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Effect sizes are commonly interpreted using heuristics established by Cohen (e.g., small: r = .1, medium r = .3, large r = .5), despite mounting evidence that these guidelines are mis-calibrated to the effects typically found in psychological research. This study’s aims were to 1) describe the distribution of effect sizes across multiple instruments, 2) consider factors qualifying the effect size distribution, and 3) identify examples as benchmarks for various effect sizes. For aim one, effect size distributions were illustrated from a large, diverse sample of 9/10-year-old children. This was done by conducting Pearson’s correlations among 161 variables representing constructs from all questionnaires and tasks from the Adolescent Brain and Cognitive Development Study® baseline data. To achieve aim two, factors qualifying this distribution were tested by comparing the distributions of effect size among various modifications of the aim one analyses. These modified analytic strategies included comparisons of effect size distributions for different types of variables, for analyses using statistical thresholds, and for analyses using several covariate strategies. In aim one analyses, the median in-sample effect size was .03, and values at the first and third quartiles were .01 and .07. In aim two analyses, effects were smaller for associations across instruments, content domains, and reporters, as well as when covarying for sociodemographic factors. Effect sizes were larger when thresholding for statistical significance. In analyses intended to mimic conditions used in “real-world” analysis of ABCD data, the median in-sample effect size was .05, and values at the first and third quartiles were .03 and .09. To achieve aim three, examples for varying effect sizes are reported from the ABCD dataset as benchmarks for future work in the dataset. In summary, this report finds that empirically determined effect sizes from a notably large dataset are smaller than would be expected based on existing heuristics.

Attention deficit/hyperactivity disorder is associated with numerous neurocognitive deficits, including poor working memory and difficulty inhibiting undesirable behaviors that cause academic and behavioral problems in children. Prior work has attempted to determine how these differences are instantiated in the structure and function of the brain, but much of that work has been done in small samples, focused on older adolescents or adults, and used statistical approaches that were not robust to model overfitting. The current study used cross-validated elastic net regression to predict a continuous measure of ADHD symptomatology using brain morphometry and activation during tasks of working memory, inhibitory control, and reward processing, with separate models for each MRI measure. The best model using activation during the working memory task to predict ADHD symptomatology had an out-of-sample R2 = 2% and was robust to residualizing the effects of age, sex, race, parental income and education, handedness, pubertal status, and internalizing symptoms from ADHD symptomatology. This model used reduced activation in task positive regions and reduced deactivation in task negative regions to predict ADHD symptomatology. The best model with morphometry alone predicted ADHD symptomatology with an R2 = 1% but this effect dissipated when including covariates. The inhibitory control and reward tasks did not yield generalizable models. In summary, these analyses show, with a large and well-characterized sample, that the brain correlates of ADHD symptomatology are modest in effect size and captured best by brain morphometry and activation during a working memory task.

IntroductionTobacco smoking remains the leading cause of preventable death worldwide. Smoking reduction can be recommended to people unmotivated to quit, but evidence on trajectories of reduction and associated outcomes is mixed.MethodsIn a secondary analysis of five randomised, placebo-controlled trials of nicotine replacement therapy, we used latent class analysis and elastic net regression to determine latent smoking trajectories using cigarettes-per-day (CPD) across 26 weeks. Participants were adults who smoked daily without intention to quit in the next month. We used predictive modelling and receiver operator characteristic area under-the-curve (AUC) to assess smoking cessation after 1 year.ResultsParticipants (n=2066) smoked a mean 27.26±9.74 CPD at baseline. Three distinct smoking patterns emerged: Class 1 (n=186, 10%) achieved the greatest reduction in CPD (2-week mean 57% reduction) with subsequent reduction; Class 2 (n=803, 45%) saw a 2-week mean 50% reduction and remained at that level and Class 3 (n=794, 45%) reduced by a 2-week mean of 22% and returned to near-baseline CPD. Older, male participants with lower anxiety and lower nicotine dependence were more likely to be in Class 1. Abstinence rates at 1 year (~50 weeks after reduction) were 37.6% for Class 1, 4.2% for Class 2 and 2.3% for Class 3.Using latent class assignment as a predictor improved prediction of smoking cessation at 1 year follow-up over prediction using baseline characteristics by 14.4% (AUC=0.776±0.010, p=0.002). Those who reduced their CPD minimally were nearly 90% less likely to achieve cessation than those who reduced by over 50% (ORs: Class 2=0.111±0.013, Class 3=0.070±0.005).ConclusionsFindings suggest adults who are unmotivated to quit at baseline but reduce their smoking by more than half are most likely to achieve smoking cessation. A lack of early reduction success could indicate that greater support is needed to help people to quit.

