Chemogenetic modulation of astrocytes and microglia: State-of-the-art and implications in neuroscience.

Insights into the role astrocytes and microglia play in normal and diseased brain functioning has expanded drastically over the last decade. Recently, chemogenetic tools have emerged as cutting-edge techniques, allowing targeted and spatiotemporal precise manipulation of a specific glial cell type. As a result, significant advances in astrocyte and microglial cell function have been made, showing how glial cells can intervene in central nervous system (CNS) functions such as cognition, reward and feeding behavior in addition to their established contribution in brain diseases, pain, and CNS inflammation. Here, we discuss the latest insights in glial functions in health and disease that have been made through the application of chemogenetics. We will focus on the manipulation of intracellular signaling pathways induced by activation of the designer receptors exclusively activated by designer drugs (DREADDs) in astrocytes and microglia. We will also elaborate on some of the potential pitfalls and the translational potential of the DREADD technology.

Cannabis-dependent adolescents show differences in global reward-associated network topology: A functional connectomics approach.

Adolescence may be a period of increased vulnerability to the onset of drug misuse and addiction due to changes in developing brain networks that support cognitive and reward processing. Cannabis is a widely misused illicit drug in adolescence which can lead to dependence and alterations in reward-related neural functioning. Concerns exist that cannabis-related alterations in these reward networks in adolescence may sensitize behaviour towards all forms of reward that increase the risk of further drug use. Taking a functional connectomics approach, we compared an acutely abstinent adolescent cannabis-dependent (CAN) group with adolescent controls (CON) on global measures of network topology associated with anticipation on a monetary incentive delay task. In the presence of overall superior accuracy, the CAN group exhibited superior global connectivity (clustering coefficient, efficiency, characteristic path length) during monetary gain anticipation compared with the CON group. Additional analyses showed that the CAN group exhibited significantly greater connectivity strength during monetary gain anticipation across a subnetwork that included mesocorticolimbic nodes involving both interhemispheric and intrahemispheric connections. We discuss how these differences in reward-associated connectivity may allude to subtle functional alterations in network architecture in adolescent cannabis-dependence that could enhance the motivation for nondrug reward during acute abstinence.

Naltrexone differentially modulates the neural correlates of motor impulse control in abstinent alcohol-dependent and polysubstance-dependent individuals.

Identifying key neural substrates in addiction disorders for targeted drug development remains a major challenge for clinical neuroscience. One emerging target is the opioid system, where substance-dependent populations demonstrate prefrontal opioid dysregulation that predicts impulsivity and relapse. This may suggest that disturbances to the prefrontal opioid system could confer a risk for relapse in addiction due to weakened 'top-down' control over impulsive behaviour. Naltrexone is currently licensed for alcohol dependence and is also used clinically for impulse control disorders. Using a go/no-go (GNG) task, we examined the effects of acute naltrexone on the neural correlates of successful motor impulse control in abstinent alcoholics (AUD), abstinent polysubstance-dependent (poly-SUD) individuals and controls during a randomised double blind placebo controlled fMRI study. In the absence of any differences on GNG task performance, the AUD group showed a significantly greater BOLD response compared to the control group in lateral and medial prefrontal regions during both placebo and naltrexone treatments; effects that were positively correlated with alcohol abstinence. There was also a dissociation in the positive modulating effects of naltrexone in the orbitofrontal cortex (OFC) and anterior insula cortex (AIC) of the AUD and poly-SUD groups respectively. Self-reported trait impulsivity in the poly-SUD group also predicted the effect of naltrexone in the AIC. These results suggest that acute naltrexone differentially amplifies neural responses within two distinct regions of a salience network during successful motor impulse control in abstinent AUD and poly-SUD groups, which are predicted by trait impulsivity in the poly-SUD group.

Smokers and ex-smokers have shared differences in the neural substrates for potential monetary gains and losses.

