Distinct neural networks predict cocaine versus cannabis treatment outcomes.

Treatment outcomes for individuals with substance use disorders (SUDs) are variable and more individualized approaches may be needed. Cross-validated, machine-learning methods are well-suited for probing neural mechanisms of treatment outcomes. Our prior work applied one such approach, connectome-based predictive modeling (CPM), to identify dissociable and substance-specific neural networks of cocaine and opioid abstinence. In Study 1, we aimed to replicate and extend prior work by testing the predictive ability of the cocaine network in an independent sample of 43 participants from a trial of cognitive-behavioral therapy for SUD, and evaluating its ability to predict cannabis abstinence. In Study 2, CPM was applied to identify an independent cannabis abstinence network. Additional participants were identified for a combined sample of 33 with cannabis-use disorder. Participants underwent fMRI scanning before and after treatment. Additional samples of 53 individuals with co-occurring cocaine and opioid-use disorders and 38 comparison subjects were used to assess substance specificity and network strength relative to participants without SUDs. Results demonstrated a second external replication of the cocaine network predicting future cocaine abstinence, however it did not generalize to cannabis abstinence. An independent CPM identified a novel cannabis abstinence network, which was (i) anatomically distinct from the cocaine network, (ii) specific for predicting cannabis abstinence, and for which (iii) network strength was significantly stronger in treatment responders relative to control particpants. Results provide further evidence for substance specificity of neural predictors of abstinence and provide insight into neural mechanisms of successful cannabis treatment, thereby identifying novel treatment targets. Clinical trials registation: "Computer-based training in cognitive-behavioral therapy web-based (Man VS Machine)", registration number: NCT01442597 . "Maximizing the Efficacy of Cognitive Behavior Therapy and Contingency Management", registration number: NCT00350649 . "Computer-Based Training in Cognitive Behavior Therapy (CBT4CBT)", registration number: NCT01406899 .

Cocaine self-administration behavior is associated with subcortical and cortical morphometry measures in individuals with cocaine use disorder.

Background: Individual differences in gray-matter morphometry in the limbic system and frontal cortex have been linked to clinical features of cocaine use disorder (CUD). Self-administration paradigms can provide more direct measurements of the relationship between the regulation of cocaine use and gray-matter morphometry when compared to self-report assessments.Objectives: Our goal was to investigate associations with self-administration behavior in subcortical and cortical brain regions. We hypothesized the number of cocaine infusions self-administered would be correlated with gray-matter volumes (GMVs) in the striatum, amygdala, and hippocampus. Due to scarcity in human studies, we did not hypothesize subcortical directionality. In the frontal cortex, we hypothesized thickness would be negatively correlated with self-administered cocaine.Methods: We conducted an analysis of cocaine self-administration and structural MRI data from 33 (nFemales = 10) individuals with moderate-to-severe CUD. Self-administration lasted 60-minutes and cocaine (8, 16, or 32 mg/70 kg) was delivered on an FR1 schedule (5-minute lockout). Subcortical and cortical regression analyses were performed that included combined bilateral regions and age, experimental variables and use history as confounders.Results: Self-administered cocaine infusions were positively associated with caudal GMV (b = 0.18, p = 0.030) and negatively with putamenal GMV (b = -0.10, p = 0.041). In the cortical model, infusions were positively associated with insular thickness (b = 0.39, p = 0.008) and women appeared to self-administer cocaine more frequently (b = 0.23, p = 0.019).Conclusions: Brain morphometry features in the striatum and insula may contribute to cocaine consumption in CUD. These differences in morphometry may reflect consequences of prolonged use, predisposed vulnerability, or other possibilities.Clinical Trial Numbers: NCT01978431; NCT03471182.

Dissociable neural substrates of opioid and cocaine use identified via connectome-based modelling.

