A systematic review and meta-analysis of neuromodulation therapies for substance use disorders.

While pharmacological, behavioral and psychosocial treatments are available for substance use disorders (SUDs), they are not always effective or well-tolerated. Neuromodulation (NM) methods, including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS) may address SUDs by targeting addiction neurocircuitry. We evaluated the efficacy of NM to improve behavioral outcomes in SUDs. A systematic literature search was performed on MEDLINE, PsychINFO, and PubMed databases and a list of search terms for four key concepts (SUD, rTMS, tDCS, DBS) was applied. Ninety-four studies were identified that examined the effects of rTMS, tDCS, and DBS on substance use outcomes (e.g., craving, consumption, and relapse) amongst individuals with SUDs including alcohol, tobacco, cannabis, stimulants, and opioids. Meta-analyses were performed for alcohol and tobacco studies using rTMS and tDCS. We found that rTMS reduced substance use and craving, as indicated by medium to large effect sizes (Hedge's g > 0.5). Results were most encouraging when multiple stimulation sessions were applied, and the left dorsolateral prefrontal cortex (DLPFC) was targeted. tDCS also produced medium effect sizes for drug use and craving, though they were highly variable and less robust than rTMS; right anodal DLPFC stimulation appeared to be most efficacious. DBS studies were typically small, uncontrolled studies, but showed promise in reducing misuse of multiple substances. NM may be promising for the treatment of SUDs. Future studies should determine underlying neural mechanisms of NM, and further evaluate extended treatment durations, accelerated administration protocols and long-term outcomes with biochemical verification of substance use.

Randomized trial of mindfulness- and reappraisal-based regulation of craving training among daily cigarette smokers.

OBJECTIVE: Craving predicts smoking, yet existing interventions may not adequately target regulation of craving. We evaluated two versions of regulation of craving-training (ROC-T), a computerized intervention with intensive practice of strategies when exposed to smoking-related images. METHOD: Ninety-two nicotine-dependent daily smokers were randomized to mindfulness-based therapy (MBT) ROC-T focusing on mindful acceptance, and cognitive behavioral therapy (CBT) ROC-T focusing on reappraisal or no intervention control. The ROC task was administered pre- and postintervention to assess changes in cue-induced craving and mindfulness- and reappraisal-based regulation of craving. RESULTS: MBT and CBT-versus control-showed significantly greater reductions in smoking during the intervention phase (baseline to Week 4), corresponding to large (d = -1.08, 95% CI [-1.64, -0.52]) and medium-to-large effect sizes (d = -0.69, 95% CI [-1.22, -0.15]), respectively. During follow-up (Week 4-16), CBT showed significant increases in smoking, whereas MBT and control did not. For the entire study (baseline to Week 16), MBT showed significantly greater reductions in smoking compared to control (d = -1.6, 95% CI [-2.56, -0.66]) but CBT was not significantly different than control (d = -0.82, 95% CI [-1.77, 0.13]). There were no effects on smoking when directly comparing MBT and CBT. Quit rates were low across the sample, with no difference among conditions. MBT and CBT-versus control-significantly reduced cue-induced craving. CBT (but not MBT)-versus control-significantly improved reappraisal-based regulation of craving. Both MBT and CBT-versus control-significantly improved mindfulness-based regulation of craving. CONCLUSIONS: MBT- and CBT-ROC-T may reduce cue-induced craving and smoking, and MBT may be more durable than CBT. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Connectome-based prediction of craving in gambling disorder and cocaine use disorder.

INTRODUCTION: Craving, involving intense and urgent desires to engage in specific behaviours, is a feature of addictions. Multiple studies implicate regions of salience/limbic networks and basal ganglia, fronto-parietal, medial frontal regions in craving in addictions. However, prior studies have not identified common neural networks that reliably predict craving across substance and behavioural addictions. METHODS: Functional magnetic resonance imaging during an audiovisual cue-reactivity task and connectome-based predictive modelling (CPM), a data-driven method for generating brain-behavioural models, were used to study individuals with cocaine-use disorder and gambling disorder. Functions of nodes and networks relevant to craving were identified and interpreted based on meta-analytic data. RESULTS: Craving was predicted by neural connectivity across disorders. The highest degree nodes were mostly located in the prefrontal cortex. Overall, the prediction model included complex networks including motor/sensory, fronto-parietal, and default-mode networks. The decoding revealed high functional associations with components of memory, valence ratings, physiological responses, and finger movement/motor imagery. CONCLUSIONS: Craving could be predicted across substance and behavioural addictions. The model may reflect general neural mechanisms of craving despite specificities of individual disorders. Prefrontal regions associated with working memory and autobiographical memory seem important in predicting craving. For further validation, the model should be tested in diverse samples and contexts.