Despite an increased understanding of nicotine addiction, there is a scarcity of research comparing the neural correlates of non-drug reward between smokers and ex-smokers. Long-term changes in reward-related brain functioning for non-drug incentives may elucidate patterns of functioning that potentially contribute to ongoing smoking behaviour in current smokers. Similarly, examining the effects of previous chronic nicotine exposure during a period of extended abstinence may reveal whether there are neural correlates responsible for non-drug reward processing that are different from current smokers. The current study, therefore, sets out to examine the neural correlates of reward and loss anticipation, and their respective outcomes, in smokers, ex-smokers and matched controls using a monetary incentive delay task during functional magnetic resonance imaging. Here, we report that in the absence of any significant behavioural group differences, both smokers and ex-smokers showed a significantly greater activation change in the lateral orbitofrontal/anterior insular cortex compared with smokers when anticipating both potential monetary gains and losses. We further report that ex-smokers showed a significantly greater activation change in the ventral putamen compared with both controls and smokers and in the caudate compared with controls during the anticipation of potential monetary losses only. The results suggest that smoking may sensitize striato-orbitofrontal circuitry subserving motivational processes for loss avoidance and reward gain in nicotine addiction.

Naltrexone ameliorates functional network abnormalities in alcohol-dependent individuals.

Naltrexone, an opioid receptor antagonist, is commonly used as a relapse prevention medication in alcohol and opiate addiction, but its efficacy and the mechanisms underpinning its clinical usefulness are not well characterized. In the current study, we examined the effects of 50-mg naltrexone compared with placebo on neural network changes associated with substance dependence in 21 alcohol and 36 poly-drug-dependent individuals compared with 36 healthy volunteers. Graph theoretic and network-based statistical analysis of resting-state functional magnetic resonance imaging (MRI) data revealed that alcohol-dependent subjects had reduced functional connectivity of a dispersed network compared with both poly-drug-dependent and healthy subjects. Higher local efficiency was observed in both patient groups, indicating clustered and segregated network topology and information processing. Naltrexone normalized heightened local efficiency of the neural network in alcohol-dependent individuals, to the same levels as healthy volunteers. Naltrexone failed to have an effect on the local efficiency in abstinent poly-substance-dependent individuals. Across groups, local efficiency was associated with substance, but no alcohol exposure implicating local efficiency as a potential premorbid risk factor in alcohol use disorders that can be ameliorated by naltrexone. These findings suggest one possible mechanism for the clinical effects of naltrexone, namely, the amelioration of disrupted network topology.

Acute naltrexone does not remediate fronto-striatal disturbances in alcoholic and alcoholic polysubstance-dependent populations during a monetary incentive delay task.

There is a concerted research effort to investigate brain mechanisms underlying addiction processes that may predicate the development of new compounds for treating addiction. One target is the brain's opioid system, because of its role in the reinforcing effects of substances of abuse. Substance-dependent populations have increased numbers of the mu opioid receptor (MOR) in fronto-striatal regions that predict drug relapse, and demonstrate disturbances in these regions during the processing of non-drug rewards. Naltrexone is currently licensed for alcohol and opiate dependence, and may remediate such disturbances through the blockade of MORs in fronto-striatal reward circuitry. Therefore, we examined the potential acute modulating effects of naltrexone on the anticipation of, and instrumental responding for, non-drug rewards in long-term abstinent alcoholics, alcoholic poly substance-dependent individuals and controls using a monetary incentive delay (MID) task during a randomized double blind placebo controlled functional MRI study. We report that the alcoholic poly substance-dependent group exhibited slower and less accurate instrumental responding compared to alcoholics and controls that was less evident after acute naltrexone treatment. However, naltrexone treatment was unable to remediate disturbances within fronto-striatal regions during reward anticipation and 'missed' rewards in either substance-dependent group. While we have not been able to identify the underlying neural mechanisms for improvement observed with naltrexone in the alcoholic poly-substance dependent group, we can confirm that both substance-dependent groups exhibit substantial neural deficits during an MID task, despite being in long-term abstinence.

The Modulatory Effects of Atomoxetine on Aberrant Connectivity During Attentional Processing in Cocaine Use Disorder.

