Neural Cue Reactivity Research Articles

Machine learning based classification of excessive smartphone users via neuronal cue reactivity

Excessive Smartphone Use (ESU) poses a significant challenge in contemporary society, yet its recognition as a distinct disorder remains ambiguous. This study aims to address this gap by leveraging functional magnetic resonance imaging (fMRI) data and machine learning techniques to classify ESU and non-excessive smartphone users (n-ESU) based on their neural Cue-Reactivity (CR) signatures. By conducting a CR task and analyzing brain activation patterns, we identified spatial similarities between addictive smartphone use and established addictive disorders. Our approach involved employing Support Vector Machines (SVM) for classification, enhanced with feature selection methods such as Recursive Feature Elimination (RFE) and Model-based Selection and dimensionality reduction methods such as and Principal Component Analysis (PCA) to mitigate the challenges posed by limited dataset size and high dimensionality of fMRI data. The results demonstrate the effectiveness of our classification model, achieving accuracies of up to 79.9 %. Furthermore, we observed region-specific activations contributing significantly to classification accuracy, highlighting the potential biomarkers associated with ESU. External validation on longitudinal data revealed the necessity for larger training datasets to improve model generalizability. Additionally, feature selection techniques proved crucial for optimizing model performance, particularly in datasets with combined information from multiple sources. Our findings underscore the importance of incorporating more data to enhance model stability and generalizability, with implications for advancing the understanding and treatment of ESU and related disorders. Overall, our study demonstrates the promise of machine learning approaches in elucidating neural correlates of ESU and informing targeted interventions for affected individuals.

Biological sex and hormonal contraceptive associations with drug cue reactivity in cannabis use disorder

Biological sex differences in Cannabis Use Disorder (CUD) progression, cannabis withdrawal severity, and pharmacotherapy response have been reported, suggesting that CUD mechanisms may differ by sex. Drug cue reactivity is an established predictor of drug use behavior, but the literature on sex differences in drug cue reactivity is mixed, including in CUD. One possible moderator of sex differences in drug cue reactivity is hormonal contraceptive (HC) use. The aim of the present study was to test whether sex differences in neural cannabis cue reactivity and craving varied by female HC use in a CUD sample. As part of a larger study, 152 adults reporting frequent cannabis use completed a drug cue reactivity task during electrocenphalogram recording. Late positive potential (LPP) amplitude modulation by cannabis cues was used to measure neural cue reactivity. Craving after the cue reactivity task was also assessed. Males (n = 74) and naturally-cycling females (n = 26), who did not differ from each other, showed significantly greater LPP enhancement to cannabis vs. neutral cues compared to HC-using females (n = 52), an effect mostly driven by neutral cues. Craving was significantly higher in naturally-cycling but not HC-using females compared to males, but only in covariate-unadjusted analyses. Exploratory analyses of HC and menstrual phase characteristics indicate a progesterone-related mechanism may underlie HC effects on cannabis cue reactivity. The present study's results suggest that mixed findings on drug cue reactivity sex differences may be due to variability in HC use, which has implications for sex-specific models of CUD progression and treatment.

Stress-Induced Sensitization of Insula Activation Predicts Alcohol Craving and Alcohol Use in Alcohol Use Disorder

BackgroundStress and alcohol cues trigger alcohol consumption and relapse in alcohol use disorder. However, the neurobiological processes underlying their interaction are not well understood. Thus, we conducted a randomized, controlled neuroimaging study to investigate the effects of psychosocial stress on neural cue reactivity and addictive behaviors. MethodsNeural alcohol cue reactivity was assessed in 91 individuals with alcohol use disorder using a validated functional magnetic resonance imaging (fMRI) task. Activation patterns were measured twice, at baseline and during a second fMRI session, prior to which participants were assigned to psychosocial stress (experimental condition) or a matched control condition or physical exercise (control conditions). Together with fMRI data, alcohol craving and cortisol levels were assessed, and alcohol use data were collected during a 12-month follow-up. Analyses tested the effects of psychosocial stress on neural cue reactivity and associations with cortisol levels, craving, and alcohol use. ResultsCompared with both control conditions, psychosocial stress elicited higher alcohol cue–induced activation in the left anterior insula (familywise error–corrected p < .05) and a stress- and cue-specific dynamic increase in insula activation over time (F22,968 = 2.143, p = .007), which was predicted by higher cortisol levels during the experimental intervention (r = 0.310, false discovery rate–corrected p = .016). Cue-induced insula activation was positively correlated with alcohol craving during fMRI (r = 0.262, false discovery rate–corrected p = .032) and alcohol use during follow-up (r = 0.218, false discovery rate–corrected p = .046). ConclusionsResults indicate a stress-induced sensitization of cue-induced activation in the left insula as a neurobiological correlate of the effects of psychosocial stress on alcohol craving and alcohol use in alcohol use disorder, which likely reflects changes in salience attribution and goal-directed behavior.

