Bayesian lesion-deficit inference with Bayes factor mapping: key advantages, limitations, and a toolbox.

Statistical lesion-symptom mapping is largely dominated by frequentist approaches with null hypothesis significance testing. They are popular for mapping functional brain anatomy but are accompanied by some challenges and limitations. The typical analysis design and the structure of clinical lesion data are linked to the multiple comparison problem, an association problem, limitations to statistical power, and a lack of insights into evidence for the null hypothesis. Bayesian lesion deficit inference (BLDI) could be an improvement as it collects evidence for the null hypothesis, i.e. the absence of effects, and does not accumulate α-errors with repeated testing. We implemented BLDI by Bayes factor mapping with Bayesian t-tests and general linear models and evaluated its performance in comparison to frequentist lesion-symptom mapping with a permutation-based family-wise error correction. We mapped the voxel-wise neural correlates of simulated deficits in an in-silico-study with 300 stroke patients, and the voxel-wise and disconnection-wise neural correlates of phonemic verbal fluency and constructive ability in 137 stroke patients. Both the performance of frequentist and Bayesian lesion-deficit inference varied largely across analyses. In general, BLDI could find areas with evidence for the null hypothesis and was statistically more liberal in providing evidence for the alternative hypothesis, i.e. the identification of lesion-deficit associations. BLDI performed better in situations in which the frequentist method is typically strongly limited, for example with on average small lesions and in situations with low power, where BLDI also provided unprecedented transparency in terms of the informative value of the data. On the other hand, BLDI suffered more from the association problem, which led to a pronounced overshoot of lesion-deficit associations in analyses with high statistical power. We further implemented a new approach to lesion size control, adaptive lesion size control, that, in many situations, was able to counter the limitations imposed by the association problem, and increased true evidence both for the null and the alternative hypothesis. In summary, our results suggest that BLDI is a valuable addition to the method portfolio of lesion-deficit inference with some specific and exclusive advantages: it deals better with smaller lesions and low statistical power (i.e. small samples and effect sizes) and identifies regions with absent lesion-deficit associations. However, it is not superior to established frequentist approaches in all respects and therefore not to be seen as a general replacement. To make Bayesian lesion-deficit inference widely accessible, we published an R toolkit for the analysis of voxel-wise and disconnection-wise data

Reducing alertness does not affect line bisection bias in neurotypical participants.

Alertness, or one's general readiness to respond to stimulation, has previously been shown to affect spatial attention. However, most of this previous research focused on speeded, laboratory-based reaction tasks, as opposed to the classical line bisection task typically used to diagnose deficits of spatial attention in clinical settings. McIntosh et al. (Cogn Brain Res 25:833-850, 2005) provide a form of line bisection task which they argue can more sensitively assess spatial attention. Ninety-eight participants were presented with this line bisection task, once with and once without spatial cues, and both before and after a 50-min vigilance task that aimed to decrease alertness. A single participant was excluded due to potentially inconsistent behaviour in the task, leaving 97 participants for the full analyses. While participants were, on a group level, less alert after the 50-min vigilance task, they showed none of the hypothesised effects of reduced alertness on spatial attention in the line bisection task, regardless of with or without spatial cues. Yet, they did show the proposed effect of decreased alertness leading to a lower level of general attention. This suggests that alertness has no effect on spatial attention, as measured by a line bisection task, in neurotypical participants. We thus conclude that, in neurotypical participants, the effect of alertness on spatial attention can be examined more sensitively with tasks requiring a speeded response compared to unspeeded tasks

Automatic place-value activation in magnitude-irrelevant parity judgement

Research on multi-digit number processing suggests that, in Arabic numerals, their place-value magnitude is automatically activated, whenever a magnitude-relevant task was employed. However, so far, it is unknown, whether place-value is also activated when the target task is magnitude-irrelevant. The current study examines this question using the parity congruency effect in two-digit numbers: It describes that responding to decade-digit parity congruent numbers (e.g., 35, 46; same parity of decades and units) is faster than to decade-digit parity incongruent numbers (e.g., 25; 36; different parities of decades and units). Here we investigate the (a-) symmetry of the parity congruency effect; i.e. whether it makes a difference whether participants are assessing the parity of the unit digit or the decade digit. We elaborate, how and why such an asymmetry is related to place-value processing, because the parity of the unit digit only interferes with the parity of the decade digit, while the parity of the decade digit interferes with both the parity of the unit digit and the integrated parity of the whole two-digit number. We observed a significantly larger parity congruency effect in the decade parity decision than in the unit parity decision. This suggests that automatic place-value processing also takes place in a typical parity judgment task, in which magnitude is irrelevant. Finally, because of the cross-lingual design of the study, we can show that these results and their implications were language-independent

Dataset for "Reducing alertness does not affect line bisection bias in neurotypical participants"