BACKGROUND: Cocaine use disorder is associated with cognitive deficits that reflect dysfunctional processing across neural systems. Because there are currently no approved medications, treatment centers provide behavioral interventions that have only short-term efficacy. This suggests that behavioral interventions are not sufficient by themselves to lead to the maintenance of abstinence in patients with cocaine use disorder. Self-control, which includes the regulation of attention, is critical for dealing with many daily challenges that would benefit from medication interventions that can ameliorate cognitive neural disturbances. METHODS: To address this important clinical gap, we conducted a randomized, double-blind, placebo-controlled, crossover design study in patients with cocaine use disorder (n = 23) and healthy control participants (n = 28). We assessed the modulatory effects of acute atomoxetine (40 mg) on attention and conflict monitoring and their associated neural activation and connectivity correlates during performance on the Eriksen flanker task. The Eriksen flanker task examines basic attentional processing using congruent stimuli and the effects of conflict monitoring and response inhibition using incongruent stimuli, the latter of which necessitates the executive control of attention. RESULTS: We found that atomoxetine improved task accuracy only in the cocaine group but modulated connectivity within distinct brain networks in both groups during congruent trials. During incongruent trials, the cocaine group showed increased task-related activation in the right inferior frontal and anterior cingulate gyri, as well as greater network connectivity than the control group across treatments. CONCLUSIONS: The findings of the current study support a modulatory effect of acute atomoxetine on attention and associated connectivity in cocaine use disorder.

Abnormal Brain Networks Related to Drug and Nondrug Reward Anticipation and Outcome Processing in Stimulant Use Disorder: A Functional Connectomics Approach.

BACKGROUND: Drug addiction is associated with blunted neural responses to nondrug rewards, such as money, but heightened responses to drug cues that predict drug-reward outcomes. This dissociation underscores the role of incentive context in the attribution of motivational salience, which may reflect a narrowing toward drug-related goals. This hypothesis, however, has scarcely been investigated. METHODS: To address this important scientific gap, the current study performed an empirical assessment of differences in salience attribution by comparing patients with stimulant use disorder (SUD) (n = 41) with control participants (n = 48) on network connectivity related to anticipation and outcome processing using a modified monetary incentive delay task. We hypothesized increased task-related activation and connectivity to drug rewards in patients with SUD, and reduced task-related activation and connectivity to monetary rewards during incentive processing across brain networks. RESULTS: In the presence of behavioral and regional brain activation similarities, we found that patients with SUD showed significantly less connectivity involving three separate distributed networks during monetary reward anticipation, and drug and monetary reward outcome processing. No group connectivity differences for drug reward anticipation were identified. Additional graph theory analyses revealed that patients with SUD had longer path lengths across these networks, all of which positively correlated with the duration of stimulant drug use. CONCLUSIONS: Specific disruptions in connectivity in networks related to the anticipation of nondrug reward together with more general dysconnectivity in the processing of rewarding outcomes suggest an insensitivity to consequences. These observations support the notion of a predominance of habitual control in patients with SUD.

Reduced neural functional connectivity during working memory performance in methamphetamine use disorder.

BACKGROUND: Methamphetamine misuse, a surging cause of morbidity and mortality worldwide, identifies Methamphetamine Use Disorder (MUD) as a critical public health problem. Treatment for MUD typically is sought during early abstinence when patients are experiencing cognitive difficulties that may hamper their engagement in treatment and recovery. Cognitive difficulties, particularly those that involve executive functions, likely reflect disruptions in neural functioning involving multiple brain areas and circuits. METHODS: To extend knowledge in this area, we compared individuals with MUD (MUD group, n = 30) in early abstinence (3-11 days abstinent) with a healthy control group (HC, n = 33) on brain activation and network connectivity and topology, using functional magnetic resonance imaging (fMRI) during performance on an N-back working memory task. The N-back task involves the maintenance and manipulation of information in short-term memory and engages multiple neural processes related to executive functioning. The task was administered at two working-memory difficulty loads (1-back and 2-back). RESULTS: Compared with the HC group, the MUD group had worse task performance but no differences in task-related brain activation. Network-based statistics analyses, however, revealed that the MUD group exhibited less functional network connectivity at both difficulty loads of the N-back task than the HC group. Additional graph theory analyses showed that path lengths were longer, and clustering was lower across these networks, which also exhibited disrupted small-world properties in the MUD group. CONCLUSION: These results suggest a decoupling in network dynamics that may underlie deficits in cognition during early abstinence in MUD patients.

Unravelling the brain metabolome: A review of liquid chromatography - mass spectrometry strategies for extracellular brain metabolomics.

