Prenatal Cannabis and Tobacco Co-Exposure and Its Association with Behavioural Outcomes in Middle Childhood: Co-exposition prénatale au cannabis et au tabac et son association avec les résultats comportementaux au cours de l'enfance intermédiaire.

OBJECTIVES: Cannabis legalization has triggered an increase in prenatal cannabis use. Given that tobacco is commonly co-used with cannabis, determining outcomes associated with prenatal cannabis and tobacco co-exposure is crucial. While literature exists regarding the individual effects of prenatal cannabis and tobacco exposure on childhood behaviour, there is a gap regarding their combined use, which may have interactive effects. Therefore, we investigated whether prenatal cannabis and tobacco co-exposure was associated with greater externalizing and internalizing problems in middle childhood compared to prenatal exposure to either substance alone or no exposure. METHODS: Baseline data from the Adolescent Brain Cognitive Development (ABCD) Study (collected in children ages 9-11) were used to explore differences in externalizing and internalizing scores derived from the Childhood Behavior Checklist across four groups: children with prenatal cannabis and tobacco co-exposure (CT, n = 290), children with prenatal cannabis-only exposure (CAN, n = 225), children with prenatal tobacco-only exposure (TOB, n = 966), and unexposed children (CTL, n = 8,311). We also examined if the daily quantity of tobacco exposure modulated the effect of cannabis exposure on outcomes. RESULTS: Adjusting for covariates, a 2 × 2 ANCOVA revealed significant main effects for prenatal cannabis (p = 0.03) and tobacco exposure (p < 0.001), and a significant interaction effect on externalizing scores (p = 0.032); no significant main effects or interactions were found for internalizing scores. However, interactions between daily quantity of cannabis and tobacco exposure significantly predicted both externalizing and internalizing scores (p < 0.01). CONCLUSIONS: These findings indicate that co-exposure is associated with greater externalizing problems than exposure to either substance alone, which did not differ from each other. Further, greater tobacco exposure may amplify the negative effect of cannabis exposure on both externalizing and internalizing behaviours in children. These findings underscore the need for interventions that target cannabis and tobacco co-use in pregnant women to circumvent their adverse impact on middle childhood behaviour.

Prenatal Cannabis and Tobacco Co-exposure and its Association with Middle Childhood BehavioursPlain Language SummaryGiven the high rates of both cannabis and tobacco use during pregnancy, we explored if their combined use was associated with greater problematic behaviour in 10-year-old children compared to either substance alone or no substance use. We found that children with prenatal co-exposure had greater externalizing behaviours, such as attention problems and aggression, compared to children with prenatal exposure to one of the substances or no exposure. Prenatal co-exposure, cannabis-only exposure and tobacco-only exposure had no effect on childhood internalizing behaviours (e.g., depression, anxiety). However, the amount of tobacco consumed by the mother amplified the negative effect of cannabis on both childhood externalizing and internalizing behaviours. These findings emphasize the need for specialized treatment for cannabis and tobacco co-use in pregnant women to circumvent the adverse impact of these substances on externalizing behaviours in middle childhood.

First Used Nicotine/Cannabis Product and Associated Outcomes in Late Adolescents.

BACKGROUND: Nicotine and tobacco product (NTP) and cannabis use are common in adolescence/young adulthood and increase risk for negative psychosocial outcomes. This study investigated associations among adolescent/young adults' initial experiences with NTPs, lifetime frequency of substance use, substance-related problems, and mental health symptoms. METHOD: Adolescents and young adults enrolled in a study on NTP and cannabis use were asked at what age they initiated the use of NTPs and were assigned to groups based on which product or substance(s) they reported using at the earliest age. Participants who reported use of NTPs (in isolation, without cannabis) first (N = 78, "NTP-only"), simultaneous use of NTPs and cannabis first (e.g., blunt or bowl; N = 25, "Simult-only"), use of both NTPs in isolation and simultaneous use at the same age (N = 48, "NTP + Simult"), and no NTP use (N = 53, "NTP-naïve") were compared on substance use, substance-related problems, and mental health symptoms. RESULTS: Groups differed on lifetime frequency of NTP, simultaneous, and cannabis use, with NTP users reporting more substance use episodes and substance-related problems than the NTP-naïve group. The lifetime frequency of cannabis use did not differ across NTP use groups. NTP use was associated with increased anxiety and depression, with no significant differences between groups. CONCLUSIONS: Adolescents and young adults who use nicotine may be at increased risk for greater nicotine use and mental health consequences, but initiating NTP use simultaneously with cannabis may not increase the risk of negative outcomes above and beyond nicotine initiation. Prospective longitudinal research is needed to establish temporal associations between first-used NTP/cannabis products and relevant outcomes.

