A pilot study of basal ganglia and thalamus structure by high dimensional mapping in children with Tourette syndrome

Background: Prior brain imaging and autopsy studies have suggested that structural abnormalities of the basal ganglia (BG) nuclei may be present in Tourette Syndrome (TS). These studies have focused mainly on the volume differences of the BG structures and not their anatomical shapes.  Shape differences of various brain structures have been demonstrated in other neuropsychiatric disorders using large-deformation, high dimensional brain mapping (HDBM-LD).  A previous study of a small sample of adult TS patients demonstrated the validity of the method, but did not find significant differences compared to controls. Since TS usually begins in childhood and adult studies may show structure differences due to adaptations, we hypothesized that differences in BG and thalamus structure geometry and volume due to etiological changes in TS might be better characterized in children. Objective: Pilot the HDBM-LD method in children and estimate effect sizes. Methods: In this pilot study, T1-weighted MRIs were collected in 13 children with TS and 16 healthy, tic-free, control children. The groups were well matched for age.  The primary outcome measures were the first 10 eigenvectors which are derived using HDBM-LD methods and represent the majority of the geometric shape of each structure, and the volumes of each structure adjusted for whole brain volume. We also compared hemispheric right/left asymmetry and estimated effect sizes for both volume and shape differences between groups. Results: We found no statistically significant differences between the TS subjects and controls in volume, shape, or right/left asymmetry.  Effect sizes were greater for shape analysis than for volume. Conclusion: This study represents one of the first efforts to study the shape as opposed to the volume of the BG in TS, but power was limited by sample size. Shape analysis by the HDBM-LD method may prove more sensitive to group differences

Differential engagement of anterior cingulate corte subdivisions for cognitive and emotional function.

Abstract Functional differentiation of dorsal (dACC) and rostral (rACC) anterior cingulate cortex for cognitive and emotional function has received considerable indirect support. Using fMRI, parallel tasks, and within-subject analysis, the present study directly tested the proposed specialization of ACC subdivisions. A Task  Region interaction confirmed more dACC activation during color-word distractors and more rACC activation during emotion-word distractors. Activity in ACC subdivisions differentially predicted behavioral performance. Connectivity with prefrontal and limbic regions also supported distinct dACC and rACC roles. Findings provide direct evidence for differential engagement of ACC subdivisions in cognitive and emotional processing and for differential functional connectivity in the implementation of cognitive control and emotion regulation. Results point to an anatomical and functional continuum rather than segregated operations

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Item Retention as a Feature Selection Task: Developing Abbreviated Measures Using Shapley Values

Creating abbreviated measures from existing questionnaires is important for avoiding lengthy assessment procedures and reducing respondent burden while improving response quality. Though factor analytic strategies have mainly been used to guide item retention for abbreviated questionnaires, others have suggested conceptualizing item retention as a feature selection task amenable to machine learning approaches. The present study tested a machine learning-guided approach to item retention, specifically item-level importance as measured by Shapley values for the prediction of total score, to create abbreviated versions of the Penn State Worry Questionnaire (PSWQ) in a sample of 3,906 secondary school students in the Netherlands. Results showed that Shapley values were a useful measure for determining item retention in creating abbreviated versions of the PSWQ, demonstrating concordance with the full PSWQ. As item-level importance varied based on the proportion of the worry distribution predicted (e.g., high versus low PSWQ scores), item retention is dependent on the intended purpose of the abbreviated measure. Illustrative examples are presented using Shapley values to guide item retention for abbreviated PSWQ versions targeting the entire total score distribution and targeting high scores specifically. Future studies should determine best practices for creating abbreviated measures by comparing machine learning and factor analytic approaches

Associations of Family Distress, Family Income, and Acculturation on Cognitive Performance using the NIH Toolbox: Implications for Clinical and Research Settings

Neuropsychologists commonly evaluate raw scores on cognitive tests in relation to a defined reference group to make qualitative interpretations about an individual’s performance. However, these interpretations are only as relevant as the standardized frame of reference used for comparison,which relies on sample size and representativeness. There is growing recognition that the use of conventional norms (e.g., age, sex, years of education, and race) as proxies to capture a broader range of cultural and socioeconomic variability is suboptimal, limiting sample representativeness. The present study evaluated the incremental utility of family income, family conflict, and bidimensional acculturation, above and beyond age, gender, maternal years of education, and race on NIH-Toolbox cognitive performance. A regression-based norming procedure was used as this method may provide more precise estimates of cognitive performance relative to traditional normative tables. Greater family income and lower scores on the Family Environment Scale predicted better performance on the NIH Toolbox subtests, though the effect sizes were very small (r < .05). Scores on the Vancouver Index of Acculturation were not predictive of cognitive performance. Lastly, there were no significant differences between the original NIH Toolbox and new demographically corrected T-scores (Mdiff < 0.50). By traditional statistical standards, the NIH-TB appears to be robust to these sociocultural differences in children between ages 9–10. Practical and clinical contexts in which these small effects may have meaningful impact are discussed

Both reactive and proactive control are deficient in children with ADHD and predictive of clinical symptoms.

Cognitive control deficits are a hallmark of attention deficit hyperactivity disorder (ADHD) in children. Theoretical models posit that cognitive control involves reactive and proactive control processes but their distinct roles and inter-relations in ADHD are not known, and the contributions of proactive control remain vastly understudied. Here, we investigate the dynamic dual cognitive control mechanisms associated with both proactive and reactive control in 50 children with ADHD (16F/34M) and 30 typically developing (TD) children (14F/16M) aged 9-12 years across two different cognitive controls tasks using a within-subject design. We found that while TD children were capable of proactively adapting their response strategies, children with ADHD demonstrated significant deficits in implementing proactive control strategies associated with error monitoring and trial history. Children with ADHD also showed weaker reactive control than TD children, and this finding was replicated across tasks. Furthermore, while proactive and reactive control functions were correlated in TD children, such coordination between the cognitive control mechanisms was not present in children with ADHD. Finally, both reactive and proactive control functions were associated with behavioral problems in ADHD, and multi-dimensional features derived from the dynamic dual cognitive control framework predicted inattention and hyperactivity/impulsivity clinical symptoms. Our findings demonstrate that ADHD in children is characterized by deficits in both proactive and reactive control, and suggest that multi-componential cognitive control measures can serve as robust predictors of clinical symptoms