Rachel E. Thayer

Longitudinal characterization of white matter maturation during adolescence.

BACKGROUND Late adolescence is comprised of considerable developmental transitions, though brain maturational changes during this period are subtle and difficult to quantitatively evaluate from standard brain imaging acquisitions. To date, primarily cross-sectional studies have characterized typical developmental changes during adolescence, but these processes need further description within a longitudinal framework. METHOD To assess the developmental trajectory of typical white matter development, we examined 22 healthy adolescents with serial diffusion tensor images (DTI) collected at a mean age of 17.8 years and 16-months later. Diffusion parameters fractional anisotropy, and mean, radial, and axial diffusivity were subjected to whole-brain voxelwise time point comparisons using tract-based spatial statistics. RESULTS At follow-up, adolescents showed a significant change (>or=153 contiguous voxels each at p<0.01) in diffusion properties, including in bilateral superior longitudinal fasciculi, superior corona radiata, anterior thalamic radiations, and posterior limb of the internal capsule. Overall, correlations with cognitive performances suggested behavioral improvement corresponding with white matter changes. CONCLUSION These longitudinal DTI findings support continued microstructural change in white matter during late adolescence, and suggest ongoing refinement of projection and association fibers into early adulthood.

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.

Daily Marijuana Use Is Not Associated with Brain Morphometric Measures in Adolescents or Adults

Recent research has suggested that marijuana use is associated with volumetric and shape differences in subcortical structures, including the nucleus accumbens and amygdala, in a dose-dependent fashion. Replication of such results in well controlled studies is essential to clarify the effects of marijuana. To that end, this retrospective study examined brain morphology in a sample of adult daily marijuana users (n = 29) versus nonusers (n = 29) and a sample of adolescent daily users (n = 50) versus nonusers (n = 50). Groups were matched on a critical confounding variable, alcohol use, to a far greater degree than in previously published studies. We acquired high-resolution MRI scans, and investigated group differences in gray matter using voxel-based morphometry, surface-based morphometry, and shape analysis in structures suggested to be associated with marijuana use, as follows: the nucleus accumbens, amygdala, hippocampus, and cerebellum. No statistically significant differences were found between daily users and nonusers on volume or shape in the regions of interest. Effect sizes suggest that the failure to find differences was not due to a lack of statistical power, but rather was due to the lack of even a modest effect. In sum, the results indicate that, when carefully controlling for alcohol use, gender, age, and other variables, there is no association between marijuana use and standard volumetric or shape measurements of subcortical structures.

Adolescents’ fMRI Activation to a Response Inhibition Task Predicts Future Substance Use

BACKGROUND Deficient behavioral regulation may be a risk factor for substance use disorders in adolescents. Abnormalities in brain regions critical to cognitive control have been linked to more intense and problematic future substance use (e.g., Durazzo, Gazdzinski, Mon, & Meyerhoff, 2010; Falk, Berkman, Whalen, & Lieberman, 2011; Paulus, Tapert, & Schuckit, 2005). The goal of this study was to examine the degree to which brain response to an inhibition task measured in mid-adolescence can predict substance use 18 months later. METHOD Adolescents aged 16-19 (N=80) performed a go/no-go response inhibition task during fMRI at project baseline, and were followed 18 months later with a detailed interview on substance use and dependence symptoms. Participants were 39 high frequency users and 41 demographically similar low frequency users (458 versus 2 average lifetime drug use occasions at baseline, respectively). RESULTS Across all subjects, no-go trials produced significant increases in neural response in the ventromedial prefrontal cortex and a region including the left angular and supramarginal gyri (p(FWE)<.01, cluster threshold ≥ 30 voxels). Less ventromedial prefrontal activation but more left angular gyrus activation predicted higher levels of substance use and dependence symptoms in the following 18 months, particularly for those who were high frequency users in mid-adolescence (p<.05). CONCLUSIONS These findings are consistent with studies showing that impairments in cognitive control have strong associations with substance use. We found a predictive relationship between atypical activation patterns at baseline and substance use behavior 18 months later, particularly among adolescents with histories of previous heavy use.