Preliminary Evidence for Cannabis and Nicotine Urinary Metabolites as Predictors of Verbal Memory Performance and Learning Among Young Adults.

OBJECTIVE: Verbal memory deficits are linked to cannabis use. However, self-reported episodic use does not allow for assessment of variance from other factors (e.g., cannabis potency, route of consumption) that are important for assessing brain-behavior relationships. Further, co-occurring nicotine use may moderate the influence of cannabis on cognition. Here we utilized objective urinary measurements to assess the relationship between metabolites of cannabis, 11-nor-9-carboxy-∆9-tetrahydrocannabinol (THCCOOH), and nicotine (cotinine) on verbal memory in young adults. METHOD: Adolescents and young adults (n = 103) aged 16-22 completed urinary drug testing and verbal memory assessment (RAVLT). Linear regressions examined the influence of THCCOOH and cotinine quantitative concentrations, and their interaction, on RAVLT scores, controlling for demographics and alcohol. Cannabis intake frequency was also investigated. Secondary analyses examined whether past month or recency of use related to performance, while controlling for THCCOOH and cotinine concentrations. RESULTS: THCCOOH concentration related to both poorer total learning and long delay recall. Cotinine concentration related to poorer short delay recall. Higher frequency cannabis use status was associated with poorer initial learning and poorer short delay. When comparing to self-report, THCCOOH and cotinine concentrations were negatively related to learning and memory performance, while self-report was not. CONCLUSIONS: Results confirm the negative relationship between verbal memory and cannabis use, extending findings with objective urinary THCCOOH, and cotinine concentration measurements. No moderating relationship with nicotine was found, though cotinine concentration independently associated with negative short delay performance. Findings support the use of both urinary and self-report metrics as complementary methods in substance use research.

Parental Family History of Alcohol Use Disorder and Neural Correlates of Response Inhibition in Children From the Adolescent Brain Cognitive Development (ABCD) Study.

BACKGROUND: Youth whose parents have alcohol use disorder (AUD) are at higher risk for earlier initiation and greater magnitude of alcohol use, and have a higher likelihood of developing an AUD than their peers without parental history of AUD. This increased risk may be partly attributable to altered development of inhibitory control and related neural circuitry. This study examined neural activation during a motor response inhibition Stop Signal Task (SST) in substance-naïve youth aged 9 to 10 years with and without parental family history of AUD. METHODS: Baseline cross-sectional survey and functional magnetic resonance imaging (fMRI) data were drawn from 6,898 youth in the US-based Adolescent Brain Cognitive Development Study. Generalized additive mixed models were conducted to examine the association between maternal, paternal, and parental (both mother and father) family history of AUD with neural activation during successful and failed response inhibition. Family history interactions with sex and stratification by ethnicity were explored. RESULTS: Of 6,898 participants, 951 (14%) were family history positive for any parental AUD. Paternal history of AUD was associated with greater activation for successful inhibition in the right medial orbital frontal gyrus, compared to youth with no family history. Maternal history of AUD was associated with greater activation for failed response inhibition among females in the cerebellum, compared to females with no such history. Parental history (both mother and father) of AUD was associated with greater activation during successful inhibition in the left paracentral gyri and left superior parietal lobule. Maternal history and parental history of AUD findings were accounted for by a family history of substance use disorder in general. All effect sizes were relatively small. CONCLUSIONS: Substance-naïve children with a parental family history of AUD exhibit greater neural activation in some regions of the fronto-basal ganglia and cerebellar networks when they successfully or unsuccessfully inhibit a response as compared to children with no such family history. This unique neural response pattern could reflect a compensatory response and may represent an inherent neurobiological vulnerability to risk-related behaviors in these youth which will be examined in future longitudinal analyses of this cohort.

Neuropsychological Trajectories Associated with Adolescent Alcohol and Cannabis Use: A Prospective 14-Year Study.

OBJECTIVES: Alcohol and cannabis remain the substances most widely used by adolescents. Better understanding of the dynamic relationship between trajectories of substance use in relation to neuropsychological functioning is needed. The aim of this study was to examine the different impacts of within- and between-person changes in alcohol and cannabis use on neuropsychological functioning over multiple time points. METHODS: Hierarchical linear modeling examined the effects of alcohol and cannabis use on neuropsychological functioning over the course of 14 years in a sample of 175 adolescents (aged 12-15 years at baseline). RESULTS: Time-specific fluctuations in alcohol use (within-person effect) predicted worse performance across time on the Wechsler Abbreviated Scale of Intelligence Block Design subtest (B = -.05, SE = .02, p = .01). Greater mean levels of percent days of cannabis use across time (between-person effect) were associated with an increased contrast score between Delis-Kaplan Executive Function System Color Word Inhibition and Color Naming conditions (B = .52, SE = .14, p < .0001) and poorer performance over time on Block Design (B = -.08, SE = .04, p = .03). Neither alcohol and/nor cannabis use over time was associated with performance in the verbal memory and processing speed domains. CONCLUSIONS: Greater cumulative cannabis use over adolescence may be linked to poorer inhibitory control and visuospatial functioning performance, whereas more proximal increases in alcohol consumption during adolescence may drive alcohol-related performance decrements in visuospatial functioning. Results from this prospective study add to the growing body of literature on the impact of alcohol and cannabis use on cognition from adolescent to young adulthood.

Screen media activity and brain structure in youth: Evidence for diverse structural correlation networks from the ABCD study.

The adolescent brain undergoes profound structural changes which is influenced by many factors. Screen media activity (SMA; e.g., watching television or videos, playing video games, or using social media) is a common recreational activity in children and adolescents; however, its effect on brain structure is not well understood. A multivariate approach with the first cross-sectional data release from the Adolescent Brain Cognitive Development (ABCD) study was used to test the maturational coupling hypothesis, i.e. the notion that coordinated patterns of structural change related to specific behaviors. Moreover, the utility of this approach was tested by determining the association between these structural correlation networks and psychopathology or cognition. ABCD participants with usable structural imaging and SMA data (N = 4277 of 4524) were subjected to a Group Factor Analysis (GFA) to identify latent variables that relate SMA to cortical thickness, sulcal depth, and gray matter volume. Subject scores from these latent variables were used in generalized linear mixed-effect models to investigate associations between SMA and internalizing and externalizing psychopathology, as well as fluid and crystalized intelligence. Four SMA-related GFAs explained 37% of the variance between SMA and structural brain indices. SMA-related GFAs correlated with brain areas that support homologous functions. Some but not all SMA-related factors corresponded with higher externalizing (Cohen's d effect size (ES) 0.06-0.1) but not internalizing psychopathology and lower crystalized (ES: 0.08-0.1) and fluid intelligence (ES: 0.04-0.09). Taken together, these findings support the notion of SMA related maturational coupling or structural correlation networks in the brain and provides evidence that individual differences of these networks have mixed consequences for psychopathology and cognitive performance.

Adolescent Brain Development: Implications for Understanding Risk and Resilience Processes Through Neuroimaging Research.

This special section focuses on research that utilizes neuroimaging methods to examine the impact of social relationships and socioemotional development on adolescent brain function. Studies include novel neuroimaging methods that further our understanding of adolescent brain development. This special section has a particular focus on how study findings add to our understanding of risk and resilience. In this introduction to the special section, we discuss the role of neuroimaging in developmental science and provide a brief review of neuroimaging methods. We present key themes that are covered in the special section articles including: (1) emerging methods in developmental neuroscience, (2) emotion-cognition interaction, and (3) the role of social relationships in brain function. We conclude our introduction with future directions for integrating developmental neuroscience into the study of adolescence, and highlight key points from the special section's commentaries which include information on the landmark Adolescent Brain Cognitive Development (ABCD) study.

Earlier Alcohol Use Onset Predicts Poorer Neuropsychological Functioning in Young Adults.

