Brain tract structure predicts relapse to stimulant drug use.

Diffusion tractography allows identification and measurement of structural tracts in the human brain previously associated with motivated behavior in animal models. Recent findings indicate that the structural properties of a tract connecting the midbrain to nucleus accumbens (NAcc) are associated with a diagnosis of stimulant use disorder (SUD), but not relapse. In this preregistered study, we used diffusion tractography in a sample of patients treated for SUD (n = 60) to determine whether qualities of tracts projecting from medial prefrontal, anterior insular, and amygdalar cortices to NAcc might instead foreshadow relapse. As predicted, reduced diffusion metrics of a tract projecting from the right anterior insula to the NAcc were associated with subsequent relapse to stimulant use, but not with previous diagnosis. These findings highlight a structural target for predicting relapse to stimulant use and further suggest that distinct connections to the NAcc may confer risk for relapse versus diagnosis.

Similarity and difference in large-scale functional network alternations between behavioral addictions and substance use disorder: a comparative meta-analysis.

Behavioral addiction (BA) and substance use disorder (SUD) share similarities and differences in clinical symptoms, cognitive functions, and behavioral attributes. However, little is known about whether and how functional networks in the human brain manifest commonalities and differences between BA and SUD. Voxel-wise meta-analyses of resting-state functional connectivity (rs-FC) were conducted in BA and SUD separately, followed by quantitative conjunction analyses to identify the common and distinct alterations across both the BA and SUD groups. A total of 92 datasets with 2444 addicted patients and 2712 healthy controls (HCs) were eligible for the meta-analysis. Our findings demonstrated that BA and SUD exhibited common alterations in rs-FC between frontoparietal network (FPN) and other high-level neurocognitive networks (i.e. default mode network (DMN), affective network (AN), and salience network (SN)) as well as hyperconnectivity between SN seeds and the Rolandic operculum in SSN. In addition, compared with BA, SUD exhibited several distinct within- and between-network rs-FC alterations mainly involved in the DMN and FPN. Further, altered within- and between-network rs-FC showed significant association with clinical characteristics such as the severity of addiction in BA and duration of substance usage in SUD. The common rs-FC alterations in BA and SUD exhibited the relationship with consistent aberrant behaviors in both addiction groups, such as impaired inhibition control and salience attribution. By contrast, the distinct rs-FC alterations might suggest specific substance effects on the brain neural transmitter systems in SUD.

Widespread reductions in cortical thickness following ketamine abuse.

BACKGROUND: Esketamine is a version of ketamine that has been approved for treatment-resistant depression, but our previous studies showed a link between non-medical use of ketamine and brain structural and functional alterations, including dorsal prefrontal grey matter reduction among chronic ketamine users. In this study, we sought to determine cortical thickness abnormalities following long-term, non-medical use of ketamine. METHODS: We acquired structural brain images for patients with ketamine use disorder and drug-free healthy controls. We used FreeSurfer software to measure cortical thickness for 68 brain regions. We compared cortical thickness between the 2 groups using analysis of covariance with covariates of age, gender, educational level, smoking, drinking, and whole-brain mean cortical thickness. RESULTS: We included images from 95 patients with ketamine use disorder and 169 controls. Compared with healthy controls, patients with ketamine use disorder had widespread decreased cortical thickness, with the most extensive reductions in the frontal (including the dorsolateral prefrontal cortex) and parietal (including the precuneus) lobes. Increased cortical thickness was not observed among ketamine users relative to comparison participants. Estimated total lifetime ketamine consumption was correlated with reductions in the right inferior parietal and the right rostral middle frontal cortical thickness. LIMITATIONS: We conducted a retrospective cross-sectional study, but longitudinal studies are needed to further validate decreased cortical thickness after nonmedical use of ketamine. CONCLUSION: This study provided evidence that, compared with healthy controls, chronic ketamine users have widespread reductions in cortical thickness. Our study underscores the importance of the long-term effects of ketamine on brain structure and serves as a reference for the antidepressant use of ketamine.

Spectrum of Thoracic Imaging Findings in the Setting of Substance Abuse.

