***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: BACKGROUND Excessive discounting of future rewards has been observed in a variety of disorders and has been linked both to valuation of the past and to memory of past events . METHODS To explore the functionality of discounting and memory , we examined whether training of working memory would result in less discounting of future rewards . In this study , 27 adults in treatment for stimulant use were r and omly assigned to receive either  working memory training or control training according to a yoked experimental design . Measures of delay discounting and several other cognitive behaviors were assessed pre- and posttraining . RESULTS Rates of discounting of delayed rewards were significantly reduced among those who received memory training but were unchanged among those who received control training ; other cognitive assessment s were not affected by memory training .  Discount rates were positively correlated with memory training performance measures . CONCLUSIONS To our knowledge , this is the first study demonstrating that neurocognitive training on working memory decreases delay discounting . These results offer further evidence of a functional relationship between delay discounting and working memory UNLABELLED Recent animal studies demonstrate that compulsive cocaine seeking strongly reduces prelimbic frontal cortex activity , while optogenetic stimulation of this brain area significantly inhibits compulsive cocaine seeking , providing a strong rationale for applying brain stimulation to reduce cocaine consumption . Thus , we employed repetitive transcranial magnetic stimulation ( rTMS ) , to test if dorsolateral prefrontal cortex ( DLPFC ) stimulation might prevent cocaine use in humans . Thirty-two cocaine-addicted patients were r and omly assigned to either the experimental group ( rTMS ) on the left DLPFC , or to a control group ( pharmacological agents ) during a 29-day study ( Stage 1 ) . This was followed by a 63-day follow-up ( Stage 2 ) , during which all participants were offered rTMS treatment . Amongst the patients who completed Stage 1 , 16 were in the rTMS group ( 100 % ) and 13 in the control group ( 81 % ) . No significant adverse events were noted . During Stage 1 , there were a significantly higher number of cocaine-free urine drug tests in the rTMS group compared to control ( p=0.004 ) . Craving for cocaine was also significantly lower in the rTMS group compared to the controls ( p=0.038 ) . Out of 13 patients who completed Stage 1 in the control group , 10 patients received rTMS treatment during Stage 2 and showed significant improvement with favorable outcomes becoming comparable to those of the rTMS group . The present preliminary findings support the safety of rTMS in cocaine-addicted patients , and suggest its potential therapeutic role for rTMS-driven PFC stimulation in reducing cocaine use , providing a strong rationale for developing larger placebo-controlled studies . Trial name : Repetitive transcranial magnetic stimulation ( rTMS ) in cocaine abusers , URL : 〈http://www.is rct n.com/IS RCT N15823943?q=&filters=&sort=&offset=8&total Results = 13530&page=1&pageSize=10 & search Type = basic- search 〉 , REGISTRATION NUMBER IS RCT N15823943 Recent reports of inflated false-positive rates ( FPRs ) in  FMRI group analysis tools by Eklund and associates in 2016 have become a large topic within ( and outside ) neuroimaging . They concluded that existing parametric methods for determining statistically significant clusters had greatly inflated FPRs ( " up to 70 % , " mainly due to the faulty assumption that the noise spatial autocorrelation function is Gaussian shaped and stationary ) , calling into question potentially " countless " previous results ; in contrast , nonparametric methods , such as their approach , accurately reflected nominal 5 % FPRs . They also stated that AFNI showed " particularly high " FPRs compared to other software , largely due to a bug in 3dClustSim . We comment on these points using their own results and figures and by repeating some of their simulations . Briefly , while parametric methods show some FPR inflation in those tests ( and assumptions of Gaussian-shaped spatial smoothness also appear to be generally incorrect ) , their emphasis on reporting the single worst result from thous and s of simulation cases greatly exaggerated the scale of the problem . Importantly , FPR statistics depends on " task " paradigm and voxelwise p value threshold ; as such , we show how results of their study provide useful suggestions for FMRI study design and analysis , rather than simply a catastrophic downgrading of the field 's earlier results . Regarding AFNI ( which we maintain ) , 3dClustSim 's bug effect was greatly overstated-their own results show that AFNI results were not " particularly " worse than others . We describe further up date s in AFNI for characterizing spatial smoothness more appropriately ( greatly reducing FPRs , although some remain > 5 % ) ; in addition , we outline two newly implemented permutation/r and omization-based approaches producing FPRs clustered much more tightly about 5 % for voxelwise p ≤ 0.01 Significance Functional MRI ( fMRI ) is 25 years old , yet surprisingly its most common statistical methods have not been vali date d using real data . Here , we used  resting-state fMRI data from 499 healthy controls to conduct 3 million task group analyses . Using this null data with different experimental design s , we estimate the incidence of significant results . In theory , we should find 5 % false positives ( for a significance threshold of 5 % ) , but instead we found that the most common software packages for fMRI analysis ( SPM , FSL , AFNI ) can result in false-positive rates of up to 70 % . These results question the validity of a number of fMRI studies and may have a large impact on the interpretation of weakly significant neuroimaging results . The most widely used task functional magnetic resonance imaging ( fMRI ) analyses use parametric statistical methods that depend on a variety of assumptions . In this work , we use real resting-state data and a total of 3 million r and om task group analyses to compute empirical familywise error rates for the fMRI software packages SPM , FSL , and AFNI , as well as a nonparametric permutation method . For a nominal familywise error rate of 5 % , the parametric statistical methods are shown to be conservative for voxelwise inference and invalid for clusterwise inference . Our results suggest that the principal cause of the invalid cluster inferences is spatial autocorrelation functions that do not follow the assumed Gaussian shape . By comparison , the nonparametric permutation test is found to produce nominal results for voxelwise as well as clusterwise inference . These findings speak to the need of validating the statistical methods being used in the field of neuroimaging Impulsive delayed reward discounting ( DRD ) is an important behavioral process in alcohol use disorders ( AUDs ) , reflecting incapacity to delay gratification . Recent work in neuroeconomics has begun to unravel the neural mechanisms supporting DRD , but applications of neuroeconomics in relation to AUDs have been limited . This study examined the neural mechanisms of DRD preferences in AUDs , with emphasis on dissociating activation patterns based on DRD choice type and level of cognitive conflict . Heavy drinking adult men with ( n = 13 ) and without ( n = 12 ) a diagnosis of an AUD completed a monetary DRD task during a functional magnetic resonance imaging scan . Participant responses were coded based on choice type ( impulsive versus restrained ) and level of cognitive conflict ( easy versus hard ) . AUD+ participants exhibited significantly more impulsive DRD decision‐making . Significant activation during DRD was found in several decision‐making regions , including dorsolateral prefrontal cortex ( DLPFC ) , insula , posterior parietal cortex ( PPC ) , and posterior cingulate . An axis of cognitive conflict was also observed , with hard choices associated with anterior cingulate cortex and easy choices associated with activation in supplementary motor area . AUD+ individuals exhibited significant hyperactivity in regions associated with cognitive control ( DLPFC ) and prospect i ve thought ( PPC ) and exhibited less task‐related deactivation of areas associated with the brain 's default network during DRD decisions . This study provides further clarification of the brain systems supporting DRD in general and in relation to AUDs AIMS To contrast functional connectivity on ventral and dorsal striatum networks in cocaine dependence relative to pathological gambling , via a resting-state functional connectivity approach ; and to determine the association between cocaine dependence-related neuroadaptations indexed by functional connectivity and impulsivity , compulsivity and drug relapse . DESIGN Cross-sectional study of 20 individuals with cocaine dependence ( CD ) , 19 individuals with pathological gambling ( PG ) and 21 healthy controls ( HC ) , and a prospect i ve cohort study of 20 CD followed-up for 12 weeks to measure drug relapse . SETTING AND PARTICIPANTS CD and PG were recruited through consecutive admissions to a public clinic specialized in substance addiction treatment ( Centro Provincial de Drogodependencias ) and a public clinic specialized in gambling treatment ( AGRAJER ) , respectively ; HC were recruited through community advertisement in the same area in Granada ( Spain ) . MEASUREMENTS Seed-based functional connectivity in the ventral striatum ( ventral cau date and ventral putamen ) and dorsal striatum ( dorsal cau date and dorsal putamen ) , the Kirby delay-discounting question naire , the reversal-learning task and a dichotomous measure of cocaine relapse indicated with self-report and urine tests . FINDINGS CD relative to PG exhibit enhanced connectivity between the ventral cau date seed and subgenual anterior cingulate cortex , the ventral putamen seed and dorsomedial pre-frontal cortex and the dorsal putamen seed and insula ( P≤0.001 , kE=108 ) . Connectivity between the ventral cau date seed and subgenual anterior cingulate cortex is associated with steeper delay discounting ( P≤0.001 , kE=108 ) and cocaine relapse ( P≤0.005 , kE=34 ) . CONCLUSIONS Cocaine dependence-related neuroadaptations in the ventral striatum of the brain network