Switch Trials Research Articles

Interactions between language and inhibitory control: Evidence from a combined language switching and Stroop paradigm

Aims and objectives: This study assessed bilinguals’ language control (LC) and inhibitory control (IC) performance (switch costs and Stroop effects) simultaneously in the same participants to investigate how these processes influence each other. Design: Seventy-four Turkish-English bilinguals were presented with Turkish (L1) or English (L2) color words printed either in congruent or incongruent ink color and instructed to name the ink color of these words in the presentation language. Stimuli’s language and congruency were either the same as in the previous trial or different. Data and analysis: Reaction times (RTs), switch costs (mean RTs on language repetition subtracted from switch trials), and the Stroop effects (mean RTs on congruent subtracted from incongruent trials) were analyzed using the linear mixed-effect model. Findings: The switch costs were larger on incongruent than congruent, and the Stroop effects were larger on language switch than repetition trials. This means that the LC performance decreased while resolving conflict, and the IC performance decreased during switching language, indicating that these two share a common IC mechanism. However, the switch costs and Stroop effects across L1 and L2 were symmetrical in all conditions, leaving the previous interpretation uncertain. Besides, the Stroop effects were larger when followed by congruent than incongruent trials during language repetition, whereas they were equal during switching. This means that the ability to adjust performance by previous experience was disrupted during language switching. Moreover, for the high-L2 proficiency group, this ability was diminished in language repetition trials too. These results indicate that rather than inhibition, other processes may primarily mediate bilinguals’ LC. Originality: This study provides evidence for how language and inhibitory control influence each other by combining language switching and Stroop paradigms. Furthermore, it investigates the sequential congruency effects (SCE). Significance/implications: This study shows that SCE investigation may provide significant theoretical implications.

The First Interchangeable Biosimilar Insulin: Insulin Glargine-yfgn.

On March 23, 2020, all insulin products were reclassified as biologics instead of drugs under the Biological Price Competition and Innovation (BPCI) Act of 2009. This allows biosimilar insulin products to be manufactured when the patent expires for the reference biologic, sometimes called the originator or brand name product. A biosimilar product may not be substituted for the reference biologic at the pharmacy counter unless the biosimilar undergoes further switch trials to earn the designation as an interchangeable biosimilar. Insulin glargine-yfgn 100 units/mL is the first biosimilar insulin to attain interchangeable status with the reference insulin glargine. In the INSTRIDE 1 and INSTRIDE 2 trials, insulin glargine-yfgn has proven noninferiority regarding blood glucose reduction and adverse effect profile versus reference insulin glargine; even in the INSTRIDE 3 trial in which treatment of diabetes was switched between insulin glargine-yfgn and reference insulin glargine throughout the trial without statistically significant changes to glucose levels or adverse effects. Insulin glargine-yfgn may be substituted at the pharmacy counter without consultation with the prescriber, in accordance with state laws. In suit with other biosimilars, insulin glargine-yfgn's list price is significantly lower than other insulin glargine products. This increases market competition leading to decreases in costs of other insulin glargine products. Many patients who could not previously afford insulin therapy may now have significantly improved access to treatment. Providers will need education to increase awareness of these new biosimilars and interchangeable biosimilar insulin products, cost benefits, and substitution allowances.

Task switching challenge to reveal abnormal brain‐heart signatures in cognitively healthy individuals with abnormal CSF amyloid/tau