Recent binge drinking predicts smaller cerebellar volumes in adolescents

The current study examined the effects of recent binge drinking on cerebellar morphometry in a sample of healthy adolescents. Participants were 106 teenagers (46 bingers and 60 controls) aged 16-19 who received a high-resolution magnetic resonance imaging (MRI) scan. FreeSurfer segmented and quantified the volume of each cerebellum. Maximum drinks during a binge in the past 3 months and duration since last binge were examined as predictors of cerebellar volume, after controlling for potentially confounding variables. In the 106 teens, higher peak drinks predicted smaller left hemisphere cerebellar gray and whitematter, and right hemisphere cerebellar gray matter, and marginally predicted smaller right hemisphere cerebellar white matter. Gender did not moderate these effects. More intense adolescent binge drinking is linked to smaller cerebellar volumes even in healthy teens, above and beyond variability attributable to risk factors for binge drinking. Longitudinal research is needed to see if cerebellar volumes worsen with protracted drinking and recover with abstinence. Interventions aimed at improving brain structure in adolescent binge drinkers are necessary given the high prevalence of risky drinking in youth.

White Matter Integrity, Substance Use, and Risk Taking in Adolescence

White matter development is important for efficient communication between brain regions, higher order cognitive functioning, and complex behaviors. Adolescents have a higher propensity for engaging in risky behaviors, yet few studies have explored associations between white matter integrity and risk taking directly. Altered white matter integrity in mid-adolescence was hypothesized to predict subsequent risk taking behaviors 1.5 years later. Adolescent substance users (predominantly alcohol and marijuana, n = 47) and demographically similar nonusers (n = 49) received diffusion tensor imaging at baseline (ages 16-19), and risk taking measures at both baseline and an 18-month follow-up (i.e., at ages 17-20). Brain regions of interest were the fornix, superior corona radiata, superior longitudinal fasciculus, and superior fronto-occipital fasciculus. In substance-using youth (n = 47), lower white matter integrity at baseline in the fornix and superior corona radiata predicted follow-up substance use (ΔR2 = 10-12%, ps < .01), and baseline fornix integrity predicted follow-up delinquent behaviors (ΔR2 = 10%, p < .01) 1.5 years later. Poorer fronto-limbic white matter integrity was linked to a greater propensity for future risk taking behaviors among youth who initiated heavy substance use by mid-adolescence. Most notable were relationships between projection and limbic-system fibers and future substance-use frequency. Subcortical white matter coherence, along with an imbalance between the maturation levels in cognitive control and reward systems, may disadvantage the resistance to engage in risk taking behaviors during adolescence.

Adolescent marijuana users have elevated risk-taking on the balloon analog risk task

Objective: Adolescents who engage in regular marijuana use may have a higher propensity to take unsafe risks despite the possible negative consequences. We compared adolescents with a history of regular marijuana use to non-using teens on a behavioral measure of risk-taking. Given the involvement of the pre-frontal cortex in both risk-taking and executive functioning, we also examined whether risk-taking was associated with measures of executive functioning. Method: Fifty-eight demographically similar community youth (ages 17–20; 29% female), including 24 marijuana users and 34 non-using controls, completed the computerized Balloon Analog Risk Task (BART; Lejuez et al., 2002) and measures of substance use and executive function. Primary BART outcome measures included total number of popped balloons and average adjusted pumps (mean pumps excluding popped balloons). Results: Marijuana users had more popped balloons than controls (p<0.05) but did not differ on average adjusted pumps. Using hierarchical multiple regression controlling for age, riskier BART performance (popped balloons) was predictive of past 18-month hard drug use (β=0.30; p<0.05). Having a higher number of popped balloons was also predictive of past 18-month marijuana use (p<0.05), but age was a stronger predictor than marijuana use. Marijuana users performed worse on one test of executive functioning (psychomotor set-shifting, p<0.05), but this did not correlate with risk-taking. Conclusions: Our finding of elevated risk-taking among marijuana users is consistent with previous research that substance users may have impaired risk processing. Further, our results suggest that risk-taking is not always associated with executive dysfunction, implying the involvement of distinct neural subsystems.

