Direct digital sensing of protein biomarkers in solution.

The detection of proteins is of central importance to biomolecular analysis and diagnostics. Typical immunosensing assays rely on surface-capture of target molecules, but this constraint can limit specificity, sensitivity, and the ability to obtain information beyond simple concentration measurements. Here we present a surface-free, single-molecule microfluidic sensing platform for direct digital protein biomarker detection in solution, termed digital immunosensor assay (DigitISA). DigitISA is based on microchip electrophoretic separation combined with single-molecule detection and enables absolute number/concentration quantification of proteins in a single, solution-phase step. Applying DigitISA to a range of targets including amyloid aggregates, exosomes, and biomolecular condensates, we demonstrate that the assay provides information beyond stoichiometric interactions, and enables characterization of immunochemistry, binding affinity, and protein biomarker abundance. Taken together, our results suggest a experimental paradigm for the sensing of protein biomarkers, which enables analyses of targets that are challenging to address using conventional immunosensing approaches.

Speech fluency in bilinguals who stutter: Language proficiency and attentional demands as mediating factors.

PURPOSE: The current study examines how speech disfluencies manifest themselves in the two languages of bilingual persons who stutter, starting from the hypothesis that stuttering is associated with an attentional deficit at the level of speech production. METHODS: Twenty-eight bilingual people who stutter performed a spontaneous and a controlled speech production task, once in their dominant and once in their non-dominant language. The controlled production task (i.e. a network description task) was carried out once under a full-attention condition and once under a divided-attention condition where a non-linguistic, pitch discrimination task was performed simultaneously. RESULTS: In both the spontaneous and the controlled speech task, bilingual persons who stutter produced more (typical and stuttering-like) disfluencies in their L2 than in their L1. Furthermore, whereas the typical disfluencies increased when attention was directed away from speech production, stuttering-like disfluencies decreased. This effect was however restricted to L2. In addition, L2 proficiency was generally found to be a predicting factor, with higher proficiency leading to fewer disfluencies. CONCLUSIONS: These results suggest that speaking in a non-dominant language increases both typical and stuttering-like disfluencies in bilingual persons who stutter, but also that these two types of dysfluencies differ regarding their attentional origins. Our findings offer further support for attentional accounts of stuttering and have both theoretical and clinical implications.

Does Extreme Language Control Training Improve Cognitive Control? A Comparison of Professional Interpreters, L2 Teachers and Monolinguals.

There is currently a lively debate in the literature whether bilingualism leads to enhanced cognitive control or not. Recent evidence suggests that knowledge of more than one language does not always suffice for the manifestation of a bilingual cognitive control advantage. As a result, ongoing research has focused on modalities of bilingual language use that may interact with the bilingual advantage. In this study, we explored the cognitive control performance of simultaneous interpreters. These highly proficient bilinguals comprehend information in one language while producing in the other language, which is a complex skill requiring high levels of language control. In a first experiment, we compared professional interpreters to monolinguals. Data were collected on interference suppression (flanker task), prepotent response inhibition (Simon task), and short-term memory (digit span task). The results showed that the professional interpreters performed similarly to the monolinguals on all measures. In Experiment 2, we compared professional interpreters to monolinguals and second language teachers. Data were collected on interference suppression (advanced flanker task), prepotent response inhibition (advanced flanker task), attention (advanced flanker task), short-term memory (Hebb repetition paradigm), and updating (n-back task). We found converging evidence for our finding that experience in interpreting may not lead to superior interference suppression, prepotent response inhibition, and short-term memory. In fact, our results showed that the professional interpreters performed similarly to both the monolinguals and the second language teachers on all tested cognitive control measures. We did, however, find anecdotal evidence for a (small) advantage in short-term memory for interpreters relative to monolinguals when analyzing composite scores of both experiments together. Taken together, the results of the current study suggest that interpreter experience does not necessarily lead to general cognitive control advantages. However, there may be small interpreter advantages in short-term memory, suggesting that this might be an important cognitive control aspect of simultaneous interpreting. The results are discussed in the light of ongoing debates about bilingual cognitive control advantages.