Alertness, or one’s general readiness to respond to stimulation, has previously been shown to affect spatial attention. However, most of this previous research focused on speeded, laboratory-based reaction tasks, as opposed to the classical line bisection task typically used to diagnose deficits of spatial attention in clinical settings. McIntosh et al. (2005) provide a form of line bisection task which they argue can more sensitively assess spatial attention. Ninety-eight participants were presented with this line bisection task, once with and once without spatial cues, and both before and after a 50-minute vigilance task that aimed to decrease alertness. A single participant was excluded due to potentially inconsistent behaviour in the task, leaving 97 participants for the full analyses. While participants were, on a group level, less alert after the 50-minute vigilance task, they showed none of the hypothesised effects of reduced alertness on spatial attention in the line bisection task, regardless of with or without spatial cues. Yet, they did show the proposed effect of decreased alertness leading to a lower level of general attention. This suggests that alertness has no effect on spatial attention, as measured by a line bisection task, in neurotypical participants. We thus conclude that, in neurotypical participants, the effect of alertness on spatial attention can be examined more sensitively with tasks requiring a speeded response compared to unspeeded tasks

Automatic place-value activation in magnitude-irrelevant parity judgement

Research on multi-digit number processing suggests that, in Arabic numerals, their place-value magnitude is automatically activated, whenever a magnitude-relevant task was employed: However, so far, it is unknown, whether place-value is also activated when the target task is magnitude-irrelevant. The current study examines this question by using the parity congruency effect in two-digit numbers: It describes that responding to decade-digit parity congruent numbers (e.g., 35, 46; same parity of decades and units) is faster than to decade-digit parity incongruent numbers (e.g., 25; 36; different parities of decades and units). Here we investigate the (a-)symmetry of the parity congruency effect; i.e. whether it makes a difference whether participants are assessing the parity of the unit digit or the decade digit. We elaborate, how and why such an asymmetry is related to place-value processing, because the parity of the unit digit only interferes with the parity of the decade digit, while the parity of the decade digit interferes with both the parity of the unit digit and the integrated parity of the whole two-digit number. We observed a significantly larger parity congruency effect in the decade parity decision than in the unit parity decision. This suggests that automatic place-value processing also takes place in a typical parity judgment task, in which magnitude is irrelevant. Finally, because of the cross-lingual design of the study, we can show that these results and their implications were language-independent

Automatic place-value activation in magnitude-irrelevant parity judgement

Research on multi-digit number processing suggests that, in Arabic numerals, the magnitude of a number is automatically processed based on the place-value system. The current study examined whether this automatic processing extends to magnitude-irrelevant parity processing by using the parity congruency effect. The parity status of a decade digit influences parity judgment of multi-digit numbers, e.g., response to 25 (decade digit parity incongruent) is slower than 35 (congruent). Here we investigated whether the parity congruency effect in Arabic two-digit numbers depends on whether participants are assessing the parity of the unit digit or the parity of the decade digit. Furthermore, we explored whether the parity congruency effects are modulated by the order of units and decades in number words (German, units first in the number word: one-and-twenty) and those from a non-inverted language (English, decades first: twenty-one). Language groups did not differ in the parity congruency effects. In both groups, however, we found a significantly larger parity congruency effect in the decade parity decision than in the unit parity decision. This suggests that automatic place-value processing takes place in a typical parity judgment task, because the parity of the unit digit only interferes with the parity of the decade digit, while the parity of the decade digit interferes with the parity of the unit digit and the place-value integrated whole two-digit number. Thus, this study indicates that automatic place-value processing generalizes over tasks in which participants do not need to explicitly refer to numerical magnitude

Pro-resolving lipid mediator Resolvin D1 serves as a marker of lung disease in cystic fibrosis.

BACKGROUND:Cystic fibrosis (CF) is an autosomal recessive genetic disorder that affects multiple organs, including the lungs, pancreas, liver and intestine. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) locus lead to defective proteins and reduced Cl- secretion and Na+ hyperabsorption in the affected organs. In addition, patients suffering from CF display chronic inflammation that contributes to the pathogenesis of CF. Recent work suggests that CF patients have a reduced capacity to biosynthesize specialized pro-resolving lipid mediators (SPMs), which contributes to the development and duration of the unwanted inflammation. Alterations in the metabolism of arachidonic acid (AA) and docosahexaenoic acid (DHA) to specialized pro-resolving mediators (SPMs), like lipoxins (LXs), maresins (MaRs), protectins (PDs) and resolvins (Rvs), may play a major role on clinical impact of airway inflammation in CF. METHODS:In this study, our aims were to detect and quantitate Resolvin D1 (RvD1) in sputum and plasma from patients with CF and compare levels of RvD1 with biomarkers of inflammation and lung function. We studied 27 CF patients aged 6 to 55 years (median 16 years) in a prospective approach. RESULTS:DHA can be found in the plasma of our CF patients in the milligram range and is decreased in comparison to a healthy control group. The DHA-derived pro-resolving mediator Resolvin D1 (RvD1) was also present in the plasma (286.4 ± 50 pg/ mL, mean ± SEM) and sputum (30.0 ± 2.6 pg/ mL, mean ± SEM) samples from our patients with CF and showed a positive correlation with sputum inflammatory markers. The plasma concentrations of RvD1 were ten times higher than sputum concentrations. Interestingly, sputum RvD1/ IL-8 levels showed a positive correlation with FEV1 (rs = 0.3962, p< 0.05). CONCLUSIONS:SPMs, like RvD1, are well known to down-regulate inflammatory pathways. Our study shows that the bioactive lipid mediator RvD1, derived from DHA, was present in sputum and plasma of CF patients and may serve as a representative peripheral biomarker of the lung resolution program for CF patients