A Correction to this paper has been published: https://doi.org/10.1038/s41398-021-01320-y

The stop‐signal task (SST) is one of the most common fMRI tasks of response inhibition, and its performance measure, the stop‐signal reaction‐time (SSRT), is broadly used as a measure of cognitive control processes. The neurobiology underlying individual or clinical differences in response inhibition remain unclear, consistent with the general pattern of quite modest brain–behavior associations that have been recently reported in well‐powered large‐sample studies. Here, we investigated the potential of multivariate, machine learning (ML) methods to improve the estimation of individual differences in SSRT with multimodal structural and functional region of interest‐level neuroimaging data from 9‐ to 11‐year‐olds children in the ABCD Study. Six ML algorithms were assessed across modalities and fMRI tasks. We verified that SST activation performed best in predicting SSRT among multiple modalities including morphological MRI (cortical surface area/thickness), diffusion tensor imaging, and fMRI task activations, and then showed that SST activation explained 12% of the variance in SSRT using cross‐validation and out‐of‐sample lockbox data sets (n = 7298). Brain regions that were more active during the task and that showed more interindividual variation in activation were better at capturing individual differences in performance on the task, but this was only true for activations when successfully inhibiting. Cortical regions outperformed subcortical areas in explaining individual differences but the two hemispheres performed equally well. These results demonstrate that the detection of reproducible links between brain function and performance can be improved with multivariate approaches and give insight into a number of brain systems contributing to individual differences in this fundamental cognitive control process. We investigated the potential of multivariate, machine learning (ML) methods to improve the estimation of individual differences in stop‐signal reaction time (SSRT) with region of interest‐level multimodal structural and functional neuroimaging data from the ABCD Study. Six ML algorithms were assessed across modalities and fMRI tasks. As expected, SSRT was best explained by stop‐signal task activation with 12% of individual differences in SSRT explained in cross‐validation and out‐of‐sample lockbox data sets. Brain regions that were more active during the task and that showed more interindividual variation in activation were better at capturing individual differences in performance on the task, but this was only true for activations when successfully inhibiting.

Exposure to maltreatment during childhood is associated with structural changes throughout the brain. However, the structural differences that are most strongly associated with maltreatment remain unclear given the limited number of whole-brain studies. The present study used machine learning to identify if and how brain structure distinguished young adults with and without a history of maltreatment. Young adults (ages 18–21, n = 384) completed an assessment of childhood trauma exposure and a structural MRI as part of the IMAGEN study. Elastic net regularized regression was used to identify the structural features that identified those with a history of maltreatment. A generalizable model that included 7 cortical thicknesses, 15 surface areas, and 5 subcortical volumes was identified (area under the receiver operating characteristic curve = 0.71, p < 0.001). Those with a maltreatment history had reduced surface areas and cortical thicknesses primarily in fronto-temporal regions. This group also had larger cortical thicknesses in occipital regions and surface areas in frontal regions. The results suggest childhood maltreatment is associated with multiple measures of structure throughout the brain. The use of a large sample without exposure to adulthood trauma provides further evidence for the unique contribution of childhood trauma to brain structure. The identified regions overlapped with regions associated with psychopathology in adults with maltreatment histories, which offers insights as to how these disorders manifest.