BACKGROUND: Neurodevelopment may be shaped by environmental factors such as alcohol intake. Over 20% of U.S. high school students begin drinking before age 14, and those who initiated drinking before age 14 are 4 times more likely to develop psychosocial, psychiatric, and substance use difficulties than those who began drinking after turning 20. Little is known, however, about how the age of alcohol use onset influences brain development. METHODS: This study prospectively examined the effects of alcohol use onset age on neurocognitive functioning in healthy adolescent drinkers (N = 215). Youth were administered a neuropsychological battery before substance use initiation (M = 13.6 years, SD = 0.8) and on average 6.8 years later (M = 20.2 years, SD = 1.5). Hierarchical linear regressions examined if earlier ages of onset for first and regular (i.e., weekly) alcohol use adversely influenced neurocognition, above and beyond baseline neurocognition, substance use severity, and familial and social environment factors. RESULTS: As hypothesized, an earlier age of first drinking onset (AFDO) predicted poorer performance in the domains of psychomotor speed and visual attention (ps<0.05, N = 215) and an earlier age of weekly drinking onset (AWDO) predicted poorer performances on tests of cognitive inhibition and working memory, controlling for baseline neuropsychological performance, drinking duration, and past-year marijuana use (ps<0.05, N = 127). No relationship between AFDO and AWDO was found with verbal learning and memory and visuospatial ability. CONCLUSIONS: This is the first study to assess the association between age of adolescent drinking onset and neurocognitive performance using a comprehensive test battery. This study suggests that early onset of drinking increases risk for alcohol-related neurocognitive vulnerabilities and that initiation of any or weekly alcohol use at younger ages appears to be a risk factor for poorer subsequent neuropsychological functioning. Findings have important implications for public policies related to the legal drinking age and prevention programming. Further studies are needed to replicate these preliminary findings and better understand mediating processes and moderating conditions.

Neural predictors of alcohol use and psychopathology symptoms in adolescents.

Adolescence is a period marked by increases in risk taking, sensation seeking, and emotion dysregulation. Neurobiological models of adolescent development propose that lagging development in brain regions associated with affect and behavior control compared to regions associated with reward and emotion processing may underlie these behavioral manifestations. Cross-sectional studies have identified several functional brain networks that may contribute to risk for substance use and psychopathology in adolescents. Determining brain structure measures that prospectively predict substance use and psychopathology could refine our understanding of the mechanisms that contribute to these problems, and lead to improved prevention efforts. Participants (N = 265) were healthy substance-naïve adolescents (ages 12-14) who underwent magnetic resonance imaging and then were followed annually for up to 13 years. Cortical thickness and surface area measures for three prefrontal regions (dorsolateral prefrontal cortex, inferior frontal gyrus, and orbitofrontal cortex) and three cortical regions from identified functional networks (anterior cingulate cortex, insular cortex, and parietal cortex) were used to predict subsequent binge drinking, externalizing symptoms, and internalizing symptoms. Thinner dorsolateral prefrontal cortex and inferior frontal cortex in early adolescence predicted more binge drinking and externalizing symptoms, respectively, in late adolescence (ps < .05). Having a family history of alcohol use disorder predicted more subsequent binge drinking and externalizing symptoms. Thinner parietal cortex, but not family history, predicted more subsequent internalizing symptoms (p < .05). This study emphasizes the temporal association between maturation of the salience, inhibition, and executive control networks in early adolescence and late adolescent behavior outcomes. Our findings indicate that developmental variations in these brain regions predate behavioral outcomes of substance use and psychopathology, and may therefore serve as prospective biomarkers of vulnerability.

Investigating sex differences and age of onset in emotion regulation, executive functioning, and cannabis use in adolescents and young adults.