Opioid use disorder is a major public health crisis. While effective treatments are available, outcomes vary widely across individuals and relapse rates remain high. Understanding neural mechanisms of treatment response may facilitate the development of personalized and/or novel treatment approaches. Methadone-maintained, polysubstance-using individuals (n = 53) participated in fMRI scanning before and after substance-use treatment. Connectome-based predictive modeling (CPM)-a recently developed, whole-brain approach-was used to identify pretreatment connections associated with abstinence during the 3-month treatment. Follow-up analyses were conducted to determine the specificity of the identified opioid abstinence network across different brain states (cognitive vs. reward task vs. resting-state) and different substance use outcomes (opioid vs. cocaine abstinence). Posttreatment fMRI data were used to assess network changes over time and within-subject replication. To determine further clinical relevance, opioid abstinence network strength was compared with healthy subjects (n = 38). CPM identified an opioid abstinence network (p = 0.018), characterized by stronger within-network motor/sensory connectivity, and reduced connectivity between the motor/sensory network and medial frontal, default mode, and frontoparietal networks. This opioid abstinence network was anatomically distinct from a previously identified cocaine abstinence network. Relationships between abstinence and opioid and cocaine abstinence networks replicated across multiple brain states but did not generalize across substances. Network connectivity measured at posttreatment related to abstinence at 6-month follow-up (p < 0.009). Healthy comparison subjects displayed intermediate network strengths relative to treatment responders and nonresponders. These data indicate dissociable anatomical substrates of opioid vs. cocaine abstinence. Results may inform the development of novel opioid-specific treatment approaches to combat the opioid epidemic.

Bayesian network mediation analysis with application to the brain functional connectome.

The brain functional connectome, the collection of interconnected neural circuits along functional networks, facilitates a cutting-edge understanding of brain functioning, and has a potential to play a mediating role within the effect pathway between an exposure and an outcome. While existing mediation analytic approaches are capable of providing insight into complex processes, they mainly focus on a univariate mediator or mediator vector, without considering network-variate mediators. To fill the methodological gap and accomplish this exciting and urgent application, in the article, we propose an integrative mediation analysis under a Bayesian paradigm with networks entailing the mediation effect. To parameterize the network measurements, we introduce individually specified stochastic block models with unknown block allocation, and naturally bridge effect elements through the latent network mediators induced by the connectivity weights across network modules. To enable the identification of truly active mediating components, we simultaneously impose a feature selection across network mediators. We show the superiority of our model in estimating different effect components and selecting active mediating network structures. As a practical illustration of this approach's application to network neuroscience, we characterize the relationship between a therapeutic intervention and opioid abstinence as mediated by brain functional sub-networks.

Hyperbolic discounting rates and risk for problematic alcohol use in youth enrolled in the Adolescent Brain and Cognitive Development study.

Adolescence is the peak period for the emergence of substance use, which can lead to long-term psychosocial, occupational and interpersonal complications. Ongoing large-scale, longitudinal, consortium initiatives, such as the Adolescent Brain and Cognitive Development (ABCD) study, offer unprecedented opportunities to elucidate key risk factors for problematic substance use in a well-powered sample and to examine how changes in risk factors relate to symptoms across time. Delay discounting has been proposed as a putative risk marker for early substance-use initiation and other forms of psychopathology. However, the extent to which other factors (e.g., socio-economic status and cognitive ability) influence discounting behaviour in young adolescents is not well established. The present study leverages data from the ABCD study (n = 11 045) to assess associations between core demographic and familial variables and delay discounting in youth-operationalized using hyperbolic discounting rates (k)-before the onset of significant psychopathology. Model estimates revealed significant effects of individual difference factors (e.g., sex and socio-economic status) and alcohol risk status (based on family history) on delay discounting. No significant differences were observed in the primary sample when comparing the presence of parent drug problems or prenatal drug exposures. These effects will require replication in later waves of ABCD. Nonetheless, these results provide support for delay discounting as a potential risk marker for problematic alcohol use and demonstrate a relationship between key demographic variables and adolescent discounting behaviour. Further, these results provide an empirical baseline from which developmental trajectories of delay discounting and substance use may be tracked throughout future waves of ABCD.

The effects of prenatal stress on neural responses to infant cries in expectant mothers and fathers.

The perinatal period is characterized by distinct neurobiological and psychological changes initiated prenatally, which may both facilitate postpartum caregiving and increase vulnerability to stress. Parents need to adapt to the high demands of caregiving, which include responding to salient infant cues, such as infant cries. Therefore, assessing the impact of prenatal stress exposure on parents' neural processing of infant cries may elucidate mechanisms conferring early risk for detrimental perinatal outcomes. Using event-related potentials, we examined whether prenatal perceived stress affected neural markers of perceptual (N1, P2) and attentional (LPP) processes elicited by high- and low-distress infant cries in expectant mothers (n = 38) and fathers (n = 30). Results evidenced that prenatal perceived stress impacted parents' sustained attentional processing (LPP) of infant cries, but not early perceptual responses (N1, P2). Specifically, higher levels of prenatal perceived stress were associated with a greater LPP response to low-distress, but not high-distress, infant cries. There were no parental sex differences in prenatal perceived stress or neural responses to infant cries. Increased attentional processing of low-distress cries in highly stressed parents may reflect uncertainty regarding infant distress level, thereby requiring more attentional resources. Overall, our results suggest that prenatal stress impacts processing of infant cues, even before birth.