Cognate effects and cognitive control in patients with parallel and differential bilingual aphasia.

BACKGROUND: Until today, there is no satisfying explanation for why one language may recover worse than another in differential bilingual aphasia. One potential explanation that has been largely unexplored is that differential aphasia is the consequence of a loss of language control rather than a loss of linguistic representations. Language control is part of a general control mechanism that also manages non-linguistic cognitive control. If this system is impaired, patients with differential aphasia could still show bilingual language activation, but they may be unable to manage activation in non-target languages, so that performance in another language is hindered. AIMS: To investigate whether a loss of cognitive control, rather than the loss of word representations in a particular language, might underlie differential aphasia symptoms. METHODS & PROCEDURES: We compared the performance of seven bilinguals with differential and eight bilinguals with parallel aphasia with 19 control bilinguals in a lexical decision and a flanker task to assess bilingual language co-activation and non-linguistic control respectively. OUTCOMES & RESULTS: We found similar cognate effects in the three groups, indicating similar lexical processing across groups. Additionally, we found a larger non-linguistic control congruency effect only for the patients with differential aphasia. CONCLUSIONS & IMPLICATIONS: The present data indicate preserved language co-activation for patients with parallel as well as differential aphasia. Furthermore, the results suggest a general cognitive control dysfunction, specifically for differential aphasia. Taken together, the results of the current study provide further support for the hypothesis of impaired cognitive control abilities in patients with differential aphasia, which has both theoretical and practical implications.

Serial-order learning impairment and hypersensitivity-to-interference in dyscalculia.

In the context of heterogeneity, the different profiles of dyscalculia are still hypothetical. This study aims to link features of mathematical difficulties to certain potential etiologies. First, we wanted to test the hypothesis of a serial-order learning deficit in adults with dyscalculia. For this purpose we used a Hebb repetition learning task. Second, we wanted to explore a recent hypothesis according to which hypersensitivity-to-interference hampers the storage of arithmetic facts and leads to a particular profile of dyscalculia. We therefore used interfering and non-interfering repeated sequences in the Hebb paradigm. A final test was used to assess the memory trace of the non-interfering sequence and the capacity to manipulate it. In line with our predictions, we observed that people with dyscalculia who show good conceptual knowledge in mathematics but impaired arithmetic fluency suffer from increased sensitivity-to-interference compared to controls. Secondly, people with dyscalculia who show a deficit in a global mathematical test suffer from a serial-order learning deficit characterized by a slow learning and a quick degradation of the memory trace of the repeated sequence. A serial-order learning impairment could be one of the explanations for a basic numerical deficit, since it is necessary for the number-word sequence acquisition. Among the different profiles of dyscalculia, this study provides new evidence and refinement for two particular profiles.

Verbal and nonverbal cognitive control in bilinguals and interpreters.

The present study explored the relation between language control and nonverbal cognitive control in different bilingual populations. We compared monolinguals, Dutch-French unbalanced bilinguals, balanced bilinguals, and interpreters on the Simon task (Simon & Rudell, 1967) and the Attention Network Test (ANT; Fan, McCandliss, Sommer, Raz, & Posner, 2002). All bilingual groups showed a smaller congruency effect in the Simon task than the monolingual group. They were also faster overall in the ANT. Furthermore, interpreters outperformed unbalanced, but not balanced, bilinguals in terms of overall accuracy on both tasks. In the ANT, the error congruency effect was significantly smaller for interpreters and balanced bilinguals. Using a measure of switching fluency in language production, this study also found direct evidence for a relation between language control and executive control. This relation was only observed in balanced bilinguals, where fluent switching was correlated with the Simon effect. These findings support the existence of a bilingual advantage and also indicate that different patterns of bilingual language use modulate the nature and extent of a cognitive control advantage in multilingual populations.