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Abstract One of the most critical challenges in using noninvasive brain stimulation (NIBS) techniques for the treatment of psychiatric and neurologic disorders is inter- and intra-individual variability in response to NIBS. Response variations in previous findings suggest that the one-size-fits-all approach does not seem the most appropriate option for enhancing stimulation outcomes. While there is a growing body of evidence for the feasibility and effectiveness of individualized NIBS approaches, the optimal way to achieve this is yet to be determined. Transcranial electrical stimulation (tES) is one of the NIBS techniques showing promising results in modulating treatment outcomes in several psychiatric and neurologic disorders, but it faces the same challenge for individual optimization. With new computational and methodological advances, tES can be integrated with real-time functional magnetic resonance imaging (rtfMRI) to establish closed-loop tES-fMRI for individually optimized neuromodulation. Closed-loop tES-fMRI systems aim to optimize stimulation parameters based on minimizing differences between the model of the current brain state and the desired value to maximize the expected clinical outcome. The methodological space to optimize closed-loop tES fMRI for clinical applications includes (1) stimulation vs. data acquisition timing, (2) fMRI context (task-based or resting-state), (3) inherent brain oscillations, (4) dose-response function, (5) brain target trait and state and (6) optimization algorithm. Closed-loop tES-fMRI technology has several advantages over non-individualized or open-loop systems to reshape the future of neuromodulation with objective optimization in a clinically relevant context such as drug cue reactivity for substance use disorder considering both inter and intra-individual variations. Using multi-level brain and behavior measures as input and desired outcomes to individualize stimulation parameters provides a framework for designing personalized tES protocols in precision psychiatry.

Addiction medicine is a dynamic field that encompasses clinical practice and research in the context of societal, economic, and cultural factors at the local, national, regional, and global levels. This field has evolved profoundly during the past decades in terms of scopes and activities with the contribution of addiction medicine scientists and professionals globally. The dynamic nature of drug addiction at the global level has resulted in a crucial need for developing an international collaborative network of addiction societies, treatment programs and experts to monitor emerging national, regional, and global concerns. This protocol paper presents methodological details of running longitudinal surveys at national, regional, and global levels through the Global Expert Network of the International Society of Addiction Medicine (ISAM-GEN). The initial formation of the network with a recruitment phase and a round of snowball sampling provided 354 experts from 78 countries across the globe. In addition, 43 national/regional addiction societies/associations are also included in the database. The surveys will be developed by global experts in addiction medicine on treatment services, service coverage, co-occurring disorders, treatment standards and barriers, emerging addictions and/or dynamic changes in treatment needs worldwide. Survey participants in categories of (1) addiction societies/associations, (2) addiction treatment programs, (3) addiction experts/clinicians and (4) related stakeholders will respond to these global longitudinal surveys. The results will be analyzed and cross-examined with available data and peer-reviewed for publication.

Understanding the dose-response relationship is crucial in studying the effects of brain stimulation techniques, such as transcranial direct current stimulation (tDCS). The dose-response relationship refers to the relationship between the received stimulation dose and the resulting response, which can be described as a function of the dose at various levels, including single/multiple neurons, clusters, regions, or networks. Here, we are focused on the received stimulation dose obtained from computational head models and brain responses which are quantified by functional magnetic resonance imaging (fMRI) data. In this randomized, triple-blind, sham-controlled clinical trial, we recruited sixty participants with methamphetamine use disorders (MUDs) as a sample clinical population who were randomly assigned to receive either sham or active tDCS. Structural and functional MRI data, including high-resolution T1 and T2-weighted MRI, resting-state functional MRI, and a methamphetamine cue-reactivity task fMRI, were acquired before and after tDCS. Individual head models were generated using the T1 and T2-weighted MRI data to simulate electric fields. In a linear approach, we investigated the associations between electric fields (received dose) and changes in brain function (response) at four different levels: voxel level, regional level (using atlas-based parcellation), cluster level (identifying active clusters), and network level (task-based functional connectivity). At the voxel level, regional level, and cluster level, no FDR-corrected significant correlation was observed between changes in functional activity and electric fields. However, at the network level, a significant positive correlation was found between frontoparietal connectivity and the electric field at the frontopolar stimulation site (r = 0.42, p corrected = 0.02; medium effect size). Our proposed pipeline offers a methodological framework for analyzing tDCS effects by exploring dose-response relationships at different levels, enabling a direct link between electric field variability and the neural response to tDCS. The results indicate that network-based analysis provides valuable insights into the dependency of tDCS neuromodulatory effects on the individual's regional current dose. Integration of dose-response relationships can inform dose optimization, customization, or the extraction of predictive/treatment-response biomarkers in future brain stimulation studies.

Abstract Background Considerable number of people still use opium worldwide and many believe in opium’s health benefits. However, several studies proved the detrimental effects of opium on the body, especially the cardiovascular system. Herein, we aimed to provide the first evidence regarding the effects of opium use on one-year major adverse cardiovascular events (MACE) in the patients with ST-elevation MI (STEMI) who underwent primary PCI. Methods We performed a propensity score matching of 2:1 (controls: opium users) that yielded 518 opium users and 1036 controls. Then, we performed conventional statistical and machine learning analyses on these matched cohorts. Regarding the conventional analysis, we performed multivariate analysis for hazard ratio (HR) of different variables and MACE and plotted Kaplan Meier curves. In the machine learning section, we used two tree-based ensemble algorithms, Survival Random Forest and XGboost for survival analysis. Variable importance (VIMP), tree minimal depth, and variable hunting were used to identify the importance of opium among other variables. Results Opium users experienced more one-year MACE than their counterparts, although it did not reach statistical significance (Opium: 72/518 (13.9%), Control: 112/1036 (10.8%), HR: 1.27 (95% CI: 0.94–1.71), adjusted p-value = 0.136). Survival random forest algorithm ranked opium use as 13th, 13th, and 12th among 26 variables, in variable importance, minimal depth, and variable hunting, respectively. XGboost revealed opium use as the 12th important variable. Partial dependence plot demonstrated that opium users had more one-year MACE compared to non-opium-users. Conclusions Opium had no protective effects on one-year MACE after primary PCI on patients with STEMI. Machine learning and one-year MACE analysis revealed some evidence of its possible detrimental effects, although the evidence was not strong and significant. As we observed no strong evidence on protective or detrimental effects of opium, future STEMI guidelines may provide similar strategies for opium and non-opium users, pending the results of forthcoming studies. Governments should increase the public awareness regarding the evidence for non-beneficial or detrimental effects of opium on various diseases, including the outcomes of primary PCI, to dissuade many users from relying on false beliefs about opium’s benefits to continue its consumption.

Abstract Background With increasing obese populations worldwide, developing interventions to modulate food-related brain processes and functions is particularly important. Evidence suggests that transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) may modulate the reward–control balance towards facilitation of cognitive control and possible suppression of reward-related mechanisms that drive food cue-induced craving. This protocol describes a clinical trial that investigates the neurocognitive mechanisms of action for tDCS to modulate food cue-reactivity and cravings in people with obesity. Method The NeuroStim-Obesity trial is a prospective, randomized, sham-controlled, double-blind single-session tDCS trial targeting food craving in those with obesity or overweighed. Once randomized, 64 adults with obesity or overweighed complete one session in which they receive either active or sham tDCS over the DLPFC (anode F4 and cathode F3, 2 mA intensity for 20 min). The primary outcome is change in neural response to the food cue-reactivity task in the ventral striatum after a single-session bilateral tDCS compared to sham stimulation. Secondary outcomes include changes in food craving evaluated by the Food Craving Questionnaire-State (FCQ-S). We will also explore the predictive role of brain structure and functional networks assessed by structural and functional magnetic resonance imaging (MRI) during both task performance and the resting-state that are acquired pre- and post-intervention to predict response to tDCS. Discussion The results will provide novel insight into neuroscience for the efficacy of tDCS and will advance the field towards precision medicine for obesity. Exploratory results will examine the potential predictive biomarkers for tDCS response and eventually provide personalized intervention for the treatment of obesity. Trial registration Iranian Registry of Clinical Trials (IRCT) IRCT20121020011172N4 . Retrospectively registered on 4 June 2020

Background: Abnormalities in frontoparietal network (FPN) were observed in many neuropsychiatric diseases including substance use disorders. A growing number of studies are using dual-site-tACS with frontoparietal synchronization to engage this network. However, a computational pathway to inform and optimize parameter space for frontoparietal synchronization is still lacking. In this case study, in a group of participants with methamphetamine use disorders, we proposed a computational pathway to extract optimal electrode montage while accounting for stimulation intensity using structural and functional MRI. Methods: Sixty methamphetamine users completed an fMRI drug cue-reactivity task. Four main steps were taken to define electrode montage and adjust stimulation intensity using 4x1 high-definition (HD) electrodes for a dual-site-tACS; (1) Frontal seed was defined based on the maximum electric fields (EF) predicted by simulation of HD montage over DLPFC (F3/F4 in EEG 10–10), (2) frontal seed-to-whole brain context-dependent correlation was calculated to determine connected regions to frontal seeds, (3) center of connected cluster in parietal cortex was selected as a location for placing the second set of HD electrodes to shape the informed montage, (4) individualized head models were used to determine optimal stimulation intensity considering underlying brain structure. The informed montage was compared to montages with large electrodes and classic frontoparietal HD montages (F3-P3/F4-P4) in terms of tACS-induced EF and ROI-to-ROI task-based/resting-state connectivity. Results: Compared to the large electrodes, HD frontoparietal montages allow for a finer control of the spatial peak fields in the main nodes of the FPN at the cost of lower maximum EF (large-pad/HD: max EF[V/m] = 0.37/0.11, number of cortical sub-regions that EF exceeds 50% of the max = 77/13). For defining stimulation targets based on EF patterns, using group-level head models compared to a single standard head model results in comparable but significantly different seed locations (6.43 mm Euclidean distance between the locations of the frontal maximum EF in standard-space). As expected, significant task-based/resting-state connections were only found between frontal-parietal locations in the informed montage. Cue-induced craving score was correlated with frontoparietal connectivity only in the informed montage (r = −0.24). Stimulation intensity in the informed montage, and not in the classic HD montage, needs 40% reduction in the parietal site to reduce the disparity in EF between stimulation sites. Conclusion: This study provides some empirical insights to montage and dose selection in dual-site-tACS using individual brain structures and functions and proposes a computational pathway to use head models and functional MRI to define (1) optimum electrode montage for targeting FPN in a context of interest (drug-cue-reactivity) and (2) proper transcranial stimulation intensity.

Abstract Cue-induced drug craving and disinhibition are two essential components of continued drug use and relapse in substance use disorders. While these phenomena develop and interact across time, the temporal dynamics of their underlying neural activity remain under-investigated. To explore these dynamics, an analysis of time-varying activation was applied to fMRI data from 62 men with methamphetamine use disorder in their first weeks of recovery in an abstinence-based treatment program. Using a mixed block-event, factorial cue-reactivity/Go-NoGo task and a sliding window across the task duration, dynamically-activated regions were identified in three linear mixed effects models (LMEs). Habituation to drug cues across time was observed in the superior temporal gyri, amygdalae, left hippocampus, and right precuneus, while response inhibition was associated with the sensitization of temporally-dynamic activations across many regions of the inhibitory frontoparietal network. Methamphetamine-related response inhibition was associated with temporally-dynamic activity in the parahippocampal gyri and right precuneus (corrected p-value

IntroductionIn the modern obesogenic environment, heightened reactivity to food-associated cues plays a major role in overconsumption by evoking appetitive responses. Accordingly, functional magnetic resonance imaging (fMRI) studies have implicated regions of the salience and rewards processing in this dysfunctional food cue-reactivity, but the temporal dynamics of brain activation (sensitization or habituation over time) remain poorly understood.MethodsForty-nine obese or overweight adults were scanned in a single fMRI session to examine brain activation during the performance of a food cue-reactivity task. A general linear model (GLM) was used to validate the activation pattern of food cue reactivity in food > neutral contrast. The linear mixed effect models were used to examine the effect of time on the neuronal response during the paradigm of food cue reactivity. Neuro-behavioral relationships were investigated with Pearson’s correlation tests and group factor analysis (GFA).ResultsA linear mixed-effect model revealed a trend for the time-by-condition interactions in the left medial amygdala [t(289) = 2.21, β = 0.1, P = 0.028], right lateral amygdala [t(289) = 2.01, β = 0.26, P = 0.045], right nucleus accumbens (NAc) [t(289) = 2.81, β = 0.13, P = 0.005] and left dorsolateral prefrontal cortex (DLPFC) [t(289) = 2.58, β = 0.14, P = 0.01], as well as in the left superior temporal cortex [42 Area: t(289) = 2.53, β = 0.15, P = 0.012; TE1.0_TE1.2 Area: t(289) = 3.13, β = 0.27, P = 0.002]. Habituation of blood-oxygenation-level-dependent (BOLD) signal during exposure to food vs. neutral stimuli was evident in these regions. We have not found any area in the brain with significant increased response to food-related cues over time (sensitization). Our results elucidate the temporal dynamics of cue-reactivity in overweight and obese individuals with food-induced craving. Both subcortical areas involved in reward processing and cortical areas involved in inhibitory processing are getting habituated over time in response to food vs. neutral cues. There were significant bivariate correlations between self-report behavioral/psychological measures with individual habituation slopes for the regions with dynamic activity, but no robust cross-unit latent factors were identified between the behavioral, demographic, and self-report psychological groups.DiscussionThis work provides novel insights into dynamic neural circuit mechanisms supporting food cue reactivity, thereby suggesting pathways in biomarker development and cue-desensitization interventions.

Addiction medicine is a rapidly growing field with many young professionals seeking careers in this field. However, early-career professionals (ECPs) face challenges such as a lack of competency-based training due to a shortage of trainers, limited resources, limited mentorship opportunities, and establishment of suitable research areas. The International Society of Addiction Medicine (ISAM) New Professionals Exploration, Training & Education (NExT) committee, a global platform for early-career addiction medicine professionals (ECAMPs), conducted a two-phase online survey using a modified Delphi-based approach among ECAMPs across 56 countries to assess the need for standardized training, research opportunities, and mentorship. A total of 110 respondents participated in Phase I (online key informant survey), and 28 respondents participated in Phase II (online expert group discussions on three themes identified in Phase I). The survey found that there is a lack of standardized training, structured mentorship programs, research funding, and research opportunities in addiction medicine for ECAMPs. There is a need for standardized training programs, improving research opportunities, and effective mentorship programs to promote the next generation of addiction medicine professionals and further development in the entire field. The efforts of ISAM NExT are well-received and give a template of how this gap can be addressed.

Abstract Recent studies suggest that transcranial electrical stimulation (tES) can be performed during functional magnetic resonance imaging (fMRI). The novel approach of using concurrent tES‐fMRI to modulate and measure targeted brain activity/connectivity may provide unique insights into the causal interactions between the brain neural responses and psychiatric/neurologic signs and symptoms, and importantly, guide the development of new treatments. However, tES stimulation parameters to optimally influence the underlying brain activity may vary with respect to phase difference, frequency, intensity, and electrode's montage among individuals. Here, we propose a protocol for closed‐loop tES‐fMRI to optimize the frequency and phase difference of alternating current stimulation (tACS) for two nodes (frontal and parietal regions) in individual participants. We carefully considered the challenges in an online optimization of tES parameters with concurrent fMRI, specifically in its safety, artifact in fMRI image quality, online evaluation of the tES effect, and parameter optimization method, and we designed the protocol to run an effective study to enhance frontoparietal connectivity and working memory performance with the optimized tACS using closed‐loop tES‐fMRI. We provide technical details of the protocol, including electrode types, electrolytes, electrode montages, concurrent tES‐fMRI hardware, online fMRI processing pipelines, and the optimization algorithm. We confirmed the implementation of this protocol worked successfully with a pilot experiment.

Transcranial direct current stimulation (tDCS) is a promising intervention for reducing craving/consumption in individuals with substance use disorders. However, its exact mechanism of action has not yet been well explored. We aimed to examine the network-based effects of tDCS while people with methamphetamine use disorders (MUDs) were exposed to drug cues. In a randomized, double-blind sham-controlled trial with a crossover design, 15 participants with MUDs were recruited to receive 20 min of active/sham tDCS with an anode/cathode over F4/F3. MRI data, including structural and task-based functional MRI during a standard drug cue-reactivity task, were collected immediately before and after stimulation sessions. Craving scores were also recorded before and after MRI scans. Individualized head models were generated to determine brain regions with strong electric fields (EFs). Using atlas-based parcellation of head models, averaged EFs were extracted from the main nodes of three large-scale networks that showed abnormalities in MUDs; executive control (ECN), default mode (DMN), and ventral attention (VAN) networks. Main nodes with high EF intensity were used as seed regions for task-based functional connectivity (FC) [using generalized psychophysiological interaction (gPPI)] and activity [using a general linear model (GLM)] calculations. Subjective craving showed a significant reduction in immediate craving after active (–15.42 ± 5.42) compared to sham (–1 ± 2.63). In seed-to-whole brain results, the PFC node in ECN showed an enhanced PPI connectivity with precuneus and visual cortex; the cluster center in MNI (6, –84, –12); the PFC node in DMN showed a decreased PPI connectivity with contralateral parietal cortex;(–48, –60, 46). ROI-to-ROI results showed increased PPI connectivity within/between ECN-VAN while connectivity between ECN-DMN decreased. In line with connectivity, functional activity in the right PFC node in DMN decreased after tDCS while activity in PFC nodes of ECN/VAN increased. EF calculations in PFC nodes revealed that EF in DMN was outward, while the direction of EFs was inward in ECN/VAN. This study provides new insight into neural circuitry underlying MUDs that can be modulated by tDCS at the network level and specifically suggests that bilateral tDCS increases cortical excitability in ECN and VAN, while it has opposite effects on DMN that may be related to the direction of EFs.

Introduction: A brief neuroscience-informed psychoeducation program (Neuroscience-Informed Psychoeducation for Recovery [NIPER]) was developed to promote awareness (metacognition) in the main cognitive domains affected by drug and alcohol use to increase willingness to invest time and effort in the brain and cognition recovery process. The primary aim of this pilot study was to determine the feasibility and acceptability of the NIPER program and its potential effectiveness in increasing metacognition, psychological wellbeing, and willingness for the brain and cognition recovery programs among patients with Substance Use Disorders (SUDs). Methods: A total of 56 patients with SUDs were recruited from four outpatient treatment centers in Tehran City, Iran. They participated in four 90-min weekly sessions delivered adjunct to their routine treatment. The program’s effectiveness was measured in terms of metacognition and psychological wellbeing at baseline and the end of the program. The rate of adherence and participation and willingness to continue with brain and cognition recovery programs were measured as feasibility outcomes. Results: A total of 51 participants completed the study. Compared to the baseline assessments, patients reported more problems in dimensions of attention, memory, inhibitory control, decision making, motor/speech, interoception, insight, and a higher level of psychological wellbeing (t=4.66; P

Abstract Background Neurocognitive deficits (NCDs) and associated meta-cognition difficulties associated with chronic substance use often delay the learning and change process necessary for addiction recovery and relapse prevention. However, very few cognitive remediation programs have been developed to target NCDs and meta-cognition for substance users. The study described herein aims to investigate the efficacy of a multi-component neurocognitive rehabilitation and awareness program termed “Neurocognitive Empowerment for Addiction Treatment” (NEAT). NEAT is a fully manualized, cartoon-based intervention involving psychoeducation, cognitive practice, and compensatory strategies relevant across 10 major cognitive domains, including aspects of attention, memory, executive functions, and decision-making. Method/design In a single-blind randomized controlled trial (RCT), 80 female opioid and/or methamphetamine users will be recruited from an addiction recovery program providing an alternative to incarceration for women with substance use-related offenses. Eight groups of 9–12 participants will be randomized into NEAT or treatment-as-usual (TAU). NEAT involves 14 90-min sessions, delivered twice weekly. The primary outcome is change in self-reported drug craving from before to after intervention using Obsessive Compulsive Drug Use Scale. Secondary and exploratory outcomes include additional psychological, neurocognitive, and structural and functional neuroimaging measures. Clinical measures will be performed at five time points (pre- and post-intervention, 3-, 6-, and 12-month follow-up); neuroimaging measures will be completed at pre- and post-intervention. Discussion The present RCT is the first study to examine the efficacy of an adjunctive neurocognitive rehabilitation and awareness program for addiction. Results from this study will provide initial information concerning potential clinical efficacy of the treatment, as well as delineate neural mechanisms potentially targeted by this novel intervention. Trial registration ClinicalTrials.gov NCT03922646 . Registered on 22 April 2019

Introduction: The Iranian Brain Imaging Database (IBID) was initiated in 2017, with 5 major goals: provide researchers easy access to a neuroimaging database, provide normative quantitative measures of the brain for clinical research purposes, study the aging profile of the brain, examine the association of brain structure and function, and join the ENIGMA consortium. Many prestigious databases with similar goals are available. However, they were not done on an Iranian population, and the battery of their tests (e.g. cognitive tests) is selected based on their specific questions and needs. Methods: The IBID will include 300 participants (50% female) in the age range of 20 to 70 years old, with an equal number of participants (#60) in each age decade. It comprises a battery of cognitive, lifestyle, medical, and mental health tests, in addition to several Magnetic Resonance Imaging (MRI) protocols. Each participant completes the assessments on two referral days. Results: The study currently has a cross-sectional design, but longitudinal assessments are considered for the future phases of the study. Here, details of the methodology and the initial results of assessing the first 152 participants of the study are provided. Conclusion: IBID is established to enable research into human brain function, to aid clinicians in disease diagnosis research, and also to unite the Iranian researchers with interests in the brain.

Abstract Two challenges to optimizing transcranial direct current stimulation (tDCS) are selecting between, often similar, electrode montages and accounting for inter-individual differences in response. These two factors are related by how tDCS montage determines current flow through the brain considered across or within individuals. MRI-based computational head models (CHMs) predict how brain anatomy determines electric field (EF) patterns for a given tDCS montage. Because conventional tDCS produces diffuse brain current flow, stimulation outcomes may be understood as modulation of global networks. Therefore, we developed a network-led, rather than region-led, approach. We specifically considered two common “frontal” tDCS montages that nominally target the dorsolateral prefrontal cortex; asymmetric “unilateral” (anode/cathode: F4/Fp1) and symmetric “bilateral” (F4/F3) electrode montages. CHMs of 66 participants were constructed. We showed that cathode location significantly affects EFs in the limbic network. Furthermore, using a finer parcellation of large-scale networks, we found significant differences in some of the main nodes within a network, even if there is no difference at the network level. This study generally demonstrates a methodology for considering the components of large-scale networks in CHMs instead of targeting a single region and specifically provides insight into how symmetric vs asymmetric frontal tDCS may differentially modulate networks across a population.

Neural reactivity to food cues may play a central role in overeating and excess weight gain. Functional magnetic resonance imaging (fMRI) studies have implicated regions of the reward network in dysfunctional food cue-reactivity, but neural interactions underlying observed patterns of signal change remain poorly understood. Fifty overweight and obese participants with self-reported cue-induced food craving viewed food and neutral cues during fMRI scanning. Regions of the reward network with significantly greater food versus neutral cue-reactivity were used to specify plausible models of task-related neural interactions underlying the observed blood oxygenation level-dependent (BOLD) signal, and a bi-hemispheric winning model was identified in a dynamic causal modeling (DCM) framework. Neuro-behavioral correlations are investigated with group factor analysis (GFA) and Pearson’s correlation tests. The ventral tegmental area (VTA), amygdalae, and orbitofrontal cortices (OFC) showed significant food cue-reactivity. DCM suggests these activations are produced by largely reciprocal dynamic signaling between these regions, with food cues causing regional disinhibition and an apparent shifting of activity to the right amygdala. Intrinsic self-inhibition in the VTA and right amygdala is negatively correlated with measures of food craving and hunger and right-amygdalar disinhibition by food cues is associated with the intensity of cue-induced food craving, but no robust cross-unit latent factors were identified between the neural group and behavioral or demographic variable groups. Our results suggest a rich array of dynamic signals drive reward network cue-reactivity, with the amygdalae mediating much of the dynamic signaling between the VTA and OFCs. Neuro-behavioral correlations suggest particularly crucial roles for the VTA, right amygdala, and the right OFC-amygdala connection but the more robust GFA identified no cross-unit factors, so these correlations should be interpreted with caution. This investigation provides novel insights into dynamic circuit mechanisms with etiologic relevance to obesity, suggesting pathways in biomarker development and intervention.

Computational modelling is a promising approach to parse dysfunctional cognitive processes in substance use disorders (SUDs), but it is unclear how much these processes change during the recovery period. We assessed 1-year follow-up data on a sample of treatment-seeking individuals with one or more SUDs (alcohol, cannabis, sedatives, stimulants, hallucinogens, and/or opioids; 'N' = 83) that were previously assessed at baseline within a prior computational modelling study. Relative to healthy controls (HCs; 'N' = 48), these participants were found at baseline to show altered learning rates and less precise action selection while completing an explore-exploit decision-making task. Here we replicated these analyses when these individuals returned and re-performed the task 1 year later to assess the stability of baseline differences. We also examined whether baseline modelling measures could predict symptoms at follow-up. Bayesian and frequentist analyses indicated that: (a) group differences in learning rates were stable over time (posterior probability = 1); and (b) intra-class correlations (ICCs) between model parameters at baseline and follow-up were significant and ranged from small to moderate (.25 ≤ ICCs ≤ .54). Exploratory analyses also suggested that learning rates and/or information-seeking values at baseline were associated with substance use severity at 1-year follow-up in stimulant and opioid users (.36 ≤ 'r's ≤ .43). These findings suggest that learning dysfunctions are moderately stable during recovery and could correspond to trait-like vulnerability factors. In addition, computational measures at baseline had some predictive value for changes in substance use severity over time and could be clinically informative.

