***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: 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 BACKGROUND Tobacco smoking is the leading cause of preventable death in developed countries . Our previous studies in animal models and humans suggest that repeated activation of cue-induced craving networks followed by electromagnetic stimulation of the dorsal prefrontal cortex ( PFC ) can cause lasting reductions in drug craving and consumption . We hypothesized that disruption of these circuitries by deep transcranial magnetic stimulation ( TMS ) of the PFC and insula bilaterally can induce smoking cessation . METHODS Adults ( N = 115 ) who smoke at least 20 cigarettes/day and failed previous treatments were recruited from the general population . Participants were r and omized to receive 13 daily sessions of high-frequency , low-frequency or sham stimulation following , or without , presentation of smoking cues . Deep TMS was administered using an H-coil version targeting the lateral PFC and insula bilaterally . Cigarette consumption was evaluated during the treatment by measuring cotinine levels in urine sample s and recording participants ' self-reports as a primary outcome variable . Dependence and craving were assessed using st and ardized question naires . RESULTS High ( but not low ) frequency deep TMS treatment significantly reduced cigarette consumption and nicotine dependence . The combination of this treatment with exposure to smoking cues enhanced reduction in cigarette consumption leading to an abstinence rate of 44 % at the end of the treatment and an estimated 33 % 6 months following the treatment . CONCLUSIONS This study further implicates the lateral PFC and insula in nicotine addiction and suggests the use of deep high-frequency TMS of these regions following presentation of smoking cues as a promising treatment strategy AIMS As alcohol dependency is characterized by severe executive function deficits , we examined the influence of high-frequency ( HF ) repetitive transcranial magnetic stimulation ( rTMS ) applied to the right dorsolateral prefrontal cortex ( DLPFC ) on executive functioning in recently detoxified alcohol-dependent patients . METHODS In this r and omized , single blind , sham (placebo)-controlled , crossover study , we included 50 detoxified alcohol-dependent patients . We examined the effect of a single right DLPFC HF-rTMS session on commission errors , mean reaction times ( RTs ) and intra-individual reaction time variability ( IIRTV ) during a Go-NoGo task ( 50 % Go/50 % NoGo condition ) in 29 alcohol-dependent patients . Patients completed this cognitive task immediately before and immediately after the stimulation session . In order to avoid carry-over effects between stimulation sessions , a 1-week inter-session interval was respected . Because rTMS treatment has been shown to affect subjective craving , all patients were also assessed with the Obsessive Compulsive Drinking Scale ( OCDS ) . RESULTS After both stimulation conditions , we observed a significant decrease of commission errors , without differences between active and sham HF-rTMS stimulation . No significant difference was observed between active and sham stimulation on mean RT . However , only active stimulation result ed in a significant decrease in IIRTV . No effects of stimulation were found for the craving measurements . CONCLUSION Our findings suggest that in recently detoxified alcohol-dependent patients , one right-sided HF-rTMS session stabilizes cognitive performance during executive control tasks , implying that active stimulation reduces patients ' proneness to attentional lapses Drug-related cues induce craving , which may perpetuate drug use or trigger relapse in addicted individuals .  Craving is also under the influence of other factors in daily life , such as drug availability and self-control . Neuroimaging studies using drug cue paradigms have shown frontal lobe involvement in this context ual influence on cue reactivity , but have not clarified how and which frontal area accounts for this phenomenon . We explored frontal lobe contributions to cue-induced drug craving under different intertemporal drug availability conditions by combining transcranial magnetic stimulation and functional magnetic resonance imaging in smokers . We hypothesized that the dorsolateral prefrontal cortex ( DLPFC ) regulates craving during changes in intertemporal availability . Subjective craving was greater when cigarettes were immediately available , and this effect was eliminated by transiently inactivating the DLPFC with transcranial magnetic stimulation . Functional magnetic resonance imaging demonstrated that the signal most proportional to subjective craving was located in the medial orbitofrontal cortex across all context s , whereas the DLPFC most strongly encoded intertemporal availability information . The craving-related signal in the medial orbitofrontal cortex was attenuated by inactivation of the DLPFC , particularly when cigarettes were immediately available . Inactivation of the DLPFC also reduced craving-related signals in the anterior cingulate and ventral striatum , areas implicated in transforming value signals into action . These findings indicate that DLPFC builds up value signals based on knowledge of drug availability , and support a model wherein aberrant circuitry linking dorsolateral prefrontal and orbitofrontal cortices may underlie addiction BACKGROUND Addiction is associated with dorso-lateral prefrontal cortex ( DLPFC ) dysfunction and altered brain-oscillations . High frequency repetitive transcranial magnetic stimulation ( HFrTMS ) over DLPFC reportedly reduces drug craving . Its effects on neuropsychological , behavioural and neurophysiological are unclear . METHODS We assessed psychological , behavioural and neurophysiological effects of 4 sessions of 10-min adjunctive HFrTMS over the left DLPFC during two weeks during a residential programme for alcohol detoxification . Participants were r and omized to active HFrTMS ( 10 Hz , 100 % motor threshold ) or sham . Immediately before the first and after the last session , 32-channels EEG was recorded and alcohol craving Visual Analogue Scale , Symptom Check List-90-R ,  Numeric Stroop task  and Go/No-go task administered . Tests were repeated at 