Cumulative Effects of Resting-State Connectivity Across All Brain Networks Significantly Correlate with Attention-Deficit Hyperactivity Disorder Symptoms.

Identification of replicable neuroimaging correlates of attention-deficit hyperactivity disorder (ADHD) has been hindered by small sample sizes, small effects, and heterogeneity of methods. Given evidence that ADHD is associated with alterations in widely distributed brain networks and the small effects of individual brain features, a whole-brain perspective focusing on cumulative effects is warranted. The use of large, multisite samples is crucial for improving reproducibility and clinical utility of brain-wide MRI association studies. To address this, a polyneuro risk score (PNRS) representing cumulative, brain-wide, ADHD-associated resting-state functional connectivity was constructed and validated using data from the Adolescent Brain Cognitive Development (ABCD, N = 5,543, 51.5% female) study, and was further tested in the independent Oregon-ADHD-1000 case-control cohort (N = 553, 37.4% female). The ADHD PNRS was significantly associated with ADHD symptoms in both cohorts after accounting for relevant covariates (p < 0.001). The most predictive PNRS involved all brain networks, though the strongest effects were concentrated among the default mode and cingulo-opercular networks. In the longitudinal Oregon-ADHD-1000, non-ADHD youth had significantly lower PNRS (Cohen's d = -0.318, robust p = 5.5 × 10-4) than those with persistent ADHD (age 7-19). The PNRS, however, did not mediate polygenic risk for ADHD. Brain-wide connectivity was robustly associated with ADHD symptoms in two independent cohorts, providing further evidence of widespread dysconnectivity in ADHD. Evaluation in enriched samples demonstrates the promise of the PNRS approach for improving reproducibility in neuroimaging studies and unraveling the complex relationships between brain connectivity and behavioral disorders.

Gene-by-Environment Interaction Effects of Social Adversity on Externalizing Behavior in ABCD Youth.

This study tested whether multiple domains of social adversity, including neighborhood opportunity/deprivation and life stress, moderate genetic (A), common environmental (C), and unique environmental (E) influences on externalizing behaviors in 760 same-sex twin pairs (332 monozygotic; 428 dizygotic) ages 10-11 from the ABCD Study. Proportion of C influences on externalizing behavior increased at higher neighborhood adversity (lower overall opportunity). A decreased and C and E increased at lower levels of educational opportunity. A increased at lower health-environment and social-economic opportunity levels. For life stress, A decreased and E increased with number of experienced events. Results for educational opportunity and stressful life experiences suggest a bioecological gene-environment interaction pattern such that environmental influences predominate at higher levels of adversity, whereas limited access to healthcare, housing, and employment stability may potentiate genetic liability for externalizing behavior via a diathesis-stress mechanism. More detailed operationalization of social adversity in gene-environment interaction studies is needed.

Long-Term RCT outcomes for adolescent alcohol and cannabis use within a predominantly Hispanic sample.

Because adolescents are unlikely to seek, receive, or complete treatment for alcohol and/or cannabis misuse, it is important to enhance the lasting impact of clinical contacts when they do occur. Adolescents (N = 506; 72.5% Hispanic) were randomized to motivational interviewing (MI) versus alcohol and cannabis education (ACE). Latent growth models estimated change over time. Significant reductions in alcohol use were observed, with slightly greater reductions by 12-month follow-up for MI. Both interventions significantly reduced cannabis use, with no treatment group differences. When outcomes were examined comparing Hispanic to non-Hispanic participants, there were no significant differences in intervention efficacy by group. MI's inherently client-centered and culturally adaptive approach may contribute to its equitable degree of behavior change for youth across race/ethnic backgrounds.

Correlates of HIV Testing across the lifespan - adolescence through later adulthood - among sexual minority men in the US who are not on PrEP.

Regular HIV testing is an essential component of the HIV prevention and care cascade. Sexual minority males (SMM) account for most new HIV infections in the US and testing rates among SMM vary substantially across the lifespan. Research has largely overlooked the developmental context of HIV testing. The current study compared correlates of HIV testing among adolescents (aged 13-17; n = 1,641), emerging adults (aged 18-29; n = 50,483), early adults (aged 30-39; n = 25,830), middle adults (aged 40-64; n = 25,326), and late adults (65 and older; n = 1,452) who were recruited online. Overall, HIV testing rates were lowest among adolescent SMM. Having condomless anal sex in the past 3-months was a consistentpredictor of HIV testing across all age cohorts.The association between relationship status and frequency of HIV testing varied across ages. Being in a non-monogamous relationship (versus single) was associated with more frequent HIV testing among adolescent and emerging adult SMM , while being in a monogamous relationship (versus single) was associated with lower odds of HIV testing among early, middle, and late adults.