ABSTRACT: Substance abuse continues to be prevalent nationwide and can lead to a myriad of chest pathologies. Imaging findings are vast and can include nodules, masses, ground-glass opacities, airspace disease, and cysts. Radiologists with awareness of these manifestations can assist in early identification of disease in situations where information is unable to be obtained from the patient. This review focuses on thoracic imaging findings associated with various forms of substance abuse, which are organized by portal of entry into the thorax: inhalation, ingestion, and injection.

Multi-level prediction of substance use: Interaction of white matter integrity, resting-state connectivity and inhibitory control measured repeatedly in every-day life.

Substance use disorders are characterized by inhibition deficits related to disrupted connectivity in white matter pathways, leading via interaction to difficulties in resisting substance use. By combining neuroimaging with smartphone-based ecological momentary assessment (EMA), we questioned how biomarkers moderate inhibition deficits to predict use. Thus, we aimed to assess white matter integrity interaction with everyday inhibition deficits and related resting-state network connectivity to identify multi-dimensional predictors of substance use. Thirty-eight patients treated for alcohol, cannabis or tobacco use disorder completed 1 week of EMA to report substance use five times and complete Stroop inhibition testing twice daily. Before EMA tracking, participants underwent resting state functional MRI and diffusion tensor imaging (DTI) scanning. Regression analyses were conducted between mean Stroop performances and whole-brain fractional anisotropy (FA) in white matter. Moderation testing was conducted between mean FA within significant clusters as moderator and the link between momentary Stroop performance and use as outcome. Predictions between FA and resting-state connectivity strength in known inhibition-related networks were assessed using mixed modelling. Higher FA values in the anterior corpus callosum and bilateral anterior corona radiata predicted higher mean Stroop performance during the EMA week and stronger functional connectivity in occipital-frontal-cerebellar regions. Integrity in these regions moderated the link between inhibitory control and substance use, whereby stronger inhibition was predictive of the lowest probability of use for the highest FA values. In conclusion, compromised white matter structural integrity in anterior brain systems appears to underlie impairment in inhibitory control functional networks and compromised ability to refrain from substance use.

Latent profiles of substance use, early life stress, and attention/externalizing problems and their association with neural correlates of reinforcement learning in adolescents.

BACKGROUND: Adolescent substance use, externalizing and attention problems, and early life stress (ELS) commonly co-occur. These psychopathologies show overlapping neural dysfunction in the form of reduced recruitment of reward processing neuro-circuitries. However, it is unclear to what extent these psychopathologies show common v. different neural dysfunctions as a function of symptom profiles, as no studies have directly compared neural dysfunctions associated with each of these psychopathologies to each other. METHODS: In study 1, a latent profile analysis (LPA) was conducted in a sample of 266 adolescents (aged 13-18, 41.7% female, 58.3% male) from a residential youth care facility and the surrounding community to investigate substance use, externalizing and attention problems, and ELS psychopathologies and their co-presentation. In study 2, we examined a subsample of 174 participants who completed the Passive Avoidance learning task during functional magnetic resonance imaging to examine differential and/or common reward processing neuro-circuitry dysfunctions associated with symptom profiles based on these co-presentations. RESULTS: In study 1, LPA identified profiles of substance use plus rule-breaking behaviors, attention-deficit hyperactivity disorder, and ELS. In study 2, the substance use/rule-breaking profile was associated with reduced recruitment of reward processing and attentional neuro-circuitries during the Passive Avoidance task (p < 0.05, corrected for multiple comparisons). CONCLUSIONS: Findings indicate that there is reduced responsivity of striato-cortical regions when receiving outcomes on an instrumental learning task within a profile of adolescents with substance use and rule-breaking behaviors. Mitigating reward processing dysfunction specifically may represent a potential intervention target for substance-use psychopathologies accompanied by rule-breaking behaviors.

Do mindfulness-based interventions change brain function in people with substance dependence? A systematic review of the fMRI evidence.