AbstractBackgroundAlpha oscillations during task switching reveals general attention (low alpha) and higher executive attentional control (high alpha). Alpha oscillations have been related to heart rate variability (HRV), both change in Alzheimer’s disease (AD). We aim to explore if task switching challenge with quantitative electroencephalography (qEEG) can reveal abnormal alpha power and HRV in individuals with high risk of AD, and we predict HRV improves qEEG’s detection of high AD risk.MethodWe compared alpha power during task switching testing between two groups of cognitively healthy participants (52‐91 years) based on different cerebrospinal fluid (CSF) amyloid/tau ratio: normal (CH‐NAT, n=19) or pathological amyloid/tau ratio (CH‐PAT, n=27). Participants were required to name the color or word of a colored word for each stimulus, with two sequential stimuli per trial. Alpha event‐related desynchronization (ERD) was analyzed during low load, repeat trials (color‐color or word‐word) and high load, switch trials (color‐word or word‐color). HRV was assessed from 5‐minute ECG recording during rest or task, including: standard deviation of RR‐intervals (SDNN), root mean squared of successive differences (RMSSD) in the time domain, as well as high (HF) and low frequency (LF) in the frequency domain. We trained a binary classifier to predict the CH‐PATs using a 30 random split of training (80%) and testing (20%) data and two‐layer, fully connected neural network after identifying significant qEEG and HRV features.ResultWe found that low alpha power was less negative in CH‐PATs than CH‐NATs (Central: ‐0.18±0.66 vs. ‐0.72±0.72, p=0.011, Cohen’s d=0.79; Parietal: ‐0.25±0.75 vs. ‐0.83±0.92, p=0.024, Cohen’s d=0.70) (Fig. 1). Furthermore, we observed significant HR and LF changes from resting to task state only in CH‐PATs, but not in CH‐NATs (Fig. 2). After identifying brain features and heart features, we explored the HRV effect on brain features’ test accuracy.ConclusionThese results suggest: 1) low alpha power during task switching challenge differs between CH‐PATs and CH‐NATs; 2) HRV suggests hyperactive autonomic regulations from resting to task in CH‐PATs, but not CH‐NATs. qEEG reveals interaction of brain and heart features in early AD pathology that may help early diagnosis and monitoring of novel therapies.

Dynamic Transitions between Neural States Are Associated with Flexible Task Switching during a Memory Task.

Flexible behavior requires switching between different task conditions. It is known that such task switching is associated with costs in terms of slowed RT, reduced accuracy, or both. The neural correlates of task switching have usually been studied by requiring participants to switch between distinct task conditions that recruit different brain networks. Here, we investigated the transition of neural states underlying switching between two opposite memory-related processes (i.e., memory retrieval and memory suppression) in a memory task. We investigated 26 healthy participants who performed a think/no-think task while being in the fMRI scanner. Behaviorally, we show that it was more difficult for participants to suppress unwanted memories when a no-think was preceded by a think trial instead of another no-think trial. Neurally, we demonstrate that think-no-think switches were associated with an increase in control-related and a decrease in memory-related brain activity. Neural representations of task condition, assessed by decoding accuracy, were lower immediately after task switching compared with the nonswitch transitions, suggesting a switch-induced delay in the neural transition toward the required task condition. This suggestion is corroborated by an association between condition-specific representational strength and condition-specific performance in switch trials. Taken together, we provided neural evidence from the time-resolved decoding approach to support the notion that carryover of the previous task set activation is associated with the switching cost, leading to less successful memory suppression.

Effect of Low-Frequency Repetitive Transcranial Magnetic Stimulation on Executive Function and Its Neural Mechanism: An Event-Related Potential Study.

Objective: Executive function refers to the conscious control of thinking and behavior in psychological process. Executive dysfunction widely exists in a variety of neuropsychiatric diseases, and is closely related to the decline of daily living ability and function. This study intends to explore the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) on executive function and its neural mechanism by using event-related potential (ERP), so as to provide basis for further study on the relationship between cerebral cortex and executive function.Methods: Task switching paradigm was used to study the cognitive flexibility in executive function. Thirty-one healthy subjects were randomly assigned to receive rTMS stimulations (1 Hz rTMS or sham rTMS) to the left dorsolateral prefrontal cortex (DLPFC) twice. The switching task and the electroencephalography EEG recordings were performed before (pre-rTMS/pre-sham rTMS) and immediately after the end of the rTMS application (post-rTMS/post-sham rTMS).Results: The analysis of RTs showed that the main effects of switching and time were statistically significant. Further analysis revealed that the RT of rTMS stimulation was longer than sham rTMS at post-stimulation. ERP analysis showed that there was a significant switching effect in frontal and central scalp location, and the P2 amplitude in switch trials was greater than that in non-switch trials. At post-stimulation, the N2 amplitude of rTMS is more negative than that of sham rTMS at non-switch trials, whereas no such difference was found at switch trials. The P3 amplitude and LPC amplitude are significantly reduced by rTMS at post-stimulation.Conclusion: Low-frequency rTMS of the left DLPFC can cause decline of cognitive flexibility in executive function, resulting in the change of N2 amplitude and the decrease of P3 and LPC components during task switching, which is of positive significance for the evaluation and treatment of executive function.