The future of translational research on alcohol use disorder.

In March 2019, a scientific meeting was held at the University of California, Los Angeles (UCLA) Luskin Center to discuss approaches to expedite the translation of neurobiological insights to advances in the treatment of alcohol use disorder (AUD). A guiding theme that emerged was that while translational research in AUD is clearly a challenge, it is also a field ripe with opportunities. Herein, we seek to summarize and disseminate the recommendations for the future of translational AUD research using four sections. First, we briefly review the current landscape of AUD treatment including the available evidence-based treatments and their uptake in clinical settings. Second, we discuss AUD treatment development efforts from a translational science viewpoint. We review current hurdles to treatment development as well as opportunities for mechanism-informed treatment. Third, we consider models of translational science and public health impact. Together, these critical insights serve as the bases for a series of recommendations and future directions. Towards the goal of improving clinical care and population health for AUD, scientists are tasked with bolstering the clinical applicability of their research findings so as to expedite the translation of knowledge into patient care.

Correction of respiratory artifacts in MRI head motion estimates.

Head motion represents one of the greatest technical obstacles in magnetic resonance imaging (MRI) of the human brain. Accurate detection of artifacts induced by head motion requires precise estimation of movement. However, head motion estimates may be corrupted by artifacts due to magnetic main field fluctuations generated by body motion. In the current report, we examine head motion estimation in multiband resting state functional connectivity MRI (rs-fcMRI) data from the Adolescent Brain and Cognitive Development (ABCD) Study and comparison 'single-shot' datasets. We show that respirations contaminate movement estimates in functional MRI and that respiration generates apparent head motion not associated with functional MRI quality reductions. We have developed a novel approach using a band-stop filter that accurately removes these respiratory effects from motion estimates. Subsequently, we demonstrate that utilizing a band-stop filter improves post-processing fMRI data quality. Lastly, we demonstrate the real-time implementation of motion estimate filtering in our FIRMM (Framewise Integrated Real-Time MRI Monitoring) software package.

Exploring Cannabis and Alcohol Co-Use in Adolescents: A Narrative Review of the Evidence.

Objective: Amidst the evolving policy surrounding cannabis legalization in the United States, cannabis use is becoming increasingly prevalent as perceptions of harm decrease, particularly among adolescents. Cannabis and alcohol are commonly used by adolescents and are often used together. However, developmental research has historically taken a "single substance" approach to examine the association of substance use and adolescent brain and behavior rather than examining co-(or poly-substance) use of multiple substances, such as cannabis and alcohol. Thus, the acute effects of cannabis and alcohol, and the impact of co-use of cannabis and alcohol on the adolescent brain, cognitive function and subsequent psychosocial outcomes remains understudied. This narrative review aims to examine the effects of cannabis and alcohol on adolescents across a number of behavioral and neurobiological outcomes. Methods: The PubMed and Google Scholar databases were searched for the last 10 years to identify articles reporting on acute effects of cannabis and alcohol administration, and the effects of cannabis and alcohol on neuropsychological, neurodevelopmental, neural (e.g., structural and functional neuroimaging), and psychosocial outcomes in adolescents. When adolescent data were not available, adult studies were included as support for potential areas of future direction in adolescent work. Results: Current studies of the impact of cannabis and alcohol on adolescent brain and behavior have yielded a complicated pattern. Some suggest that the use of cannabis in addition to alcohol during adolescence may have a "protective" effect, yielding neuropsychological and structural brain outcomes that are better than those for adolescents who use only alcohol. However, other adolescent studies suggest that cannabis and alcohol co-use is associated with negative health and social outcomes such as poorer academic performance and impaired driving. Conclusion: Variation in study methodologies, policy-level limitations and our limited understanding of the developmental neurobiological effects of cannabis preclude the straightforward interpretation of the existing data on adolescent cannabis and alcohol use. Further research on this topic is requisite to inform the development of effective intervention and prevention programs for adolescent substance users, which hinge on a more comprehensive understanding of how cannabis-and its intersection with alcohol-impacts the developing brain and behavior.

Hunting for What Works: Adolescents in Addiction Treatment.