BACKGROUND: Substance use disorders (SUDs) affect ~ 35 million people globally and are associated with strong cravings, stress, and brain alterations. Mindfulness-based interventions (MBIs) can mitigate the adverse psychosocial outcomes of SUDs, but the underlying neurobiology is unclear. Emerging findings were systematically synthesised from fMRI studies about MBI-associated changes in brain function in SUDs and their associations with mindfulness, drug quantity, and craving. METHODS: PsycINFO, Medline, CINAHL, PubMed, Scopus, and Web of Science were searched. Seven studies met inclusion criteria. RESULTS: Group by time effects indicated that MBIs in SUDs (6 tobacco and 1 opioid) were associated with changes in the function of brain pathways implicated in mindfulness and addiction (e.g., anterior cingulate cortex and striatum), which correlated with greater mindfulness, lower craving and drug quantity. CONCLUSIONS: The evidence for fMRI-related changes with MBI in SUD is currently limited. More fMRI studies are required to identify how MBIs mitigate and facilitate recovery from aberrant brain functioning in SUDs.

Disrupted functional connectivity of the brain reward system in substance use problems: A meta-analysis of functional neuroimaging studies.

Extensive literature suggests that the brain reward system is crucial in understanding the neurobiology of substance use disorders. However, evidence of reliable deficits in functional connectivity across studies on substance use problems remains limited. Therefore, a voxel-wise seed-based meta-analysis using brain regions of the reward system as seeds of interest was conducted on 96 studies representing 5757 subjects with substance use problems. The ventromedial prefrontal cortex exhibited hyperconnectivity with the ventral striatum and hypoconnectivity with the amygdala and hippocampus. The executive striatum showed hyperconnectivity with the motor thalamus and dorsolateral prefrontal cortex and hypoconnectivity with the anterior cingulate cortex and anterior insula. Finally, the limbic striatum was found to be hyperconnected to the orbitofrontal cortex and hypoconnected to the precuneus compared with healthy subjects. The current study provided meta-analytical evidence of deficient functional connectivity between brain regions of the reward system and cortico-striato-thalamocortical loops in addiction. These results are consistent with deficits in motivation and habit formation occurring in addiction, and they highlight alterations in brain regions involved in socio-emotional processing and attention salience.

Selective α3ß4 Nicotinic Acetylcholine Receptor Ligand as a Potential Tracer for Drug Addiction.

α3ß4 Nicotinic acetylcholine receptor (nAChR) has been recognized as an emerging biomarker for the early detection of drug addiction. Herein, α3ß4 nAChR ligands were designed and synthesized to improve the binding affinity and selectivity of two lead compounds, (S)-QND8 and (S)-T2, for the development of an α3ß4 nAChR tracer. The structural modification was achieved by retaining the key features and expanding the molecular structure with a benzyloxy group to increase the lipophilicity for blood-brain barrier penetration and to extend the ligand-receptor interaction. The preserved key features are a fluorine atom for radiotracer development and a p-hydroxyl motif for ligand-receptor binding affinity. Four (R)- and (S)-quinuclidine-triazole (AK1-AK4) were synthesized and the binding affinity, together with selectivity to α3ß4 nAChR subtype, were determined by competitive radioligand binding assay using [3H]epibatidine as a radioligand. Among all modified compounds, AK3 showed the highest binding affinity and selectivity to α3ß4 nAChR with a Ki value of 3.18 nM, comparable to (S)-QND8 and (S)-T2 and 3069-fold higher affinity to α3ß4 nAChR in comparison to α7 nAChR. The α3ß4 nAChR selectivity of AK3 was considerably higher than those of (S)-QND8 (11.8-fold) and (S)-T2 (294-fold). AK3 was shown to be a promising α3ß4 nAChR tracer for further development as a radiotracer for drug addiction.

Neural substrates of substance use disorders.

PURPOSE OF REVIEW: Substance use disorders account for a tremendous burden to society, yet despite substantial progress in basic studies, our understanding of the brain-basis of these disorders is still emerging. This review summarizes the recent findings of neuroimaging studies with substance use disorder individuals. RECENT FINDINGS: Resting-state functional connectivity studies support for some but not all substances of abuse and disruption in executive control. Structural neuroimaging findings point towards reduced subcortical volumes, which may emerge as an interaction between preexisting factors and recent substance use. Longitudinal studies implicate some of the same core brain structures and their functional role that have also been identified via case-control studies. Finally, meta-analyses support the idea of dysregulation of cortical control over subcortical salience processing. SUMMARY: Although progress has been made and there is both structural and functional imaging evidence of an imbalance between brain structures involved in executive control and salience processing, there is emerging evidence that brain-behaviour relationships, which are core to discovering the neural processes that lead to and maintain substance use, are small and require larger consortia that prospectively examine individuals with substance use disorder.