Do All Integrase Strand Transfer Inhibitors Have the Same Lipid Profile? Review of Randomised Controlled Trials in Naïve and Switch Scenarios in HIV-Infected Patients.

In this study, we aim to explore the effects on lipids of integrase strand transfer inhibitors (INSTIs) in naïve and switch randomised controlled trials, and compare them with protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). We reviewed phase 3/4 randomised clinical trials in the Cochrane and PubMed databases that compare an INSTI with a boosted PI, an NNRTI, or another INSTI plus one or two nucleoside/nucleotide reverse transcriptase inhibitors (NtRTIs) in naïve patients and switching strategies in HIV-infected patients. We reported the baseline plasma concentration of total cholesterol (TC), low and high-density lipoprotein cholesterol (LDL-c, HDL-c), triglycerides (TG), and the TC/HDL-c ratio, as well as the change at weeks 48 and 96, when available. In naïve HIV-infected patients, raltegravir (RAL) and dolutegravir (DTG) have a more favourable lipid profile compared with NNRTI and boosted PI. Elvitegravir (EVG/c) has a superior lipid profile compared with efavirenz and is similar to that observed with ritonavir-boosted atazanavir except in TG, which increases less with EVG/c. In naïve patients, RAL, DTG, and bictegravir (BIC) produce a similar, slight increase in lipids. In switching trials, the regimen change based on a boosted PI or efavirenz to RAL, DTG, or BIC is associated with clinically significant decreases in lipids that are minor when the change is executed on EVG/c. No changes were observed in lipids by switching trials between INSTIs. In summary, RAL, DTG, and BIC have superior lipid profiles compared with boosted-PI, efavirenz, and EVG/c, in studies conducted in naïve participants, and they are associated with a clinically significant decrease in lipoproteins by switching studies.

Rule Perseveration during Task-Switching in Brain Tumor: A Severe Form of Task-Setting Impairment.

It has been proposed that at least two distinct processes are engaged during task-switching: reconfiguration of the currently relevant task-set and interference resolution arising from the competing task-set. Whereas in healthy individuals the two are difficult to disentangle, their disruption is thought to cause different impairments in brain-damaged patients. Yet, the observed deficits are inconsistent across studies and do not allow drawing conclusions regarding their independence. Forty-one brain tumor patients were tested on a task-switching paradigm. We compared their performance between switch and repeat trials (switch cost) to assess rule reconfiguration, and between trials requiring the same response (congruent) and a different response for the two tasks (incongruent) to assess interference control. In line with previous studies, we found the greatest proportion of errors on incongruent trials, suggesting an interference control impairment. However, a closer look at the distribution of errors between two task rules revealed a rule perseveration impairment: Patients with high error rate on incongruent trials often applied only one task rule throughout the task and less frequently switched to the alternative one. Multivariate lesion-symptom mapping analysis unveiled the relationship between lesions localized in left orbitofrontal and posterior subcortical regions and perseveration scores, measured as absolute difference in accuracy between two task rules. This finding points to a more severe task-setting impairment, not reflected as a mere switching deficit, but instead as a difficulty in creating multiple stable task representations, in line with recent accounts of OFC functions suggesting its critical role in representing task states.

Cognitive ocular motor deficits and white matter damage chronically after sports-related concussion.

