***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Importance Betel-quid ( BQ ) is the fourth most popular psychoactive agent worldwide . An emerging trend across Asia is the addictive consumption of BQ , which is associated with oral cancer and other health consequences . Objective To investigate the validity and pattern of DSM-5–defined BQ use disorder ( BUD ) and its association with oral potentially malignant disorder ( OPMD ) among Asian population s. Design , Setting , and Participants In-person interviews were conducted from January 1 , 2009 , to February 28 , 2010 , among a r and om sample of 8922 noninstitutionalized adults from the Asian Betel-quid Consortium study , an Asian representative survey of 6 BQ-endemic population s. Statistical analysis was performed from January 1 , 2015 , to December 31 , 2016 . Main Outcomes and Measures Participants were evaluated for BUD using DSM-5 criteria for substance use disorder and for OPMD using a clinical oral examination . Current users of BQ with 0 to 1 symptoms were classified as having no BUD , those with 2 to 3 symptoms as having mild BUD , those with 4 to 5 symptoms as having moderate BUD , and those with 6 or more symptoms as having severe BUD . Results Among the 8922 participants ( 4564 women and 4358 men ; mean [ SD ] age , 44.2 [ 0.2 ] years ) , DSM-5 symptoms showed sufficient unidimensionality to act as a valid measure for BUD . The 12-month prevalence of DSM-5–defined BUD in the 6 study population s was 18.0 % ( mild BUD , 3.2 % ; moderate BUD , 4.3 % ; and severe BUD , 10.5 % ) . The 12-month proportion of DSM-5–defined BUD among current users of BQ was 86.0 % ( mild BUD , 15.5 % ; moderate BUD , 20.6 % ; and severe BUD , 50.0 % ) . Sex , age , low educational level , smoking , and drinking were significantly associated with BUD . Among individuals who used BQ , family use , high frequency of use , and amount of BQ used were significantly linked to moderate to severe BUD . Compared with individuals who did not use BQ , those who used BQ and had no BUD showed a 22.0-fold ( 95 % CI , 4.3 - 112.4 ) risk of OPMD ( P < .001 ) , whereas those with mild BUD showed a 9.6-fold ( 95 % CI , 1.8 - 56.8 ) risk ( P = .01 ) , those with moderate BUD showed a 35.5-fold ( 95 % CI , 4.3 - 292.3 ) risk ( P = .001 ) , and those with severe BUD showed a 27.5-fold ( 95 % CI , 1.6 - 461.4 ) risk of OPMD ( P = .02 ) . Individuals with moderate to severe BUD who used BQ and had the symptom of tolerance had a 153.4-fold ( 95 % CI , 33.4 - 703.6 ) higher risk of OPMD than those who did not use BQ , and those with moderate to severe BUD who used BQ and had a larger amount or longer history of BQ use had an 88.9-fold ( 95 % CI , 16.6 - 476.5 ) higher risk of OPMD than those who did not use BQ . Conclusions and Relevance This international study gathered data about  BQ users across 6 Asian population s , and it demonstrates that DSM-5 symptoms could fulfill a BUD construct . Most current Asian users of BQ already have BUD , which is correlated with risk of OPMD . Among individuals with moderate to severe BUD who used BQ , tolerance and a larger amount or longer history of BQ use are the key symptoms that correlated with enhanced risk of OPMD . These findings play an important role in providing a new indication of an additional psychiatric management plan for users of BQ who have BUD Background : Disturbances in the regulation of reward and aversion in the brain may underlie disorders such as obesity and eating disorders . We previously showed that the cannabis receptor subtype ( CB1 ) inverse agonist rimonabant , an antiobesity drug withdrawn due to depressogenic side effects , diminished neural reward responses yet increased aversive responses ( Horder et al. , 2010 ) . Unlike rimonabant , tetrahydrocannabivarin is a neutral CB1 receptor antagonist ( Pertwee , 2005 ) and may therefore produce different modulations of the neural reward system . We hypothesized that tetrahydrocannabivarin would , unlike rimonabant , leave intact neural reward responses but augment aversive responses . Methods : We used a within-subject , double-blind design . Twenty healthy volunteers received a single dose of tetrahydrocannabivarin ( 10 mg ) and placebo in r and omized order on 2 separate occasions . We measured the neural response to rewarding ( sight and /or flavor of chocolate ) and aversive stimuli ( picture of moldy strawberries and /or a less pleasant strawberry taste ) using