Neural responses to gaming content on social media in young adults.

Excessive gaming can impair both mental and physical health, drawing widespread public and clinical attention, especially among young generations. People are now more exposed to gaming-related content on social media than before, and this exposure may have a significant impact on their behavior. However, the neural mechanisms underlying this effect remain unexplored. Using functional magnetic resonance imaging (fMRI), this study aimed to investigate the neural activity induced by gaming-related content on social media among young adults casually playing online games. While being assessed by fMRI, the participants watched gaming-related videos and neutral (nongaming) videos on social media. The gaming-related cues significantly activated several brain areas, including the medial prefrontal cortex, posterior cingulate cortex, hippocampus, thalamus, superior/middle temporal gyrus, precuneus and occipital regions, compared with the neutral cues. Additionally, the participants' gaming desire levels positively correlated with a gaming-related cue-induced activation in the left orbitofrontal cortex and the right superior temporal gyrus. These findings extend previous studies on gaming cues and provide useful information to elucidate the effects of gaming-related content on social media in young adults. Continued research using real-world gaming cues may help improve our understanding of promoting gaming habits and provide support to individuals vulnerable to gaming addiction.

Current perspectives on brain circuits involved in food addiction-like behaviors.

There is an emerging view that the increased availability of energy-dense foods in our society is contributing to excessive food consumption which could lead to food addiction-like behavior. Particularly, compulsive eating patterns are predominant in people suffering from eating disorders (binge-eating disorder, bulimia and anorexia nervosa) and obesity. Phenotypically, the behavioral pattern exhibits a close resemblance to individuals suffering from other forms of addiction (drug, sex, gambling). Growing body of evidence in neuroscience research is showing that excessive consumption of energy-dense foods alters the brain circuits implicated in reward, decision-making, control, habit formation, and emotions that are central to drug addiction. Here, we review the current understanding of the circuits of food addiction-like behaviors and highlight the future possibility of exploring those circuits to combat obesity and eating disorders.

Driving innovation in addiction treatment: role of transcranial magnetic stimulation.

Addictions comprises heterogenous psychiatric conditions caused by the complex interaction of genetic, neurobiological, psychological, and environmental factors with a chronic relapsing-remitting pattern. Despite the long-standing efforts of preclinical and clinical research studies, addiction field has seen relatively slow progress when it comes to the development of new therapeutic interventions, most of which failed to demonstrate a significant efficacy. This is likely due to the very complex interplay of many factors that contribute to both the development and expression of addictions. The imbalance between the salience and the reward brain network circuitry has been proposed as the neurobiological mechanisms explaining the pathognomonic symptoms of addictions.Non-invasive neuromodulation techniques have been proposed as a promising therapeutic intervention to restore these brain circuits dysfunctions. Here, we propose a multi-level strategy to innovate the diagnosis and the treatment of addictive disorders.

Effects of retrieval-extinction training on internet gaming disorder.

Background and aims: Internet gaming disorder (IGD) leads to serious impairments in cognitive functions, and lacks of effective treatments. Cue-induced craving is a hallmark feature of this disease and is associated with addictive memory elements. Memory retrieval-extinction manipulations could interfere with addictive memories and attenuate addictive syndromes, which might be a promising intervention for IGD. The aims of this study were to explore the effect of a memory retrieval-extinction manipulation on gaming cue-induced craving and reward processing in individuals with IGD. Methods: A total of 49 individuals (mean age: 20.52 ± 1.58) with IGD underwent a memory retrieval-extinction training (RET) with a 10-min interval (R-10min-E, n = 24) or a RET with a 6-h interval (R-6h-E, n = 25) for two consecutive days. We assessed cue-induced craving pre- and post-RET, and at the 1- and 3-month follow-ups. The neural activities during reward processing were also assessed pre- and post-RET. Results: Compared with the R-6h-E group, gaming cravings in individuals with IGD were significantly reduced after R-10min-E training at the 3-month follow-up (P < 0.05). Moreover, neural activities in the individuals with IGD were also altered after R-10min-E training, which was corroborated by enhanced reward processing, such as faster responses (P < 0.05) and stronger frontoparietal functional connectivity to monetary reward cues, while the R-6h-E training had no effects. Discussion and Conclusions: The two-day R-10min-E training reduced addicts' craving for Internet games, restored monetary reward processing in IGD individuals, and maintained long-term efficacy.