The analysis of the brain extracellular metabolome is of interest for numerous subdomains within neuroscience. Not only does it provide information about normal physiological functions, it is even more of interest for biomarker discovery and target discovery in disease. The extracellular analysis of the brain is particularly interesting as it provides information about the release of mediators in the brain extracellular fluid to look at cellular signaling and metabolic pathways through the release, diffusion and re-uptake of neurochemicals. In vivo samples are obtained through microdialysis, cerebral open-flow microperfusion or solid-phase microextraction. The analytes of potential interest are typically low in concentration and can have a wide range of physicochemical properties. Liquid chromatography coupled to mass spectrometry has proven its usefulness in brain metabolomics. It allows sensitive and specific analysis of low sample volumes, obtained through different approaches. Several strategies for the analysis of the extracellular fluid have been proposed. The most widely used approaches apply sample derivatization, specific stationary phases and/or hydrophilic interaction liquid chromatography. Miniaturization of these methods allows an even higher sensitivity. The development of chiral metabolomics is indispensable, as it allows to compare the enantiomeric ratio of compounds and provides even more challenges. Some limitations continue to exist for the previously developed methods and the development of new, more sensitive methods remains needed. This review provides an overview of the methods developed for sampling and liquid chromatography-mass spectrometry analysis of the extracellular metabolome.

Current Approaches to Monitor Macromolecules Directly from the Cerebral Interstitial Fluid.

Gaining insights into the pharmacokinetic and pharmacodynamic properties of lead compounds is crucial during drug development processes. When it comes to the treatment of brain diseases, collecting information at the site of action is challenging. There are only a few techniques available that allow for the direct sampling from the cerebral interstitial space. This review concerns the applicability of microdialysis and other approaches, such as cerebral open flow microperfusion and electrochemical biosensors, to monitor macromolecules (neuropeptides, proteins, …) in the brain. Microdialysis and cerebral open flow microperfusion can also be used to locally apply molecules at the same time at the site of sampling. Innovations in the field are discussed, together with the pitfalls. Moreover, the 'nuts and bolts' of the techniques and the current research gaps are addressed. The implementation of these techniques could help to improve drug development of brain-targeted drugs.

Differences in "bottom-up" and "top-down" neural activity in current and former cigarette smokers: Evidence for neural substrates which may promote nicotine abstinence through increased cognitive control.

Drug-related stimuli, through conditioning, are thought to acquire incentive motivational properties that code possible reward availability and elicit an attentional bias, possibly through increased "bottom-up" neural processing. The processes underlying this attentional bias are considered important in the maintenance of addiction, and crucially, in relapse among substance users attempting to remain abstinent. Equally, impaired "top-down" cognitive control may impair the ability to restrain "bottom-up" pre-potent behaviours, such as drug use, following exposure to drug-related stimuli. Two experiments sought to identify the neural loci of bottom-up/top-down processing during fMRI. Experiment 1 utilised an attentional bias paradigm to examine the behavioural and neural responses to neutral, emotionally evocative and smoking-related cues in control (n=13), ex-smoking (n=10 - abstinent >12months) and smoking (n=13 - mean >6.5years of use) groups. Experiment 2 used a go/no-go paradigm to examine the neural correlates of motor response inhibition and error monitoring in the same sample. The results of Experiment 1 demonstrated that, across conditions, current smokers had significantly less neural activity in cortical but significantly more activity in subcortical areas compared to both controls and ex-smokers. Ex-smokers exhibited more neural activity than both control and smoker groups in prefrontal cortical regions. Similarly, Experiment 2 revealed that smokers had reduced neural activity in prefrontal cortical regions during motor response inhibition compared to controls while ex-smokers demonstrated greater neural activity in prefrontal cortical regions compared to both controls and smokers during error monitoring. The results reveal cortical and subcortical differences between current smokers and controls and a general pattern of increased prefrontal cortical activity in ex-smokers. These findings may suggest that elevated topdown control might be an important characteristic of successful abstinence in individuals formerly dependent on nicotine.

Prefrontal hypoactivation during cognitive control in early abstinent methamphetamine-dependent subjects.

Individuals who abuse methamphetamine (MA) perform at levels below those of healthy controls on tests that require cognitive control. As cognitive control deficits may influence the success of treatment for addiction, we sought to help clarify the neural correlates of this deficit. MA-dependent (n=10, abstinent 4-7 days) and control subjects (n=18) performed a color-word Stroop task, which requires cognitive control, during functional MRI (fMRI). The task included a condition in which participants were required to respond to one stimulus dimension while ignoring another conflicting dimension, and another condition without conflict. We compared the groups on performance and neural activation in the two conditions. MA-dependent subjects made more errors and responded more slowly than controls. Controlling for response times in the incongruent condition, voxel-wise mixed effects analyses (whole-brain corrected) demonstrated that MA-dependent subjects had less activation than control subjects in the right inferior frontal gyrus, supplementary motor cortex/anterior cingulate gyrus and the anterior insular cortex during the incongruent condition only. MA-dependent subjects did not exhibit greater activation in any brain region in either of the Stroop conditions. These preliminary findings suggest that hypofunction in cortical areas that are important for executive function underlies cognitive control deficits associated with MA dependence.

Increased ventral striatal BOLD activity during non-drug reward anticipation in cannabis users.

Despite an increased understanding of the pharmacology and long-term cognitive effects of cannabis in humans, there has been no research to date examining its chronic effects upon reward processing in the brain. Motivational theories regarding long-term drug use posit contrasting predictions with respect to how drug users are likely to process non-drug incentives. The reward deficiency syndrome (RDS) of addiction posits that there are deficits in dopamine (DA) motivational circuitry for non-drug rewards, such that only drugs of abuse are capable of normalizing DA in the ventral striatum (VS). Alternatively, the opponent process theory (OPT) holds that in individuals prone to drug use, there exists some form of mesolimbic hyperactivity, in which there is a bias towards reward-centred behaviour concomitant with impulsivity. The current study examined BOLD responses during reward and loss anticipation and their outcome deliveries in 14 chronic cannabis users and 14 drug-naive controls during a monetary incentive delay (MID) task. Despite no significant behavioural differences between the two groups, cannabis users had significantly more right VS BOLD activity during reward anticipation. Correlation analyses demonstrated that this right VS BOLD response was significantly correlated with life-time use and reported life-time cannabis joints consumed. No correlations between cannabis abstinence and BOLD responses were observed. We also observed a number of group differences following outcome deliveries, most notably hypoactivity in the left insula cortex in response to loss and loss avoidance outcome notifications in the cannabis group. These results may suggest hypersensitivity during instrumental response anticipation for non-drug rewards and a hyposensitivity to loss outcomes in chronic cannabis users; the implications of which are discussed with respect to the potentially sensitizing effects of cannabis for other rewards.

Disturbances across whole brain networks during reward anticipation in an abstinent addiction population.

The prevalent spatial distribution of abnormalities reported in cognitive fMRI studies in addiction suggests there are extensive disruptions across whole brain networks. Studies using resting state have reported disruptions in network connectivity in addiction, but these studies have not revealed characteristics of network functioning during critical psychological processes that are disrupted in addiction populations. Analytic methods that can capture key features of whole brain networks during psychological processes may be more sensitive in revealing additional and widespread neural disturbances in addiction, that are the provisions for relapse risk, and targets for medication development. The current study compared a substance addiction (ADD; n = 83) group in extended abstinence with a control (CON; n = 68) group on functional MRI (voxel-wise activation) and global network (connectivity) measures related to reward anticipation on a monetary incentive delay task. In the absence of group differences on MID performance, the ADD group showed reduced activation predominantly across temporal and visual regions, but not across the striatum. The ADD group also showed disruptions in global network connectivity (lower clustering coefficient and higher characteristic path length), and significantly less connectivity across a sub-network comprising frontal, temporal, limbic and striatal nodes. These results show that an addiction group in extended abstinence exhibit localised disruptions in brain activation, but more extensive disturbances in functional connectivity across whole brain networks. We propose that measures of global network functioning may be more sensitive in highlighting latent and more widespread neural disruptions during critical psychological processes in addiction and other psychiatric disorders.

Shared and divergent neural reactivity to non-drug operant response outcomes in current smokers and ex-smokers.