functional magnetic resonance imaging . Volunteers rated pleasantness , intensity , and wanting for each stimulus . Results : There were no significant differences between groups in subjective ratings . However , tetrahydrocannabivarin increased responses to chocolate stimuli in the midbrain , anterior cingulate cortex , cau date , and putamen . Tetrahydrocannabivarin also increased responses to aversive stimuli in the amygdala , insula , mid orbitofrontal cortex , cau date , and putamen . Conclusions : Our findings are the first to show that treatment with the CB1 neutral antagonist tetrahydrocannabivarin increases neural responding to rewarding and aversive stimuli . This effect profile suggests therapeutic activity in obesity , perhaps with a lowered risk of depressive side effects Persistent dose-related cognitive decrements have been reported in 28-day abstinent heavy marijuana ( MJ ) users . However , the neural substrates of these decrements in cognitive performance are not known . This study aim ed to determine if 25-day abstinent MJ users show persistent dose-related alterations in performance and brain activity using PET H(2)(15)O during the Iowa Gambling Task-IGT ( a decision-making task ) . Eleven heavy MJ users and 11 non-drug users participated . The MJ group resided in an inpatient research unit at the NIH/NIDA-IRP for 25 days prior to testing to ensure abstinence . A dose-related association was found between increased MJ use and lower IGT performance and alterations in brain activity . The MJ group showed greater activation in the left cerebellum and less activation in the right lateral orbitofrontal cortex ( OFC ) and the right dorsolateral prefrontal cortex ( DLPFC ) than the Control group . When the MJ group was divided into Moderate ( 8 - 35 joints/week ) and Heavy users ( 53 - 84 joints/week ) , the Heavy MJ group showed less activation in the left medial OFC and greater activation in the left cerebellum than the Moderate group . However , brain activity and task performance were similar between the Moderate MJ users and the Control group , suggesting a " threshold effect " . These preliminary findings indicate that very heavy users of MJ have persistent decision-making deficits and alterations in brain activity . Specifically , the Heavy MJ users may focus on only the immediate reinforcing aspects of a situation ( i.e. , getting high ) while ignoring the negative consequences . Thus , faulty decision-making could make an individual more prone to addictive behavior and more resistant to treatment . Finally , it is unclear if these neurologic findings will become progressively worse with continued heavy MJ use or if they will resolve with abstinence from MJ use BACKGROUND Despite gradual underst and ing of the multidimensional health consequences of betel-quid chewing , information on the effects of dependent use is scant . AIMS To investigate the 12-month prevalence patterns of betel-quid dependence in six Asian population s and the impact of this dependence on oral potentially malignant disorders ( OPMD ) . METHOD A multistage r and om sample of 8922 participants was recruited from Taiwan , mainl and China , Indonesia , Malaysia , Sri Lanka and Nepal . Participants were evaluated for betel-quid dependency using DSM-IV and ICD-10 criteria and assessed clinical ly for oral mucosal lesions . RESULTS The 12-month prevalence of dependence was 2.8 - 39.2 % across the six Asian sample s , and 20.9 - 99.6 % of those who chewed betel-quid were betel-quid dependent . Men dominated the prevalence among the east Asian sample s and women dominated the prevalence in south-east Asian sample s. ' Time spent chewing ' and ' craving ' were the central dependence domains endorsed by the Chinese and southern/south-east Asian sample s respectively , whereas the Nepalese sample s endorsed ' tolerance ' and ' withdrawal ' . Dependency was linked to age , gender , schooling years , drinking , smoking , tobacco-added betel-quid use and environmental accessibility of betel-quid . Compared with non-users , those with betel-quid dependency had higher pre-neoplastic risks ( adjusted odds ratios 8.0 - 51.3 ) than people with non-dependent betel-quid use ( adjusted odds ratio 4.5 - 5.9 ) in the six Asian population s. CONCLUSIONS By elucidating differences in domain-level symptoms of betel-quid dependency and individual and environmental factors , this study draws attention to the population -level psychiatric