A history of concussion has been linked to long-term cognitive deficits; however, the neural underpinnings of these abnormalities are poorly understood. This study recruited 26 asymptomatic male Australian footballers with a remote history of concussion (i.e. at least six months since last concussion), and 23 non-collision sport athlete controls with no history of concussion. Participants completed three ocular motor tasks (prosaccade, antisaccade and a cognitively complex switch task) to assess processing speed, inhibitory control and cognitive flexibility, respectively. Diffusion tensor imaging data were acquired using a 3 T MRI scanner, and analysed using tract-based spatial statistics, to investigate white matter abnormalities and how they relate to ocular motor performance. Australian footballers had significantly slower adjusted antisaccade latencies compared to controls (P = 0.035). A significant switch cost (i.e. switch trial error > repeat trial error) was also found on the switch task, with Australian footballers performing increased magnitude of errors on prosaccade switch trials relative to prosaccade repeat trials (P = 0.023). Diffusion tensor imaging analysis found decreased fractional anisotropy, a marker of white matter damage, in major white matter tracts (i.e. corpus callosum, corticospinal tract) in Australian footballers relative to controls. Notably, a larger prosaccade switch cost was significantly related to reduced fractional anisotropy in anterior white matter regions found to connect to the prefrontal cortex (i.e. a key cortical ocular motor centre involved in executive functioning and task switching). Taken together, Australian footballers with a history of concussion have ocular motor deficits indicative of poorer cognitive processing speed and cognitive flexibility, which are related to reduce white matter integrity in regions projecting to important cognitive ocular motor structures. These findings provide novel insights into the neural mechanisms that may underly chronic cognitive impairments in individuals with a history of concussion.

Management of Infections in SCD Patients Treated with HU in the Framework of Escort HU

▪Background and methodThis study aims to investigate on infections in sickle cell patients treated with hydroxycarbamide (hydroxyurea, HU) for symptomatic sickle-cell syndromes enrolled in the multicentric prospective non-interventional cohort study ESCORT HU (European Sickle Cell Disease COhoRT - HydroxyUrea). The first patient was enrolled in ESCORT HU in January 2009, and by June 2017, 1844 patients were enrolled in the cohort.The increased susceptibility to infections of sickle-cell disease (SCD) affected patients is well known and likely results from several causes, including impaired splenic function, defects in complement activation, micronutrient deficiencies, and tissue ischemia. Splenectomy has been considered for a long time at high risk of early and late infections and of death in children (particularly aged 4 years or below) and adults with SCD. Although antibiotics and vaccines measures have been a huge step forward in preventive care, infections remain a major cause of morbidity and mortality in the developed countries and even more so in the developing world. Hydroxyurea (HU) is registered in Europe and in the US to prevent the recurrence of painful vaso-occlusive crises including acute chest syndrome. In Europe the marketing authorization for HU covers adults, adolescents and children older than 2 years suffering from symptomatic Sickle Cell Syndrome. HU is a well-tolerated fetal hemoglobin (Hb) inducer, with dose-dependent myelosuppression being the main short-term side-effect. Concerns have been raised about the possibility of HC as a predisposing factor for infections due to its myelosuppressive property.We present here a snapshot of infections collected in SCD patients enrolled in the prospective study cohort ESCORT HU. Children (≥ 2 years) and adults were enrolled from four European countries: France, Germany, Greece and Italy. Data are collected through an electronic Case Report Form (e-CRF). An analysis of these infections has been performed.ResultsFrom January 2009 until June 2017, 1841 patients (1016 adults and 822 children) have been enrolled in ESCORT HU. 746 infections were collected in the database in 437 patients (25.5%), of which 231 children and 206 adults. Hb Genotypes were SS (89.02%) or Sβ0 (4.35%) in 408/ 437 patients (93.3%) (see table 1).Features of the infections are reported in table 2. Bacterial infections were reported more frequently (42.4%), followed by viral infections including parvovirus B19 (26%). In 227 cases (31%), the type of infection was not specified. The spleen status was reported sporadically.As expected, infections were more frequent in children (52.4% in children vs 46.9% in adults), despite the fact that most of them received penicillin prophylaxis. Nevertheless the number of episodes of infection per patients was quite similar between adults and children: 350 infections were reported in 206 adults (1.70 per patients) and 386 in 231 children (1.67 per patient). 60% of patients (adults as well as children) experienced one episode of infection whereas 40% reported several infections. A small number of patients (33/431) had more than 3 infectious episodes. According to the investigators, infections were more severe in adults (15.14%) than in children (8.84%), but more frequently led to hospitalization in children than in adults (34.4% vs 24.4%). Antibiotics were widely prescribed for these episodes in 77.1% (adults) and 82.6% (children) of infections. No death due to infectious episode has been reported in the cohort.ConclusionsDespite an appropriate management of patients with sickle cell disease in Europe with antibiotic prophylaxis and recommendations for vaccinations (including routine vaccines and immunization against S. pneumoniae, N. meningitidis and H. influenzae), in Europe the incidence of infections remains high and is responsible for many hospitalizations. No increase of infectious risk has been reported in placebo-controlled clinical trials comparing HU and placebo in children (Baby HUG, MSH trial, SWitCH and TWitCH trials, Jain et al 2010) but comparisons with untreated SCD cohorts are required to better evaluate the incidence of infections in SCD patients treated with HU. [Display omitted] DisclosuresGalactéros:Addmedica: Membership on an entity's Board of Directors or advisory committees. De Montalembert:Addmedica: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Ribeil:Addmedica: Membership on an entity's Board of Directors or advisory committees; Vitalaire: Other: Non-financial support; Novartis: Other: Non-financial support. Kordes:Addmedica: Membership on an entity's Board of Directors or advisory committees. Grosse:Addmedica: Membership on an entity's Board of Directors or advisory committees. Brousse:Add Medica: Membership on an entity's Board of Directors or advisory committees. Oevermann:Addmedica: Membership on an entity's Board of Directors or advisory committees. Lobitz:Addmedica: Membership on an entity's Board of Directors or advisory committees.