Shapes of subcortical structures in adolescents with and without familial history of substance use disorder.

It has been suggested that intergenerational transmission of risk for substance use disorder (SUD) manifests in the brain anatomy of substance naïve adolescents. While volume and shapes of subcortical structures (SSS) have been shown to be heritable, these structures, especially the pallidum, putamen, nucleus accumbens, and hippocampus, have also been associated with substance use disorders. However, it is not clear if those anatomical differences precede substance use or are the result of that use. Therefore, we examined if volume and SSS of adolescents with a family history (FH+) of SUD differed from adolescents without such a history (FH-). Because risk for SUD is associated with anxiety and impulsivity, we also examined correlations between these psychological characteristics and volume/SSS. Using structural MRI and FSL software, we segmented subcortical structures and obtained indices of SSS and volumes of 64 FH+ and 58 FH- adolescents. We examined group differences in volume and SSS, and the correlations between volume/SSS and trait anxiety and impulsivity. FH+ adolescents had a significant inward deformation in the shape of the right anterior hippocampus compared to FH- adolescents, while the volume of this structure did not differ between groups. Neither shape nor volume of the other subcortical structures differed between groups. In the FH+ adolescents, the left hippocampus shape was positively correlated with both trait anxiety and impulsivity, while in FH- adolescents a negative correlation pattern of SSS was seen in the hippocampus. SSS appears to capture local anatomical features that traditional volumetric analysis does not. The inward shape deformation in the right anterior hippocampus in FH+ adolescents may be related to the known increased risk for behavioral dysregulation leading to SUD in FH+ offspring. Hippocampus shape also exhibits opposite patterns of correlation with anxiety and impulsivity scores across the FH+ and FH- adolescents. These novel findings may reveal neural correlates, not captured by traditional volumetric analysis, of familial transmission of increased vulnerability to SUD.

How do substance use disorders compare to other psychiatric conditions on structural brain abnormalities? A cross-disorder meta-analytic comparison using the ENIGMA consortium findings.

Alcohol use disorder (AUD) and cannabis use disorder (CUD) are associated with brain alterations particularly involving fronto-cerebellar and meso-cortico-limbic circuitry. However, such abnormalities have additionally been reported in other psychiatric conditions, and until recently there has been few large-scale investigations to compare such findings. The current study uses the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium method of standardising structural brain measures to quantify case-control differences and to compare brain-correlates of substance use disorders with those published in relation to other psychiatric disorders. Using the ENIGMA protocols, we report effect sizes derived from a meta-analysis of alcohol (seven studies, N = 798, 54% are cases) and cannabis (seven studies, N = 447, 45% are cases) dependent cases and age- and sex-matched controls. We conduct linear analyses using harmonised methods to process and parcellate brain data identical to those reported in the literature for ENIGMA case-control studies of major depression disorder (MDD), schizophrenia (SCZ) and bipolar disorder so that effect sizes are optimally comparable across disorders. R elationships between substance use disorder diagnosis and subcortical grey matter volumes and cortical thickness were assessed with intracranial volume, age and sex as co-variates . After correcting for multiple comparisons, AUD case-control meta-analysis of subcortical regions indicated significant differences in the thalamus, hippocampus, amygdala and accumbens, with effect sizes (0.23) generally equivalent to, or larger than |0.23| those previously reported for other psychiatric disorders (except for the pallidum and putamen). On measures of cortical thickness, AUD was associated with significant differences bilaterally in the fusiform gyrus, inferior temporal gyrus, temporal pole, superior frontal gyrus, and rostral and caudal anterior cingulate gyri. Meta-analysis of CUD case-control studies indicated reliable reductions in amygdala, accumbens and hippocampus volumes, with the former effect size comparable to, and the latter effect size around half of that reported for alcohol and SCZ. CUD was associated with lower cortical thickness in the frontal regions, particularly the medial orbitofrontal region, but this effect was not significant after correcting for multiple testing. This study allowed for an unbiased cross-disorder comparison of brain correlates of substance use disorders and showed alcohol-related brain anomalies equivalent in effect size to that found in SCZ in several subcortical and cortical regions and significantly greater alterations than those found in MDD in several subcortical and cortical regions. Although modest, CUD results overlapped with findings reported for AUD and other psychiatric conditions, but appear to be most robustly related to reduce thickness of the medial orbitofrontal cortex.