Coronavirus disease 2019 (COVID-19) is escalating all over the world and has higher morbidities and mortalities in certain vulnerable populations. People Who Use Drugs (PWUD) are a marginalized and stigmatized group with weaker immunity responses, vulnerability to stress, poor health conditions, high-risk behaviors, and lower access to health care services. These conditions put them at a higher risk of COVID-19 infection and its complications. In this paper, an international group of experts on addiction medicine, infectious diseases, and disaster psychiatry explore the possible raised concerns in this issue and provide recommendations to manage the comorbidity of COVID-19 and Substance Use Disorder (SUD).

Background: The COVID-19 pandemic has broadly disrupted biomedical treatment and research including non-invasive brain stimulation (NIBS). Moreover, the rapid onset of societal disruption and evolving regulatory restrictions may not have allowed for systematic planning of how clinical and research work may continue throughout the pandemic or be restarted as restrictions are abated. The urgency to provide and develop NIBS as an intervention for diverse neurological and mental health indications, and as a catalyst of fundamental brain research, is not dampened by the parallel efforts to address the most life-threatening aspects of COVID-19; rather in many cases the need for NIBS is heightened including the potential to mitigate mental health consequences related to COVID-19. Objective: To facilitate the re-establishment of access to NIBS clinical services and research operations during the current COVID-19 pandemic and possible future outbreaks, we develop and discuss a framework for balancing the importance of NIBS operations with safety considerations, while addressing the needs of all stakeholders. We focus on Transcranial Magnetic Stimulation (TMS) and low intensity transcranial Electrical Stimulation (tES) - including transcranial Direct Current Stimulation (tDCS) and transcranial Alternating Current Stimulation (tACS). Methods: The present consensus paper provides guidelines and good practices for managing and reopening NIBS clinics and laboratories through the immediate and ongoing stages of COVID-19. The document reflects the analysis of experts with domain-relevant expertise spanning NIBS technology, clinical services, and basic and clinical research – with an international perspective. We outline regulatory aspects, human resources, NIBS optimization, as well as accommodations for specific demographics. Results: A model based on three phases (early COVID-19 impact, current practices, and future preparation) with an 11-step checklist (spanning removing or streamlining in-person protocols, incorporating telemedicine, and addressing COVID-19-associated adverse events) is proposed. Recommendations on implementing social distancing and sterilization of NIBS related equipment, specific considerations of COVID-19 positive populations including mental health comorbidities, as well as considerations regarding regulatory and human resource in the era of COVID-19 are outlined. We discuss COVID-19 considerations specifically for clinical (sub-)populations including pediatric, stroke, addiction, and the elderly. Numerous case-examples across the world are described. Conclusion: There is an evident, and in cases urgent, need to maintain NIBS operations through the COVID-19 pandemic, including anticipating future pandemic waves and addressing effects of COVID-19 on brain and mind. The proposed robust and structured strategy aims to address the current and anticipated future challenges while maintaining scientific rigor and managing risk.

Introduction: As one of the major health problems in the present century, the COVID-19 pandemic affected all parts of the global communities and the health of substance users are potentially at a greater risk of harm. This global study has been designed and conducted by the International Society of Addiction Medicine Practice and Policy Interest Group (ISAM-PPIG) to understand better the health related issues of people with Substance Use Disorders (SUD) as well as responses of the relevant health care systems during the pandemic. Methods: This is a cross-sectional study using convenient sampling. The data gathering was carried out with two follow-up stages each two months apart through an online conducted survey prepared using Google platform. The survey started by emergence of COVID-19 as a pandemic in March 2020 and respondents were followed till September 2020 when most of the initial lockdowns by most countries are supposed to be reopened. Ethics and Dissemination: The study was approved by the ethics committee of University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. The results will be published in relevant peer reviewing journals and communicated with different international stakeholders.

The brain response to drug-related cues is an important marker in addiction-medicine. However, the temporal dynamics of this response in repeated exposure to cues are not well known. In an fMRI drug cue-reactivity task, the presence of rapid habituation or sensitization was investigated by modeling time and its interaction with condition (drug>neutral) using an initial discovery-sample. Replication of this temporal response was tested in two other clinical populations all abstinent during their early recovery (treatment). Sixty-five male participants (35.8 ± 8.4 years-old) with methamphetamine use disorder (MUD) were recruited as the discovery-sample from an abstinence-based residential treatment program. A linear mixed effects model was used to identify areas with a time-by-condition interaction in the discovery-sample. Replication of these effects was tested in two other samples (29 female with MUD from a different residential program and 22 male with opioid use disorder from the same residential program as the discovery sample). The second replication sample was re-tested within two weeks. In the discovery-sample, clusters within the VMPFC, amygdala and ventral striatum showed both a main effect of condition and a condition-by-time interaction, indicating a habituating response to drug-related but not neutral cues. The estimates for the main effects and interactions were generally consistent between the discovery and replication-samples across all clusters. The re-test data showed a consistent lack of drug > neutral and habituation response within all selected clusters in the second cue-exposure session. The VMPFC, amygdala and ventral striatum show habituation in response to drug-related cues which is consistent among different clinical populations. This habituated response in the first session of cue-exposure and lack of reactivity in the second session of exposure may be important for informing the development of cue-desensitization interventions.

Abstract Background In addition to numerous general health problems, drug dependents manifest various oral health disorders. Our aim was to investigate the oral health status and its determinants among in-treatment opiate dependents. Methods As part of a comprehensive cross-sectional survey on opiate dependents admitted to methadone maintenance centers in Tehran, Iran, we conducted a clinical study in two centers from different socioeconomic areas. A trained dentist conducted face to face interviews and clinical oral examinations based on World Health Organization (WHO) criteria for Decayed, Missing, Filled Teeth (DMFT) index and Community Periodontal Index (CPI) on volunteer patients. Student’s t-test, Mann-Whitney U, Kruskal Wallis, and Chi2 tests, in addition to linear and logistic regression models served for statistical analysis (p

Abstract Introduction More than one‐thousand trials with functional magnetic resonance imaging (fMRI) as an outcome measure were registered in clinicaltrials.gov at the time of writing this article. However, 93% of these registered trials are still not completed with published results and there is no picture available about methodological dimensions of these ongoing trials with fMRI as an outcome measure. Methods We collected trials that use fMRI as an outcome measure in the ClinicalTrials.gov registry on 13 October 2018 and reviewed each trial's record entry. Eligible trials’ characteristics were extracted and summarized. Results In total, 1,386 clinical trials were identified that reported fMRI in their outcome measures with fMRI as the only primary outcome in 33% of them. 82% of fMRI trials were started after 2011. The most frequent intervention was drug (pharmacological intervention) (29%). 57% of trials had parallel assignment design and 20% were designed for cross‐over assignment. For task‐based fMRI, cognitive systems (46%) based on Research Domain Criteria (RDoC) was the most frequent domain of tasks. Less than one‐third of trials (28%) registered at least one region of interest for their analysis. Food cue reactivity task, pain perception task, n‐back task, and monetary incentive delay task were recruited in more than 25 registered trials. Conclusion The number of fMRI trials (fMRI as an outcome measure) with both task and rest protocols is growing rapidly. Our study suggests a growing need for harmonization and standardized checklists on both methods and analysis for preregistration of fMRI‐based outcomes in clinical trials.

Background: The coronavirus disease 2019 (COVID-19) pandemic has impacted people with substance use disorders (SUDs) worldwide, and healthcare systems have reorganized their services in response to the pandemic.Methods: One week after the announcement of the COVID-19 as a pandemic, in a global survey, 177 addiction medicine professionals described COVID-19-related health responses in their own 77 countries in terms of SUD treatment and harm reduction services. The health responses were categorized around (1) managerial measures and systems, (2) logistics, (3) service providers, and (4) vulnerable groups.Results: Respondents from over 88% of countries reported that core medical and psychiatric care for SUDs had continued; however, only 56% of countries reported having had any business continuity plan, and 37.5% of countries reported shortages of methadone or buprenorphine supplies. Participants of 41% of countries reported partial discontinuation of harm-reduction services such as needle and syringe programs and condom distribution. Fifty-seven percent of overdose prevention interventions and 81% of outreach services were also negatively impacted.Conclusions: Participants reported that SUD treatment and harm-reduction services had been significantly impacted globally early during the COVID-19 pandemic. Based on our findings, we highlight several issues and complications resulting from the pandemic concerning people with SUDs that should be tackled more efficiently during the future waves or similar pandemics. The issues and potential strategies comprise the following: (1) helping policymakers to generate business continuity plans, (2) maintaining the use of evidence-based interventions for people with SUDs, (3) being prepared for adequate medication supplies, (4) integrating harm reduction programs with other treatment modalities, and (5) having specific considerations for vulnerable groups such as immigrants and refugees.

Introduction: Some communicators resort to negative appeals such as fear to encourage consumers to healthy behaviors. Nonetheless, the effectiveness of this type of content is yet questioned. Present study has been conducted to investigate how fear intensity and fear type applied in anti-obesity advertisements prompt preventive behavior among consumers. Methods: 208 college students in Tehran province were randomly classified in 7 groups (6 experimental and 1 control group) based on a factorial design; 2 (fear intensity: high and low) x 3 (fear type: physical, social, and reappraisal). Research hypotheses were tested applying appropriate statistical tests including structural equation modeling and analysis of variance, based on data gathered through questionnaire and interventions such as presenting participants with visual contents. Findings: it was revealed that there is a significant and positive relationship between the perceived severity and perceived fear, as well as between perceived susceptibility and perceived fear, and also between perceived fear and behavioral intention. Analysis of variance confirmed the significant main effect of fear intensity on behavioral intention. The main effect of the fear type on behavioral intention was not approved. However, findings indicate the significant interaction effect of fear intensity and fear type on behavioral intention so that highly intense messages that representing physical harm and lowly intense messages that representing social harm stimulate more behavioral intention. Conclusion: It is concluded that applying fear appeal in health warning advertisements is effective in inviting consumers to healthy behavior, especially once a proper combination of the type and intensity of fear is applied in messages.

Introduction: The response variability between subjects, which is one of the fundamental challenges facing transcranial direct current stimulation (tDCS), can be investigated by understanding how the current is distributed through the brain. This understanding can be obtained by means of computational methods utilizing finite element (FE) models. Materials and Methods: In this study, the effect of realistic geometry and white matter anisotropy on the head electrical current density intensity (CDI) distribution was measured using a magnetic resonance imaging (MRI)-derived FE model at the whole brain, below electrodes, and cellular levels. Results: The results revealed that on average, the real geometry changes the CDI in gray matter and the WM by 29% and 55%, respectively. In addition, WM anisotropy led to an 8% and 36% change of CDI across GM and WM, respectively. The results indicated that for this electrode configuration, the maximum CDI occurs not below the electrode, but somewhere between the electrodes, and its locus varies greatly between individuals. In addition, by investigating the effect of current density components on cellular excitability, significant individual differences in the level of excitability were detected. Conclusion: Accordingly, consideration of the real geometry in computational modeling is vital. In addition, WM anisotropy does not significantly influence the CDI on the gray matter surface, however, it alters the CDI inside the brain; therefore, it can be taken into account, especially, when stimulation of brain’s internal regions is proposed. Finally, to predict the outcome result of tDCS, the examination of its effect at the cellular level is of great importance.

Abstract Drug addiction has been associated with lack of insight into one’s own abilities. However, the scope of metacognition impairment among drug users in general and opiate dependent individuals in particular is not fully understood. Investigating the impairments of metacognitive ability in Substance Dependent Individuals (SDIs) in different cognitive tasks could contribute to the ongoing debate over whether metacognition has domain-general or domain-specific neural substrates. We compared metacognitive self-monitoring ability of a group of SDIs during methadone maintenance treatment (n = 23) with a control group (n = 24) in a memory and a visual perceptual task. Post decision self judgements of probability of correct choice were obtained through trial by trial confidence ratings and were used to compute metacognitive ability. Results showed that despite comparable first order performance in the perceptual task, SDIs had lower perceptual metacognition than the control group. However, although SDIs had poorer memory performance, their metacognitive judgements in the memory task were as accurate as the control group. While it is commonly believed that addiction causes pervasive impairment in cognitive functions, including metacognitive ability, we observed that the impairment was only significant in one specific task, the perceptual task, but not in the memory task.