191-OR: Similar Hypoglycemia Duration with Once-Weekly Insulin Icodec vs. Insulin Glargine U100 in Insulin Naïve or Experienced Patients with T2D

Insulin icodec* (icodec) is a novel once-weekly basal insulin analog in development. This post hoc analysis explored hypoglycemia duration using double-blinded CGM (Dexcom G6®) data from 2 phase 2, randomized, open-label, treat-to-target 16-week trials. One trial compared 3 titration algorithms of icodec vs. insulin glargine U100 (IGlar U100) in 205 insulin-naïve patients with T2D (NCT03951805), the other assessed 154 basal insulin-treated patients with T2D switching from any daily basal insulin to icodec with or without a 100% loading dose vs. IGlar U100 (NCT03922750). In line with ATTD guidelines, a hypoglycemic episode was defined as a CGM period of interstitial glucose (IG) <70 mg/dL for at least 15 min, ending when IG ≥70 mg/dL for at least 15 min. In the titration trial, hypoglycemia duration was similar across all arms: median overall hypoglycemic episode duration (IQR) was 35.0 (20.0, 70.0) min for icodec titrations A (SMBG 80-130 mg/dL ±21 U/wk) and B (80-130 mg/dL ±28 U/wk) and for IGlar U100 (80-130 mg/dL ±4 U/day), and 39.0 (24.0, 70.0) min for icodec titration C (70-108 mg/dL ±28 U/wk). The distribution pattern of hypoglycemic episodes by duration was similar across all treatment arms. Results were similar for nocturnal hypoglycemic episodes. Similarly, in the switch trial, the duration of hypoglycemia was similar between arms, irrespective of loading dose use: median overall hypoglycemic episode duration (IQR) was 40.0 (20.0, 75.0) min for icodec with loading dose, 40.0 (25.0, 80.0) min for icodec without loading dose, and 35.0 (20.0, 60.0) min for IGlar U100.The distribution pattern of hypoglycemic episodes by duration was similar across treatment arms. Similar results were seen for the nocturnal period. In conclusion, CGM-derived hypoglycemic episode duration was similar with icodec vs. IGlar U100 in insulin-naïve and insulin-experienced patients with T2D, regardless of titration algorithm or initial loading dose use. *Proposed INN. Disclosure R. J. Silver: Advisory Panel; Self; Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk. M. Asong: Employee; Self; Novo Nordisk A/S. K. Begtrup: None. M. M. Koefoed: Employee; Self; Novo Nordisk. S. R. Heller: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk, Zealand Pharma A/S, Consultant; Self; Zealand Pharma A/S, Other Relationship; Self; Dexcom, Inc., Eli Lilly and Company, MannKind Corporation, Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk. J. Rosenstock: Board Member; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Consultant; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Research Support; Self; Applied Therapeutics, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Genentech, Inc., Intarcia Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Oramed Pharmaceuticals, Inc., Pfizer Inc., REMD Biotherapeutics, Sanofi.