Erotic cue exposure increases neural reward responses without modulating temporal discounting

Abstract Humans prefer smaller sooner over larger later rewards, a tendency denoted as temporal discounting. Discounting of future rewards is increased in multiple maladaptive behaviors and clinical conditions. Although temporal discounting is stable over time, it is partly under contextual control. Appetitive (erotic) cues might increase preferences for immediate rewards, although evidence to date remains mixed. Reward circuit activity was hypothesized to drive increases in temporal discounting following cue exposure, yet this was never tested directly. We examined erotic vs. neutral cue exposure effects on subsequent temporal discounting in a preregistered within-subjects study in healthy male participants (n = 38). Functional magnetic resonance imaging assessed neural cue-reactivity, value-computations, and choice-related effects. We replicated previous findings of value-coding in ventromedial prefrontal cortices, striatum, and cingulate cortex. Likewise, as hypothesized, lateral prefrontal cortex activity increased during delayed reward choices, potentially reflecting cognitive control. Erotic cue exposure was associated with increased activity in attention and reward circuits. Contrary to preregistered hypotheses, temporal discounting was unaffected by cue exposure, and cue responses in reward circuits did not reliably predict changes in behavior. Our results raise doubts on the hypothesis that upregulation of (dopaminergic) reward systems following erotic cue exposure is sufficient to drive myopic approach behavior towards immediate rewards.

Emotional food-cue-reactivity in anorexia nervosa and bulimia nervosa: An electroencephalography study.

Food-cue-reactivity entails neural and experiential responses to the sight and smell of attractive foods. Negative emotions can modulate such cue-reactivity and this might be central to the balance between restrictive versus bulimic symptomatology in Anorexia Nervosa (AN) and Bulimia Nervosa (BN). Pleasantness ratings and electrocortical responses to food images were measured in patients with AN (n = 35), BN (n = 32) and matched healthy controls (HC, n = 35) in a neutral state and after idiosyncratic negative emotion induction while electroencephalography (EEG) was recorded. The EEG data were analyzed using a mass testing approach. Individuals with AN showed reduced pleasantness for foods compared to objects alongside elevated widespread occipito-central food-object discrimination between 170 and 535 ms, indicative of strong neural cue-reactivity. Food-object discrimination was further increased in the negative emotional condition between 690 and 1200 ms over centroparietal regions. Neither of these effects was seen in individuals with BN. Emotion modulated food-cue-reactivity in AN might reflect a decreased appetitive response in negative mood. Such specific (emotion-)regulatory strategies require more theoretical work and clinical attention. The absence of any marked effects in BN suggests that emotional cue-reactivity might be less prominent in this group or quite specific to certain emotional contexts or food types. Negative affectivity is a risk factor for the development of eating disorders and individuals with eating disorders experience problems with emotion regulation. To better understand the effects of negative emotions, the present study investigated how they affected neural correlates of food perception in anorexia nervosa and bulimia nervosa.

IL-6, but not TNF-α, response to alcohol cues and acute consumption associated with neural cue reactivity, craving, and future drinking in binge drinkers