Thalamic volume and functional connectivity are associated with nicotine dependence severity and craving.

Tobacco smoking is associated with deleterious health outcomes. Most smokers want to quit smoking, yet relapse rates are high. Understanding neural differences associated with tobacco use may help generate novel treatment options. Several animal studies have recently highlighted the central role of the thalamus in substance use disorders, but this research focus has been understudied in human smokers. Here, we investigated associations between structural and functional magnetic resonance imaging measures of the thalamus and its subnuclei to distinct smoking characteristics. We acquired anatomical scans of 32 smokers as well as functional resting-state scans before and after a cue-reactivity task. Thalamic functional connectivity was associated with craving and dependence severity, whereas the volume of the thalamus was associated with dependence severity only. Craving, which fluctuates rapidly, was best characterized by differences in brain function, whereas the rather persistent syndrome of dependence severity was associated with both brain structural differences and function. Our study supports the notion that functional versus structural measures tend to be associated with behavioural measures that evolve at faster versus slower temporal scales, respectively. It confirms the importance of the thalamus to understand mechanisms of addiction and highlights it as a potential target for brain-based interventions to support smoking cessation, such as brain stimulation and neurofeedback.

TMS for the functional evaluation of cannabis effects and for treatment of cannabis addiction: A review.

The knowledge about the effects of cannabis on human cortical brain processes is increasing. In this regard, transcranial magnetic stimulation (TMS) enables the evaluation of central nervous system function, including drug effects. Moreover, repetitive TMS (rTMS) has been used therapeutically in several substance use disorders. In this scoping review, we summarize and discuss studies that have employed TMS and rTMS techniques in users of cannabis for recreational purposes. In subjects with a history of persistent cannabis use, TMS studies showed reduced short-interval cortical inhibition (SICI). This observation points more at neurobiological changes of chronic cannabis use than to a direct effect of cannabis on gamma-aminobutyric acid (GABA) A receptors. Moreover, individuals vulnerable to becoming long-term users of cannabis may also have underlying pre-existing abnormalities in SICI. Of note, the use of cannabis is associated with an increased risk of schizophrenia, and the down-regulation of GABAergic function may play a role. Less frequent cannabis use and spontaneous craving were observed following rTMS applied to the dorsolateral prefrontal cortex (DLPFC). There is emerging evidence that the posterior cingulate cortex and the precuneus are potential targets for rTMS intervention in cannabis use disorder. However, larger and randomized trials should corroborate these encouraging findings.

Brain responses to drug cues predict craving changes in abstinent heroin users: A preliminary study.

BACKGROUND: Loss of control over drug intake occurring in drug addiction is believed to result from disruption of reward circuits, including reduced responsiveness to natural rewards (e.g., monetary, sex) and heightened responsiveness to drug reward. Yet few studies have assessed reward deficiency and related brain responses in abstinent heroin users with opioid use disorder, and less is known whether the brain responses can predict cue-induced craving changes following by prolonged abstinence. METHOD: 31 heroin users (age: 44.13±7.68 years, male: 18 (58%), duration of abstinence: 85.2 ± 52.5 days) were enrolled at a mandatory detoxification center. By employing a cue-reactivity paradigm including three types of cues (drug, sexual, neutral), brain regional activations and circuit-level functional coupling were extracted. Among the 31 heroin users, 15 were followed up longitudinally to assess cue induced craving changes in the ensuing 6 months. RESULTS: One way analysis of variance results showed that heroin users have differential brain activations to the three cues (neutral, drug and sexual) in the left dorsolateral prefrontal cortex (DLPFC), insula, orbiotofrontal cortex (OFC) and the bilateral thalamus. Drug cue induced greater activations in left DLPFC, insula and OFC compared to sexual cue. The psychophysiological interactions (PPI) analysis revealed negative couplings of the left DLPFC and the left OFC, bilateral thalamus, putamen in heroin users during drug cue exposure. In the 6-month follow-up study, both drug cue induced activation of the left DLPFC and the functional coupling of the left DLPFC-bilateral thalamus at baseline was correlated with craving reductions, which were not found for sexual cues. CONCLUSION: Our preliminary study provided novel evidence for the reward deficiency theory of opioid use disorder. Our findings also have clinical implications, as drug cue induced activation of the left DLPFC and functional coupling of left DLPFC-bilateral thalamus may be potential neuroimaging markers for craving changes during prolonged abstinence. Evidently, the findings in the current preliminary study should be confirmed by large sample size in the future.