Effects of family history of substance use disorder on reward processing in adolescents with and without attention-deficit/hyperactivity disorder.

Patients with attention-deficit/hyperactivity disorder (ADHD) often develop early onset substance use disorder (SUD) and show poor treatment outcomes. Both disorders show similar reward-processing alterations, but it is unclear whether these are associated with familial vulnerability to SUD. Our aim was to investigate effects of family history of SUD (FH) on reward processing in individuals with and without ADHD, without substance misuse. Behavioural and functional magnetic resonance imaging (fMRI) data from a modified monetary incentive delay task were compared between participants with and without FH (FH positive [FH+]: n = 76 and FH negative [FH-]: n = 69; 76 with ADHD, aged 16.74 ± 3.14, 82 males), while accounting for continuous ADHD scores. The main analysis showed distinct positive association between ADHD scores and reaction times during neutral versus reward condition. ADHD scores were also positively associated with anticipatory responses of dorsolateral prefrontal cortex, independent of FH. There were no main FH effects on brain activation. Yet, FH+ participants showed distinct neural alterations in ventrolateral prefrontal cortex (VLPFC), dependent on ADHD. This was driven by positive association between ADHD scores and VLPFC activation during reward outcome, only in FH+. Sensitivity analysis with stricter SUD index showed hyperactivation of anterior cingulate cortex for FH+, independent of ADHD, during reward anticipation. There were no FH or ADHD effects on activation of ventral striatum in any analysis. Findings suggest both FH and ADHD effects in circuits of reward and attention/memory during reward processing. Future studies should examine whether these relate to early substance use initiation in ADHD and explore the need for adjusted SUD prevention strategies.

Common abnormality of gray matter integrity in substance use disorder and obsessive-compulsive disorder: A comparative voxel-based meta-analysis.

The objective of the current study is to determine robust transdiagnostic brain structural markers for compulsivity by capitalizing on the increasing number of case-control studies examining gray matter volume (GMV) alterations in substance use disorders (SUD) and obsessive-compulsive disorder (OCD). Voxel-based meta-analysis within the individual disorders and conjunction analysis were employed to reveal common GMV alterations between SUDs and OCD. Meta-analytic coordinates and signed brain volumetric maps determining directed (reduced/increased) GMV alterations between the disorder groups and controls served as the primary outcome. The separate meta-analysis demonstrated that SUD and OCD patients exhibited widespread GMV reductions in frontocortical regions including prefrontal, cingulate, and insular. Conjunction analysis revealed that the left inferior frontal gyrus (IFG) consistently exhibited decreased GMV across all disorders. Functional characterization suggests that the IFG represents a core hub in the cognitive control network and exhibits bidirectional (Granger) causal interactions with the striatum. Only OCD showed increased GMV in the dorsal striatum with higher changes being associated with more severe OCD symptomatology. Together the findings demonstrate robustly decreased GMV across the disorders in the left IFG, suggesting a transdiagnostic brain structural marker. The functional characterization as a key hub in the cognitive control network and casual interactions with the striatum suggest that deficits in inhibitory control mechanisms may promote compulsivity and loss of control that characterize both disorders.

Subtypes of inhibitory and reward activation associated with substance use variation in adolescence: A latent profile analysis of brain imaging data.

The present study identified subgroups based on inhibitory and reward activation, two key neural functions involved in risk-taking behavior, and then tested the extent to which subgroup differences varied by age, sex, behavioral and familial risk, and substance use. Participants were 145 young adults (18-21 years old; 40.0% female) from the Michigan Longitudinal Study. Latent profile analysis (LPA) was used to establish subgroups using task-based brain activations. Demographic and substance use differences between subgroups were then examined in logistic regression analyses. Whole-brain task activations during a functional magnetic resonance imaging go/no-go task and monetary incentive delay task were used to identify beta weights as input for LPA modeling. A four-class model showed the best fit with the data. Subgroups were categorized as: (1) low inhibitory activation/moderate reward activation (39.7%), (2) moderate inhibitory activation/low reward activation (22.7%), (3) moderate inhibitory activation/high reward activation (25.2%), and (4) high inhibitory activation/high reward activation (12.4%). Compared with the other subgroups, Class 2 was older, less likely to have parental alcohol use disorder, and had less alcohol use. Class 4 was the youngest and had greater marijuana use. Classes 1 and 3 did not differ significantly from the other subgroups. These findings demonstrate that LPA applied to brain activations can be used to identify distinct neural profiles that may explain heterogeneity in substance use outcomes and may inform more targeted substance use prevention and intervention efforts.