problems of betel-quid chewing that undermine health consequences for OPMD in six Asian communities BACKGROUND Healthy individuals performing response suppression tasks activate anterior cingulate cortex with occurrence of false alarm error responses to nontargets . Fundamental questions include whether this error-related activation provides a signal contributing to behavioral control and , given generally poorer performance on such tasks by addicts , whether this signal is disrupted in addiction . METHODS We used rapid , event-related functional magnetic resonance imaging to study 13 individuals with opiate dependence and 26 healthy control individuals performing a Go/NoGo task .  RESULTS Compared with controls , opiate addicts exhibited an attenuated anterior cingulate cortex error signal and significantly poorer task performance . In controls , the individual level of event-related anterior cingulate cortex activation accompanying false alarm error positively predicted task performance , particularly sensitivity in discriminating targets from nontargets . CONCLUSIONS The attenuation of this error signal in anterior cingulate cortex may play a role in loss of control in addiction and other forms of impulsive behavior Health risks stemming from betel-quid ( BQ ) chewing are frequently overlooked by people . Up date d epidemiological data on the increased BQ use among Asian population s using comparable data collection methods have not been widely available . To investigate the prevalence , patterns of practice and associated types of oral preneoplastic disorders , an intercountry Asian Betel-quid Consortium study ( the ABC study ) was conducted for Taiwan , Mainl and China , Malaysia , Indonesia , Nepal and Sri Lanka . A r and om sample of 8,922 subjects was recruited , and the data were analyzed using survey- data modules adjusted for the complex survey design .  Chewing rates among men ( 10.7 - 43.6 % ) were significantly higher than women ( 1.8 - 34.9 % ) in Taiwan , Mainl and China , Nepal and Sri Lanka , while women 's rates ( 29.5 - 46.8 % ) were higher than that for men ( 9.8 - 12.0 % ) in Malaysia and Indonesia . An emerging , higher proportion of new-users were identified for Hunan in Mainl and China ( 11.1 - 24.7 % ) , where Hunan chewers have the unique practice of using the dried husk of areca fruit rather than the solid nut universally used by others . Men in the Eastern and South Asian study communities were deemed likely to combine chewing with smoking and drinking ( 5.6 - 13.6 % ) . Indonesian women who chewed BQ exhibited the highest prevalence of oral lichen planus , oral submucous fibrosis and oral leukoplakia ( 9.1 - 17.3 % ) . Lower schooling , alcohol drinking and tobacco smoking were identified as being associated with BQ chewing . In conclusion , the ABC study reveals the significant cultural and demographic differences contributing to practice patterns of BQ usage and the great health risks that such practice s pose in the Asian region PURPOSE To explore the acute effect of betel quid ( BQ ) use on functional network connectivity by comparing the global functional brain networks and their subsets before and immediately after BQ chewing . MATERIAL S AND METHODS Resting-state functional magnetic resonance imaging ( fMRI ) was performed in 27 healthy male participants before and just after chewing BQ on a 3.0 T scanner with a gradient-echo echo planar imaging sequence .  Independent component analysis ( ICA ) was used to determine components that represent the brain 's functional networks and their spatial aspects of functional connectivity . A paired t-test was used for exploring the connectivity differences in each network before and after BQ chewing . RESULTS Sixteen networks were identified by ICA . Nine of them showed connectivity differences before and after BQ chewing ( P < 0.05 false discovery rate corrected ) : ( A ) orbitofrontal , ( B ) left frontoparietal , ( C ) visual , ( D ) right frontoparietal , ( E ) anterior default mode , ( F ) medial frontal/anterior cingulate ( G ) frontotemporal , ( H ) occip 
    Output:
    
BQ duration and severity of betel quid dependence were associated with majority of alterations in BQ chewers .
Conclusion : Betel quid chewing is associated with brain alterations in structure , metabolism and function in the cognitive , reward , and impulsivity circuits which are greatly influenced by duration and severity of betel quid dependence