Cigarette craving modulation is more feasible than resistance modulation for heavy cigarette smokers: empirical evidence from functional MRI data.

BACKGROUND: Modulation of cigarette craving and neuronal activations from nicotine-dependent cigarette smokers using real-time functional MRI (rtfMRI)-based neurofeedback (rtfMRI-NF) has been previously reported. OBJECTIVES: The aim of this study was to evaluate the efficacy of rtfMRI-NF training in reducing cigarette cravings using fMRI data acquired before and after training. METHODS: Treatment-seeking male heavy cigarette smokers (N = 14) were enrolled and randomly assigned to two conditions related to rtfMRI-NF training aiming at resisting the urge to smoke. In one condition, subjects underwent conventional rtfMRI-NF training using neuronal activity as the neurofeedback signal (activity-based) within regions-of-interest (ROIs) implicated in cigarette craving. In another condition, subjects underwent rtfMRI-NF training with additional functional connectivity information included in the neurofeedback signal (functional connectivity-added). Before and after rtfMRI-NF training at each of two visits, participants underwent two fMRI runs with cigarette smoking stimuli and were asked to crave or resist the urge to smoke without neurofeedback. Cigarette craving-related or resistance-related regions were identified using a general linear model followed by paired t-tests and were evaluated using regression analysis on the basis of neuronal activation and subjective craving scores (CRSs). RESULTS: Visual areas were mainly implicated in craving, whereas the superior frontal areas were associated with resistance. The degree of (a) CRS reduction and (b) the correlation between neuronal activation and CRSs were statistically significant (P < 0.05) in the functional connectivity-added neurofeedback group for craving-related ROIs. CONCLUSION: Our study demonstrated the feasibility of altering cigarette craving in craving-related ROIs but not in resistance-related ROIs via rtfMRI-NF training.

Use of Real-Time Functional Magnetic Resonance Imaging-Based Neurofeedback to Downregulate Insular Cortex in Nicotine-Addicted Smokers.

It has been more than a decade since the first functional magnetic resonance imaging (fMRI)-based neurofeedback approach was successfully implemented. Since then, various studies have demonstrated that participants can learn to voluntarily control a circumscribed brain region. Consequently, real-time fMRI (rtfMRI) provided a novel opportunity to study modifications of behavior due to manipulation of brain activity. Hence, reports of rtfMRI applications to train self-regulation of brain activity and the concomitant modifications in behavioral and clinical conditions such as neurological and psychiatric disorders [e.g., schizophrenia, obsessive compulsive Disorder (OCD), stroke] have rapidly increased. Neuroimaging studies in addiction research have shown that the anterior cingulate cortex, orbitofrontal cortex, and insular cortex are activated during the presentation of drug-associated cues. Also, activity in both left and right insular cortices have been shown to be highly correlated with drug urges when participants are exposed to craving-eliciting cues. Hence, the bilateral insula is of particular importance in researching drug urges and addiction due to its role in the representation of bodily (interoceptive) states. This study explores the use of rtfMRI neurofeedback for the reduction in blood oxygen-level dependent (BOLD) activity in bilateral insular cortices of nicotine-addicted participants. The study also tests if there are neurofeedback training-associated modifications in the implicit attitudes of participants towards nicotine-craving cues and explicit-craving behavior.

PPARγ activation by pioglitazone does not suppress cravings for alcohol, and is associated with a risk of myopathy in treatment seeking alcohol dependent patients: a randomized controlled proof of principle study.