A novel effect of PDLIM5 in α7 nicotinic acetylcholine receptor upregulation and surface expression.

Nicotinic acetylcholine receptors (nAChRs) are widespread throughout the central nervous system. Signaling through nAChRs contributes to numerous higher-order functions, including memory and cognition, as well as abnormalities such as nicotine addiction and neurodegenerative disorders. Although recent studies indicate that the PDZ-containing proteins comprising PSD-95 family co-localize with nicotinic acetylcholine receptors and mediate downstream signaling in the neurons, the mechanisms by which α7nAChRs are regulated remain unclear. Here, we show that the PDZ-LIM domain family protein PDLIM5 binds to α7nAChRs and plays a role in nicotine-induced α7nAChRs upregulation and surface expression. We find that chronic exposure to 1 µM nicotine upregulated α7, ß2-contained nAChRs and PDLIM5 in cultured hippocampal neurons, and the upregulation of α7nAChRs and PDLIM5 is increased more on the cell membrane than the cytoplasm. Interestingly, in primary hippocampal neurons, α7nAChRs and ß2nAChRs display distinct patterns of expression, with α7nAChRs colocalized more with PDLIM5. Furthermore, PDLIM5 interacts with α7nAChRs, but not ß2nAChRs in native brain neurons. Knocking down of PDLIM5 in SH-SY5Y abolishes nicotine-induced upregulation of α7nAChRs. In primary hippocampal neurons, using shRNA against PDLIM5 decreased both surface clustering of α7nAChRs and α7nAChRs-mediated currents. Proteomics analysis and isothermal titration calorimetry (ITC) results show that PDLIM5 interacts with α7nAChRs through the PDZ domain, and the interaction between PDLIM5 and α7nAChRs can be promoted by nicotine. Collectively, our data suggest a novel cellular role of PDLIM5 in the regulation of α7nAChRs, which may be relevant to plastic changes in the nervous system.

Disentangling craving- and valence-related brain responses to smoking cues in individuals with nicotine use disorder.

Tobacco smoking is one of the leading causes of preventable death and disease worldwide. Most smokers want to quit, but relapse rates are high. To improve current smoking cessation treatments, a better understanding of the underlying mechanisms of nicotine dependence and related craving behaviour is needed. Studies on cue-driven cigarette craving have been a particularly useful tool for investigating the neural mechanisms of drug craving. Here, functional neuroimaging studies in humans have identified a core network of craving-related brain responses to smoking cues that comprises of amygdala, anterior cingulate cortex, orbitofrontal cortex, posterior cingulate cortex and ventral striatum. However, most functional Magnetic Resonance Imaging (fMRI) cue-reactivity studies do not adjust their stimuli for emotional valence, a factor assumed to confound craving-related brain responses to smoking cues. Here, we investigated the influence of emotional valence on key addiction brain areas by disentangling craving- and valence-related brain responses with parametric modulators in 32 smokers. For one of the suggested key regions for addiction, the amygdala, we observed significantly stronger brain responses to the valence aspect of the presented images than to the craving aspect. Our results emphasize the need for carefully selecting stimulus material for cue-reactivity paradigms, in particular with respect to emotional valence. Further, they can help designing future research on teasing apart the diverse psychological dimensions that comprise nicotine dependence and, therefore, can lead to a more precise mapping of craving-associated brain areas, an important step towards more tailored smoking cessation treatments.

Extended amygdala, conditioned withdrawal and memory consolidation.

Opioid withdrawal can be associated to environmental cues through classical conditioning. Exposure to these cues can precipitate a state of conditioned withdrawal in abstinent subjects, and there are suggestions that conditioned withdrawal can perpetuate the addiction cycle in part by promoting the storage of memories. This review discusses evidence supporting the hypothesis that conditioned withdrawal facilitates memory consolidation by activating a neurocircuitry that involves the extended amygdala. Specifically, the central amygdala, the bed nucleus of the stria terminalis, and the nucleus accumbens shell interact functionally during withdrawal, mediate expression of conditioned responses, and are implicated in memory consolidation. From this perspective, the extended amygdala could be a neural pathway by which drug-seeking behaviour performed during a state of conditioned withdrawal is more likely to become habitual and persistent.

Relationship between Negative Running Addiction and Eating Disorder Patterns in Runners.