Efficacy of single-session transcranial direct current stimulation on addiction-related inhibitory control and craving: a randomized trial in males with Internet gaming disorder.

BACKGROUND: Transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (dlPFC) may reduce substance use and other addictive behaviours. However, the cognitive mechanisms that underpin such effects remain unclear. Impaired inhibitory control linked to hypoactivation of the prefrontal cortex may allow craving-related motivations to lead to compulsive addictive behaviours. However, very few studies have examined whether increasing the activation of the dlPFC via anodal tDCS could enhance inhibitory control over addiction-related distractors. The current study aimed to enrich empirical evidence related to this issue. METHODS: Thirty-three males with Internet gaming disorder underwent active (1.5 mA for 20 minutes) and sham tDCS 1 week apart, in randomized order. We assessed inhibitory control over gaming-related distractors and craving pre- and post-stimulation. RESULTS: Relative to sham treatment, active tDCS reduced interference from gaming-related (versus non-gaming) distractors and attenuated background craving, but did not affect cue-induced craving. LIMITATIONS: This study was limited by its relatively small sample size and the fact that it lacked assessments of tDCS effects on addictive behaviour. Future tDCS studies with multiple sessions in larger samples are warranted to examine the effects on addictive behaviours of alterations in addiction-related inhibitory control. CONCLUSION: These findings demonstrate that stimulation of the dlPFC influences inhibitory control over addiction-related cues and addiction-related motivation. This is the first empirical study to suggest that enhanced inhibitory control may be a cognitive mechanism underlying the effects of tDCS on addictions like Internet gaming disorder. Our finding of attenuated background craving replicated previous tDCS studies. Intriguingly, our finding of distinct tDCS effects on 2 forms of craving suggests that they may have disparate underlying mechanisms or differential sensitivity to tDCS. CLINICAL TRIALS #: NCT03352973.

Clinical prediction of extra-medical use of prescription pain relievers from a representative United States sample.

Use of prescription opioids 'beyond the bounds' of medical guidance can lead to opioid dependence. Yet recent efforts to predict extra-medical use of prescription pain relievers (EMPPR) have relied on electronic medical or pharmacy records. Because peak incidence of EMPPR occurs during adolescence- a time of relative health- administrative data may be inadequate. In this study, with data from a United States (US) population sample, we develop and internally validate an EMPPR prediction model. We analyzed data from 234,593 individuals aged 12-to-17-years, as sampled by the US National Survey of Drug Use and Health, 2004-2018, an annual cross-sectional survey. We encoded 14 predictors with onset prior to EMPPR initiation, including age, sex, and facets of drug and psychiatric history. We ranked these predictors by clinical utility before sequentially adding each to a regularized logistic regression model. On held-out test data (n = 23,685), the model performs well with 14 predictors, with an area under the precision recall curve (AUPRC) is 0.155. The area under the receiver operator curve (AUC) is 0.819, exceeding a recent benchmark on this dataset. Results are robust to survey redesign that occurred in 2015, and are not moderated by past-year use of medical services. In conclusion, while selection of predictors is limited to those with known timing prior to initiation of EMPPR rather than any cross-sectional variable, this model discriminates well. Good classification occurs even with a small set of clinically available predictors- age, a history of depression and alcohol, cigarette, and cannabis use.

Altered intrinsic connectivity distribution in internet gaming disorder and its associations with psychotherapy treatment outcomes.