Negative and interactive effects of sex, aging, and alcohol abuse on gray matter morphometry

Chronic alcohol use is associated with declines in gray matter (GM) volume, as is the normal aging process. Less apparent, however, is how the interaction between aging and heavy alcohol use affects changes in GM across the lifespan. There is some evidence that women are more vulnerable to the negative effects of alcohol use on GM than men. In the current study, we examined whether localized GM was related to measures of alcohol use disorder (e.g., AUDIT score) in a large sample (N = 436) of participants, ages 18–55 years, with a range of disease severity, using both voxel‐based morphometry (VBM) and surface‐based morphometry (SBM). We also explored whether GM associations with alcohol use disorder (AUD) severity are moderated by sex and age. Results showed significant negative associations between AUD severity and GM volume throughout temporal, parietal, frontal, and occipital lobes. Women showed more negative effects of alcohol use than men for cortical thickness in left orbitofrontal cortex, but evidence for increased vulnerability based on sex was limited overall. Similarly, a specific age by alcohol use interaction was observed for volume of right insula, but other regional or global interactions were not statistically supported. However, significant negative associations between heavy alcohol use and GM volumes were observed as early as 18–25 years. These findings support that alcohol has deleterious effects on global and regional GM above and beyond age, and, of particular importance, that regional associations emerge in early adulthood. Hum Brain Mapp 37:2276–2292, 2016.

Developmental Cognitive Neuroscience of Adolescent Sexual Risk and Alcohol Use

Abstract 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.ResumenAdolescentes humanos participan en muy altas tasas de relaciones sexuales sin protección. Este comportamiento tiene un alto potencial de consecuencias para la salud que no están intencionales, y que son severos y sostenidos, incluyendo VIH/SIDA. A pesar de estos consecuencias para la salud, sabemos muy poco de los factores neurales y cognitivos que influyen los decisiones de comportamiento sexual y la coincidencia potencial de estos mechanismos con los que forman la base de comportamientos de riesgo que son fuertemente asociadas con relaciones sexuales sin protección, incluyendo el uso del alcohol. Así, en esto revisión, evaluamos la neurociencia del desarrollo del riesgo sexual y el uso de alcohol en adolescentes humanos poniendo el acento en las implicaciones de prevención y intervención pertinentes.

Associations between fractional anisotropy and problematic alcohol use in juvenile justice-involved adolescents

Abstract Background: Studies have shown associations between heavy alcohol use and white matter alterations in adolescence. Youth involved with the juvenile justice system engage in high levels of risk behavior generally and alcohol use in particular as compared to their non-justice-involved peers. Objectives: This study explored white matter integrity among justice-involved adolescents. Analyses examined fractional anisotropy (FA) and mean diffusivity (MD) between adolescents with low and high levels of problematic alcohol use as assessed by the Alcohol Use Disorders Identification Test (AUDIT). Methods: Participants (N = 125; 80% male; 14–18 years) completed measures assessing psychological status and substance use followed by diffusion tensor imaging (DTI). DTI data for low (n = 51) and high AUDIT (n = 74) adolescents were subjected to cluster-based group comparisons on skeletonized FA and MD data. Results: Whole-brain analyses revealed significantly lower FA in clusters in the right and left posterior corona radiata (PCR) and right superior longitudinal fasciculus (SLF) in the high AUDIT group, as well as one cluster in the right anterior corona radiata that showed higher FA in the high AUDIT group. No differences in MD were identified. Exploratory analyses correlated cluster FA with measures of additional risk factors. FA in the right SLF and left PCR was negatively associated with impulsivity. Conclusion: Justice-involved adolescents with alcohol use problems generally showed poorer FA than their low problematic alcohol use peers. Future research should aim to better understand the nature of the relationship between white matter development and alcohol use specifically as well as risk behavior more generally.