Contribution of TSPO imaging in the understanding of the state of gliosis in substance use disorders.

PURPOSE: Recent research in last years in substance use disorders (SUD) synthesized a proinflammatory hypothesis of SUD based on reported pieces of evidence of non-neuronal central immune signalling pathways modulated by drug of abuse and that contribute to their pharmacodynamic actions. Positron emission tomography has been shown to be a precious imaging technique to study in vivo neurochemical processes involved in SUD and to highlight the central immune signalling actions of drugs of abuse. METHODS: In this review, we investigate the contribution of the central immune system, with a particular focus on translocator protein 18 kDa (TSPO) imaging, associated with a series of drugs involved in substance use disorders (SUD) specifically alcohol, opioids, tobacco, methamphetamine, cocaine, and cannabis. RESULTS: The large majority of preclinical and clinical studies presented in this review converges towards SUD modulation of the neuroimmune responses and TSPO expression and speculated a pivotal positioning in the pathogenesis of SUD. However, some contradictions concerning the same drug or between preclinical and clinical studies make it difficult to draw a clear picture about the significance of glial state in SUD. DISCUSSION: Significant disparities in clinical and biological characteristics are present between investigated populations among studies. Heterogeneity in genetic factors and other clinical co-morbidities, difficult to be reproduced in animal models, may affect findings. On the other hand, technical aspects including study designs, radioligand limitations, or PET imaging quantification methods could impact the study results and should be considered to explain discrepancies in outcomes. CONCLUSION: The supposed neuroimmune component of SUD provides new therapeutic approaches in the prediction and treatment of SUD pointing to the central immune signalling.

Altered neural activities during response inhibition in adults with addiction: a voxel-wise meta-analysis.

BACKGROUND: Previous literature has extensively investigated the brain activity during response inhibition in adults with addiction. Inconsistent results including both hyper- and hypo-activities in the fronto-parietal network (FPN) and the ventral attention network (VAN) have been found in adults with addictions, compared with healthy controls (HCs). METHODS: Voxel-wise meta-analyses of abnormal task-evoked regional activity were conducted for adults with substance dependence (SD) and behavioral addiction during response inhibition tasks to solve previous inconsistencies. Twenty-three functional magnetic resonance imaging studies including 479 substance users, 38 individuals with behavioral addiction and 494 HCs were identified. RESULTS: Compared with HCs, all addictions showed hypo-activities in regions within FPN (inferior frontal gyrus and supramarginal gyrus) and VAN (inferior frontal gyrus, middle temporal gyrus, temporal pole and insula), and hyper-activities in the cerebellum during response inhibition. SD subgroup showed almost the same activity patterns, with an additional hypoactivation of the precentral gyrus, compared with HCs. Stronger activation of the cerebellum was associated with longer addiction duration for adults with SD. We could not conduct meta-analytic investigations into the behavioral addiction subgroup due to the small number of datasets. CONCLUSION: This meta-analysis revealed altered activation of FPN, VAN and the cerebellum in adults with addiction during response inhibition tasks using non-addiction-related stimuli. Although FPN and VAN showed lower activity, the cerebellum exhibited stronger activity. These results may help to understand the neural pathology of response inhibition in addiction.

A voxel-wise meta-analysis of task-based functional MRI studies on impaired gain and loss processing in adults with addiction.