Alterations in brain connectivity have been implicated in internet gaming disorder (IGD). However, little is known about alterations in whole-brain connectivity and their associations with long-term treatment outcomes. Here, we used a relatively new analytic approach, intrinsic connectivity distribution (ICD) analysis, to examine brain connectivity in 74 IGD participants and 41 matched healthy controls (HCs) and conducted post hoc seed-based resting-state functional connectivity (rsFC) analyses based on the ICD findings. We also examined how these findings related to outcomes involving a craving behavioral intervention (CBI) for IGD. IGD participants showed less whole-brain connectivity in the left angular gyrus and ventromedial prefrontal cortex (vmPFC) compared with HC participants. Seed-based rsFC analyses revealed that the left angular gyrus in the IGD group showed less connectivity with areas involved in the default-mode network and greater connectivity with areas in the salience and executive control networks. CBI was associated with improved connectivity within regions in the default-mode network and regions across the default-mode and salience networks. ICD-identified connectivity differences in the left angular gyrus and vmPFC were related to changes in craving and severity of addiction 6 months after the intervention. The findings suggest that IGD is associated with alterations in brain connectivity that may be sensitive to interventions. Thus, the findings have implications for understanding mechanisms underlying CBI effects and for further treatment development.

Childhood trauma moderates inhibitory control and anterior cingulate cortex activation during stress.

OBJECTIVE: The anterior cingulate cortex (ACC) is critical for both stress and inhibitory control processes and has been implicated in childhood trauma. This prospective study tested the hypothesis that early trauma moderates the association between inhibitory control during late childhood and ACC stress reactivity during adolescence. METHOD: Sixty-four adolescents were stratified into higher- or lower-childhood-trauma groups. Inhibitory control was indicated by fewer errors on a Stroop Color-Word task. Personalized stress cues during functional magnetic resonance imaging assessed neural correlates of stress in adolescents. RESULTS: Using a priori-defined anterior (rCZa) and posterior rostral cingulate zones of the ACC, associated with Stroop Color-Word task performance in prior meta-analyses, Stroop errors correlated inversely with activation in the rCZa during stress-cue exposure (r = -.23, p = .04). Childhood trauma moderated the association between Stroop errors and rCZa stress reactivity (interaction = -1.26, p = .02, 95%CI = -2.33,-0.20), where Stroop errors were inversely associated with brain activation among those with higher childhood trauma (simple slopes = -.83, p = .007, 95%CI = -1.40,-0.25). Low stress-related rCZa activation inversely (R2 = 0.19, b = -0.43, p = .001, 95%CI = -4.11,-1.06) and Stroop errors directly (R2 = 0.09, b = 0.27, p = .048, 95%CI = 0.02, 5.8) associated with baseline subjective anxiety while controlling for childhood trauma. CONCLUSIONS: This is the first study to demonstrate a moderating role of childhood trauma on the relationship between inhibitory control and stress-related ACC activation. Childhood trauma may portend neurodevelopmental changes that impede recruitment of control-associated ACC-functioning during distress, which may relate to dysregulation of stress-induced affective responses. Further work is needed to elucidate relationships between childhood trauma and addictive behaviors precipitated by stress.

Ten simple rules for predictive modeling of individual differences in neuroimaging.

Establishing brain-behavior associations that map brain organization to phenotypic measures and generalize to novel individuals remains a challenge in neuroimaging. Predictive modeling approaches that define and validate models with independent datasets offer a solution to this problem. While these methods can detect novel and generalizable brain-behavior associations, they can be daunting, which has limited their use by the wider connectivity community. Here, we offer practical advice and examples based on functional magnetic resonance imaging (fMRI) functional connectivity data for implementing these approaches. We hope these ten rules will increase the use of predictive models with neuroimaging data.

Double-Blind Placebo-Controlled Trial of Galantamine for Methadone-Maintained Individuals With Cocaine Use Disorder: Secondary Analysis of Effects on Illicit Opioid Use.

BACKGROUND AND OBJECTIVES: Concurrent use of cocaine and opioids is a persistent and challenging problem, particularly within methadone maintenance settings, and there are no approved pharmacotherapies for this population. Galantamine, a cholinesterase inhibitor, was found in a randomized clinical trial to reduce cocaine use among methadone-maintained individuals who were also cocaine dependent. Because of the potential of galantamine to reduce multiple drugs of abuse, it may also reduce opioid use. METHODS: We conducted a secondary analysis of a randomized, double-blind, placebo-controlled trial of 120 methadone-maintained individuals with concurrent cocaine dependence. Participants were randomized to galantamine or placebo in a 12-week trial with a 6-month follow-up (97% of intention to treat sample reached for final follow-up). RESULTS: There was a significant main effect for galantamine over placebo on percent of urine specimens that were negative for opioids, both within treatment (77% for galantamine vs 62% for placebo, F = 5.0, P = 0.027) and through a 6-month follow-up (81% vs 59%, respectively, F = 10.8, P = 0.001). This effect was seen regardless of whether participants used nonprescribed opioids during the baseline period. Galantamine effects were seen early in treatment, with participants in placebo submitting the first opioid-positive urine specimen significantly sooner than participants in galantamine (median day 15 vs 53, Wilcoxon = 5.7, P = 0.02). CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: If these results are supported in future trials, galantamine may hold promise across multiple drugs of abuse, including opioids. (Am J Addict 2019;28:238-245).