RATIONALE: Proinflammatory processes have been implicated in alcohol addiction, craving, and relapse, while studies in experimental animals have suggested that activation of peroxisome proliferator-activated receptor gamma (PPARγ) inhibits proinflammatory signaling. Accordingly, it is hypothesized that medications with PPARγ activity may have therapeutic potential in alcohol dependence. OBJECTIVES: We conducted a double-blind, placebo-controlled mechanistic proof of principle study in alcohol-dependent inpatients to investigate the effect of pioglitazone on alcohol craving. METHODS: Participants were treated for withdrawal, if needed, and then randomized to pioglitazone (target dose 45 mg/day) or placebo. Once at target dose, they completed two experimental manipulations: guided imagery, which used personalized auditory scripts to induce alcohol cravings, and a low-dose challenge with i.v. lipopolysaccharide (LPS; 0.8 ng/kg) or placebo, on two separate sessions, in counterbalanced order. Behavioral and endocrine responses as well as CSF levels of proinflammatory cytokines were evaluated. RESULTS: The study was prematurely terminated after randomization of 16 subjects, following an independent review that established a high risk of myopathy in the active treatment group. Analysis of those who completed the study indicated that pioglitazone was associated with elevated, rather than suppressed alcohol cravings in response to alcohol-associated stimuli. LPS did not induce cravings for alcohol and thus did not lend itself to evaluating pioglitazone effects; however, pioglitazone increased the neuroendocrine stress response to LPS. CSF levels of IL-6, TNF-α, or MCP-1 were unaffected by pioglitazone treatment. CONCLUSIONS: Both safety and efficacy biomarker data suggest that pioglitazone lacks potential as a medication for the treatment of alcohol dependence. CLINICAL TRIAL REGISTRATION: NCT01631630.

Disrupting the path to craving: Acting without awareness mediates the link between negative affect and craving.

Low treatment utilization, relapse, and chronicity are characteristic of substance use disorders (SUDs). Craving is an important predictor of relapse. Individuals with an SUD report using various coping strategies in response to negative affect, two of which are investigated in the current study: suppression and acting with awareness. Suppression is typically understood to be avoidance of unwanted experience through turning attention away from unwanted stimuli. Acting with awareness (AWA) is a facet of mindfulness, which includes turning toward experience with kindness and curiosity, even when the experience is unwanted. Evidence suggests mindfulness may reduce craving, while suppression has been associated with increased craving. In the current study, participants (N = 210) had recently completed inpatient or intensive outpatient SUD treatment followed by a randomized controlled trial of aftercare. Participants completed measures within 2 weeks following the completion of the aftercare intervention. Negative affect and severity of dependence were both positively associated with craving. Structural equation modeling evaluated AWA and suppression as partial mediators of the link between negative affect and craving. Suppression was positively associated and AWA was negatively associated with craving. Mediation analyses revealed the indirect effect of negative affect on craving through AWA was significant, but the path through suppression was not. These findings suggest that AWA may inhibit the development of craving from negative affect, but further research is needed. Future research should investigate the path from negative affect to craving with greater temporal resolution to evaluate how these phenomena function with increased ecological validity. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Wearable sensor-based detection of stress and craving in patients during treatment for substance use disorder: A mixed methods pilot study.

AIMS: To determine the accuracy of a wearable sensor to detect and differentiate episodes of self-reported craving and stress in individuals with substance use disorders, and to assess acceptability, barriers, and facilitators to sensor-based monitoring in this population. METHODS: This was an observational mixed methods pilot study. Adults enrolled in an outpatient treatment program for a substance use disorder wore a non-invasive wrist-mounted sensor for four days and self-reported episodes of stress and craving. Continuous physiologic data (accelerometry, skin conductance, skin temperature, and heart rate) were extracted from the sensors and analyzed via various machine learning algorithms. Semi-structured interviews were conducted upon study completion, and thematic analysis was conducted on qualitative data from semi-structured interviews. RESULTS: Thirty individuals completed the protocol, and 43 % (N = 13) were female. A total of 41 craving and 104 stress events were analyzed. The differentiation accuracies of the top performing models were as follows: stress vs. non-stress states 74.5 % (AUC 0.82), craving vs. no-craving 75.7 % (AUC 0.82), and craving vs. stress 76.8 % (AUC 0.8). Overall participant perception was positive, and acceptability was high. Emergent themes from the exit interviews included a perception of connectedness and increased mindfulness related to wearing the sensor, both of which were reported as helpful to recovery. Barriers to engagement included interference with other daily wear items, and perceived stigma. CONCLUSIONS: Wearable sensors can be used to objectively differentiate episodes of craving and stress, and individuals in recovery from substance use disorder are accepting of continuous monitoring with these devices.