Objective and designPreclinical studies suggest learned immune system responses to alcohol cues and consumption may contribute to alcohol's pharmacodynamic properties and/or Alcohol Use Disorder (AUD) pathogenesis. Mechanistically, these immune alterations may be associated with increased craving and alcohol consumption, both acutely and over time. We sought to characterize this relationship in a randomized, counter-balanced, crossover neuroimaging experiment which took place between June 2020–November 2021. MethodsThirty-three binge drinkers (BD) and 31 non-binge, social drinkers (SD), matched for demographic and psychological variables, were exposed to alcohol cues and water cues in two separate 7 T functional magnetic resonance imaging (fMRI) scans. Each scan was followed by the Alcohol Taste Test (ATT) of implicit motivation for acute alcohol. Craving measures and blood cytokine levels were collected repeatedly during and after scanning to examine the effects of alcohol cues and alcohol consumption on craving levels, Tumor necrosis factor alpha (TNF-α), and Interleukin 6 (IL-6) levels. A post-experiment one-month prospective measurement of participants’ “real world” drinking behavior was performed to approximate chronic effects. ResultsBD demonstrated significantly higher peak craving and IL-6 levels than SD in response to alcohol cues and relative to water cues. Ventromedial Prefrontal Cortex (VmPFC) signal change in the alcohol-water contrast positively related to alcohol cue condition craving and IL-6 levels, relative to water cue condition craving and IL-6 levels, in BD only. Additionally, peak craving and IL-6 levels were each independently related to ATT alcohol consumption and the number of drinks consumed in the next month for BD, again after controlling for craving and IL-6 repones to water cues. However, TNF-α release in the alcohol cue condition was not related to craving, neural activation, IL-6 levels, immediate and future alcohol consumption in either group after controlling for water cue condition responses. ConclusionsIn sum, BD show greater craving and IL-6 release in the alcohol cue condition than SD, both of which were associated with prefrontal cue reactivity, immediate alcohol consumption, and future alcohol consumption over the subsequent 30 days. Alcohol associated immune changes and craving effects on drinking behavior may be independent of one another or may be indicative of a common pathway by which immune changes in BD could influence motivation to consume alcohol. Trial registrationClinical Trials NCT04412824.

Neural cue reactivity is not stronger in male than in female patients with alcohol use disorder.

Males consume more alcohol than females, and alcohol use disorder (AUD) is more prevalent in males than females. However, females progress faster to AUD. Sex differences in neural alcohol cue reactivity were previously observed in young social drinkers, indicating a role of hypersensitivity to alcohol-related cues in very early stages of addiction. To our knowledge, this is the first study on patients diagnosed with AUD to test sex differences in neural reactivity to alcohol cues in order to widen previous findings. We analyzed data from previous studies, using a well-established functional magnetic resonance imaging (fMRI) paradigm to compare neural reactivity to alcohol cues between 42 female and 124 male patients with AUD (mean age 45 and 46 years) in predefined regions of interest that were implicated by previous studies (ventral and dorsal striatum as well as caudate, putamen, amygdala, hippocampus, insula, anterior cingulate cortex, and medial prefrontal cortex) using independent samples t-tests. Post-hoc, effect size calculations were performed. Throughout all nine regions of interest, we found no statistically significant sex differences in neural reactivity toward alcoholic pictures alone or in comparison to neutral pictures (p > 0.05, FDR-corrected). Post-hoc effect size estimates indicated a magnitude between 0.137 and 0.418 (Hedge's g) on alcohol reactivity to alcohol cues compared to neutral cues and indicate very small to less than medium effect sizes in the direction of higher cue reactivity in female patients. Previous studies showed sex differences in neural alcohol cue reactivity in younger social and problematic alcohol drinkers, i.e., stronger striatal cue-reactivity in males. After correction for multiple comparisons, we did not observe significant sex differences in a cohort of middle-aged females and males with AUD. Sex differences that are present during early phases of addiction development might disappear at later stages of AUD and might thus be considered as clinically less relevant in patients with more severe AUD.

Neural cue-reactivity in pathological gambling as evidence for behavioral addiction: a systematic review.

Increasing incidence of problem gambling has led to prioritizing the problem from the point of view of public health. Additionally, gambling disorder has been recently classified as a behavioral addiction, with implications for both its diagnosis and treatment. However, the shared neural substrate of addictions, to substances and behavioral, is still discussed. Thus, this systematic review aims to provide up-to-date knowledge from the past five years (2017-2022) concerning the neural correlates of gambling related stimuli (cue-reactivity) on the basis of a previous review (Brevers et al., Cognitive, Affective and Behavioral Neuroscience 18:718-729, 2019). A total of five studies were included in the review. Activation of brain areas related to memory, reward and executive functions could be the underlying mechanism of this behavioral addiction. Specifically, nucleus accumbens and striatum (ventral and dorsal), parahippocampal regions, the right amygdala and several prefrontal cortex regions have systematically been found more active in those subjects exposed to gambling-related cues. Also, the insula could play a pivotal role connecting these three systems in a highly integrated neural network with several implications for reward processing modulation, associative learning and top-down attentional regulation to improve saliency of addiction-related cues. These results are consistent with previous findings on other substance addictions, such as alcohol, tobacco, marijuana or cocaine. The study of neural reactivity to stimuli related to addiction could be useful as a biomarker of the severity of the disorder, the efficacy of the treatment, the risk of relapse, in addition to being an objective criterion to measure the effectiveness of prevention campaigns.