BACKGROUND: Young adults have historically high levels of cannabis use at a time which coincides with emotional and cognitive development. Age of regular onset of cannabis use and sex at birth are hypothesized to influence the relationship between cannabis use and cognition. Here we investigated past 6-month cannabis use in relation to emotional and executive functioning. We further considered age of onset and sex in subgroup analyses. METHOD: Young adults (N = 225; ages 16-22) completed a substance use interview and cognitive battery, including the Emotional Word-Emotional Face Stroop and NIH toolbox executive functioning tasks. Linear regressions examined relationships between past 6-month cannabis use episodes and performance. Subgroup analyses investigated whether age of onset or sex impacted relationships. RESULTS: After correcting for multiple comparisons, greater past 6-month cannabis use episodes were related to poorer Emotional Stroop Congruent Accuracy (p = .0004, FDR-p = .002) and List Sorting Working Memory (p = .02, FDR-p = .10) performance. Younger age of regular use onset marginally related to lower Emotional Stroop Congruent Accuracy performance (p = .03, FDR-p = .13). There were no cannabis use by sex interactions on cognition. CONCLUSIONS: Consistent with prior findings, results suggest small reductions in cannabis-related performance in processing speed during emotional Stroop and working memory tasks. Age of onset was modestly related to Stroop performance, but not sex. Longitudinal studies which detail patterns of cannabis and other substance use are needed to better assess brain-behavior relationships and other factors (e.g., age of onset of regular use, sex) which could influence cannabis-related impairments in cognitive functioning.

The effects of nicotine use during adolescence and young adulthood on gray matter cerebral blood flow estimates.

Nicotine and tobacco product (NTP) use remains prevalent in adolescence/young adulthood. The effects of NTPs on markers of brain health during this vulnerable neurodevelopmental period remain largely unknown. This report investigates associations between NTP use and gray matter cerebral blood flow (CBF) in adolescents/young adults. Adolescent/young adult (16-22 years-old) nicotine users (NTP; N = 99; 40 women) and non-users (non-NTP; N = 95; 56 women) underwent neuroimaging sessions including anatomical and optimized pseudo-continuous arterial spin labeling scans. Groups were compared on whole-brain gray matter CBF estimates and their relation to age and sex at birth. Follow-up analyses assessed correlations between identified CBF clusters and NTP recency and dependence measures. Controlling for age and sex, the NTP vs. non-NTP contrast revealed a single cluster that survived thresholding which included portions of bilateral precuneus (voxel-wise alpha < 0.001, cluster-wise alpha < 0.05; ≥7 contiguous voxels). An interaction between NTP group contrast and age was observed in two clusters including regions of the left posterior cingulate (PCC)/lingual gyrus and right anterior cingulate cortex (ACC): non-NTP exhibited positive correlations between CBF and age in these clusters, whereas NTP exhibited negative correlations between CBF and age. Lower CBF from these three clusters correlated with urine cotinine (rs=-0.21 - - 0.16; ps < 0.04) and nicotine dependence severity (rs=-0.16 - - 0.13; ps < 0.07). This is the first investigation of gray matter CBF in adolescent/young adult users of NTPs. The results are consistent with literature on adults showing age- and nicotine-related declines in CBF and identify the precuneus/PCC and ACC as potential key regions subserving the development of nicotine dependence.

Neurite Orientation Dispersion and Density Imaging (NODDI) of Brain Microstructure in Adolescent Cannabis and Nicotine Use.

INTRODUCTION: Despite evidence suggesting deleterious effects of cannabis and nicotine tobacco product (NTP) use on white matter integrity, there have been limited studies examining white matter integrity among users of both cannabis and nicotine. Further, updated white matter methodology provides opportunities to investigate use patterns on neurite orientation dispersion and density (NODDI) indices and subtle tissue changes related to the intra- and extra-neurite compartment. We aimed to investigate how cannabis and NTP use among adolescents and young adults interacts to impact the white matter integrity microstructure. MATERIALS AND METHODS: A total of 221 participants between the ages of 16 and 22 completed the Customary Drinking and Drug Use Record (CDDR) to measure substance use, and underwent a magnetic resonance imaging (MRI) session. Participants were divided into NTP-control and NTP groupings and cannabis-control and cannabis groupings (≥26 NTP/cannabis uses in past 6 months). Tract-Based Spatial Statistics (TBSS) and two-way between-subjects ANOVA investigated the effects of NTP use group, cannabis use group, and their interaction on fractional anisotropy (FA) and NODDI indices while controlling for age and biological sex. RESULTS: NTP use was associated with decreased FA values and increased orientation dispersion in the left anterior capsule. There were no significant effects of cannabis use or the interaction of NTP and cannabis use on white matter outcomes. DISCUSSION: NTP use was associated with altered white matter integrity in an adolescent and young adult sample. Findings suggest that NTP-associated alterations may be linked to altered fiber tract geometry and dispersed neurite structures versus myelination, as well as differential effects of NTP and cannabis use on white matter structure. Future work is needed to investigate how altered white matter is related to downstream behavioral effects from NTP use.