The effects of mindfulness-based yogic breathing on craving, affect, and smoking behavior.

Breathing practices are often incorporated into treatments for tobacco dependence, but there is little direct research testing the efficacy of breathing practices. This study examined the effects of a mindfulness-based yogic breathing (MB) intervention versus active treatment (cognitive strategy [CS]) and no-treatment (NT) control groups on craving, affect, withdrawal, and smoking behavior. Smokers (N = 60; 50% female; 83% African American) were randomized to receive 20 min of MB, CS, or NT. Participants completed self-report measures before and after the manipulation and then took part in a 50-min smoking choice procedure. Afterward, participants were advised to use the techniques they learned and self-monitor smoking for 24 hr. They received 3 reminder text messages and returned to the lab the following day. MB and CS were more effective than NT in decreasing craving to smoke and perceived nicotine withdrawal. MB, but not CS, was more effective than NT in reducing negative affect. MB reduced the risk of smoking by more than twofold relative to both CS and NT during the smoking choice procedure. Participants in the MB condition smoked fewer cigarettes than those in the CS and NT conditions in the 24 hr following the manipulation. There were no differential effects of the manipulations on state mindfulness or positive affect. Mindful yogic breathing appears to be particularly effective in alleviating the acute negative effects of smoking abstinence and decreasing smoking behavior. Mindful breathing techniques are safe, simple, and cost-effective strategies that deserve additional research attention, especially among underserved populations of smokers. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Brain Stimulation to Modulate Food Intake and Eating Behavior.

PURPOSE OF REVIEW: Appetitive behaviors are mediated through homeostatic and reward signaling of brain circuits. There has been increasing interest in the use of neuromodulation techniques aimed at targeting brain regions such as the lateral prefrontal and subcortical regions associated with dysregulation of eating behaviors. RECENT FINDINGS: Invasive brain stimulation techniques have demonstrated promising results in treating severe and enduring anorexia nervosa and morbid obesity. In addition, non-invasive techniques have been shown to successfully reduce food craving, hunger ratings, and calorie intake as well as binge/purge symptoms in eating disorders. Brain stimulation offers promising results for treating symptoms associated with eating disorders and modifying appetitive behaviors including craving and caloric consumption. Future research should focus on identifying optimal frequency and duration of stimulation and employ longitudinal studies to assess long-term effectiveness on clinical outcomes such as eating disorder symptomatology, weight loss, and sustained improvements in eating behaviors over time.

Current understanding of premonitory networks in migraine: A window to attack generation.

AIM: To describe neuronal networks underlying commonly reported migraine premonitory symptoms and to discuss how these might precipitate migraine pain. BACKGROUND: Migraine headache is frequently preceded by a distinct and well characterized premonitory phase including symptoms like yawning, sleep disturbances, alterations in appetite and food intake and hypersensitivity to certain external stimuli. Recent neuroimaging studies strongly suggest the hypothalamus as the key mediator of the premonitory phase and also suggested alterations in hypothalamic networks as a mechanism of migraine attack generation. When looking at the vast evidence from basic research within the last decades, hypothalamic and thalamic networks are most likely to integrate peripheral influences with central mechanisms, facilitating the precipitation of migraine headaches. These networks include sleep, feeding and stress modulating centers within the hypothalamus, thalamic pathways and brainstem centers closely involved in trigeminal pain processing such as the spinal trigeminal nucleus and the rostral ventromedial medulla, all of which are closely interconnected. CONCLUSION: Taken together, these networks represent the pathophysiological basis for migraine premonitory symptoms as well as a possible integration site of peripheral so-called "triggers" with central attack facilitating processes.

Distinct gene alterations between Fos-expressing striatal and thalamic neurons after withdrawal from methamphetamine self-administration.