Introduction: Various treatment methods for drug abusers will result in different success rates. This is partly due to different neural assumptions and partly due to various rate of relapse in abusers because of different circumstances. Investigating the brain activation networks of treated subjects can reveal the hidden mechanisms of the therapeutic methods. Methods: We studied three groups of subjects: heroin abusers treated with abstinent based therapy (ABT) method, heroin abusers treated with Methadone Maintenance Therapy (MMT) method, and a control group. They were all scanned with functional magnetic resonance imaging (fMRI), using a 6-block task, where each block consisted of the rest-craving-rest-neutral sequence. Using the dynamic causal modeling (DCM) algorithm, brain effective connectivity network (caused by the drug craving stimulation) was quantified for all groups. In this regard, 4 brain areas were selected for this analysis based on previous findings: ventromedial prefrontal cortex (VMPFC), dorsolateral prefrontal cortex (DLPFC), amygdala, and ventral striatum. Results: Our results indicated that the control subjects did not show significant brain activations after craving stimulations, but the two other groups showed significant brain activations in all 4 regions. In addition, VMPFC showed higher activations in the ABT group compared to the MMT group. The effective connectivity network suggested that the control subjects did not have any direct input from drug-related cue indices, while the other two groups showed reactions to these cues. Also, VMPFC displayed an important role in ABT group. In encountering the craving pictures, MMT subjects manifest a very simple mechanism compared to other groups. Conclusion: This study revealed an activation network similar to the emotional and inhibitory control networks observed in drug abusers in previous works. The results of DCM analysis also support the regulatory role of frontal regions on bottom regions. Furthermore, this study demonstrates the different effective connectivity patterns after drug abuse treatment and in this way helps the experts in the field.

Although there is general consensus that altered brain structure and function underpins addictive disorders, clinicians working in addiction treatment rarely incorporate neuroscience-informed approaches into their practice. We recently launched the Neuroscience Interest Group within the International Society of Addiction Medicine (ISAM-NIG) to promote initiatives to bridge this gap. This article summarizes the ISAM-NIG key priorities and strategies to achieve implementation of addiction neuroscience knowledge and tools for the assessment and treatment of substance use disorders. We cover two assessment areas: cognitive assessment and neuroimaging, and two interventional areas: cognitive training/remediation and neuromodulation, where we identify key challenges and proposed solutions. We reason that incorporating cognitive assessment into clinical settings requires the identification of constructs that predict meaningful clinical outcomes. Other requirements are the development of measures that are easily-administered, reliable, and ecologically-valid. Translation of neuroimaging techniques requires the development of diagnostic and prognostic biomarkers and testing the cost-effectiveness of these biomarkers in individualized prediction algorithms for relapse prevention and treatment selection. Integration of cognitive assessments with neuroimaging can provide multilevel targets including neural, cognitive, and behavioral outcomes for neuroscience-informed interventions. Application of neuroscience-informed interventions including cognitive training/remediation and neuromodulation requires clear pathways to design treatments based on multilevel targets, additional evidence from randomized trials and subsequent clinical implementation, including evaluation of cost-effectiveness. We propose to address these challenges by promoting international collaboration between researchers and clinicians, developing harmonized protocols and data management systems, and prioritizing multi-site research that focuses on improving clinical outcomes.

Background: There is a trade-off between drug-related impulsive process and cognitive reflective process among ex-drug abusers. The present study aimed to investigate the impulsive effects of methamphetamine-related stimuli on working memory (WM) performance by manipulating WM load in abstinent ex-methamphetamine users.Methods: Thirty abstinent ex-methamphetamine users and 30 nonaddict matched control participants were recruited in this study. We used a modified Sternberg task in which participants were instructed to memorize three different sets of methamphetamine-related and non–drug-related words (three, five, or seven words) while performing a secondary attention-demanding task as an interference.Results: Repeated-measures ANOVA revealed that reaction times of abstinent ex-methamphetamine users increased during low WM load (three words) compared to the control group (p = 0.01). No significant differences were observed during high WM loads (five or seven words) (both p’s > 0.1). Besides, reaction times of the experimental group during trials with high interference (three, five, or seven words) were not significantly different compared to the control group (p > 0.2).Conclusion: These findings imply that increasing WM load may provide an efficient buffer against attentional capture by salient stimuli (i.e., methamphetamine-related words). This buffer might modify the effect of interference bias. Besides, presenting methamphetamine-related stimuli might facilitate the encoding phase due to bias toward task-relevant stimuli. This finding has an important implication, suggesting that performing concurrent demanding tasks may reduce the power of salient stimuli and thus improve the efficiency of emotional regulation strategies.

IntroductionCognitive deficits are frequent after coronary artery bypass graft (CABG) surgery and consequently could lead to a decrease in quality of life. This is the first study that has been conducted with the aim of examining the efficacy of a computerized cognitive rehabilitation therapy (CCRT) in improving quality of life in patients after CABG surgery.MethodsIn this study, an interventional trial with pre-, post-, and follow-up assessments in active (CCRT), active control and control groups was conducted. Seventy-five patients after CABG surgery were selected and assigned to the groups (n = 25 for each group). CCRT consists of four modules of attention, working memory, response inhibition and processing speed training with graded schedule in 20-min sessions three times per week within 8 weeks. Cognitive functions (attention and working memory) were assessed by the tests of continuous performance, Flanker, useful field of view and digit span at three time points: pre- and post-intervention (T0 and T1) and 6-month follow-up (T2). Quality of life was assessed by the SF-36 questionnaire at the same time points. The CCRT group received the cognitive rehabilitation for 2 months, active control group received a sham version of CCRT in an equal time duration and control group did not receive any cognitive intervention.ResultsRepeated measures analysis of variance (ANOVA) revealed a time by group interaction on cognitive functions, with CCRT producing a significant improvement at T1 (p < 0.01) and these improvements were maintained at T2. Moreover, in CCRT and active control groups, quality of life (QoL) improved at T1 and these improvements remained stable throughout follow-up (T2). However, improvement of QoL in CCRT group was greater than improvement of QoL in the other two groups at T1. Pearson’s correlation analysis shows a positive correlation between QoL improvement and sustained attention and working memory enhancement (p < 0.05).ConclusionCognitive rehabilitation can lead to a significant improvement in the cognitive functions that have been trained in patients receiving CABG. Interestingly enough, cognitive rehabilitation can also improve quality of life in patients after CABG surgery and this improvement is maintained for at least 6 months.

This study aimed to examine the effects of chronic methamphetamine use on the topological organization of whole-brain functional connectivity network (FCN) by reconstruction of neural-activity time series at resting-state. The EEG of 36 individuals with methamphetamine use disorder (IWMUD) and 24 normal controls (NCs) were recorded, pre-processed and source-reconstructed using standardized low-resolution tomography (sLORETA). The brain FCNs of participants were constructed and between-group differences in network topological properties were investigated using graph theoretical analysis. IWMUD showed decreased characteristic path length, increased clustering coefficient and small-world index at delta and gamma frequency bands compared to NCs. Moreover, abnormal changes in inter-regional connectivity and network hubs were observed in all the frequency bands. The results suggest that the IWMUD and NCs have distinct FCNs at all the frequency bands, particularly at the delta and gamma bands, in which deviated small-world brain topology was found in IWMUD.