Traumatic brain injury, working memory-related neural processing, and alcohol experimentation behaviors in youth from the ABCD cohort.

Adolescent traumatic brain injury (TBI) has long-term effects on brain functioning and behavior, impacting neural activity under cognitive load, especially in the reward network. Adolescent TBI is also linked to risk-taking behaviors including alcohol misuse. It remains unclear how TBI and neural functioning interact to predict alcohol experimentation during adolescence. Using Adolescent Brain Cognitive Development (ABCD) study data, this project examined if TBI at ages 9-10 predicts increased odds of alcohol sipping at ages 11-13 and if this association is moderated by neural activity during the Emotional EN-Back working memory task at ages 11-13. Logistic regression analyses showed that neural activity in regions of the fronto-basal ganglia network predicted increased odds of sipping alcohol by ages 11-13 (p < .05). TBI and left frontal pole activity interacted to predict alcohol sipping (OR = 0.507, 95% CI [0.303 - 0.846], p = .009) - increased activity predicted decreased odds of alcohol sipping for those with a TBI (OR = 0.516, 95% CI [0.314 - 0.850], p = .009), but not for those without (OR = 0.971, 95% CI [0.931 -1.012], p = .159). These findings suggest that for youth with a TBI, increased BOLD activity in the frontal pole, underlying working memory, may be uniquely protective against the early initiation of alcohol experimentation. Future work will examine TBI and alcohol misuse in the ABCD cohort across more time points and the impact of personality traits such as impulsivity on these associations.

A preliminary investigation of physical and mental health features of cannabis & nicotine co-use among adolescents and young adults by sex.

INTRODUCTION: Cannabis and nicotine/tobacco products (NTP) are commonly co-used in adolescence and young adulthood; however, limited research has been done on predictive health behaviors to co-use. The current study is a preliminary investigation into the relationships of modifiable health behaviors on cannabis and NTP co-use in adolescents and young adults. METHOD: 221 participants (ages 16-22) were characterized into cannabis use only (N = 55), NTP use only (N = 20), cannabis and NTP co-use (used cannabis and NTP; N = 96) and control (no use; N = 50) groups based on past 30-day use. Self-report measures for physical activity, sleep quality, mental health, and reward responsivity were utilized. Participants were given a comprehensive neurocognitive battery. Logistic regressions of self-report measures and fluid intelligence composite scores on substance use group status were run stratified by sex. RESULTS: Higher approach reward sensitivity traits were associated with increased likelihood of cannabis use only (Odds Ratio (OR) = 1.15, p = .036) in female participants. Increased aerobic activity was associated with decreased likelihood of cannabis use only (OR = 0.91, p = .047) and cannabis and NTP co-use (OR = 0.88, p = .007) in female participants. Higher anxiety was associated with increased likelihood of cannabis NTP co-use (OR = 1.51, p = 0.025) in male participants. DISCUSSION: Several health behaviors were linked with cannabis use and cannabis and NTP co-use in both females and male adolescents and young adults. Health markers differed by sex suggesting differing mechanisms of substance co-use. This study informs targetable health behaviors for prevention and intervention efforts.

The Combined Effects of Nicotine and Cannabis on Cortical Thickness Estimates in Adolescents and Emerging Adults.

Early life substance use, including cannabis and nicotine, may result in deleterious effects on the maturation of brain tissue and gray matter cortical development. The current study employed linear regression models to investigate the main and interactive effects of past-year nicotine and cannabis use on gray matter cortical thickness estimates in 11 bilateral independent frontal cortical regions in 223 16-22-year-olds. As the frontal cortex develops throughout late adolescence and young adulthood, this period becomes crucial for studying the impact of substance use on brain structure. The distinct effects of nicotine and cannabis use status on cortical thickness were found bilaterally, as cannabis and nicotine users both had thinner cortices than non-users. Interactions between nicotine and cannabis were also observed, in which cannabis use was associated with thicker cortices for those with a history of nicotine and tobacco product (NTP) use in three left frontal regions. This study sheds light on the intricate relationship between substance use and brain structure, suggesting a potential modulation of cannabis' impact on cortical thickness by nicotine exposure, and emphasizing the need for further longitudinal research to characterize these interactions and their implications for brain health and development.