BACKGROUND: Methamphetamine (Meth) seeking progressively increases after withdrawal (incubation of Meth craving). We previously demonstrated a role of anterior intralaminar nucleus of thalamus (AIT) to dorsomedial striatum (DMS) projections in this incubation. Here, we examined molecular alterations in DMS and AIT neurons activated (identified by neuronal activity marker Fos) during "incubated" Meth-seeking relapse test after prolonged withdrawal. METHODS: We trained male rats to self-administer Meth or saline (control condition) for 10 days (6 hr/day). Using fluorescence-activated cell sorting, we examined gene expression in Fos-positive (activated during a 2-hr relapse test) and Fos-negative (nonactivated) DMS and AIT neurons. RESULTS: In DMS, we found increased mRNA expressions of immediate early genes (IEGs) (Arc, Egr1, Npas4, Fosb), Trkb, glutamate receptors subunits (Gria3, Grin1, Grin2b, Grm1), and epigenetic enzymes (Hdac3, Hdac5, Crebbp) in Fos-positive neurons, compared with Fos-negative neurons. In AIT, we found that fewer genes (Egr1, Fosb, TrkB, Grin1, and Hdac5) exhibited increased mRNA expression in Fos-positive neurons. Unexpectedly, in both brain regions, gene alterations described above also occurred in drug-naïve saline self-administration control rats. CONCLUSIONS: These results demonstrated that transcriptional regulations in Fos-positive neurons activated during the relapse tests are brain region-specific but are not uniquely associated with drug exposure during the self-administration training.

Effects of Cognitive Strategies on Neural Food Cue Reactivity in Adults with Overweight/Obesity.

OBJECTIVE: Functional magnetic resonance imaging (fMRI) studies of obesity have revealed key roles for reward-related and inhibitory control-related activity in response to food cues. This study examines how cognitive strategies impact neural food cue reactivity. METHODS: In a within-participants, block-design, fMRI paradigm, 30 participants (24 women; mean BMI = 31.8) used four mind-sets while viewing food: "distract" (cognitive behavioral therapy based), "allow" (acceptance and commitment therapy based), "later" (focusing on long-term negative consequences), and "now" (control; focusing on immediate rewards). Participants rated cravings by noting urges to eat on four-point Likert scales after each block. RESULTS: Self-reported cravings significantly differed among all conditions (pairwise comparisons P < 0.05). Cravings were lowest when participants considered long-term consequences (LATER mind-set: 1.7 [SD 0.7]), were significantly higher when participants used the DISTRACT (1.9 [SD 0.7]) and ALLOW (2.3 [SD 0.9]) mind-sets, and were highest when participants used the NOW mind-set (3.2 [SD 0.7]). These behavioral differences were accompanied by differences in neural food cue reactivity. The LATER mind-set (long-term consequences) led to greater inhibitory-control activity in the dorsolateral prefrontal cortex. The cognitive behavioral therapy-based DISTRACT mind-set was associated with greater activity in executive function and reward-processing areas, whereas the ALLOW mind-set (acceptance and commitment therapy) elicited widespread activity in frontal, reward-processing, and default-mode regions. CONCLUSIONS: Because focusing on negative long-term consequences led to the greatest decrease in cravings and increased inhibitory control, this may be a promising treatment strategy for obesity.

Hypothalamic Responses to Cocaine and Food Cues in Individuals with Cocaine Dependence.

BACKGROUND: Individuals with cocaine addiction are characterized by under-responsiveness to natural reinforcers. As part of the dopaminergic pathways, the hypothalamus supports motivated behaviors. Rodent studies suggested inter-related roles of the hypothalamus in regulating drug and food intake. However, few studies have investigated hypothalamic responses to drugs and food or related cues in humans. METHODS: We examined regional responses in 20 cocaine-dependent and 24 healthy control participants exposed to cocaine/food (cocaine dependent) and food (healthy control) vs neutral cues during functional magnetic resonance imaging. We examined the relationship between imaging findings and clinical variables and performed mediation analyses to examine the inter-relationships between cue-related activations, tonic cocaine craving, and recent cocaine use. RESULTS: At a corrected threshold, cocaine-dependent participants demonstrated higher activation to cocaine than to food cues in the hypothalamus, inferior parietal cortex, and visual cortex. Cocaine-dependent participants as compared with healthy control participants also demonstrated higher hypothalamic activation to food cues. Further, the extent of these cue-induced hypothalamic activations was correlated with tonic craving, as assessed by the Cocaine Craving Questionnaire, and days of cocaine use in the prior month. In mediation analyses, hypothalamic activation to cocaine and food cues both completely mediated the relationship between the Cocaine Craving Questionnaire score and days of cocaine use in the past month. CONCLUSIONS: The results were consistent with the proposition that the mechanisms of feeding and drug addiction are inter-linked in the hypothalamus and altered in cocaine addiction. The findings provide new evidence in support of hypothalamic dysfunction in cocaine addiction.