Current studies show an increase in the risk of eating disorders in runners. Since it is known that abusive exercise can be both a cause and a consequence of such developments, the main objective of the present study was to examine the risk and possible relationships between negative running addiction (NRA), as measured by the reduced and validated SAS-40 scale, and the tendency to be a compulsive eater (measured by YFAS 2.0), anorexia nervosa (AN), and/or bulimia nervosa (BN) (measured by EAT-40). This study highlights the novelty of researching the level of influence of NRA on each defined eating disorder. METHOD: A total of 167 Spanish-speaking federated runners in cross-country and track running (42% women and 58% men), with an average age of 24 years and an average BMI of 21 kg/m2, responded to an online questionnaire that asked about sociodemographic data and the Spanish versions of the SAS-40, YFAS 2, YFAS 3, and YFAS 4. Through a quantitative methodology using logistic regressions-the coefficient of determination and Pearson's correlation coefficient-we created a sample analysis that related the significant items of the DSM-V to the results of the questionnaires administered, as well as their relationship with the practice of the sport in question and various variables of the environment. RESULTS: The rates of CE, AN, and BN were 65, 11.4, and 16.2%, respectively. The tendency towards CE increased with a lower weight (r = 0.156, p < 0.05), not having been overweight in childhood (r = 0.151, p < 0.05), and being a long-distance runner (r = 0.123 p < 0.05). The risk of AN increased with the absence of menstruation for more than 3 months (r = 0.271 p < 0.01), having suffered from childhood obesity (r = 0.213 p < 0.05), and being underweight (r = 0.064 p < 0.05). The risk of BN increased with having suffered from childhood obesity (r = 0.194 p < 0.05), having a higher weight (r = 0.140, p < 0.05), and practicing athletics, especially the relay modality (r = 0.044 p < 0.05). CONCLUSIONS: A considerable number of runners are at risk of suffering from some type of eating disorder. A significant relationship was observed between long-distance runners and the risk of eating disorders (AN, BN, and CE), and the association is stronger for CE than for AN and BN. Lastly, childhood experiences (such as being obese/a healthy weight) were notorious for increasing the risk of eating disorders. Further studies are needed to research each particular parameter and the relationships between the possible levels of dependence on exercise. LEVEL OF EVIDENCE: Level III, cohort analytic study.

Interoception and alcohol: Mechanisms, networks, and implications.

Interoception refers to the perception of the internal state of the body and is increasingly being recognized as an important factor in mental health disorders. Drugs of abuse produce powerful interoceptive states that are upstream of behaviors that drive and influence drug intake, and addiction pathology is impacted by interoceptive processes. The goal of the present review is to discuss interoceptive processes related to alcohol. We will cover physiological responses to alcohol, how interoceptive states can impact drinking, and the recruitment of brain networks as informed by clinical research. We also review the molecular and brain circuitry mechanisms of alcohol interoceptive effects as informed by preclinical studies. Finally, we will discuss emerging treatments with consideration of interoception processes. As our understanding of the role of interoception in drug and alcohol use grows, we suggest that the convergence of information provided by clinical and preclinical studies will be increasingly important. Given the complexity of interoceptive processing and the multitude of brain regions involved, an overarching network-based framework can provide context for how focused manipulations modulate interoceptive processing as a whole. In turn, preclinical studies can systematically determine the roles of individual nodes and their molecular underpinnings in a given network, potentially suggesting new therapeutic targets and directions. As interoceptive processing drives and influences motivation, emotion, and subsequent behavior, consideration of interoception is important for our understanding of processes that drive ongoing drinking and relapse.

The role of the nucleus accumbens and ventral pallidum in feeding and obesity.

Obesity is a growing global epidemic that stems from the increasing availability of highly-palatable foods and the consequent enhanced calorie consumption. Extensive research has shown that brain regions that are central to reward seeking modulate feeding and evidence linking obesity to pathology in such regions have recently started to accumulate. In this review we focus on the contribution of two major interconnected structures central to reward processing, the nucleus accumbens and the ventral pallidum, to obesity. We first review the known literature linking these structures to feeding behavior, then discuss recent advances connecting pathology in the nucleus accumbens and ventral pallidum to obesity, and finally examine the similarities and differences between drug addiction and obesity in the context of these two structures. The understanding of how pathology in brain regions involved in reward seeking and consumption may drive obesity and how mechanistically similar obesity and addiction are, is only now starting to be revealed. We hope that future research will advance knowledge in the field and open new avenues to studying and treating obesity.