Plasma calcium concentration during detoxification predicts neural cue-reactivity and craving during early abstinence in alcohol-dependent patients

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.

BDNF influences neural cue-reactivity to food stimuli and food craving in obesity

There is increasing evidence that brain-derived neurotrophic factor (BDNF) impacts on the development of obesity. We are the first to test the hypothesis that BDNF levels might be associated with neural reactivity to food cues in patients suffering from obesity and healthy controls. We assessed visual food cue-induced neural response in 19 obese patients and 20 matched controls using functional magnetic resonance imaging and analyzed the associations between BDNF levels, food cue-reactivity and food craving. Whole-brain analysis in both groups revealed that food cues elicited higher neural activation in clusters of mesolimbic brain areas including the insula (food > neutral). Patients suffering from obesity showed a significant positive correlation between plasma BDNF levels and visual food cue-reactivity in the bilateral insulae. In addition, patients suffering from obesity with positive food cue-induced insula activation also reported significantly higher food craving than those with low cue-reactivity—an effect that was absent in normal weight participants. The present findings implicate that BDNF levels in patients suffering from obesity might be involved in food craving and obesity in humans. This highlights the importance to consider BDNF pathways when investigating obesity and obesity treatment.

P.016 Unraveling the role of cigarette use in neural cannabis cue reactivity in heavy cannabis users

P.016 Unraveling the role of cigarette use in neural cannabis cue reactivity in heavy cannabis users

Temporal Dynamics of Large-Scale Networks Predict Neural Cue Reactivity and Cue-Induced Craving

BackgroundCue reactivity, a core characteristic of substance use disorders, commonly recruits brain regions that are key nodes in neurocognitive networks, including the default mode network (DMN) and salience network (SN). Whether resting-state temporal dynamic properties of these networks relate to subsequent cue reactivity and cue-induced craving is unknown. MethodsThe resting-state data of 46 nicotine-dependent participants were assessed to define temporal dynamic properties of DMN and SN states. Temporal dynamics focused on the total time across the scan session that brain activity resides in these specific states. Using regression models, we examined how the total time in each state related to neural reactivity to smoking cues within key DMN (posterior cingulate cortex, medial prefrontal cortex) or SN (anterior insula, dorsal anterior cingulate cortex) nodes. Mediation analyses were subsequently conducted to study how neural cue reactivity mediates the relationship between total time in state at rest and subjective cue-induced craving. ResultsIncreased time spent in the DMN state and decreased time spent in the SN state predicted subsequent cue-induced increases in the anterior insula and dorsal anterior cingulate cortex, respectively. Cue-induced anterior insula and dorsal anterior cingulate cortex activity significantly mediated the relationship between time spent in DMN/SN and cue-induced subjective craving. ConclusionsOur findings showed a significant relationship between resting-state dynamics of the DMN/SN and task-activated SN nodes that together predicted cue-induced craving changes in nicotine-dependent individuals. These findings propose a neurobiological pathway for cue-induced craving that begins with resting-state temporal dynamics, suggesting that brain responding to external stimuli is driven by resting temporal dynamics.

Convergent cross-sectional and longitudinal evidence for gaming-cue specific posterior parietal dysregulations in early stages of internet gaming disorder.

