation to change. Therefore, this study aimed to examine the effect of a brief intervention on motivation to change drinking behavior and neural alcohol taste Cue Reactivity. Methods: Non-treatment-seeking heavy drinkers were randomized to receive a brief drinking intervention (n = 22) or an attention-matched control (n = 24). Three indices of motivation to change were assessed at baseline and after the intervention or control session: importance, confidence, and readiness. Immediately following the intervention or control session, participants also underwent an functional magnetic resonance imaging (fMRI) during which they completed an alcohol taste Cues paradigm. Results: There was a significant effect of the brief intervention on increasing ratings of importance of changing drinking behavior, but not on ratings of confidence or readiness to change. Ratings of importance after the intervention or control session were associated with neural alcohol taste Cue Reactivity, but notably, this effect was only significant for participants who received the intervention. Individuals in the intervention condition showed a positive association between ratings of importance and activation in the precuneus, posterior cingulate, and insula. Conclusions: The brief drinking intervention was successful at improving one dimension of motivation to change among non-treatment-seeking heavy drinkers. The brief intervention moderated the relationship between ratings of importance and brain activation in circuitry associated with interoceptive awareness and self-reflection. Together, findings represent an initial step toward understanding the neurobiological mechanisms through which a brief intervention may improve motivation to change.
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The Effects of Pharmacological Opioid Blockade on Neural Measures of Drug Cue-Reactivity in Humans
Neuropsychopharmacology, 2016Co-Authors: Kelly E Courtney, Dara G Ghahremani, Lara A RayAbstract:Interactions between dopaminergic and opioidergic systems have been implicated in the reinforcing properties of drugs of abuse. The present study investigated the effects of opioid blockade, via naltrexone, on functional magnetic resonance imaging (fMRI) measures during methamphetamine Cue-Reactivity to elucidate the role of endogenous opioids in the neural systems underlying drug craving. To investigate this question, non-treatment seeking individuals with methamphetamine use disorder ( N =23; 74% male, mean age=34.70 (SD=8.95)) were recruited for a randomized, placebo controlled, within-subject design and underwent a visual methamphetamine Cue-Reactivity task during two blood-oxygen-level dependent (BOLD) fMRI sessions following 3 days of naltrexone (50 mg) and matched time for placebo. fMRI analyses tested naltrexone-induced differences in BOLD activation and functional connectivity during Cue processing. The results showed that naltrexone administration reduced Cue-Reactivity in sensorimotor regions and related to altered functional connectivity of dorsal striatum, ventral tegmental area, and precuneus with frontal, visual, sensory, and motor-related regions. Naltrexone also weakened the associations between subjective craving and precuneus functional connectivity with sensorimotor regions and strengthened the associations between subjective craving and dorsal striatum and precuneus connectivity with frontal regions. In conclusion, this study provides the first evidence that opioidergic blockade alters neural responses to drug Cues in humans with methamphetamine addiction and suggests that naltrexone may be reducing drug Cue salience by decreasing the involvement of sensorimotor regions and by engaging greater frontal regulation over salience attribution.
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neural substrates of Cue Reactivity association with treatment outcomes and relapse
Addiction Biology, 2016Co-Authors: Kelly E Courtney, Joseph P Schacht, Kent E Hutchison, Daniel J O Roche, Lara A RayAbstract:Given the strong evidence for neurological alterations at the basis of drug dependence, functional magnetic resonance imaging (fMRI) represents an important tool in the clinical neuroscience of addiction. fMRI Cue-Reactivity paradigms represent an ideal platform to probe the involvement of neurobiological pathways subserving the reward/motivation system in addiction and potentially offer a translational mechanism by which interventions and behavioral predictions can be tested. Thus, this review summarizes the research that has applied fMRI Cue-Reactivity paradigms to the study of adult substance use disorder treatment responses. Studies utilizing fMRI Cue-Reactivity paradigms for the prediction of relapse and as a means to investigate psychosocial and pharmacological treatment effects on Cue-elicited brain activation are presented within four primary categories of substances: alcohol, nicotine, cocaine and opioids. Lastly, suggestions for how to leverage fMRI technology to advance addiction science and treatment development are provided.
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the effect of alcohol priming on neural markers of alcohol Cue Reactivity
American Journal of Drug and Alcohol Abuse, 2015Co-Authors: Kelly E Courtney, Dara G Ghahremani, Lara A RayAbstract:AbstractBackground: Priming doses of alcohol are associated with increased desire to drink and disinhibitory effects on subsequent control over drinking. Despite the importance of alcohol priming in the Cue-Reactivity literature, the effects of priming on brain responses to alcohol Cues remains unclear. Furthermore, evidence suggests this relationship may be moderated by OPRM1 genotype. Methods: Twenty individuals with alcohol dependence (six females; 90% Caucasian; mean age = 29.4) who were prospectively genotyped on the OPRM1 gene underwent two functional magnetic resonance imaging (fMRI) sessions, before and after a priming dose of alcohol, each including a gustatory alcohol Cue Reactivity paradigm and self-reported craving measures. Results: Self-reported alcohol craving generally increased and remained higher for alcohol versus water Cue presentations across pre- and post-priming scans. Compared to alcohol Cues delivered during the post-priming scan, alcohol Cues delivered pre-priming were associated...
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effects of naltrexone on adolescent alcohol Cue Reactivity and sensitivity an initial randomized trial
Addiction Biology, 2014Co-Authors: Robert Miranda, Peter M Monti, Lara A Ray, Jennifer W Tidey, Robert M Swift, Alexander Blanchard, Elizabeth K Reynolds, Thomas H Chun, Alicia Justus, Chad J GwaltneyAbstract:Adolescent alcohol use is associated with myriad adverse consequences and contributes to the leading causes of mortality among youth. Despite the magnitude of this public health problem, evidenced-based treatment initiatives for alcohol use disorders in youth remain inadequate. Identifying promising pharmacological approaches may improve treatment options. Naltrexone is an opiate receptor antagonist that is efficacious for reducing drinking in adults by attenuating craving and the rewarding effects of alcohol. Implications of these findings for adolescents are unclear; however, given that randomized trials of naltrexone with youth are non-existent. We conducted a randomized, double-blinded, placebo-controlled cross-over study, comparing naltrexone (50 mg/daily) and placebo in 22 adolescent problem drinkers aged 15-19 years (M = 18.36, standard deviation = 0.95; 12 women). The primary outcome measures were alcohol use, subjective responses to alcohol consumption, and alcohol-Cue-elicited craving assessed in the natural environment using ecological momentary assessment methods, and craving and physiological Reactivity assessed using standard alcohol Cue Reactivity procedures. Results showed that naltrexone reduced the likelihood of drinking and heavy drinking (P's ≤ 0.03), blunted craving in the laboratory and in the natural environment (P's ≤ 0.04), and altered subjective responses to alcohol consumption (P's ≤ 0.01). Naltrexone was generally well tolerated by participants. This study provides the first experimentally controlled evidence that naltrexone reduces drinking and craving, and alters subjective responses to alcohol in a sample of adolescent problem drinkers, and suggests larger clinical trials with long-term follow-ups are warranted.