Spontaneously Hypertensive Rat substrains show differences in model traits for addiction risk and cocaine self-administration: Implications for a novel rat reduced complexity cross.

Forward genetic mapping of F2 crosses between closely related substrains of inbred rodents - referred to as a reduced complexity cross (RCC) - is a relatively new strategy for accelerating the pace of gene discovery for complex traits, such as drug addiction. RCCs to date were generated in mice, but rats are thought to be optimal for addiction genetic studies. Based on past literature, one inbred Spontaneously Hypertensive Rat substrain, SHR/NCrl, is predicted to exhibit a distinct behavioral profile as it relates to cocaine self-administration traits relative to another substrain, SHR/NHsd. Direct substrain comparisons are a necessary first step before implementing an RCC. We evaluated model traits for cocaine addiction risk and cocaine self-administration behaviors using a longitudinal within-subjects design. Impulsive-like and compulsive-like traits were greater in SHR/NCrl than SHR/NHsd, as were reactivity to sucrose reward, sensitivity to acute psychostimulant effects of cocaine, and cocaine use studied under fixed-ratio and tandem schedules of cocaine self-administration. Compulsive-like behavior correlated with the acute psychostimulant effects of cocaine, which in turn correlated with cocaine taking under the tandem schedule. Compulsive-like behavior also was the best predictor of cocaine seeking responses. Heritability estimates indicated that 22 %-40 % of the variances for the above phenotypes can be explained by additive genetic factors, providing sufficient genetic variance to conduct genetic mapping in F2 crosses of SHR/NCrl and SHR/NHsd. These results provide compelling support for using an RCC approach in SHR substrains to uncover candidate genes and variants that are of relevance to cocaine use disorders.

Attention bias modification in drug addiction: Enhancing control of subsequent habits.

A relapse in addiction is often precipitated by heightened attention bias to drug-related cues, underpinned by a subcortically mediated transition to habitual/automatized responding and reduced prefrontal control. Modification of such automatized attention bias is a fundamental, albeit elusive, target for relapse reduction. Here, on a trial-by-trial basis, we used electroencephalography and eye tracking with a task that assessed, in this order, drug cue reactivity, its instructed self-regulation via reappraisal, and the immediate aftereffects on spontaneous (i.e., not instructed and automatized) attention bias. The results show that cognitive reappraisal, a facet of prefrontal control, decreased spontaneous attention bias to drug-related cues in cocaine-addicted individuals, more so in those with less frequent recent use. The results point to the mechanisms underlying the disruption of automatized maladaptive drug-related attention bias in cocaine addiction. These results pave the way for future studies to examine the role of such habit disruption in reducing compulsive drug seeking outside the controlled laboratory environment, with the ultimate goal of developing a readily deployable cognitive-behavioral and personalized intervention for drug addiction.

Associations of the Big Five and locus of control with problem gambling in a large Australian sample.

Gambling may range from being a recreational leisure activity to a behavioral addiction. A rising number of gamblers experience adverse consequences from gambling, termed problem gambling, which may become a challenge for the individual and society. With the present research, we aimed to investigate the correlates of problem gambling. We used a large sample of more than 12,500 individuals (46% male, Mage = 48, SDage = 18) from the Household, Income, and Labour Dynamics in Australia (HILDA) Survey and analyzed sociodemographic and personality variables (Big Five, locus of control) as well as the extent of problem gambling. Findings showed that male sex and a lower level of education were related to problem gambling, but personality traits were predictive of problem gambling over and above sociodemographic variables. Specifically, a low level of emotional stability, an external locus of control, and, to a lesser extent, a low level of conscientiousness and a high level of extraversion were predictive of problem gambling, whereas openness and agreeableness were not. These results remained constant across various robustness analyses. Our findings reveal the importance of including personality traits when explaining gambling behavior.

Self-Injury Is My Drug: The Functions of Describing Nonsuicidal Self-Injury as an Addiction.