Exaggerated reactivity to drug-cues and emotional dysregulations represent key symptoms of early stages of substance use disorders. The diagnostic criteria for (Internet) gaming disorder strongly resemble symptoms for substance-related addictions. However, previous cross-sections studies revealed inconsistent results with respect to neural cue reactivity and emotional dysregulations in these populations. To this end, the present fMRI study applied a combined cross-sectional and longitudinal design in regular online gamers (n = 37) and gaming-naïve controls (n = 67). To separate gaming-associated changes from predisposing factors, gaming-naive subjects were randomly assigned to 6 weeks of daily Internet gaming or a non-gaming condition. At baseline and after the training, subjects underwent an fMRI paradigm presenting gaming-related cues and non-gaming-related emotional stimuli. Cross-sectional comparisons revealed gaming-cue specific enhanced valence attribution and neural reactivity in a parietal network, including the posterior cingulate in regular gamers as compared to gaming naïve-controls. Longitudinal analysis revealed that 6 weeks of gaming elevated valence ratings as well as neural cue-reactivity in a similar parietal network, specifically the posterior cingulate in previously gaming-naïve controls. Together, the longitudinal design did not reveal supporting evidence for altered emotional processing of non-gaming associated stimuli in regular gamers whereas convergent evidence for increased emotional and neural reactivity to gaming-associated stimuli was observed. Findings suggest that exaggerated neural reactivity in posterior parietal regions engaged in default mode and automated information processing already occur during early stages of regular gaming and probably promote continued engagement in gaming behavior.

Interaction between behavioral inhibition and neural alcohol cue-reactivity in ADHD and alcohol use disorder

RationaleCompared to the general population, adult Attention-Deficit / Hyperactivity Disorder (ADHD) is more prevalent in patients with Alcohol Use Disorder (AUD). Impaired behavioral inhibition is a common characteristic in both ADHD and AUD. Relapse risk is increased in patients with AUD and comorbid, untreated ADHD and in AUD patients with increased neural cue-reactivity.ObjectivesIn this study, we examined the interaction between neural correlates of behavioral inhibition and alcohol cue-reactivity with a hybrid imaging task.MethodsOut of 69 adult study participants, we included n = 49 in our final analyses: Individuals had a diagnosis of either AUD (n = 13), ADHD (n = 14) or both (n = 5), or were healthy controls (HC; n = 17). The functional magnetic resonance imaging paradigm aimed to examine the combined effects of both an interference-inhibition task (“Simon-task”) and an alcohol cue-reactivity task. Instead of segregating by diagnostic group, we pursued a dimensional approach in which we compared measures of AUD and ADHD severity, as well as the interaction of both, using multiple regression analyses.ResultsThe four groups did not differ on the behavioral level on either the inhibition task or the alcohol cue-reactivity task. However, brain activation in frontal control and reward-related regions during completion of the combined tasks were related to ADHD and AUD severity (symptom load). During presentation of both alcohol cues and the inhibition task, participants with higher AUD and ADHD symptom load exhibited greater BOLD (blood oxygen level dependent) responses in subcortical reward-related regions.ConclusionsOur findings support the hypothesis that ADHD additionally diminishes inhibition ability in individuals with AUD. This may increase relapse risk when confronted with alcohol cues. Further, it is crucial for patients with comorbid AUD and ADHD to take into account not only reduced cognitive control over behavioral inhibition but also simultaneously heightened alcohol cue-reactivity.

Examining neural reactivity to gambling cues in the age of online betting.

The goal of this review is to provide new insights as to how and why functional magnetic resonance imaging (fMRI) research on gambling cue reactivity can contribute to significant progress towards the understanding of gambling disorder. After having offered a detailed description of experimental paradigms and a comprehensive summary of findings related to gambling cue reactivity, the present review suggests methodological avenues for future research. The fMRI literature on problem gambling has identified the main neural pathways associated with reactivity to gambling cues. Yet, the current knowledge on the key factors underlying cue reactivity in gambling is still very incomplete. Here, we suggest that the recent expansion of online sports betting calls for a new line of research offering a fine-grained and up-to-date approach of neural cue reactivity in gambling disorder. Experimental designs that investigate individual-specific and study-specific factors related to sports betting have the potential to foster progress towards efficient treatment and prevention of gambling disorder.

S211. Sex Differences in Neural Cue-Reactivity are Moderated by Early Life and Currently Perceived Stress in a Population of Heavy Drinkers

S211. Sex Differences in Neural Cue-Reactivity are Moderated by Early Life and Currently Perceived Stress in a Population of Heavy Drinkers

Cue Reactivity in the Ventral Striatum Characterizes Heavy Cannabis Use, Whereas Reactivity in the Dorsal Striatum Mediates Dependent Use