The Wisconsin Card Sorting Test: Split-Half Reliability Estimates for a Self-Administered Computerized Variant

Self-administered computerized assessment has the potential to increase the reach of neuropsychological assessment. The present study reports the first split-half reliability estimates for a self-administered computerized variant of the Wisconsin Card Sorting Test (WCST), which is considered as a gold standard for the neuropsychological assessment of executive functions. We analyzed data from a large sample of young volunteers (N = 375). Split-half reliability estimates for perseveration errors, set-loss errors, and inference errors were all above 0.90. Split-half reliability estimates for response time measures on switch and repeat trials exceeded 0.95. Our results indicated sufficient split-half reliability for a self-administered computerized WCST, paving the way for an advanced digital assessment of executive functions. We discuss potential effects of test formats, administration variants, and sample characteristics on split-half reliability.

Efficacy and Safety of Adalimumab Biosimilars: Current Critical Clinical Data in Rheumatoid Arthritis.

Adalimumab, as a TNF inhibitor biologic for the treatment of rheumatoid arthritis, is one of the top-selling drugs worldwide. As its various patents have gradually expired, experiments on its biosimilars are constantly being implemented. In this review, we summarized clinical trials of seven biosimilars currently approved by the FDA and/or EMA for the treatment of rheumatoid arthritis, namely: ABP 501 (Amjevita/Amgevita/Solymbic), BI 695501 (Cyltezo), SB5 (Imraldi/Hadlima), GP2017 (Hyrimoz/Hefiya/Halimatoz), MSB11022 (Idacio), FKB327 (Hulio), and PF-06410293 (Abrilada). Overall, these biosimilars showed similar efficacy, safety, and immunogenicity to adalimumab. All biosimilar switching trials indicated that switching from adalimumab to a biosimilar does not have a significant impact on efficacy, safety, and immunogenicity.

Structuralist mental representation of dual-action demands: Evidence for compositional coding from dual tasks with low cross-task dimensional overlap

The present study asks how behavioral (dual-action) demands in dual tasks are mentally represented and whether changes in representation might govern practice-related dual-task performance improvements. Three different representation accounts were empirically tested based on the idea that dual-action demands required in a dual-task trial might be represented in different ways. According to a compositional (Structuralist) account, component tasks remain structurally intact when combined with another task. In contrast, a holistic (Gestalt) account posits that dual-action requirements in dual tasks are represented holistically and entirely distinct from its component action requirements. Finally, a contextual change account assumes that a change in context (e.g., from single- to dual-action requirement) generally impedes response retrieval, similar to repeating a response while the task context switches. To address this issue, we analyzed trial-by-trial effects in a single/dual switch paradigm (SDS paradigm, involving a randomized mix of single- and dual-task trials within blocks). Specifically, we analyzed performance in an extensive dual-task training setting (involving training sessions across several days) combining an auditory-vocal task and a visual-manual task. The results indicated that, throughout practice, nearly all relevant comparisons of performance between complete switch trials (e.g., between the two single tasks) and partial repetition trials (e.g., from dual to single task) revealed partial repetition benefits, that is, for both the auditory-vocal and the visual-manual task, and for both single- and dual-task performance analyses. Therefore, dual-action requirements in the present dual-task setting are mentally represented in a compositional, Structuralist fashion, probably due to low between-task dimensional overlap.

Continuous theta-burst stimulation modulates language-related inhibitory processes in bilinguals: evidence from event-related potentials.

The dorsolateral prefrontal cortex (DLPFC) is activated when bilinguals switch between languages. Language switching can also elicit the N2 event-related potential (ERP). This ERP component appears to capture the cognitive control processes related to conflict monitoring, response selection and response inhibition. In the present study, continuous theta-burst stimulation (cTBS) was used to examine the role of the left DLPFC in bilingual language switching, using a picture-naming task. Participants in the study were 17 Afrikaans-English bilinguals. The picture-naming task consisted of non-switch and switch trials. On non-switch trials, participants named two consecutive pictures in the same language. On switch trials, participants named consecutive pictures in different languages (e.g., Afrikaans and then English). The participants completed three testing sessions. In each session, participants received either cTBS to the left DLPFC or the vertex, or sham stimulation, and then completed the picture-naming task. The results showed that following DLPFC stimulation, the N2 ERP was attenuated on switch trials compared to non-switch trials. Vertex or sham stimulation did not modulate the N2 ERP. cTBS did not affect language switching at the behavioural level. These results provide support for the role of the left DLPFC in the cognitive control processes underlying bilingual language switching. Furthermore, the study demonstrates that these processes can be modulated via non-invasive brain stimulation and the effects detected at the neural level.

Neural differences in the temporal cascade of reactive and proactive control for bilinguals and monolinguals.

This study explored differences in sustained top-down attentional control (i.e., proactive control) and spontaneous types of control (i.e., reactive control) in bilingual and monolingual speakers. We modified a Color-Word Stroop task to varying levels of conflict and included switching trials in addition to more "traditional" inhibition Stroop conditions. The task was administered during scalp electroencephalography (EEG) to evaluate the temporal course of cognitive control during trials. The behavioral Stroop effect was observed across the whole sample; however, there were no differences in accuracy or response time between the bilingual and monolingual groups. Event-related potentials (ERPs) were calculated for the N200, N450, and conflict Sustained Potential (SP). On the pure-blocked incongruent trials, the bilingual group displayed reduced signal during interference suppression (N450) and increased later signal, as indexed by the conflict SP. On the mixed-block incongruent trials, both the bilinguals and monolinguals displayed increased later signal at the conflict SP. This suggests that proactive control may be a default mode for bilinguals on tasks requiring inhibition. In the switching trials, that place high demands on the executive control component of shifting, the language groups did not differ. Overall, these results suggest processing differences between bilinguals and monolinguals extend beyond early response inhibition processes. Greater integration of proactive and reactive control may be needed to sort conflicting language environments for bilinguals, which may be transferring to domain-general mechanisms.

A change of mind: Globus pallidus activity and effective connectivity during changes in choice selections.

The basal ganglia are a group of interconnected subcortical nuclei that plays a key role in multiple motor and cognitive processes, in a close interplay with several cortical regions. Two conflicting theories postulate that the basal ganglia pathways can either foster or suppress the cortico-striatal output or, alternatively, they can stabilize or destabilize the cortico-striatal circuit dynamics. These different approaches significantly impact the understanding of observable behaviours and cognitive processes in healthy, as well as clinical populations. We investigated the predictions of these models in healthy participants (N=28), using dynamic causal modeling of fMRI BOLD activity to estimate time- and context-dependent changes in the indirect pathway effective connectivity, in association with repetitions or changes of choice selections. We used two multi-option tasks that required the participants to adapt to uncontrollable environmental changes, by performing sequential choice selections, with and without value-based feedbacks. We found that, irrespective of the task, the trials that were characterized by changes in choice selections (switch trials) were associated with a neural response that mostly overlapped with a network commonly described for the encoding of uncertainty. More interestingly, dynamic causal modeling and family-wise model comparison identified with high likelihood a directed causal relation from the external to the internal part of the globus pallidus (i.e., the short indirect pathway in the basal ganglia), in association with the switch trials. This finding supports the hypothesis that the short indirect pathway in the basal ganglia drives instability in the network dynamics, resulting in changes in choice selection.

More change in task repetition, less cost in task switching: Behavioral and event-related potential evidence.

Previous studies have shown that the probability of task switching can vary the level of cognitive control and modulate the size of switch costs. However, it is unclear whether switch costs would be affected by a task-repetition context formed by varying the degree of response (and task-relevant stimulus property) change within the task repetition sequences while the probability of task switching remains constant. In the present study, participants were presented with a string of digits (e.g., ②②②). Basing on stimulus color, they were required to indicate either the presented digit, or the number of presented digits. Before task switching, stimulus and response in consecutive task-repeat trials varied more or less frequently. Behavioral results showed that the frequent-change context elicited smaller switch costs than the rare-change context. Event-related potential (ERP) results indicated that: (1) the frequent-change context evoked greater fronto-central N2 amplitudes for both task-repeat and task-switch trials, implying that cognitive control increased due to the variation of stimulus and response associations; (2) for the task switch trials, smaller P300 amplitudes were evoked in the frequent-change context than the rare-change context, reflecting the promoted task-set reconfiguration. These findings suggest that, the more change in stimulus and response during task repetition, the higher the overall level of cognitive control and the higher efficiency of task-switching.