ABSTRACT: Adolescents and emerging adults who engage in nonsuicidal self-injury (NSSI) often participate in online activity regarding their self-injury. Of particular importance are the potential benefits and risks associated with online NSSI activity, including how individuals describe their NSSI experiences. One way that individuals describe these experiences is by discussing NSSI as an addiction. Accordingly, we used thematic analysis to explore why individuals may use addiction references to describe their NSSI experiences. To do this, we examined 71 posts from a popular NSSI social network. Four themes emerged: difficulty inherent in stopping, authentication, warn others, and communicate the plight of the behavior. Findings highlight a number of avenues for research as well as implications for clinicians working with clients who self-injure perceive NSSI as an addiction. Mental health professionals can leverage their understanding of clients' perceptions of NSSI to better serve this population.

Neurochemical substrates linked to impulsive and compulsive phenotypes in addiction: A preclinical perspective.

Drug compulsion manifests in some but not all individuals and implicates multifaceted processes including failures in top-down cognitive control as drivers for the hazardous pursuit of drug use in some individuals. As a closely related construct, impulsivity encompasses rash or risky behaviour without foresight and underlies most forms of drug taking behaviour, including drug use during adverse emotional states (i.e., negative urgency). While impulsive behavioural dimensions emerge from drug-induced brain plasticity, burgeoning evidence suggests that impulsivity also predates the emergence of compulsive drug use. Although the neural substrates underlying the apparently causal relationship between trait impulsivity and drug compulsion are poorly understood, significant advances have come from the interrogation of defined limbic cortico-striatal circuits involved in motivated behaviour and response inhibition, together with chemical neuromodulatory influences from the ascending neurotransmitter systems. We review what is presently known about the neurochemical mediation of impulsivity, in its various forms, and ask whether commonalities exist in the neurochemistry of compulsive drug-motivated behaviours that might explain individual risk for addiction.

Epigenetics of addiction.

Substance use disorders are complex biopsychosocial disorders that have substantial negative neurocognitive impact in various patient populations. These diseases involve the compulsive use of licit or illicit substances despite adverse medicolegal consequences and appear to be secondary to long-lasting epigenetic and transcriptional adaptations in brain reward and non-reward circuits. The accumulated evidence supports the notion that repeated drug use causes changes in post-translational histone modifications and in DNA methylation/hydroxymethylation processes in several brain regions. This review provides an overview of epigenetic changes reported in models of cocaine, methamphetamine, and opioid use disorders. The accumulated data suggest that future therapeutic interventions should focus on the development of epigenetic drugs against addictive diseases.

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.

Contrasting effects of the α7 nicotinic receptor antagonist methyllycaconitine in different rat models of heroin reinstatement.

BACKGROUND: α7 Nicotinic acetylcholine receptors are implicated in the reinstatement of drug-seeking, an important component of relapse. We showed previously that the α7 nicotinic acetylcholine receptor antagonist, methyllycaconitine, specifically attenuated morphine-primed reinstatement of conditioned place preference in rodents and this effect was mediated in the ventral hippocampus. AIMS: The purpose of this study was to evaluate α7 nicotinic acetylcholine receptor antagonism in reinstatement of the conditioned place preference for the more widely abused opioid, heroin, and to compare the effect of α7 nicotinic acetylcholine receptor blockade on reinstatement of heroin-seeking and heroin self-administration in an intravenous self-administration model of addictive behaviour. METHODS: Rats were trained to acquire heroin conditioned place preference or heroin self-administration; both followed by extinction of responding. Methyllycaconitine or saline was given prior to reinstatement of drug-primed conditioned place preference, or drug-prime plus cue-induced reinstatement of intravenous self-administration, using two protocols: without delivery of heroin in response to lever pressing to model heroin-seeking, or with heroin self-administration, using fixed and progressive ratio reward schedules, to model relapse. RESULTS: Methyllycaconitine had no effect on acquisition of heroin conditioned place preference or lever-pressing for food rewards. Methyllycaconitine blocked reinstatement of heroin-primed conditioned place preference. Methyllycaconitine did not prevent drug-prime plus cue-induced reinstatement of heroin-seeking, reinstatement of heroin self-administration, or diminish the reinforcing effect of heroin. CONCLUSIONS: The α7 nicotinic acetylcholine receptor antagonist, methyllycaconitine, prevented reinstatement of the opioid conditioned place preference, consistent with a role for α7 nicotinic acetylcholine receptors in the retrieval of associative memories of drug liking. The lack of effect of methyllycaconitine in heroin-dependent rats in two intravenous self-administration models suggests that α7 nicotinic acetylcholine receptors do not play a role in later stages of heroin abuse.