Although adolescents are developmentally distinct from adults, they often receive addiction treatment based on adult models. This is problematic because adolescents face significantly different conditions in addiction treatment, including distinct basic biological and neurodevelopmental stages, unique sociodevelopmental concerns, distinctive addiction trajectories, and, in turn, disparate treatment goals and outcomes. In sum, it can be difficult for even savvy clinicians to know how to approach addiction treatment with this important age group. In an effort to help clinicians and researchers consider substance use via a neurodevelopmental lens, we approached this review with 4 goals: (i) characterize the prevalence, and related health and safety implications of substance use within this age group; (ii) identify the nature of the adolescent brain, including characteristic features of this phase of neurodevelopment relevant to adolescent substance use treatment; (iii) provide an overview of current adolescent addiction interventions and avenues to improve clinical treatment and clinical research efforts for adolescents; and (iv) examine the intersection between the nature of the developing brain and adolescent substance use, and utilize that information to inform alternative routes and directions for substance use treatment in this critical age group. This review concludes by offering a novel neurodevelopmental model and framework to examine substance use interventions, along with a series of recommendations to optimize adolescent substance use treatment and clinical research.

The Somatic Marker Hypothesis and Sexual Decision Making: Understanding the Role of Iowa Gambling Task Performance and Daily Sexual Arousal on the Sexual Behavior of Gay and Bisexual Men.

Background: The sexual decision-making literature suggests that sexual arousal and behavior are associated. The somatic marker hypothesis suggests that individual neuropsychological differences in decision making, as measured by the Iowa Gambling Task (IGT), may moderate these associations; however, this hypothesis has yet to be tested with event-level sexual behavior data. Purpose: We hypothesized that (a) daily sexual arousal would be positively associated with likelihood of engaging in sex and condomless anal sex (CAS) and (b) IGT scores would moderate these associations such that the associations would be stronger among those with higher IGT scores. Methods: We used daily diary data from 334 highly sexually active gay and bisexual men to examine the main and interaction effects of sexual arousal and IGT scores on sexual engagement and CAS. Results: As hypothesized, daily sexual arousal was positively associated with greater odds of both sexual engagement and CAS with casual male partners. Individual-level IGT performance significantly moderated the day-level association between arousal and sexual engagement, which was stronger for men with higher IGT scores. There was no main effect of IGT scores on either sexual behavior outcome, nor did it moderate the association between arousal and CAS. Conclusions: These findings highlight the influence of sexual arousal on sexual engagement, which differed by IGT scores; the effect of arousal on CAS was much less variable and may not be moderated by neurocognitive factors. This study supports the importance of exploring integrated behavioral/biomedical interventions to improve individual decision making to prevent HIV infection.

Sexual risk-taking and subcortical brain volume in adolescence.

Background: The developmental period of adolescence marks the initiation of new socioemotional and physical behaviors, including sexual intercourse. However, little is known about neurodevelopmental influences on adolescent sexual decision-making. Purpose: We sought to determine how subcortical brain volume correlated with condom use, and whether those associations differed by gender and pubertal development. Methods: We used FreeSurfer to extract subcortical volume among N = 169 sexually experienced youth (mean age 16.07 years; 31.95% female). We conducted multiple linear regressions to examine the relationship between frequency of condom use and subcortical volume, and whether these associations would be moderated by gender and pubertal development. Results: We found that the relationship between brain volume and condom use was better accounted for by pubertal development than by gender, and moderated the association between limbic brain volume and condom use. No significant relationships were observed in reward areas (e.g., nucleus accumbens) or prefrontal cortical control areas. Conclusions: These data highlight the potential relevance of subcortical socioemotional processing structures in adolescents' sexual decision-making.

Risky Sex in High-Risk Adolescents: Associations with Alcohol Use, Marijuana Use, and Co-Occurring Use.

Risky sexual behavior and substance use appear to be interconnected behaviors among adolescents, but data are scarce regarding the extent to which sexual risk behavior is associated with high levels of marijuana and alcohol use, both separately and in combination. 301 adolescents were recruited from a short-term detention facility, and substance use and risky sexual behavior were assessed. We found that adolescents who frequently used marijuana, but not alcohol, reported significantly less risky sex as well as greater intentions to use condoms than either adolescents who frequently used alcohol, but not marijuana, or adolescents who frequently used both substances. Substance use status as a predictor of future risky sexual behavior followed a similar pattern. When designing interventions to reduce substance use in the context of risky sex, it might be especially effective to target efforts toward reducing harm associated with alcohol use, either alone or in combination with marijuana use.

Featured Article: Adolescent Condom Use and Connectivity in the Social-Planful Brain.