Addiction to cigarettes presents with considerable health risks and induces high costs on healthcare resources. While the majority of cigarette smokers endorse the desire to quit, only a small percentage of quit attempts lead to full abstinence. Failure to achieve abstinence may arise from maladaptive reactivity in fronto-striatal regions that track positive and negative valence outcomes, thus biasing the choice to smoke in the presence of alternative, non-drug reinforcement. Alternatively, long-term nicotine abstinence may reveal neural substrates of adaptive valence outcome processing that promote and maintain smoking cessation. The present study set out to examine the neural correlates of operant response outcomes in current smokers, ex-smokers and matched controls using a monetary incentive delay task during functional MRI. Here we report that compared to controls, both current smokers and ex-smokers showed significantly less activation change in the left amygdala during positive response outcomes, and in the anterior cingulate cortex, during both positive and negative response outcomes. Ex-smokers, however, demonstrated significantly greater activation change compared to smokers and controls in the right amygdala during negative response outcomes. Activation change in the anterior cingulate cortex and middle frontal gyrus of smokers was significantly negatively correlated with nicotine dependence and cigarette pack-years. These results suggest a pattern of shared and divergent reactivity in current smokers and ex-smokers within corticolimbic regions that track both positive and negative operant response outcomes. Exaggerated adaptive processing in ex-smokers may promote long-term smoking cessation through amplified negative valence outcome monitoring.

Opioid Antagonists and the A118G Polymorphism in the µ-Opioid Receptor Gene: Effects of GSK1521498 and Naltrexone in Healthy Drinkers Stratified by OPRM1 Genotype.

This corrects the article DOI: 10.1038/npp.2016.60.

Pharmacodynamics of diazepam co-administered with methadone or buprenorphine under high dose conditions in opioid dependent patients.

BACKGROUND: Benzodiazepine abuse is common among methadone- and buprenorphine-maintained patients; however interactions between these drugs under high dose conditions have not been adequately examined under controlled conditions. OBJECTIVE: To investigate the effects of co-administering diazepam with methadone or buprenorphine under high dose conditions. DESIGN: Double-blind, randomly ordered, 2 x 2 cross-over design in which the effects of diazepam dose (0mg versus 40 mg) and opioid dose (100% versus 150% normal dose) were examined over four sessions in methadone- and buprenorphine-maintained patients. PARTICIPANTS: Four methadone- and seven buprenorphine-prescribed patients without concurrent dependence on other substances or significant medical co-morbidity. MEASURES: Physiological (pulse rate, blood pressure, pupil size, respiratory rate and peripheral SpO2), subjective (ARCI, VAS ratings) and performance (reaction time, cancellation task and Digit Symbol Substitution Test, DSST) measures were taken prior to and for 6h post-dosing. RESULTS: High dose diazepam was associated with time-dependent increases in the intensity of subjective drug effects (strength of drug effect, sedation) and decreases in psychological performance (reaction time, DSST) for both methadone and buprenorphine patients. These effects were generally independent of the opioid dose administered. High dose opioid administration (150% normal dose) was associated with reductions in overall SpO2 levels and performance (reaction time, DSST) in the methadone patients, but had virtually no impact on pharmacodynamic responses in the buprenorphine group. CONCLUSION: High dose diazepam significantly alters subjective drug responses and psychological performance in patients maintained on methadone and buprenorphine.

The neurobiology of addiction: the perspective from magnetic resonance imaging present and future.

BACKGROUND AND AIMS: Addiction is associated with severe economic and social consequences and personal tragedies, the scientific exploration of which draws upon investigations at the molecular, cellular and systems levels with a wide variety of technologies. Magnetic resonance imaging (MRI) has been key to mapping effects observed at the microscopic and mesoscopic scales. The range of measurements from this apparatus has opened new avenues linking neurobiology to behaviour. This review considers the role of MRI in addiction research, and what future technological improvements might offer. METHODS: A hermeneutic strategy supplemented by an expansive, systematic search of PubMed, Scopus and Web of Science databases, covering from database inception to October 2015, with a conjunction of search terms relevant to addiction and MRI. Formal meta-analyses were prioritized. RESULTS: Results from methods that probe brain structure and function suggest frontostriatal circuitry disturbances within specific cognitive domains, some of which predict drug relapse and treatment response. New methods of processing imaging data are opening opportunities for understanding the role of cerebral vasculature, a global view of brain communication and the complex topology of the cortical surface and drug action. Future technological advances include increases in MRI field strength, with concomitant improvements in image quality. CONCLUSIONS: The magnetic resonance imaging literature provides a limited but convergent picture of the neurobiology of addiction as global changes to brain structure and functional disturbances to frontostriatal circuitry, accompanied by changes in anterior white matter.

Acute D3 Antagonist GSK598809 Selectively Enhances Neural Response During Monetary Reward Anticipation in Drug and Alcohol Dependence.

This corrects the article DOI: 10.1038/npp.2016.289.