How time shapes cognitive control: A high-density EEG study of task-switching

Task-switching is one of the most popular paradigms to investigate cognitive control. The main finding of interest is the switch cost: RTs in switch trials are longer than RTs in repetition trials. Despite the massive amount of research in these topics, little is known about the underlying temporal dynamics of the cortical regions involved in these phenomena.Here we used high density EEG to unveil the spatiotemporal neural dynamics associated with both the switch cost and to its modulation over time (time-on-task effect), as two markers of cognitive control reflecting effortful and procedural mechanisms, respectively. We found that, as a function of task practice, the switch cost decreased and both the switch-positivity and the switch-negativity event-related responses increased, although the latter showed a larger modulatory effect. At a source level, this effect was revealed by a progressively higher activation of the left middle and superior frontal gyrus.

Dietary lutein plus zeaxanthin and choline intake is interactively associated with cognitive flexibility in middle-adulthood in adults with overweight and obesity

ABSTRACT Background The xanthophyll carotenoids lutein+zeaxanthin and the dietary component choline have been linked to benefits in cognition. However, knowledge on the interactive influence of these dietary components on cognitive function is sparse. Design 80 middle-aged adults with overweight and obesity (Body Mass Index: (BMI) ≥25.0 kg/m²), completed 7-day diet records, venous blood draws, heterochromatic flicker photometry, assessment of intelligence quotient (IQ), and a cognitive flexibility task while undergoing electroencephalographic recording for event-related potential (ERP) extraction. Multiplicative interaction terms and hierarchical linear regressions, controlling for age, BMI, sex, annual household income, and IQ were utilized to assess independent and interactive contributions of dietary and biomarker data on Switch task outcomes. Results Higher intake of lutein+zeaxanthin and choline was associated interactively, but not independently, with faster reaction time (RT), after controlling for pertinent covariates. Dietary intake of lutein+zeaxanthin and choline was associated with serum lutein concentrations, but not with plasma choline metabolites nor macular pigmentation. Plasma phosphatidylcholine (PC) concentrations were associated with higher accuracy in Switch trials, while no other biomarkers were associated with cognitive outcomes. Dietary intake and biomarker data were not related to the N2 nor P3 ERP component. Conclusions Among a sample of adults with overweight and obesity, greater intake of choline and lutein+zeaxanthin was associated with faster performance on a cognitive flexibility task. Future work examining methods of increasing consumption of both of these dietary components as a possible means of improving or maintaining cognitive flexibility among adults with overweight and obesity is therefore warranted.

The Effect of Bilingualism on Cue-Based vs. Memory-Based Task Switching in Older Adults.

Findings suggest a positive impact of bilingualism on cognition, including the later onset of dementia. However, it is not clear to what extent these effects are influenced by variations in attentional control demands in response to specific task requirements. In this study, 20 bilingual and 20 monolingual older adults performed a task-switching task under explicit task-cuing vs. memory-based switching conditions. In the cued condition, task switches occurred in random order and a visual cue signaled the next task to be performed. In the memory-based condition, the task alternated after every second trial in a predictable sequence without presenting a cue. The performance of bilinguals did not vary across experimental conditions, whereas monolinguals experienced a pronounced increase in response latencies and error rates in the cued condition. Both groups produced similar switch costs (difference in performance on switch trials as opposed to repeating trials within the mixed-task block) and mixing costs (difference in performance on repeat trials of a mixed-task block as opposed to trials of a single-task block), but bilinguals produced them with lower response latencies. The cognitive benefits of bilingualism seem not to apply to executive functions per se but to affect specific cognitive processes that involve task-relevant context processing. The present results suggest that lifelong bilingualism could promote in older adults a flexible adjustment to environmental cues, but only with increased task demands. However, due to the small sample size, the results should be interpreted with caution.