Gray-matter relationships to diagnostic and transdiagnostic features of drug and behavioral addictions.

Alterations in neural structure have been reported in both cocaine-use disorder and gambling disorder, separately, suggesting similarities across addiction diagnoses. Individual variation in neural structure has also been associated with impulsivity, a dimensional construct implicated in addictions. This study combines categorical (diagnosis-based) and dimensional (transdiagnostic) approaches to identify neural structural alterations linked to addiction subtypes and trait impulsivity, respectively, across individuals with gambling disorder (n = 35), individuals with cocaine-use disorder (n = 37) and healthy comparison individuals (n = 37). High-resolution T1-weighted data were analyzed using modulated voxel-based morphometry (VBM). Statistical analyses were conducted using whole-brain general-linear models, corrected for family-wise error (pFWE < .05). Categorical analyses indicated a main effect of diagnostic group on prefrontal (dorsal anterior cingulate and ventromedial prefrontal cortex) gray matter volumes (GMVs), involving decreased GMVs among cocaine-use disorder participants only. Dimensional analyses indicated a negative association between trait impulsivity and cortical (insula) and subcortical (amygdala and hippocampus) GMVs across all participants. Conjunction analysis indicated little anatomical overlap between regions identified as differentiating diagnostic groups and regions covarying with impulsivity. These data provide first evidence of neural structural differences between gambling disorder and an illicit substance-use disorder. They further indicate dissociable effects of diagnostic groupings and trait impulsivity on neural structure among individuals with behavioral and drug addictions. Study findings highlight the importance of considering both categorical and dimensional (e.g. Research Domain Criteria; RDoC) analysis approaches within the context of addictions research.

Substance-use initiation moderates the effect of stress on white-matter microstructure in adolescents.

BACKGROUND: While childhood stress may contribute risk to substance-use initiation and differences in brain white-matter development, understanding of the potential impact of substance-use initiation on the relationship between experienced stress and white-matter microstructure remains limited. OBJECTIVES: This study examined whether substance-use initiation moderated the effect of perceived stress on white-matter differences using measures of primary white-matter fiber anisotropy. METHODS: Forty adolescents (age 14.75 ± .87 years) were assessed on the Perceived Stress Scale, and 50% were determined to have presence of substance-use initiation. White-matter microstructure was examined using primary-fiber orientations anisotropy, which may reflect white-matter integrity, modeled separately from other fiber orientations in the same voxels. Analyses were conducted on regions of interest previously associated with childhood stress and substance use. RESULTS: Lower perceived stress and presence of substance-use initiation were related to greater right cingulum primary-fiber measures. Substance-use-initiation status moderated the association between perceived stress and right cingulum primary-fiber measures, such that higher perceived stress was associated with lower right cingulum primary-fiber anisotropy in adolescents without substance-use initiation, but not in those with substance-use initiation. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Findings in primary-fiber anisotropy suggest differences in right cingulum white-matter integrity is associated with substance-use initiation in higher-stress adolescents. This reflects a possible pre-existing risk factor, an impact of early substance use, or a combination thereof. Examination of potential markers associated with substance-use initiation in white-matter microstructure among stress-exposed youth warrant additional investigation as such biomarkers may inform efforts relating to tailored interventions. (Am J Addict 2018;27:217-224).

Activation of the ventral and dorsal striatum during cue reactivity in Internet gaming disorder.