Social cognitive influences associated with susceptibility to nicotine and tobacco use in youth in the ABCD Study.

INTRODUCTION: Chronic use of nicotine and tobacco products (NTP) continues to be a leading cause of morbidity and mortality. Uptake is most common among youth and young adults but knowledge about effective prevention and intervention approaches is insufficient. The goal of the present study was to examine the impact of social cognitive factors on NTP risk over time among youth in the national ABCD cohort. METHODS: Participants (n=11,880, 47.8% female) were 9-10 years old at baseline, and completed multiple assessments of NTP use and related cognitions over two years. Structural equation modeling was used to estimate concurrent and prospective associations between social cognitive factors (peer and parent NTP use and perceptions of peer approval and harms from e-cigarette use) and risk for NTP use. RESULTS: Participant NTP use was primarily of e-cigarettes. Higher levels of parental and especially peer NTP use were significant prospective predictors of greater risk of NTP use. Lower perceived harm from and higher peer approval of e-cigarette use were significant predictors of heightened current but not future NTP risk. CONCLUSION: Findings suggest that youth perceptions of peer NTP use is a key predictor of the likelihood of use and a potential target for interventions designed to prevent or reduce e-cigarette and other NTP use in youth. IMPLICATIONS: findings indicate that perceived peer use is a more powerful predictor of nicotine and tobacco product (NTP) use than cognitive factors or parental use, even at early ages when youth NTP use is uncommon. This suggests a need for additional early intervention targeting perceptions of and responding to peer NTP use.

Nicotine use during late adolescence and young adulthood is associated with changes in hippocampal volume and memory performance.

Background: With the advent of electronic nicotine delivery systems, the use of nicotine and tobacco products (NTPs) among adolescents and young adults remains high in the US. Use of e-cigarettes additionally elevates the risk of problematic use of other substances like cannabis, which is often co-used with NTPs. However, their effects on brain health, particularly the hippocampus, and cognition during this neurodevelopmental period are poorly understood. Methods: Healthy late adolescents/young adults (N = 223) ages 16-22 completed a structural MRI to examine right and left hippocampal volumes. Memory was assessed with the NIH Toolbox Picture Sequence Memory Test (PSMT) and Rey Auditory Verbal Learning Test (RAVLT). Cumulative 6-month NTP and cannabis episodes were assessed and modeled continuously on hippocampal volumes. Participants were then grouped based on 6-month NTP use to examine relationships with the hippocampus and memory: current users (CU) endorsed weekly or greater use; light/abstinent users (LU) endorsed less than weekly; and never users (NU). Results: NTP use predicted larger hippocampal volumes bilaterally while cannabis use had no impact nor interacted with NTP use. For memory, larger left hippocampal volumes were positively associated with PSMT performance, RAVLT total learning, short delay and long delay recall for the NU group. In contrast, there was a negative relationship between hippocampal volumes and performances for LU and CU groups. No differences were detected between NTP-using groups. Conclusion: These results suggest that the hippocampus is sensitive to NTP exposure during late adolescence/young adulthood and may alter typical hippocampal morphometry in addition to brain-behavior relationships underlying learning and memory processes.

EMG-projected MEG high-resolution source imaging of human motor execution: Brain-muscle coupling above movement frequencies.