BACKGROUND: Disturbances in gain and loss processing have been extensively reported in adults with addiction, a brain disorder characterized by obsession with addictive substances or behaviours. Previous studies have provided conflicting results with respect to neural abnormalities in gain processing in addiction, and few investigations into loss processing. METHODS: We conducted voxel-wise meta-analyses of abnormal task-evoked regional activities in adults with substance dependence and gambling addiction during the processing of gains and losses not related to their addiction (mainly monetary). We identified 24 studies, including 465 participants with substance dependence, 81 with gambling addiction and 490 healthy controls. RESULTS: Compared with healthy controls, all participants with addictions showed hypoactivations in the prefrontal cortex, striatum and insula and hyperactivations in the default mode network during gain anticipation; hyperactivations in the prefrontal cortex and both hyper- and hypoactivations in the striatum during loss anticipation; and hyperactivations in the occipital lobe during gain outcome. In the substance dependence subgroup, activity in the occipital lobe was increased during gain anticipation but decreased during loss anticipation. LIMITATIONS: We were unable to conduct meta-analyses in the gambling addiction subgroup because of a limited data set. We did not investigate the effects of clinical variables because of limited information. CONCLUSION: The current study identified altered brain activity associated with higher- and lower-level function during gain and loss processing for non-addiction (mainly monetary) stimuli in adults with substance dependence and gambling addiction. Adults with addiction were more sensitive to anticipatory gains than losses at higher- and lower-level brain areas. These results may help us to better understand the pathology of gain and loss processing in addiction.

Mapping cortical and subcortical asymmetries in substance dependence: Findings from the ENIGMA Addiction Working Group.

Brain asymmetry reflects left-right hemispheric differentiation, which is a quantitative brain phenotype that develops with age and can vary with psychiatric diagnoses. Previous studies have shown that substance dependence is associated with altered brain structure and function. However, it is unknown whether structural brain asymmetries are different in individuals with substance dependence compared with nondependent participants. Here, a mega-analysis was performed using a collection of 22 structural brain MRI datasets from the ENIGMA Addiction Working Group. Structural asymmetries of cortical and subcortical regions were compared between individuals who were dependent on alcohol, nicotine, cocaine, methamphetamine, or cannabis (n = 1,796) and nondependent participants (n = 996). Substance-general and substance-specific effects on structural asymmetry were examined using separate models. We found that substance dependence was significantly associated with differences in volume asymmetry of the nucleus accumbens (NAcc; less rightward; Cohen's d = 0.15). This effect was driven by differences from controls in individuals with alcohol dependence (less rightward; Cohen's d = 0.10) and nicotine dependence (less rightward; Cohen's d = 0.11). These findings suggest that disrupted structural asymmetry in the NAcc may be a characteristic of substance dependence.

Common neurofunctional dysregulations characterize obsessive-compulsive, substance use, and gaming disorders-An activation likelihood meta-analysis of functional imaging studies.

Compulsivity and loss of behavioral control represent core symptoms in obsessive-compulsive disorder (OCD), substance use disorder (SUD), and internet gaming disorder (IGD). Despite elaborated animal models suggesting that compulsivity is mediated by cortico-striatal circuits and a growing number of neuroimaging case-control studies, common neurofunctional alterations in these disorders have not been systematically examined. The present activation likelihood estimation (ALE) meta-analysis capitalized on previous functional magnetic resonance imaging (fMRI) studies to determine shared neurofunctional alterations among the three disorders. Task-based fMRI studies of individuals with SUD, OCD, or IGD were obtained. ALE was performed within each disorder. Next, contrast and conjunction meta-analyses were performed to determine differential and common alterations. Task-paradigm classes were group according to Research Domain Criteria (RDoC) domains to determine contributions of underlying behavioral domains. One hundred forty-four articles were included representing data from n = 6897 individuals (SUD = 2418, controls = 2332; IGD = 361, controls = 360; OCD = 715, controls = 711) from case-control studies. Conjunction meta-analyses revealed shared alterations in the anterior insular cortex between OCD and SUDs. SUD exhibited additionally pronounced dorsal-striatal alterations compared with both, OCD and IGD. IGD shared frontal, particularly cingulate alterations with all SUDs, while IGD demonstrated pronounced temporal alterations compared with both, SUD and OCD. No robust overlap between IGD and OCD was observed. Across the disorders, neurofunctional alterations were mainly contributed by cognitive systems and positive valence RDoC domains. The present findings indicate that neurofunctional dysregulations in prefrontal regions engaged in regulatory-control represent shared neurofunctional alterations across substance and behavioral addictions, while shared neurofunctional dysregulations in the anterior insula may mediate compulsivity in substance addiction and OCD.