Hypothalamic regulation of headache and migraine.

BACKGROUND: The clinical picture, but also neuroimaging findings, suggested the brainstem and midbrain structures as possible driving or generating structures in migraine. FINDINGS: This has been intensely discussed in the last decades and the advent of modern imaging studies refined the involvement of rostral parts of the pons in acute migraine attacks, but more importantly suggested a predominant role of the hypothalamus and alterations in hypothalamic functional connectivity shortly before the beginning of migraine headaches. This was shown in the NO-triggered and also in the preictal stage of native human migraine attacks. Another headache type that is clinically even more suggestive of hypothalamic involvement is cluster headache, and indeed a structure in close proximity to the hypothalamus has been identified to play a crucial role in attack generation. CONCLUSION: It is very likely that spontaneous oscillations of complex networks involving the hypothalamus, brainstem, and dopaminergic networks lead to changes in susceptibility thresholds that ultimately start but also terminate headache attacks. We will review clinical and neuroscience evidence that puts the hypothalamus in the center of scientific attention when attack generation is discussed.

Associations between dispositional mindfulness, craving, and drinking in alcohol-dependent patients: An ecological momentary assessment study.

Hazardous alcohol use remains a significant global public health problem. A better understanding of relapse may assist the development of new interventions. Low levels of dispositional mindfulness may be a risk factor for craving and alcohol use, but few studies have examined these associations prospectively in an alcohol-dependent sample. In an ecological momentary assessment (EMA) study, Dutch alcohol dependent patients (N = 43) carried around a personal digital assistant for 4 weeks while trying to maintain abstinence. Participants completed assessments at random times 3 times per day, and when they felt a strong urge to drink or came to the brink of drinking without doing so. At each assessment, stress, negative affect, craving, recent drinking, and attentional or approach bias were assessed. Dispositional mindfulness was assessed at baseline with the Mindful Attention Awareness Scale (MAAS). More mindful individuals (higher MAAS scores) reported lower craving than less mindful individuals. There was no evidence that stress, negative affect, attentional bias, or approach bias mediated the association between MAAS and craving. However, there was evidence for an indirect path from MAAS to drinking such that higher mindfulness was associated with lower craving ratings that in turn were associated with less drinking. There was no evidence that MAAS significantly moderated associations between stress/negative affect/cognitive biases and craving, or between craving and drinking. In sum, more mindful recovering alcohol dependent patients reported lower craving ratings than less mindful patients, and this association appeared to be independent of stress/negative affect and cognitive biases. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Exploiting the "video game craze": A case study of the tobacco industry's use of video games as a marketing tool.

BACKGROUND: Video games have grown in popularity since the 1970s, and tobacco imagery is present in a substantial subset of games, including those oriented to youth. Much like exposure to tobacco content in films, exposure to tobacco content in video games may influence smoking uptake and use; however, the tobacco industry's role in facilitating or promoting the use of tobacco imagery in video games is unclear. We explored the industry's interest in and use of video games to market their products to youth and young adults. METHODS: We retrieved and analyzed archival tobacco industry documents. We supplemented information from the documents with current and archived versions of several brand and corporate websites and one website containing user-supplied information on video games. RESULTS: Tobacco companies recognized the youth appeal and marketing potential of video games as early as 1980. Initial marketing ideas included incorporating video game themes into product packaging and design. More fully realized plans focused on incorporating video games into product promotions in bars, as a high visibility way to attract younger patrons and increase long-term marketing opportunities by generating names for tobacco company direct-marketing databases. Tobacco companies also incorporated video games into in-home product promotions, primarily as components of brand websites, in order to enhance brand image and generate repeat website traffic. A similar desire to attract and keep visitors led to discussions about the inclusion of video games on corporate youth smoking prevention websites, although only one company, Lorillard, followed through. CONCLUSIONS: Video game players are an attractive target market for tobacco companies. Video games, as used by these companies, facilitate consumer engagement with particular tobacco brands or particular corporate messages. Eliminating the use of video games as a promotional vehicle may require limiting tobacco marketing in both physical and online environments.