The aim of this study was to examine the validity of a 2-choice audio-vocal reaction time (RT) probe task for measuring the changes in attentional demand during practice and learning of a discrete motor task. Twenty participants practiced the motor task across 3 days and were probed with the RT task during either the preparation or execution phase of the primary task. As practice progressed, participants improved in the primary task performance and shortened the RTs to the probe task. This indicated that less attention was required to plan and execute the movement and suggested that the RT probe task was a sensitive and valid tool to measure changes in attentional demands across practice. The authors implemented several additional experimental controls to address possible confounders including unintentional learning of the probe task, primary-secondary task trade-off effects, and compliance with task priority instructions. These experimental controls further ensured the validity of the probe paradigm and interpretability of the dual-task cost findings. Our experimental methods provided confirmatory evidence for the validity of the 2-choice RT task as a means to assess attentional demands during motor learning.
The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification.