Dissociable theta networks underlie the switch and mixing costs during task switching.

During task-switching paradigms, both event-related potentials and time-frequency analyses show switch and mixing effects at frontal and parietal sites. Switch and mixing effects are associated with increased power in broad frontoparietal networks, typically stronger in the theta band (~4-8 Hz). However, it is not yet known whether mixing and switch costs rely upon common or distinct networks. In this study, we examine proactive and reactive control networks linked to task switching and mixing effects, and whether strength of connectivity in these networks is associated with behavioural outcomes. Participants (n = 197) completed a cued-trials task-switching paradigm with concurrent electroencephalography, after substantial task practice to establish strong cue-stimulus-response representations. We used inter-site phase clustering, a measure of functional connectivity across electrode sites, to establish cross-site connectivity from a frontal and a parietal seed. Distinct theta networks were activated during proactive and reactive control periods. During the preparation interval, mixing effects were associated with connectivity from the frontal seed to parietal sites, and switch effects with connectivity from the parietal seed to occipital sites. Lateralised occipital connectivity was common to both switch and mixing effects. After target onset, frontal and parietal seeds showed a similar pattern of connectivity across trial types. These findings are consistent with distinct and common proactive control networks and common reactive networks in highly practised task-switching performers.

Impact of time of onset of symptom of ST-segment elevation myocardial infarction on 1-year rehospitalization for heart failure and mortality.

Circadian patterns in ST-segment elevation myocardial infarction (STEMI) patients have been previously reported, but little is known about the impact of time dependence of symptom onset on long-term prognosis. Our study population consisted of 11,731 STEMI patients treated by primary percutaneous coronary intervention (PPCI), enrolled in the Singapore Myocardial Infarction Registry (SMIR). Analysis of STEMI incidence trends over the 24-hour period showed the highest rate of symptom onset in the morning, with the peak incidence at 09:00 am. Patients with symptom onset in between 00:00 am-5:59 am showed the highest prevalence of diabetes (P = .010) and anterior STEMI (P < .001) and had the longest ischemic time (P < .001). After adjusting for confounders, we found an association between time of symptom onset of STEMI and rehospitalization for heart failure (HF) at 1 year, with symptom onset between 06:00 pm-11:59 pm and 00:00 am-05:59 am having an estimated 30% to 50% higher risk of rehospitalization for HF at 1 year. Moreover, symptom onset remained a predictor of worse prognosis only in the subgroup of patients with symptoms lasting longer than 120 minutes. The results of this study demonstrate for the first time that rehospitalization for HF in STEMI patients treated with PPCI has a dependence on the time of onset of symptoms, with prolonged ischemia time playing a pivotal role. This may be an additional risk factor to identify those who warrant closer monitoring and more rigorous optimization of their treatment at follow-up, to improve their outcomes.

Frontal theta predicts specific cognitive control-induced behavioural changes beyond general reaction time slowing.

Investigations into the neurophysiological underpinnings of control suggest that frontal theta activity is increased with the need for control. However, these studies typically show this link by reporting associations between increased theta and RT slowing - a process that is contemporaneous with cognitive control but does not strictly reflect the specific use of control. In this study, we assessed frontal theta responses that underpinned the switch cost in task switching - a specific index of cognitive control that does not rely exclusively on RT slowing. Here, we utilised a single-trial regression approach to assess 1) how cognitive control demands beyond simple RT slowing were linked to midfrontal theta and 2) whether midfrontal theta effects remained stable over time. In a large cohort that included a longitudinal subsample, we found that midfrontal theta was modulated by switch costs, with enhanced theta power when preparing to switch vs. repeating a task. These effects were reliable after a two-year interval (Cronbach's α.39-0.74). In contrast, we found that trial-by-trial modulations of midfrontal theta power predicted the size of the switch cost - so that switch trials with increased theta produced smaller switch costs. Interestingly, these relationships between theta and behaviour were less stable over time (Cronbach's α 0-0.61), with participants first using both delta and theta bands to influence behaviour whereas after two years only theta associations with behaviour remained. Together, these findings suggest midfrontal theta supports the need for control beyond simple RT slowing and reveal that midfrontal theta effects remain relatively stable over time.

Does cognitive control ability mediate the relationship between reward-related mechanisms, impulsivity, and maladaptive outcomes in adolescence and young adulthood?

Neurobiological models explain increased risk-taking behaviours in adolescence and young adulthood as arising from staggered development of subcortical reward networks and prefrontal control networks. In this study, we examined whether individual variability in impulsivity and reward-related mechanisms is associated with higher level of engagement in risky behaviours and vulnerability to maladaptive outcomes and whether this relationship is mediated by cognitive control ability. A community sample of adolescents, young adults, and adults (age = 15-35 years) completed self-report measures and behavioural tasks of cognitive control, impulsivity, and reward-related mechanisms, and self-reported level of maladaptive outcomes. Behavioural, event-related potential (ERP), and multivariate pattern analysis (MVPA) measures of proactive control were derived from a task-switching paradigm. Adolescents, but not young adults, reported higher levels of impulsivity, reward-seeking behaviours and maladaptive outcomes than adults. They also had lower cognitive control ability, as measured by both self-report and task-based measures. Consistent with models of risk-taking behaviour, self-reported level of cognitive control mediated the relationship between self-reported levels of impulsivity and psychological distress, but the effect was not moderated by age. In contrast, there was no mediation effect of behavioural or EEG-based measures of cognitive control. These findings suggest that individual variability in cognitive control is more crucial to the relationship between risk-taking/impulsivity and outcomes than age itself. They also highlight large differences in measurement between self-report and task-based measures of cognitive control and decision-making under reward conditions, which should be considered in any studies of cognitive control.

Theta frontoparietal connectivity associated with proactive and reactive cognitive control processes.

Cognitive control involves both proactive and reactive processes. Paradigms that rely on reactive control have shown that frontoparietal oscillatory synchronization in the theta frequency band is associated with interference control. This study examines whether proactive control is also associated with connectivity in the same frontoparietal theta network or involves a distinct neural signature. A task-switching paradigm was used to differentiate between proactive and reactive control processes, involved in preparing to switch or repeat a task and resolving post-target interference, respectively. We confirm that reactive control is associated with frontoparietal theta connectivity. Importantly, we show that proactive control is also associated with theta band oscillatory synchronization but in a different frontoparietal network. These findings support the existence of distinct proactive and reactive cognitive control processes that activate different theta frontoparietal oscillatory networks.

Jointly modeling behavioral and EEG measures of proactive control in task switching.

In this study, we implement joint modeling of behavioral and single-trial electroencephalography (EEG) data derived from a cued-trials task-switching paradigm to test the hypothesis that trial-by-trial adjustment of response criterion can be linked to changes in the event-related potentials (ERPs) elicited during the cue-target interval (CTI). Specifically, we assess whether ERP components associated with preparation to switch task and preparation of the relevant task are linked to a response criterion parameter derived from a simple diffusion decision model (DDM). Joint modeling frameworks characterize the brain-behavior link by simultaneously modeling behavioral and neural data and implementing a linking function to bind these two submodels. We examined three joint models: The first characterized the core link between EEG and criterion, the second added a switch preparation input parameter and the third also added a task preparation input parameter. The criterion-EEG link was strongest just before target onset. Inclusion of switch and task preparation parameters did not improve the performance of the criterion-EEG link but was necessary to accurately model the ERP waveform morphology. While we successfully jointly modeled latent model parameters and EEG data from a task-switching paradigm, these findings show that customized cognitive models are needed that are tailored to the multiple cognitive control processes underlying task-switching performance. This is the first paper to implement joint modeling of behavioral measures and single-trial electroencephalography (EEG) data derived from the cue-target interval in a cued-trials task-switching paradigm. Model hyperparameters showed a strong link between response criterion and the pre-target negativity amplitude. Additional parameters (switch preparation, task preparation) were necessary to model the cue-locked ERP waveform morphology. This is consistent with multiple cognitive control processes underlying proactive control and points to the need for more nuanced models of task-switching performance.

Task-switching costs have distinct phase-locked and nonphase-locked EEG power effects.

Event-related potentials (ERPs) and total time-frequency power analyses have shown that performance costs during task switching are related to differential preparation to switch tasks (switch cost) and repeat the same task (mixing cost) during both proactive control (cue-to-target interval; CTI) and reactive control (post-target). The time-frequency EEG signal is comprised of both phase-locked activity (associated with stimulus-specific processes) and nonphase-locked activity (represents processes thought to persist over longer timeframes and do not contribute to the average ERP). In the present study, we used a cued task-switching paradigm to examine whether phase-locked and nonphase-locked power are differentially modulated by switch and mixing effects in intervals associated with the need for proactive control (CTI) and reactive control (post-target interval). Phase-locked activity was observed in the theta and alpha bands, closely resembled that seen for total power, and was consistent with switch and mixing ERP positivities. Nonphase-locked analyses showed theta and alpha power effects for both switch and mixing effects early in the CTI and as well as more sustained alpha and beta activity around cue onset, and extending from mid-CTI into the post-target interval. Nonphase-locked activity in pretarget alpha and posttarget theta power were both correlated with response time mixing cost. These findings provide novel insight into phase-locked and nonphase-locked activity associated with switch and mixing costs that are not evident with ERP or total time-frequency analyses.

Independent Predictors of Cardiac Mortality and Hospitalization for Heart Failure in a Multi-Ethnic Asian ST-segment Elevation Myocardial Infarction Population Treated by Primary Percutaneous Coronary Intervention.

We aimed to identify independent predictors of cardiac mortality and hospitalization for heart failure (HHF) from a real-world, multi-ethnic Asian registry [the Singapore Myocardial Infarction Registry] of ST-segment elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention. 11,546 eligible STEMI patients between 2008 and 2015 were identified. In-hospital, 30-day and 1-year cardiac mortality and 1-year HHF rates were 6.4%, 6.8%, 8.3% and 5.2%, respectively. From the derivation cohort (70% of patients), age, Killip class and cardiac arrest, creatinine, hemoglobin and troponin on admission and left ventricular ejection fraction (LVEF) during hospitalization were predictors of in-hospital, 30-day and 1-year cardiac mortality. Previous ischemic heart disease (IHD) was a predictor of in-hospital and 30-day cardiac mortality only, whereas diabetes was a predictor of 1-year cardiac mortality only. Age, previous IHD and diabetes, Killip class, creatinine, hemoglobin and troponin on admission, symptom-to-balloon-time and LVEF were predictors of 1-year HHF. The c-statistics were 0.921, 0.901, 0.881, 0.869, respectively. Applying these models to the validation cohort (30% of patients) showed good fit and discrimination (c-statistic 0.922, 0.913, 0.903 and 0.855 respectively; misclassification rate 14.0%, 14.7%, 16.2% and 24.0% respectively). These predictors could be incorporated into specific risk scores to stratify reperfused STEMI patients by their risk level for targeted intervention.

Platelet inhibition to target reperfusion injury trial: Rationale and study design.

BACKGROUND: In ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PPCI), current oral P2Y12 platelet inhibitors do not provide maximal platelet inhibition at the time of reperfusion. Furthermore, administration of cangrelor prior to reperfusion has been shown in pre-clinical studies to reduce myocardial infarct (MI) size. Therefore, we hypothesize that cangrelor administered prior to reperfusion in STEMI patients will reduce the incidence of microvascular obstruction (MVO) and limit MI size in STEMI patients treated with PPCI. METHODS: The platelet inhibition to target reperfusion injury (PITRI) trial, is a phase 2A, multi-center, double-blinded, randomized controlled trial, in which 210 STEMI patients will be randomized to receive either an intravenous (IV) bolus of cangrelor (30 µg/kg) followed by a 120-minute infusion (4 µg/kg/min) or matching saline placebo, initiated prior to reperfusion (NCT03102723). RESULTS: The study started in October 2017 and the anticipated end date would be July 2020. The primary end-point will be MI size quantified by cardiovascular magnetic resonance (CMR) on day 3 post-PPCI. Secondary endpoints will include markers of reperfusion, incidence of MVO, MI size, and adverse left ventricular remodeling at 6 months, and major adverse cardiac and cerebrovascular events. SUMMARY: The aim of the PITRI trial is to assess whether cangrelor administered prior to reperfusion would reduce acute MI size and MVO, as assessed by CMR.

Event-Related Potential Responses to Task Switching Are Sensitive to Choice of Spatial Filter.