Studies conducted in drug addiction suggest a transition in processing of drug-related cues from the ventral to the dorsal component of the striatum. However, this process has not been studied in a behavioral addiction. Assessment of this process in a non-drug addiction can provide insight into the pathophysiology of both substance and behavioral addictions. Thirty-nine male Internet gaming disorder (IGD) subjects and 23 male matched healthy controls (HCs) participated in functional magnetic resonance imaging during performance of a cue-reactivity task involving alternating presentation of Internet gaming-related stimuli (game cues) and general Internet surfing-related stimuli (control cues). Cue-induced neural activations in the ventral and dorsal striatum (DS) were compared between IGD and HC participants. Associations between cue-reactivity within these regions and cue-induced craving and severity and duration of IGD were also explored. IGD participants exhibited higher cue-induced activations within both the ventral and DS when compared with HCs. Within the IGD group, activity within the left ventral striatum (VS) was correlated negatively with cue-induced craving; positive associations were found between activations within the DS (right putamen, pallidum and left caudate) and duration of IGD. Cue-induced activity within the left putamen was negatively associated with right VS volumes among IGD participants. Consistent with studies in substance addictions, our results suggest that a transition from ventral to dorsal striatal processing may occur among individuals with IGD, a condition without the impact of substance intake.

Relationships Between Perceived Family Gambling and Peer Gambling and Adolescent Problem Gambling and Binge-Drinking.

The study systematically examined the relative relationships between perceived family and peer gambling and adolescent at-risk/problem gambling and binge-drinking. It also determined the likelihood of at-risk/problem gambling and binge-drinking as a function of the number of different social groups with perceived gambling. A multi-site high-school survey assessed gambling, alcohol use, presence of perceived excessive peer gambling (peer excess-PE), and family gambling prompting concern (family concern-FC) in 2750 high-school students. Adolescents were separately stratified into: (1) low-risk, at-risk, and problem/pathological gambling groups; and, (2) non-binge-drinking, low-frequency-binge-drinking, and high-frequency-binge-drinking groups. Multinomial logistic regression showed that relative to each other, FC and PE were associated with greater likelihoods of at-risk and problem/pathological gambling. However, only FC was associated with binge-drinking. Logistic regression revealed that adolescents who endorsed either FC or PE alone, compared to no endorsement, were more likely to have at-risk and problem/pathological gambling, relative to low-risk gambling. Adolescents who endorsed both FC and PE, compared to PE alone, were more likely to have problem/pathological gambling relative to low-risk and at-risk gambling. Relative to non-binge-drinking adolescents, those who endorsed both FC and PE were more likely to have low- and high-frequency-binge-drinking compared to FC alone or PE alone, respectively. Family and peer gambling individually contribute to adolescent at-risk/problem gambling and binge-drinking. Strategies that target adolescents as well as their closely affiliated family and peer members may be an important step towards prevention of harm-associated levels of gambling and alcohol use in youths.

Decreased functional connectivity between ventral tegmental area and nucleus accumbens in Internet gaming disorder: evidence from resting state functional magnetic resonance imaging.

BACKGROUND: Internet gaming disorder (IGD) has become an increasing mental health problem worldwide. Decreased resting-state functional connectivity (rsFC) between the ventral tegmental area (VTA) and the nucleus accumbens (NAcc) has been found in substance use and is thought to play an important role in the development of substance addiction. However, rsFC between the VTA and NAcc in a non-substance addiction, such as IGD, has not been assessed previously. The current study aimed to investigate: (1) if individuals with IGD exhibit alterations in VTA-NAcc functional connectivity; and (2) whether VTA-NAcc functional connectivity is associated with subjective Internet craving. METHODS: Thirty-five male participants with IGD and 24 healthy control (HC) individuals participated in resting-state functional magnetic resonance imaging. Regions of interest (left NAcc, right NAcc and VTA) were selected based on the literature and were defined by placing spheres centered on Talairach Daemon coordinates. RESULTS: In comparison with HCs, individuals with IGD had significantly decreased rsFC between the VTA and right NAcc. Resting-state functional connectivity strength between the VTA and right NAcc was negatively correlated with self-reported subjective craving for the Internet. CONCLUSIONS: These results suggest possible neural functional similarities between individuals with IGD and individuals with substance addictions.

At-Risk/Problematic Shopping and Gambling in Adolescence.