are associated with increased impulsivity and higher rate of cocaine relapse Aims We investigated reciprocal prospect i ve relationships between multiple behavioural impulsivity tasks ( assessing delay discounting , risk-taking and disinhibition ) and alcohol involvement ( consumption , drunkenness and problems ) among adolescents . We hypothesized that performance on the tasks would predict subsequent alcohol involvement , and that alcohol involvement would lead to increases in behavioural impulsivity over time . Design Cross-lagged prospect i ve design in which impulsivity and alcohol involvement were assessed five times over 2 years ( once every 6 months , on average ) . Setting Classrooms in secondary schools in North West Engl and . Participants Two hundred and eighty-seven adolescents ( 51.2 % male ) who were aged 12 or 13 years at study enrolment . Measurements Participants reported their alcohol involvement and completed computerized tasks of disinhibition , delay discounting and risk-taking  at each assessment . Cross-sectional and prospect i ve relationships between the variables of interest were investigated using cross-lagged analyses . Findings All behavioural impulsivity tasks predicted a composite index of alcohol involvement 6 months later ( all Ps < 0.01 ) , and these prospect i ve relationships were reliable across the majority of time-points . Importantly , we did not observe the converse relationship across time : alcohol involvement did not predict performance on behavioural impulsivity tasks at any subsequent time point . Conclusions Several measures of impulsivity predict escalation in alcohol involvement in young adolescents , but alcohol use does not appear to alter impulsivity BACKGROUND Impulsive decision making is a hallmark of frequently occurring addiction disorders including alcohol dependence ( AD ) . Therefore , ameliorating impulsive decision making is a promising target for the treatment of AD . Previous studies have shown that modafinil enhances cognitive control functions in various psychiatric disorders . However , the effects of modafinil on delay discounting and its underlying neural correlates have not been investigated as yet . The aim of the current study was to investigate the effects of modafinil on neural correlates of impulsive decision making in abstinent AD patients and healthy control ( HC ) subjects . METHOD A r and omized , double-blind , placebo-controlled , within-subjects cross-over study using functional magnetic resonance imaging ( fMRI ) was conducted in 14 AD patients and 16 HC subjects . All subjects participated in two fMRI sessions in which they either received a single dose of placebo or 200 mg of modafinil 2 h before the session . During fMRI , subjects completed a delay-discounting task to measure impulsive decision making . RESULTS Modafinil improved impulsive decision making in AD pateints , which was accompanied by enhanced recruitment of frontoparietal regions and reduced activation of the ventromedial prefrontal cortex . Moreover , modafinil-induced enhancement of functional connectivity between the superior frontal gyrus and ventral striatum was specifically associated with improvement in impulsive decision making . CONCLUSIONS These findings indicate that modafinil can improve impulsive decision making in AD patients through an enhanced coupling of prefrontal control regions and brain regions coding the subjective value of rewards . Therefore , the current study supports the implementation of modafinil in future clinical trials for AD Although higher delay discounting rates have been linked to cigarette smoking , little is known about the stability of delay discounting , whether delay discounting promotes smoking acquisition , whether smoking contributes to impulsive choices , or if different relationships exist in distinct subgroups . This study sought to fill these gaps within a prospect i ve longitudinal cohort study ( N=947 ) spanning mid-adolescence to young adulthood ( age 15 - 21 years old ) .  Smoking and delay discounting  were measured across time . Covariates included peer and household smoking , academic performance , depression , novelty seeking , inattention 
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Behaviorally , significantly steeper DRD was present in individuals with addictive disorders across studies , reproducing earlier findings .
Among individuals with addictive disorders , there was substantial evidence of greater neural activity in the executive control network during choices for larger-delayed rewards ( delayed gratification ) relative to choices for smaller-immediate rewards ( immediate gratification ) , particularly in dorsolateral prefrontal cortex , as well as moderate evidence of greater recruitment of the default mode , salience , and reward valuation networks during larger-delayed choices .
In functional connectivity fMRI studies , there was moderate evidence for greater connectivity between the executive control , salience , and default mode networks in individuals exhibiting addictive behavior .
As a whole , this review suggests consistent differences in neural activation and connectivity relating to DRD in individuals with addictive disorders .