Introduction: A fixed hemodynamic response function (HRF) is commonly used for functional magnetic resonance imaging (fMRI) analysis. However, HRF may vary from region to region and subject to subject. We investigated the effect of locally estimated HRF (in functionally homogenous parcels) on activation detection sensitivity in a heroin cue reactivity study. Methods: We proposed a novel exploratory method for brain parcellation based on a probabilistic model to segregate the brain into spatially connected and functionally homogeneous components. Then, we estimated HRF and detected activated regions in response to an experimental task in each parcel using a joint detection estimation (JDE) method. We compared the proposed JDE method with the general linear model (GLM) that uses a fixed HRF and is implemented in FEAT (as a part of FMRIB Software Library, version 4.1). Results: 1) Regions detected by JDE are larger than those detected by fixed HRF, 2) In group analysis, JDE found areas of activation not detected by fixed HRF. It detected drug craving a priori “regions-of-interest” in the limbic lobe (anterior cingulate cortex [ACC], posterior cingulate cortex [PCC] and cingulate gyrus), basal ganglia, especially striatum (putamen and head of caudate), and cerebellum in addition to the areas detected by the fixed HRF method, 3) JDE obtained higher Z-values of local maxima compared to those obtained by fixed HRF. Conclusion: In our study of heroin cue reactivity, our proposed method (that estimates HRF locally) outperformed the conventional GLM that uses a fixed HRF.

Introduction: Chronic use of most psychoactive drugs may lead to substance dependence and drug addiction. Drug addiction is a chronically relapsing disorder, and current pharmacological and behavioral therapies are not fully efficient. Attentional bias (AB) is hypothesized to have a causal contribution to substance abuse, addiction development and, maintenance. Transcranial direct current stimulation (tDCS) has been of increasing interest in the past few years as a means for modulating neuroplasticity of the human brain. Although several studies have reported promising therapeutic effects for tDCS in drug abusers, there is no consensus about optimal electrode montages and target brain regions. This study was aimed to compare effectiveness of several electrode montages in modifying AB.Methods and Materials: Ninety early-abstinent methamphetamine users were recruited from several residential drug-rehabilitation centers in Tehran province. They were randomly assigned to six groups with different electrode montages, targeting the left or right dorsolateral prefrontal cortex (DLPFC) as follows: Two conditions with anodal tDCS over the right DLPFC (return electrode placed over the left shoulder or left supraorbital ridge), three conditions with the anode positioned over the left DLPFC (return electrode over the right shoulder, right supraorbital ridge, or contralateral DLPFC), and one sham condition. Active stimulation intensity was 2 mA DC, delivered for 13 min followed by a 20-min rest and another 13 min of stimulation. The probe detection task (PDT) was performed to assess AB. The positive and negative affect scale (PANAS), and the depression anxiety stress scales (DASS) were used to assess baseline affective status before the intervention.Results: Mixed model analysis showed that the left DLPFC/right shoulder and left DLPFC/right DLPFC montages reduced AB toward drug-cues in comparison with sham stimulation.Conclusion: Our findings indicate that anodal stimulation over the left DLPFC reduces AB in methamphetamine users. This study offers promising findings for further studies investigating tDCS as a clinical device to modify AB in drug users.

Objective: Verbal fluency tests (VFTs) are widely used in clinical practice and research to assess executive functions and are highly sensitive to frontal lobe lesions. However, using VFTs in different cultures and languages needs further considerations. The aim of this study was to provide a Persian (Farsi) version of verbal fluency with preliminary normative data. Method: In the first phase, 50 healthy native Persian-speaking individuals completed 1-minute VFT for all 32 letters in Persian to find letters with highest frequency. In the second phase, 100 healthy participants (50 females) were recruited into 5 age groups that were matched by gender and education. Participants were instructed to do 1-minute VFT for the 3 selected letters (phonemic VFT) and 3 categories (animal, supermarket, and fruit) (semantic VFT). For data analysis, one-way ANOVA was performed. Results: In the first phase, 3 letters (Pe standing for /P/, Meem for /M/ and Kaaf for /K/) had the highest frequency in word production (12 in average) and had been chosen for Persian phonemic VFT. Participants were assessed with the 3 selected letters (/P/: 12.28±3.607, /M/: 12.54±3.907, and /K/: 12.48±3.708) and 3 semantic categories (animal: 21.67±5.119, supermarket: 21.19±4.907, and fruit: 19.58±4.439) with 1-minute time limitation for each test. The results showed that education was significantly (p

Introduction: Drug craving could be described as a motivational state which drives drug dependents towards drug seeking and use. Different types of self-reports such as craving feeling, desire and intention, wanting and need, imagery of use, and negative affect have been attributed to this motivational state. By using subjective self-reports for different correlates of drug craving along with functional neuroimaging with cue exposure paradigm, we investigated the brain regions that could correspond to different dimensions of subjective reports for heroin craving. Methods: A total of 25 crystalline-heroin smokers underwent functional magnetic resonance imaging (fMRI), while viewing heroin-related and neutral cues presented in a block-design task. During trial intervals, subjects verbally reported their subjective feeling of cue induced craving (CIC). After fMRI procedure, participants reported the intensity of their “need for drug use” and “drug use imagination” on a 0-100 visual analog scale (VAS). Afterwards, they completed positive and negative affect scale (PANAS) and desire for drug questionnaire (DDQ) with 3 components of “desire and intention to drug use,” “negative reinforcement,” and “loss of control.” Results: The study showed significant correlation between “subjective feeling of craving” and activation of the left and right anterior cingulate cortex, as well as right medial frontal gyrus. Furthermore, the “desire and intention to drug use” was correlated with activation of the left precentral gyrus, left superior frontal gyrus, and left middle frontal gyrus. Subjects also exhibited significant correlation between the “need for drug use” and activation of the right inferior temporal gyrus, right middle temporal gyrus, and right parahippocampal gyrus. Correlation between subjective report of “heroin use imagination” and activation of the cerebellar vermis was also observed. Another significant correlation was between the “negative affect” and activation of the left precuneus, right putamen, and right middle temporal gyrus. Discussion: This preliminary study proposes different neural correlates for various dimensions of subjective craving self-reports. It could reflect multidimensionality of cognitive functions corresponding with drug craving. These cognitive functions could represent their motivational and affective outcomes in a single item “subjective craving feeling” or in self-reports with multiple dissociable items, such as intention, need, imagination, or negative feeling. The new psychological models of drug craving for covering various dimensions of subjective craving self-reports based on their neurocognitive correspondence could potentially modify craving assessments in addiction medicine.