Magnetoencephalography (MEG) is a non-invasive functional imaging technique for pre-surgical mapping. However, movement-related MEG functional mapping of primary motor cortex (M1) has been challenging in presurgical patients with brain lesions and sensorimotor dysfunction due to the large numbers of trials needed to obtain adequate signal to noise. Moreover, it is not fully understood how effective the brain communication is with the muscles at frequencies above the movement frequency and its harmonics. We developed a novel Electromyography (EMG)-projected MEG source imaging technique for localizing early-stage (-100 to 0 ms) M1 activity during ~l min recordings of left and right self-paced finger movements (~1 Hz). High-resolution MEG source images were obtained by projecting M1 activity towards the skin EMG signal without trial averaging. We studied delta (1-4 Hz), theta (4-7 Hz), alpha (8-12 Hz), beta (15-30 Hz), gamma (30-90 Hz), and upper-gamma (60-90 Hz) bands in 13 healthy participants (26 datasets) and three presurgical patients with sensorimotor dysfunction. In healthy participants, EMG-projected MEG accurately localized M1 with high accuracy in delta (100.0%), theta (100.0%), and beta (76.9%) bands, but not alpha (34.6%) or gamma/upper-gamma (0.0%) bands. Except for delta, all other frequency bands were above the movement frequency and its harmonics. In three presurgical patients, M1 activity in the affected hemisphere was also accurately localized, despite highly irregular EMG movement patterns in one patient. Altogether, our EMG-projected MEG imaging approach is highly accurate and feasible for M1 mapping in presurgical patients. The results also provide insight into movement-related brain-muscle coupling above the movement frequency and its harmonics.

Longitudinal changes in white matter integrity among adolescent substance users.

BACKGROUND: The influence of repeated substance use during adolescent neurodevelopment remains unclear as there have been few prospective investigations. The aims of this study were to identify longitudinal changes in fiber tract integrity associated with alcohol- and marijuana-use severity over the course of 1.5 years. METHODS: Adolescents with extensive marijuana- and alcohol-use histories by mid-adolescence (n = 41) and youth with consistently minimal if any substance use (n = 51) were followed over 18 months. Teens received diffusion tensor imaging and detailed substance-use assessments with toxicology screening at baseline and 18-month follow-ups (i.e., 182 scans in all), as well as interim substance-use interviews each 6 months. RESULTS: At an 18-month follow-up, substance users showed poorer white matter integrity in 7 tracts: (i) right superior longitudinal fasciculus, (ii) left superior longitudinal fasciculus, (iii) right posterior thalamic radiations, (iv) right prefrontal thalamic fibers, (v) right superior temporal gyrus white matter, (vi) right inferior longitudinal fasciculus, and (vii) left posterior corona radiata (ps < 0.01). More alcohol use during the interscan interval predicted higher mean diffusivity (i.e., worsened integrity) in right (p < 0.05) and left (p = 0.06) superior longitudinal fasciculi, above and beyond baseline values in these bundles. Marijuana use during the interscan interval did not predict change over time. More externalizing behaviors at Time 1 predicted lower fractional anisotropy and higher radial diffusivity (i.e., poorer integrity) of the right prefrontal thalamic fibers (p < 0.025). CONCLUSIONS: Findings add to previous cross-sectional studies reporting white matter disadvantages in youth with substance-use histories. In particular, alcohol use during adolescent neurodevelopment may be linked to reductions in white matter quality in association fiber tracts with frontal connections. In contrast, youth who engage in a variety of risk-taking behaviors may have unique neurodevelopmental trajectories characterized by truncated development in fronto-thalamic tracts, which could have functional and clinical consequences in young adulthood.

Early adolescent cortical thinning is related to better neuropsychological performance.

Adolescence is characterized by significant neuromaturation, including extensive cortical thinning, particularly in frontal regions. The goal of this study was to examine the behavioral correlates of neurostructural development in early adolescence. Participants were 185 healthy 12- to 14-year-olds (44% female) recruited from local schools. Participants completed a comprehensive neuropsychological test battery and magnetic resonance imaging session. Cortical surface reconstruction and thickness estimates were performed via FreeSurfer. Age and cortical thickness were negatively correlated in 10 brain regions, 7 of which were in frontal areas (ß = −.15 to −.25, ps ≤ .05). Hierarchical linear regressions examined the influence of cortical thickness on working memory, attention, verbal learning and memory, visuospatial functioning, spatial planning and problem solving, and inhibition, controlling for age and intracranial volume. Thinner parietal cortices predicted better performances on tests of verbal learning and memory, visuospatial functioning, and spatial planning and problem solving (ß = −.14 to −.24, ps ≤ .05). Age, spanning from 12 to 14 years, accounted for up to 6% of cortical thickness, suggesting substantial thinning during early adolescence, with males showing more accelerated thinning than females between ages 12 and 14. For both males and females, thinner parietal association cortices corresponded with better neurocognitive functioning above and beyond age alone.