Objective: To reduce rates of sexually transmitted infections (STIs) and unwanted pregnancy among adolescents, it is critical to investigate brain connectivity that may underlie adolescents' sexual health decision-making in the context of intercourse. This study explored relationships between adolescent condom use frequency and the brain's resting-state functional connectivity, to identify differential patterns of social-affective processing among sexually active youth. Methods: In this study, N = 143 sexually active adolescents (68.5% male, Mage = 16.2 years, SD = 1.06) completed magnetic resonance imaging and reported past 3-month frequency of condom use. Resting-state connectivity, seeded on a social region of the brain, the temporoparietal junction (TPJ), was assessed to determine its correspondence with protected sex (condom use). Results: Condom use was associated with positive connectivity between the left TPJ and bilateral inferior frontal gyrus (IFG). This relationship was observed in adolescent males only; no connectivity differences were observed with adolescent females. Conclusions: This study reflects functional synchrony between nodes of the "social brain," including the TPJ, and a region of planfulness and control, the IFG. The relationship between these regions suggests that adolescents who have more coordinated systems of communication between these critical components of the brain are more likely to be successful in planning and engaging in safer sexual decision-making; for young males, this differentiated more frequent from less frequent condom use. In turn, interventions designed to reduce STIs/human immunodeficiency virus may benefit from targeting social-planfulness dimensions to help youth implement safer sex behaviors.

Neural Correlates of Risky Sex and Response Inhibition in High-Risk Adolescents.

Adolescence is a neurodevelopmental period of heightened sexual risk taking. Neuroimaging can help elucidate crucial neurocognitive mechanisms underlying adolescent sexual risk behavior, yet few empirical studies have investigated this neural link. To address this gap in the literature, we examined the association between neurocognitive function during response inhibition-a known correlate of risk behaviors-and frequency of intercourse without a condom among adolescents. We examined the correlation between condom use and fMRI-based Stroop response in a large ethnically diverse sample of high-risk adolescents (n = 171). Partially replicating previous literature, sexual risk was positively correlated with blood-oxygen-level-dependent (BOLD) activation in the middle frontal gyrus during response inhibition, highlighting the relevance of this region during risky sexual decision making within this age group.

Working memory capacity and addiction treatment outcomes in adolescents.

BACKGROUND: Brief addiction treatments including motivational interviewing (MI) have shown promise with adolescents, but the factors that influence treatment efficacy in this population remain unknown. One candidate is working memory, the ability to hold a fact or thought in mind. This is relevant, as in therapy, a client must maintain and manipulate ideas while working with a clinician. Working memory depends upon brain structures and functions that change markedly during neurodevelopment and that can be negatively impacted by substance use. OBJECTIVES: In a secondary analysis of data from a clinical trial for adolescent substance use comparing alcohol/marijuana education and MI, we evaluated the relationship between working memory and three-month treatment-outcomes with the hypothesis that the relationship between intervention conditions and outcome would be moderated by working memory. METHODS: With a diverse sample of adolescents currently using alcohol and/or marijuana (N = 153, 64.7% male, 70.6% Hispanic), we examined the relationship between baseline measures of working memory and alcohol and cannabis-related problem scores measured at the three-month follow-up. RESULTS: The results showed that lower working memory scores were associated with poorer treatment response only for alcohol use, and only within the education group. No relationship was found between working memory and treatment outcomes in the MI group. CONCLUSION: The results suggest that issues with working memory capacity may interfere with adolescents' ability to process and implement didactic alcohol and marijuana content in standard education interventions. These results also suggest that MI can be implemented equally effectively across the range of working memory functioning in youth.

Orbitofrontal cortex connectivity as a mechanism of adolescent behavior change.

An increasing number of studies have implicated the role of network functional connectivity in addiction. Yet, none have examined functional connectivity as a potential mechanism of adolescent behavior change. We examined the underlying neural mechanism of a promising treatment for adolescents, motivational interviewing (MI). We began by employing psychophysiological interaction (PPI) to evaluate network response in a sample of adolescent cannabis users (N=30). Next, we examined correlations between network connectivity and clinical metrics of treatment outcome. PPI analyses seeded on the orbitofrontal cortex (OFC) showed significant increases in functional connectivity across the inferior frontal gyrus (IFG), precentral gyrus, anterior and posterior cingulate gyrus, supplementary motor area (SMA), superior frontal gyrus, pallidus, caudate, and parahippocampal gyrus. Further, greater functional connectivity between the OFC and anterior cingulate/medial frontal gyrus was associated with less behavior change (e.g., greater post-treatment cannabis problems). These data support the role of the OFC network as a mechanism of adolescent treatment response.