Event-related potential (ERP) studies using the task-switching paradigm show that multiple ERP components are modulated by activation of proactive control processes involved in preparing to repeat or switch task and reactive control processes involved in implementation of the current or new task. Our understanding of the functional significance of these ERP components has been hampered by variability in their robustness, as well as their temporal and scalp distribution across studies. The aim of this study is to examine the effect of choice of reference electrode or spatial filter on the number, timing and scalp distribution of ERP elicited during task-switching. We compared four configurations, including the two most common (i.e., average mastoid reference and common average reference) and two novel ones that aim to reduce volume conduction (i.e., reference electrode standardization technique (REST) and surface Laplacian) on mixing cost and switch cost effects in cue-locked and target-locked ERP waveforms in 201 healthy participants. All four spatial filters showed the same well-characterized ERP components that are typically seen in task-switching paradigms: the cue-locked switch positivity and target-locked N2/P3 effect. However, both the number of ERP effects associated with mixing and switch cost, and their temporal and spatial resolution were greater with the surface Laplacian transformation which revealed rapid temporal adjustments that were not identifiable with other spatial filters. We conclude that the surface Laplacian transformation may be more suited to characterize EEG signatures of complex spatiotemporal networks involved in cognitive control.

Frontoparietal theta oscillations during proactive control are associated with goal-updating and reduced behavioral variability.

Low frequency oscillations in the theta range (4-8Hz) are increasingly recognized as having a crucial role in flexible cognition. Such evidence is typically derived from studies in the context of reactive (stimulus-driven) control processes. However, little research has explored the role of theta oscillations in preparatory control processes. In the current study, we explored the extent of theta oscillations during proactive cognitive control and determined if these oscillations were associated with behavior. Results supported a general role of theta oscillations during proactive cognitive control, with increased power and phase coherence during the preparatory cue interval. Further, theta oscillations across frontoparietal electrodes were also modulated by proactive control demands, with increased theta phase synchrony and power for cues signaling the need for goal updating. Finally, we present novel evidence of negative associations between behavioral variability and both power and phase synchrony across many of these frontoparietal electrodes that were associated with the need for goal updating. In particular, greater consistency in frontoparietal theta oscillations, indicated by increased theta phase and power during mixed-task blocks, resulted in more consistent task-switching performance. Together, these findings provide new insight into the temporal dynamics and functional relevance of theta oscillations during proactive cognitive control.

Coronary-pulmonary arteriovenous fistula used as proximal anastomotic site for saphenous vein grafts in patient with porcelain aorta.

Coronary artery bypass grafting in patients with porcelain aorta and calcified great vessels is associated with a high risk of systemic embolism. Various techniques have been suggested to minimize that risk. We describe the case of a patient with left main coronary disease and a severely calcified ascending aorta, who could not undergo cardiopulmonary bypass. To the best of our knowledge, this is the 1st reported use of a congenital coronary-pulmonary arteriovenous fistula as a proximal anastomotic site for saphenous vein grafts, to achieve optimal revascularization in a patient with porcelain aorta.

Comparison of novel 6.5 Fr sheathless guiding catheters versus 5 Fr guiding catheters for transradial coronary intervention.

AIMS: To assess the safety and efficacy of a novel sheathless (SH) 6.5 Fr (French) hydrophilic-coated guiding catheter (GC) compared to the standard 5 Fr GCs in transradial coronary interventions (TRI). METHODS AND RESULTS: Patients undergoing TRI with 6.5 Fr SH or 5 Fr GCs were included. Baseline characteristics and in-hospital outcomes were recorded. Primary endpoints were procedural success and presence of radial pulse at discharge. Secondary endpoints were successful GC support, in-hospital adverse events, access-site complications, procedural duration and contrast load. There were 269 patients with 146 procedures in each group. The SH GC group had more non-ST elevation MI, in-stent restenosis, high-risk and bifurcation lesions. Procedural success in both arms was 95.2%. One patient in each group (0.7%) experienced radial artery occlusion (RAO) after TRI, without clinical sequelae. One access-site haematoma and one minor stroke occurred in the 5 Fr group (none in the SH group, both p=ns). Mean procedure time (52±21 vs. 45±21 minutes, p=0.004) and contrast load (160±45 ml vs. 140±45 ml, p=0.003) were greater in the SH group. CONCLUSIONS: Both 6.5 Fr SH GCs and 5 Fr GCs achieved high procedural TRI success with low RAO rates. The SH GC eliminated the disadvantages of the 5 Fr GC whilst maintaining the advantage of low RAO rates, and may become the GC of choice in TRI.