Elevated levels of both pathological gambling (PG) and problem shopping (PS) have been reported among adolescents, and each is associated with a range of other negative health/functioning measures. However, relationships between PS and PG, particularly during adolescence, are not well understood. In this study, we explored the relationship between different levels of problem-gambling severity and health/functioning characteristics, gambling-related social experiences, gambling behaviors and motivations among adolescents with and without at-risk/problematic shopping (ARPS). Survey data from Connecticut high school students (n = 2,100) were analyzed using bivariate analyses and logistic regression modeling. Although at-risk/problematic gambling (ARPG) was not increased among adolescents with ARPS, adolescents with ARPG (vs non-gamblers) were more likely to report having experienced a growing tension or anxiety that could only be relieved by shopping and missing other obligations due to shopping. In comparison to the non-ARPS group, a smaller proportion of respondents in the ARPS group reported paid part-time employment, whereas a greater proportion of respondents reported excessive gambling by peers and feeling concerned over the gambling of a close family member. In general, similar associations between problem-gambling severity and measures of health/functioning and gambling-related behaviors and motivations were observed across ARPS and non-ARPS adolescents. However, associations were weaker among ARPS adolescents for several variables: engagement in extracurricular activities, alcohol and caffeine use and gambling for financial reasons. These findings suggest a complex relationship between problem-gambling severity and ARPS. They highlight the importance of considering co-occurring risk behaviors such as ARPS when treating adolescents with at-risk/problem gambling.

Increased temporo-insular engagement in unmedicated bipolar II disorder: an exploratory resting state study using independent component analysis.

OBJECTIVES: Despite numerous structural and functional magnetic resonance imaging studies, the neurobiology of bipolar disorder (BD) is still incompletely understood. Resting-state functional magnetic resonance imaging (rsFMRI) allows for the study of intrinsic functional connections between brain areas, which may reflect the pathophysiology of BD. Most previous rsFMRI studies conducted in BD have included a majority of medicated patients, making simple interpretation with respect to pathophysiology difficult. METHODS: Participants were 15 antipsychotic agent- and mood-stabilizer-naïve young adults with bipolar II disorder (BD-II), and 20 healthy controls group-matched for gender, age, and cognitive ability. Independent component analysis (ICA) was used to identify eight commonly studied resting-state networks (RSNs). Between-group comparisons were conducted using dual regression and corrected for family-wise error (FWE) across space and the number of components (pFWE < 0.05). RESULTS: In comparison to controls, participants with BD-II had increased coherence across several brain regions, including the bilateral insula and putamen, across a temporo-insular network. No between-group differences in engagement of the default mode network were found. CONCLUSIONS: This was the first ICA-based rsFMRI study conducted among unmedicated individuals with BD. Given the young age (mean = 23 years) and antipsychotic agent- and mood-stabilizer-naïve status of our participants with BD-II, temporo-insular functional connectivity is a candidate vulnerability marker for BD. Further work is needed to relate resting-state differences to detailed understanding of pathophysiology.

Identification of a Composite Latent Dimension of Reward and Impulsivity Across Clinical, Behavioral, and Neurobiological Domains Among Youth.

BACKGROUND: Individual differences in reward processing are central to heightened risk-taking behaviors during adolescence, but there is inconsistent evidence for the relationship between risk-taking phenotypes and the neural substrates of these behaviors. METHODS: Here, we identify latent features of reward in an attempt to provide a unifying framework linking together aspects of the brain and behavior during early adolescence using a multivariate pattern learning approach. Data (N = 8295; n male = 4190; n female = 4105) were acquired as part of the Adolescent Brain Cognitive Development (ABCD) Study and included neuroimaging (regional neural activity responses during reward anticipation) and behavioral (e.g., impulsivity measures, delay discounting) variables. RESULTS: We revealed a single latent dimension of reward driven by shared covariation between striatal, thalamic, and anterior cingulate responses during reward anticipation, negative urgency, and delay discounting behaviors. Expression of these latent features differed among adolescents with attention-deficit/hyperactivity disorder and disruptive behavior disorder, compared with those without, and higher expression of these latent features was negatively associated with multiple dimensions of executive function and cognition. CONCLUSIONS: These results suggest that cross-domain patterns of anticipatory reward processing linked to negative features of impulsivity exist in both the brain and in behavior during early adolescence and that these are representative of 2 commonly diagnosed reward-related psychiatric disorders, attention-deficit/hyperactivity disorder and disruptive behavior disorder. Furthermore, they provide an explicit baseline from which multivariate developmental trajectories of reward processes may be tracked in later waves of the ABCD Study and other developmental cohorts.