Developmental Cognitive Neuroscience of Adolescent Sexual Risk and Alcohol Use.

Human adolescents engage in very high rates of unprotected sex. This behavior has a high potential for unintended, serious, and sustained health consequences including HIV/AIDS. Despite these serious health consequences, we know little about the neural and cognitive factors that influence adolescents' decision-making around sex, and their potential overlap with behaviorally co-occurring risk behaviors, including alcohol use. Thus, in this review, we evaluate the developmental neuroscience of sexual risk and alcohol use for human adolescents with an eye to relevant prevention and intervention implications.

What Works? An Empirical Perspective on How to Retain Youth in Longitudinal Human Immunodeficiency Virus (HIV) and Substance Risk Reduction Studies.

BACKGROUND: Low retention rates are a problem for longitudinal studies involving adolescents, and this is particularly true for justice-involved youth. METHODS: This study evaluates (1) strategies used to retain high-risk adolescents participating in a longitudinal research project; (2) the extent to which retention efforts were different in a justice-involved versus a non-justice-involved (school-based) sample; and (3) differential characteristics of justice-involved versus school-based adolescents that might explain differences in retention difficulty. RESULTS: Compared with the school-based youth, justice-involved youth required significantly more phone calls to be successfully reached. Additionally, baseline substance use (alcohol and marijuana use frequency) was higher in the justice-involved sample and significantly related to retention difficulty. CONCLUSIONS: High retention rates for justice-involved and substance-using youth are possible with focused efforts on frequent communication and effortful contact.

Peer review of human studies run amok: a break in the fiduciary relation between scientists and the public.

Peer review aims to ensure the quality and credibility of research reporting. Conducted by volunteer scientists who receive no guidance or direction, peer review widely varies from fast and facilitative, to unclear and obstructive. Poor quality is an issue because most science research is publicly funded, whereby scientists must make an effort to quickly disseminate their findings back to the public. An unfortunately not uncommon barrier in this process is ineffective peer review. Most scientists agree that when done well, editors and reviewers drive and maintain the high standards of science. At the same time, ineffective peer review can cause great delay with no introduced improvement in final product. These delays and requests interfere with the path of communication between scientist and public, at a great cost to editors, reviewers, authors and those who stand to benefit from application of the results of the studies. We offer a series of concrete recommendations to improve this process.

Prediction Rules Identify Which Young Adults Have Higher Rates of Heavy Episodic Drinking After Exposure to 12-Week Text Message Interventions.

BACKGROUND: An alcohol text message intervention recently demonstrated effects in reducing heavy episodic drinking (HED) days at the three month follow-up in young adults with a history of hazardous drinking. An important next step in understanding intervention effects involves identifying baseline participant characteristics that predict who will benefit from intervention exposure to support clinical decision-making and guide further intervention development. To identify baseline characteristics that predict HED, this exploratory study used a prediction rule ensemble (PRE). Compared to more complex decision-tree methods (e.g., random forest), PREs have comparable performance, while generating simpler rules that can directly identify subgroups that do or do not respond to intervention. METHODS: This secondary analysis examined data from 916 young adults who reported HED (68.5% female, mean age = 22.1, SD = 2.1), were enrolled in an alcohol text message randomized clinical trial and who completed baseline assessment and the three month follow-up. A PRE with ten fold cross-validation, which included 21 baseline variables representing sociodemographic characteristics (e.g., sex, age, race, ethnicity, college enrollment), alcohol consumption (frequency of alcohol consumption, quantity consumed on a typical drinking day, frequency of HED), impulsivity subscales (i.e., negative urgency, positive urgency, lack of premeditation, lack of perseverance, sensation seeking), readiness to change, perceived peer drinking and HED-related consequences, and intervention status were used to predict HED at the three month follow-up. RESULTS: The PRE identified 12 rules that predicted HED at three months (R2 = 0.23) using 7 baseline features. Only two cases (0.2%) were not classified by the 12 rules. The most important features for predicting three month HED included baseline alcohol consumption, negative urgency score, and perceived peer drinking. CONCLUSIONS: The rules provide interpretable decision-making tools that predict who has higher alcohol consumption following exposure to alcohol text message interventions using baseline participant characteristics (prior to intervention), which highlight the importance of interventions related to negative urgency and peer alcohol use.