To identify neuroimaging biomarkers of alcohol dependence (AD) from structural magnetic resonance imaging, it may be useful to develop classification models that are explicitly generalizable to unseen sites and populations. This problem was explored in a mega‐analysis of previously published datasets from 2,034 AD and comparison participants spanning 27 sites curated by the ENIGMA Addiction Working Group. Data were grouped into a training set used for internal validation including 1,652 participants (692 AD, 24 sites), and a test set used for external validation with 382 participants (146 AD, 3 sites). An exploratory data analysis was first conducted, followed by an evolutionary search based feature selection to site generalizable and high performing subsets of brain measurements. Exploratory data analysis revealed that inclusion of case‐ and control‐only sites led to the inadvertent learning of site‐effects. Cross validation methods that do not properly account for site can drastically overestimate results. Evolutionary‐based feature selection leveraging leave‐one‐site‐out cross‐validation, to combat unintentional learning, identified cortical thickness in the left superior frontal gyrus and right lateral orbitofrontal cortex, cortical surface area in the right transverse temporal gyrus, and left putamen volume as final features. Ridge regression restricted to these features yielded a test‐set area under the receiver operating characteristic curve of 0.768. These findings evaluate strategies for handling multi‐site data with varied underlying class distributions and identify potential biomarkers for individuals with current AD. To identify neuroimaging biomarkers of alcohol dependence (AD) from structural magnetic resonance imaging, we developed classifiers on data collected from multiple sites. Exploratory data analysis revealed that inclusion of case‐ and control‐only sites led to the inadvertent learning of site‐effects. Evolutionary‐based feature selection leveraging leave‐one‐site‐out cross‐validation, to combat unintentional learning, yielded a test‐set area under the receiver operating characteristic curve of 0.768.

While there is substantial evidence that cannabis use is associated with differences in human brain development, most of this evidence is correlational in nature. Bayesian causal network (BCN) modeling attempts to identify probable causal relationships in correlational data using conditional probabilities to estimate directional associations between a set of interrelated variables. In this study, we employed BCN modeling in 637 adolescents from the IMAGEN study who were cannabis naïve at age 14 to provide evidence that the accelerated prefrontal cortical thinning found previously in adolescent cannabis users by Albaugh et al. [ 1 ] is a result of cannabis use causally affecting neurodevelopment. BCNs incorporated data on cannabis use, prefrontal cortical thickness, and other factors related to both brain development and cannabis use, including demographics, psychopathology, childhood adversity, and other substance use. All BCN algorithms strongly suggested a directional relationship from adolescent cannabis use to accelerated cortical thinning. While BCN modeling alone does not prove a causal relationship, these results are consistent with a body of animal and human research suggesting that adolescent cannabis use adversely affects brain development.

The field of neuroimaging has truly become data rich, and as such, novel analytical methods capable of gleaning meaningful information from large stores of imaging data are in high demand. Those methods that might also be applicable on the level of individual subjects, and thus potentially useful clinically, are of special interest. In this dissertation we introduce just such a method, called nonlinear functional mapping (NFM), and demonstrate its application in the analysis of resting state fMRI (functional Magnetic Resonance Imaging) from a 242-subject subset of the IMAGEN project, a European study of risk-taking behavior in adolescents that includes longitudinal phenotypic, behavioral, genetic, and neuroimaging data. Functional mapping employs a computational technique inspired by biological evolution to discover and mathematically characterize interactions among ROI (regions of interest), without making linear or univariate assumptions. Statistics of the resulting interaction relationships comport with recent independent work, constituting a preliminary cross-validation. Furthermore, nonlinear terms are ubiquitous in the models generated by NFM, suggesting that some of the interactions characterized here are not discoverable by standard linear methods of analysis. One such nonlinear interaction is discussed in the context of a direct comparison with a procedure involving pairwise correlation, designed to be an analogous linear version of functional mapping. Another such interaction suggests a novel distinction in brain function between drinking and non-drinking adolescents: a tighter coupling of ROI associated with emotion, reward, and interceptive processes such as thirst, among drinkers. Finally, we outline many improvements and extensions of the methodology to reduce computational expense, complement other analytical tools like graph-theoretic analysis, and possibly allow for voxel level functional mapping to eliminate the necessity of ROI selection.