1-month follow-up . RESULTS 17 subjects ( mean age 44.7 years , 4 F ) were assessed . Active rTMS subjects performed better at Stroop test at end of treatment ( p=0.036 ) and follow up ( p=0.004 ) and at Go-NoGo at end of treatment ( p=0.05 ) and follow up ( p=0.015 ) . Depressive symptoms decreased at end of active treatment ( p=0.036 ) . Active-TMS showed an overall decrease of fast EEG frequencies after treatment compared to sham ( p=0.026 ) . No significant modifications over time or group emerged for craving and number of drinks at follow up . CONCLUSION 4 HFrTMS sessions over two weeks on the left DLPFC can improve inhibitory control task and selective attention and reduce depressive symptoms . An overall reduction of faster EEG frequencies was observed . Nonetheless , this schedule is ineffective in reducing craving and alcohol intake BACKGROUND Prior research in substance dependence has suggested potential anti-craving effects of repetitive transcranial magnetic stimulation ( rTMS ) when applied to the dorsolateral prefrontal cortex ( DLPFC ) . However , no single sham-controlled session studies applied to the right DLPFC have been carried-out in recently detoxified alcohol-dependent patients . Furthermore , no studies examined the effect of a single HF-rTMS session on craving in these patients ' natural habitat . METHODS To further investigate the effect of high-frequency (HF)-rTMS of the right DLPFC on alcohol craving , we performed a prospect i ve , single-blind , sham-controlled study involving 36 hospitalized patients with alcohol dependence syndrome . After successful detoxification , patients were allocated receiving one active or one sham HF-rTMS session . The obsessive-compulsive drinking scale ( OCDS ) was administered to evaluate the extent of craving just before and after the HF-rTMS session ( on Friday ) , on Saturday and Sunday during the weekend at home , and on Monday when the patient returned to the hospital . RESULTS One single blind sham-controlled HF-rTMS session applied to the right DLPFC did not result in changes in craving ( neither immediately after the stimulation session , nor in patients ' natural environment during the weekend ) . CONCLUSIONS One HF-rTMS stimulation session applied to the right DLPFC had no significant effects on alcohol craving in alcohol dependent patients . One such session could have been too short to alter alcohol craving in a sample of alcohol dependent patients Dopamine is implicated in movement , learning , and motivation , and in illnesses such as Parkinson 's disease , schizophrenia , and drug addiction . Little is known about the control of dopamine release in humans , but research in experimental animals suggests that the prefrontal cortex plays an important role in regulating the release of dopamine in subcortical structures . Here we used [(11)C]raclopride and positron emission tomography to measure changes in extracellular dopamine concentration in vivo after repetitive transcranial magnetic stimulation ( rTMS ) of the dorsolateral prefrontal cortex in healthy human subjects . Repetitive TMS of the left dorsolateral prefrontal cortex caused a reduction in [(11)C]raclopride binding in the left dorsal cau date nucleus compared with rTMS of the left occipital cortex . There were no changes in binding in the putamen , nucleus accumbens , or right cau date . This shows that rTMS of the prefrontal cortex induces the release of endogenous dopamine in the ipsilateral cau date nucleus . This finding has implication s for the therapeutic and research use of rTMS in neurological and psychiatric disorders BACKGROUND Positron emission tomography ( PET ) imaging studies have shown that addiction to a number of substances of abuse is associated with a decrease in dopamine D(2/3 ) receptor binding and decreased presynaptic dopamine release in the striatum . Some studies have also shown that these reductions are associated with the severity of addiction . For example , in cocaine dependence , low dopamine release is associated with the choice to self-administer cocaine . The goal of the present study was to investigate these parameters of striatal dopamine transmission in heroin dependence and their association with drug seeking behavior . METHODS Heroin-dependent and healthy control subjects were scanned with [(11)C]raclopride before and after stimulant administration ( methylpheni date ) to measure striatal D(2/3 ) receptor binding and presynaptic dopamine release . After the PET scans , the heroin-dependent subjects performed heroin self-administration sessions . RESULTS Both striatal D(2/3 ) receptor binding and dopamine release were reduced in the heroin-dependent subjects compared with healthy control subjects . However , neither PET measure of dopamine transmission predicted the choice to self-administer heroin . CONCLUSIONS These findings show that heroin addiction , like addiction to other drugs of abuse , is associated with low D(2/3 ) receptor binding and low presynaptic dopamine . However , neither of these outcome measures was associated with the choice to self-administer heroin We used PET (15)O and a modified version of the Stroop task to determine if 25-day abstinent heavy marijuana ( MJ ) users have persistent deficits in executive cognitive functioning ( ECF ) and brain activity . Performance on a modified version of the Stroop task and brain activity was compared between 25-day abstinent , heavy marijuana users ( n = 11 ) , and a matched comparison group ( n = 11 ) . The 25-day abstinent marijuana users showed no deficits in performance on the modified version of the Stroop task when compared to the comparison group . Despite the lack of performance differences , the marijuana users showed hypoactivity in the 
    Output:
    
Effects of other rTMS protocol s on craving were not significant .
However , when examining substance consumption , excitatory rTMS of the left DLPFC and excitatory deep TMS ( dTMS ) of the bilateral DLPFC and insula revealed significant consumption-reducing effects , compared with sham stimulation .
Excitatory repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex appears to have an acute effect on reducing craving and substance consumption in patients with substance dependence .
The anti-craving effect may be associated with stimulation dose