BackgroundAnimal models of addiction suggest that the transition from incentive-driven drug use to habitual and ultimately compulsive drug use is mediated by a shift from ventral to dorsal striatal cue control over drug seeking. Previous studies in human cannabis users reported elevated trait impulsivity and neural cue reactivity in striatal circuits; however, these studies were not able to separate addiction-related from exposure-related adaptations. MethodsTo differentiate the adaptive changes, the current functional magnetic resonance imaging study examined behavioral and neural cue reactivity in dependent (n = 18) and nondependent (n = 20) heavy cannabis users and a nonusing reference group (n = 44). ResultsIrrespective of dependence status, cannabis users demonstrated elevated trait impulsivity as well as increased ventral striatal reactivity and striatal frontal coupling in response to drug cues. Dependent users selectively exhibited dorsal striatal reactivity and decreased striatal limbic coupling during cue exposure. An exploratory analysis revealed that higher ventral caudate neural cue reactivity was associated with stronger cue-induced arousal and craving in dependent users, whereas this pattern was reversed in nondependent users. ConclusionsTaken together, the current findings suggest that exaggerated responses of the ventral striatal reward system may promote excessive drug use in humans, whereas adaptations in dorsal striatal systems engaged in habit formation may promote the transition to addictive use.

Neural cue reactivity during acute abstinence predicts short-term smoking relapse.

In smokers, neural responses to smoking cues can be sensitive to acute abstinence, but the degree to which abstinence-related cue reactivity contributes to relapse is not fully understood. This study addressed this question in a sample of 75 smokers who were motivated to quit smoking. Participants underwent blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) during presentation of visual smoking cues and neutral stimuli on two occasions: once during smoking satiety and once following 24-hour abstinence (order counterbalanced). Following the imaging sessions, participants received brief smoking cessation counseling prior to a short-term (7-day) quit attempt. The primary smoking cessation outcome was biochemically confirmed 7-day relapse. The secondary smoking cessation outcome measure was total number of self-reported days of abstinence. During abstinence (vs satiety), smoking cue reactivity was significantly increased only in the anterior cingulate cortex (ACC); other regions showing a cue (vs neutral) response did not exhibit an abstinence effect in the stringent whole-brain analysis. Participants who showed greater smoking cue reactivity in the ACC during acute abstinence (compared with smoking satiety) were more likely to relapse (OR=2.10 per standard deviation increase in percent signal change [abstinence minus smoking satiety], 95% CI: 1.05 to 4.20, P=0.036). Greater abstinence-induced change in ACC activation also predicted fewer total days abstinent (β=-0.63, 95% CI=0.43 to 0.66, P<0.0001). This study provides the first evidence that changes in smoking cue reactivity in the ACC during acute abstinence predict smoking relapse, thereby improving our understanding of the neurobiology of smoking cessation.

Elucidating the Effect of a Brief Drinking Intervention Using Neuroimaging: A Preliminary Study.

Brief interventions have empirical support for acutely reducing alcohol use among non-treatment-seeking heavy drinkers. Neuroimaging techniques allow for the examination of the neurobiological effect of behavioral interventions, probing brain systems putatively involved in clinical response to treatment. Few studies have prospectively evaluated whether psychosocial interventions attenuate neural cue reactivity that in turn reduces drinking in the same population. This study aimed to examine the effect of a brief intervention on drinking outcomes, neural alcohol cue reactivity, and the ability of neural alcohol cue reactivity to prospectively predict drinking outcomes. Non-treatment-seeking heavy drinking participants were randomized to receive a brief interview intervention (n=22) or an attention-matched control (n=24). Immediately following the intervention or control, participants underwent a functional magnetic resonance imaging scan comprised of the alcohol taste cues paradigm. Four weeks after the intervention (or control), participants completed a follow-up visit to report on their past-month drinking. Baseline and follow-up percent heavy drinking days (PHDD) were calculated for each participant. There was no significant effect of the brief intervention on PHDD at follow-up or on modulating neural activation to alcohol relative to water taste cues. There was a significant association between neural response to alcohol taste cues and PHDD across groups (Z>2.3, p<0.05), such that individuals who had greater neural reactivity to alcohol taste cues in the precuneus and prefrontal cortex (PFC) had fewer PHDD at follow-up. This study did not find an effect of the brief intervention on alcohol use in this sample, and the intervention was not associated with differential neural alcohol cue reactivity. Nevertheless, greater activation of the precuneus and PFC during alcohol cue exposure predicted less alcohol use prospectively suggesting that these neural substrates subserve the effects of alcohol cues on drinking behavior.

Effects of leptin and ghrelin on neural cue-reactivity in alcohol addiction: Two streams merge to one river?

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.